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Printed Hearing The Committee on Energy and Commerce Issues Relating to Ephedra-containing Dietary Supplements. <DOC>
[108th Congress House Hearings]
[From the U.S. Government Printing Office via GPO Access]
[DOCID: f:89966.wais]
ISSUES RELATING TO EPHEDRA-CONTAINING DIETARY SUPPLEMENTS
=======================================================================
HEARINGS
before the
SUBCOMMITTEE ON
OVERSIGHT AND INVESTIGATIONS
and the
SUBCOMMITTEE ON
COMMERCE, TRADE, AND CONSUMER PROTECTION
of the
COMMITTEE ON ENERGY AND COMMERCE
HOUSE OF REPRESENTATIVES
ONE HUNDRED EIGHTH CONGRESS
FIRST SESSION
__________
JULY 23 and 24, 2003
__________
Serial No. 108-43
__________
Printed for the use of the Committee on Energy and Commerce
Available via the World Wide Web: http://www.access.gpo.gov/congress/
house
__________
89-966 U.S. GOVERNMENT PRINTING OFFICE
WASHINGTON : 2003
----------------------------------------------------------------------------
For Sale by the Superintendent of Documents, U.S. Government Printing Office
Internet: bookstore.gpo.gov Phone: toll free (866) 512-1800; (202) 512ÿ091800
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COMMITTEE ON ENERGY AND COMMERCE
W.J. ``BILLY'' TAUZIN, Louisiana, Chairman
MICHAEL BILIRAKIS, Florida JOHN D. DINGELL, Michigan
JOE BARTON, Texas Ranking Member
FRED UPTON, Michigan HENRY A. WAXMAN, California
CLIFF STEARNS, Florida EDWARD J. MARKEY, Massachusetts
PAUL E. GILLMOR, Ohio RALPH M. HALL, Texas
JAMES C. GREENWOOD, Pennsylvania RICK BOUCHER, Virginia
CHRISTOPHER COX, California EDOLPHUS TOWNS, New York
NATHAN DEAL, Georgia FRANK PALLONE, Jr., New Jersey
RICHARD BURR, North Carolina SHERROD BROWN, Ohio
Vice Chairman BART GORDON, Tennessee
ED WHITFIELD, Kentucky PETER DEUTSCH, Florida
CHARLIE NORWOOD, Georgia BOBBY L. RUSH, Illinois
BARBARA CUBIN, Wyoming ANNA G. ESHOO, California
JOHN SHIMKUS, Illinois BART STUPAK, Michigan
HEATHER WILSON, New Mexico ELIOT L. ENGEL, New York
JOHN B. SHADEGG, Arizona ALBERT R. WYNN, Maryland
CHARLES W. ``CHIP'' PICKERING, GENE GREEN, Texas
Mississippi KAREN McCARTHY, Missouri
VITO FOSSELLA, New York TED STRICKLAND, Ohio
ROY BLUNT, Missouri DIANA DeGETTE, Colorado
STEVE BUYER, Indiana LOIS CAPPS, California
GEORGE RADANOVICH, California MICHAEL F. DOYLE, Pennsylvania
CHARLES F. BASS, New Hampshire CHRISTOPHER JOHN, Louisiana
JOSEPH R. PITTS, Pennsylvania TOM ALLEN, Maine
MARY BONO, California JIM DAVIS, Florida
GREG WALDEN, Oregon JAN SCHAKOWSKY, Illinois
LEE TERRY, Nebraska HILDA L. SOLIS, California
ERNIE FLETCHER, Kentucky
MIKE FERGUSON, New Jersey
MIKE ROGERS, Michigan
DARRELL E. ISSA, California
C.L. ``BUTCH'' OTTER, Idaho
Dan R. Brouillette, Staff Director
James D. Barnette, General Counsel
Reid P.F. Stuntz, Minority Staff Director and Chief Counsel
______
Subcommittee on Oversight and Investigations
JAMES C. GREENWOOD, Pennsylvania, Chairman
MICHAEL BILIRAKIS, Florida PETER DEUTSCH, Florida
CLIFF STEARNS, Florida Ranking Member
RICHARD BURR, North Carolina DIANA DeGETTE, Colorado
CHARLES F. BASS, New Hampshire JIM DAVIS, Florida
GREG WALDEN, Oregon JAN SCHAKOWSKY, Illinois
Vice Chairman HENRY A. WAXMAN, California
MIKE FERGUSON, New Jersey BOBBY L. RUSH, Illinois
MIKE ROGERS, Michigan JOHN D. DINGELL, Michigan,
W.J. ``BILLY'' TAUZIN, Louisiana (Ex Officio)
(Ex Officio)
______
Subcommittee on Commerce, Trade, and Consumer Protection
CLIFF STEARNS, Florida, Chairman
FRED UPTON, Michigan JAN SCHAKOWSKY, Illinois
BARBARA CUBIN, Wyoming Ranking Member
JOHN SHIMKUS, Illinois HILDA L. SOLIS, California
JOHN B. SHADEGG, Arizona EDWARD J. MARKEY, Massachusetts
Vice Chairman EDOLPHUS TOWNS, New York
GEORGE RADANOVICH, California SHERROD BROWN, Ohio
CHARLES F. BASS, New Hampshire JIM DAVIS, Florida
JOSEPH R. PITTS, Pennsylvania PETER DEUTSCH, Florida
MARY BONO, California BART STUPAK, Michigan
LEE TERRY, Nebraska GENE GREEN, Texas
ERNIE FLETCHER, Kentucky KAREN McCARTHY, Missouri
MIKE FERGUSON, New Jersey TED STRICKLAND, Ohio
DARRELL E. ISSA, California DIANA DeGETTE, Colorado
C.L. ``BUTCH'' OTTER, Idaho JOHN D. DINGELL, Michigan,
W.J. ``BILLY'' TAUZIN, Louisiana (Ex Officio)
(Ex Officio)
(ii)
C O N T E N T S
__________
Page
Hearings held:
July 23, 2003................................................ 1
July 24, 2003................................................ 173
Testimony of:
Beales, J. Howard, III, Director, Bureau of Consumer
Protection, Federal Trade Commission....................... 238
Bechler, Pat................................................. 13
Birch, Adolpho A., III, Counsel for Labor Relations, National
Football League............................................ 193
Boozer, Carol, Obesity Research Center, St. Luke's Roosevelt
Hospital................................................... 103
Brown, David, former President of Metabolife................. 92
Chinery, Robert, President, Cytodyne Technologies............ 106
Colker, Carlon M., Chief Executive Officer and Medical
Director, Peak Wellness, Inc............................... 115
Conklin, Kelly, Cytodyne Technologies........................ 113
Crosse, Marcia, Acting Director, Health Care-Public Health
and Science Issues, U.S. General Accounting Office......... 44
Culmo, Cynthia, former official, Texas Department of Health.. 41
Ellis, Michael, Founder and Director of Metabolife
International.............................................. 92
Fox, Roseann, Customer Service Representative, NVE
Pharmaceuticals............................................ 121
Garber, Donald P., Commissioner, Major League Soccer......... 199
Helton, Mike, President, National Association for Stock Car
Auto Racing................................................ 196
Hermann, Robert, Vice President, Metabolife International.... 101
Hymsfield, Steven B., Deputy Director of Obesity Research
Center, St. Luke's Roosevelt Hospital...................... 18
Manfred, Robert D., Jr., Executive Vice President, Labor
Relations/Human Resources, Major League Baseball........... 185
McClellan, Hon. Mark B., Commissioner, Food and Drug
Administration............................................. 228
Mitten, Matthew J., Associate Dean for Academic Affairs,
Marquette University Law School, Director, National Sports
Law Institute, The National Collegiate Athletic Association 203
Occhifinto, Robert, President, NVE Pharmaceuticals........... 119
Orza, Eugene D., Associate General Counsel, Major League
Baseball Players Association............................... 189
Riggins, Kevin, Sean Riggins Foundation for Substance-Free
Schools.................................................... 14
Rodriguez, Daniel, Head Nurse, Metabolife.................... 92
Schreck, Russell, Chief Executive Officer, Metabolife
International.............................................. 99
Vasquez, Michael, Law Offices of Fred G. Cohen............... 17
Woosley, Raymond, Vice President for Health Sciences, Arizona
Health Sciences Center..................................... 32
Zipes, Douglas P., Distinguished Professor of Medicine,
Pharmacology and Toxicology, Director, Division of
Cardiology, Krannert Institute of Cardiology............... 35
Additional material submitted for the record:
American College of Obstetricians and Gynecologists, prepared
statement of............................................... 170
Baden, Michael M., M.D., letter dated 17 July 2003, to Hon
James C. Greenwood......................................... 166
Metabolife, responses to committee questions................. 169
(iii)
ISSUES RELATING TO EPHEDRA-CONTAINING DIETARY SUPPLEMENTS
----------
WEDNESDAY, JULY 23, 2003
House of Representatives,
Committee on Energy and Commerce,
Subcommittee on Oversight and Investigations,
Washington, DC.
The subcommittee met, pursuant to notice, at 10 a.m., in
room 2123, Rayburn House Office Building, James C. Greenwood
(chairman) presiding.
Members present: Representatives Greenwood, Stearns, Burr,
Bass, Walden, Tauzin (ex officio), Deutsch, DeGette, Davis,
Schakowsky, Waxman, Rush, and Dingell (ex officio).
Also present: Representatives Barton and Susan Davis.
Staff present: Alan Slobodin, majority counsel; Mark
Paoletta, majority counsel; Casey Hemard, majority counsel;
Kelli Andrews, majority counsel; Tom Dilenge, majority counsel;
William Carty, legislative clerk; David Nelson, minority
investigator and economist; Nicole Kenner, minority research
assistant; and Jessica McNiece, minority staff assistant.
Mr. Greenwood. Meeting will come to order.
I ask the guests please take seats.
We welcome everyone this morning, particularly our
witnesses.
I want to warn you all that we are probably going to be
begin votes in something like 15 to 20 minutes, and so we will
have disruption. But hopefully after those votes we will have a
relatively uninterrupted hearing.
Without objection the subcommittee will proceed pursuant to
Committee Rule 4E. So ordered.
The Chair recognizes himself for an opening statement.
Good morning and welcome to the first day of hearings on
issues relating to Ephedra-containing dietary supplements.
Baltimore Orioles pitcher Steve Bechler and high school
athlete Sean Riggins probably thought they were helping
themselves with the ephedra supplements either to lose weight
to enhance athletic performance. Tragically, these two young
men, 23 years of age and 16 years of age respectively, died.
And coroners who investigated their cases believed ephedra
played a role in their deaths.
Steve Bechler and Sean Riggins were 2 of an estimated 12 to
17 million Americans who consume more than 3 billion doses of
ephedra products every year. With the ephedra reportedly found
in more than 200 weight loss aids and energy booster, ephedra
based products have grown in popularity in the past decade,
especially with athletes and those trying to lose weight
quickly.
The millions of Americans who are motivated, some might
call it desperate, to lose weight quickly are ideal targets for
the marketers of ephedra-containing supplements. They advertise
the seductive promise to ``lose weight and enhance your
energy'' simply with a couple of pills everyday. But are these
ephedra products safe? Have the risks of these products been
assessed and disclosed? These are the general questions of our
inquiry today.
Let us begin with what ephedra is. It's a stimulant derived
from the Chinese herb mahuang. The herbal form has been used in
China for thousands of years to treat, temporarily, asthma and
other respiratory conditions, a major argument with the dietary
supplement promoters have used to rebut claims that ephedra is
unsafe. Over the past decade these companies, including
Metabolife, Cytodyne and NVE Pharmaceuticals, which are
represented at this hearing today, have manufactured ephedra-
containing products. But it promoted them for different
purposes.
Moreover, most of these new age ephedra products contain a
dosage combination of ephedrine and caffeine as the primary
active ingredients, as well as other active ingredients
including stimulants, many of which have not been in use for
thousands of years as have the traditional Chinese herbal form.
Ephedra is a complex substance that has placed the Food and
Drug Administration in a regulatory quandary. As a botanical,
ephedra meets the condition of a dietary supplement regulated
under the Dietary Supplement Health and Education Act of 1994,
referred to as DSHEA. Under this law dietary supplement
manufacturers are not required to prove that their products are
safe or effective before introducing them into the market, as
drug manufacturers are required to do. Moreover, once the
products are on the market, FDA has the burden of proving that
a product is not safe in order to take regulatory action.
But ephedra also contains ephedrine as its principle active
ingredient. And synthetic ephedrine and other ephedrine
alkaloids are regulated as drugs. Synthetic ephedrine is
available over the counter and in some prescription drugs but
is not offered in combination with caffeine or other
stimulants. And there are no synthetic ephedrine products
approved for long term use.
The result of this legal and regulatory framework is that
dietary supplements containing ephedrine-caffeine combinations
are widely available and subject to less regulation than drugs
that contain ephedrine which are not permitted to have
ephedrine-stimulant combinations. Does this make any sense?
Ephedra has been linked to serious side effects, including
stroke, seizure, heart attack and death. In 1997 the FDA
attempted to restrict access to ephedra significantly based on
adverse event reports. In April 1999 internal FDA memo about
the agency's in-depth analysis of 18 adverse event reports
concluded that ``these products may constitute a significant
public health hazard.'' Similarly, a March 2000 internal FDA
memo concluded that ``the most plausible and likely
interpretation'' is that there is ``is causative association
between ephedra supplements and the cardiovascular and central
nervous system adverse events reviews.''
As of September 27, 2002 FDA had received approximately
1800 adverse event reports related to ephedrine. But this may
not be representative of the true number of adverse events
associated with ephedrine. FDA has estimated that it receives
reports for less than 1 percent of the adverse events related
to dietary supplements, and just last summer Metabolife
released information on nearly 15,000 adverse event reports
they had received since 1997 concerning its ephedra containing
product Metabolife 356.
Now this last fact is particularly disturbing, given that
Metabolife had represented to FDA that it had ``never received
one notice from a consumer of any serious adverse event which
has been asserted to be associated with the ingestion of
Metabolife 356.''
In response to a recent Rand Corporation report which
provided additional analysis of safety concerns that may be
associated with ephedra-containing supplements, the Department
of Health and Human Services began regulatory proceedings to
increase protections for consumers. And for the first time
issued a statement cautioning the public about the use of
ephedra-containing supplements, particular in combination with
strenuous exercise or other stimulants. And one expert recently
hired by FDA to review industry sponsored safety data
recommended that ephedra be made available only by
prescription.
The foregoing should suggest that we must take company
representations with more than a grain of salt. Ephedra
promoted as a seemingly safe thousand year old traditional
Chinese medicine is no such thing. There is a difference
between the product and its uses in China as compared to this
country, as already mentioned. Indeed, the expert information
provided by China's State Drug Administration seems to indicate
that higher dose ephedra is sent to the U.S. and lower dose
ephedra is provided to the Chinese market. FDA inspection of
one Chinese ephedra manufacturer showed that the ephedra
intended for the United States had been spiked with additional
natural ephedra extract to increase its potency.
Ephedra companies also have toted various studies to
support claims of proven safety. However, on close examination
serious questions have been raised about the conduct and the
results of these studies we will inquire about today. For
example, certain emails we have uncovered appear to indicate
that one ephedra company was trying to influence the work of
one of its researchers to make the study more marketable. Yet
another ephedra company has told the committee it has never
tested the safety or efficacy of any of its roughly 80 ephedra-
containing products. In fact, we have learned that after the
company pulled one product off the market, at the time of the
controversy over the death of Sean Riggins, its president, a
high school graduate with no medical training, decided to
change the formulation of the product by increasing the amount
of the ephedrine and changing the name without consulting any
scientific or health experts.
We also must question the industry claim that most adverse
side effects associated with ephedra occur when people do not
use the supplements according to the manufacturer's direction.
A GAO analysis of internal adverse event reports from one such
manufacturer, which was conducted at our request and will be
released at this hearing today, found that amount the subset of
claims in which adequate usage and dosage information was
provided by the consumer, the consumer was following the
manufacturer's recommended guidelines the vast majority of the
time.
This morning we will hear from two families who have
witnessed firsthand the risks associated with ephedra. We will
hear from Steve Bechler's mother and father and from Sean
Riggins' dad. And let me thank you all for coming here today to
share with us your tragic and personal experiences.
On the first panel we also will hear from Michael Vasquez,
a nurse who worked for Metabolife in 1999 and who will discuss
how the company handled complaints of serious adverse health
events.
We also are fortunate to have five independent experts on
issues relating to ephedra safety.
Our second panel will be appearing before us only briefly.
Michael Ellis, David Brown and Daniel Rodriguez all of
Metabolife, have appeared before us this morning pursuant to
subpoena. All three are expected to assert their constitutional
right against self-incrimination and will not provide any
evidence or testimony to the subcommittee today.
On our third panel will be representatives of 3 companies
that manufacture ephedrine-containing products; Metabolife,
Cytodyne and NVE Pharmaceuticals. Joining the companies will be
2 scientists who have performed research on Cytodyne and
Metabolife's products.
I would like to thank all of our witnesses for attending.
And now recognize the ranking member of the subcommittee,
Mr. Deutsch for his opening statement.
Mr. Deutsch. Mr. Chairman, I'd like to yield to the ranking
Democrat of the full committee to make his opening statement.
Mr. Greenwood. The Chair recognizes the ranking member, Mr.
Dingell.
Mr. Dingell. Mr. Chairman, I thank the distinguished
ranking member of the subcommittee for his courtesy to me. And
I am very appreciative.
I thank you also, Mr. Chairman, for convening these 2 days
of hearings on a very important topic: The failure of the
United States to properly regulate the use of the herbal form
of a stimulate drug that has caused death and other serious
health problems. I repeat, it kills.
It is available in the United States not only as a drug,
but as a dietary supplement called ephedra. We shall see today
how unscrupulous operators with disdain for public health
consequences of their actions have bent, broken or otherwise
abused a law which is too weak to sell products that can and do
kill and seriously injured the uninformed user.
Further, they have made claims in their advertising that
attract those who are extremely vulnerable; young people hoping
to make their high school sports teams or overweight persons
hoping to lose pounds without adopting healthy diets or regular
exercise.
There are some in the industry that would have us accept
the notion that ephedra is only an outlier. That the law is
sound and only this single substance needs to be banned. I do
not believe that that is the truth, and I believe they know
better.
I believe that these hearings will reveal that it is
because of a combination of weak language in a statute which
was passed in a burst of unwisdom in the U.S. Senate, clever
uncovering and use of legal loopholes, and, shoddy and poorly
funded enforcement that the law cannot be used to adequately
protect the public from these modern day patent medicine
peddlers and snake oil salesmen. Given the state of law, at
least as currently interpreted, there is simply no way that
even educated consumers can distinguish between dietary
supplements that can provide real benefit at an affordable
price and often dangerous rip-offs that have become pervasive,
at least amongst the heavily advertised products of this
industry. I will point out that this industry is full of
shysters, they are not properly required to label the products
or to be regulated as to either safety, efficacy or the quality
of manufacturing practices.
I hope that these hearings and others will come to provide
us with information needed to reform the underlying statute on
a bipartisan basis. Frankly, this is one of the shameful
statutes on the books which does not protect the American
people and scoundrels are enriching themselves by this device.
American consumers deserve to be able to get vitamins and other
supplements that will enhance their lives without falling prey
to charlatans and scoundrels that promise the impossible but
not only deliver disappoint at best, but disaster at worst.
Thank you, Mr. Chairman.
Mr. Greenwood. The Chair thanks the gentleman for his
statement and now recognizes the Chairman of the Full
Committee, the gentleman from Louisiana, Mr. Tauzin.
Chairman Tauzin. Thank you, Mr. Chairman.
Today's hearing represents a continuation of the incredibly
work the subcommittee has done on behalf of the American
people. And I want to thank all of you on the subcommittee on
both sides of the aisle for that.
You have helped protect consumers. You have helped protect
investors and parents concerned about the safety of their
children.
We are here today to shine the light, the spotlight of
congressional inquiry on what is truly a life and death issue;
the safety of ephedra-containing dietary supplements. These
supplements marketed and used to spur weight loss or increase
athletic or sexual performance and can be bought in any 7-
Eleven, any convenience store or gas station by anyone
including those under 18.
The issue for today's hearing is whether continuation of
such a policy for ephedra makes sense, given what we have
learned about the dangers of ephedra.
It also, I believe, shines a spotlight on the debate we
will have the floor tomorrow on the FDA's role in protecting
the safety and efficacy of drugs under FDA regulation in our
society. Some will be asking us tomorrow to vote to allow
importation of drugs from other countries without FDA
certification of safety. I think today we will learn the
dangers of that kind of a policy.
Under current Federal law companies that make and market
these supplements do not have to test the safety of their
products, nor do they have to prove that they work as
advertised. The 1994 Congress passed a law that restricted
FDA's regulation of these products on a theory, the theory that
dietary supplements are more akin to food products than actual
drugs. That might have made sense then and remains a sensible
approach for the vast majority of dietary supplements. But with
this regulatory leniency comes a heavy dose of corporate
responsibility and accountability, and one which based upon
this committee's investigation to date appears to have been
willfully ignored by ephedra manufacturers.
We learned that these ephedra supplement makers have been
engaged in some highly questionable behavior--from producing
products without any safety testing, to promoting safety and
efficacy based on dubious industry-sponsored studies; from
making changes to their products to increase doses of
stimulants without any kind of scientific or health review, all
the way to hiding thousands of consumer health complaints from
regulatory authorities. Such conduct is simply unacceptable.
The argument that the Federal Government does not yet
require these companies to act any differently is not excuse
for their blatant disregard for health and safety of their
consumers. If they do not clean up their act, I can promise we
will do it for them.
I know that the FDA has authority to take action against
dietary supplements if there is evidence of safety problems. It
certainly seems to me that in the past the agency has failed to
confront aggressively enough this growing problem. I am
extremely pleased that Secretary of Health, Secretary Thompson
and our Administrator of the FDA Dr. McCellan have taken a much
more proactive and aggressive approach to dealing with the
dangers of ephedra. And I am anxious today to hear the
witnesses, particularly those of you who had personal losses as
a result of, I think, the abuses of this particular product.
Let me say again, we created our FDA. We created it with
the authority to investigate and to make certain that the drugs
that are used in our society are used in a safe manner. That
they are safe drugs. That their efficacy is tested. And that
the people who manufacture them and sell them in this country
always--always operate their business and produce their
products with safety in mind. That appears not to be the case
with ephedra, and that appears to be a reason why this Congress
needs to take a much more aggressive position when it comes to
this particular product.
And I yield back the balance of my mine.
Mr. Greenwood. The Chair thanks the gentleman and
recognizes, again, the ranking member from Florida, Mr.
Deutsch.
Mr. Deutsch. Thank you, Mr. Chairman.
And thank you for having this hearing, but also thank the
witnesses for being here. I appreciate particularly the witness
who have had family members who have been lost.
We are doing our job today as the Oversight and
Investigation Subcommittee of the Commerce Committee, in that
we are the people that are the elected representative
overseeing the FDA. And when the FDA fails, it is our
responsibility.
I look forward to the testimony, not just from the family
members, but from the medical people and industry people.
Clearly there is an issue in terms of what has happened and,
obviously, it is our job to try to prevent that from every
happening to another family in America.
And I look forward to the witnesses.
Thank you, Mr. Chair.
Mr. Greenwood. The Chair thanks the gentleman and
recognizes the gentleman from Oregon, Mr. Walden.
Mr. Walden. Well, thank you very much, Mr. Chairman.
I want to thank you and your stuff for working with me over
the past several months to shine some light on the safety of
dietary supplements that contain ephedra.
If you had asked me a year ago about ephedra, I would have
had to admit that I was not very familiar with it. I suspect
that many of my constituents, probably Ernie and Pat Bechler,
would have said the same thing.
I would like to welcome the Bechlers and thank them for
traveling thousands of miles to be with us today. I make that
trip back and forth to Oregon every week, so I realize the
sacrifice they have had to make to be with us.
I also want to extend my sincere condolences to them and
the other members of their family on the loss of their son,
Steve.
A lot has changed in a year. On February 17, 2003 I opened
the sports section of the Medford Mail Tribune and read the
terrible news that Steve Bechler, a young man from Medford,
Oregon, my district, whose talent brought him all the way to
spring training camp of the Baltimore Orioles, had collapsed
during field drills and was being treated in a Florida
hospital. News broke later that day that Steve died as a result
of multiple organ failure.
The Broward County Medical Examiner indicated that the
dietary supplement Xenadrine RFA-1, similar to this, which
contains the herbal supplement ephedra might have contributed
to Steve's death.
Since learning about ephedra in such a disturbing way, I
was shocked to discover that anyone of any age can walk into a
store anywhere in our country and purchase dietary supplements
off the shelf that contain the same substance that played a
role in Steve Bechler's death, and that of others.
Nowhere on the label of these supplements is a little black
warning box or the statement that says may cause death. I am
particularly troubled that middle school and high school
athletes, teenagers, not only have access to a substance that
has been called into question and linked to so many serious
health complications, but daily are bombarded by advertisements
telling them how this is the miracle way, this is the easy way
to lose weight, this is the simple way to get strong; all the
other things that go with some of the advertising that some
courts have ruled to be misleading.
Unfortunately, the Food and Drug Administration must sit
and wait for tragedies to occur since dietary supplements such
as Xenadrine RFA-1 can be marketed and sold without FDA
approval. For such products FDA must prove the supplement is
unsafe and causes harm before it can be removed from the
market. The burden of proof to verify that the supplement is
hazardous rests with the FDA rather than with the supplement
manufacturer. Yet manufacturers of dietary supplements are not
required by law to provide reports of adverse events to the
FDA. Therefore, at best, FDA has a dull set of instruments to
work with including voluntary post-marketing reporting of
adverse events, data from poison control centers, reports and
inquiries from consumers and health care providers and
complaints from trade competitors to better understand the
safety of dietary supplements and to track potentially
dangerous supplements. I truly fear that this passive system
may be placing unsuspecting consumers at high risk.
For these reasons, my colleague from New York John Sweeney
and I introduced H.R. 1075, the Ephedra Public Protection Act
legislation that shifts the burden of proof from the FDA to the
dietary supplement manufacturer to demonstrate that products
containing ephedra are safe prior to such supplements entering
the marketplace. I am hopeful the full committee will consider
this legislation in the coming months.
Mr. Chairman, thank you again for your dedication to this
issue and to ensuring the safety of all consumers. I look
forward to the testimony of our witnesses, and I am optimistic
that this hearing and the one tomorrow will move us closer to
effectively addressing and mitigating the risk posed by dietary
supplements that contain ephedra.
Mr. Greenwood. The Chair thanks the gentleman, and thanks
him for his good work on this issue.
The gentlelady from Colorado, Ms. DeGette.
Ms. DeGette. Thank you, Mr. Chairman.
And before making my statement, I would like to recognize a
colleague from California, Ms. Davis, who is joining us not on
this committee, but who has been a leader both in the
California in the legislature and also here in the U.S.
Congress in attempts to regulate ephedra.
Mr. Greenwood. The Chair welcomes her participation.
Ms. DeGette. Thanks.
Today's hearing addresses a topic that I know concerns all
of us, which is the potential dangers of the dietary supplement
ephedra and the extent to which this is being marketed to
unsuspecting customers.
Ephedra is a potent plant product, both the herbal and
chemical formulations of this drug are precursors for
methamphetamine, a powerful stimulate that is infamous as a
drug of abuse. And as we have heard today, it is also billed as
a weight loss supplement. Often times people think because
something is herbal, it is not harmful. But as we are learning
so tragically, that is not true.
I am interested in learning more from the numerous critical
experts on our panels today, and I want to thank the Chairman
for calling those experts. I think they will be very helpful in
understanding the extent of this issue.
Also, we will explore the effects of the Dietary Supplement
Health Education Act, which was passed in 1994. And, frankly,
there are many, many questions about its efficacy that have
arise since then.
Some say that the law has allowed buyer beware to replace
safe and effective when used as directed. I am concerned that
consumers are not given enough understandable information under
this law. Some of the witnesses on today's panel believe only a
physician can make an informed decision on the use of ephedra.
Other witnesses will argue the opposite. This is an important
debate and I look forward to hearing all perspectives on it,
with the bottom line being it is our job as Members of Congress
to protect our constituents and the unsuspecting public.
Ephedrine and caffeine combinations are illegal when sold
as a drug, for example, but not when packaged as a supplement.
I am hoping to hear more testimony today on the soundness of
that policy.
In addition to the questions about the science that is
informing the discussion of ephedra and the legislation that
regulates it, I am also concerned that magazine and Internet
advertising is purposely aimed at the gullible, like young
people who have heard so much about hoping to improve their
athletic performance or overweight individual hoping that a
pill will work better than their last diet.
Tomorrow we will hear testimony from the FDA and the FTC.
Their insight and assistance is invaluable, but frankly we do
not have much more time to sit around waiting for something to
happen to resolve the current regulatory confusion.
I believe the committee has a responsibility to listen and
consider the lessons of this 2 day hearing, and I look forward
to hearing all of our witness.
And, again, I would like to thank the Bechlers and Mr.
Riggins for coming today, Mr. Chairman.
Mr. Greenwood. The Chair thanks the gentlelady who yields
back the balance of her time.
And recognizes the gentleman from New Hampshire, Mr. Bass,
for his opening statement.
Mr. Bass. Thank you very much, Mr. Chairman. I appreciate
your holding this hearing. I will be very brief. Obviously,
this is a very disturbing issue, it has ramifications not only
for an analysis of the regulatory structure surrounding the
control and use of dietary supplements, but also the types of
recommendations that we might be able to make so that this
committee can take some action quickly to protect Americans,
American consumers in instances where they may unknowingly be
putting their lives in danger.
I think that this is a hearing that is way overdue. I am
glad the Chairman put it together, and I look forward to
hearing the testimony of the witnesses.
Mr. Greenwood. The Chair thanks the gentleman and
recognizes the gentlelady from Chicago, Ms. Schakowsky for an
opening statement.
Ms. Schakowsky. Thank you, Mr. Chairman. I am glad that we
are going to have an opportunity over the next 2 days to hear
about the harmful effects of ephedra or how it has impacted the
American public, and what can be done to prevent future
injuries and death.
I hope we will act quickly making the necessary changes to
keep this often harmful product out of the hands who face such
enormous risks from it.
I thank our witnesses for coming today to share with us how
ephedra had effected their lives. It's terrible that lives,
often very young lives, have been lost because an industry has
been allowed to sell and market a product that is both
unregulated and known to have potentially lethal consequences.
Of course, I particularly want to thank Mr. Riggins from my
home State of Illinois, and the Bechlers who have suffered a
terrible, terrible tragedy and now are committed to educating
the public about the grave dangers that ephedra poses. And I
thank you so very much for doing that.
Those of us in Congress and in the public need to hear your
stories. We also need to keep in mind that you're representing
countless numbers of people who have also been tragically
affected by dietary supplements. The bottom line is when used
as a dietary supplement, ephedra does more harm than good and
it should be removed from the market.
On May 25, 2003 Illinois Governor Rod Blagojevich, a former
member of this body, took the bold step of banning the sale of
ephedra throughout Illinois. Illinois is currently the only
State to ban the sale of this dietary supplement. I support
that ban and believe now that we need a national solution. As
long as ephedra sits on convenient store shelves in every other
State, consumers will continue to assume the product is safe
and does not pose a real risk. Dieters will continue to use it
lose weight, athletes will use it to improve their game and
truck drivers and students alike will use it to stay awake.
Unfortunately, some of them will die from using ephedra as
well.
Supplements are not held to the same standard as
prescriptions and over-the-counter drugs. These manufacturers
do not have to prove that their products are safe or effective.
The lack of regulation means that consumers cannot be sure how
much ephedra these supplements accurately contain. We know
concentration can vary from dose to dose, or whether they
contain other compounds with possible health effects.
What we know about ephedra is bad enough, but there is also
much about ephedra we do not know. We do not know how many
people have had their lives ended or their health ruined by
ephedra. We cannot be sure what ingredients are contained in
the pills, the amounts used or if the ingredients are
consistent throughout product. We do not know how the
supplements are products. They can and have been manufactured
in bathtubs, basements and garages. The lack of transparency
afforded to the supplement industry is unacceptable. Consumers
should have the ability to make informed decisions about what
they choose to put in their bodies. We owe it to the victims
and their families to take this supplement off the shelves
before anymore unsuspecting consumers, before anymore of our
children fall victim to the harmful effects of ephedra and the
predatory marketing of this industry.
Thank you, Mr. Chairman.
Mr. Greenwood. The Chair thanks the gentlelady and
recognizes the gentleman from California, Mr. Waxman for his
opening statement.
Mr. Waxman. Thank you very much, Mr. Chairman, for holding
this hearing. It is important that we examine the question of
ephedra and the harm it is doing to Americans who are taking
this medication without any understanding that it could be
doing them an enormous amount of harm. And I thank the
witnesses for being here today.
In 1994 Congress passed a law called the Dietary Supplement
Health and Education Act, or DSHEA, and the hope was that this
law would ensure that consumers had access to dietary
supplements that could improve health, such as calcium and
folic acid. The law largely deregulated the business of dietary
supplements. And over the years it has become clear that one
unintended consequence of that law has been that consumers are
inadequately protected from potentially dangerous supplements.
The subject of today's hearing, ephedra, is the best example,
but not the only one, of how this law fails consumers.
Evidence has mounted about the harm from ephedra. Medical
organizations have been weighing in from the AMA, the American
Heart Association, the American Academy of Family Physicians.
They have called on the FDA to prohibit the sale of ephedra as
a dietary supplement because of the unreasonable risk
associated with these products. Now the FDA says, however, that
they think the law ties their hands. I do not agree with them
in their interpretation of the law. I think there is enough
harm that has been shown from ephedra for them to act. But what
we are left with is a product for which there is no evidence of
long term positive health outcomes and increasing evidence of
various serious side effects. And FDA has not taken the product
off the market.
It is time to change this law so that a body count does not
have to be amassed before FDA can take a dangerous product off
the market.
And I want to pay tribute to my colleague Representative
Susan Davis. She has been a leader in this issue in the
California legislature and here now that she is in Washington.
She and I are planning to introduce legislation that will give
FDA greater access to information to understand that the
product does post a health risk and that will let FDA protect
consumers from unsafe products.
It is all too possible that there is another ephedra
already on store shelves, a product that can cause serious
injury that has no demonstrable long term health benefit. We
must not let the ephedra story repeat itself.
I am pleased that we are holding this hearing. I look
forward to the testimony of the witnesses. And I hope it will
help us legislate in the way that we need to protect the
American people.
Mr. Greenwood. The Chair thanks the gentleman.
And now with unanimous consent permit all of the members of
the subcommittee to have their opening statements entered into
the record, as well as a written statement from the American
College of Obstetricians and Gynecologists.
We are now going to recess. I am hoping that we can be back
here close to 11. I cannot promise that because funny things
happen when we get on the floor of the House of
Representatives. But we will recess until the end of this
series of votes.
[Brief recess.]
Mr. Greenwood. The committee will come to order.
And the Chair thanks all of our witnesses, again, and all
those others in attendance for bearing with us.
And the Chair recognizes the gentleman from Illinois, Mr.
Rush for his opening statement.
Mr. Rush. Thank you, Mr. Chairman.
Mr. Chairman, I am pleased that we are holding this hearing
today so that we can begin to come to some clarity on the role
that the industry played when it may have mischaracterized the
ill-effects of the dietary supplements that contain ephedra.
Ephedra based products have grown in popularity in the last
decade, especially with athletes and those who are trying to
lose weight quickly.
Twelve to 17 million Americans consume more than 3 billion
serving of ephedra products every year. This is precisely why
we must investigate this issue. There are too many consumers
who could be adversely effected by this herb.
We have all seen the reports of deaths that have been
associated with products that contain ephedra. We know that the
Orioles pitcher Steve Bechler collapsed on a practice field
while attending spring training. His teammates reported that
they saw Bechler take a dietary supplement that contained
ephedra. You may hear reports that the links between his death
and the supplement are not conclusive. So if the reports are
not conclusive, then there needs to be an investigation.
Mr. Chairman, we should let the facts speak for themselves.
If there is nothing wrong with these products, then the
investigation should go smoothly. However, I have a strong feel
that this investigation will not go smoothly because the
evidence they may demonstrate that these products can be linked
to serious side effects, including seizure, stroke and heart
attack and most critically, death.
The American Medical Association and the American Heart
Associations have both called for a ban on ephedra based
products, and my own State of Illinois has banned the sale of
ephedra. Our military has also weighed in. They have ordered
that these products be removed from all stores on military
bases worldwide.
It is clear that the panelists who represent the
manufacturers of ephedra based products have a lot of evidence
to overcome.
Mr. Chairman, I want to thank you for your leadership on
this particular issue, and I want to commend you for this
outstanding hearing.
And I yield back the balance of my time.
Mr. Greenwood. Are there any other members who wish to make
opening statements? That being the case, the Chair calls the
first panel. Our witnesses are: Mr. and Mrs. Ernie Bechler of
San Diego, California; and from Medford Oregon Mr. Kevin
Riggins of the Sean Riggins Foundation for Substance-Free
Schools; Mr. Michael Vasquez of the law offices of Fred G.
Cohen; Dr. Steven Hymsfield, M.D., Deputy Director of Obesity
Research Center of St. Luke's Roosevelt Hospital in New York;
Dr. Raymond Woosley, M.D., Ph.D., Vice President for Health
Sciences, Arizona Health Sciences Center; Dr. Douglas Zipes,
M.D., Distinguished Professor of Medicine, Pharmacology and
Toxicology, Director of the Division of Cardiology at Krannert
Institute of Cardiology, which is in Indiana; Dr. Cynthia
Culmo, a former official with the Texas Department of Health;
Dr. Marcia Crosse, Acting Director, Health Care-Public Health
and Science Issues at the U.S. General Accounting Office.
We welcome all of our witnesses. I believe you have been
informed that pursuant to the rules of this committee, we take
our testimony during investigative hearings under oath. And so
I need to ask if any of you object to giving your testimony
under oath?
Seeing no such objection, I would inform you that also
pursuant to our rules, your entitled to be represented by
counsel. Do any of you wish to be represented by counsel?
Mr. and Mrs. Bechler, you do. And if you would identify
your counsel to your right, Mr. Bechler? And if you would
identify yourself, sir, using the microphone and making sure it
is on.
Mr. France. Jim France on behalf of Mr. and Mrs. Bechler.
Mr. Greenwood. Okay. I would then ask the witnesses to
stand and raise your right hands, please.
[Witnesses sworn.]
Mr. Greenwood. Okay. You are all under oath.
And I believe we are going to begin with the Bechlers.
Again, welcome. Thank you for being with us this morning, and
you are recognized to give your testimony. And you will need to
use--which one is going to start testifying. Mrs. Bechler,
Mom's going to do that. Okay.
TESTIMONY OF PAT BECHLER; KEVIN RIGGINS, SEAN RIGGINS
FOUNDATION FOR SUBSTANCE-FREE SCHOOLS; MICHAEL VASQUEZ, LAW
OFFICES OF FRED G. COHEN; STEVEN B. HYMSFIELD, DEPUTY DIRECTOR
OF OBESITY RESEARCH CENTER, ST. LUKE'S ROOSEVELT HOSPITAL;
RAYMOND WOOSLEY, VICE PRESIDENT FOR HEALTH SCIENCES, ARIZONA
HEALTH SCIENCES CENTER; DOUGLAS P. ZIPES, DISTINGUISHED
PROFESSOR OF MEDICINE, PHARMACOLOGY AND TOXICOLOGY, DIRECTOR,
DIVISION OF CARDIOLOGY, KRANNERT INSTITUTE OF CARDIOLOGY;
CYNTHIA CULMO, FORMER OFFICIAL, TEXAS DEPARTMENT OF HEALTH; AND
MARCIA CROSSE, ACTING DIRECTOR, HEALTH CARE-PUBLIC HEALTH AND
SCIENCE ISSUES, U.S. GENERAL ACCOUNTING OFFICE
Ms. Bechler. On February 16, 2003 we got a call from the
Baltimore Orioles that Steve had collapsed on the field. He was
23 years old, and he was married for 2 months, had a child on
the way, which was born April 22. Now he has a daughter that
will never know how great his daddy was, and she will never be
with him.
He started baseball at 7 and wanted to work at this Myles
Field, which was a big stadium in our town, home town. He said,
``Mom, 1 day I am going to play here,'' and he did. He played
Little League, Babe Ruth and was always an All Star. And then
he hit the big time and he played big league, and that was
shortly lived and was a dream cut short.
I do not know how long Steve was taking this exactly. But
the Cytodyne, they have received dozens of complaints from the
consumers, some my son's age, complaints of strokes and heart
attacks. They ignored these complaints. They knew about all the
complaints that were compiled by the FDA. Hundreds of deaths,
hundreds of serious injuries, strokes.
They lied to our son about their product being safe. They
knew there were questions about its safety. They sponsored
clinical studies with the results that it showed problems and
questions about Xenadrine. Whether it worried or whether it was
safe, they manipulated the results in the study they advertised
in claims of its safety. It was an herbal vitamin, a life herb.
They paid researchers and in the companies to distort the
facts of whether they were really safe or not. They seduced
advertisers and son to take it with the flukes of promises of
hopes of dropping massive weight or muscle mass fast and safe.
They lied about the testimonies that stated extreme weight
loss, which he was 10 pounds overweight.
The testimony advertised that Cytodyne was a strong and--
they took bodies building type people and paid them to fatten
and given their multiple products that led my son to believe
that he could achieve the huge weight loss and fat loss in a
few short weeks.
They took our pride and joy from us, and his wife and his
baby. And they took our baby from our lives. Steve was our
lives. And his daughter will never know him.
How many Steve Bechlers or Sean Riggins have to die to
prove that these are not safe.
They paid--we need to get this off the market. We have got
to help other children. They want the extra boost that think
they can make them better athletes, and it does not. All it
does is encourage kids to take and make it easy for them to
take it.
Please, let us get this out of the hands of children.
Thank you.
Mr. Greenwood. Thank you, Ms. Bechler. And we know how
proud you are of Steve, and I think at this moment he is very
proud of you.
Mr. Bechler, did you want to add anything?
Mr. Bechler. No, sir.
Mr. Greenwood. Okay. Well, perhaps you might to respond to
some questions later on.
Mr. Riggins, thank you also for being here on behalf of
your son and you are recognized.
TESTIMONY OF KEVIN RIGGINS
Mr. Riggins. Thank you, Mr. Chairman.
I am here today to represent several people; myself, my
wife and a lot of people that have lost children to a dietary
supplement called ephedra. I am happy and proud to say that I
am also representing the American Heart Association, Midwest
affiliate. They have been with us for several months now in our
efforts in Illinois, and their President, Dr. Robert Banow, has
stated what you all have stated to us; that ephedra is
dangerous, it kills and it needs to be off the market.
My son Sean was 16 years old. He's a phenomenal athlete,
football player, wrestler, martial artist and yet he and
several of his friends on the football team decided that they
could get an energy boost to enhance their performance by
taking these products that contain ephedra. And on September 3
last year Sean had a heart attack and died in our home. The
cause of the heart attack, ephedra.
I do not have to tell you about the dangers of this
product. You know that it is a stimulate, you know that it
effects the cardiovascular system and the central nervous
system.
I do not have to tell you about the Dietary Supplement
Health and Education Act. You told us about it. You already
know. It allows these companies to put these products out with
virtually no regulation and no oversight. The majority of these
companies, in my opinion and the opinion of anyone who has gone
through what we have gone through, these companies are
illegitimate companies. They are no more than drug pushers
because they are marketing a deadly substance and they do not
care.
Seventeen and a half billion dollars, that is how much
dietary supplement companies made last year as a whole. The
claim is that ephedra is only 1 percent of that. I personally
do not believe that. I think it is more toward 10 percent or
better.
We know it is deadly, we know it kills. In my home State of
Illinois our legislators realized that as well, and we passed
the Ephedra Prohibition Act unanimously through both Houses: 56
to nothing in the Senate, 117 to nothing in the House. And we
had previously spoken to the Governor and he promised that he
would sign it when they passed it through the Houses. It went
into effect in May, and Illinois became the first State to ban
the sale of ephedra products.
And today I come before you and ask you as our Federal
legislators to do the same thing. Because we do not know how
many people have died. We do not know how many people out there
have lost children, such as the Bechlers and ourselves.
Ephedra has been in the dark for years and years and it is
this type of forum that we need to bring it out into the light,
let people see it for what it really is so that they can be
aware that this is not the miracle pill. This is not a magic
elixir that will help them lose weight and enhance their
performance. It is poison. It killed my son. It killed the
Bechler's son. And how many other children do we have to lose
before we decide that this is poison and remove it from the
market?
Several weeks ago we all celebrated Father's Day. A few
weeks before that, Mother's Day. For our family and for several
other families--excuse me, a 100 or so other families. Those
holidays will never ever be the same again. There is no
celebration for us. And I ask you to make sure that no other
family has to deal with what the Riggins and the Bechlers and
God knows how many other families have had to deal with.
Thank you.
[The prepared statement of Kevin Riggins follows:]
Prepared Statement of Kevin S. Riggins, Founder and Director, The Sean
Riggins Foundation for Substance Free Schools
Honorable Representatives, my name is Kevin Riggins. My wife and I
live in Lincoln, Illinois. On September 3, 2002, we lived every
parent's worst nightmare when our only child, Sean Riggins, died from a
heart attack. Sean was a gifted athlete, excelling in football,
wrestling and Tae Kwon Do. He had no congenital heart problems and he
was in the peak of health. He had just passed his athletic physical
examination in order to start football. As we were to find out later,
the heart attack had been brought on by the usage of a dietary
supplement called ephedra. My wife and I were not familiar with this
particular substance; in fact, we had no idea that Sean had been taking
it. As we were to discover later through investigation and
conversations with Sean's teammates, numerous teenagers, including
athletes, and young people trying to lose weight, were using these
products. The teens could buy these pills at the corner gas stations
with pocket change. The little packages, which promote weight loss,
performance and energy enhancement, were being sold right next to the
Twinkies and candy bars, in fact, the use of these products was so
casual, none of the kids believed that they were taking a drug. With
the marketing style and the ease in which they could be obtained, the
teens thought nothing of it. ``They sell these things in the stores,
they are not illegal, so they must be okay''. This was a quote from one
of my sons friends. As it turns out, the vast majority of the American
public believes this as well. As Americans, we believe that our
regulatory organizations, in this case the F.D.A., are protecting our
interests by not allowing dangerous products to be sold, especially in
regards to what we put in our bodies. In the case of ephedra, we could
not be more wrong. As you well know, The Dietary Supplement Health and
Education Act of 1994, allows dietary supplement companies to operate
with virtually no federal oversight. A company does not need a license
to produce these products nor are there any no pre-market approval
requirements. There have never been any Good Manufacturing Practice
guidelines developed for these companies and they have a voluntary
adverse event reporting system. When a supplement poses a risk of
serious injury or death, the burden of proof falls to the Government to
prove cause and effect. This is the exact opposite of the rules and
regulations set up for drug companies. It is no surprise that the
supplement industry wants no changes to be effected in the federal
requirements. This is an 18 billion dollar per year industry which does
not seem to care that it is producing products that kill. According to
the FDA and several medical organizations including the American Heart
Association and the American Medical association, ephedra has killed at
least 117 persons and accounts for almost 20, 000 serious adverse
events. Please bear in mind that these are reported adverse events. The
supplement companies do not divulge these facts readily or willingly,
therefore, we truly do not know how many citizens have been affected by
these products. The Poison Control Center recently published a study
showing that ephedra is the most dangerous dietary supplement on the
market. They used adverse event reports, from the industry, to come to
this conclusion. The Ephedra Education Council immediately labeled the
study as ``garbage''. They claimed that utilizing adverse event reports
was not a valid way of conducting studies such as this. Conversely,
they have touted the Rand Corporations study of ephedra's safety and
efficacy as bearing out what they have said all along; that ephedra is
safe if used as directed. This, of course, is not true. The Rand study
was inconclusive. Ironically, the Rand Corporation utilized the
available adverse event reports in conducting the study. It seems that
the industry only agrees with a study if it agrees with there agenda.
The industry claims that there are 55 studies that show the safety and
efficacy of ephedra. They bring out physicians, pathologists and other
scientists to bolster their claims that ephedra is safe and effective.
What they do not say, is that the large portion of these studies are
commissioned, financed, supervised and published by the supplement
companies, many times using their own people to conduct the studies.
The ephedra industry has, unfortunately, become a collection of rogue
corporations that care for nothing but the bottom line. Look at the
criminal records of some of the CEO's of these companies, and you will
see a pattern of criminal activities and corruption. These are the
facts, not innuendo, not speculation. Ephedra is a dangerous drug that
is being sold as an innocuous weight loss aid and stimulant. Here in
Illinois, our general assembly recognized that fact. In November, 2002,
I began a campaign to educate our state lawmakers on the dangers of
ephedra, and to encourage them to take action. On May 28, 2003, those
efforts came to fruition, when after a unanimous yea vote in both
house, Gov. Rod Blagojevich signed the Ephedra Prohibition Act making
Illinois the first state in the nation to ban ephedra products. Now
there are several other states taking up the initiative as well,
however, I believe that you, our national leaders, need to take up the
cause at the federal level and protect our citizens from this dangerous
substance. Labeling requirements are not enough, as we have seen
studies that show dosage variations of up to 154% between pills in the
same bottle. This makes the dosage requirements listed on the label of
no use. Age limitations are not enough; less than ten percent of the
adverse events associated with ephedra were attributed to persons under
the age of eighteen. The only logical course of action is to remove
ephedra from the market completely, and impose stricter regulations on
dietary supplement companies to ensure the purity and safety of their
products. This is not an issue of trying to stifle business or over-
regulating legitimate companies, this is an issue of protecting the
American consumers and ensuring the public health. No other family
should have to suffer the loss of a child, be that child 16 or 46. My
wife and I will never get over the loss of our son, but we can try to
make sure that it does not happen again, and to do that, I need your
help. Look past the industry rhetoric and all of the misdirection and
obfuscation. Help us get ephedra off of the market. The industry will
survive and so will our American brothers and sisters. Thank you.
Mr. Greenwood. We thank you, Mr. Riggins. We thank you very
much.
Our next witness is Mr. Michael Vasquez, and he has
patiently waited remotely in San Diego. Can you hear us, Mr.
Vasquez?
Mr. Vasquez. Yes, sir.
Mr. Greenwood. Okay. And I see that you are represented by
attorney?
Mr. Vasquez. Yes, sir.
Mr. Greenwood. And Mr. Attorney, could you identify
yourself, please.
Mr. Cohen. Yes. My name is Fred Cohen.
Mr. Greenwood. Okay. And we thank you.
Mr. Vasquez, we appreciate your patience and you are now
recognized to give your testimony.
TESTIMONY OF MICHAEL VASQUEZ
Mr. Vasquez. My name is Michael Vasquez. I am a California
licensed registered nurse and public health nurse.
I was employed at Metabolife from August 1999 to November
1999. I had a work related injury at Metabolife in which the
case is still pending. I worked as a health information call
center staff for Metabolife's Health Information line.
At the time of my employment, I was one of 10 licensed
registered nurses that stock the health line. My immediate
supervisor was Mr. Daniel Rodriguez. Mr. Dan Rodriguez provided
me a 2 day orientation and training for myself and also for
another new employee named Linda Rodriguez. We were taught how
to answer phones and trained how to take--and document comment,
complaints from consumers that were using Metabolife's 356 and
other products.
As part of my job description I took a variety of consumer
calls in regards to positive comments about Metabolife's 356
such as it's working great for them. Other calls were callers
who were frustrated that the product was not working for them.
And at times took calls from consumers that were experiencing
side effects or as the company would classify it as alleged
adverse events.
Complaints from taking the products would vary from
abdominal cramps to potential signs in terms of stroke, heart
attack, seizures.
I averaged taking 7 to 10 calls a day that were strictly
related to alleged adverse effects. Other nurses had a variety
of a number of calls regarding alleged adverse events that were
reported on any given day.
All the calls were documented and entered into a computer
data base in which consumers, if they cooperated, gave personal
information such as their name, age, gender, contact phone
number and general health status, medical condition if any,
description of medications if they were taking any, amount of
Metabolife 356 being taken, their eating habits. General
complaints of the consumers and what recommendations we nurses
were giving out to them.
We received calls from emergency room doctors that wanted
to know what ingredients were in the product. And they would
request us to fax them an ingredient list because a patient of
theirs had either a heart attack, seizures or sometimes death.
We had weekly staff meetings that were attended by Mr.
Daniel Rodriguez, who was my immediate supervisor, the medical
director Dr. Randy Smith and the other nurses and the chemist.
We would talk about the different callers and other health
related issues directly related to Metabolife 356 being used.
During our lunch breaks the nurses would compare notes and
discuss concerns about the product we received in regards to
the different alleged adverse events reported, such as stroke,
seizure, heart attack and other severe condition which made us
wonder whether the product was safe to take or whether the
callers were really telling the truth or not. We nurses had
discussions on the actual studies the company claimed to have
done and wonder about the validity of it.
At the time I was employed at Metabolife I created a daily,
weekly and monthly log which all the nurses had to complete.
The logs contained information about how many calls were being
answered, emails that were being answered, literature that was
sent out and alleged adverse events that were being reported.
All of these were being entered into a computer data base.
For consumers that called the health line and reported
having moderate to severe alleged adverse events, we were
trained and taught to get as much information possible. From
then on we had to forward this information to Daniel Rodriguez,
which was my supervisor, and then he would take care of follow
up on each of those cases.
I am here today on my free will knowing the ramifications
that questions may be asked why am I testifying. And after
hearing Mr. Bechler and Mrs. Bechler and Mr. Riggins and
probably other people out there that are taking ephedra related
products, I feel for them.
As a nurse you are supposed to help people and do no harm.
But as a human being knowing that product that can and probably
is dangerous, I cannot in good conscience condone the use of
it.
Thank you, sir.
Mr. Greenwood. Thank you, Mr. Vasquez. We thank you very
much for coming forward and for joining us as you have today.
Mr. Heymsfield, you are recognized for your statement, sir.
TESTIMONY OF STEVEN B. HEYMSFIELD
Mr. Heymsfield. Thank you.
Mr. Greenwood. You need to push the button to turn the
microphone on.
Mr. Heymsfield. Thank you.
Following release of the extensive Rand report on March 26
of this year, the Journal of the American Medical Association
recommended to the public that the risks of adverse health
effects from ephedra products far outweigh the possible minimal
benefits. The linkages between ephedra containing products and
serious side effects, even death, are now well established.
When ingested alone or together with natural sources of
caffeine, ephedra alkaloids are potent stimulates that trigger
an array of body reactions, some with devastating effects in
predisposed individuals.
Almost 100 years ago Samuel Hopkins Adams in a series of
articles ``The Great American Fraud'' decried that gullible
America will swallow an appalling amount of opiates and
narcotics and a wide assortment of other potent drugs. Hopkins
was reacting to the ground swell of contempt for patent
medicines that were long on promise, but that failed to
disclose the risk of toxic contents. Within a year, on June 30,
1906, President Theodore Roosevelt enacted the Food and Drug
Act.
Almost two-thirds of Americans are now overweight or obese
and many are not only gullible, as in Adams' day, but search in
desperation for a treatment. Ephedra products sold in the
context of dietary supplements rather than drugs as
traditionally regulated by the FDA are viewed by many unwitting
consumers as yet one more chance to satisfy their passion for
thinness.
In early 1997 my colleagues and I at the New York Obesity
Research Center carried out one of the first U.S. controlled
clinical trials of mahuang, the botanical source of ephedra
alkaloids. I was struck in this pilot study of a commercial
product by the stimulant effects observed in ephedra treated
patients compared to controls. Heart palpitations, agitation
and insomnia, all of which are recognized actions of
sympathomimetic agents, as this family of drugs is referred to.
Within the next year I participated with others at our
center as a study designer and only physician member in a
larger and more rigorous controlled clinical trial of a potent
product that contained not only ephedra, but a natural source
of the ephedra amplifying factor caffeine. My earlier
observations and suppositions were confirmed and extended.
Stimulate side effects were present more often in the product
treated group and led some patients to drop out or to be
dropped from the study prematurely.
The subjects in this study are not representative of the
general public because they were medically screened and
monitored. Patients with underlying conditions that might pose
risk during treatment were excluded from the study.
My original project, formulated now over 6 years ago, has
proven to be accurate. When taken by hundreds of thousands of
consumers the stimulate effects of ephedra caffeine in
combination leads predictably to some pathmathomimetic adverse
side effects in some individuals, serious injuries in others
and a small but critically important group death. This leads me
to pose the question how could this vicious experiment be
carried out on Americans?
I pose here, based on my own experience and opinions, three
means by which consumers and regulations were shielded from the
growing body of information linking ephedra products with risk.
The first, as we've already heard, are some major
manufacturers of ephedra products withheld information on
reported adverse events while at the same time touting product
safety. I as a physician had clinical research on less than 200
patients, yet I had documented the typical adverse event
profile associated when ephedra ingested alone or in
combination with caffeine. I surmised in the late 1990's that
manufacturers must be withholding adverse events information as
their reported absence of side effect was discordant with my
own research data.
Radio ads and some product labels during this time period
hailed the ephedra caffeine mixture as independently laboratory
tested or clinical tested for safety. Some provided misleading
scientific references in their product literature or websites.
Second, when those few investigators with experience in the
areas spoke out, they were challenged by some manufacturers
with lawsuits. When my colleague, Dr. George Blackburn at
Harvard publicly spoke of risks, he was unsuccessfully sued,
but a bitter, painful and costly process nevertheless.
When I later publicly expressed my own safety concerns,
attempts were made by a manufacturer to pressure me into
silence from every direction; through the university, the
hospital, by placing false but nevertheless damaging
advertisements in major newspapers and by positioning me as
having competitive industry ties.
Third, my professional view having carried out peer review
research in the area for over 30 years, is that several of the
widely cited ephedra studies are technically flawed and biased.
They inappropriately highlight product effectiveness while at
the same time minimize risks.
Through my experience with the ephedra products I have
served as an expert witness in a number of lawsuits against
manufacturers. This has provided me with the unique opportunity
to review confidential documents, some of which are now
publicly available, that reveal either serious errors or
intentional fabrication that inappropriately provide an overly
positive impression of some ephedra products.
Unsavory manufacturers learned quickly that a supportive
published paper, whatever the quality, helps to gain
credibility while neutralizing even the most ardent academic or
governmental skeptic.
The ephedra products are banned in many parts of the world,
and a similar trend is now taking place in some parts of the
United States. Samuel Hopkins Adams was ultimately sued by
manufacturers because of the articles he wrote, and I'll say
unsuccessfully, following his milestone report. But this had
little effect on the momentum shortly thereafter to create the
FDA.
The time is right for you as legislators to again protect
the American public by taking a strong and visionary position
on dangerous dietary supplements for weight control.
Thank you.
[The prepared statement of Steven B. Heymsfield follows:]
Prepared Statement of Steven B. Heymsfield, Professor of Medicine,
Columbia University, College of Physicians and Surgeons, Deputy
Director, New York Obesity Research Center, St. Luke's-Roosevelt
Hospital Center
WHAT IS A DIETARY SUPPLEMENT?
There exist three categories of chemical agents available for
weight loss treatment. The first two categories are prescription drugs
and over-the-counter drugs. The Federal Drug Administration (FDA)
regulates these agents under carefully controlled guidelines for safety
and efficacy. The process is particularly rigorous for weight loss
agents as over 60% of Americans are now overweight or obese, excess
adiposity effects increasing numbers of vulnerable children and
adolescents, and drug treatments for weight loss have a notorious past
history of both abuse and damaging physical and behavioral effects
extending back over a century. Prescription and over-the-counter drugs
are rigorously tested using modern scientific guidelines and procedures
to ensure public and individual safety.
In 1994 a third category of agents emerged referred to as ``dietary
supplements''. The term dietary supplements is a legal one as stated by
the FDA:
``FDA regulates dietary supplements under a different set of
regulations than those covering ``conventional'' foods and drug
products (prescription and Over-the-Counter). Under the Dietary
Supplement Health and Education Act of 1994 (DSHEA), the
dietary supplement manufacturer is responsible for ensuring
that a dietary supplement is safe before it is marketed. FDA is
responsible for taking action against any unsafe dietary
supplement product after it reaches the market. Generally,
manufacturers do not need to register with FDA nor get FDA
approval before producing or selling dietary supplements.
Manufacturers must make sure that product label information is
truthful and not misleading.
FDA's post-marketing responsibilities include monitoring
safety, e.g. voluntary dietary supplement adverse event
reporting, and product information, such as labeling, claims,
package inserts, and accompanying literature. The Federal Trade
Commission regulates dietary supplement advertising.''
Dietary supplements for weight loss, unlike traditional drugs,
often include multiple ingredients; the word ``supplement'' is
misleading as most agents do not ``add'' to the natural body stores of
the compound nor does the agent usually prevent or correct a deficiency
state.
what are some of the most popular weight loss products?
Weight loss can be produced when ingestion or absorption of
calories or energy is less than energy released from the body as heat.
Dietary supplements purportedly produce weight loss by suppressing
appetite, reducing absorption, increasing heat production or metabolic
rate, and changing the proportion of calories stored as fat and muscle.
The ephedra alkaloids, discussed below, are thought to suppress
appetite and increase energy expenditure, by two different mechanisms.
These actions are enhanced with herbal sources of caffeine and aspirin
are added to the ephedra-containing product.
Some agents are reported to reduce fat and thus energy absorption
from the gastrointestinal tract, notably chitosan. Chitin is a
substance derived from the exoskeletons (shells) of arthropods such as
crabs, shrimps, and lobster.
Some dietary supplements reportedly increase the storage of
ingested nutrient as muscle and decrease the proportion stored as fat.
These include the herbal ingredient garcinia cambogia and the widely
used group of compounds referred to as chromium picolinate and other
chromium salts.
My colleagues and I have reviewed these agents in a recent report
(1).
I would now like to focus some specific comments on dietary
supplements that include MaHuang as the main active ingredient. I
select MaHuang because consumers are exposed with these products to a
potentially dangerous family of ingredients, the ephedra alkaloids,
that not only produce weight loss but that may lead to strokes and
heart attacks with associated disability and death in selected
susceptible patients.
A key concern is that overweight and obese patients are
particularly vulnerable to taking purported dietary supplement weight
loss products because they are often desperate, want to lose weight
quickly, find physician evaluations time consuming and costly, and have
often tried dietary and medical therapies of limited current
effectiveness.
By avoiding medical oversight, overweight and obese consumers
purchasing dietary supplements make the false assumption that dietary
supplements and herbal preparations are inordinately safe and may pose
no or very little risk. Moreover, many overweight and obese consumers
harbor ``silent'' diseases such as high blood pressure and narrowing of
the coronary arteries that manifest under the biological conditions
produced with ingestion of the purported weight loss agent. The
overweight consumer of dietary supplements who harbors a potentially
silent killer may be bypassing the critical medical oversight needed to
detect, prevent, or treat a serious underlying medical condition. A
large percentage of overweight and obese Americans have undiagnosed and
untreated medical conditions (2).
WHAT IS MAHUANG?
MaHuang, now defined as a dietary supplement in the US, is
primarily used today as an ingredient in herbal weight loss products
and acts to lower appetite and potentially increases energy expenditure
through stimulant mechanisms (3-12).
MaHuang is the Chinese name of Ephedra sinica, an acrid tasting
stimulant herb (1). Other Ephedra species include Ephedra equisentina
and Ephedra intermedia.
WHAT ARE THE ACTIVE INGREDIENTS IN MAHUANG?
The ephedra alkaloids represent a family of compounds that vary in
proportion depending on plant species, harvest season, weather
conditions, geographic location, and other factors. The ephedra content
of dietary may vary substantially from label claims (13).
The ephedra alkaloids include the major component, up to 90%, (-)-
ephedrine, up to 30% pseudoephedrine, and lesser amounts of (+/-)-
norephedrine or phenylpropanolamine, and (+)-norpseudoephedrine or
cathine. The +/- refers to the three dimensional positioning of atoms
within the molecule and this feature of a molecule may influence its
biological activity.
Ephedrine, an ephedra extract, was synthesized in 1927 and is also
widely used today in weight loss and other pharmaceutical preparations,
particularly in Europe. Although studies are limited, the
pharmacokinetics of synthetic and botanical forms of ephedrine appear
similar (14; Appendix I); some questions on drug disposition remain and
more studies are needed (15). Pharmacokinetic properties of a drug
describe its absorption, distribution, and elimination from the body.
The chemical structures of ephedrine and other ephedra alkaloids
are very similar to the hormones epinephrine or adrenaline and nor-
epinephrine. These are the ``flight and fight'' hormones that have many
important biological effects including increasing blood pressure,
respiration, heart rate, and arousal. Ephedra alkaloids are also very
similar in structure to the banned group of chemical compounds referred
to as amphetamines (Appendix II). Widely used five decades ago for
weight loss and other stimulant effects, amphetamines are addicting and
have many serious other side effects.
HOW DOES MAHUANG PRODUCE WEIGHT LOSS?
Ephedrine alkaloids appear to exert their main weight loss effects
by suppressing appetite and thus food intake via central
``sympathomimetic'' (beta-agonist) actions. Ephedrine alkaloids also
appear to have a small effect on increasing energy expenditure (16).
Taken collectively, the ephedra family of compounds promotes negative
energy balance and weight loss by lowering both energy intake and
increasing energy expenditure. Ephedrine and other Ephedra alkaloids
have variable stimulant effects (1,16).
Ephedrine and ephedra alkaloids alone have modest weight loss
effects and their efficacy appears to be enhanced by addition of
caffeine and aspirin either as the pharmaceutical grade ingredients or
as their natural counterparts such as Guarana and Willow-bark,
respectively (17-21).
Addition of caffeine (i.e., ``Guarana'') and aspirin (i.e., Willow-
bark) to MaHuang purportedly potentiates the actions of ephedrine.
Caffeine competitively antagonizes adenosine receptors and may be an
adrenaline antagonist; adenosine is a hormone produced by endothelial
cells that dilates blood vessels. Many commercial weight loss
preparations include varying proportions of these three components.
Caffeine has a small thermogenic (i.e., heat-producing) effect in
humans (16,17). Aspirin has actions that also potentiate ephedrine
actions.
IS MAHUANG EFFECTIVE AS A WEIGHT LOSS AGENT?
There are many studies that have examined the effectiveness of
ephedrine alone or in combination with other ingredients; fewer studies
examine the weight loss effects of ephedra alkaloids in combination
with other natural sources of caffeine and aspirin. The collective
studies strongly support the premise that ephedrine, particularly in
combination with caffeine and also aspirin, promote significant short-
term (3-6 months) weight loss when ingested as part of an intervention
program including dietary and lifestyle management. Long-term (>6
months) controlled trials with large and diverse subject populations
are lacking. The evidence for ephedra efficacy is summarized in the
recent Rand Report (Appendix III).
The efficacy of MaHuang, separate from that of chemically
synthesized ephedrine, is supported by fewer published abstracts and
papers, although conceptually, there is no reason to expect a ``large''
difference between ``natural'' ephedra and chemically-synthesized
ephedrine. As noted earlier, the pharmacokinetics of chemically
synthesized and botanical sources of ephedrine appear similar (Appendix
I).
A major limitation of reviewed research is that most studies
administered ephedrine or MaHuang in forms that mimic commercially
available preparations and thus: the efficacy of ephedrine as a sole
weight loss agent is not entirely clear and is questionable; the
efficacy of ephedrine with varying amounts of caffeine and aspirin is
difficult to ascertain as studies failed to include varying amounts of
these other agents independent of ephedrine or as separate experimental
limbs in controlled trials.
Ephedrine is used in association with caffeine and aspirin, or
their herbal equivalents guarana and willow bark, to produce the ``fat-
burning stack (18).'' The stack has some evidence to support its
efficacy and is used in Europe. The three compounds, when taken in the
following ratio, 200 mg caffeine/60mg epihedrine/300mg aspirin,
produces a significant thermogenic effect. Very limited published
information is available on the safety and efficacy of the ``stack'' or
related products.
A concern is that the concentration of ephedrine in the plant and
method of preparation vary widely among products (13). Product labels
may therefore not reflect actual ingredient content or bioavailability.
ARE EPHEDRA-CONTAINING PRODUCTS SAFE?
Why do we know that ephedra alkaloids may be unsafe in some
consumers? Scientists know that ephedra alkaloids, particular when used
in combination with potentiating agents that include caffeine and
aspirin, produce variable increases in blood pressure, heart rate,
cardiac output, and respiration (Table 1). These effects in susceptible
individuals can trigger heart attacks and strokes. These effects are
well summarized in JAMA's patient page attached in Appendix IV.
The molecular basis of the stimulant effect for the class of
compounds, ``sympathomimetic agents'', is well known. While the effects
of ephedra alkaloids alone or in combination are often small in
magnitude and transient, given the large and potentially medically
vulnerable obese population taking these agents we can predict that
some individuals will have a relatively large drug-induced biological
effect. Others may have only a small effect, but remain medically
vulnerable due to silent underlying heart or cerebrovascular diseases.
Many of the patients taking these agents do so in the complete absence
of medical supervision or evaluation. They may inadvertently take a
large dose due to product variation or consciously in the hope of
boosting their weight loss. Unsupervised, they may unduly exercise or
take excessive amounts of caffeinated beverages or aspirin. The
predictable result, given the millions of Americans taking these
products, is serious medical events including heart attacks and
strokes.
Given the well-recognized risks of this group of dietary
supplements and the appropriate lack of interest in the area by
pharmaceutical companies, there exist very few careful safety and
efficacy trials that meet the current standards set forth for
evaluation of pharmaceutical weight loss agents.
In the studies carried out by my colleagues and I using a
commercial weight loss product containing ephedra and caffeine as
active ingredients, some patients in the ``active'' treatment group
experienced untoward effects at ``usual'' doses such as palpitations,
blood pressure elevations, and other typical stimulant effects that led
to their discontinuation in the study (21). I have observed similar
effects in other unpublished ephedra studies carried out at our
institution. These effects are the well characterized sympathomimetic
effects that I mentioned earlier and that support our projection that
some medically unscreened patients with underlying disease may suffer
heart attacks and strokes following ingestion of this or similar
dietary supplements. This projection is supported by the study of
Haller and Benowitz (23)(Appendix V) and Bent et al (Appendix VI).
A concern regarding the well controlled clinical trials is that
subjects were appropriately medically screened prior to entry into the
trial so as to reduce the medical risks of those exposed. One such
trial was carried out at our institution (22) and only those subjects
deemed medically acceptable were entered into treatment. Rigorous
testing of blood pressure and heart rhythm was used to detect and
eliminate those subjects who may have suffered a serious adverse event
during the trial. The lack of serious injuries and side effects in
trials such as these cannot be interpreted as a safety endorsement as
the actual consumer population still includes the medically vulnerable
and unscreened individual who may harbor a potentially lethal silent
disease manifest by ingestion of ephedra alkaloids.
Specifically, concerns have been raised about the safety of
products containing MaHuang/ephedra. Several serious case-reports of
adverse effects and fatalities have appeared in the literature.
Strokes, myocardial infarction, and cardiac arrhythmias are reported in
association with ephedra ingestion. Benowitz and Haller (23; Appendix
VI) provided the FDA with an independent review of adverse events
related to ephedra alkaloid containing supplements. The authors
concluded that ephedra alkaloids may pose a health risk for selected
individuals. Some of the reported side effects in patients occurred
within the commonly used therapeutic ranges.
Ephedrine alone or combination with other ingredients may raise
heart rate and blood pressure (e.g., systolic BP increase 3-7 mmHg) in
some subjects (1-23), although the magnitude and length of time for
which these adverse effects remain evident is not well established.
Restlessness, headache, and insomnia have been reported by subjects
ingesting some commercial dietary supplements and with synthetic
ephedrine-caffeine combinations. Subjects with bleeding tendencies may
be at risk when taking aspirin-like compounds.
MaHuang taken alone or combination with other agents may place
certain subjects at risk of adverse and potentially fatal effects. More
long-term safety data, beyond six months, is needed, particularly in
selected populations such as the elderly.
Finally, there exists particularly vulnerable populations such as
pregnant or lactating women, the elderly, and subjects with eating
disorders in whom particular concern exists for their use of weight
loss dietary supplements.
SHOULD THE REGULATIONS FOR DIETARY SUPPLEMENTS BE CHANGED?
Although my review here has been brief and focused, we can envision
four groups of dietary supplement for weight loss: safe and
ineffective; effective but unsafe; ineffective and unsafe; effective
and safe. At present most of the available dietary supplements fall
into one of the first two categories.
Safe and ineffective: This group of products provides false hope to
the unwitting highly vulnerable overweight or obese consumer and may
delay their entry into an appropriate medical or nutritional care
system.
Effective but unsafe: This group of products is more dangerous and
actual product efficacy will lure consumers into trying the product
while erroneously assuming dietary supplements, because of their herbal
or natural ingredients are unduly safe compared to their pharmaceutical
counterparts. As stated in the JAMA patient papge (Appendix IV), the
risks of ephedra far outweigh benefits.
Improved product safety testing, quality control, labeling, and
nomenclature are all needed in order to forestall or eliminate the
problems now inherent with the dietary supplement category of weight
loss products.
Table 1. Patterns of Signs and Symptoms Associated With Dietary
Supplements Containing Ephedrine Alkaloids \1\
------------------------------------------------------------------------
Clinical Signs and symptoms
Organ/system involved significance
------------------------------------------------------------------------
Cardiovascular system........... Serious........... Dysrhythmias,
Less clinically severe
significant. hypertension,
cardiac arrest,
angina,
myocardial,
infarction, and
stroke \2\
Tachycardia, mild
hypertension,
palpitations.
Nervous system.................. Serious........... Psychosis,
Less clinically suicidal, altered
significant. or loss of
consciousness
(including
disorientation or
confusion), and
seizures.
Anxiety,
nervousness,
tremor,
hyperactivity,
insomnia, altered
behavior, memory
changes.
Gastrointestinal (GI)........... Serious........... Altered serum
Less clinically enzymes,
significant. hepatitis.
GI distress
(nausea,
vomiting,
diarrhea,
constipation).
Dermatologic.................... Serious........... Exfoliative
Less clinically dermatitis
significant. Less clinically
significant
Nonspecific
rashes.
General manifestations.......... Numbness,
tingling,
dizziness,
fatigue,
lethargy,
weakness.
------------------------------------------------------------------------
\1\ Reproduced from Federal Register: June 4, 1997 (Volume 62, Number
107), Dietary Supplements Containing Ephedrine Alkaloids.
\2\ For the purposes of this document, strokes (i.e., cerebrovascular
accidents) are considered to be related to the cardiovascular system,
because predisposing or inciting factors include hypertension,
dysrhythmias and ischemia, although it is recognized that the
consequences affect the central nervous system.
References
Allison D, Fontaine K, Heshka S, Mentore J, Heymsfield SB,
Alternative Treatments for Weight Loss: A Critical Review. Food Science
and Nutrition. Food and Nutrition, 41(1): 1-28(2001).
Davidson M, DiGirolamo M, Foreyt J, Halstead C, Hauptman J, Heber
D, Heimburger D, Heymsfield SB, Lucas C, Robbins D, Chung J. Long-term
weight control and reduction in risk factors in obese subjects
receiving orlistat: a lipase inhibitor. JAMA 281 (3): 235-242, 1999.
Astrup A, Lundsgaard C, Madsen J, Christensen NJ. Enhanced
thermogenic responsiveness during chronic ephedrine treatment in man.
Am J Clin Nutr 1985;42:83-94.
Astrup A, Madsen J, Holst J., and Christensen NJ. The Effect of
Chronic Ephedrine Treatment on Substrate Utilization, the
Sympathoadrenal Activity, and Energy Expenditure During Glucose-Induced
Thermogenesis in Man. Metabolism 1986:35; 260-265.
Astrup A, Toubro S, Cannon S, Hein P, Breum L, Madsen J. Caffeine:
a double-blind, placebo-controlled study of its thermogenic, metabolic,
and cardiovascular effects in healthy volunteers. Am J Clin Nutr
1990;51:759-67.
Astrup A, Toubro S, Cannon S, Hein P, Madsen J: Thermogenic,
metabolic, and cardiovascular effects of a sympathomimetic agent,
ephedrine. Current Therapeutic Research 1990;48:10871100.
Astrup A, Toubro S, Cannon S, Hein P, Madsen J: Thermogenic
synergism between ephedrine and caffeine in healthy volunteers: a
double blind placebocontrolled study. Metabolism 1991;40.
Astrup, A., Breum, L., Toubro, S., Hein P., and Quaade, F . The
effect and safety of an ephedrine/caffeine compound compared to
ephedrine, caffeine and placebo in obese subjects on an energy
restricted diet. A double blind trial. International Journal of Obesity
& Related Metabolic Disorders. 1992;16(4):269-77.
Astrup, A., Beuman, B., Christensen, NJ, Toubro, Thorbeck, G,
Victor OJ, and Quaade, F. The effect of ephedrine/caffeine mixture on
energy expenditure and body composition in obese women. Metabolism 41:
686-688, 1992.
Astrup A, Toubro S. Thermogenic, metabolic, and cardiovascular
responses to ephedrine and caffeine in man. International Journal of
Obesity and Related Metabolic Disorders 1993;17 (suppl):S41-S43.
Astrup, A., Breum, L., and Toubro, S. Pharmacological and clinical
studies of ephedrine sand other thermogenic agonists. Obesity Res.
1995;3 Suppl 4:537S-540S.
Breum L, Pedersen JK, Ahlstrom F, FrimodtMoller J. Comparison of an
ephedrine/caffeine combination and dexfenfluramine in the treatment of
obesity: a double-blind, multi-centre trial in general practice.
International Journal of Obesity and Related Metabolic Disorders
1994;18:99-103.
Gurley BJ, Gardner SF, Hubbard MA. Content Versus label Claims in
Ephedra-Containing Dietary Supplements. Am J Health-Syst Pharm
2000;57:963-9.
Gurley BJ, Gardner SF, White LM, Wang P. Ephedrine pharmacokinetics
after the ingestion of nutritional supplements containing Ephedra
sinica. Therapeut Drug Mort 1998 20:439-445.
White LM, Gardner SF, Gurley BJ, Marx MA, Wang PL, Estes M.
Pharmacokinetics and cardiovascular effects of MaHuang in normotensive
adults. J Clin Pharmacol 1997 37:116-22.
Dulloo AG, Miller DS: The thermogenic properties of ephedrine/
methylxanthine mixtures:human studies. Int J Obesity 1986;10:467481.
Daly PA, Krieger DR, Dulloo AG, Young JB, Landsberg L: Ephedrine,
caffeine and aspirin: safety and efficacy for treatment of human
obesity. Int J Obes and Relat Metab Disord 1993;17:S73S78.
Malchow-Moller, A., Larsen, S., Hey, H., Stokholm, K. H., Juhl, E.,
and Quaade, F . Ephedrine as an anorectic: the story of the 'Elsinore
pill'. International Journal of Obesity. 1981;5(2):183-187.
Pasquali, R., Casimirri, F., Melchionda, N., Grossi, G.,
Bortoluzzi, L., Morselli , Labate, A. M., Stefanini., C., and Raitano,
A . Effects of chronic administration of ephedrine during very-low-
calorie diets on energy expenditure, protein metabolism and hormone
levels in obese subjects. Clinical Science. 1992;82(1):85-92.
Toubro S, Astrup A, Breum L, Quaade F: Safety and efficacy of
longterm treatment with ephedrine, caffeine, and ephedrine/caffeine
mixture. Int J Obes and Relat Metab Disord 1993;17:S69S72.
Boozer CN, Nasser JA, Heymsfield SB, Wang V, Chen JL, Solomon JL.
An Herbal Supplement Containing Ma Huang-Guarana for Weight Loss: a
Randomized, Double-Blind Trial. Intern J Obesity 2001:25:316-324.
Boozer CN, Daly PA, Homel P, Solomon JL, Blanchard D, Nasser JA,
Strauss R, Meredith T.Herbal ephedra/caffeine for weight loss: a 6-
month randomized safety and efficacy trial. Int J Obes Relat Metab
Disord 2002 May;26(5):593-604
Benowitz NL, Haller CA. Adverse Cardiovascular and Central Nervous
System Events Associated with Dietary Supplements Containing Ephedra
Alkaloids. New Engl J Med
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Mr. Greenwood. Thank you very much, Dr. Heymsfield.
Dr. Woosley.
TESTIMONY OF RAYMOND WOOSLEY
Mr. Woosley. Mr. Chairman Greenwood, members of the
Committee and Congresswoman Davis.
Thank you for the opportunity to testify before this
Committee on this very important topic.
Since 1995 I have served as a consultant to the Center for
Food Safety and Nutrition of the FDA addressing their concern
over the large number of reports of serious adverse reactions
to ephedra-containing dietary supplement. I am very proud in
2001, I was awarded the FDA Commissioners' special citation for
my work on ephedra for the FDA.
I have no financial interest in this question, and I do not
represent any particular organization. But, since 1995, I and
many other consultants to the FDA have recommended that the FDA
take steps to have nonprescription products containing
ephedrine removed from the market. I based this recommendation
on my experience as a scientist and as a physician studying the
actions of drugs in humans.
My credentials are summarized in my written testimony. I
have been a professor of pharmacology and medicine at
Vanderbilt University, Georgetown University and I am now Vice
President for Health Sciences at the University of Arizona. For
39 years I have studied the actions of drugs in humans.
In 1995 and again in the year 2000 I was asked by the FDA
to perform an in depth review of over 230 reports of adverse
events related to the use of dietary supplements containing
ephedra alkaloids. Each time I recommended these products be
removed from the market because of a danger to the public. In
congressional hearings I have made that recommendation.
Many agencies and regulatory bodies, such as Health Canada,
the Canadian equivalent to our FDA, have already taken action
to protect the public from these products.
We have heard that Illinois has banned the sale of these
products and New York and California are considering
legislation to take such action.
The U.S military and the National Football League prohibit
the use of ephedra-containing products.
The American Medical Association, the American Heart
Association, the American Society for Clinical Pharmacology and
Therapeutics and many other professional organizations have
called for FDA action to remove these products from the market.
What does it take? Dozens of deaths reported to the FDA and
an unknown number of unreported deaths are reason enough for
the FDA to take action. They are authorized.
The FDA has failed to act and only called for further
study. They contracted with the Rand Corporation to perform an
analysis of the published studies of these products. People
died while this document was being created, needlessly. And,
unfortunately, this analysis is not even relevant to the way
ephedra is used in this nation today.
Because these products are taken as nonprescription dietary
supplements and they are used without any medical supervision
or medical screening, yet the scientific papers reviewed by
Rand, every subject was screened by a physician or by a medical
practitioner. If they had pre-existing medical conditions, they
couldn't be enrolled. People enrolled in these trials were
followed with close supervision. That isn't the way ephedra is
used by the public today. So the analysis by Rand is really
irrelevant. It is interesting, it is consistent, but it is
irrelevant.
As an example, in the study by Boozer et.al., it is often
cited as evidence for the safety of these products, the
investigators excluded one of every 10 subjects that they
interviewed because they had medical conditions that made
ephedra and the caffeine product combination that they were
studying, in their estimation unsafe. Studies with that medical
screening are not feasible or even ethical, because the general
knowledge in the medical community, the medical community knows
that ephedra-containing products are dangerous. Any
institutional review board responsible for the protection of
human subjects will not approve a research protocol unless it
includes medical screening and monitoring for safety. So this
cannot be further studied. We do not need further study.
It, therefore, is not surprising that the published reports
using medical screening failed to detect the kind of toxicity
that we have heard about today and the FDA has looked at for
over 8 years. The available evidence clearly shows that these
products cause harm to some individuals, harm that cannot be
prevented by warning labels. Because most patients do not know
that they are at risk. Based on the Boozer trial, approximately
10 percent of patients who would like to take a dietary
supplement for weight loss do not know that they have a medical
condition until they are screened.
In summary, I strongly encourage you to ask the FDA to take
action to ban the marketing of dietary supplements that contain
ephedra. I also ask you to consider enacting legislation that
will more accurately distinguish between drugs such as ephedra
and dietary supplements. That will assist the FDA in regulating
these products.
Ephedra containing products, and many others, are not
dietary supplements. That is, they are not a necessary
ingredient in a healthy diet. They are drugs and they should be
regulated as drugs. Please do not call for warnings. Please do
not call for more studies. People will die while those studies
and those warnings are ineffective.
[The prepared statement of Raymond Woosley follows:]
Prepared Statement of Raymond L. Woosley, Vice President for Health
Sciences, University of Arizona
Mr. Chairman and members of the Committee: Thank you for the
opportunity to testify before the Committee on the very important
topic, i.e. the dangers of dietary supplements that contain ingredients
from the plant ephedra or the chemical ephedrine. Since 1995, I have
served as a consultant to the Center for Food Safety and Nutrition of
the Food and Drug Administration to address their concern over the
large number of severe adverse reactions with ephedrine-containing
dietary supplements reported to the FDA. In 2001, I was awarded the FDA
Commissioner's Special Citation for my work on ephedrine for the FDA. I
have no financial interests in this question and I do not represent any
particular organization.
I have consistently recommended that the FDA take steps to have
non-prescription products containing ephedrine removed from the market.
In 2001, I joined Public Citizen, a consumer advocacy organization, and
filed a citizen's petition calling for an FDA ban on ephredrine-
containing dietary supplements. I base this recommendation on my almost
forty years of experience as a scientist and physician studying the
actions of drugs in humans. In 1967, I obtained a PhD in pharmacology,
i.e., the study of the actions of drugs. I obtained an MD from the
University of Miami and then trained in Internal Medicine at Vanderbilt
University. I then completed a fellowship in the subspecialty of
clinical pharmacology, i.e. the study of the actions of drugs in
humans. I rose to the rank of Professor of Medicine and Pharmacology at
Vanderbilt University before moving to Georgetown University School of
Medicine to Chair the Department of Pharmacology. I am now Vice
President for Health Sciences at the University of Arizona and Director
of one of the seven Centers for Education and Research on Therapeutics
funded by the Agency for Healthcare Research and Quality. For the last
39 years I have studied the actions of drugs. I have been asked to
serve as an advisor to the NIH, the FDA, the DOD and all of the leading
pharmaceutical companies on the actions of drugs in humans. My
experience has given me a broad perspective and an expertise in the
toxicity of drugs. I served as co-director of the NIH-sponsored Cardiac
Arrhythmia Suppression Trial that found certain drugs designed to save
lives were actually causing tens of thousands of deaths each year. I
also served as leader of the team that determined the mechanism of
cardiac toxicity caused by terfenadine (Seldane <SUP>'</SUP>) which
served as the basis for its ultimate removal from the market. I
currently lead a team of scientists who are studying 50 prescription
drugs that have the potential to induce life-threatening arrhythmias.
In 1995 and again in 2000, I was asked by the FDA to review over
230 reports of adverse events related to the use of dietary supplements
containing ephedra alkaloids. The following is the conclusion of my
most recent report: ``The occurrence of serious side effects makes the
use of ephedrine containing products as dietary supplements at dosages
that can increase blood pressure and heart rate in susceptible
individuals unacceptable without medical supervision.''
Many agencies and regulatory bodies such as Health Canada have
already taken action to protect the public from ephedrine-containing
products. Two states have banned the sale of these products and the
California legislature is now considering such action. The US Military
and the National Football League prohibit the use of ephedrine-
containing products. The American Medical Association, the American
Heart Association, the American Society for Clinical Pharmacology and
Therapeutics, and many other professional organizations have called for
FDA action to remove these products from the market. Dozens of deaths
reported to the FDA and an unknown number of unreported deaths are
reason enough for the FDA to take action. However, a year ago, the FDA
refused to act on our petition and called for further study. They
contracted with the RAND Corporation to perform an analysis of the
published studies and FDA reports of adverse events that might pertain
to the safety and effectiveness of dietary supplements containing
ephedrine or ephedrine with caffeine taken for weight loss or exercise
enhancement.
However, such an analysis is not relevant to the way ephedrine is
used by the public. Since these products are taken as non-prescription
``dietary supplements'', they are used without any medical screening or
medical supervision. However, the scientific papers that were analyzed
by RAND were studies in which subjects had been screened for pre-
existing medical conditions and were followed during the trials under
medical supervision. As an example, in the study by Boozer et al. (Int.
J. Obes. Relat. Metab. Disord. 26(5):593-604, 2002) that is often cited
as evidence for the safety of these products, the investigators
excluded one of every ten subjects they screened because they found
medical conditions that made ephedra/caffeine, in their estimation,
unsafe. RAND could not find published trials that truly addressed the
question posed by FDA. Such studies without medical screening are not
feasible or ethical because of the general knowledge in the medical
community that ephedrine-containing products are dangerous. Any
Institutional Review Board responsible for the protection of human
subjects would not approve a research protocol unless it included
medical screening and monitoring for safety. It is therefore not
surprising that the published reports that include only small numbers
of subjects who had been medically screened failed to detect the type
of toxicity reported to the FDA.
The ephedrine industry has raised doubts about the validity of the
adverse events reported to the FDA. Determination of causation for rare
adverse events can be difficult when analyzing a single report.
However, one must consider the totality of evidence for scientific
validity and consistency with the drugs pharmacologic actions. After
considering the information in the adverse events reported and the
totality of information about ephedrine, I concluded that the use of
these products causes a serious health risk to the public. Decades of
experience summarized in textbooks of medicine and pharmacology support
this conclusion. The RAND analysis of these reports failed to
adequately consider the pharmacology and clinical pharmacology of
adrenaline-like chemicals such as ephedrine. Also, the consistency of
the evidence across a range of chemically-related substances must be
considered. The relative safety and efficacy of other drugs that have
similar pharmacologic actions is especially relevant. Every drug with
adrenalin-like actions that increases blood pressure and heart rate,
i.e. they mimic the human body's emergency ``autonomic'' nervous
system, has been already associated with serious cardiovascular and
neurologic adverse events. Likewise, the actions of drugs that
antagonize the effects of ephedrine should be considered. For example,
drugs that block the actions of adrenaline reduce the incidence of
strokes and heart attacks. The ephedrine data are consistent with the
observation of a high risk of stroke with the diet pills containing
phenylpropanolamine (PPA), a drug with almost the same chemical
structure as ephedrine. In this case, the FDA took action to remove
products with PPA from the market.
Another related weakness of the RAND assessment is the absence of
consideration of the genetic diversity that we know exists in large
populations of people. Most of the studies reviewed enrolled only 50-
200 patients and all had been medically screened. It is very unlikely
that these studies would include any of the 1 in 10,000 patients at
risk for super-sensitivity to ephedrine due to a genetic variant that
would be otherwise silent.
The available evidence clearly shows that these products cause harm
in some individuals that cannot be prevented by warning labels because
most patients will not know they are at risk of experiencing adverse
effects. Based upon the Boozer trial, approximately 10% of patients
will have medical conditions that place them at increased risk of
adverse effects. I hope you will take swift action to protect these
people.
RECOMMENDATIONS
In summary, I strongly encourage you to ask the FDA to ban these
products. I have no doubt that these products are causing needless
death and disability to people.
I also ask you to consider enacting legislation that will more
accurately distinguish between ``drugs'' and ``dietary supplements''
and clarify how the FDA should regulate these products. Many of the
products that are marketed as dietary supplements and especially the
ephedrine-containing products are in fact drugs because they are not
normal constituents of a healthy diet. The ephedrine products are being
used by and being promoted to the public for weight loss. Without
medical supervision these products present a clear and serious danger
to the public and should be regulated as medicines and banned for use
without a prescription.
Thank you for the opportunity to provide this statement for the
record.
Mr. Greenwood. I thank you very much, Dr. Woosley.
Dr. Zipes.
TESTIMONY OF DOUGLAS P. ZIPES
Mr. Zipes. Mr. Chairman, members of the committee, Ms.
Davis, I am a clinical cardiologist and my area of expertise is
in heart rhythm problems.
I would like to start with a potential conflict of
interest. I am an expert witness for Plaintiff for McDonald's
v. Twin Labs, which is an ephedra case, but I am also expert
for Defense of four pharmaceutical companies with drugs
unrelated to ephedra.
Ephedra and ephedrine actions on the heart and blood
vessels are to produce an adrenaline like effect. This is a
stimulant, a ``fight'' or ``flight'' type reaction. It is also
a brain stimulant and it is related to methamphetamine or
speed.
Caffeine also has actions on the heart and blood vessels
and is also a stimulate, and therefore adds to the effects of
ephedra actions. And, indeed, an exercising individual super
imposes even additional adrenaline effect on the actions of
these two drugs.
So in general what happens? The blood pressure elevates,
the heart rate elevates, there's elevated stress on the heart.
These changes can reduce a very critical electrolyte, potassium
in the blood and all these changes then can cause heart rhythm
disorders ranging from palpitations due to premature beats or
ventricular fibrillation. This is the abnormal heart rhythm
coming from the bottom chamber of the heart at rates of 4 to
600 times a minute that produce sudden death.
Now what evidence exists that ephedra compounds can produce
these effects? Certainly animal and clinical studies establish
the adrenaline like effects. That is not in argument. The
question is, though, what are the adverse effects? And they
come from adverse event reports, case reports and some
controlled trials.
Now, in general adverse event reports and case reports
provide less robust data than controlled clinical trials. But
they may be the only source of information about infrequently
occurring side effects, those that occur in less than 1 in a
1,000 or so individuals. However, we can establish criteria
that allow us to investigate those adverse event reports. And I
have six here which I use when I evaluate a drug.
Is there a temporal relationship between ingestion and
adverse event?
Is an appropriate dose taken to have an adverse effect?
Are all other causes for the adverse event recognized and
ruled out?
Is there biological plausibility? By that I mean, the known
influence of the adrenaline stimulation of these drugs can
cause these events. We know that from animal and clinical
investigation. Is there a D or rechallenge? In other words,
when the drug is stopped, do the adverse events stop or if the
drug is taken again, is there another adverse events and are
there supported published literature?
And I would suggest that many of the published reports on
ephedra and ephedrine compounds include individuals who
unquestionably meet these criteria.
So I think to a reasonable degree of medical and scientific
certainty, it is my opinion that ephedra, ephedrine compounds
can cause the following adverse events:
There are minor adverse events such as nausea, dry mouth,
shakiness and insomnia, but critically the major events on the
heart are palpations but ventricular fibrillation and sudden
death.
My recommendations to the committee are that they recognize
that ephedra and ephedrine are drugs, they are not dietary
supplements. Recognize that they are capable of provoking harm
including ventricular fibrillation and sudden death. Element
over-the-counter use based on minor proven benefits and
potential for major harm, and regulate its use by applying FDA
criteria to ephedra and ephedrine compounds as is applied for
all other drugs.
Thank you for your attention.
[The prepared statement of Douglas Zipes follows:]
Prepared Statement of Douglas P. Zipes, Distinguished Professor of
Medicine, Pharmacology and Toxicology, Emeritus, Director of the
Krannert Institute of Cardiology and Division of Cardiology, Indiana
University School of Medicine
I. INTRODUCTION
I am a clinical cardiologist and scientist specializing in heart
rhythm disturbances. The findings and opinions that follow are based
upon my education, training and experience in medicine, cardiology,
cardiovascular pharmacology, cardiac electrophysiology, and review of
the medical literature.
Recent articles in the medical literature highlight the concern of
medical practitioners with the overall quality, safety, and efficacy of
some herbal products.\1\ In my opinion, the Dietary Supplement Health
and Education Act (DSHE) passed in 1994 has not provided a satisfactory
framework to protect the public health by allowing dietary supplements
to be marketed without prior approval of efficacy or safety by the FDA.
Though DSHE limits certain health claims for dietary supplements, these
products are marketed in such a way that consumers believe they are
effective to cure or treat many of the conditions that afflict the
population, including obesity. Laboratory analysis of these products
\2\ has disclosed that there is considerable variation in the
composition of herbal supplements from one manufacturer to another and
often from lot to lot from the same manufacturer. Most of these herbal
products have not been tested rigorously, with the accepted norm of
standardized, controlled, prospective, randomized trials that we use to
test medical drugs and devices. In addition to lack of efficacy for the
claimed use, some of these products produce important side effects
either directly or by interactions between the herbal remedies and
prescription drugs and over-the-counter (OTC) drugs. Due to limitations
in the reporting system, it is estimated that less than one percent
(1%) of the adverse effects caused by dietary supplements are reported
to the FDA.\3\ The current regulatory framework requires that, if a
safety concern arises, the burden of proof for safety lies not with the
manufacturer but with the FDA to prove that the product is unsafe. In
particular, dietary supplements containing ephedra and caffeine
illustrate the health risks posed to consumers from the current system
and will be the focus of this report.
II. NORMAL HEART FUNCTION
The heart and blood vessels provide oxygen and nourishment to every
cell of the body and remove waste material by circulating blood
throughout the body. The heart contracts, pumping about 5 quarts (4.7
liters) of blood every minute, or 1800 gallons (6768 liters) of blood
every day. Oxygenated blood is pumped from the left ventricle to the
body to provide oxygen and nutrients, while returning (de-oxygenated)
blood is pumped through the lungs from the right ventricle to remove
carbon dioxide and become re-oxygenated. This continuous cycle of
synchronized contractions is driven by the heart's electrical system.
A healthy heart beats steadily and rhythmically at a rate of about
60 to 100 beats per minute when at rest (normal sinus rhythm). During
strenuous exercise, the heart can increase the amount of blood it pumps
fourfold. The normal heart beats approximately 38 million times per
year, or about 3 billion times in a normal lifespan. The sinus node, a
small group of specialized cells in the top right portion of the
heart's upper chamber (atrium), serves as the pacemaker, initiating and
orchestrating each heartbeat. Other tissues in the heart wait for the
arrival of each sinus-generated beat, almost like electricity traveling
over a wire, and fire in an orderly sequence, from the atria to the
ventricles, to produce each heartbeat.
Multiple factors can influence the rate of discharge of the sinus
node and can cause other tissues in the heart to fire prematurely and
usurp control of the heartbeat. Among these factors, the autonomic
nervous system is most prominent.\4\ Predominantly two groups of nerves
make up the autonomic nervous system: vagus nerves and sympathetic
nerves. The vagus nerves exert an inhibitory effect on heart function
by release of a substance called acetylcholine, slowing the heart rate,
slowing conduction from the atria to bottom chambers (ventricles),
lessening the strength of heart muscle contraction and dilating blood
vessels. They oppose the action of sympathetic nerves. Sympathetic
nerves are stimulatory by release of substances known collectively as
catecholamines (adrenaline or epinephrine, and noradrenaline or
norepinephrine), causing an increase in the heart rate, a quickening of
conduction between the atria and ventricles, an increase in the
strength of heart muscle contraction, and, for the most part, a
constriction of the blood vessels. These actions result in an increase
in blood pressure and also can provoke spontaneous discharge of the
heartbeat from areas other than the sinus node. When heart tissue other
than the sinus node initiates a heartbeat, this results in arrhythmias,
or disorders of the heartbeat. The extent of the heartbeat disorder can
range from a single premature beat, often felt as a ``thump'' in the
chest or palpitation, to a lethal heart rhythm called ventricular
fibrillation. The latter arrhythmia is the major cause of sudden
cardiac death. It is a disorganized, rapid (400-600 times per minute)
heart rhythm originating in the bottom chambers (ventricles) and
preventing blood flow to the brain, which causes death in 3-5 minutes
unless reversed.\5\<SUP>,</SUP>\6\
III. ACTION OF EPHEDRA AND CAFFEINE ON THE HEART AND BLOOD VESSELS
A. Ephedra/ephedrine
The ephedra products under discussion are marketed as dietary
supplements for weight loss and to boost energy. These preparations
stimulate both the heart and blood vessels, and the brain. They are
chemically related to methamphetamine.\7\ Most of these ephedra
substances contain extracts of the ma huang plant, which is referred to
as ephedra. Ephedra contains primarily ephedrine, which is a
sympathomimetic amine. That means its actions mimic those actions
produced by stimulation of the sympathetic nerves, noted above. Ephedra
does this by both a direct effect on stimulating alpha and beta 1 and
beta 2-adrenergic receptors, as the body's own catecholamines do, and
indirectly by stimulating the release of the body's store of
catecholamines and another compound called dopamine (20-30% increase).
Ephedra can be chemically synthesized as ephedrine, rather than
extracted from a plant, and has the same actions.
B. Caffeine
Most of these ephedra products also contain caffeine, typically
extracts from guarana seed. Caffeine causes an anti-vagal effect by
antagonizing the actions of adenosine, and can therefore promote
vasoconstriction (blood pressure elevation) and increase the release of
epinephrine, norepinephrine and dopamine.
Importantly, an exercising individual normally activates the
autonomic nervous system to decrease vagal, and increase sympathetic,
activity. These changes summate with the actions of ephedra and
caffeine.
C. Physiologic effects
The result of the actions of ephedra and caffeine noted above is
to:
1) Elevate the blood pressure
2) Elevate the heart rate
3) Put more stress on the heart (needs more oxygen)
4)Reduce the potassium level in the blood
These responses to ephedra/caffeine compounds can cause abnormal
heart rhythms ranging from single premature beats to ventricular
fibrillation and sudden death
IV. WHAT EVIDENCE EXISTS TO SHOW THAT EPHEDRA COMPOUNDS CAN CAUSE
CARDIOVASCULAR HARM?
Many animal and clinical studies have established the physiologic
actions on the heart and blood vessels of the vagus and sympathetic
nerves, catecholamines, and sympathomimetic amines like ephedra and
ephedrine, as well as the actions of caffeine. No controversy exists
about the physiologic actions of these drugs. The major issue under
discussion is whether these ephedra/caffeine combinations have
pathophysiologic actions, that is, can they cause bodily harm.
Information to support the latter comes mostly from adverse event
reports (AERs) and case reports, which are not as ``robust'' as
clinical studies. Still, more than 1200 serious reactions related to
ephedra have been reported to the FDA, and it is suspected that the
actual number of events is undoubtedly far greater due to the under-
reporting noted earlier.\7\ These include strokes, arrhythmias,
myocardial infarction, psychosis, and death.\8\<SUP>,</SUP>\9\
Apparently, 13,000 complaints have been registered with the
manufacturer of Metabolife 356, including several hundred patients who
required hospitalization and 80 incidents of serious injury or
death.\10\ Canadian authorities have requested the voluntary recall of
health products containing ephedra, noting its enhanced toxicity when
combined with caffeine.\11\
The reason for relying on AER and case report data is due to the
relative infrequency of the adverse events. If a drug causes an adverse
effect in only 1 of 1000 treated patients, then many patients have to
be treated before a statistically significant result is noted. Such
studies can be impossibly expensive to perform. And while information
from AERs is less acceptable as proof of an effect, criteria can be
applied to help establish validity. These include the following six
criteria:
1) Temporal relation between taking the drug and the adverse response
2) Appropriate dose taken to have an effect
3) No other cause recognized to have produced the effect
4) Biologic plausibility, that is, the known action of the drug is
consistent with the adverse response
5) De-and re-challenge, that is, stopping the drug eliminates further
adverse responses, or re-starting the drug produces the same
adverse response
6) Similar supportive data in published medical literature
Most of the reports on ephedra/caffeine compounds meet all six of
these criteria. Some examples follow.
The report by Haller and Benowitz applied reasoning similar to the
above 6 criteria in evaluating 140 AER reports submitted to the FDA
between June 1997 and March 1998 and considered that 31% were
definitely related to supplements containing ephedra and 31% possibly
related. Ten events resulted in death and 13 produced a disability,
representing 26% of the definite/probable and possible cases.
Palpitations or tachycardia (rapid heart beat) occurred in 13.
Samenuk et al \9\ analyzed 37 patients from 926 cases of possible
ma huang toxicity reported to the FDA between 1995 and 1997 and found
that the compound was temporally related to stroke, heart attack, and
sudden death at the normally taken doses in 36 of 37 people.
Gardner et al \12\ treated 10 healthy men with 2 Metabolife 356
caplets (12 ephedra and 40mg caffeine in each) 3 times daily for 2
weeks and found that at day 3, all subjects reported adverse effects,
most commonly dry mouth, shakiness and insomnia. Two men reported chest
pain, two had large numbers of premature atrial beats and one had a 3
beat run of ventricular tachycardia.
AERs were noted in an 8 week controlled prospective weight loss
study of 72 mg/day ephedrine and 240 mg/day caffeine.\13\ Boozer et al
noted systolic pressure (4mm Hg) and heart rate (7 bpm) were higher in
the ephedra group. One of thirty-five subjects left the study early due
to elevated blood pressure and four due to palpitations with (1) or
without (3) chest pain. Four additional subjects left the study after
week 2 due to increased blood pressure, palpitations or extreme
irritability. None left the study in the placebo group because of side
effects. In a later 6-month study, Boozer \14\ found treated patients
had increases in heart rate (4 bpm), blood pressure (3-5 mm Hg), dry
mouth, insomnia, and heartburn.
An important recent review of the relative safety of ephedra
products analyzed the number of adverse reactions adjudicated by poison
control centers in the US in 2001 to be attributable to several
commonly used herbal products. They found that products containing
ephedra alone or combined with other herbs or substances accounted for
64% of all adverse reactions, yet these products represented only 0.82%
of herbal sales. The relative risks for adverse reactions among ephedra
users were 100-fold greater than the risk among users of other herbal
products.\15\
A comprehensive literature review of 59 articles that corresponded
to 52 controlled clinical trials of ephedrine or herbal ephedra for
weight loss or athletic performance found that short term use was
associated with approximately 2 pounds weight loss per month compared
with placebo. There was a modest effect on very short-term athletic
performance. However, there was a two to three times increase in the
risk of nausea, vomiting, psychiatric symptoms, autonomic
hyperactivity, and palpitations. The number of individuals studied were
insufficient to evaluate events with a risk of less than 1.0 per
thousand.\16\
V. SUPPORTING INFORMATION
Supporting information about the potential harm of catecholamines
and sympathomimetic agents can be found in multiple sources. For
example, plasma norepinephrine concentration is independently related
to the subsequent risk of mortality.\17\ Patients who have sustained
ventricular arrhythmias have a selective increase in cardiac
sympathetic activity.\18\<SUP>,</SUP>\19\ In addition, use of
sympathomimetic drugs leads to increased risk of hospitalization for
arrhythmias in patients with congestive heart failure.\20\ Plasma
norepinephrine predicts survival and cardiovascular events in patients
with end-stage renal disease.\21\ Large stores of noradrenaline in the
heart have been related to sudden death.\22\
VI. WHAT CAN ACCOUNT FOR THE APPARENT UNPREDICTABLE SPORADIC EVENTS?
The following can explain the above individual reactions to
recommended doses of ephedra/caffeine compounds:
1) Variable absorption occurs, so that the amount of drug in the body
can vary from one person to the next.
2) Variability in active drug content of botanical, as shown by Gurley
et al.\2\
3) Presence or absence of underlying disease or drugs. It is possible
that patients with pre-existing conditions such as coronary
disease or high blood pressure, or who are taking other drugs
that may interact with the ephedra/caffeine compounds, are at
increased risk for an adverse response.
4) Variability in electrolytes, particularly potassium that can
predispose to the development of arrhythmias.
5) Herbal products may contain undeclared pharmaceuticals or heavy
metals.
6) Genetic influences. There exist some patients with genetic changes
in the autonomic nervous system that make them susceptible to
large outpouring of catecholamines which could put them at risk
of developing an arrhythmia, heart attack or
stroke.\23\<SUP>,</SUP>\24\ Also, some patients have inherited
electrical abnormalities that do not become manifest until
triggered by an external source like a drug.\25\ This drug
could have totally benign actions in all other individuals
without the inherited abnormality.
VII. EPHEDRA/CAFFEINE AND EXERCISE
Many ephedra products are marketed for sports nutrition or for
weight loss. The directions for use suggest that they should be taken
before exercise. During exercise, the oxygen requirements of the heart
increase dramatically. If the oxygen supply falls behind the demands of
the heart, such a response can trigger abnormal heart rhythms. Oxygen
consumption of the heart is directly related to wall stress and heart
rate, both of which increase during exercise. The effects of the
ephedra/caffeine drugs exacerbate these responses. Serious arrhythmias
can develop because of this constellation of events. As physicians, we
know that humans are biologic organisms that are imperfect. Humans do
not run with absolute precision like a Swiss watch. Slight variations
in blood pressure, heart rate, and conduction of the heart's impulse
can make a difference between having an arrhythmia that produces sudden
death and not having one. These responses are often unpredictable.
Numerous sport organizations, including the NCAA, NFL, and
International Olympic Committee, prohibit the use of ephedra-containing
products.\15\
VIII. RECOMMENDATIONS:
Because of our inability to predict who might have an adverse
response to these drugs, because of their minimal (if any) therapeutic
effect and because of the potential for major adverse responses, I
would recommend the following:
1) Recognize that ephedra and ephedrine are drugs, not dietary
supplements
2) Recognize that they are capable of provoking harm, including
ventricular fibrillation and sudden death
3) Eliminate over-the-counter use based on minor proven benefit and
potential for major harm
4) Regulate their use by applying FDA criteria to distribution of
ephedra/caffeine compounds as is done for all other drugs
References:
1. DeSmet TAGM. Herbal Remedies. N Engl J Med. 2002;347:246-256.
2. Gurley DJ, Gardner SF, Hubbard MA. Content versus Label Claims
in Ephedra-containing Dietary Supplements. Am J Health Syst Pharm.
2000;57:963-969.
3. Adverse Event Reporting for Dietary Supplements: An Inadequate
Safety Valve. Washington, DC: Office of Inspector General, April 2001.
(report #OEI-01-00-00-180).
4. Schwartz PJ, Zipes DP. Autonomic Modulation of Cardiac
Arrhythmias. In: Cardiac Electrophysiology. From Cell to Bedside.
Edition 3. Ed. Zipes DP, Jalife J, W.B. Saunders, Orlando. pp 300-314,
2000.
5. Zipes DP, Wellens HJJ. Sudden Cardiac Death. Circulation.
1998;98:2334-2351.
6. Priori SG, Aliot E, Blomstrom-Lundqvist C, Bossaert L,
Breithardt G, Brugada P, Camm AJ, Cappato R, Cobbe SM, DiMario C, Maron
BJ, McKenna WJ, Pedersen AK, Ravens U, Schwartz PJ, Trusz-Gluza M,
Vardas P. Wellens HJ, Zipes DP. Task Force on Sudden Cardiac Death of
the European Society of Cardiology. Eur Heart J. 2001;22(16):1374-1450.
7. Marcus DM, Grollman, AP. Botanical Medicines--the Need for New
Regulations. New England Journal of Medicine. 2002;347:2073-2076.
8. Haller CA, Benowitz NL. Adverse Cardiovascular and Central
Nervous System Events Associated with Dietary Supplements Containing
Ephedra Alkaloids. N Engl J Med 2000;343:1833-1838.
9. Samenuk D, Link MS, Homoud MK, et al. Adverse Cardiovascular
Events Temporally Associated with Ma Huang, an Herbal Source of
Ephedrine. Mayo Clinic Proceedings. 2002;77:12-16.
10. Hilts PJ. US in Criminal Inquiry on Metabolife Product. New
York Times. August 16, 2002:C1.
11. Health Canada Requests Recall of Certain Products Containing
Ephedra/Ephedrine. Ottawa, Ont: Health Canada, January 9, 2002
(accessed November 27, 2002 at http//:www.hc-sc.gc.ca/English/
protection/warnings/2002/2002--01E.htm).
12. Gardner SF, Franks AM, Gurley DJ, et al. Effect of a
Multicomplement, Ephedra-containing Dietary Supplement (Metabolife 356)
on Holter Monitoring and Hemostatic Parameters in Healthy Volunteers.
Am J of Cardiol 2003;91:1510-1513.
13. Boozer C, Nasser J, Heymsfield S, et al. An Herbal Supplement
Containing Ma Huang-Guarana for Weight Loss: a Randomized Double Blind
Trial. Int J Obes Relat Metab Disord. 2001;25:316-324.
14. Boozer CN, Daly PA, Homel P, et al. Herbal Ephedra/Caffeine for
Weight Loss: a Six Month Randomized Safety and Efficacy Trial. Int J
Obes. 2002;26:593-604.
15. Bent S, Tiedt TN, Odden MC, et al. The Relative Safety of
Ephedra Compared with Other Herbal Products. Ann Int Med. 2003;138:468-
471.
16. Shekelle P, Hardy M, Morton SC, et al. Ephedra and Ephedrine
for Weight Loss and Athletic Performance Enhancement: Clinical Efficacy
and Side Effects. Prepared for Agency for Healthcare Research and
Quality, U.S. Department of Health and Human Services. (Contract No.
290-97-0001, Task Order No. 9) (AHRQ Publication No. 03-E-022), 2003.
17. Cohn JN, Levine TD, Olvarin T, et al. Plasma Norepinephrine as
a Guide to Prognosis in Patients with Chronic Congestive Heart Failure.
N Engl J Med. 1984;311:819-823.
18. Meredith IT, Broughton A, Jennings GL, et al. Evidence of a
Selective Increase in Cardiac Sympathetic Activity in Patients with
Sustained Ventricular Arrhythmias. N Engl J Med. 1991;325:618-624.
19. Zipes DP. Sympathetic Stimulation and Arrhythmias. Editorial. N
Engl J Med. 1991;325:656-657.
20. Bouvy ML, Heerdink ER, DeBruin ML, et al. Use of
Sympathomimetic Drugs Leads to Hospitalization for Arrhythmias in
Patients with Congestive Heart Failure. Arch Int Med. 2000;160:2477-
2480.
21. Zoccali C, Mallamaci F, Parlongo S. Plasma Norepinephrine
Predicts Survival and Incident Cardiovascular Events in Patients with
End-stage Renal Disease. Circulation. 2002;105:1354-1359.
22. Brunner-LaRocca HP, Esler MD, Jennings GL. Effect of Cardiac
Sympathetic Nervous Activity on Mode of Death in Congestive Heart
Failure. European Heart Journal. 2001;22:1069-1071.
23. Drede M, Wiesmann F, Jahns R. Feedback Inhibition of
Catecholamine Release by Two Different Alpha2-Adrenoceptor Subtypes
Prevents Progression of Heart Failure. Circulation. 2002;106:2491-
2496.)
24. Hein L, Altman JD, Kobilka, BK. Two Functionally Distinct
Alpha2-Adrenergic Receptors Regulate Sympathetic Neurotransmission.
Nature. 1999;402:181-184.
25. Yang P, Kanki H, Drolet B, et al. Allelic Variance in Long QT
Disease Genes and Patients with Drug-associated Torsades de Pointes.
Circulation. 2002;105:1943-1948.
Mr. Greenwood. Thank you, Dr. Zipes and your very excellent
presentation. I appreciate that.
Dr. Culmo?
TESTIMONY OF CYNTHIA CULMO
Ms. Culmo. Good morning.
Thank you, Mr. Chairman, Honorable Representative Greenwood
and the committee members and Congresswoman Davis for this
opportunity to participate in this important and critical
discussion.
I appreciate the honor, but I would be remiss not to
mention or point out that I do not have a doctorate degree so
Ms. is the appropriate salutation.
I have served as the previous Director for Drugs and
Medical Devices for the Texas Department of Health and the
chairperson for the Drugs, Devices and Cosmetics Committee for
the Association of Food and Drug Officials. And I still serve
as a member of the United States Pharmacopeia Expert Panel for
Dietary Supplement Information.
My comments are based upon my knowledge and experience in
these positions for the last 12 years, and as an expert witness
in civil lawsuits with dietary supplement companies.
I have no financial interest with this issue.
A primary premise of DSHEA is that dietary supplements are
assumed to be safe for consumption and beneficial to health. I
do not believe that these products do or can meet that safety
assumption. I'll summarize my most concerning points.
There have been more serious adverse event reports for
dietary supplements containing ephedra alkaloids than for any
other type of dietary supplement, or the OTC, over-the-counter
phenylpropanolamine drug products which were withdrawn from the
U.S. markets last year due to the increased risk of hemorrhagic
stroke in young women. The serious adverse events have already
been discussed by everyone here. They are known, documented and
expected consequences of the use of ephedrine.
Pharmacologically in the body there is no difference
between natural and synthetic ephedrine. They act the same in
the body. By regulation drug products containing ephedrine
cannot be combined with any other stimulate based upon the
potential for abuse and safety concerns. Not so for dietary
supplements.
Currently marketed dietary supplements for enhanced
athletic performance, increased energy and weight loss don't
just contain ephedrine. Almost all of the multi-ingredient
products contain ephedrine with other stimulants, diuretics,
laxatives and other active ingredients. These multi-ingredients
can interact with each other and other products, drugs and/or
foods and they have well known counter-indications as well as
documented and well known drug disease interactions. Studies
identifying these complex interactions which have definite
effect on the safety of these products are available.
The United States has developed a rigorous and widely
emulated system for evaluation and approval of new drugs. The
United States, however, did not emulate countries such as Japan
and Germany which accommodated national traditions by
developing special regulations for traditional medicines and
dietary supplements in general.
In Europe the European Union is developing specific
regulations on botanical products under the drug system. The EU
directives regulate the manufacturing, the distribution, the
marketing and approval of herbal products in addition to
requirements for post-market surveillance.
Although the industry routinely claims that their products
are not drugs, they are posed to the consumer as drug products
by their claims, the manner in which they are advertised, the
way the information is shared by health professionals, which
some are sold by these health professionals and doctors, and
they are advertised the infamous PDR, the Physicians Desk
Reference; all of which can mislead the consumer.
Many of the studies the industry uses to support safety
came from foreign data for prescription drugs using
pharmaceutical ephedrine and caffeine. These products are not
the same. None of these studies can be used to support the
safety of dietary supplements. Recently the Danish government
withdrew the prescription drug Letigen. This is the product
that the Astrup studies utilized and that the industry
routinely references and bases the safety and efficacy of these
products on.
Also note, it is a product that has only two active
ingredients in it. Nothing like the multi-ingredient products
in the United States. Letigen is an ephedrine caffeine weight
loss product removed from the market due to the same types of
adverse events reports FDA has received on ephedrine containing
dietary supplements.
There are numerous methodology problems with a relatively
few studies in the United States, including being too small,
not using marketed products, the infamous Boozer 6 month study
did not use Metabolife 356. So the results of these studies
cannot be applied to the general population for efficacy, much
less safety. Companies always say in report, especially to the
media and you will probably hear it in this hearing today, that
billions of doses of ephedra have been used safely. Everyone
needs to remember that these are doses sold, maybe, not
consumed. This is another example of false and misleading
information.
DSHEA shifted the requirement of proving a product is
unsafe to the government. Many States have had to pick up this
tremendous burden because of the apparent inability of the
Federal Government to effectively address safety issues
associated with these products. Under DSHEA safety is addressed
after harm has already occurred. The standards and the criteria
of safety have never been defined by FDA or the court.
A major question yet to be answered is what is questionable
or unreasonable risk that causes a product to be adulterated?
The most egregious safety problems with a dietary supplement
for enhanced performed, increased energy and weight loss right
now, obviously, are products containing ephedrine. The
situation is not a scientific issue any longer. It is a
political issue run by a political agenda. There are ongoing
conflicts between good public health and the industry's
economic needs with politics frequently serving as the referee.
Consumers are being misled and they are not getting the
full story about the risk associated with these products. They
cannot make an informed decision about appropriate use.
Labeling and warnings cannot solve the safety issues. The
warnings and the labels will not help when you do not know that
you have a condition that places you at increased risk.
A firm which has recently been sued is using the defense
that the victim was overweight and out of shape. Where do any
of these products say that being overweight, exercising which
is usually recommended and taking these products are dangerous?
In the past the States have indicated and continue to
experience numerous problems associated with dietary
supplements with ephedrine and have recommended a number of
solutions:
Except for traditional nutrients such as vitamins and
minerals prohibit or limit botanicals and other natural
products to a single ingredient. This is what Health Canada has
done with ephedra. If you are going to be taking combination
products as a dietary supplement, then they should be required
to have pre-market review for safety.
Require the manufacturers and the distributors to register
with FDA and list their products and ingredients. This is going
to be one of the requirements due to bioterrorism now. But this
will enable FDA to develop appropriate product data bases to
evaluate products, adverse event reports and their
interactions.
Institute mandatory adverse event reports. Analogous to
what is required for drugs, biologics and medical devices.
These are active ingredients and they should be treated as
such, otherwise why are not these studies being done by the
companies in an effort to somewhat substantiate their efficacy
claims?
Implement an integrated adverse event reporting system
within the FDA. Adverse event report, evaluation and risk
management is best directed by regulatory agencies.
Define the criteria for DSHEA, the standard of significant
or unreasonable risk. What is the standard to prove that a
product is safe? From a science perspective if what is
currently known about ephedra supplements and cannot meet the
standard, what in the world will?
Create a specific center within FDA for traditional
medicines and dietary supplements for regulatory oversight, and
appropriate funding and improve authority to the FDA is
necessary for all of the above.
In conclusion, I appreciate this opportunity to provide you
with my comments. It's tragic that once again deaths have had
to occur to bring this topic one more time to the forefront for
discussion. Hopefully, this time actions will be taken and
other unsuspecting victims will be spared.
I have no doubt that products currently marketed dietary
supplements for increased energy, improved athletic performance
and weight loss purposes are either not safe or of unknown
safety and the public health is not being adequately protected.
I believe that a total ban of these products is the only
ethically acceptable public health solution. Warnings and
dosage and ingredient limitations are not going to address this
public health risk.
This is simple. How many more bodies does it take? I would
agree with Dr. Woosley, no more studies, no more labeling
requirements. The FDA is neglecting its duties and
responsibilities to protect the public health. Public health
decisions should not be allowed to be ruled by politics or by
referring scientific decisions to the court. It is time to
place the politics and the money aside at the Federal level and
act as the responsible public health agency that the general
public considers the FDA to be and to which it is charged.
You the politicians must, too, be responsible and support
this charge for the public, your constituents.
Thank you very much.
Mr. Greenwood. Thank you, Ms. Culmo. We appreciate your
testimony very much.
Dr. Crosse?
TESTIMONY OF MARCIA CROSSE
Ms. Crosse. Yes, Mr. Chairman, members of the subcommittee
and Representative Davis, I am pleased to have the opportunity
to testify as the subcommittee considers dietary supplements
that contain ephedra.
Reports of adverse health events associated with such
supplements, including reports of heart attacks, strokes,
seizure and death have been received by FDA and others
including Metabolife International, the manufacturer of a
dietary supplement containing ephedra, Metabolife 356. Because
of concerns surrounding the marketing and use of supplements
containing ephedra you asked us to examine FDA's analysis of
adverse events reports it has received about such supplements,
how the adverse events reported to Metabolife International
illustrate the health risks of dietary supplements containing
ephedra, and FDA's actions in the oversight of such
supplements.
Because dietary supplements are generally marketed without
prior FDA review of their safety, FDA relies on voluntary
reports of adverse events from consumers, health professionals,
manufacturers and others in its efforts to oversee the safety
of marketed dietary supplements. Based on over 2000 adverse
event reports it has received on supplements containing
ephedra, FDA has determined that such supplements pose a
significant public health hazard. The number of adverse event
reports FDA has received for dietary supplements containing
ephedra is 15 times greater than the number it has received for
the next most commonly reported herbal dietary supplement.
While it is difficult to establish with certainty that a
particular adverse event has been caused by the use of ephedra,
based on the pattern of adverse event reports it has received
and the scientific literature it has reviewed, FDA has
concluded that ephedra poses a risk of cardiovascular and
nervous system effects among consumers who are young to middle-
aged.
In our review of health related call records from
Metabolife International, we identified adverse events that
were consistent with the types of adverse events reported to
FDA and with the documented physiological effects of ephedra.
We identified over 14,000 call records that contained reports
of at least one adverse event among consumers of Metabolife
356. Among these were 92 serious events--heart attacks,
strokes, seizures and deaths--and over 1,000 events of the
types that FDA has identified as serious or potentially serious
including chest pain and significant elevations in blood
pressure.
Many of the serious events were among relatively young
consumers. More than one-third concerned consumers who were
under age 30.
In addition, we found that most of the serious adverse
events occurred among consumers who followed the usage
guidelines on the Metabolife 356 label. The consumers did not
take more of the product or take it for a longer period than
the company recommended.
FDA has taken some actions specifically focused on dietary
supplements containing ephedra, as we have heard about. The
agency has issued warnings to manufacturers that focus on
improper labeling and issued warnings to consumers,
particularly about dietary supplements that contain both
ephedra and stimulants such as caffeine.
In 1997 FDA issued a proposed rule that, among other
things, would require a health warning on the label and
prohibit a supplement from containing both ephedra and a
stimulant. This rule has not been finalized and many dietary
supplements that contain both ephedra and stimulant ingredients
including Metabolife 356 continue to be marketed. In the
meantime, FDA has banned over-the-counter drugs that contain
such combinations.
In summary, Mr. Chairman, significant concerns have been
identified regarding dietary supplements that contain ephedra.
Because the regulatory framework for dietary supplements is
primarily a post-marketing program and FDA does not review the
safety of dietary supplements before they are marketed, adverse
event reports are important sources of information about the
health risks of dietary supplements containing ephedra. The
adverse event reports FDA received for dietary supplements
containing ephedra and the consistency of those reports with
the scientific literature led the agency to conclude 3 years
ago that these supplements pose a significant public health
hazard. It is, therefore, important that FDA move forward
quickly in determining what further actions are warranted.
Mr. Chairman, this completed my prepared statement. I would
be happy to answer any questions you or other members may have.
[The prepared statement of Marcia Crosse follows:]
Prepared Statement of Marcia Crosse, Acting Director, Health Care-
Public Health and Science Issues, U.S. General Accounting Office
Mr. Chairman and Members of the Subcommittee: I am pleased to be
here today as the Subcommittee considers concerns about the safety of
dietary supplements containing ephedra. More than half of U.S. adults
are overweight or obese, and more than one-third are trying to lose
weight. Many Americans have turned to dietary supplements to help them
lose weight. The most widely used weight loss supplement ingredient is
ephedra, which is also referred to as ma huang.<SUP>1</SUP> The dietary
supplement industry has estimated that as many as 3 billion servings of
dietary supplements containing ephedra are consumed each year in the
United States. Medical experts have expressed concerns about the safety
of dietary supplements containing ephedra. Reports of adverse health
events associated with such supplements, including reports of heart
attack, stroke, seizure, and death, have been received by the Food and
Drug Administration (FDA) and others, including Metabolife
International, the manufacturer of a dietary supplement containing
ephedra, Metabolife 356.
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\1\ The active ingredients in ephedra are ephedrine alkaloids.
Ephedrine alkaloids that are not from an herbal or botanical source (or
a derivative thereof), such as synthetic ephedrine alkaloids, may not
be marketed as dietary supplements.
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The Dietary Supplement Health and Education Act of 1994 (DSHEA)
created a framework for FDA's regulation of dietary supplements as part
of its oversight of food safety.<SUP>2</SUP> Since dietary supplements
are generally marketed without prior FDA review of their safety, FDA
relies on voluntary reports of adverse events from consumers, health
professionals, manufacturers, and others in its effort to oversee the
safety of marketed dietary supplements.
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\2\ Pub. L. No. 103-417, 108 Stat. 4325.
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Because of concerns surrounding the safety of dietary supplements
containing ephedra, you asked us to discuss some of the findings from
our prior work on ephedra. My remarks today will focus on (1) FDA's
analysis of adverse event reports it has received about dietary
supplements containing ephedra, (2) how the adverse events reported in
the call records received by Metabolife International illustrate the
health risks of dietary supplements containing ephedra, and (3) FDA's
actions in the oversight of dietary supplements containing ephedra.
This testimony is based primarily on our earlier reports on dietary
supplements, including our March 2003 review of health-related call
records received by Metabolife International.<SUP>3</SUP> For this
testimony, we also conducted additional analyses of the data in the
Metabolife International call records, obtained updated information
from FDA about its oversight efforts and adverse event reports that it
has received concerning ephedra, and reviewed FDA analyses of the
safety of dietary supplements containing ephedra. We conducted our work
from June 2003 through July 2003 in accordance with generally accepted
government auditing standards.
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\3\ U.S. General Accounting Office, Dietary Supplements:
Uncertainties in Analyses Underlying FDA's Proposed Rule on Ephedrine
Alkaloids, GAO/HEHS/GGD-99-90 (Washington, D.C.: July 2, 1999); Health
Products for Seniors: ``Anti-Aging'' Products Pose Potential for
Physical and Economic Harm, GAO-01-1129 (Washington, D.C.: Sept. 7,
2001); Dietary Supplements for Weight Loss: Limited Federal Oversight
Has Focused More on Marketing Than on Safety, GAO-985T (Washington,
D.C.: July 31, 2002); and Dietary Supplements: Review of Health-Related
Call Records for Users of Metabolife 356, GAO-03-494 (Washington, D.C.:
Mar. 31, 2003).
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In summary, FDA has determined that dietary supplements containing
ephedra pose a significant public health hazard based on the 2,277
adverse events reports it has received. The number of adverse event
reports FDA has received for dietary supplements containing ephedra is
15 times greater than the number it has received for the next most
commonly reported herbal dietary supplement. While it is difficult to
establish with certainty that a particular adverse event has been
caused by the use of ephedra, based on the pattern of adverse event
reports it has received and the scientific literature it has reviewed,
FDA has concluded that ephedra poses a risk of cardiovascular and
nervous system effects among consumers who are young to middle-aged.
The types of adverse events that we identified in the health-
related call records from Metabolife International were consistent with
the types of adverse events reported to FDA and with the documented
physiological effects of ephedra. Although the call records contained
limited information for most of the reports, we identified 14,684 call
records that contained reports of at least one adverse event among
consumers of Metabolife 356. Our count of 92 serious events--heart
attacks, strokes, seizures, and deaths--was similar to that of other
reviews of the call records, including counts by Metabolife
International and its consultants. Many of the serious events were
reported among relatively young consumers--more than one-third
concerned consumers who reported an age under 30. In addition, for the
call records containing information on the amount of product consumed
or length of product use, we found that most of the reported serious
adverse events occurred among consumers who followed the usage
guidelines on the Metabolife 356 label--the consumers reported that
they did not take more of the product or take it for a longer period
than the company recommended.
As part of its oversight of dietary supplements, FDA has taken some
actions specifically focused on dietary supplements containing ephedra.
FDA has issued warnings to manufacturers that focus on improper product
labeling, issued warnings to consumers, and issued a proposed rule in
1997 that, among other things, would require a health warning on the
label of dietary supplements containing ephedra and prohibit a dietary
supplement from containing both ephedrine alkaloids--the active
ingredient in ephedra--and a stimulant. FDA subsequently banned the
sale of certain classes of over-the-counter drugs containing ephedrine
and related alkaloids in combination with an analgesic or stimulant. As
the 1997 proposed rule has not been finalized, there is no rule
prohibiting the marketing of dietary supplements with similar
ingredients, and many dietary supplements with ephedra, such as
Metabolife 356, also include caffeine or other stimulants. To receive
comments on new evidence, FDA recently reopened the comment period for
the proposed rule, and FDA reported to us that the agency is in the
process of reviewing comments it has received and has not reached a
decision regarding further action.
BACKGROUND
Ephedra, the most widely used ingredient in dietary supplements for
weight loss, is a powerful stimulant that can affect the nervous and
cardiovascular systems. Adverse events among consumers of dietary
supplements containing ephedra have been described in scientific
literature and in detailed adverse event reports. Because of concerns
about the risks of ephedra, medical organizations, states, and athletic
associations have sought to reduce the use of dietary supplements
containing ephedra.
FDA Oversight of Dietary Supplements under DSHEA
Under DSHEA, FDA regulates dietary supplements, including vitamins,
minerals, herbs and other botanicals, amino acids, certain other
dietary substances, and derivatives of these items. DSHEA requires that
dietary supplement labels include a complete list of ingredients and
the amount of each ingredient in the product.<SUP>4</SUP> Dietary
supplements may not contain synthetic active ingredients that are sold
in over-the-counter drugs and prescription medications and cannot be
promoted as a treatment, prevention, or cure for a specific disease or
condition.
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\4\ Products may include ``proprietary blends,'' which must list
all ingredients but do not need to list the amount of each ingredient.
---------------------------------------------------------------------------
Under DSHEA, manufacturers are responsible for ensuring the safety
of dietary supplements they sell. Dietary supplements do not need
approval from FDA before they are marketed; thus FDA generally
addresses safety concerns only after dietary supplements are marketed.
DSHEA does not require manufacturers to register with FDA,<SUP>5</SUP>
identify the products they manufacture, or provide reports of adverse
events to FDA. Mechanisms that FDA uses to oversee dietary supplements
and other products it regulates differ (see app. I for more details).
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\5\ However, manufacturers and distributors of dietary supplements
are required to register with FDA no later than December 13, 2003,
under the Public Health Security and Bioterrorism Preparedness and
Response Act of 2002, Pub. L. No. 107-188, 116 Stat. 594. FDA issued a
proposed rule in February 2003 to implement the requirement. See 68
Fed. Reg. 5378 (Feb. 3, 2003).
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Since manufacturers of dietary supplements are not required to
provide reports of adverse events to FDA, the agency relies on
voluntary postmarket reporting of adverse events to better understand
the safety of dietary supplements. Some individual adverse event
reports are especially valuable to FDA because they include enough
information to help FDA determine if the adverse event was likely
caused by the supplement. These reports include information about the
receipt of medical care, health care professionals' attribution of
adverse events to the consumption of dietary supplements, the
consumer's appropriate use of the products, the consumer's use of other
products, underlying health conditions and other alternative
explanations for the adverse event, and the consistency of symptoms
with the documented effects of the dietary supplement.
FDA, through the Department of Justice, can take enforcement action
in court against dietary supplements that are adulterated to remove
them from the market.<SUP>6</SUP> A dietary supplement is considered
adulterated under a number of circumstances, including when it
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\6\ ``Adulterated'' is the statutory term used to describe dietary
supplements and other FDA-regulated products that are unsuitable for
marketing. It is illegal to market any adulterated product.
presents a ``significant or unreasonable risk of illness or injury''
under the conditions of use recommended or suggested in its
labeling, or under ordinary conditions of use if there are no
suggestions or recommendations in the labeling, or
bears or contains any ``poisonous or deleterious substance'' which
may render it injurious to health under the conditions of use
recommended or suggested in its labeling.
Instead of going to court, FDA may choose to take administrative
action to prohibit the sale of dietary supplements it considers to be
adulterated. FDA can promulgate a regulation declaring a particular
dietary supplement to be adulterated. FDA has not taken this action
with any dietary supplement. FDA can also issue an advisory letter
explaining why it considers the dietary supplement to be adulterated.
The advisory letter provides guidance to the industry regarding FDA's
opinion and notifies the public that FDA may take legal action against
firms or individuals that do not follow the letter's advice. FDA has
done this for two dietary supplement ingredients, comfrey and
aristolochic acid.
In addition, although it has never been done, the Secretary of
Health and Human Services (HHS) may declare that a dietary supplement
is adulterated because it poses an ``imminent hazard'' to public health
or safety. In doing so, the Secretary must initiate an administrative
hearing to affirm or withdraw the declaration.
Health Concerns about Ephedra
Ephedra has been associated with numerous adverse health effects.
As we previously reported,<SUP>7</SUP> case reports and scientific
literature have suggested that ephedrine alkaloids can increase blood
pressure in those with normal blood pressure, predispose certain
individuals to rapid heart rate, and cause stroke, among other things.
We also reported descriptions of adverse events associated with
ephedrine alkaloids that affected the central nervous system, such as
seizures, mania, and paranoid psychoses. FDA has received reports of
adverse events associated with dietary supplements containing ephedra,
including heart attack, stroke, seizure, psychosis, and death, that are
consistent with the scientific literature. In February 2003, the RAND
Corporation released a review of the scientific evidence on the safety
and efficacy of dietary supplements containing ephedra <SUP>8</SUP> and
concluded that a sufficient number of cases of these same types of
events had occurred in young adults to warrant further scientific study
of the causal relationship between ephedra and these serious adverse
events. RAND also found that use of ephedra or ephedrine plus caffeine
is associated with a number of other adverse effects, including an
increased risk of nausea, vomiting, heart palpitations, and psychiatric
symptoms such as anxiety and change in mood.
---------------------------------------------------------------------------
\7\ GAO/HEHS/GGD-99-90.
\8\ Paul Shekelle, et al., Ephedra and Ephedrine for Weight Loss
and Athletic Performance Enhancement: Clinical Efficacy and Side
Effects. Evidence Report/Technology Assessment No. 76 (prepared by
Southern California Evidence-based Practice Center, RAND, under
Contract No. 290-97-0001, Task Order No. 9). AHRQ Publication No. 03-
E022 (Rockville, Md.: Agency for Healthcare Research and Quality,
February 2003).
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Because of these health concerns, many organizations and
jurisdictions have taken actions aimed at reducing the use of dietary
supplements containing ephedra. The American Medical Association and
the American Heart Association have urged FDA to ban the sale of
dietary supplements containing ephedra. In January 2002, Health Canada
issued a Health Advisory for Canadians not to use certain products
containing ephedra, especially those that also contain caffeine and
other stimulants. In 2003, Illinois banned the sale of products
containing ephedra and other states have similar bans under
consideration. In addition, some states have banned the sale of such
products to minors or required label warnings. Several sports
organizations, including the NCAA, the National Football League, the
U.S. Olympic Committee, and the International Olympic Committee, have
banned the use of ephedra by their athletes.
In 2003, General Nutrition Centers, the nation's largest specialty
retailer of nutritional supplements, discontinued the sale of products
containing ephedra, as have three other major retail outlets. Some
manufacturers have stopped producing dietary supplements containing
ephedra. Other manufacturers continue to offer dietary supplements
containing ephedra while also offering similar products that are
ephedra-free.<SUP>9</SUP>
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\9\ Some ephedra-free products include other herbal stimulants,
such as Citrus aurantium. Citrus aurantium contains synephrine, which
is chemically similar to the ephedrine and pseudoephedrine found in
many over-the-counter and allergy medicines and in dietary supplements
containing ephedra.
---------------------------------------------------------------------------
ADVERSE EVENT REPORTS HAVE LED FDA TO CONCLUDE THAT DIETARY SUPPLEMENTS
CONTAINING EPHEDRA POSE A SIGNIFICANT PUBLIC HEALTH HAZARD
Using the adverse event reports it has received and evidence from
the scientific literature, FDA has concluded that dietary supplements
containing ephedra pose a ``significant public health hazard.'' FDA and
others have received thousands of reports of adverse events among users
of dietary supplements containing ephedra, more than for any other
dietary supplement ingredient. Metabolife International also received
thousands of reports of adverse events.
More Adverse Events Have Been Reported for Products Containing Ephedra
Than for Any Other Dietary Supplement
FDA has received more reports of adverse events for dietary
supplements containing ephedra than for any other dietary supplement
ingredient. In addition, poison control centers and one manufacturer,
Metabolife International, have received thousands of reports of adverse
events associated with dietary supplements containing ephedra. From
February 22, 1993, through July 14, 2003, FDA received 2,277 reports of
adverse events associated with dietary supplements containing ephedra,
which was 15 times more reports than it received for the next most
commonly reported herbal dietary supplement, St. John's
wort.<SUP>10</SUP>
---------------------------------------------------------------------------
\10\ In total, FDA received 5,574 adverse reports for dietary
supplements during that period. The total number of reports of adverse
events for ephedra products includes 135 reports from the Metabolife
International call records that FDA designated as serious adverse
events.
---------------------------------------------------------------------------
Other organizations also have received a large number of adverse
event reports for dietary supplements containing ephedra. The American
Association of Poison Control Centers received 1,428 reports of adverse
events associated with dietary supplements containing ephedra, either
alone or in combination with other botanical dietary supplement
ingredients, in 2002,<SUP>11</SUP> nearly two-thirds as many as FDA
received over a 10-year period. The centers noted that there were more
reports of adverse events for ephedra-containing dietary supplements
than for others. Further, as we reported in March 2003, Metabolife
International had 14,684 health-related call records that contained
reports of adverse events associated with its product, Metabolife 356,
from May 1997 through July 2002.<SUP>12</SUP> Neither the American
Association of Poison Control Centers nor Metabolife International is
required to report these adverse events to FDA.
---------------------------------------------------------------------------
\11\ William A. Watson, et al., ``2002 Annual Report of the
American Association of Poison Control Centers Toxic Exposure
Surveillance System,'' American Journal of Emergency Medicine (in
press). See also Stephen Bent, et al., ``The Relative Safety of Ephedra
Compared with Other Herbal Products,'' Annals of Internal Medicine,
vol. 138 (2003), 468-471.
\12\ GAO-03-494.
---------------------------------------------------------------------------
FDA Has Determined That the Adverse Event Reports and Scientific
Literature Indicate That Dietary Supplements Containing Ephedra
Pose a Significant Public Health Hazard
From the adverse event reports it has received and the scientific
literature it has reviewed, FDA concluded in March 2000 that dietary
supplements containing ephedra pose a significant public health hazard
that primarily involves consumers who are young to middle-aged and can
result in adverse cardiovascular and nervous system
effects.<SUP>13</SUP> It further concluded that many of the adverse
events were serious, resulting in morbidity and mortality that would
not be expected in a young population and that could further compromise
the health of more vulnerable older adults or those with underlying
conditions.
---------------------------------------------------------------------------
\13\ Food and Drug Administration, Assessment of Public Health
Risks Associated with the Use of Ephedrine Alkaloid-containing Dietary
Supplements (Mar. 31, 2000) (Docket No. 00N-1200).
---------------------------------------------------------------------------
A study commissioned by FDA estimated that the agency receives
reports for less than 1 percent of adverse events associated with
dietary supplements.<SUP>14</SUP> Although causality cannot be
determined based on the individual adverse event reports FDA receives,
the agency uses these reports to identify possible risks to consumers
from dietary supplements. As we have previously reported, there are
well-known weaknesses in the current system of voluntary reporting of
adverse events, such as different interpretations in determining an
adverse event, underreporting, difficulties estimating population
exposure, and poor report quality.<SUP>15</SUP> Despite these
limitations, FDA maintains that even isolated reports can be definitive
in associating products with an adverse effect if the report contains
sufficient evidence, such as supporting medical documents, a temporal
relationship between the product and effect, and evidence of
dechallenge and rechallenge.<SUP>16</SUP>
---------------------------------------------------------------------------
\14\ U.S. Department of Health and Human Services, Office of
Inspector General, Adverse Event Reporting for Dietary Supplements: An
Inadequate Safety Valve, OEI-01-00-00180 (Washington, D.C.: Apr. 2001).
\15\ GAO/HEH/GGD-99-90.
\16\ Dechallenge is evident when signs and symptoms resolve or
improve when a consumer stops using a product, and rechallenge is
evident when symptoms recur when the consumer resumes using the
product.
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METABOLIFE INTERNATIONAL CALL RECORDS CONTAIN REPORTS OF ADVERSE EVENTS
THAT ARE CONSISTENT WITH THE TYPES OF ADVERSE EVENTS REPORTED TO FDA
The types of adverse events that we identified in the Metabolife
International call records are consistent with the types of adverse
events reported to FDA and with the documented physiological effects of
ephedra. As we recently reported, most of the Metabolife International
call records contained limited information about the event and the
consumer. Nonetheless, the call records contribute to existing
knowledge about adverse events that have been associated with ephedra
use. In our review, we identified 14,684 call records that contained
reports of at least one adverse event among consumers of Metabolife
356. Within these call records, we found 92 reports of serious adverse
events--heart attacks, strokes, seizures, and deaths--a count that was
similar to that of other reviews of the call records. In addition, the
call records contain reports of serious adverse events in consumers who
were young and among those who used the product within the recommended
guidelines. These findings are consistent with reports FDA has received
regarding dietary supplements containing ephedra.
Consumer Information in the Metabolife International Call Records Was
Limited
In our review of health-related call records for users of
Metabolife 356,<SUP>17</SUP> we found that the information in the call
records was limited. Call records were sometimes difficult to read and
interpret, and consumer information was not consistently recorded. In
some cases, the evidence for a report of an adverse event was limited
to a single word on a call record. In other cases, information was
entered into a form developed by Metabolife International with multiple
boxes for consumer- and event-related information. Most call records
did not document complete information about the consumer's age, sex,
weight, and height. Because the company did not systematically follow
up on calls reporting adverse events, and the adverse events were not
reported to FDA, it is not possible to gather more complete information
or medical records.
---------------------------------------------------------------------------
\17\ GAO-03-494.
---------------------------------------------------------------------------
METABOLIFE INTERNATIONAL CALL RECORDS CONTAINED REPORTS OF THOUSANDS OF
ADVERSE EVENTS, SOME OF WHICH WERE SERIOUS, AMONG CONSUMERS OF
METABOLIFE 356
As we reported in March 2003, we identified 14,684 call records
that contained at least one report of an adverse event among consumers
of Metabolife 356.<SUP>18</SUP> The types of reported adverse events
were consistent with the cardiovascular and central nervous system
effects that have been associated with ephedra products in the
literature, adverse event reports received by FDA, other case reports,
and RAND's review. Within the call records, we identified 92 reports of
heart attack, stroke, seizure, and death (see table 1).<SUP>19</SUP>
Our count of reports of these serious adverse events was similar to
that of other reviews of the Metabolife International call records,
including counts by Metabolife International and its
consultants.<SUP>20</SUP>
---------------------------------------------------------------------------
\18\ A single call record may have had more than one complaint.
\19\ We highlighted these serious adverse events because they are
identified in FDA's proposed label warning for dietary supplements
containing ephedra. See 68 Fed. Reg. 10417 (Mar. 5, 2003).
\20\ Metabolife International has not issued a report on its review
of the call records, but provided us with a list of the calls it
believed to report heart attack, stroke, seizure, and death. Metabolife
International also commissioned reviews by three consultants (see GAO-
03-494).
Table 1: Number of Reports of Heart Attack, Stroke, Seizure, or Death in
Metabolife International Call Records
------------------------------------------------------------------------
Type of adverse event Number\1\
------------------------------------------------------------------------
Heart attack................................................. 18
Stroke....................................................... 26
Seizure...................................................... 43
Death........................................................ 5
------------------------------------------------------------------------
Source: Metabolife International.
Note: GAO analysis of 14,684 health-related call records provided by
Metabolife International.
\1\ The counts do not represent unique consumers because a single call
record may have more than one complaint and because some consumers
called the Metabolife health information phone line more than once.
We also found 1,079 reports of other types of adverse events that
FDA identified as serious or potentially serious.<SUP>21</SUP> These
included chest pain, significant elevations in blood pressure, systemic
rash, and urinary infection. In addition to these 1,079 reports, we
found records that contained reports of a broad range of other types of
adverse events, including changes in heart rate such as palpitations
and increased heart rate; blood in stool; blood in urine; bruising;
hair loss; and menstrual irregularity.<SUP>22</SUP>
---------------------------------------------------------------------------
\21\ In its 1997 proposed rule on dietary supplements containing
ephedra, FDA identified as serious or potentially serious some types of
adverse events for which the agency had received reports. See 62 Fed.
Reg. 30678 (June 4, 1997).
\22\ Within the complete set of call records, we also found 332
reports of visits to either an emergency department or a hospital.
According to FDA officials, unlike most adverse events related to
foods, adverse event reports it had received related to ephedra
products commonly involved a visit to a physician or an emergency room.
FDA considers a hospitalization or prolongation of an existing
hospitalization to be a serious adverse event. Metabolife International
records did not consistently distinguish between an actual
hospitalization and ``going to the hospital,'' which may not have
resulted in an actual hospitalization.
---------------------------------------------------------------------------
Reports of Serious Adverse Events Involved Consumers Who Were
Relatively Young
Within the subset of call records that contained information on
age, the distribution of ages suggests that a relatively young
population was experiencing the reported serious adverse events. Among
the call records that contained a report of a serious event, 44 percent
included information on age.<SUP>23</SUP> For these call records, more
than one-third concerned consumers who reported an age under 30--the
average reported age was 38 (ranging from 17 to 65). As noted above,
FDA has also received reports of serious adverse events occurring in a
population of young adults. Because we do not know the age profile of
all Metabolife 356 consumers, we cannot determine if the age
distribution among those reporting serious adverse events in the
Metabolife International call records reflects that age profile.
---------------------------------------------------------------------------
\23\ For the entire set of the Metabolife International call
records, 42 percent contained information on the age of the consumer.
---------------------------------------------------------------------------
Serious Adverse Events Were Reported among Consumers Who Used
Metabolife 356 within Recommended Guidelines
Within the subset of Metabolife International call records that
contained information on how the product was used by the consumer, most
of the reported serious adverse events occurred among consumers who
reported using the product within the guidelines on the Metabolife 356
label--that is, who reported that they did not take more of the product
or take it for a longer period than recommended.<SUP>24</SUP>
Information about product use, however, was incomplete--40 and 55
percent of the call records that reported a serious event contained
information about the amount of Metabolife 356 used and the duration of
use, respectively. Among the call records that reported a serious
adverse event and also contained information about product use, 97
percent of consumers reported using an amount of product within the
recommended guidelines. Similarly, 71 percent of those consumers
reported using the product for a length of time that was within the
recommended guidelines.<SUP>25</SUP> This pattern is consistent with
findings from FDA's review of adverse events associated with ephedra
products.<SUP>26</SUP>
---------------------------------------------------------------------------
\24\ The product label recommends that adults take one to two
caplets two to three times per day or every 4 hours, not to exceed
eight caplets per day. The label also recommends that persons should
not use the product for more than 12 weeks and that exceeding the
recommended amount may cause serious adverse health effects, including
heart attack or stroke.
\25\ For all call records containing information on the amount of
product used or duration of use, 99 and 91 percent of consumers,
respectively, reported using the product within the guidelines
recommended on the label.
\26\ Food and Drug Administration, March 2000.
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FDA HAS TAKEN SOME ACTIONS TO OVERSEE DIETARY SUPPLEMENTS CONTAINING
EPHEDRA
As part of its oversight of dietary supplements, FDA has taken some
actions specifically focused on dietary supplements containing ephedra.
FDA has issued warnings that focus on improper product labeling, issued
warnings to consumers, and issued a proposed rule in 1997 that, among
other things, would require a health warning on the label of dietary
supplements containing ephedra and prohibit a dietary supplement from
containing both ephedra and a stimulant. However, parts of this rule
remain under consideration 6 years after it was first proposed.
As we previously reported, FDA has focused its enforcement actions
regarding dietary supplements on improper labeling.<SUP>27</SUP> For
example, in February 2003, FDA issued warning letters to 26 firms that
sell dietary supplements containing ephedra. All of these letters
advised marketers that label claims for enhancement of physical
performance were unsubstantiated and the products were therefore
misbranded.
---------------------------------------------------------------------------
\27\ GAO-02-98-ST.
---------------------------------------------------------------------------
FDA and HHS have also directly warned consumers about the safety of
dietary supplements containing ephedra. In February 1995, FDA issued a
press release warning consumers about a specific dietary supplement
product that contained both ephedra and caffeine, because it had
determined that the product represented a threat to public health.
Further, in February 2003, the Secretary of HHS issued a statement to
caution people against using dietary supplements containing ephedra and
indicated that FDA continues to have serious concerns about the risks
of these dietary supplements.
FDA has also taken actions in its oversight of dietary supplements
in general. Specifically, FDA has conducted facility inspections
<SUP>28</SUP> and proposed good manufacturing practice (GMP)
regulations <SUP>29</SUP> that focus on product quality in general, not
the safety of an individual ingredient.
---------------------------------------------------------------------------
\28\ Since 1999, FDA, its state partners, and state contractors
have inspected 6 percent of the known dietary supplement manufacturing
and repacking facilities annually. Inspections focus on sanitation,
buildings and facilities, equipment, production, and process controls.
\29\ In March 2003, FDA issued proposed GMP regulations for dietary
ingredients and dietary supplements. See 68 Fed. Reg. 12158 (Mar. 13,
2003). The comment period for the proposed GMPs was extended until Aug.
11, 2003. See 68 Fed. Reg. 27008 (May 19, 2003). GMP regulations are
important in ensuring that the product is not contaminated and contains
what the label reports. They do not, however, address the safety of any
individual ingredient, such as ephedra.
---------------------------------------------------------------------------
FDA first issued a proposed rule to regulate dietary supplements
containing ephedrine alkaloids in 1997.<SUP>30</SUP> The proposed rule
would
\30\ 62 Fed. Reg. 30678 (June 4, 1997).
---------------------------------------------------------------------------
define the amount of ephedrine alkaloids in a serving of dietary
supplement at and above which the product would be deemed
adulterated (8 milligrams),
establish labeling requirements regarding maximum frequency of use
and daily serving limits,
require that labels on these supplements contain a statement warning
that the product should not be used for more than 7 days,
prohibit the use of ephedrine alkaloids with ingredients that have a
known stimulant effect (e.g., caffeine),
prohibit labeling claims that promote long-term intake of the
supplements to achieve the purported purpose,
require a warning statement in conjunction with claims that encourage
short-term excessive intake to enhance the purported effect,
and
require that specific warning statements appear on product labels.
Our 1999 report on the proposed rule was critical of the science
FDA used to support the serving size and duration of use limits in the
proposed rule.<SUP>31</SUP> However, we did not conclude that dietary
supplements containing ephedra were safe, and we commented that the
adverse events reported to FDA were serious enough to warrant FDA's
further investigation of ephedra safety. Primarily, we were concerned
that FDA used only 13 adverse event reports to establish serving limits
and had weak support for proposed limits on duration of use. Partly as
a result of our review, FDA withdrew the sections of the proposed rule
on serving size and duration of use limits.<SUP>32</SUP>
---------------------------------------------------------------------------
\31\ GAO/HEHS/GGD-99-90.
\32\ 65 Fed. Reg. 17474 (Apr. 3, 2000).
---------------------------------------------------------------------------
In the interim, FDA has taken action to regulate certain drugs that
contain ephedrine, the active ingredient in ephedra. In September 2001,
FDA issued a final rule stating that certain over-the-counter drugs
containing ephedrine and related alkaloids in combination with an
analgesic or stimulant could not be marketed as over-the-counter
drugs.<SUP>33</SUP> There currently is no similar rule prohibiting the
marketing of dietary supplements containing ephedra in combination with
analgesics or stimulants, such as caffeine. As a result, dietary
supplements may contain ingredients that are prohibited in drugs. In
fact, many dietary supplements with ephedra, such as Metabolife 356,
also include caffeine. The proposed rule contains a provision that
would prohibit dietary supplements from containing both ephedra and
other stimulants.
---------------------------------------------------------------------------
\33\ See 66 Fed. Reg. 49276 (Sept. 27, 2001).
---------------------------------------------------------------------------
In March 2003, almost 6 years after the initial proposal, FDA
reopened the comment period for the remaining provisions of this
proposed rule for 30 days.<SUP>34</SUP> FDA sought comments on three
areas:
---------------------------------------------------------------------------
\34\ 68 Fed. Reg. 10417 (Mar. 5, 2003).
New evidence on health risks associated with ephedra.
Whether the currently available evidence and medical literature
demonstrate that dietary supplements containing ephedra pose a
``significant or unreasonable risk of illness or injury'' under
the conditions of use recommended or suggested in their
labeling, or under ordinary conditions of use if there are no
suggestions in the labeling.
A new warning label for ephedra products that warns about reports of
serious adverse events after the use of ephedra, including
heart attack, seizure, stroke, and death; cautions that the
risk can increase with the dose, with strenuous exercise, and
with other stimulants such as caffeine; specifies certain
groups (such as women who are pregnant or breast feeding and
persons under 18) who should not use these products; and lists
other diseases, such as heart disease and high blood pressure,
that should rule out the use of ephedrine alkaloids.
On July 14, 2003, FDA reported to us that the agency is in the
process of reviewing the comments and has not reached a decision
regarding further action. While FDA has not attempted to ban the
marketing of dietary supplements containing ephedra, the agency has
sought, in these comments, additional information that would help it
determine whether or not such action would be warranted.
CONCLUDING OBSERVATIONS
Because the regulatory framework for dietary supplements is
primarily a postmarketing program and FDA does not review the safety of
dietary supplements before they are marketed, adverse event reports are
important sources of information about the health risks of dietary
supplements containing ephedra. It is often difficult to demonstrate
conclusively that a single reported adverse event was caused by
ephedra, but some individual reports, particularly when they are
complemented by follow-up investigation of the case, can be especially
informative. Although the information in the Metabolife International
call records we examined was limited, the types of adverse events we
observed were consistent with the known risks of ephedra, including
serious events such as five reports of death. Based on the pattern of
adverse event reports FDA has received and the consistency of those
reports with the known effects of ephedra from the scientific
literature, the agency concluded 3 years ago that dietary supplements
containing ephedra pose a ``significant public health hazard.'' FDA is
currently reviewing information that will help the agency determine
what further actions are warranted.
Mr. Chairman, this completes my prepared statement. I would be
happy to respond to any questions you or other Members of the
Subcommittee may have at this time.
Appendix I: Mechanisms for FDA Oversight of Different Types of Products
--------------------------------------------------------------------------------------------------------------------------------------------------------
Voluntary
Premarket postmarket Mandatory Safety-
Product Manufacturer approval Specific good adverse manufacturer related
Product class registration registration of manufacturing event reporting of labeling
products practices reporting adverse requirements
system events
--------------------------------------------------------------------------------------------------------------------------------------------------------
Dietary supplements................................... X \1\ Proposed in X Some
2003\2\
Conventional foods.................................... X\1\ X X \3\ Some
Food additives........................................ X\1\ X X X X
Monograph drugs \4\................................... X X X X X
New Drug Application drugs \5\........................ X X X X X X X
Infant formula \1\.................................... X X Proposed in X X X
1996\6\
--------------------------------------------------------------------------------------------------------------------------------------------------------
Source: GAO analysis of U.S Department of Health and Human Services, Office of Inspector General, Adverse Event Reporting for Dietary Supplements: An
Inadequate Safety Valve.
\1\ Under the Public Health Security and Bioterrorism Preparedness and Response Act of 2002, Pub.L. No. 107-188, 116 Stat. 594, manufacturers and
distributors are required to registered with FDA no later than December 13, 2003.
\2\ FDA proposed good manufacturing practices in March 2003. Comments are due to FDA by August 11, 2003. Regulations regarding the packaging of dietary
supplements containing iron were issued in 1997.
\3\ FDA does not collect or evaluate all adverse event reports on all conventional food. In addition, excluded from this system are the investigations
FDA conducts following food-borne illness outbreaks.
\4\ Monograph drugs are typically over-the-counter drugs that must adhere to specific safety standards set for each ingredient and do not undergo
clinical testing.
\5\ New Drug Applications must be submitted to FDA for all prescription drugs and some over-the-counter drugs prior to marketing. This application must
include data that demonstrate the safety and efficacy of the product.
\6\ The comment period for the proposed good manufacturing practices regulation was reopened in June 2003, and closes August 26, 2003.
Mr. Greenwood. Thank you very much, Dr. Crosse.
The Chair recognizes himself for inquiry, and I'm going to
start out with the question to Dr. Woosley. I think I know the
answer to this, but I would like to present it for the record.
The President of one of the ephedra companies has proposed
funding a long term study of ephedra to settle some of these
issues. What is your response to that?
Mr. Woosley. Mr. Chairman, you are right, you do know my
answer. As I said, we do not need further studies.
In the first place, this is an unethical study that would
have to be done. You would have to expose people without
medical supervision and without medical screening to ephedra in
order to answer this question. Because that is the way it is
being used by the public.
That study will never get passed an institutional review
board. We sort of hold ourselves here and we ask, do you think
we could go back to our institutional review board with a study
proposal and get it approved to answer this question does
unsupervised use of ephedra-containing alkaloids have any
health benefit or risk? The answer is no, that study cannot be
done. And it does not need to be done. This study has been done
in the public and the deaths are documented and the testimony
has been provided.
Mr. Greenwood. Thank you, sir.
Second question that I would like you and/or Dr. Zipes to
respond to. Cytodyne Technologies has provided this committee
with a report by Dr. Michael Baden to dispute the cause of Mr.
Bechler's death. Mr. Baden says that there are no medical
articles linking health stroke and ephedra.
And at this time I would like, without objection, enter
into the record the report of the Broward County, Florida
Coroner, dated July 23, 2003, which was a response to Dr.
Baden's study regarding the role of the ephedra-containing food
supplement in the death of Steven Bechler.
[The information referred to follows:]
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Mr. Greenwood. Would you respond to Mr. Baden's statement?
Mr. Woosley. Yes, Mr. Chairman.
There are numerous reports of ephedra inducing heatstroke.
There are animal studies documenting the ability of these
compounds to cause excessive temperature in animals. This is a
known pharmacologic effect of this entire class of compounds.
Drugs like ephedrine that cause your blood vessels to
constrict prevent your body from releasing heat, and especially
during exercise but it does not always require exercise. The
body temperature can reach levels that cause stroke, cause
death. It is well documented in the medical literature.
Mr. Greenwood. Dr. Zipes, do you want to add to that?
Mr. Zipes. Mr. Chairman, I would certainly agree with what
Dr. Woosley has said.
I think it is very important to recognize that we are
different people. There is biologic pleomorphism, we are not
all the same. We do not respond all the same to the same drug.
We now know, as an example, that there are generic influences
of this ``fight'' or ``flight'' type reaction that I spoke
about. There are individuals who have an excessive response
with an excessive release of adrenaline and do not take it back
up into the nerves so that it is floating in the body and can
cause a lot of the problems that we are talking about.
So that there would be no way to do a prospective trial and
screen for all of these individuals who may represent the bulk
of the adverse responses that we are seeing. And it is because
of this heterogeneity that exists that there may be 1 in a
1,000 or more that would have an adverse response.
Mr. Greenwood. And it seems to me as I have pondered this
issue for the last several months that the real line of
demarcation should not be whether the product is made from a
plant that comes from somewhere in the world or not, but it is
the extent of the physiological response that it engenders in
human beings that is the real question, and particularly the
extent of the potentially life threatening physiological
response. And that seems to me to be our duty to take under
consideration.
Let me turn to Mr. Vasquez. Can you hear me still, Mr.
Vasquez?
Mr. Vasquez. Yes, sir.
Mr. Greenwood. Thank you for remaining and for your
patience.
When you worked at Metabolife did you hear your coworkers
voice any concerns about the safety of the company's products?
Mr. Vasquez. Yes, sir. We had discussions in the lunchroom
in regards to, you know, the calls that we took. As nurses we
would compare notes, like I said earlier. And basically, you
know, ask questions about whether--is this product really safe
or why we get so many calls. And you have to wonder, I mean, if
people are taking the product and they see an 800 number on the
bottle, they call it. And they would ask why am I feeling like
this, whatever symptoms they are complaining about or calling
for. Is this normal, they would ask.
And it was basically a health concern from a medical
perspective.
Mr. Greenwood. Do you know if one of your coworkers whom
you had heard voice such concerns was fired for doing that?
Mr. Vasquez. When I was no longer employed in the company I
inquired about this specific nurse and they said that she was
let go because she was very vocal about the product, whether
you know, it was doing more harm than good.
Mr. Greenwood. Were you warned or persuaded by your
supervisor at Metabolife not direct complainants to describe
their symptoms but instead to just take their name and phone
number and give that to your supervisor?
Mr. Vasquez. It would depend on the severity of the call.
Some if it is minor like abdominal cramps, then you know you
would document that. We documented all calls. But if it was
moderate to severe, you had a procedure where we would take as
much information as we can get without being judgmental and I
would forward it to my supervisor Mr. Daniel Rodriguez. And we
were basically left in the dark and we would not know what
happened to that specific case. Mr. Rodriguez was the one who
was basically the key person that would follow up on specific
case.
Mr. Greenwood. Did anyone at Metabolife including your
supervisor at the Health Information Line, Mr. Rodriguez,
monitor your responses to customers who were complaining of
adverse events or negative side effects as a result of taking
Metabolife?
Mr. Vasquez. Like I said earlier, there were 10 registered
nurses on staff and Mr. Rodriguez and the medical director, Dr.
Smith, had the ability to listen to all the calls that were
coming in. And if they heard something, specifically Dan
Rodriguez, heard something that one of the nurses would say,
right after the call he would critique, for example, myself and
say probably you should have answered that call that way.
Mr. Greenwood. Did you feel under any pressure to conduct
yourself in those phone calls in any way other than you would
given what you said earlier in your testimony that you wanted
to just do no harm?
Mr. Vasquez. At times, yes. Because as a nurse it seemed
like the telemarketer script the kind of answer you would give
out and, you know, I was trained as a nurse, I went to school,
nursing school. You know, basically you had to really be more
impersonal than you cared.
While I was working there there was no nurse/patient/
consumer relationship that would, you know, you would be
looking out for the best interest of the caller rather than
the----
Mr. Greenwood. Did you feel that you were functioning more
as a marketer of the drug than as an advocate for the patient?
Mr. Vasquez. Definitely I wouldn't say marketer, because
they had a lot of advertisement. So not as a marketer. But more
like, you know, less of an advocate from a medical
professional, I would say so.
Mr. Greenwood. Thank you, sir. My time has expired.
The gentlelady from Colorado is recognized for 5 minutes.
Ms. DeGette. Thank you, Mr. Chairman.
My first question is for the Bechlers and for Mr. Riggins,
because there are a lot of dietary supplements being sold now
in the stores and, you know, all my middle aged friends and I
sit around and talk about what we should be taking to make
ourselves feel better. And listening to all the testimony
today, it kind of makes me realize people probably think that
these products are safe because they are not prescription drugs
or a doctor's order is not required. Do you think that that's
probably true, Mrs. Bechler?
Ms. Bechler. I do. In fact, my son as I hear it from his
wife----
Ms. DeGette. Just move that a little closer. That helps.
Yes.
Ms. Bechler. As I hear it from his wife, she got it at
workout place that she worked out at. And so you----
Ms. DeGette. So they were giving it out at the gym?
Ms. Bechler. Yes. In fact, my other son and I worked out at
a gym and they have it there. So why would not you natural
think that it is going to be as natural and it is herbal, and
it is safe.
Ms. DeGette. And, Mr. Riggins, what is your view on that?
Mr. Riggins. In our discussions with kids, and when I say
kids I am not just talking about high school students. We are
talking about college athletes as well, college students that
are looking to lose weight and with the general public. We have
found that when you start bringing the awareness out, when you
tell them that the FDA does not have--only has minimal control
over these companies, the majority of the people are appalled
at that. They just cannot understand how come a law will allow
a company just to run, as one individual put it, helter
skelter.
Ms. DeGette. But up until they know that information, they
just assume that the product is safe because it is being
allowed to just be sold helter skelter to the consumers, would
you not agree?
Mr. Riggins. That is exactly right. Exactly right.
Ms. DeGette. Thank you.
Dr. Heymsfield, I was intrigued by your testimony where you
were talking about the product labeling and you were talking
about when you began doing your research there was no product
labeling as to the dangers, and in fact some of the labels said
clinical tested. Is that correct?
Mr. Heymsfield. Well, some of the bottles had statements,
for example, ``independently laboratory tested for safety.''
Ms. DeGette. Have you looked at bottle of Metabolife
recently?
Mr. Heymsfield. I have not looked at a recent bottle, no.
Ms. DeGette. Okay. I have got one here in my hands.
Mr. Heymsfield. Yes.
Ms. DeGette. And there this big warning on the side of the
label here. Are you familiar with that warning?
Mr. Heymsfield. Yes. Yes.
Ms. DeGette. Do you know when they started putting that
warning on these bottles?
Mr. Heymsfield. I am not aware of the date of when that
appeared.
Ms. DeGette. Does anyone else know roughly when this
warning started appearing?
Mr. France. Jim France here, attorney for the Bechlers. I
believe it was early 2001.
Mr. Greenwood. Excuse me. I have to quickly swear you in if
you are going to actually speak.
[Witness sworn.]
Mr. Greenwood. Okay. You are under oath now.
Ms. DeGette. Mr. France, proceed.
Mr. France. Yes. In 1999 they were using another label that
had ``independently laboratory tested for safety'' where that
silver decal is on the front.
Ms. DeGette. This right here?
Mr. France. Yes. And then there was a class action lawsuit
called Gasperoni v. Metabolife that occurred in the year 2000.
And as a part of that settlement it is my understanding that
they could not advertise that their product was independently
laboratory tested for safety anymore and they put that little
decal on the front. And then they started selling the product--
--
Ms. DeGette. It is a butterfly.
Mr. France. Yes. It is a silver decal----
Ms. DeGette. It is a butterfly.
Mr. France. It is a butterfly. They put the butterfly over
the safety claim in 2001, I believe.
Ms. DeGette. And that is when they put the safety warnings
on?
Mr. France. And they added additional safety warning
information, but they failed to include the fact that they had
received thousands of AERs.
Ms. DeGette. Okay. Thank you.
Going back to Dr. Heymsfield. Thank you for helping us,
sir.
You said that the studies were flawed that were done by the
companies. I am wondering if you can tell me quickly some of
the reasons why you feel those studies were flawed?
Mr. Heymsfield. Well, this is my opinion, but some of the
published papers, for example, would report that effects were
statistically significant. And that has very specific meaning
to a scientist. But actually when you investigate the raw data
in the actual statistics, they did not achieve specific
significance. That was never revealed in the papers. They were
misrepresented. And I could give you many examples like that of
where----
Ms. DeGette. And I think in addition, Dr. Woosley and
others said that the studies were not scientifically controlled
because IRB would ever approve that kind of a study?
Mr. Heymsfield. Well, no longer. I mean, at the time the
adverse events were not as clearly recognized. But I today I
agree with them.
Ms. DeGette. Okay. Thank you.
Mr. Greenwood. The time of the gentlelady has expired. The
gentleman from New Hampshire is recognized to inquire for 5
minutes.
Mr. Bass. Thank you, Mr. Chairman. I have one question. Do
any of the doctors here see any medicinal value to ephedra? Is
there any reason--Okay. That is the only question I have.
I will yield the rest of my time to my friend Mr. Walden.
Mr. Walden. Thank you very much.
I would like to address my first question to the Bechlers,
and I know this is a difficult one, but how did you feel when
the Broward County Coroner concluded that ephedra was ``a
significant factor'' in your son's death?
Mr. Bechler. When they told us about it, we knew it had to
be something. It just was not heatstroke because he was in
perfect condition. I mean, there was nothing wrong with our
son. Nothing.
Mr. Walden. There have been reports that I have read in the
press that said he was terribly overweight. How overweight was
he went he went into camp?
Ms. Bechler. Ten pounds.
Mr. Bechler. Ten pounds.
Mr. Walden. Ten pounds?
Mr. Bechler. His body fat was less than it was a year
before.
Ms. Bechler. Which the Orioles was impressed about.
Mr. Walden. You need to turn on your mike.
Ms. Bechler. Which the Orioles were impressed about with
just the 10 pounds, but his body fat had gone down.
Mr. Walden. Okay. And I guess I want to ask Mr. France this
question, because I was reading the testimony last night of the
President of Nutraquest, Inc., former Xenadrine Technologies,
Mr. Chinery, is that right? And in it he says we sold over 20
million bottles of Xenadrine RFA-1, which is what I think what
your son took. About 1.2 billion servings. And I understand the
comment of our other witness on that. And received 450
complaints during the 5 years we sold the product. The great
majority of our complaints were from mild or transitory
effects. Based on all the available scientific information we
did not have any reason to believe that Xenadrine RFA-1 caused
anything but mild transitory effects. We relied upon studies
not only on Xenadrine RFA-1 but also on studies on other
ephedra dietary supplements and on Xenadrine's principle
ingredients, ephedra and caffeine.
Studies including the Cantox Report show that ephedra based
products are effective and safe when used properly.
Mr. France, first of all, are you familiar with any studies
that would confirm that? Would what I have reasoned indicate to
the contrary?
And second, are you aware of any court documents relating
to how others have perceived the credibility of these
witnesses?
Mr. France. Yes, I am. First of all, there was a trial
against Xenadrine in which Mr. Chinery testified about a month
and a half ago. And during that trial several of the alleged
clinical studies that took place on Xenadrine RFA-1 were
discussed by expert witnesses on both sides. And to reiterate
what Dr. Hymsfield said, there was manipulation of research
data found and disclosed during that trial. The trial judge
found there were significant problems with several of the
studies that Xenadrine was holding to prove efficacy and/or
safety.
And more importantly, the trial judge found in its verdict,
a written verdict, that Mr. Chinery, Mr. Conklin, who is here
today, Dr. Colker had no credibility. And the judge sat through
almost 7 weeks----
Mr. Walden. The judge said that?
Mr. France. The judge said that in a written opinion. And I
have it here today.
Mr. Walden. Mr. Chairman, would it be possible to have that
written opinion entered into the record?
Mr. Greenwood. Without objection, it will be incorporated
into the record.
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Mr. Walden. Thank you.
Mr. France. So, if you want to follow up, in terms of
assessing what Mr. Chinery says, in view of the fact that I was
at the trial and I prosecuted that case, and also observed Mr.
Chinery, Mr. Conklin, Dr. Colker who performed these alleged
studies on Xenadrine RFA-1, at least one of them, the Peak
Wellness, I question highly what Mr. Chinery had to say.
Mr. Walden. All right.
Dr. Woosley, is Xenadrine considered a stimulate?
Mr. Woosley. Yes.
Mr. Walden. And what is it and what is its purpose as a
dietary supplement for weight loss?
Mr. Woosley. Well, it contains ephedra and ephedrine, which
is the major stimulant.
Mr. Walden. Okay. And as we understand it, there may be
other ingredients contained in these ephedra caffeine dietary
supplements including the one I just referenced, so that is why
I am asking your opinion on this. It is Tyrosine?
Mr. Woosley. Tyrosine.
Mr. Walden. Considered a stimulant?
Mr. Woosley. No. It's an amino acid which in high doses
might have pharmacologic effect, but not in the doses likely to
be used in these products.
Mr. Walden. Is L-carnatine considered a stimulate?
Mr. Woosley. Carnatine, no.
Mr. Walden. Okay. What is its purpose?
Mr. Woosley. It is argued. People would not agree about its
purpose. It is taken by many people to stimulate muscle growth,
but there is no scientific evidence that I am aware of, except
in carnatine deficiency.
There are inherited disorders where people do not have
enough carnatine, but it is very rare.
Mr. Walden. What properties does salicine have, that is
white oak bark or something?
Mr. Woosley. It is--probably, and I would have to say that
whether the product that is put in there is exactly what the
pharmacopeia would say is often not the same. But Salicine is
thought to thought to be a salicylic acid base. It is like
aspirin.
Mr. Walden. Can it cause bleeding?
Mr. Woosley. Yes in high doses. In the doses that are
there, we do not know.
Most of these products have never been studied
scientifically.
Mr. Walden. Because some of these say you should not take
aspirin with them.
Mr. Woosley. That is theoretically correct. But, again
Mr. Walden. Is salicine similar to aspirin in that respect,
the way it may interact?
Mr. Woosley. It is chemically similar to aspirin, but
frankly we have no idea what those drugs could do in those
products because they have never been tested.
Mr. Walden. No idea?
Mr. Woosley. No idea.
Mr. Walden. Thank you, Mr. Chairman.
Mr. Greenwood. The Chair thanks the gentleman.
In the absence of other members of the minority party, the
Chair will recognize the gentlelady from Colorado again for 5
minutes.
Ms. DeGette. Thank you, Mr. Chairman.
Mr. Vasquez, I would like to summarize your testimony a
little. Our information is that during October 1999 you
received about 5 adverse event calls per day and sometimes as
many as 13 daily.
Consumers called reporting massive heart attacks and
strokes. And you took calls where consumers said that their
hearts were pounding in their chests right there. You also took
calls reporting Metabolife 356 induced cardiac arrhythmia. And
also with information indicating that one out of every five
adverse event calls you received were for cardiovascular
symptoms.
In addition, you received about 10 calls from emergency
room physicians and you and other Metabolife nurses faxed the
Metabolife 356 ingredient list to emergency room physicians.
During that approximately 2 plus months you worked at
Metabolife International you received 5 to 20 calls regarding
heart attack complaints associated with using Metabolife 356.
Is that a pretty good summary of your experience at the
company?
Mr. Vasquez. Correct. Yes.
Ms. DeGette. Thank you.
ow, Mr. Vasquez, we were informed that you attended
meetings where Metabolife 356 adverse events were discussed. In
those meetings you told our staff that you were instructed to
be on heighten security alert in case the FDA or DEA were
calling. Is that correct?
Mr. Vasquez. Correct. Yes.
Ms. DeGette. And who were the instructors giving you these
warnings to be on heightened alert?
Mr. Vasquez. My supervisor, Mr. Daniel Rodriguez.
Ms. DeGette. And what did Mr. Rodriguez tell you you were
supposed to do if you received calls from the FDA or the DEA?
Mr. Vasquez. Well, basically, just to be careful and if
they had any questions, transfer the call to the legal team,
the legal department of the company.
Ms. DeGette. And you also said that you were instructed not
to use the term ``side effect'' on the phone with callers. Is
that right?
Mr. Vasquez. Correct. That was primarily because according
to Mr. Rodriguez, Metabolife 356 is a dietary supplements, that
it is not a drug. That is why he----
Ms. DeGette. So you were instructed not to say side
effects, right?
Mr. Vasquez. Correct.
Ms. DeGette. Now you were concerned about that directive,
were you not?
Mr. Vasquez. Yes.
Ms. DeGette. And did you express your reservations to the
company?
Mr. Vasquez. Yes. I told them why is that the case. And he
said, well, because the product is a dietary supplements. And I
said well--and he told me it is a matter of legal words what to
use and what not to use. So that is why I was instructed not to
use the words side----
Ms. DeGette. And who was it again that instructed you not
to use that word?
Mr. Vasquez. Mr. Daniel Rodriguez.
Ms. DeGette. Thank you.
One last question, Dr. Woosley. Is citrus aurantium a
stimulant?
Mr. Woosley. It probably has stimulant properties. It has
chemicals in it like adrenaline. And again, these products have
not been studied adequately.
Ms. DeGette. Thank you.
Thank you, Mr. Chairman. And I yield back.
Mr. Greenwood. The Chair thanks the gentlelady.
The Chair recognizes himself for 5 minutes.
Dr. Zipes, can an otherwise healthy person die from simply
taking an ephedra supplement?
Mr. Zipes. Mr. Chairman, the answer to that is yes. The
adrenaline response if excessive, can make a normal heart
create this rhythm called fibrillation that produces sudden
death. We know this from many instances. We know this in animal
studies.
I can take a normal dog or pig and produce this with an
excessive dose of adrenaline. And we know it from the clinical
studies as well.
So without any question the answer is yes.
Mr. Woosley. Mr. Chairman, if I may?
Mr. Greenwood. Please do.
Mr. Woosley. Can I make one other point? We have heard
mention of ``massive heart attack'' taking adrenaline, taking
the ephedra compounds. And we have heard palpitations. In
actual fact those are probably linked, because when the lay
public speaks of a massive heart attack, it is usually due to
this ventricular fibrillation. It is not an actual heart
attack, per se, but it is this abnormal heart rhythm that kills
approximately 450,000 people in the United States every year.
And it is the immediate sudden death, someone dying quite
rapidly.
So it is one end of the extreme of the palpitations where
they may be symptomatic from irregular heart beats that when it
gets so severe, produces fibrillation and sudden death, which
is often called a massive heart attack.
Mr. Greenwood. That triggers a question in my mind. Under
what circumstances of someone dying like that would there
necessarily be a coroner's examination and an inquiry that
would determine whether, for instance, a product like ephedra
was in that person's body? I would think that, it would seem to
me that the rules for when you necessarily have an autopsy and
coroner's examination do not necessarily apply to people having
heart attacks?
Mr. Woosley. That is correct. Only if someone were
suspecting a drug like ephedra would you do the appropriate
blood tests to try to document how much was in the blood
stream.
Mr. Greenwood. Someone like myself could get up in the
morning, take one or two of these pills, or whatever it is, go
to the gym, be doing the usual workout, have a heart attack and
not--it would seem to me it would not be necessarily likely
that anybody would ever search the contents of my stomach. They
just said, oh, he is 52 years old and heart attack.
Mr. Woosley. That is exactly right. And if an autopsy were
done in an otherwise normal individual, there would be nothing
found in the heart that would indicate that this was, indeed,
ephedra induced.
One other point we have not made that needs to be made, and
that is the drug ephedra can interact with other drugs that the
patient may be--the individual may be taking for appropriate
medical reasons. In addition, there may be underlying heart
disease in a 52 year old might have underlying coronary disease
that might predispose to developing this ventricular
fibrillation and sudden death when now having the added
stimulus of ephedra.
Mr. Greenwood. Thank you.
Let me address a question to you, Ms. Crosse.
Some have said that your report about the Metabolife call
records demonstrated that Metabolife 356 is safe when used as
directed. Is this true?
Ms. Crosse. No, we did not take an overall judgment about
the safety of Metabolife 356, but we did point out that the
reports in the call records contained information that pointed
to some serious adverse events that occurred with users of this
product. Many of the call records, however, did not contain the
necessary information that would allow you to draw a conclusion
about an individual user. However, we did see that the
consumers of this product were using it, by and large, within
the recommended guidelines on the product label. Over 90
percent of those who experienced a serious adverse event used
the product within the recommended dose. Over 70 percent used
the product within the recommended duration--and those are for
those who were having the most serious side effects, the most
serious adverse events associated with the product.
For those who were having less serious or potentially
serious adverse events, over 90 percent of those users reported
that they were within both the dose and duration that was
recommended on the product label.
Mr. Greenwood. Let me address a question to Ms. Culmo. In
your capacity were you ever aware of a company using the
results of a study conducted with regard to one product and
then trying to misapply to another product?
Ms. Culmo. Yes. In the Texas Department of Health public
docket there is one particular study that on at least, I think
it is 4 situations, companies used the same report and just
whited out the name at the top of the report, typed in their
name and submitted it to our docket. So, yes, there is
definitely examples of that and proof.
Mr. Greenwood. Okay. I thank the panel.
Mr. Bechler, you had a comment that you would like to make.
Mr. Bechler. Yes, I do.
Mr. Chairman, I would like to thank everybody for their
testimony and the professionals that they have here. I would
like to thank all of you up there for being here to try to get
this situation taken care of.
And I just wanted everybody to know that I hope that Mr.
Riggins and my son did not die in vain, and that you all take
this into consideration before anybody else dies, that we do
something about it now.
Mr. Greenwood. Well, you can count on that, sir.
We thank you very much for both Mr. and Mrs. Bechler and
you Mr. Riggins, for what we know is an extraordinarily
excruciatingly difficult thing to do. We would not bring you
here unless we intended to take this very seriously. And as
someone has said, I think it might have been Ms. Culmo, that
let us not do another investigation, another study and just
recycle this thing. We are going to try to get to the end of
this story. And the appropriate end of this story very shortly.
We thank you very much.
The Chair notes we have a series of votes that may take
another hour plus. The Chair regrets that, but that is the way
things work here.
So we are going to thank this panel, excuse this panel. But
we would ask that if any of the expert witnesses are able to
remain with us, if their travel plans permit, to remain with us
because we may want to call upon you again.
But we will return in about an hour to bring forward this
second panel. Thank you again.
[Brief recess.]
Mr. Greenwood. The meeting will come to order.
The Chair apologizes for what we know is a torturously long
pause in our activities, but it is one in which we have no
choice.
And I will call forward our second panel, Mr. Michael
Ellis, Mr. David Brown and Mr. Daniel Rodriguez. Please come to
the witness table, gentlemen.
Michael Ellis is the founder and Director of Metabolife
International. David Brown is a former President of Metabolife.
And Daniel Rodriguez is the head nurse working at Metabolife
handling consumer complaints.
They are all here with us today pursuant to a subpoena.
On July 3, 2003 the committee invited these three
individuals to voluntarily testify at this hearing, but they
declined.
On July 10 of this year the subcommittee authorized
subpoenas to be issued to compel their appearance, which were
subsequently issued by Chairman Tauzin and served. My
understanding is that these witnesses will rely on their
Constitutional right not to testify at today's hearing and will
not provide any evidence or testimony to this subcommittee.
I believe that this privilege, which is the only basis upon
which a witness may refuse to cooperate with an inquiry by this
House, the People's House of Representatives, should be
personally exercised before the members as is our standard
practice in such cases. That is why we have insisted on the
appearances of Mr. Ellis, Mr. Brown and Mr. Rodriguez today.
Given the importance of their testimony to this
subcommittee's fact-finding processes, I would hope that these
men might reconsider their decisions to invoke their Fifth
Amendment rights today and decide to cooperate with this
critically important investigation.
Mr. Ellis, Mr. Brown, Mr. Rodriguez, I know that each of
you is represented by counsel today who will advise you with
respect to your appearance, as is your right under the rules of
the House and the rules of the committee.
Mr. Ellis is represented by Andrew Robertson of the law
firm LaBella & McNamara.
Mr. Brown is represented by Gordon Greenberg of the law
firm McDermott, Will & Emery.
And Mr. Rodriguez is represented by Lee Blalack of the law
firm O'Melvaney & Myers.
As such I understand that each of you is aware that the
subcommittee is holding an investigation hearing today and in
doing so, has the practice of taking testimony under oath. At
this time would you please, stand, raise your right hand and I
will swear you in.
[Witnesses sworn.]
Mr. Greenwood. Okay. You may please be seated.
The Chair will then recognize himself for questioning of
the witnesses.
Oh, I am sorry. You are now under oath and you may give a 5
minute oral statement for the record if you choose to. Does
anyone choose to do that? Apparently not.
TESTIMONY OF MICHAEL ELLIS, FOUNDER AND DIRECTOR OF METABOLIFE
INTERNATIONAL; DAVID BROWN, FORMER PRESIDENT OF METABOLIFE; AND
DANIEL RODRIGUEZ, HEAD NURSE, METABOLIFE
Mr. Greenwood. The Chairman then will recognize himself for
questioning of the witness. My first question is for Mr. Ellis.
As the one time president of a company selling supplement
products ingested by millions of consumers, did Metabolife ever
conduct any studies on the risks associated with use of its
product Metabolife 356 or did you put sales above safety?
Mr. Ellis. I respectfully decline.
Mr. Greenwood. Would you please push the button your
microphone?
Mr. Ellis. Thank you. I am sorry.
Mr. Greenwood. That is quite all right.
Mr. Ellis. I respectfully decline to answer that question
in this proceedings based upon my privilege against self-
incrimination, sir.
Mr. Greenwood. Okay. Let me be clear. Are you refusing to
answer the question on the basis of the protections afforded to
you under the Fifth Amendment to the United States
Constitution?
Mr. Ellis. Yes, sir.
Mr. Greenwood. And will you invoke your Fifth Amendment
rights in response to all of our questions today?
Mr. Ellis. Yes, sir.
Mr. Greenwood. Then you are excused from the witness table
at this time. But I advise you that you remain subject to the
process of the committee and that if the need is such, then we
may recall you.
Mr. Ellis. Thank you, sir.
Mr. Greenwood. You may be excused.
My next question is for Mr. Brown.
Mr. Brown, welcome.
As the one time president of a company selling supplement
products ingested by millions of consumers why did it take
several years for Metabolife to send into the FDA the 14,000
customer complaint call records, many of them involving serious
adverse medical events after years of insisting that Metabolife
had received no such complaints.
Mr. Brown. Mr. Chairman, members of the committee, under
normal circumstances I would be happy to be here with the
committee and answer all of your questions. Unfortunately, due
to an investigation by the Justice Department in California, I
think it would be inappropriate for me to answer your questions
today. And, therefore, I am going to follow the advice of my
attorney and out of prudence decline to answer the committee's
questions today based upon my rights under the Fifth Amendment
of the Constitution.
Mr. Greenwood. Very well said. And that is indeed your
right. But let me clear, are you refusing to answer the
question on the basis of the protections afforded to you under
the Fifth Amendment to the United States Constitution?
Mr. Brown. Yes, sir.
Mr. Greenwood. Okay. And will you invoke your Fifth
Amendment rights in response to all of our questions today?
Mr. Brown. Yes.
Mr. Greenwood. Then you are excused from the witness table
at this time. But I advise you that you remain subject to the
process of the committee and that if the committee's need is
such, then we may recall you.
Mr. Greenberg. Mr. Chairman, one housecleaning matter if I
may.
We submitted 4 letters to the committee for its
consideration. We would request that those 4 letters be part of
the record of today's proceedings, please.
Ms. DeGette. Reserving the right to object. We have not
seen the letters.
Mr. Greenwood. The gentlelady would like to preserve her
right. We will provide her with all of the letters, the four
letters.
Ms. DeGette. Thank you, Mr. Chairman.
Mr. Greenberg. Thank you, Mr. Chairman.
Chairman Tauzin. Mr. Chairman, I will also make an inquiry
of the Chair. When a witness refuses to testify under the
protection of the Fifth Amendment, is that witness permitted to
enter information into the record by way of letter when that
witnesses refuses to make personal comments or to answer
questions before this committee?
Mr. Greenwood. I am advised, Mr. Chairman, that the
question is a pertinent one. We will review the letters and we
will advise Mr. Brown and his attorney as to our conclusion on
that matter.
Chairman Tauzin. I simply, if the Chair will continue to
yield, I simply would like to in the intervening time pose an
objection, if that is proper, to the introduction of testimony
by way of letters to this committee to witnesses who refuse to
give oral testimony and to answer questions before this
committee for any purpose. And I would like that objective
lodged into the record.
Ms. DeGette. If the Chairman will yield?
Chairman Tauzin. I think----
Mr. Greenwood. The Chair will yield to the gentlelady from
Colorado.
Ms. DeGette. One of the reasons I reserved the right to
object is I am not sure that--I have not seen the letters. I
have no idea what they say. But if they contain substantive
testimony, a witness cannot have it both ways; both asserting
their rights to their Fifth Amendment privilege and submitting
testimony. And I would submit if these letters contain
substantive testimony, the witness may be waiving his right
under the Fifth--and subject to further subpoena to come back
to this committee and testify under oath.
Mr. Stearns. Mr. Chairman, can I ask a question?
Mr. Greenwood. The gentleman from Florida.
Mr. Stearns. Mr. Chairman, if we accept the letters, would
Mr. Brown be willing to answer questions based upon the
contents of that letter?
Mr. Greenberg. If I may respond, Mr. Chairman?
Mr. Greenwood. Please do.
Mr. Greenberg. The letters contain no substantive
testimony. They describe our position as Mr. Brown has
presented and the sequence of events in corresponding with the
committee asking the committee to take consideration that it
would not be worthwhile to have Mr. Brown travel here for this
proceedings in light of what we were facing today. And that is
the substance of our letters. No substantive testimony
whatsoever.
Chairman Tauzin. Mr. Chairman?
Mr. Greenwood. Mr. Chairman.
Chairman Tauzin. If that is the purpose of the letters,
they have no relevance to these proceedings. And I would object
to their entry into the record.
Mr. Greenwood. The Chair registers the objection and the
letters will not be made a part of the record.
And Mr. Brown is dismissed.
The next question is for Mr. Rodriguez.
Mr. Rodriguez, as the supervisor of nurses and company
representatives handling customer complaints about the
Metabolife product, some of them relating to serious adverse
medical events, did you in fact instruct these nurses and
representatives not to obtain from these callers critical
information about these adverse health effects?
Mr. Blalack. Mr. Chairman, may I be heard on behalf of Mr.
Rodriguez?
Mr. Greenwood. You may.
Mr. Blalack. My name is Lee Blalack, and I am counsel for
Mr. Rodriguez. As I have advised the subcommittee in a letter
that I distributed to all of the members, including staff, Mr.
Rodriguez is a witness cooperating with the Department of
Justice investigation in the Southern District of California.
He has been interviewed by the Justice Department, has given
testimony to a grand jury in that proceeding pursuant to
immunity.
Given the fact that he would be testifying today under oath
on the very same subject matter about which he is giving
cooperative testimony in the grand jury proceeding, we asked
the subcommittee to consider a grant of immunity to permit him
to testify today. That request was denied, and we submitted to
the Chair an affidavit from Mr. Rodriguez attesting that if he
was compelled to appear, he would have to assert his
Constitutional rights against self-incrimination under those
circumstances. And that if he was compelled to appear, he would
not be provide any substantive answers to questions.
Under those circumstances, Mr. Chairman, we think it is
appropriate that the subcommittee, as is its right, to test
that claim if it sees appropriate, but to do so under its rules
in Executive Session under Rule 11(k)(5). Because under those
circumstances the testimony would--the purpose of the question
would have no meaning except to expose him to ridicule and
defaming him in the context of his community at home with the
press, quite frankly. And so under Rule 11(k)(5) which states
whenever a witness, it is asserted by a witness that the
evidence or testimony that the witness would give at a hearing
may tend to defame, degrade or incriminate, then such testimony
upon a majority vote of the subcommittee may be taken in
Executive Session.
And, Mr. Chairman, we would request that that be invoked at
this time. And we do not wish to offer any substantive
testimony or evidence into the record. We would like to enter
into the record transcripts from prior hearings at the House
and the Senate in which this procedure has been employed to
move into Executive Session for purposes of taking the
assertion of the Fifth Amendment privilege of a witness away
from the cameras and the media.
Mr. Walden. Mr. Chairman, I have a motion at the desk.
Mr. Greenwood. The gentleman will suspend.
The witness, Mr. Rodriguez, has invoked Rule 11, clause
(2)(k)(5) of the rules of the House of Representatives which
provides that whenever it is asserted by a witness that the
evidence or testimony the witness would give may tend to
defame, degrade or incriminate the witness, the subcommittee
must vote as to whether to continue to proceed with receiving
such testimony in open session or whether it should go into
executive session to hear such testimony.
The Chair now recognizes Mr. Walden for the purpose of
offering a motion.
Mr. Walden. Mr. Chairman, I have a motion at the desk.
Mr. Greenwood. The Clerk will read the motion.
The Clerk. Motion by Mr. Walden. Mr. Walden moves that the
testimony of the witness invoking his Fifth Amendment
privileges not to testify may not tend to defame, degrade or
incriminate such a witness, and that therefore the subcommittee
should remain in open session.
Mr. Greenwood. The Chair recognizes himself on the motion.
It is the Chair's legal view upon consultation with
committee counsel that this rule is inapplicable in situations
in which it is clear by the witness' own prehearing
communications with the committee that the witness will not
provide any evidence or testimony at all, but will instead
invoke his Fifth Amendment right not to testify in response to
any and all questions posed by the subcommittee.
The witness in this case has claimed through counsel that
the very act of asserting his Fifth Amendment rights may tend
to defame, degrade or incriminate him. I strongly disagree with
this assertion based on the longstanding constitutional rule
and the judicial context that no negative inference may be
drawn from a witness' assertion of his Fifth Amendment rights.
The Chair would thus urge all members to vote to continue
this proceeding in an open session and would recognize any
other member at this point for purpose of debate on this
question. Any members choose to be recognized? Hearing none,
the Chair----
Ms. DeGette. Actually, Mr. Chairman?
Mr. Greenwood. The gentlelady from Colorado is recognized.
Ms. DeGette. Is the purpose of this motion to say that the
committee--or maybe I can ask the author of the motion.
Mr. Walden. Certainly.
Ms. DeGette. Is the purpose to say that it is the
committee's position that whenever a witness invokes a Fifth
Amendment privilege not to testify, it is our determination
that does not defame, degrade or incriminate that witness?
Mr. Greenwood. Yes.
Ms. DeGette. In that case, Mr. Chairman, I would ask
unanimous consent that the word ``may'' from the second line be
changed to ``does.'' I do not think the motion is grammatically
correct as written.
Mr. Walden. I will leave it to the grammarians as long as
it accomplishes the same thing. I have no problem with that.
Mr. Stearns. Mr. Chairman, I like the word ``may'' better.
I think it is appropriate. I think the staff did a better job
with the word ``may.''
Ms. DeGette. Staff's agreeing it should be ``does.''
Mr. Stearns. The staff thinks it should be ``does''?
Ms. DeGette. Yes.
Mr. Greenwood. The Chair would propose----
Chairman Tauzin. Mr. Chairman, if I could?
Mr. Greenwood. Does the gentlelady withdraw her suggestion?
The Chair would ask that she would, insofar as counsel has----
Ms. DeGette. I will withdraw it, but I think it is
grammatically incorrect.
Mr. Walden. Mr. Chairman? Mr. Chairman, my understanding is
this wording tracks exactly what is in the House rules.
Mr. Greenwood. The gentlelady insists upon her wisdom, but
agrees to withdraw her objection.
Ms. DeGette. That is better.
Mr. Greenwood. Okay. Hearing no further debate, we will put
the question on the motion. All in favor say aye.
[Vote]
Mr. Greenwood. All opposed no. The Clerk will call the
roll?
The Clerk. Mr. Bilirakis?
[No response]
The. Clerk. Mr. Sterns.
Mr. Stearns. Aye.
The. Clerk. Mr. Sterns votes aye.
Mr. Burr?
[No response]
The. Clerk. Mr. Bass?
Mr. Bass. Aye.
The. Clerk. Mr. Bass votes aye.
Mr. Walden?
Mr. Walden. Aye.
The. Clerk. Mr. Walden votes aye.
Mr. Ferguson?
[No response.]
The. Clerk. Mr. Rogers?
[No response.]
The. Clerk. Mr. Tauzin?
Chairman Tauzin. Aye.
The. Clerk. Mr. Tauzin votes aye.
Mr. Deutsch?
[No response.]
The Clerk. Ms. DeGette?
Ms. DeGette. Aye.
The. Clerk. Ms. DeGette votes aye.
Mr. Davis.
Mr. Davis. Aye.
The. Clerk. Mr. Davis vote aye.
Ms. Schakowsky?
Ms. Schakowsky. Aye.
The. Clerk. Ms. Schakowsky votes aye.
Mr. Waxman?
Mr. Waxman. Aye.
The. Clerk. Mr. Waxman votes aye.
Mr. Rush?
[No response.]
The. Clerk. Mr. Dingell?
[No response.]
The Clerk. Mr. Greenwood.
Mr. Greenwood. Aye.
The. Clerk. Mr. Greenwood votes aye.
Mr. Greenwood. The Clerk will report the roll.
The. Clerk. Mr. Chairman, there are 8 ayes, no nays.
Mr. Greenwood. The motion carries. The subcommittee will
continue to proceed in open session, and I will renew my
question to Mr. Rodriguez.
Mr. Rodriguez, as the supervisor of nurses and company
representatives handling customer complaints about the
Metabolife product, some of them relating to serious adverse
medical events did you in fact instruct these nurses and
representatives not to obtain from these callers critical
information about these adverse health events?
Mr. Rodriguez. Mr. Chairman and members of the committee,
on advice of counsel I do respectfully submit my rights under
the Fifth Amendment to not testify.
Mr. Greenwood. That is your right. Let me clear now, Mr.
Rodriguez. Are you refusing to answer the question on the basis
of the protections afforded to you under the Fifth Amendment to
the United States Constitution?
Mr. Rodriguez. Yes, Mr. Chairman.
Mr. Greenwood. Okay. And will you invoke your Fifth
Amendment rights in response to all of our questions here
today?
Mr. Rodriguez. Yes, Mr. Chairman.
Mr. Greenwood. Then you are excused from the witness table
at this time, but I advise you that you remain subject to the
process of the committee and that if the committee's need is
such, then we may recall you.
Mr. Blalack. Mr. Chairman, will the request that I made
that the transcripts from the other hearings be entered into
the record, will that be granted or denied?
Mr. Greenwood. The gentleman is advised that you may submit
your documents to counsel. We will review them, but they will
not be inserted into the record.
Mr. Blalack. Okay. Thank you.
Mr. Greenwood. The Chair thanks from the gentleman.
And the Chair now calls forward the patient panel III
witness. Mr. Russell Schreck, Chief Executive Officer of
Metabolife International; Mr. Robert Hermann, Vice President
Metabolife International, Dr. Carol Boozer, Obesity Research
Center, St. Luke's Roosevelt Hospital in New York; Mr. Robert
Chinery, President of Cytodyne Technologies; Mr. Kelly Conklin
of Cytodyne Technologies; Dr. Carlon M. Colker, M.D., Chief
Executive Officer and Medical Director of Peak Wellness, Inc.
in Greenwich, Connecticut; Mr. Robert Occhifinto, President of
NVE Pharmaceuticals, and; Ms. Roseann Fox, Customer Service
Representative of NVE Pharmaceuticals.
We welcome all of our witnesses. Again, we do thank you for
your patience. We know this has been a long day and we will try
to move expeditiously from this point forward.
I believe that you have been advised, and if not I will
advise you, that this is an investigative hearing and it is the
practice of this subcommittee to take testimony under oath. Do
any of you object to giving your testimony under oath today?
Seeing no such objection, I would also advise you that pursuant
to the rules of this committee and pursuant to the rules of the
House, that you are entitled to be represented by counsel. Do
any of you wish to be represented by counsel today?
Okay. Let's start with Mr. Schreck. Do you?
Mr. Schreck. Yes, I am.
Mr. Greenwood. Would you advise the committee of the name
of your counsel?
Mr. Schreck. Lee Blalack.
Mr. Greenwood. Okay. Mr. Blalack.
Mr. Hermann, your counsel?
Mr. Hermann. Yes, Mr. Chairman. Lee Blalack.
Mr. Greenwood. The same gentleman?
Mr. Hermann. Yes, sir.
Mr. Greenwood. Dr. Boozer?
You'll each have to push the buttons on your mike. Okay.
Try that. That's much better.
Dr. Boozer. Mr. Chairman, I have with me today Mr. James
Hamilton and Ms. Pamela Davis.
Mr. Greenwood. Very well.
And do you gentleman or lady wish to be represented by
counsel today? Okay.
In that case, I would ask if you would all--oaky. I'm
sorry. Mr. Chinery, do you have counsel?
Mr. Chinery. Yes, Mr. Chairman.
Mr. Greenwood. Would you identify your counsel please?
Mr. Chinery. Hunter Carter and Shane Friedman.
Mr. Greenwood. Very well. Okay.
And Mr. Conklin, you do as well?
Mr. Conklin. Yes, sir. It is Steve Kenilman and Shane
Friedman.
Mr. Greenwood. Very well.
Mr. Colker?
Mr. Colker. John Wickman and Hunter Carter.
Mr. Greenwood. Mr. Occhifinto?
Mr. Occhifinto. William Teller.
Mr. Greenwood. And Ms. Fox?
Ms. Fox. William Teller.
Mr. Greenwood. Very well. Okay.
Now I would ask if you would please stand and raise your
right hands.
[Witnesses sworn.]
Mr. Greenwood. Okay. You are all under oath and we will
begin with Mr. Schreck, you are invited to offer your
testimony, sir. And you need to make sure your microphone is
on.
TESTIMONY OF RUSSELL SCHRECK, CHIEF EXECUTIVE OFFICER,
METABOLIFE INTERNATIONAL; ROBERT HERMANN, VICE PRESIDENT
METABOLIFE INTERNATIONAL; CAROL BOOZER, OBESITY RESEARCH
CENTER, ST. LUKE'S ROOSEVELT HOSPITAL; ROBERT CHINERY,
PRESIDENT, CYTODYNE TECHNOLOGIES; KELLY CONKLIN, CYTODYNE
TECHNOLOGIES; CARLON M. COLKER, CHIEF EXECUTIVE OFFICER AND
MEDICAL DIRECTOR, PEAK WELLNESS, INC.; ROBERT OCCHIFINTO,
PRESIDENT, NVE PHARMACEUTICALS; AND ROSEANN FOX, CUSTOMER
SERVICE REPRESENTATIVE, NVE PHARMACEUTICALS
Mr. Schreck. Chairman Greenwood and members of the
subcommittee, my name is Russell Schreck. And I am the
President and Chief Executive Officer of Metabolife
International.
Metabolife is one of the leading companies in the dietary
supplement industry. It is my privilege to appear before the
subcommittee today to discuss the many important issues of
consumer choice and health that pertain to our industry.
At the outset, Mr. Chairman, I should note for the record
that I have been with the company for a very short time and may
need to rely on my colleague for certain instances.
I am proud to be a part of Metabolife. I know that one of
the most important things that have occurred since I have been
part of the company is the enormous time and resources its
spent to cooperate with the committee.
One of the reasons we have cooperated so extensively with
the subcommittee is that we hope that your inquiry would dispel
some of the public confusion surrounding dietary supplements
containing ephedra. We are, obviously, quite sensitive to the
concerns that have been expressed regarding the proper
marketing and use of ephedra products, including by the Bechler
family and Mr. Riggins this morning. Speaking as a parent for
10 children, I can tell you that myself and Metabolife express
our deepest sorrow and sympathy to these families.
Our genuine concern notwithstanding, these events do not
shake us from our firm belief in the safety and efficacy of our
products. Our company markets one of the largest weight
control--one of the leading weight control supplements, a
product called Metabolife 356. It is not for everyone, as we
clearly state on our label. The FDA and the NIH recently
commissioned a study by the Rand Corporation which found that
dietary supplements containing ephedra such as Metabolife 356
are effective at supporting short term weight loss. Moreover,
the Rand study noted that no serious adverse events were
reported in the 52 clinical trials.
The FDA had previously found that synthetic ephedrine is
generally safe and effective at doses of 150 milligrams per day
in the over-the-counter drug such as asthma remedies. By
comparison, our label on Metabolife 356 establishes a daily
serving limit of no more than 96 milligrams per day of
ephedrine alkaloids. And because Congress had the foresight to
pass the Dietary Supplement, Health and Education Act of 1994,
millions of consumers have been able to take advantage of
ephedra products to achieve their weight loss goals. We
estimate at Metabolife that for the 5 year period ending August
2002 we have sold approximately 50 million bottles of
Metabolife 356 containing approximately 4.5 billion tablets.
Mr. Chairman, we take the questions about safety and
efficacy of our products very seriously. So even though we
believe that our products are safe, our company has a
longstanding policy of prohibiting the sale of Metabolife to
minors. We do not market Metabolife 356 as an alternative
illicit street drug and we have not promoted our product as a
means of athletic enhancement.
Anyone who has read our label know that we go to great
lengths to inform our customers about the proper use of our
products. And, as you can see, the label has been put on the
stand in the corner there.
We make it quite clear in our label that ephedra products
are not to be sold or used by minors and that customers with
preexisting medical conditions should consult a physician
before product use.
We also make clear to our customers on that label that
exceeding the recommended serving may cause serious adverse
health effects, including heart attack and stroke.
Metabolife does not oppose regulation and strongly believes
that the FDA should adopt and implement a strong science based
regulation that would restrict promotional claims, mandate
serving limits and generally require companies to act
responsibly when manufacturing and selling their products. I
say science based because we know, as you do, Mr. Chairman,
that the debaters surrounding ephedra can be very emotional. We
do not believe that the FDA should regulate based on anecdotes
or emotions, but rather should rely on science.
And as the Rand study noted, no serious adverse effects
were reported in the 52 clinical trials.
I hope that industry and policymakers can work together to
promote the safe use of a product that millions and millions of
Americans find helpful to struggle to maintain their weight.
Thank you, Mr. Chairman. I would be pleased to answer any
questions you may have.
Mr. Greenwood. Thank you, Mr. Schreck.
Mr. Hermann, you are recognized for your opening statement,
sir.
TESTIMONY OF ROBERT HERMANN
Mr. Hermann. Thank you, Mr. Chairman, for the opportunity
to address the subcommittee. My name is Bob Hermann. I am Vice
President of Operations for Metabolife. I've been in this
position since January 2000 and I have been an employee of
Metabolife for about a little over 3\1/2\ years.
My primary responsibility is for the company's
manufacturing facility and manufacturing process. Day in and
day out Metabolife employees in California and Utah work to
ensure that our products are both effective and safe. I can
personally attest to the rigorous quality control measures that
are performed on all of our products, including Metabolife 356.
Despite the fact that final rule establishing good
manufacturing process for dietary supplements has not been
issued yet, Metabolife has voluntarily implemented stringent
quality control procedures, including batch-testing, which meet
or exceed the FDA's requirement for food GMPs.
As Mr. Schreck has already indicated, Metabolife does not
oppose reasonable regulation of the marketing and the use of
dietary supplements containing ephedra. In fact, our label
makes clear, we already prohibit the sale of Metabolife 356 to
minors; we specify maximum serving limit consistent with
available clinical evidence; and we utilize blunt warning
statement to advise people with pre-existing medical conditions
to seek the counsel of a health care professional before using
our product. To, to be clear, Metabolife welcomes prudent
regulation. We ask only that it's grounded on the rigors of
clinical evidence, rather than the hearsay of anecdotal
reports.
Mr. Chairman, some of our critics have suggested that
anecdotal reports maintained by the FDA and call records kept
by Metabolife provide compelling evidence that ephedra poses a
safety hazard. We, obviously, disagree. We continue to believe
the consumer reports cannot substitute for well-controlled
scientific studies. However, you need not take our word for it.
Your own investigators at the General Accounting Office
reviewed the so called adverse event reports maintained by the
FDA and, in 1999, concluded that the reports were unreliable,
inconsistent and incapable of establishing causation. And, just
a few months ago, the GAO reported on its analysis of the
consumer calls recorded by Metabolife from May 1997 to July
2002. As you know, Mr. Chairman, Metabolife voluntarily
produced call records from our health information line for
GAO's analysis. The GAO found, and I quote, ``We cannot
establish that any of the adverse events reported in the
Metabolife International call records were caused by the use of
Metabolife 356 . . . adverse event reports by themselves are
generally not sufficient to establish that a health problem was
caused by the use of a particular product.''
But for those who reject GAO's analysis and continue to put
great stock in these reports, it is imperative to appreciate
some essential context about our call record. One of the most
important facts to understand is that Metabolife's consumer
information line was never intended to be a reporting system
for adverse health events. The information line was merely
intended to be a means for our customers to ask general
questions about the proper use of our products and to assist
them in weight loss questions. As a consequences, it should not
be surprising that, between 1997 and 2002, only about 3 of
every 100 calls pertained to health-related issues. Moreover,
based on the GAO's count, only about 6 out of 1,000 of these
health-related calls pertained to significant health
allegations, such as stroke or heart attack. In other words, a
tiny fraction of 1 percent of all recorded calls to the
consumer's information line were considered significant.
When these figures are considered and compared to
approximately 4.5 billion tablets of Metabolife sold during
this same period, one can see why the GAO concluded that
anecdotal call records are inadequate to establish a causal
link between an adverse health outcome and ephedra-containing
dietary supplements.
To appreciate how misleading anecdotal records truly are, I
encourage the subcommittee to compare reports about other
commonly used products, such as aspirin and acetaminophen, the
generic name for Tylenol. For example, in the year 2001 alone,
the American Association of Poison Control Centers received
thousands of anecdotal reports of health problems associated
with aspirin and acetaminophen. In that 1 year, there were more
than 17,000 reports to the Poison Control Centers involving
aspirin, including over 6,000 reports of health problems and
over 66 reports of death. The numbers are even more striking
for acetaminophen, 56,000 reports, including 10,000 reports of
health problems and over 120 reports of death. Despite these
glaring numbers, I think most of us would agree that aspirin
and Tylenol are safe when taken as directed.
Of course, these statistics do not provide a causal link
between these products and these health outcomes. But these
statistics do highlight the folly of attempting to craft a
meaningful regulation on what the GAO called ``unreliable''
evidence. Secretary Tommy Thompson noted this exact point in a
letter to the Public Citizen in June of last year when he
stated that ``the reports alone do not provide a scientific
basis for assessing the safety of ephedrine alkaloids or
establish a link between the reported adverse events and the
ingestion of ephedrine alkaloids.'' We agree, Mr. Chairman.
Clinical trials, not call records from consumers, are the only
sound method to evaluate the safety and efficacy of dietary
supplements containing ephedra. To my knowledge, there is not a
single well-controlled clinical study which demonstrates that
ephedra supplements are unsafe when taken as directed.
I am proud of our company and employees. We believe that we
offer our customers valuable tools in their efforts for weight
control. As a person most directly in charge of manufacturing,
I can assure this subcommittee that none of us at Metabolife
would ever permit the sale of a product that would did not feel
confident about taking ourselves or giving to our families.
Mr. Chairman, I am pleased to be here today and I am
prepared to answer your questions.
Mr. Greenwood. Thank you, Mr. Hermann.
Dr. Boozer, you are recognized for your opening statement.
Please make sure your microphone is on as well.
TESTIMONY OF CAROL BOOZER
Ms. Boozer. Mr. Chairman, members of committee and
Congresswoman Davis Thank you for your invitation to speak to
you today. I am Dr. Carol Boozer. My doctorate in science and
nutrition is from Harvard University, School of Public Health.
I am presently on the faculties of the Institute of Human
Nutrition, in the Department of Medicine at Columbia University
and at the New York Obesity Research Center at St. Luke's-
Roosevelt Hospital.
I currently receive significant research support from the
National Institutes of Health grants. My career has been
devoted to research in the areas of nutrition and obesity,
which unfortunately is currently at epidemic levels, with the
intention to prompt public health.
My interest in this issue is through my role as a scientist
who is the principle investigator in two of the very few
clinical trials of ephedra/caffeine combinations. My position
today is to promote the role of science in the policymaking
process in general and in this issue in particular.
The sudden death of any individual is tragic to the family
and friends and a loss to the country. The effort to reduce the
number of these tragedies and promote public health should be
the highest priority. Reports of serious adverse events related
to the use of ephedra must be taken seriously, and they are
useful in pointing to areas that require research. However,
they do not constitute scientific proof of an association
between ephedra consumption and injury.
Scientists have carefully considered the methodology
required to show causality. The ``gold standard'' method in
clinical studies is the randomized, double-blind, placebo-
controlled trial.
The two clinical trials of ephedra-containing products that
I conducted both used this method to assess the efficacy for
weight loss and safety. An expert statistician provided codes
to randomize subjects to two groups. Since none of the research
staff involved in the study knew the codes, there was no way
that they could bias the results by treating one group
differently from the other during the study. Only after the
study was completed and after the data had been entered into
the computer spreadsheets was the code broken by the
statistician who analyzed the data. Any differences that were
found could thus be attributed to the treatment.
Dr. Heymsfield who testified this morning was a co-author
on one study and a co-investigator on the other one. Our papers
were transparent with regard to the compounds studied.
Subject selection, numbers and reasons for dropouts. I
agree with Dr. Woosley that it would be unethical to have
tested individuals who were not healthy. In other words, we
tested people whom we could ethically test.
The two studies together included 234 men and women who
were overweight, but otherwise healthy. One study continued for
8 weeks, the other for 6 months. In both studies, those
receiving the herbal treatment lost more body weight and body
fat and had improved blood lipids compared with those receiving
who placebo. No individual in either study experienced serious
adverse event. In both studies, the herbal groups had increased
heart rate and slightly increased blood pressure relative to
placebo groups. Heart irregularities were not increased. Drop-
out rates were similar in the two groups in both studies, but
in the 8-week study, the reasons given for dropping out of the
herbal treatment group included more self-reported side
effects, primarily palpitations. In the 6-month study the drop-
outs due to side effects were very few and were similar between
the two groups. The side effects reported most by subjects in
the herbal groups were: dry mouth, insomnia, headache and
heartburn.
After the study was completed I discovered a bottle of
capsules from the study that had been mislabeled. I therefore
personally examined each of the remaining 326 bottles and
reported to the Journal and to the FDA my findings along with
the statistical analysis showing that low level of error, 1.6
percent, could not significantly alter the results or
conclusions of the study.
Studies were both published in the International Journal of
Obesity following peer review by experts in the area subsequent
to publication. There have been attacks on the studies by the
media and others.
The public is not well served by suppression of scientific
studies. The validity of scientific study does not depend on
agreement of outcome with preconceived expectation. While no
study is perfect, these studies were conducted without pressure
from the industry for a predetermined outcome, as evidenced by
their contractual agreement to publication of results
regardless of outcome. The studies were conducted with
impartiality that was assured by the randomized, double-blind,
placebo-controlled design. As noted, they were subjected to
peer-review and published in a reputable scientific journal.
While efficacy of ephedra in promoting weight loss is now
established, the safety of herbal ephedra is not proven for
different populations or with different usage. More research is
required to determine effects in people who are not healthy,
who consume ephedra at levels above those studied, or who take
it longer than 6 months, or use it in combination with
prescription or illicit drugs. But, at present, there is no
scientific data proving that consumption of ephedra/caffeine
combinations for weight loss are unsafe, when consumed in
accordance with appropriate warning labels.
Additional research on the effects of ephedra on weight
loss and in other areas, such as athletic performance, is
clearly needed. I urge those who are responsible for policy to
promote unbiased research and to be guided by its findings.
I'll be happy to answer questions.
[The prepared statement of Carol Boozer follows:]
Prepared Statement of Carol Boozer
INTRODUCTION
Thank you for the invitation to speak to you today. I am Dr. Carol
Boozer. I received my doctorate of science in nutrition from Harvard
University, School of Public Health. I am presently on the faculties of
the Institute of Human Nutrition, in the Department of Medicine at
Columbia University and at the New York Obesity Research Center at St.
Luke's-Roosevelt Hospital in New York. I have received research funding
from the National Institutes of Health and have served on NIH study
sections and as an NIH site visit reviewer. I currently receive
significant research support from NIH grants. My career has been
devoted to research in the areas of nutrition and obesity with the
intention to promote public health.
EPHEDRA STUDIES
Issues relating to ephedra are highly controversial. My interest in
this issue is through my role as a scientist who was the principal
investigator in two of the very few clinical trials of the efficacy for
weight loss and safety of herbal ephedra/caffeine combinations. My
position today is to promote the role of science in the policy making
process in general and in this issue in particular.
The sudden death of any individual is tragic to the family and
friends and a loss to the country. The effort to reduce the number of
these tragedies and promote public health should be the highest
priority. Reports of adverse events related to the use of ephedra must
be taken seriously, and they are useful in pointing to areas that
require research. They do not constitute scientific proof of an
association between ephedra consumption and injury. The reason why such
reports cannot prove cause and effect is easily understood by the
following example. If a city is considering whether installation of a
traffic light has reduced accidents at a dangerous intersection, both
the accident rate before the installation, the ``background rate'' and
the rate after installation must be known. However, even if both rates
are known, a difference in rates might not be due to the light itself
since other factors such as weather, condition of the road, or the
opening of a bar in the area could affect the rate. A reduction in the
accident rate following installation of the light cannot, in and of
itself, prove that the light caused the change.
Methodology
Scientists have carefully considered the methodology required to
show causality. The ``gold standard'' method in clinical studies is the
randomized, double-blind, placebo-controlled trial. Randomization is a
process whereby individuals are assigned to treatment groups in such a
way that the two groups are similar in all other characteristics,
except for the treatment under study. This controls for the possibility
of even unknown factors affecting one group differently from the other.
Double-blinding insures impartiality, since throughout the study
neither the participants nor the investigators know the treatment group
of any participant. Finally, inclusion of a placebo group allows
assessment of the background rate, in a group that is similar in all
aspects to the treatment group, except for the treatment under study.
The two clinical trials of ephedra-containing products that I
conducted were both randomized, double-blind, placebo-controlled
studies undertaken to assess the efficacy for weight loss and safety of
herbal/ephedra combinations. A statistician not involved in carrying
out the studies provided the randomization codes using a system that
would maximize the chance that placebo and treatment groups would on
average be similar in characteristics such as age, body weight, gender
distribution, income, education, etc. Since none of the research staff
involved in the study knew the codes, there was no way that they could
bias the results by treating one group differently from the other
during the study. Only after the study was completed and after the data
had been entered into computer spreadsheets was the code broken by the
statistician who analyzed the data. The data for the group receiving
the ephedra was then compared with the data for the group receiving
placebo. Since the groups were similar at the start of the study and
followed the same protocol with the exception of the treatment, herbal
ephedra/caffeine or placebo, any differences that were found could be
attributed to the treatment.
These two studies were the only clinical trials of ephedra and
ephedrine that were given the highest ranking for quality in the
recently published Rand Report.<SUP>1</SUP>
---------------------------------------------------------------------------
\1\ Shekelle P, M Hady, Morton SC, et al. Ephedra and Ephedrine for
Weight Loss and Athletic Performance Enhancement: Clinical Efficacy and
Side Effects. Evidence Report/Technology Assessment, Number 76, AHRQ
Publication No 03-E022, 2003.
---------------------------------------------------------------------------
Results
The two studies together included 234 men and women who were
overweight, but otherwise healthy. Half received herbal ephedra/
caffeine and half placebo. One study continued for 8 weeks, the other
for 6 months. In both studies, those receiving the herbal treatment
lost more body weight and body fat and had improved blood lipids
compared with those receiving placebo. No individual in either study
experienced a significant adverse event (defined in the scientific
community as death, heart attack, stroke, etc.). In both studies, the
herbal groups had increased heart rate and slightly increased blood
pressure relative to placebo groups. Heart monitors, used in the 6-
month study, showed that herbal treatment did not increase heart
irregularities. Drop-out rates were similar in the herbal and placebo
groups in both studies, but in the 8-week study, the reasons given for
dropping out of the herbal treatment group included more self-reported
side effects (primarily palpitations). In the 6-month study, the
numbers of individuals who dropped out due to side effects were very
low and were similar between the two groups. The side effects reported
more frequently by all subjects in the herbal groups compared with
placebo groups were: dry mouth, insomnia, headache and heartburn.
Reaction
These studies were published in the International Journal of
Obesity.\2\<SUP>,</SUP>\3\ Prior to publication, experts in the field
critically reviewed each paper and made recommendations to the editor
as to the validity of methods, interpretation of results and scientific
importance, a process called peer-review. Subsequent to publication,
there have been attacks on the studies by the media and
others.<SUP>4</SUP>
---------------------------------------------------------------------------
\2\ Boozer, CN, JA Nasser, SB Heymsfield, V Wang, MS Chen and JL
Solomon. Efficacy of an herbal mixture of Ma Huang and Guarana for
weight loss. International Journal of Obesity and Related Metabolic
Disorders 25:316-324, 2001.
\3\ Boozer CN, PA Daly, P Homel, JL Solomon, D Blanchard, JA
Nasser, R Strauss, T Meredith. Herbal Ephedra/Caffeine for Weight Loss:
A 6-Month Randomized Safety and Efficacy Trial. International Journal
of Obesity and Related Metabolic Disorders, 26:593-604, 2002.
\4\ Atkinson, RL. Editorial: The herbal ephedra and caffeine debate
continues. International Journal of Obesity and Related Metabolic
Disorders 26:589, 2002.
---------------------------------------------------------------------------
The public is not well served by suppression of scientific studies.
The value of scientific study does not depend on agreement of outcome
with preconceived expectation. While no study is perfect, these studies
were conducted without pressure from the industry sponsors for a
predetermined outcome, as evidenced by their contractual agreement to
publication of results regardless of outcome. The studies were
conducted with impartiality that was assured by the randomized, double-
blind, placebo-controlled design. They were subjected to peer-review
and published in a reputable scientific journal.
Rejection of scientific data in favor of anecdotal stories is
inconsistent with the advancement of knowledge or responsible public
health policy. The Rand Report reviewed approximately 20,000 adverse
event reports.<SUP>5</SUP> They classified events as ``sentinel'' if
they provided three things: 1) documentation that the event did occur,
2) documentation or toxicological evidence that the subject had
consumed ephedra within 24 hours prior to the adverse event, and 3)
evidence that an adequate investigation had assessed and excluded other
potential causes. Only 21, approximately 1 in 1,000 reports, reached
this level and only two of these were deaths.<SUP>6</SUP>
---------------------------------------------------------------------------
\5\ See footnote 1.
\6\ See footnote 1.
---------------------------------------------------------------------------
One estimate of ephedra consumption in the United States was 12
million people in 1999.<SUP>7</SUP> Among such a large number of
people, some adverse events would occur whether or not individuals were
taking ephedra. Data from the U.S. Government's Division of Vital
Statistics estimates the death rate from heart disease alone to be
roughly 1 in 5,500 even in young individuals, age 25-44
years.<SUP>8</SUP> Among the millions of people consuming ephedra, the
background rate of deaths and other serious adverse events would be in
the thousands, many fold higher than the 21 documented sentinel events.
That is why the Rand Report states that ``classification as a sentinel
event does not imply a proven cause and effect relationship.''
<SUP>9</SUP>
---------------------------------------------------------------------------
\7\ Haller CA, Benowitz NL. Adverse cardiovascular and central
nervous system events associated with dietary supplements containing
ephedra alkaloids. New Engl J Med 343: 1833-1838, 2000.
\8\ Minino AM and BL Smith. Deaths: Preliminary Data for 2000.
National Vital Statistics Reports, Vol 49, Number 12, 2001.
\9\ See footnote 1.
---------------------------------------------------------------------------
While efficacy of ephedra in promoting weight loss is established,
it is not my position that the safety of herbal ephedra is proven for
different populations or with different usage. Additional research
would be required to determine effects in people who are not healthy,
or who consume ephedra at levels above those studied, or for periods
longer than six months, or in combination with prescription or illicit
drugs. But, at present, there is no scientific data proving that
consumption of ephedra/caffeine combinations for weight loss are
unsafe, when consumed in accordance with appropriate warning labels.
Additional research on the effects of ephedra on weight loss and in
other areas, such as athletic performance, is clearly needed. I urge
those who are responsible for policy to promote such research and to be
guided by its findings.
Mr. Greenwood. Thank you, Dr. Boozer.
Mr. Chinery?
TESTIMONY OF ROBERT CHINERY
Mr. Chinery. Thank you, Mr. Chairman.
My name is Robert Chinery, and I am the former President of
Cytodyne Technologies, Inc. I appreciate the opportunity to
come before the subcommittee and address the issues surrounding
ephedra-based dietary supplements.
The tragic death of baseball pitcher Steve Bechler was the
catalyst for this inquiry. Our hearts go out to his wife and
new baby, his parents and entire family. Their loss must be
difficult to bear. As a husband and a father of 4, I cannot
feel anything but sympathy for his family and friends.
I would also like to extend my sympathies to the family of
Sean Riggins.
In an effort to understand what happened in this tragedy,
we retained one of the top medical examiners in the country to
review the autopsy report. Dr. Michael Baden is very well known
and highly regarded.
After review of all available records, Dr. Baden determined
that Xenadrine RFA-1 <SUP>'</SUP> did not cause or contribute
to Steve Bechler's death. Dr. Baden concluded, specifically, as
follows: ``I agree with Dr. Perper that the cause of Mr.
Bechler's death was heatstroke. However, I disagree as to the
cause of this heatstroke. It is my opinion to a reasonable
degree of medical certainty that based upon all the materials I
have thus far reviewed on my training and on my 43 years
experience as a medical examiner that Mr. Bechler died of a
heatstroke precipitated by his morbid obesity , high blood
pressure and heart disease, adverse weather conditions,
physical exertion and inadequate screening, monitoring and
medical supervision. The Xenadrine did not cause or contribute
to Mr. Bechler's death and that proper and prompt treatment
with intravenous fluids and cold wraps immediately after he
collapsed but was still conscious may have prevented Mr.
Bechler's death.''
Numerous other medical experts have made similar public
statements. The death of Steve Bechler is the first time
ephedra has been blamed as the cause of a fatal heatstroke. But
there is no repeat of heatstroke associated with ephedra in the
Cantox Report or the Rand Corporation report or in the online
medical libraries. In literally dozens of studies, ephedra-
based products have been shown to be safe when used properly.
To prevent similar or future tragedies should be the real
focus of all of us here. This focus will be lost by improperly
seeking to lay the blame on a supplement while ignoring the
real factors that may have contributed to the tragedy, such as
improper medical screening, training, and treatment by the
Baltimore Orioles. It is for these reasons that we have worked
so hard to fully cooperate with this investigation.
Cytodyne Technologies worked diligently to market its
products responsibly in the firm belief that Xenadrine RFA-1
was safe and effective when used as directed. We took a more
conservative approach with our dosage recommendation than doses
used in many of the ephedrine/caffeine studies, as well as many
of the other products on the market. Our label included very
comprehensive warning language and went even beyond recommended
industry standards.
We commissioned product specific studies to assess the
safety and efficacy of Xenadrine RFA-1. The product studies are
not required of our industry, and many of our competitors, most
in fact, have not done them.
Xenadrine RFA-1 is the subject of not one, but 7
independent clinical trials for safety and efficacy. And the
results of these studies were accepted for publication and
published in the abstract form or full length reports in well
respected peer reviewed scientific journals.
We retained and relied upon various experts such as a
medical doctor, Ph.D. level nutritional researchers and
exercise physiologist as well as other professionals such as
regulatory experts who reviewed our labels. We engaged Dr.
Carlon Colker, a respected physician as a consultant for
medical and academic advice.
In response to a small number of customer complaints
beginning in the year 2000 I asked Dr. Colker to work with our
company and the customers to learn about such complaints and
act as a referral source. Although Congress has not required
companies like ours to document or report complaints, we did
adopt the policy and practice to record and preserve that
information.
Our policy was to tell any customers concerned about
adverse effects to stop taking our product and seek medical
advice. And we offered the services of Dr. Colker as a referral
source.
We have always listened closely to customer feedback, both
negative and positive. The customer reports are well known to
be unreliable for scientific reasons. Over almost 5 years we
sold over 20 million bottles, but received only about 450
complaints. The great majority of these complaints were for
mild transient side effects. We never had any reason to believe
that Xenadrine RFA-1 caused anything but mild transitory
effects.
The available science confirms that ephedra is effective
and safe when properly used by healthy individuals. A major
report by Cantox Health Sciences International on the safety of
ephedra based products contained a comprehensive risk
assessment. The Cantox report conducted a thorough review of
the available study literature and established that ephedra is
safe when used properly according to industry recommendations.
Based on emerging new research, Cytodyne introduced a new
formulation which did not contain ephedra just over 1 year ago.
And at that time the decision was made to begin phasing our
ephedra product and to focus our efforts on the new
formulation, which we believe to be superior in efficacy. With
the discontinuation of Xenadrine RFA-1 earlier this year, the
final phaseout was completed as planned.
Let me state emphatically that our reasons for
discontinuing Xenadrine RFA-1 were not in any way based on
concerns regarding the safety or efficacy of the product. To
the contrary, it is our continued belief that the science
supports the position that Xenadrine RFA-1 is safe and
effective when used as directed.
The truth is that a ephedra supplements have been used by
tens of millions of people in recent years. Unfortunately, with
a population this large there is an expected number of medical
problems that will always occur whether people use ephedra or
not. It is not appropriate to simply blame ephedra every time
someone in that population experiences a problem.
The debate over ephedra has become a circus and to decide
the future of dietary supplements in a media frenzy would be
irresponsible. We are relieved that Congress is stepping in and
we are confident that the appropriate responsible steps will
now be taken to resolve the issue of the safety of ephedra.
As this subcommittee continues its investigation, I hope
that the massive amount of information we have already provided
to you and your staff will be helpful. And I look forward to
answering your questions.
Thank you.
[The prepared statement of Robert Chinery follows:]
Prepared Statement of Robert Chinery, Jr., President, Nutraquest Inc.
My name is Robert Chinery, Jr., and I am the President of
Nutraquest, Inc., formerly known as Cytodyne Technologies, Inc. I
appreciate the opportunity to come before the Subcommittee and address
the issues surrounding ephedra-based dietary supplements.
I have come here today to cooperate fully, as we have done
throughout the investigation by this Subcommittee, even though we are
no longer selling an ephedra-based product and are no longer marketing
any of the Cytodyne dietary supplements.
Our decision to phase out our ephedra product was a business
decision fueled by consumer demand for new and better products,
skyrocketing insurance premiums, as well as unjustified media hype
regarding ephedra. We developed, and launched in early 2002 a new--and
we think better--ephedra-free product, named Xenadrine EFX<SUP>'</SUP>.
That product met with a very positive response from consumers, and
quickly surpassed the ephedra-based Xenadrine RFA-1<SUP>'</SUP>,
further reinforcing our decision to move in this direction. As a result
of the overwhelming positive feedback from consumers, combined with the
growing anti-ephedra climate, we believed it would be better to focus
on Xenadrine EFX<SUP>'</SUP>. We began phasing out our ephedra product,
Xenadrine RFA-1<SUP>'</SUP>, by ceasing advertising and promotion of it
in early 2002. Pursuant to this planned phase-out, we completely
stopped selling it in early 2003. Let me state emphatically that we did
not discontinue the Xenadrine RFA-1<SUP>'</SUP> product because we
thought there was any merit to concerns regarding the safety or
efficacy of the product. To the contrary, it is our continued belief
that the science supports the position that Xenadrine RFA-1<SUP>'</SUP>
is safe and effective when used as directed.
Cytodyne Technologies has recently transferred to another leading
dietary supplement company all marketing and distribution rights for
Cytodyne Technologies products, except Xenadrine RFA-1<SUP>'</SUP>,
which was discontinued.
Although we stopped selling the ephedra-based Xenadrine RFA-
1<SUP>'</SUP>, we fully cooperated with this investigation because I
believe as a citizen, a businessman, a husband and father, that the
Congress and the American public should get the facts in the
investigation into ephedra-based dietary supplements.
In fully cooperating with the investigation, I have come here
voluntarily today, without subpoena, and have instructed our lawyers
since day one in this investigation to be as helpful as possible with
the Subcommittee and its staff. At great cost, we served eleven
responses and supplemental responses, produced thousands and thousands
of pages of documents, compiled data and answers for your counsel, and
came to Washington for two solid days of interviews of three witnesses.
And we have thousands or tens of thousands of pages of documents from
satisfied consumers, which we made available to the Committee for its
inspection, and we hope you will also consider. The Subcommittee's
requests have compelled us, and others, to come forward, and we have
accepted that responsibility.
The tragic death of baseball pitcher Steve Bechler was the catalyst
for this inquiry. Our hearts go out to his wife and new baby, his
parents, and entire family. Their loss must be difficult to bear. He
was a very young man and struggling hard to make his place on a major
league baseball team. He was an expectant father and was newly married.
As a father of four, I cannot feel anything but sympathy for his
family. My family and I, and all the people associated and affiliated
with Cytodyne Technologies, express our most sincere condolences to
Steve Bechler's family and friends.
In an effort to understand what happened in this tragedy, we
retained one of the top medical examiners in the country to review the
autopsy report. Dr. Michael Baden's sworn opinion is submitted to the
Subcommittee as a part of this statement. Dr. Baden is very well-known
and highly regarded. Dr. Baden examined the available information and
determined that Xenadrine RFA-1<SUP>'</SUP> did not cause or contribute
to Steve Bechler's death. Dr. Baden concluded, specifically, as
follows:
I agree with Dr. Perper that the cause of Mr. Bechler's death
was heat stroke. However, I disagree as to the cause of this
heat stroke. Mr. Bechler's poor health, vigorous exercise in
hot, muggy weather, severe obesity, abnormal fatty liver,
untreated high blood pressure, and enlarged heart are competent
factors in and of themselves to be causes of heat stroke. The
coincidental toxicologic finding of ephedrine, which is not
known to produce heat stroke, in my opinion should not have
been linked to the death by the medical examiner--just as the
medical examiner did not link the finding of increased level of
DHEA to his death.
It is my opinion, to a reasonable degree of medical
certainty, based on all of the materials I have thus far
reviewed, on my training and on my 43 years experience as a
medical examiner, that Mr. Bechler died of a heat stroke
precipitated by his morbid obesity, high blood pressure and
heart disease, adverse weather conditions, physical exertion,
and inadequate screening, monitoring and medical supervision;
that Xenadrine did not cause or contribute to Mr. Bechler's
death; and that proper and prompter treatment with intravenous
fluids and cold wraps immediately after he collapsed but was
still conscious may have prevented Mr. Bechler's death.
It should be highlighted that the death of Steve Bechler is the
first time ephedra has been blamed as the cause of a fatal heat stroke.
There is no report of heat stroke associated with ephedra in the Cantox
Report or the RAND Corporation report or found in the online medical
libraries. In literally dozens of studies, ephedra-based products have
been shown to be safe when used properly.
To prevent future or similar type tragedies should be the real
focus of all of us here. This focus will be lost by improperly seeking
to lay the blame on a supplement or an industry while ignoring the real
factors that caused or contributed to the tragedy, such as improper
medical screening, training, and treatment by the Baltimore Orioles. It
is our hope that when the true factors come to light proving ephedrine
was not the cause of Mr. Bechler's death, that appropriate and
reasonable measures will be taken to prevent tragedies like this in the
future.
I take the subject of dietary supplements very seriously. I became
involved in the supplement industry because I have used the products
myself and have experienced their benefits firsthand. After seeing the
benefits, it became my passion. I have personally taken ephedra and
caffeine products, including our Xenadrine RFA-1<SUP>'</SUP>, and it
was effective for me. My wife, our family, and many of our friends have
also taken and enjoyed the benefits of Xenadrine RFA-1<SUP>'</SUP>.
Over time, our product became one of the most successful in the dietary
supplement industry. Our company has received inspiring feedback from
tens of thousands of people who have lost weight and have improved
their quality of life using Xenadrine RFA-1<SUP>'</SUP>.
In the early 1990's, I worked for a company that sold an ephedra-
caffeine product. I was encouraged as I listened to our customers, who
were struggling to lose weight and found the ephedra-caffeine
combination products very helpful. Weight loss is difficult. America's
weight problems are steadily getting worse.
The Centers for Disease Control has posted on its website some very
powerful statistics that show Americans are increasingly overweight. As
of the year 2000, the prevalence of obesity among U.S. adults was 19.8
percent, which is a 61 percent increase since 1991. In 2000, 38.8
million American adults could be classified as obese, defined as having
a Body Mass Index, or BMI, of 30 or more. Between 2000 and 2001,
obesity climbed from 19.8 percent of American adults to 20.9 percent of
American adults. Currently, more than 44 million Americans are
considered obese according to the BMI index; that is, they have a BMI
greater than or equal to 30. This reflects an increase of 74 percent
since 1991.
Fighting this struggle is emotionally difficult for many people.
When something works, it makes a meaningful difference in their lives.
That is why, after the first supplement company I worked for was sold,
I researched many different dietary supplements and reviewed scientific
literature preparing to market a new weight loss product that provided
meaningful benefits. Based on the volumes of existing research
supporting its safety and efficacy, it seemed clear that a product
centered around the ephedrine-caffeine combination offered the best
potential.
Those numerous clinical studies showed what we still know today,
that the ephedrine-caffeine combination is one of the few combinations
that help people lose weight.
Cytodyne Technologies started out as and remains a small business.
We had until recently ten employees. The good men and women of Cytodyne
Technologies involved in marketing Cytodyne Technologies' products did
so responsibly, in the firm belief that Xenadrine RFA-1<SUP>'</SUP> was
safe and effective when used as directed. We took seriously the
scientific and other information we learned as we marketed Xenadrine
RFA-1<SUP>'</SUP>, and relied as appropriate on experts and scientific
studies. To develop and make Xenadrine RFA-1<SUP>'</SUP>, we hired a
very reputable manufacturer, run by an experienced pharmacist, that has
manufactured hundreds of other nutritional supplements. I was
personally familiar with this manufacturer and their expertise from my
experience working in the dietary supplement industry. Their products
were well-regarded. We felt that this company stood out because they
were licensed to make over-the-counter drugs, followed good
manufacturing practices, and had a higher level of attention to quality
control and a higher quality of product overall.
Although we relied initially on the clinical studies of the
ingredients ephedrine and caffeine, we took a more conservative
approach than utilized in those studies by implementing a substantially
lower dosage of ephedrine and caffeine than what was used and shown to
be safe in those studies. Our label included the most comprehensive
warning language and went even beyond industry standards. It warned
customers to consult a physician before using if they were at risk for
certain specific conditions.
We commissioned product-specific studies in marketing our product.
Product-specific studies are not required of our industry and many of
our competitors--most have not done them. We took that step, though, a
total of seven times. We think we helped start a trend in the right
direction and our tests demonstrate our efforts to be responsible.
These were independent, product-specific, double-blind, randomized, and
placebo-controlled (or, in one case, compared to a prescription
product). The results were accepted for publication and published in
abstract form or full-length reports in well respected, peer-reviewed
scientific journals such as the International Journal of Obesity. In
each study, Xenadrine was shown by statistically significant data to be
effective for weight or fat loss within the confines of the study.
These studies were also designed to measure certain specific safety
criteria, such as vital signs, blood chemistry, blood pressure and
EKGs. submissions be made a part of this record.
We retained and relied on various experts, such as a medical
doctor, Ph. D.-level nutritional researchers and exercise
physiologists, as well as other professionals, such as regulatory
counsel who reviewed our labels. We engaged Dr. Carlon Colker, a
respected physician, as a consultant after his firm, Peak Wellness,
completed the first scientific study on Xenadrine RFA-1<SUP>'</SUP>. We
wanted someone with his high level of knowledge and background as a
consultant. He provided guidance on a number of technical issues, and
kept us advised of developments in research and in the dietary
supplement industry.
When we received our first complaint alleging a serious adverse
health effect, in June of 2000, I asked Dr. Colker to work with our
company and the customers to learn about such complaints and act as a
referral source so that we could better understand the information. We
believe we are the only company that used a medical doctor in this way.
Many stories in the press have focused on customer complaints, as
opposed to scientific studies, to allege that ephedra causes serious
adverse effects. Although Congress has not required companies like ours
to document or report complaints, we did adopt a policy and practice to
record and preserve that information. We had a policy and practice in
place that any customer complaint of an adverse health effect was
directed to Mr. Conklin, who reported directly to me. Our policy was to
tell any customer concerned about adverse effects to stop taking our
product and seek medical advice, and we offered the services of Dr.
Colker as a referral source. We distinguished ourselves from many other
companies by having this system.
When asked by the Food and Drug Administration to respond to
Adverse Event Reports, we asked Dr. Colker to help us prepare the
responses. Dr. Colker gave us his assessment of information he received
about customers who called him with medical complaints, and he did not
conclude that Xenadrine caused any serious adverse health effects.
Cytodyne Technologies was advised and believes that the complaints
are anecdotal and do not indicate that Xenadrine RFA-1<SUP>'</SUP> was
unsafe, or caused any serious adverse effects for several reasons.
Customer reports are well-known to be unreliable for scientific
reasons. The General Accounting Office has issued two reports, one in
July 1999 and one earlier this year, concluding that adverse event
reports and customer call records do not prove cause and effect. Over
almost five years, we received a very small number of complaints
compared to the volume of our sales. We sold over twenty million
bottles--over a billion servings--but we received only about 450
complaints, including many during the recent months of great media
attention. The great majority of those complaints were for transient,
mild side effects.
We always took customer complaints seriously. Since I started this
company, I have listened closely to customer feedback, both negative
and positive. We never had any reason to believe that Xenadrine RFA-
1<SUP>'</SUP> caused anything but mild, transitory effects. We believed
this because we relied upon professionals and studies.
During the time we were selling Xenadrine RFA-1<SUP>'</SUP>, we did
not become aware of any reliable scientific studies finding that there
were safety problems with ephedra products. Rumors, news stories, and
unscientific information began to circulate with greater frequency, but
we did not find that kind of information reliable, nor did our medical
consultants.
Instead, the available science confirms that ephedra is effective
and safe when properly used. A major report by Cantox Health Sciences
International on the safety of ephedra-based products contained a
comprehensive risk assessment. The Cantox report conducted a thorough
review of the available study literature and established that ephedra
is safe when used properly according to industry recommendations. The
recent RAND Corporation report also confirms that ephedra works for
mild to moderate weight loss. The RAND Corporation concluded (like the
General Accounting Office did) that adverse event reports are not
reliable to support any conclusions about effects caused by dietary
supplements. The RAND Corporation report concluded that there is
insufficient evidence to conclude that ephedra poses an imminent health
hazard and that further studies need to be conducted.
In comparison to the complaints relating to adverse effects, we
received thousands and thousands more responses from satisfied
customers praising the benefits of Xenadrine RFA-1<SUP>'</SUP>. We sent
out and received back tens of thousands of customer satisfaction survey
forms, and only a tiny number of them mentioned any dissatisfaction or
adverse effects.
We also welcome a chance to respond publicly to news about a recent
ruling in a class action lawsuit against us in California. We were
surprised and dismayed by the California state court's decision because
the judge in that case disregarded the rulings of a federal judge in
Utah in 2000, who found the same advertising claims challenged in
California were true and not misleading. That federal judge conducted
days of hearings and heard the evidence. He approved the reliability
and competence of Dr. Colker's clinical study on Xenadrine RFA-
1<SUP>'</SUP>. Naturally, we relied upon that decision in believing
that our advertising was legal, true and not misleading.
Another major error, we believe, in the California case was the
total lack of any evidence that the public was misled. There was no
evidence concerning what consumers took away from our ads, nor that
consumers were misled. It is our position that the judge substituted
his personal opinion for hard evidence. We believed, and a federal
judge ruled in our favor, that our advertising claims were true and not
misleading. We will appeal this decision and we are confident that it
will be reversed.
We are just as hopeful that this Subcommittee will fairly consider
the information we have presented and be guided by the reliable
scientific information and not be caught up in the media hype.
The truth is that ephedra supplements have been used by tens of
millions of people in recent years. Unfortunately, with a population
this large, there is an expected number of medical problems that will
always occur whether those people used ephedra or not. It is not
appropriate simply to blame ephedra every time someone in that
population experiences a problem. It is unfair, unscientific,
unreliable and is an injustice to the right of the American people to
make their own choices. The debate over ephedra has become a circus,
and to decide the future of dietary supplements in a media frenzy would
be irresponsible. We are relieved that Congress is stepping in and we
are confident that the appropriate responsible steps will now be taken
to resolve the issue of the safety of ephedra.
As this Subcommittee continues its investigation, I hope that the
massive amount of information we have already provided to you and your
staff will be helpful, and I look forward to answering your questions.
Mr. Greenwood. I thank you, Mr. Chinery.
The Chair would advise the members of the committee, the
witnesses and the audience that we do have a vote in progress.
Unlike the last time we left you and did not return for 2\1/2\
hours, we will recess now. We should be back in about 15
minutes.
[Brief recess.]
Mr. Greenwood. Mr. Conklin, I believe that you are next.
And you are recognized to give your opening statement. And make
sure that microphone is facing you and turned on, please.
TESTIMONY OF KELLY CONKLIN
Mr. Conklin. Thank you, Mr. Chairman.
My name is Kelly Conklin, I am a consultant to Cytodyne LLC
and, until very recently, I worked for Cytodyne Technologies,
Inc., which is now known as Nutraquest, Inc. Cytodyne LLC
recently acquired the rights to market Cytodyne Technologies'
products, except for Xenadrine RFA-1 <SUP>'</SUP>, the ephedra-
based dietary supplement, which was discontinued as of February
this year. Although we did not have very formal titles, I
served as the Director of Public and Customer Relations for
Cytodyne Technologies, Inc. I began working part-time for
Cytodyne Technologies in 1997, while I was still employed as a
Police Officer for the Dover Township, New Jersey, Police
Department. I graduated from the New Jersey State Police
Academy first in my class in the academic and physical
components.
While I worked at Cytodyne Technologies, one of my
responsibilities was to deal with customers who contacted us
with concerns about possible adverse effects that they
experienced while taking Xenadrine RFA-1 <SUP>'</SUP>.
Beginning sometime in early 2000, Cytodyne Technologies
received such complaints and Mr. Chinery, the owner of
Cytodyne, asked me to take responsibility for handling the
complaints. We received very few complaints initially. When, in
June 2000, we received our first complaint of a potentially
serious adverse effect, Mr. Chinery arranged for us to be able
to refer such customers to Dr. Carlon Colker, and for Dr.
Colker to review that complaint and provide us with any
guidance or information that we needed.
We tried to continue to improve over time the way we took
information from callers. Many consumer calls or correspondence
were not specific enough for us to determine whether Xenadrine
RFA-1 <SUP>'</SUP> was even used, to document the effect
reported, or to ascertain information about other possible
causes. Sometimes, the consumer indicated improper use of the
product, pre-existing conditions that they thought might
account for the reported event, or other information indicating
that the connection to Xenadrine RFA-1 <SUP>'</SUP> may be
missing.
Since we at Cytodyne were not medically trained, however,
we engaged Dr. Carlon Colker to help us understand and deal
with customer complaints of alleged adverse effects. By
engaging a medical doctor to guide us in this regard, we felt
we were being very responsible. In addition, Dr. Colker
provided responses for Cytodyne Technologies concerning adverse
event report forms forwarded to Cytodyne Technologies by the
Food and Drug Administration. According to our records, the
company has received complaints of adverse effects from the use
of Xenadrine RFA-1 <SUP>'</SUP> over a several year period
during which approximately 20 million bottles of the product
were sold, each containing 120 capsules, for a total of about
1.2 billion servings. After an extensive review by the company
and its attorneys, our records indicate a total of just under
450 customers contacted Cytodyne Technologies concerning their
complaints about the use of Xenadrine RFA-1 <SUP>'</SUP>, and
most of those were for mild, transitory effects.
It was our policy and practice to advise customers that if
they were experiencing adverse effects, they should discontinue
the use of the product, and contact their physician. We made
Dr. Colker available to them to learn more about their
situation and perhaps share some information with them
concerning Xenadrine RFA-1 Dr. Colker also advised us of the
inherently unreliable nature of adverse event reports and
customer complaints, and that many scientific studies showed
ephedra-based dietary supplements to be effective and safe
within the confines of the clinical studies and when used
appropriately. Nevertheless, we paid attention to the
information reported to him and reported from him to us, which
we have of course turned over to the committee in full.
I am prepared to try to answer any questions and provide
this information to Congress and the American public.
Thank you, Mr. Chairman.
[The prepared statement of Kelly Conklin follows:]
Prepared Statement of Kelly Conklin, Cytodyne LLC
My name is Kelly Conklin, I am a consultant to Cytodyne LLC and,
until very recently, I worked for Cytodyne Technologies, Inc., which is
now known as Nutraquest, Inc. (Cytodyne LLC recently acquired the
rights to market Cytodyne Technologies' products, except Xenadrine RFA-
1<SUP>'</SUP>, the ephedra-based dietary supplement, which was
discontinued as of February this year.) Although we did not have very
formal titles, I served as the Director of Public and Customer
Relations for Cytodyne Technologies, Inc. I began working part-time for
Cytodyne Technologies in 1997, while I was still employed as a Police
Officer for the Dover Township, New Jersey, Police Department. I
graduated from the New Jersey State Police Academy first in my class in
the academic and physical components.
While I worked at Cytodyne Technologies, one of my responsibilities
was to deal with customers who contacted us with concerns about
possible adverse effects that they experienced while taking Xenadrine
RFA-1<SUP>'</SUP>. Beginning sometime in early 2000, Cytodyne
Technologies received such complaints and Mr. Chinery, the owner of
Cytodyne Technologies, asked me to take responsibility for handling the
complaints. We received very few complaints initially. When, in June
2000, we received our first complaint of a potentially serious adverse
effect, Mr. Chinery arranged for us to be able to refer such customers
to Dr. Carlon Colker, and for Dr. Colker to review that complaint and
provide us with any guidance or information that we needed.
We tried to continue to improve over time the way we took
information from callers. Many consumer calls or correspondence were
not specific enough for us to determine whether Xenadrine RFA-
1<SUP>'</SUP> was even used, to document the effect reported, or to
ascertain information about other possible causes. Sometimes, the
consumer indicated improper use of the product, pre-existing conditions
that they thought might account for the reported event, or other
information indicating that the connection to Xenadrine RFA-
1<SUP>'</SUP> was missing.
Since we at Cytodyne Technologies were not medically trained,
however, we engaged Dr. Carlon Colker to help us understand and deal
with customer complaints of alleged adverse effects. By engaging a
medical doctor to guide us in this regard, we felt we were being very
responsible. In addition, Dr. Colker provided responses for Cytodyne
Technologies concerning adverse event report forms forwarded to
Cytodyne Technologies by the Food and Drug Administration. According to
our records, the Company has received complaints of adverse effects
from the use of Xenadrine RFA-1<SUP>'</SUP> over a several year period
during which approximately 20 million bottles of the product were sold,
each containing 120 capsules, for a total of about 1.2 billion
servings. After an extensive review by the Company and its attorneys,
our records indicate a total of just under 450 customers contacted
Cytodyne Technologies concerning their complaints about the use of
Xenadrine RFA-1<SUP>'</SUP>, and most of those were for mild,
transitory effects.
It was our policy and practice to advise customers that if they
were experiencing adverse effects, they should discontinue the use of
the product, and contact their physician. We made Dr. Colker available
to them to learn more about their situation and perhaps share some
information with them concerning Xenadrine RFA-1<SUP>'</SUP>.
Dr. Colker also advised us of the inherently unreliable nature of
adverse event reports and customer complaints, and that many scientific
studies showed ephedra-based dietary supplements to be effective and
safe within the confines of the clinical studies and when used
appropriately. Nevertheless, we paid attention to the information
reported to him and reported from him to us, which we have of course
turned over to the Committee in full.
I am prepared to try to answer any questions and appreciate the
opportunity to provide this information to Congress and the American
public.
Mr. Greenwood. Thank you, Mr. Conklin.
Dr. Colker?
TESTIMONY OF CARLON M. COLKER
Dr. Colker. Mr. Chairman, Congressmen, Congresswoman, my
name is Carlon M. Colker, M.D., and I welcome this opportunity
to assist this subcommittee as it looks into ephedra-based
dietary supplements. I am the Medical Director of Peak Wellness
in Greenwich, Connecticut. Peak Wellness is a center that
provides a variety of services including traditional allopathic
medicine, preventive care, nutrition services and physical
therapy.
I am an attending physician at Beth Israel Medical Center
in New York, and Greenwich Hospital in Connecticut.
While ephedra-based dietary supplements are appropriate for
some people, they are populations for whom I think they are not
appropriate. First, those persons who have contrary indicated
conditions should not take ephedra-based products, particularly
without being monitored by a physician. Moreover, I believe
there is a significant abuse potential among the youth and
athletes.
Young people tend to fall into the scary mindset that more
is better. Although efforts are being made by responsible
retailers to prevent sales to minors, regulation to further
prevent these types of sales would be prudent. Similarly, in
general, athletes have a significant abuse potential in that
some are willing to go to extremes to get the edge.
Much attention has been paid for serious adverse events
reports or AERs, despite no correlation with any available
scientific research confirming causation. Though useful as a
tool for some aspects of general tolerability, monitoring
adverse event reports are recognized by the Department of
Health and Human Services as being extremely limited,
nonscientific and certainly not conclusive of cause and effect.
According to the published caveats issued by the Center for
Drug Evaluation and Research, adverse event reports are not, by
themselves, scientific and in no way prove cause and effect.
For any given report, AER, there is no certainty that the
suspected drug caused the reaction. It further warned the event
AER may have been related to the underlying disease for which
the drug was given to concurrent drugs being taken or may have
occurred by chance at the same time the suspected drug was
taken.
Finally, accumulated case reports or AERs cannot be used to
calculate incidents or estimates of drug risk.
As far as these points apply to dietary supplements, there
are many instances to illustrate the limits of this report
explained by the Center. Numerous examples of this poor
reliability can be found under the adverse events reporting
system, AER's Freedom of Information Reporter, FOI.
One such example cited 877 reactions including convulsions,
vomiting chest pain, tachycardia, atrial fibrillation, high
blood pressure, myocardial infarction, shock, and numerous
other serious symptoms--all attributed to ingestion of vitamin
C. Other problems include AER reports of vitamin C ``causing''
visual problems, thyroid cancer, and even mood swings and foot
fracture. So again, while a useful tool on the level of general
monitoring, the current AER monitoring system has serious
limitations in terms of accurately determining cause and should
be interpreted with great care.
I suspect it is for this reason that the Department of
Health and Human Services and the General Accounting Office
have consistently rejected the insinuation that AERs reliably
show cause and effect and that they form any basis to prove the
contention that ephedra should be banned. In sharp contrast to
this observational data, they have historically relied on the
available medical and scientific clinical research During the
Subcommittee's investigation, many references have been made to
the recent death of Steve Bechler. His death at such a young
age is profoundly upsetting and a tragedy. I feel very sad for
Mr. Bechler's wife, his baby, his family and friends. As a
physician and sports training specialist, I am concerned when
an athlete with Mr. Bechler's significant medical conditions,
repetitive history of heatstroke, and apparent lack of
conditioning and acclimatization, is pushed or pushes himself
beyond all reasonable limits. But as I have said in the past, I
do not believe that ephedra caused or contributed to his
untimely death. If I saw one case, just one, that conclusively
confirmed that ephedra was the cause of a serious injury or
death when taken as directed and by an appropriate otherwise
healthy individual, I would not be on this panel.
As this committee continues its inquiry on behalf of the
American public and the Congress, I hope that my information
will be helpful to you, and I look forward to answering your
questions.
Thank you.
[The prepared statement of Carlon M. Colker follows:]
Prepared Statement of Carlon M. Colker, Peak Wellness Inc.
My name is Carlon M. Colker, M.D., and I welcome this opportunity
to assist this Subcommittee as it looks into ephedra-based dietary
supplements. I am the Medical Director of Peak Wellness in Greenwich,
Connecticut. Peak Wellness is a center that provides a variety of
services including traditional allopathic medicine, preventive care,
nutrition services and physical therapy. I work in health and fitness
primarily as a consultant. I am an attending physician at Beth Israel
Medical Center in New York, as well as Greenwich Hospital in
Connecticut. I have been appointed by the State of Connecticut to the
posts of Assistant Medical Examiner and Probate Court physician. I am a
fellow in the American College of Nutrition, and a member of the
American College of Physicians and the American College of Sports
Medicine, among many other professional medical organizations. I
received my undergraduate degree from Manhattanville College in
Purchase, New York in 1988, and became a Doctor of Medicine after
graduating from the Sackler School of Medicine in New York in 1993,
where I was class president and received a variety of honors. I
completed my internship and residency in internal medicine at the Beth
Israel Medical Center in New York in 1996.
I have always had a self-awareness in health. I play sports, I work
out regularly, and I take my nutrition and sports seriously, both
professionally and in my personal life. I also take dietary
supplements, and I have personally taken a variety of ephedra-based
dietary supplements for the purpose of losing weight. I found that they
worked well for me, over and above any adjustments to my diet and
exercise. I also use ephedra-based products in my practice.
Among many other things, I have a medical practice, and we have a
mission in wellness--doing what we can to improve the quality of our
patients' lives and health. This includes helping our patients lose
excess weight and helping them get physically fit. In that pursuit, we
have been involved in evaluating and utilizing various diet programs,
exercise programs, and nutritional supplements, including ephedra-based
dietary supplements.
In 1999, we were approached by Cytodyne Technologies, Inc., to
perform a clinical evaluation of Xenadrine RFA-1<SUP>'</SUP>. We
designed a study protocol for a prospective, randomized, double-blinded
clinical trial to evaluate the product versus a placebo in otherwise
healthy overweight adults. The general intent of our study was to take
a limited look at the safety and efficacy of this compound within the
confines of the study, with the primary endpoint in efficacy being
weight/fat loss.
Thirty overweight adult subjects were randomized into an eight week
clinical trial and 16 subjects received Xenadrine RFA-1<SUP>'</SUP>.
The other 14 subjects received a matched placebo. All subjects were
instructed by a Registered Dietician as to specific dieting. In
addition, they were instructed in a cross-training exercise program.
Twenty-five subjects concluded the study. The Xenadrine group lost a
statistically significant amount of fat versus the placebo group. An
outside, independent statistical analysis was conducted by a Columbia
University, Ph. D. in Biostatistics.
Blood pressure, heart rate, serum chemistry, cholesterol, glucose
and caloric intake were measured. Serial electrocardiograms were also
performed. There were no notable changes in those safety parameters. We
concluded that these findings suggested that Xenadrine was safe and
effective within the confines of the study.
Our research was peer-reviewed and eventually accepted for full-
length publication in the April 2000 edition of the journal Current
Therapeutic Research. Peer review acceptance is a recognized indicator
of the competency and reliability of a given study. Moreover, this same
study, as well as the biostatistician's work, were deemed competent and
reliable by a federal judge in a decision rendered in 2000. The federal
judge also held that the study was a well-controlled clinical trial,
evaluated in an objective manner by persons qualified to do so, and
used procedures generally accepted to yield accurate and reliable
results. Furthermore, this study was well-rated by the RAND Corporation
when it engaged in a full literature review and meta-analysis at the
request of the Department of Health and Human Services.
We have clinically investigated other ephedra-based supplements, as
well as other dietary supplements. Many times, these studies did not
find efficacy or otherwise failed to support the research sponsor's
product.
I believe the study we performed for Cytodyne was a competent and
reliable study within its confines. I recognize, however, that whatever
it added to the scientific literature, it is not perfect and certainly
not the ``be-all-and-end-all'' on the subject. There have been many
other studies on ephedra-based dietary supplements and on the effects
of ephedra and caffeine for efficacy and weight/fat loss. I believe
these studies are critical in understanding the weight loss effects and
safety of ephedra-based dietary supplements.
While ephedra-based dietary supplements, including Xenadrine RFA-
1<SUP>'</SUP>, are appropriate for some people, there are populations
for whom I think ephedra-based dietary supplements are not appropriate.
First, those persons who have contraindicated conditions should not
take ephedra-based products, particularly without being monitored by
their physician. Moreover, I believe there is significant abuse
potential among youth, and among athletes. Young people tend to fall
into the scary mindset that ``more is better.'' Regulations should be
designed accordingly to prevent sales to minors. Similarly, in general,
athletes have a significant abuse potential in that some are willing to
go to extremes to get an edge.
In approximately November 1999, Cytodyne engaged me to serve as a
consulting expert. I also continued to maintain my own private medical
practice and to consult for other companies. At first, I was hired to
review ingredients and articles and to provide the company with
feedback, and to answer medical questions as they arose. In addition, I
was responsible for putting together academic information and appearing
at conferences and educational occasions. When asked, I reviewed label
questions and ingredients from time to time. I was also responsible for
informing the company if I came across something in the general
research of dietary supplements which I thought was important, and for
analyzing and reporting general market trends.
During the time I served Cytodyne as a consultant, Cytodyne asked
us to perform a comparative study evaluating Xenadrine versus a
prescription fat-blocking medication for weight loss in healthy
overweight women. The group receiving the Xenadrine RFA-1<SUP>'</SUP>
lost significantly greater weight when compared with the group
receiving the prescription fat-blocking agent. Our results were
published in abstract form.
During the time that I was consulting for Cytodyne, I also was
asked, beginning in approximately June 2000, to serve as a referral
source for certain company personnel when they felt there was a
customer question they could not answer or a customer issue they felt
was important to forward to me.
I estimate I have had roughly 60 calls from consumers with such
issues. Regarding those customer calls referred to me by Cytodyne, I
attempted to learn from the consumer what I could concerning their use
of the product, and whether label warnings or other contraindications
existed. I periodically reported the results of my conversations and my
observations to Cytodyne. I have found that these kinds of customer
calls, like adverse event reports to the FDA, are inherently unreliable
to indicate what caused the effects. In each of the cases involving
Xenadrine RFA-1<SUP>'</SUP>, I reported every one of them back to
Cytodyne. I answered customer concerns to the best of my ability, told
them to discontinue the product when appropriate, and referred them
back to their personal physician in every appropriate case.
I was also asked by Cytodyne to look at adverse event reports
received from the FDA and help them respond. As I have noted in my
correspondence to Kenneth J. Falci, Ph. D., Director of Scientific
Analysis and Support, Center for Food and Applied Nutrition, Department
of Health and Human Services, some of the reports seemed serious, but I
could not rule out the possibility that these were due to some other
cause.
I am also aware that Cytodyne developed a form for gathering
information from customers who initially made contact with the company
before the customers contacted me. Though I was not involved in the
development of this form, the form was simple enough for non-medical
operators to get important basic information. As I understand it,
Cytdoyne developed and used this form and informed callers who were
concerned about possible side effects to discontinue the use of all
products and seek medical advice. Given that, I believe that Cytodyne
acted responsibly. I am aware that Cytodyne reports having sold over 20
million bottles of Xenadrine. In light of that, the very small number
of calls, and the dispersion of those calls over time, and in light of
the types of calls and information I received, the information does not
indicate to me a disproportionate adverse event profile.
Though useful as a tool for some aspects of general tolerability
monitoring, AERs are recognized by the Department of Health and Human
Services as being extremely limited, nonscientific, and certainly not
conclusive of cause and effect. According to the published ``Caveats''
issued by Center for Drug Evaluation and Research,
Adverse events [AERs] are not by themselves scientific and in
no way prove cause and effect . . . For any given report [AER],
there is no certainty that the suspected drug caused the
reaction.
They further warn
The event [AER] may have been related to the underlying disease
for which the drug was given to concurrent drugs being taken or
may have occurred by chance at the same time the suspected drug
was taken.
Finally,
Accumulated case reports [AERs] cannot be used to calculate
incidence or estimates of drug risk.
As far as these points apply to dietary supplements, there are many
instances to illustrate the limits of this reporting as explained by
the Center. Numerous examples of this poor reliability can be found
under the Adverse Events Reporting System (AERS) Freedom of Information
(FOI) Report. One such example cited 877 reactions--including
convulsions, vomiting, chest pain, tachycardia, atrial fibrillation,
high blood pressure, myocardial infarction, shock, and numerous other
serious symptoms--all attributed to ingestion of vitamin C. Other
problems include AER reports of vitamin C ``causing'' visual problems,
thyroid cancer, and even mood swing and foot fracture.
So again, while a useful tool on the level of general monitoring,
the current AER monitoring system has serious limitations in terms of
accurately determining cause and should be interpreted with great care.
Perhaps the sharpest criticism of ephedra using AERs as a basis for
conclusion was published in the January 2002 issue of Mayo Clinic
Proceedings in which they looked at adverse cardiovascular events as
they relate to ma huang (Mayo Clin Proc. 2002;77:12-16). They admit:
Our report has the limitation of being an observational study
and as such does not definitively establish the relationship
between ma huang use and the risk of adverse cardiovascular
events.
Furthermore, they also said that their report fails to definitively
establish
. . . a causal relationship between the respective agents and
the observed adverse cardiovascular events. Additionally these
reports provide no insight on the potential biologic mechanisms
of the adverse effects of ma huang . . .
I suspect it is for this reason that the Department of Health and
Human Services and the General Accounting Office have consistently
rejected the insinuation that AERs reliably show cause and effect and
that they form any basis to prove the contention that ephedra should be
banned. In sharp contrast to this observational data, they have
historically relied on the available medical and scientific clinical
research.
Numerous clinical studies conducted by researchers like Daly,
Costello, Molnar, Dulloo, Dollery, Bell, and White, just to name a few,
have clearly researched and noted both the relative safety and efficacy
of ephedra and certain ephedra-based products when taken as directed
and by individuals appropriate to do so, and refute the impact of AERs
on the issue of safety.
During the Subcommittee's investigation, many references have been
made to the recent death of Steve Bechler. His death at such a young
age was a profoundly upsetting tragedy. I feel very sad for Mr.
Bechler's wife, baby, family and friends. As a physician and sports
training specialist, I am concerned when an athlete with Mr. Bechler's
significant medical conditions, repetitive history of heat stroke, and
apparent lack of conditioning and acclimatization, is pushed or pushes
himself beyond all reasonable limits. I do not believe that ephedra
caused or contributed to his untimely death.
As this Committee continues its inquiry on behalf of the American
public and the Congress, I hope that my information will be helpful to
you, and I look forward to answering your questions.
Mr. Greenwood. Thank you, Dr. Colker.
Mr. Occhifinto?
TESTIMONY OF ROBERT OCCHIFINTO
Mr. Occhifinto. Mr. Chairman, and other members of the
subcommittee, my name is Robert Occhifinto. I am the President
of NVE Pharmaceuticals in Newton, New Jersey.
NVE manufactures dietary supplements including products
that contain ephedra. I am here today to assist the
subcommittee in its review of the safety and effectiveness of
ephedra products.
NVE manufactures numerous dietary supplements. In addition
to our ephedra products I am here to discuss today, we
manufacture energy drinks and protein bars.
We are a substantial employer in a rural area in Sussex
County, New Jersey. At least 100 families in that are depend on
NVE for their livelihood.
Mr. Chairman, I appreciate the opportunity to testify
before the subcommittee today regarding ephedra.
Let me state first that I strongly believe in the safety
and effectiveness of NVE's products. The overwhelming
scientific evidence is that ephedra is safe and effective when
used as directed. Ephedra has been used for thousands of years.
The Rand Corporation in a study commissioned by the Department
of Health and Human Services at the request of FDA recently
reported on the safety and effectiveness of ephedra. The Rand
report examines all relevant clinical trial literature. It
concludes there is no evidence that ephedra is unsafe when used
as directed for weight loss. This government report does not
suggest the removal of ephedra from the marketplace.
Between 12 and 17 million Americans consume more than 3
billion servings of ephedra products every year. Against that
level of usage, the Rand report identified only 22 serious
events where ephedra could not be ruled out as a potential
cause.
The safety record of ephedra is comparable and in some
cases better than many of the over-the-counter pharmaceutical
products. For example, a recent study sponsored by NIH found
that acetaminophen, the active ingredient in Tylenol, is now
the leading cause of acute liver failure. Despite this finding,
the study concludes that acetaminophen is not dangerous. The
authors recommend more education to alert both patients and
doctors not to exceed the recommended dose. Acetaminophen
continues to be used as the active ingredient in several widely
used pain medications.
NVE has retained the Weinberg Group, a respect scientific
consulting firm, to review scientific on ephedra for us. The
Weinberg Group's Dr. Rosanne McTyre, a Johns Hopkins University
trained epidemiologist with more than 20 years experience
examined the Rand report in detail. This report is attached to
my written testimony as Exhibit B.
Dr. McTyre concludes that the current state of knowledge
regarding the safety of ephedra-containing products does not
warrant the removal from the marketplace. According to Dr.
McTyre, the document adverse health effects of ephedra are
minor, temporary and similar nature to drinks containing
caffeine. Serious events such heart attacks and strokes are not
conceivably links to ephedra use.
Ephedra has a mild stimulant effect and is effective for
weight reduction. The Rand report concluded that ephedra
containing dietary supplements were effective in weight loss of
2 pounds per month for a 6 month period. Ephedra is an
important tool for assisting individuals in connection with
weight management.
The subcommittee should not overlook the fact as it
considers these issues. Obesity is a serious public health
problem with staggering consequences. Recent studies indicate
that in the year 2000 about 64 percent of adult Americans were
overweight. A recent U.S. Surgeon General report predicts that
being overweight will soon match cigarette smoking as the
leading cause of premature death and disability in the United
States.
We recognize that the proper use of ephedra is essential.
NVE places extensive warnings on every ephedra-containing
product it sells. NVE labels warn consumers that consumptions
of amounts in excess of label directions could pose a risk of
severe adverse event, including stroke or heart attack. Our
labels warn against taking this product if you are pregnant,
nursing, have a family history of heart or thyroid disease.
I believe that were the first manufacturer in our industry
to put warning against use by minors our labels. We market our
products responsibly and are committed to preventing abuse.
We believe our products are safe and effective and satisfy
real consumer desire for weight management products.
NVE is committed to the safety of its products to making
sure that minors do not abuse them. To demonstrate our
commitment, I have advised the subcommittee by letter this
morning that NVE will provide funding to NIH for another
appropriate government body to independently study the long
term safety of ephedra.
We also undertake a public education campaign to alert
minors, their parents, their schools and their coaches against
the use ephedra products by minors. This education campaign
will also encourage the safe and responsible use of ephedra by
adults.
We hope that these important commitments by NVE will assist
the subcommittee and other government agencies in their
important in this area.
I am happy to answer any questions regarding our ephedra
products the subcommittee may have.
Mr. Greenwood. Thank you, Mr. Occhifinto.
Ms. Fox?
TESTIMONY OF ROSEANN FOX
Ms. Fox. Mr. Chairman, and other members of the
subcommittee, my name is Roseann Fox, and I am a customer
service representative at NVE Pharmaceuticals in Newton, New
Jersey. I have worked at NVE for 7 years and I have worked as a
customer service representative since 1999. As a customer
representative I respond to questions about how to take our
products, lost or damaged products and health concerns. When
individuals call with health concerns, I do not give them
medical advice. Instead, I advise them of the warning on the
labels and direct them to consult a physician.
I am happy to answer any questions regarding customer
relations at NVE that the subcommittee may have.
Mr. Greenwood. Thank you, Ms. Fox.
The Chair recognizes himself for 10 minutes for the purpose
of questioning. And I am going to start with you, Mr.
Occhifinto.
You do not have a college degree, medical degree or any
type of graduate degree relating to pharmacology, chemistry or
nutrition, correct?
Please bring the microphone over.
Mr. Occhifinto. No, Mr. Chairman, I do not. I have been in
this industry for 23 years and have practical on-the-job
training.
Mr. Greenwood. All right. Is it true that you formed NVE
Pharmaceuticals in 1980 upon graduation from high school?
Mr. Occhifinto. Yes, it is.
Mr. Greenwood. Where did you get the funds to begin this
business at 18 years of age?
Mr. Occhifinto. I worked for Sears Roebuck and saved up
money and opened up in a little 10 by 10 store.
Mr. Greenwood. Okay. At the time your formed NVE was a
distributor of diet products made under their label?
Mr. Occhifinto. I used to distribute products that were
manufactured by others in the small store that I had.
Mr. Greenwood. Okay. Is it true that NVE has never employed
a medical doctor, pharmacologist or chemist to formulate
ephedra containing products?
Mr. Occhifinto. Yes, it is.
Mr. Greenwood. Okay. Is it not true that the committee
staff questioned your general counsel, David Caldwell, on who
was responsible for determining the formulation of NVE's
ephedra-containing products and that it was represented to the
committee that you were the only person? Is that correct?
Mr. Occhifinto. Mr. Chairman, there is a lot of literature
out there about the formulation of the products that we
manufacture. Yes, it is.
Mr. Greenwood. Okay. But you are the guy that does that
without the medical degree or training, is that right?
Mr. Occhifinto. Yes, I am.
Mr. Greenwood. Okay. As the founder and president of NVE,
who runs the company in your absence?
Mr. Occhifinto. Walter Orichat is vice president.
Mr. Greenwood. Okay. It is our understanding that 1994 you
were convicted of a Federal charge of money laundering in New
Jersey and sentenced to 8 months prison, is that correct?
Mr. Occhifinto. No, it is not.
Mr. Greenwood. Okay. Could you correct the record?
Mr. Occhifinto. In 1991, approximately 12 years ago, I sold
a regulated compound without filing the paperwork. And in 1996
I went away for approximately 18 months and served my time.
Mr. Greenwood. For? What was the conviction?
Mr. Occhifinto. The conviction was for money laundering.
Mr. Greenwood. Okay. So that when I said it is our
understanding in 1994 you were convicted of a Federal charge of
money laundering and spent 8 months in prison, is that--what is
incorrect about that?
Mr. Occhifinto. It was 18 months.
Mr. Greenwood. Eighteen months?
Mr. Occhifinto. Yes.
Mr. Greenwood. That is what I said.
Mr. Occhifinto. I thought you said 8 months, I am sorry.
Mr. Greenwood. Well, I may have, but I meant to say 18
months.
All right. During those 18 months you were in prison who
was running NVE and making the business decisions?
Mr. Occhifinto. Roland Bossey.
Mr. Greenwood. Okay. Is it not correct that the money
laundering charges stemmed from you supplying ephedra in bulk
to a methamphetamine dealer?
Mr. Occhifinto. I do not know what happened to the material
that I supplied. I supplied it to somebody and I was charged
with supplying material without filling out the paperwork.
Mr. Greenwood. You do not know who you were supplying it
to?
Mr. Occhifinto. I know the gentleman I supplied it to. I do
not know what he actually did with the material. I know the
allegations of what he did with the material.
Mr. Greenwood. You do not know whether he was
methamphetamine dealer?
Mr. Occhifinto. Mr. Chairman, I know the allegations that
he was. I do not know the man personally.
Mr. Greenwood. Okay. Presumably since you have had over 20
years in the dietary supplement industry and are responsible
for formulating over 80 products that contain ephedra, you
would be aware of the various combinations that ephedra or
ephedrine may be used with to produce a drug?
Mr. Occhifinto. Ephedra is a dietary supplement, it's not
ephedrine, so it is not the same--the same thing on health for
ephedra as ephedrine, Mr. Chairman.
Mr. Greenwood. Has not the DEA made you aware beginning in
at least 1994 of the fact that your ephedrine and ephedra
tablets have ended up being seized in illegal methamphetamine
labs?
Mr. Occhifinto. Yes, they have.
Mr. Greenwood. Okay. Were you aware of that before the DEA
let you know about it?
Mr. Occhifinto. I was aware of it by--the DEA would always
inquire and we would always help the DEA in whatever they
needed information and requiring where shipments went to. And
we would report to DEA the shipments----
Mr. Greenwood. But you are testifying under oath here today
that you never knowingly supplied any of your products for the
purpose of them being used to produce illegal street drugs?
Mr. Occhifinto. Mr. Chairman, we discussed my conviction.
My conviction I knowingly sold ephedrine hydrochloride to
somebody who used it improperly. And after that and before
that, I know nothing else other than that.
Mr. Greenwood. Okay. And you were also convicted in the
early 1990's of a prior Federal criminal offense involving
importation of a controlled substance, hashish oil?
Mr. Occhifinto. Yes, Mr. Chairman.
Mr. Greenwood. And you were sentenced to house arrest for
18 months?
Mr. Occhifinto. No, I was not. I was on a trip with a
friend to Jamaica and he gave me a bottle of liquor to bring
back, he told me that it was because of Customs, he did not
want to pay the small duty on it. Could I carry it back. When I
got back I was aware by the Customs officer told me that there
was hash oil in it. We were both arrested at the airport, I
believe in Tampa. And the gentleman who did that took the
responsibility for that, and I got home confinement of 8
months.
Mr. Greenwood. Eight months, not 18?
Mr. Occhifinto. Yes.
Mr. Greenwood. Okay.
Mr. Occhifinto. That was 12 or 12 years ago, Mr. Chairman.
Mr. Greenwood. Very well.
Let me ask you a question, is it your company that marketed
products with names like Black Beauty and Yellow Jacket?
Mr. Occhifinto. We no longer market those products.
Mr. Greenwood. But you did, right?
Mr. Occhifinto. Yes, we did.
Mr. Greenwood. Okay. When you decided to name, where did
you get the idea of the name of Black Beauty? Is that from the
book?
Mr. Occhifinto. Just from the Disney character.
Mr. Greenwood. It was?
Mr. Occhifinto. Most of the products depict energy.
Mr. Greenwood. Okay. And you were not aware, you chose--
what was it about the Disney character that you thought it
would make a nice association with a weight loss product?
Mr. Occhifinto. Just the----
Mr. Greenwood. The svelte nature of the horse or what was
it?
Mr. Occhifinto. Well, the nature of the horse. That product
was more designed as an energy product than a weight loss
product.
Mr. Greenwood. Okay. And were you aware before you decided
to label this product Black Beauty that was a common street
drug called Black Beauty?
Mr. Occhifinto. No, it was not in my knowledge, no.
Mr. Greenwood. I knew that when I was in college. I mean,
it was pretty common knowledge that there were products of that
name that were illegal street drugs. You did not know that?
Mr. Occhifinto. Mr. Chairman, I--that was brought to my
attention about Black Beauty and the name Yellow Jacket at a
trade show sometime later after I introduced the products.
After doing some research on it, with the Yellow Jacket name, I
found out that it was a barbiturate. My product had a picture
of a bee, it was the color, yellow and black with stripes on
it. Looked like a bee. And was for energy. I did not really
think there was a problem naming it that.
Later on I found out----
Mr. Greenwood. I am just trying to figure out if you were--
what your marketing intent was when you came up with those
kinds of names, whether that was a way that you thought that
would appeal for young people, for instance?
Mr. Occhifinto. I do not condone marketing to young people.
I am one of the first people to come out with warnings not to
sell my products to minors.
Mr. Greenwood. Okay. Have you been told by any governmental
agency that you were a target of any criminal probes?
Mr. Occhifinto. To the best of my knowledge, no.
Mr. Greenwood. Okay. Is your current company currently
under investigation by the FDA?
Mr. Occhifinto. I believe we are trying to work something
with an inspection that we had with the FDA several weeks ago.
Mr. Greenwood. What was the issue there?
Mr. Occhifinto. We manufactured--we custom manufactured a
product called Stamina Rx for a company out of Atlanta, Georgia
where they supplied us all the raw materials. We simply blended
them, compounded them and shipped them back to them and to
distributors.
The FDA came in and alleged that there was a product called
Terdalophil in that product.
Mr. Greenwood. There was what?
Mr. Occhifinto. A product--that it was adulterated with a
product called Terdalophil.
Mr. Greenwood. And what is that?
Mr. Occhifinto. I believe it is a male potency product.
Mr. Greenwood. Okay. And is that product considered a
prescription drug? Do you need a prescription to get that?
Mr. Occhifinto. I believe it is.
Mr. Greenwood. Did you know that at the time of your
manufacturing?
Mr. Occhifinto. We were not provided with Terdalophil. We
were provided with herbal products. We manufactured it. The FDA
brought it to our attention that the material was contaminated
with Terdalophil or it had gotten there some other way. We do
not know how it got in the product. We did not put it in the
product.
Mr. Greenwood. All right. We are concerned about the lack
of any documentation that you have provided the committee
concerning the decisions surrounding the formulation and
marketing of your ephedra-containing products. It is very hard
to believe that a company in existence for over 20 years, as
you have described, has absolutely no documents to support its
decisions concerning formulation of products that are ingested
by human beings, products that have bee shown to have adverse
health effects in people.
Committee staff made numerous attempts to receive
responsive information from your company and NVE first through
your counsel and then by your own written representations
provided the committee with not one shred of documentation
concerning how you, Mr. Occhifinto, went about deciding to
formulate these products. Let me give you an example.
There is a document at Tab 57. It is a June 10--you see
that book there. If you want to refer to it. It is Tab 57.
June 10, 2003 letter to committee from Mr. Occhifinto
question number 21 page 6, ``After numerous attempts to receive
all documents relating to your formulation decisions and told
by your counsels that there was nothing other than perhaps your
own notes, the committee requested this follow up information.
Provide all of Bob Occhifinto's handwritten notes relating to
the formulation of any ephedra product'' and Mr. Occhifinto's
response was there are none. Is that correct, Mr. Occhifinto,
that in the 87 ephedra products that your company has sold in
the marketplace over the years you are telling this committee
under oath that absolutely no documents exist that detail the
decisionmaking and the formulation of the products?
Mr. Occhifinto. Mr. Chairman, we have extensive paperwork
on the formulas. There are no notes that were kept on any of
the products when they were manufactured. We have the formulas
and the backup paperwork every time we make a batch that
product with the formula.
Mr. Greenwood. Did you supply this committee with those
documents?
Mr. Occhifinto. I do not believe that was what was asked.
And we did supply the documents for the formula.
Mr. Greenwood. I am advised by counsel that we specifically
requested the formula cards from your company and that those
were not supplied.
Mr. Occhifinto. Mr. Chairman, if they were not supplied, we
can supply them to you. I think they were supplied, though,
because we never--there was--what we understood was the notes
about the formulas.
Mr. Greenwood. No, that was a last ditch effort to get
documentation from you because we had been told that there were
no documentation with regard to formulations with the
possibility--the only possibility being that of your personal
notes.
Mr. Occhifinto. Mr. Chairman, if they were not supplied, we
will supply them to you. There is no problem with that at all.
It must have been a miscommunication.
Mr. Greenwood. Well, we will have immediately at the
conclusion of this hearing before your attorney leaves the room
if you would be so kind, we would like you to consult with our
counsel and make sure that that offer by Mr. Occhifinto is
fulfilled as promptly as possible.
The Chair recognizes the gentlelady from Colorado for 10
minutes.
Ms. DeGette. Thank you, Mr. Chairman.
Mr. Occhifinto, just a follow up on the Chairman's
questions. How long were Yellow Jacket and Black Beauty on the
market, how many years?
Mr. Occhifinto. I do not know exactly. Approximately 2 to 3
years.
Ms. DeGette. Two to 3 years each?
Mr. Occhifinto. I believe so.
Ms. DeGette. And how much money did your company make from
each of those products during the period they were on the
market?
Mr. Occhifinto. I do not know the numbers for that.
Ms. DeGette. Can you please supplement?
I would ask unanimous consent that he supplement his answer
with that information within 20 days, if that would be all
right.
Mr. Occhifinto. That is no problem.
Ms. DeGette. Thank you.
Why did you withdraw these products, one named after a
Disney character and the other after a bumblebee, from the
market?
Mr. Occhifinto. It was brought to my attention that
marketers in the Netherlands were selling them as street drug
alternatives. As soon as it was brought to my attention, at
great expense to my company, I voluntarily recalled the product
off the market.
Ms. DeGette. Okay. And you had no knowledge before that of
any other kind of implications of those names in this country?
That is your testimony under oath today?
Mr. Occhifinto. I do not understand what you mean
``implications.''
Ms. DeGette. Well, you told Mr. Greenwood that you did not
know that Yellow Jacket and Black Beauty were the names of
illicit drugs in this country prior to that.
Mr. Occhifinto. I was made aware that some people use them
as slang terms a while ago, and at that time----
Ms. DeGette. But you did know that?
Mr. Occhifinto [continuing]. They told me--that was 20 or
30 years ago. I was--20 or 30 years ago, you know, I was 10 or
20 years old. It never occurred to me. I never saw drugs like
that. I did not know that.
Ms. DeGette. So your answer is you really did not know of
any illicit implications before you found out about this
situation in the Netherlands and withdrew them from the market?
Yes or no.
Mr. Greenwood. Will the gentlelady yield?
Ms. DeGette. Sure.
Mr. Greenwood. Your testimony under oath is that you
decided to use a Walt Disney character for a name for your
products, that you had no notion that Black Beauty had been
used as a street drug and you did not pick Dumbo, you did not
pick Pinocchio, you did not pick Goofy, you picked Black Beauty
and it was just an amazing coincidence? That is your testimony?
Mr. Occhifinto. Not until afterwards was I--was I apprised
that that was--that was the name of it. And I did not think it
was a problem, because 20 or 30 years had gone by before that
product was even on the--out there as a street drug.
Ms. DeGette. Reclaiming my time.
I asked you a simple question. You said you withdrew those
drugs from the market when you found out there was an issue in
the Netherlands. Did you know about those implications before
that? Yes or no.
Mr. Occhifinto. I knew previously that there----
Ms. DeGette. Thank you. Thank you.
Mr. Occhifinto [continuing]. Was allegations.
Ms. DeGette. Okay.
Mr. Teller. May he finish his answer, ma'am?
Ms. DeGette. Thank you, sir.
Now, Mr. Schreck, you said that your company prohibits the
sale of Metabolife to minors, correct?
You need to turn on your microphone, sir. That is okay.
Mr. Schreck. We favor the barring of sales to minors.
Ms. DeGette. No, but you said in your testimony you
prohibit the sale of Metabolife to minors, is that right? Or
did I mishear you.
Mr. Schreck. I do not think I said that, but I may have,
Congresswoman.
Ms. DeGette. How do you enforce that? Do you tell your
distributors and the retail sales not to sell it to minors?
Mr. Schreck. We communicate with them that we do not wish
to sell to minors and we do communicate to all of our sales
people this. And also----
Ms. DeGette. You have written protocols? I am sorry, I do
not mean to be rushing. They only give me a certain amount of
time. Do you have written protocols that you give to your sales
people and your distributors and the sales outlets saying do
not sell this to minors?
Mr. Schreck. We do not do that written protocol. We do have
verbal communications with them.
Ms. DeGette. So there is nothing in writing.
Mr. Schreck. And considering that our customers are with
the WalMarts of the world, we do not have great control over
enforcing what they do.
Ms. DeGette. Right. So you really cannot enforce who your
product is sold to, correct?
Mr. Schreck. Whoever WalMart will sell it to and other
people----
Ms. DeGette. I am right? Okay. Thanks.
Now, you also do not support the sale of Metabolife to
athletes, do you?
Mr. Schreck. No.
Ms. DeGette. Okay. How many doses of Metabolife do you sell
per year on an average?
Mr. Schreck. I think we have servings of, as we mentioned
earlier, over a 5 year period our servings are approximately 50
million bottles or 4.5 billion tablets. And if you would say
that there are 6 a day, you would probably be talking about--I
am rounding off in my head, something like 80 million servings.
Ms. DeGette. Okay. Over a 5 year period, right?
Mr. Schreck. Yes.
Ms. DeGette. Now, I assume that you showed us a poster of
the Metabolife bottle, you are familiar with the label on
Metabolife, is that right?
Mr. Schreck. Reasonably familiar.
Ms. DeGette. Okay. Because no the front, I was just looking
at it and there is a little seal here.
Mr. Schreck. Yes.
Ms. DeGette. Are you familiar with that seal, because it
looks like some seal of approval and it says ``Q.A.'' I am
wondering what that means.
Mr. Schreck. To tell you the truth, Congresswoman, I have
been with the company 2 months. I do not have an answer for
that.
Ms. DeGette. Mr. Hermann, do you know what Q.A. means? Do
you know what this seal means?
Mr. Hermann. Q.A. I believe you are referring to the Aceris
label that is on this----
Ms. DeGette. There is a little seal on--yes. A-C-E-R-I-S.
Mr. Hermann. Yes. Aceris is an independent company that
will come in and do a review of your GMPs and also review the
product that you are manufacturing. I believe we had that done
throughout----
Ms. DeGette. You had them come. Who are they? Do you hire
them to come in and look at your product?
Mr. Hermann. Yes. You do pay them for that. They come in
and do an independent analysis of your manufacturing
facilities.
Ms. DeGette. And based on what standards?
Mr. Hermann. They look at food GMPs primarily. They also
look at SOPs.
Ms. DeGette. I do not know what those acronyms mean, sir. I
am sorry.
Mr. Hermann. General manufacturing practices.
Ms. DeGette. Thank you.
Mr. Hermann. Or good manufacturing practices.
Ms. DeGette. Okay. So they are a trade organization?
Mr. Hermann. I am not sure.
Ms. DeGette. Okay. You do not know.
And it says here ``Quality ingredients, manufacturing,
labeling.'' Is that what they determined?
Mr. Hermann. That is on their seal, yes, ma'am.
Ms. DeGette. Okay. And it says Q.A., what does that mean?
Do you know?
Mr. Hermann. That is just part of their seal logo.
Ms. DeGette. Okay. Because it looks to me like this is like
a seal of approval. Is that why you put that on there?
Mr. Hermann. They have--they do come in and approve those
facilities. And with the manufacturing of 356 before we would
allow a third party manufacturer to manufacture our product, we
do have--we have had an independent review by Aceris to assure
that people are following their procedures.
Ms. DeGette. Okay.
Mr. Hermann. Largely that is what we are looking at.
Ms. DeGette. Okay. Thank you, sir.
And so you put this on the Metabolife bottle to tell the
consumer that someone has certified something here, right? I
mean, that is why you put it on the bottle, right?
Mr. Hermann. That product has been certified by Aceris,
yes, ma'am.
Ms. DeGette. Thank you. Okay.
Dr. Boozer, I want to ask you a few questions. There were 2
studies that were done and they included between the 2 of them
234 men and women who were overweight but otherwise healthy,
correct?
Ms. Boozer. That is right.
Ms. DeGette. And everybody agrees you did not put people in
this survey who had heart problems or other kind of problems
that would be counter-indicated by this drug, right?
Ms. Boozer. That is correct.
Ms. DeGette. Or this substance?
And so you do not really know what the effect of ephedra
would be on individuals who had heart problems or other kinds
of problems, right?
Ms. Boozer. No, we do not.
Ms. DeGette. And do you think that a study of--2 studies
with 234 people out of the admittedly millions of doses of this
that have been sold is sufficient to come up with a scientific
conclusion that this substance is safe and effective?
Ms. Boozer. I have never made that statement that it is
safe and effective.
Ms. DeGette. Okay. I know you never did. I wanted to ask
you if you thought it was.
Ms. Boozer. I think that the study had enough power or
there is a statistical method that one can use to determine
whether you have enough subjects included in the study to find
the end points that you are looking for.
Ms. DeGette. Right. And the end points you were looking for
among a small section of health, overweight adults if they lose
weight?
Ms. Boozer. That is right. That is right. So----
Ms. DeGette. Now there were also some people who withdrew
from the study because, and I am quoting from the conclusion of
your report, ``The tested product also produced several
untoward side effects leading some actively treated subjects to
withdraw from the study,'' right?
Ms. Boozer. That is the 8 week study, yes.
Ms. DeGette. Yes. So some people withdrew from it because
there were side effects?
Ms. Boozer. That is correct.
Ms. DeGette. Now, the problem we have here is this is not
an FDA approved drug so we cannot limit the distribution of
this substance to, say, people at health clubs, people who have
heart problems, children. And you did not take any of that into
effect? That was not the purpose of your study, was it?
Ms. Boozer. That is exactly right. That was not the purpose
of our study.
Ms. DeGette. And one last question, because I read over
your CV and your list of publications. You are really, and by
the way, a very highly qualified nutritional researcher,
correct?
Ms. Boozer. In the field of obesity, yes.
Ms. DeGette. In the field of obesity. You are not educated
or pretend to be a researcher in the effect of drugs on the
human body or that is not what this study was about, right?
Ms. Boozer. You are right in saying that I do not have
those qualifications. Some of the other co-authors on the
papers do have those qualifications.
Ms. DeGette. Thank you very much.
Mr. Chinery, I just have a couple of questions for you. You
were responsible for the original formulation of Xenadrine, is
that how you pronounce it? Xenadrine?
Mr. Chinery. Xenadrine.
Ms. DeGette. Xenadrine. Thank you.
We you not?
Mr. Chinery. I actually had worked with--in collaboration
with the people at our manufacturing laboratory and their
product development staff.
Ms. DeGette. What were the names of the people who helped
you develop Xenadrine?
Mr. Chinery. The primary person that I worked directly
with, his name is Mel Rich.
Ms. DeGette. And is Mel a pharmaceutical, does he have a
Ph.D? What is his educational and scientific background?
Mr. Chinery. I believe he's a registered pharmacist.
Ms. DeGette. Okay. And what was his role in developing
Xenadrine?
Mr. Chinery. He actually defined the specific formulation.
Ms. DeGette. Oh. So he developed the formula, not you?
Mr. Chinery. Well, he defined the precise formulation. I
had concepts that I presented to him and then he finalized that
formulation.
Ms. DeGette. Okay. Let me just ask one more question.
What is your academic background, sir?
Mr. Chinery. Actually, I started work on the dietary
supplement industry part time when I was in high school and I
graduated high school and worked for dietary supplement company
full time at that point.
Ms. DeGette. So your academic background is a high school
degree, correct?
Mr. Chinery. Correct.
Ms. DeGette. Thank you.
Thank you, Mr. Chairman.
Mr. Greenwood. The Chair thanks the gentlelady and
recognize the gentleman from Oregon for 10 minutes.
Mr. Walden. Thank you, Mr. Chairman.
Dr. Boozer, did the findings of your 6 month study show
that ephedra is safe?
Ms. Boozer. I have refrained from using the word safe in
defining the results of the study for this reason: I think that
it is a word that can be generalized. And I have said in the
papers that I do not think our results can be generalized
beyond the types of people we studied.
Mr. Walden. So nobody on this panel should ever use your
study to say their product is safe, is that accurate?
Ms. Boozer. I would not recommend that they do that.
Mr. Walden. Okay.
Ms. Boozer. I do not use that word.
Mr. Walden. Sometimes it is held up as the gold standard,
the best scientific research out there. And I read some of the
testimony saying we have got all these studies saying it is
safe. But yours would not be a study you would stand behind to
say that this drug is safe? Is that your testimony?
Ms. Boozer. I do not use the word safe, because as I said--
--
Mr. Walden. And you would not recommend anyone else to use
it?
Ms. Boozer. I am not saying that it is unsafe either. What
I am saying is that it is somewhat a philosophical issue. When
you say something safe, I think it is interpreted more broadly
than I believe the results of this study should be interpreted.
Mr. Walden. Thank you.
I guess there are a lot of advertisements out there that
might lead one to believe in the consumer market that some of
these products are safe, so it is good to hear that you say
your study says neither safe or unsafe. That is what you are
saying, correct?
Ms. Boozer. Well, I choose the words pretty carefully in
the study. And I said I believe that when used as directed by
the type of people that were included in this study for the
length of time and at the dosages that we used it----
Mr. Walden. Right.
Ms. Boozer [continuing]. There were no serious adverse
effects.
Mr. Walden. Okay. Thank you.
Mr. Chinery, I read with interest, obviously, your comments
quoting Dr. Baden--is it Badden or Baden?
Mr. Chinery. Baden.
Mr. Walden. Baden.
And you quote, and I think one of the other persons on the
panel used the same terminology about severe obesity when it
comes to Steve Bechler. It is in your testimony quoting Dr.
Baden.
Mr. Chinery. Yes.
Mr. Walden. And one of the other panel members used it to
describe to Mr. Bechler's condition. His family earlier today
testified he was 10 pounds overweight. Do you agree with that?
Mr. Chinery. The only information that I have had available
to me is the information that was provided by Dr. Perper's
office. And I believe the specific term ``morbid obesity'' came
from the information supplied by him.
Mr. Walden. Really? Did you or your attorneys have access
to all the public information available? Was there anything
that the autopsy investigation found that you did not have
access to that you are aware of?
Mr. Chinery. It is possible. I do know that the information
from Dr. Perper's office indicated a body weight of 320 pounds.
Mr. Walden. And was that--why was it 320 pounds?
Mr. Chinery. I am not sure why.
Mr. Walden. You do not know why, but you can use and others
can backup the fact that 320 made him morbidly obese, correct?
Mr. Chinery. Well, again----
Mr. Walden. It is what you said per Dr. Baden.
Mr. Chinery. It is based on a term used by Dr. Perper.
Mr. Walden. Okay. I appreciate knowing that. Because I have
before me, and I will ask to be entered in the record,
apparently it is already entered into the record, information
from Dr. Perper, dated July 23. He has now seen the information
that you present in your testimony. And it says, among other
things, he takes quite a number of exceptions.
It says Dr. Baden noted correctly the patient weight at the
time of the autopsy was 320 pounds and that he was 6'2'' in
height and therefore it concluded that he was morbidly obese.
However Dr. Baden admitted 2 important facts which were, and I
quote, ``The fact that Mr. Bechler's weight 3 days before his
demise was 250 pounds and no individual, no matter how much
would eat can gain 70 pounds of weight in 3 days.''
Furthermore, Mr. Bechler's gastrointestinal tract was
empty. He ate very little, if at all, during the 2 to 3 days
preceding his demise. At the time of the autopsy Mr. Bechler
was excessively bloated and deamatose. This bloating was a
result of both infusion of resuscitation fluids and his kidney
failure with lack of urination.
I think it is terribly misleading to use the terminology
that was used to say that part of his death was caused by
severe obesity. He was 10 pounds overweight 3 days before.
``Also, Mr. Baden claims that ephedra played no role in the
death of Mr. Bechler and that in general ephedra is not and
cannot be linked to the occurrence of heatstroke. In support of
that he advanced a number of statements and arguments refuted
by the following facts.''
Page 2 of this report, and again I am quoting from Dr.
Preper.
``Dr. Baden indicates that he had no access to ENT-Fire
Rescue records on February 16, the North Ridge Medical Center
Hospital records of February 16 and 17, past medical records,
the autopsy microscopic slides and photographs, and the
interviews of the witnesses to Mr. Bechler's collapse and
initial treatment.'' Okay. But then Dr. Preper goes on to say
``In the telephonic conversation with Dr. Baden I informed him
of the willingness of my office and of myself to fully disclose
and deliver all public records or materials. As a matter of
fact the attorneys for Cytodyne obtained all open records
requested.''
Mr. Chinery. My counsel is shaking his head no, which would
indicate to me that maybe there is an inconsistency with that.
Mr. Walden. We will find out.
Dr. Boozer, in the FDA's peer review of your study there
are several points that come out. And I would like to ask you
about those, because I think it is important to this whole
issue.
Ms. Boozer. Well, Congressman, I should point out that the
FDA has not provided me with a copy of that review.
Mr. Walden. Well, we will certainly make it available. It
is in the book, is it not? Do we have a tab number?
We will make it available to you.
Were you aware they were having outside people do peer
review?
Ms. Boozer. I was, and they promised that they would give
me a copy of the report before it went public.
Mr. Walden. Okay. We will get a tab number for you here.
And I believe that someone in the company had some--as part of
the deal to get information, the actual data, there was some
involvement with your company, correct?
Ms. Boozer. Columbia University?
Mr. Walden. No. To select the outside panel? The company,
was it Cytodyne had the opportunity to--Metabolife, I am sorry.
Had the opportunity to participate in the selection of the
scientists, correct?
Ms. Boozer. I do not think Metabolife had anything to do in
selection of the scientists on that panel. I think the----
Mr. Walden. Really?
Ms. Boozer. Mr. Wes Signer was counsel for the Ephedra
Education Council. I think he was the person who was
negotiating the arrangement of the panel.
Mr. Walden. Is not Metabolife a member of that council?
Ms. Boozer. They may be. I do not know.
Mr. Walden. Okay. If you would turn to Tab 113 in the book,
that may help. I assume----
Mr. Hermann. Congressman, I am sorry.
Mr. Walden. Yes.
Mr. Hermann. I do not mean to interrupt.
Mr. Walden. That is fine.
Mr. Hermann. But we are not a member of that council.
Mr. Walden. Were you ever a member of that council?
Mr. Hermann. Sir, I am not aware of that, but I know we are
not at this time.
Mr. Walden. Is Wes Signer of Patton Boggs ever represented
Metabolife?
Mr. Hermann. I am familiar with the name, but I am not
familiar with that kind of detail of whose represented us from
that standpoint, sir.
Mr. Walden. Okay. All right.
Well, I will give Dr. Boozer a moment here to look at the
reviews. Because, among other things, the main points that were
found, it was Dr. Atkinson, Esbalan and Hirsch and Kaplan, I
think, were the 4 reviewers. And the main points from 3 reviews
was that the formulation used in your study may not represent
what is being marketed. And that, I think, is a question that
is important. Was the product that was tested not actually out
on the market?
Ms. Boozer. Congressman, this was absolutely transparent in
our publications. We published entirely the information about
the product we were testing. There were 2 studies. In the one
study we were studying Metabolife 356 and in the other study we
made it absolutely clear that this was not a product that was
on the market and we listed the ingredients.
Mr. Walden. And the ingredients are?
Ms. Boozer. The ingredients are ephedra alkaloids and
herbal caffeine.
Mr. Walden. Is that the combination they used in Denmark?
Ms. Boozer. I believe they in Denmark, ephedrine, the
synthetic version is used as a prescription compound in
combination with caffeine.
Mr. Walden. Okay. And here?
Ms. Boozer. We were using the herbal equivalent.
Mr. Walden. Okay.
Ms. Boozer. We were using herbal ephedra and caffeine in
the amounts of 90 milligrams per day of ephedra alkaloids and
192 of caffeine.
Mr. Walden. Okay.
Ms. Boozer. That product--that combination, to my
knowledge, is not available on the market. That was not our
intention and we so clearly stated that in the publication.
Mr. Walden. All right.
Does that mean it does not demonstrate the efficacy of any
ephedra supplement that is on the market?
Ms. Boozer. As I say, to my knowledge there is no product
on the market that has exactly that formulation. It was not the
intent to study a specific product.
Mr. Walden. So the answer is it does not prove the efficacy
of those that are on the market, correct?
Ms. Boozer. I think it proves the efficacy of this
combination for weight loss.
Mr. Walden. Okay. But what about what is on the market,
because that is what consumers are really going into the stores
and buying?
Ms. Boozer. I think the Rand report summarized results from
52 clinical trials. And I think in their meta analysis they
accounted for the variability, not every one of those trials
had exactly the same formulation. But I would say judging from
the summation of the review of those trials, it is fair to say
that the combination of ephedra/caffeine is efficacious for
weight loss.
Mr. Walden. Okay. Yes. What happens when you mix it up with
these other ingredients? I mean, I have heard about an aspirin
related product, it performs like that. And, you know, I have
read ginseng and other things maybe mixed in. And I realize
that may not have been part of your study, but from your
experience and all can you speak to what effect that has, and
the interactions?
Ms. Boozer. Well, I think someone spoke this morning. We
really do not know. We do not know what all of those individual
ingredients or what they--we do not really know in total what
they contribute or how they interact.
Mr. Walden. Okay. Are you aware of any of the studies that
are out there on how ephedrine interacts or has been related to
the problems with heatstroke?
Ms. Boozer. No, I am not.
Mr. Walden. Okay. I would draw your attention to the last
tab in the book from June 2003 Military Medicine where this was
not an obese person, this was somebody who is very physically
fit, well trained case study where he was on a run and had
taken ephedra the night before and that day and suffered
heatstroke related issues. And, in fact, the final conclusion
here from the military is the risk of life threatening injury
may outweigh any real or perceived benefit of ephedra and
clinicians and commanders should strongly discourage its use in
active duty soldiers.
I also, when you get an opportunity to read the information
from the Broward County, Florida Medical Examiner and Trauma
Services Office, he also lays out, Mr. Preper lays out a number
of studies and literature publications relating heatstroke and
ephedra. So I would suggest for all the panel, since I have
heard from most of you that there are no literature cites out
there on that, that apparently there are. Obviously, I have not
had a chance to read them and I am not a physician. But I would
certainly draw your attention to them.
Mr. Chairman, I realize I have exhausted my time, and I
appreciate the indulgence of the committee.
Mr. Greenwood. The Chair thanks the gentleman.
The gentleman from Illinois is recognized for 10 minutes.
Mr. Rush. Thank you, Mr. Chairman.
Thanks to the witnesses for their patience.
Mr. Schreck, my first question is when were the words
``heart attack and stroke'' added to the label of your product
and why?
Mr. Schreck. I believe that was a legal--I think that
should be turned over to Mr. Hermann to answer, since he was
here when that occurred.
Mr. Rush. Mr. Hermann?
Mr. Hermann. Yes, Congressman. The language on our label
comes from a lot of different sources. Some of it from the
Dietary Supplement Act in terms of specific things and follow
up publications to that. But a lot of the warning language
comes from----
Mr. Rush. Let me be terribly specific here. I am referring
to 3 words, ``heart attack and stroke.''
Mr. Hermann. I do not know the date exactly, but those are
required in the States of Ohio and Texas, and our label
complies with that. Most recently California passed some
additional labeling requirements and we have subsequently
updated our label according to that.
As I recall, the Texas law and Ohio law were enacted since
I have joined the company, but I do not specific--I'm sorry,
Congressman. I will be more than happy to find out for you and
I will get back to you on the answer.
Mr. Rush. And my other question, which perhaps you will
need to answer by supplementing the record, was did your
company oppose those State legislatures that asked you to add
those words to your label and if so, why?
Mr. Hermann. I am sorry, Congressman, I do not know.
Mr. Rush. Okay.
Mr. Hermann. I will have to get back to you.
Mr. Rush. This is a question for Dr. Colker. I want to
refer you to Exhibit 31, and I am going to read a little
quickly given the time constraints here. This is what appears
to be an email from you to Bob Chinery, and the email, and I am
just going to go ahead and read it very quickly. It is
referring to 2 abstracts. And it says: ``While the weight loss
data are compelling, I would sense that with a full length
paper we would have a lot of explaining to do.'' And then I am
going to move the next line. ``My first impression is the
parameters are best enough left alone as they would have to be
divulged, explained in detail and scrutinized in a full length
paper. So on this particular case we will gain from a marketing
standpoint by relying on the abstract if it is accepted. On the
other hand, we risk much exposure in full length form, just ask
legal, on gaining nothing from a marketing standpoint.''
Now, have I accurately described a portion of this email?
Dr. Colker. Yes, Congressman.
Mr. Rush. Okay. Now this email was written in the context
of your responsibilities to conduct what was supposed to be an
independent scientific investigation, is that correct?
Dr. Colker. That is correct, sir.
Mr. Rush. Okay. I think you can understand why the email
appears to us to comprise both the independent and scientific
nature of your work, and I would like to give you the
opportunity to explain that.
Dr. Colker. Certainly. And I can understand how you come to
that conclusion.
I felt I was being prudent when Mr. Chinery asked me
whether this was a full length paper or whether a full length
paper should be published. I felt it was more appropriate to
give a snapshot of the primary endpoint, whether it was
statistical significant difference between groups for weight
loss and the other figures where--although there were absolute
number differences between groups, they were not statistically
significant and therefore, I would not want them to rely in
their advertising on inclusive data.
Mr. Rush. So what did you mean in the email when you said
that ``we will gain from a marketing standpoint by relying on
the abstract if it is accepted and we risk much exposure if we
use the full length form?''
Dr. Colker. I felt from a marketing standpoint I was simply
looking at it as looking out for Cytodyne in terms of feeling
that was marketable information that was achieved from the
study, while at the same time I felt that if there were any
questions given the climate at the time, I referred him to
legal.
Mr. Rush. So it was your job to provide the independent
scientific study or to provide advice and strategy on
marketing?
Dr. Colker. This particular study was an open label study.
I felt it was certainly unbiased, but I can understand how one
would read bias----
Mr. Rush. So you were fulfilling both tasks? You were
focusing on an independent scientific study and you were also
providing advice on marketing?
Dr. Colker. In this case, yes.
Mr. Rush. And you do not find those to be inconsistent
responsibilities?
Dr. Colker. They were not for me, but I can understand how
they might be viewed as such.
Mr. Rush. Okay. Back to Mr. Schreck.
In 1998 Michael Ellis wrote a letter describing how the
company handled consumer complaints, and I am going to
paraphrase. He says Metabolife has a comprehensive safety
monitoring procedures in place. We take the health of our
potential and actual customers very seriously.
Our staff has reviewed your records and find them to be
lacking in many respects, many were handwritten or illegible.
The GAO has conducted a similar analysis and said the
information in your call records was limited, sometimes
difficult to understand and interpret. In some cases the
evidence for report of an adverse event was limited to a single
word on a call record.
I want to specifically refer to Exhibit 91 in the book in
front of you. This is a notation on a day pad, dated September
21, 1998. It has the word ``heart attack'' written on it. And
that's about all.
I want to ask you to comment on the quality of this record
keeping in hindsight, and it is also a question directed to Mr.
Hermann.
Mr. Schreck. I am sorry.
Mr. Rush. I would like to ask you to comment on the quality
of this record keeping with the benefit of hindsight and in
view of the statement I read, assuming you don't object to my
characterization of the statement from the Michael Ellis letter
in 1998?
Mr. Hermann. Congressman, if I could address that, I would
be happy to answer your question.
Mr. Rush. Please.
Mr. Hermann. Our health information system was set up as a
call center. As I said earlier, to help customers with
questions that they had about how to use our product more
effectively and questions about weight loss in general. It
wasn't designed to capture adverse events. It was not
formalized in terms of obtaining any information concerning any
conditions or any reports. It was strictly used as a mechanism
to do that.
As a dietary supplement company, as you know, we are not
required to have a system in place for that. We do support the
FDA in a proposal to implement that kind of system, and we are
willing to work with the FDA to come up with a method and to
identify what categories we should identify.
Mr. Rush. Right.
Mr. Hermann. I can only apologize for this particular
record----
Mr. Rush. You do not need to apologize to me. It is other
people to apologize to, but go ahead.
Mr. Hermann. Well, I am sorry, sir. I have lost the rest of
your question.
Mr. Rush. So it was not the intention of your record
keeping process to record any adverse health events?
Mr. Hermann. That is correct. The health information line
was not set up to record adverse health events and we were not
required to do that.
Mr. Rush. Okay. I believe Mr. Chinery testified earlier
that the policy of his company was to tell customers to take
taking the product if they were experiencing adverse health
effects. Was that the policy of your company?
Mr. Hermann. Sir, I am not familiar with exactly what
happened in any of these particular incidences. I do not----
Mr. Rush. No, but I am not talking about a specific
instance. You are the vice president of your company, right? I
am asking you what the company policy was.
Mr. Hermann. Congressman, the health information area does
not report to me and it has never reported to me. I know that
based on what I have seen is our policy, that if a customer
does call in, we ask them if they have talked to their personal
physician----
Mr. Rush. You were prepared for this testimony today,
ostensively by your lawyers, I'm sure. And you knew we were
going to be asking about these questions, questions of this
nature, and you cannot say as the vice president today or
neither can Mr. Schreck as a representative what your company
policy was on this particular point?
Mr. Hermann. Congressman, I--you know, I can only tell you
what I know. And I do not know the procedures or the policies
at that time. And I am sorry. I just----
Mr. Rush. Okay. Well, I would just like to ask you if you
would supplement the record with that information.
Mr. Hermann. Certainly, Congressman. Be more than happy to
do that.
Mr. Rush. In 1999 Allen Binky, or however you pronounce his
last name, the counsel for Metabolife wrote to the FDA that
your company has never been aware of any adverse health events
by consumers of its product. Is that a correct statement, as
you understand the record here? You have no reason to question
that?
Mr. Hermann. I haven't specifically seen----
Mr. Rush. Well, let us assume I have stated correctly.
Based on your testimony I am assuming the reason your
company was never aware of any adverse health events by
consumers is you were not interested in collecting that
information if any consumer called and tried to give it to you,
is that correct?
Mr. Hermann. Congressman, I am sorry, but I had nothing to
do with that letter, with that phrase. I do not what the intent
of those comments are. And I feel very uncomfortable
speculating before this subcommittee on what it might have
intended.
I can tell you this, in the 3\1/2\ years that I have been
at Metabolife I have seen nothing but upstanding, honorable
integrity. And I cannot believe that anybody would
intentionally mislead the FDA or anybody else concerning our
products.
Mr. Rush. Well, understand. I am not suggesting anybody's
intention or misleading. I am just asking what you thought was
an appropriate policy or standard of care to adopt as a company
in terms of collecting information from people that were
calling you to report adverse health effects they were having
that they were associating with the use of your product.
Mr. Hermann. Yes, Congressman. I understand that. And I
promise to get back to you with that information.
Mr. Schreck. Congressman, may I add?
Mr. Rush. Yes, sir.
Mr. Schreck. Our company is being very proactive to improve
our call system. We have hired Life Science Research Office to
do an analysis so that we can assess our call centers and to
take any recommendations that they will give us. This report
will be completed early in the fall and I would forward it to
you, if you would like.
And also I would like to state that we gave them no
conditions and we put no conditions on the report. We asked
them to do it of their own volition and they will--they are in
the process of this study at this point. And, as I said, we
will have a report completed this fall.
Mr. Rush. So when you printed on this label or your company
for health questions and then a phone number, what were you
intending to communicate to the consumers of your product as
far as questions they could expect you to answer about health?
Mr. Hermann. That particular phone number is the MedWatch
number, I believe you are referring to. And that was required
by Texas law, and that is when we implemented that on our
label.
Mr. Rush. I understand that is what the law required. But
what did--okay.
Mr. Hermann. I am sorry, Congressman. Were you referring to
a different number?
Mr. Rush. No, sir.
I have a document suggesting that your company has stated
in the past that adverse event reports are only those reports
which have proven to be casually connected to the product. Has
that been the position of your company? Is that a fair
statement?
Mr. Hermann. I am sorry, sir. I don't--I am not familiar
with that statement.
Mr. Rush. Mr. Schreck?
Mr. Schreck. I am not either. I have never heard that
before.
Mr. Rush. How have the sales of your product fared since
the negative publicity has arisen about their use? I will
direct this to all three of you.
Mr. Schreck. The sales of our product have fallen.
Mr. Greenwood. Time of the gentleman has expired.
Mr. Rush. Okay. Thank you, Mr. Chairman.
Mr. Greenwood. The Chair thanks the gentleman.
The Chair at this point would like to call Ms. Culmo back
to the witness table. Cynthia Culmo, if you would please come
to the witness table and we will have a chair set for you. I
wanted to--and I thank you for staying so long so that we could
ask a few questions.
If you can use Mr. Schreck's microphone and, of course, you
are still under oath.
Ms. Culmo, when you were at the Texas Department of Health
did NVE, the company NVE ever come to your attention?
Ms. Culmo. Yes, they did.
Mr. Greenwood. And in what way and what actions were you
involved with with regard to this company?
Ms. Culmo. To the best of my recollection their products
became noticeable or to our attention in 1999. They were first
reported on a poison control center report.
Mr. Greenwood. And were those adverse effects that were
reported in the poison control report?
Ms. Culmo. That is correct.
Mr. Greenwood. Okay. And do you recall what kind of adverse
effects you were seeing?
Ms. Culmo. Not off the top of my head, I do not.
Mr. Greenwood. Okay. And then did the department make
contact with the company and make requests of the company or
demands of the company?
Ms. Culmo. Yes, we did. We contacted the company to inform
them that the name of their products were recognized street
alternative drug names and that they would have to discontinue
that name and also address other issues with the product.
Mr. Greenwood. And how did they respond to that?
Ms. Culmo. There are several records of correspondence.
They, obviously, objected to that position.
Mr. Greenwood. Okay. Did they ultimately--was it a direct
result of your demands that they change the name, that in fact
they did?
Ms. Culmo. No. Actually what happened is our Attorney
General's office was involved. And to the best of my
recollection they agreed to no longer sell those products in
the State of Texas under those names.
Mr. Greenwood. And so in a court supervised settlement?
Ms. Culmo. That is correct.
Mr. Greenwood. Okay. Thank you very much.
Ms. Culmo. I am sorry. I misunderstood that. There was an
agreed order.
Mr. Greenwood. An agreed order?
Ms. Culmo. Yes.
Mr. Greenwood. An agreed order? Very well.
Mr. Occhifinto, do you agree Ms. Culmo's testimony? Use
your microphone again, please, sir.
Mr. Occhifinto. I do not remember any of the circumstances,
all the circumstances. But I know that we came to an agreement
with the State of Texas.
Mr. Greenwood. Okay. When you testified earlier in response
to some questions that I asked and Ms. DeGette asked about what
caused you to change the name of your products from Black
Beauty and Yellow Jacket, you said that--I think you said that
you had heard somewhere that over in Amsterdam products--repeat
your testimony, if you will, as to what inspired you to change
the name of the product.
Mr. Occhifinto. We became aware of the product being used
improperly on the Internet from a company in the Netherlands.
Mr. Greenwood. And when was that?
Mr. Occhifinto. Within the last year, I believe.
Mr. Greenwood. Okay.
Mr. Occhifinto. Within 6 months, maybe.
Mr. Greenwood. When did you agree pursuant to a court
procedure to change the name of your product?
Mr. Occhifinto. Chairman, I do not remember that as far--
that was only for the State of Texas.
Mr. Greenwood. Right.
Mr. Occhifinto. When we spoke before, I thought you meant
in relevance to what was going on now.
Mr. Greenwood. So what you are saying is initially in 1999
the Texas Department of Health notified you that Black Beauty
and Yellow Jacket were names for street illegal drugs and
subsequent to that and a result of that you changed your
marketing nomenclature in Texas?
Mr. Occhifinto. Chairman, also on that list in Texas, they
call those 2 names slang terms. They also use slang terms for
drugs in their State are Candy, Cakes, Cookies, Eggs,
Squirrels, Biscuits, Beans, Truck Driver, Black Cadillacs.
Mr. Greenwood. Did you have any products with any of those
names?
Mr. Occhifinto. No, I did not.
Mr. Greenwood. Okay. So let us focus on the products you
were marketing.
The Texas Department of Health informed you that your
products Black Beauty and Yellow Jacket were street drug names?
Mr. Occhifinto. Yes, sir.
Mr. Greenwood. Correct. Okay. And was that the first you
learned of that or did you know that when you named them?
Mr. Occhifinto. No, I did not.
Mr. Greenwood. You did not know that when you named them?
Mr. Occhifinto. No.
Mr. Greenwood. Pure accident, coincidence?
Mr. Occhifinto. No.
Mr. Greenwood. Okay.
Mr. Occhifinto. I also tried to work things out with the
Texas Department of Health and they were not cooperative. And
then the Attorney General got involved in it and we came to an
agreement and settled with them.
Mr. Greenwood. And what did you rename your products?
Mr. Occhifinto. I renamed them for the State of Texas.
Actually, I do not sell the products in any form in the State
of Texas.
Mr. Greenwood. Okay. So when you changed--then you changed
your nationwide marketing, you no longer call them nationwide,
no longer call them, the product for instance Black Beauty?
Mr. Occhifinto. No, I did not say that, Chairman. I said we
no longer marketed those products in the State of Texas.
Mr. Greenwood. Okay. But eventually you stopped marketing
Black Beauty entirely, correct?
Mr. Occhifinto. Yes, we did.
Mr. Greenwood. Okay. And why did you do that? Why did you
change its name?
Mr. Occhifinto. Because we found that internationally
people were selling our products as an illicit drug and we did
not want to be involved in that. And we got out of the business
and we changed the name.
Mr. Greenwood. So you wanted to have an entirely different
kind of name for your product?
Mr. Occhifinto. Yes.
Mr. Greenwood. So you changed Black Beauty to?
Mr. Occhifinto. Midnight Stallion.
Mr. Greenwood. And that was to completely disassociate your
product from Black Beauty?
Mr. Occhifinto. Well, we were brought to the attention that
Black Beauty was a name that people weren't comfortable with,
so we stopped using that name.
Mr. Greenwood. Okay. Thank you.
Mr. Boozer, may I address some questions to you, please?
You do have a very impressive resume. And let me ask you a
question. What caused you to go into the field of obesity work?
Why do you do what you do?
Ms. Boozer. I think it was because of the opportunity to
work with a very famous and excellent scientist named Dr. Joel
Mayer, whom you may know. He had an outstanding reputation as
an international nutritionist and obesity expert. And I had the
opportunity to work with him at Harvard. And so, he was--
because of his expertise in obesity, I got interested in
working in that area.
Mr. Greenwood. Are you motivated, in part, by a desire to
help people who are obese to not suffer the physical and
emotion strains of their obesity?
Ms. Boozer. That is right.
Mr. Greenwood. Okay. Do people sometimes individually ask
you for advice as to how to deal with that very painful
problem?
Ms. Boozer. They do.
Mr. Greenwood. Okay. And what is your general
recommendation if someone comes to you and says I am a 120
pounds overweight and I am miserable and I do not feel like I
am healthy? What should I do, Dr. Boozer, to try to lose some
weight and maintain that weight loss?
Ms. Boozer. Well, as you know, I am not a physician so I
don't give medical advice. But, in general, I think I would not
hesitate to encourage everyone to eat a healthy diet which I
consider to be a low fat diet.
Mr. Greenwood. Right.
Ms. Boozer. And to increase exercise in their lives.
Mr. Greenwood. Right. And probably did not need to go to
Harvard to learn that, did you?
Ms. Boozer. No.
Mr. Greenwood. Okay. Because in fact, every doctor that I
have ever heard of, and just about every expert, every trainer,
they all basically say it comes down to limit your caloric
intake, increase our exercise, advice like that. Okay.
So if someone came to you and you just told them you just
testified that that's the kind of advice that you would give
them, very sound advice, very mainstream advice. Would you say
to them and take some ephedra or Xenadrine? Would you say this
is another thing you ought to do?
Ms. Boozer. No.
Mr. Greenwood. Okay. Why not?
Ms. Boozer. Well, as I said, I have worked in a medical
setting for many years as a nonphysician, and I am very
conscious of the difference between my ability to give medical
advice and that of the physician. So I would refer someone, and
I have.
Mr. Greenwood. Well, you do not need a physician. I mean,
the whole point of this hearing is that you do not need a
physician to tell you to do this.
Ms. Boozer. No, but----
Mr. Greenwood. You're qualified to suggest this. I am
qualified to suggest this. The guy in the gym is qualified to
suggest this. The guy at the minimart is qualified to suggest
this, right?
Ms. Boozer. Maybe so, but----
Mr. Greenwood. Well, you could walk into a gas station and
say ``fill her up with regular and, by the way, do you have any
ideas of what I should do to lose this unsightly 50 pounds?''
And the guy should say, sure, I got the product right here,
right?
Ms. Boozer. Right.
Mr. Greenwood. Okay. But you are an expert. But you would
not recommend this product, would you?
Ms. Boozer. As I say, I limit my advice to diet and
exercise.
Mr. Greenwood. Right. But I am asking you a very serious
question. This is a very important policy issue. Is the reason
that you would not recommend this because you're just not
qualified and perhaps if you had a medical degree you would
know when to recommend, or is the reason you do not recommend
it is because you think it's not a good idea for people to use
this to solve their weight problems?
Ms. Boozer. I have some of the same concerns that have been
expressed earlier about the widespread use of these compounds.
And while I feel that within the constraints of our study that
people were not at risk, I still would have hesitation in
advising people who are outside the constraints--such
constraints to use this because it has not been widely studied.
Mr. Greenwood. Okay. So it has not been widely studied----
Ms. Boozer. Under those conditions.
Mr. Greenwood. Right. Right. And you would not recommend it
to anyone?
Ms. Boozer. I would not recommend it, but----
Mr. Greenwood. Okay. And you, of all the people who have
testified today in this long day of hearings, you are the
obesity expert. You are the person who knows more about the
problem that this product is designed to solve than anyone who
has testified before this committee today. And your testimony
under oath is that you would not recommend this product to
anybody, is that correct?
Ms. Boozer. Well, but as I said, I do not recommend
products of any kind. My--I limit myself to diet and exercise.
Mr. Greenwood. But I thought we just went through this
exercise where you said--I am not asking you if the reason you
would not recommend this is because you do not have an MD after
your name. I am asking you if the reason that you would not
recommend this is because you do not see a good reason to
recommend it because you think nutritional guidance, reduced
caloric intake, more exercise is the better recommendation. And
this has not been studied enough to know for you to feel
confident about its efficacy and its safety.
Ms. Boozer. Well, I mean I would not recommend it to
someone without whom I had a lot of medical knowledge. For
example, what their blood pressure was and what, you know----
Mr. Greenwood. And if you had all of that, you might
recommend it, is that right?
Ms. Boozer. It is possible. If I had someone that I was
convinced met the same kind of conditions as the people who
were in our study, then I might say to them, ``Look, people
like you who took this in our study did lose weight, did have
improved blood lipids and without significant adverse event.''
Mr. Greenwood. Well, but that is----
Ms. Boozer. But without----
Mr. Greenwood. It is one thing to say this had some impact
for some people.
Ms. Boozer. That is right.
Mr. Greenwood. It is another thing entirely to say this is
what I would recommend. For instance, you could say some people
lost weight eating pizza. Some people lost weight eating high
fat foods. But I am asking you if you would recommend it.
Ms. Boozer. Well, I personally would not, but that--I
mean----
Mr. Greenwood. That is all I am asking you is you
personally. That is all I am asking. I am not asking you on
behalf of anyone else. You personally would not recommend the
product.
Thank you. My time has expired.
Ms. DeGette. Dr. Boozer, in general there is concern among
the research community about not just losing weight for obese
individuals, but keeping that weight off over time, correct?
Ms. Boozer. Very much so.
Ms. DeGette. And really the scientific evidence shows that
nutrition and exercise are the two best ways to keep off weight
long term, correct?
Ms. Boozer. Well, having said that we know that that is
extremely difficult.
Ms. DeGette. That is right.
Ms. Boozer. Our success rate with obese population is on
the order of 5 percent.
Ms. DeGette. Right. And fad diets, when people go on fad
diets, for example, they help people lose weight in the short
run but the studies show over the long run that among obese
people that lose a substantial amount of weight on fad diets,
do not keep it off, correct?
Ms. Boozer. That is exactly right. That is right.
Ms. DeGette. Now, there were 2 studies done on ephedra. One
by you, one was 8 weeks and one was 6 months, correct?
Ms. Boozer. Right.
Ms. DeGette. So I think it would be safe to say that no
study has been done to show the long term effect of weigh loss
in the population that you studied, which was admittedly a much
smaller population than is taking this supplement. There is no
evidence to show what the long term weight loss results are for
those people, correct?
Ms. Boozer. That is correct.
Ms. DeGette. Okay. I wanted to ask Dr. Colker, you said you
were a physician and a sports trainer. Do you recommend that
your patients take Xenadrine, your patients who athletes take
Xenadrine?
Dr. Colker. For some, Congresswoman, yes.
Ms. DeGette. Which ones?
Dr. Colker. The ones that are--that have some weight to
lose that I think that the benefits outweigh the risks.
Ms. DeGette. So you do not see any problem with athletes
taking ephedra, correct?
Dr. Colker. I think that I see no problem with athletes
taking ephedra products, but I will say that my issues with
athletes have more to do with the abuse potential in general. I
am not saying every athlete will abuse ephedra.
Ms. DeGette. Now, Mr. Chinery, I guess I would ask you,
what is your company's policy toward marketing ephedra to
athletes? Because on your bottle, which is right here, you say
in a little box--I assume this is something else that was
required by some State law, because it also has the same
disclaimer on Metabolife. It says: ``Keep out of the reach of
children. Not for use or sale to individuals under 18.'' Right?
Mr. Chinery. Yes.
Ms. DeGette. Now so you do not recommend it being sold to
people under the age of 18, right?
Mr. Chinery. That is correct.
Ms. DeGette. Do you have any way of stopping it from being
sold to individuals under the age of 18?
Mr. Chinery. Well, actually, I guess I should point out
that we are not actually--we're not selling it anymore. But
when we were----
Ms. DeGette. Oh, when you were. Thank you.
Mr. Chinery. When we were selling it, a number of the major
retailers such as WalMart and Target have a policy where they
require identification for somebody to purchase it.
Ms. DeGette. What about for Xenadrine?
Mr. Chinery. Yes.
Ms. DeGette. They required identification for that?
Mr. Chinery. Yes.
Ms. DeGette. Did you have any written policies on that that
you gave to your sales force?
Mr. Chinery. I do not know that we had any written policy,
no.
Ms. DeGette. Okay. So what was your policy regarding sales
of this food supplement to athletes?
Mr. Chinery. We did not have really a specific policy, but
you know, there has been a number of clinical tests done on it
and a majority of those did test it in conjunction with
exercise. So--and I know that a number of other studies----
Ms. DeGette. So you think it is okay to sell it for
athletes to use it?
Mr. Chinery. As long as it is used properly by healthy
individuals.
Ms. DeGette. Okay. Mr. Hermann, I think you said when I was
questioning you it is your company's policy not to sell
Metabolife to children or athletes, correct?
Mr. Hermann. That is correct. We do not market it to
children.
Ms. DeGette. You need to turn on your microphone. Thanks.
Mr. Hermann. I am sorry, Congresswoman.
Ms. DeGette. That is okay.
After you said that, I was thinking about what Ms. Bechler
said in the first panel and also Mr. Riggins about how they and
their families know that Metabolife is sold at health clubs. So
I was a little confused, because if it is your company's policy
not to sell Metabolife to athletes, and you tell your sales
force that, how is it being marketed then at health clubs?
Mr. Hermann. Congresswoman, health clubs are not one of our
retail outlets----
Mr. Greenwood. Your microphone still is not working.
Ms. DeGette. There. It is just not close enough.
Mr. Hermann. Health clubs are not one of the retail outlets
that we sell Metabolife to.
Ms. DeGette. Okay. So as far as you know, this is not being
distributed from health clubs?
Mr. Hermann. Not directly from us it is not, ma'am.
Ms. DeGette. Okay. Do you have any idea, Mr. Chinery,
before you withdrew your product from the market, was it being
marketed in health clubs?
Mr. Chinery. I believe some, yes.
Ms. DeGette. Okay. And Mr. Occhifinto, is your product
being marketed in health clubs?
Mr. Occhifinto. We market for weight loss.
Mr. Greenwood. Please use the microphone, sir.
Mr. Occhifinto. We market for weight loss products, and we
market toward athletes.
Ms. DeGette. Okay. Do you think it is appropriate to use
this supplement, your supplements for athletes?
Mr. Occhifinto. I never explored that.
Ms. DeGette. So you have no opinion one way or the other?
Mr. Occhifinto. No, I do not.
Ms. DeGette. Okay. I guess, one last thing, almost
everybody here talked about the Rand study. And I was confused,
because everybody here was saying that the Rand study supported
their position, but I have a quote from the Rand study, and
here is what it said. Please bear with me, but I think it is
worth reading the whole quote.
``Overall, people who received ephedra or ephedrine had
between 2.2 and 3.6 times higher odds of suffering harmful side
effects, including psychiatric symptoms, jitterness,
palpitations, nausea and vomiting than did people taking a
placebo. From the 284 reports of serious adverse events we
identified 2 deaths, 3 heart attacks, 9 strokes, 3 seizures and
5 psychiatric cases as sentinel events with prior ephedra
consumption. We identified 3 deaths, 2 heart attacks, 2
strokes, 1 seizure and 3 psychiatric cases as sentinel events
with prior ephedra consumption. In aggregate, the case report
suggests a link between products containing either ephedra and
ephedrine and catastrophic events such as sudden death, heart
attack, stroke, seizure and serous psychiatric symptoms.
Regarding safety we conclude from the clinical trials that
ephedrine and ephedra are associated with 2 or 3 times the odds
of experiencing psychiatric symptoms, autonomic symptoms, upper
gastrointestinal symptoms and palpitations.''
Do you agree with the Rand report findings? I will start,
Ms. Culmo, I do not want to leave you out. Do you agree with
those findings? We will just work our way down.
Ms. Culmo. Yes, that they are significant.
Ms. DeGette. Mr. Schreck?
Mr. Schreck. I do not agree with those. I think the Rand
study also states that there were no serious adverse effects
reports in the 52 clinical studies.
Ms. DeGette. Mr. Hermann?
Mr. Hermann. I would support what Mr. Schreck said.
Ms. DeGette. Dr. Boozer?
Ms. Boozer. Well, you know what I think the problem is, is
there is sort--I think the report actually is quite good and I
think they very carefully explain what they did, and it seemed
consistent. But I think it is a little difficult when you read
it like this to understand the difference between the control
studies and the case report study.
In the control studies they looked at over 1700 individuals
who had been studied and found no serious adverse event. And
they conclude that those studies had an 80 percent power of
detecting events at less than 1 in a 1,000.
So, in other words, they're saying that according to the
clinical trials there is no serious adverse event unless this
occurs at a rate of less than 1 per 1,0000 people. And the
clinical cause cannot show that. So then they went to the case
reports and they said now in the adverse event reports, and you
read that. But they also go on to say however those do not show
cause and effect.
Ms. DeGette. But the problem is that in the control study
they did not look at the people who were high risk because
those were not included in the studies of others.
Ms. Boozer. That is exactly right.
Ms. DeGette. And what we are saying is the people who these
terrible side effects happened to are the people who are taking
this food supplement----
Ms. Boozer. Absolutely.
Ms. DeGette [continuing]. Who are not in the control
studies, right?
Ms. Boozer. Absolutely. That is correct.
Ms. DeGette. Thank you.
I am out of time, Mr. Chairman, otherwise I would go down
the rest of the panel.
Mr. Greenwood. The Chair thanks the gentlelady and at this
moment would ask that without objection the document binders be
introduced into the record. Without objection, so will be the
case.
And the gentleman from Oregon is recognized for 10 minutes.
Mr. Walden. Thank you, Mr. Chairman. I am sorry I had to
step out for a moment.
Mr. Conklin, could you go to Tab 38 in the giant book here
of documents? Is it true that you and Mr. Chinery were not
pleased with the results that Dr. Armstrong reported for the
RFA-1 study he performed?
Mr. Chinery. I believe we not pleased the way he presented
the results of the study in the abstract.
Mr. Walden. Okay. Is your email address or was it on 10
October 2000 kpconklin@aol.com?
Mr. Chinery. Yes, sir.
Mr. Walden. Let me read an email of that date, 9:44:17 edt
to tzphd@hotmail.com. Who is that?
Mr. Chinery. That would be Dr. Tim Zigginfuss.
Mr. Walden. Got it. In part, and there are several things
here but I will just cut to the part about Armstrong. It says
``Armstrong study. I know you received the information from him
and that you need it. Can you please wipe the quote/unquote
shit off it and come up with something we can get published
that will have impact. We need this done asap. Let me know on
this one.'' What was that? What did you mean by all that?
Mr. Chinery. Well, in hindsight, sir, I guess I could have
used more appropriate wording to convey my thoughts to
Armstrong to Dr. Zigginfuss. But what I had requested was that
there was a lot of information that resulted from the study
that was not included in the abstract that Dr. Armstrong first
presented. So what we had liked to see was an abstract that
included more information from the result of the study.
Mr. Walden. Okay. And would that explain the Wednesday,
September 27, 2000 email Tab 36 from you to tzxphd@hotmail.com
and you respond: ``Okay. I sent you the study results from
Astrong'' you say. ``Could you please try to find something
positive from this, something we can salvage. Could this
possibly be a safety study. Let me know, please. This is
screwed. K'' What was that about?
Mr. Chinery. What had happened was Dr. Armstrong completed,
we will say part of the study. He did not stick to protocol
that we agreed on prior to the study commencing. And the
results, we will say it was partial results of the study. I am
not a research doctor or scientist, so I really could not
interpret the data. And what I had asked Dr. Zigginfuss to do
was to look at that and interpret it for us and he had come
back with positive results from the study at that point.
Mr. Walden. Is Tim Zigginfuss a paid consultant by
Cytodyne?
Mr. Chinery. He was, yes.
Mr. Walden. Was he during this period in 2000?
Mr. Chinery. I cannot be sure, sir.
Mr. Walden. Mr. Chinery, you are president of the company?
Mr. Chinery. I believe he was a consultant. And, actually,
he was hired to consult on having research projects
commissioned for Cytodyne products. So I believe he was at that
point.
Mr. Walden. Okay. If we could go to Tab 38. Mr. Zigginfuss.
Yes, this is from Mr. Zigginfuss. Am I saying that right,
Zigginfuss?
Mr. Chinery. Yes.
Mr. Walden. Okay. Thursday, November 9, 2000, 2:32 p.m. to
Bob C. at prosourceonline.com and cc to Mr. Conklin, subject
EMUXN study. He writes: ``Hello, guys. Just thought you might
want to hear my interpretation'' in all caps, ``of the EMU
study. Dr. Armstrong sent me the entire report with all the
numbers and it looks much better than any of us expected and
particularly what he originally communicated to Kelly. For
instance, I know using percentages can be misleading
(especially when the absolute changes are small) but check this
out.'' And then he says body weight change and goes through
that, and the placebo and fat mass change and placebo.
And then, quoting again, ``And these effects occurred
despite no statistically quote/unquote significant changes in
either groups dietary intake. However, if you look at actual
numbers as the placebo group actually reduced their total
calorie intake by 200''--it is hard to read this--``per day and
their fat intake by''--I think it is 30 but it is hard to read
this printed copy--``grams per day from pre to post testing.
Had not this happened the above changes would have been even
more dramatic. Damn I am good.''
The body change weight was small, correct? The actual loss
of weigh?
Mr. Chinery. I guess that would be subject to individual
interpretation.
Mr. Walden. Is 3.19 pounds body weight change small for the
placebo?
Mr. Chinery. Well, I think if you look at it in the full
context these people did not reduce their diets and they lost
weigh, a significant f weight, it was deemed to be
statistically significant. So therefore, I do not know that I
would agree that it is small.
Mr. Walden. Okay. But in the email he uses the percentage,
and I did not read this earlier, that 759 percent more weight
loss than in the Xene group. 3.9 pounds versus 759 percent. And
then under the fat mass change placebo versus Xene, that is 524
percent more fat loss in the Xene group. And you are talking
5.7 pounds.
Why were those percentages important to your company, and
did you use them in any of your marketing?
Mr. Chinery. I am not positive whether they were used in
marketing or not, but typically in this industry the products
that are advertised to a certain segment of the market, which
is the fitness market, that that is the say those types of
results are typically expressed.
Mr. Walden. You said you did not know whether these numbers
were used in your marketing, correct?
Mr. Chinery. I cannot be positive.
Mr. Walden. Well, did not the judge in the Park case find
that these percentage changes were misleading? Are you familiar
with the Park case?
Mr. Chinery. Yes, I am. Specific to both of these
percentages claims, I am not sure. I know that----
Mr. Walden. What about other percentages claims, were they
similar to these in terms of percentage versus the numbers?
Mr. Chinery. I think there was a lot of variability with
regard to the actual changes that took place between the 2
groups.
Mr. Walden. What does that mean?
Mr. Chinery. Well, there was other percentage claims used
in other advertising. And----
Mr. Walden. But were you not really talking about a couple
of pounds? I will give you 3 to 8 pounds, but then claimed that
the difference was hundreds of percent? Did you ever use any of
that in your advertising, 100 percent claims or more?
Mr. Chinery. Percentage claims, yes.
Mr. Walden. Was 1700 percent difference a claim used?
Mr. Chinery. Yes, it was.
Mr. Walden. And how much weight difference was that?
Mr. Chinery. I believe that claim was specific not to body
weight, but body fat.
Mr. Walden. Okay. Give me the number.
Mr. Chinery. I do not have that number off the top of my
head, but I know it was a very high----
Mr. Walden. Does counsel have that number? Did they defend
you in that case?
Mr. Chinery. That was different counsel.
Mr. Walden. Was 3860 percent used by your company?
Mr. Chinery. Yes, it was.
Mr. Walden. Was that found to be misleading in the Park
case?
Mr. Chinery. In that case it was, and in another case in
Federal court in Utah it was found to be supported by the study
and appropriate.
Mr. Walden. Okay. In either case how much--was this body
weight or fat, or what was it?
Mr. Chinery. Again, that was actually body fat.
Mr. Walden. And what was the actual number?
Mr. Chinery. I do not have the specific number, but again
the difference between the 2 groups was a very high statistical
significance in that study.
Mr. Walden. Do you think the difference of a couple of
pounds here is very high statistical significance?
Mr. Chinery. Well, it is considered a powerful number by
the people that review the study and the people that do the
statistics.
Mr. Walden. Who paid for this study?
Mr. Chinery. The study that we are looking at here, this
Eastern Michigan study?
Mr. Walden. The Armstrong?
Mr. Chinery. Yes, that was actually paid, Cytodyne provided
a grant to Phoenix Laboratories which then provided that to the
university.
Mr. Walden. Yes. Okay. Dr. Zigginfuss says ``and these
effects occurred despite no statistically significant changes
in either groups dietary intake.'' So neither group changed
their dietary intake at all?
Mr. Chinery. I believe the protocol of that study called
for no changes to dietary habits.
Mr. Walden. Yes. How long was that study?
Mr. Chinery. I believe that was a 6 week study.
Mr. Walden. Six weeks?
Mr. Chinery. Yes.
Mr. Walden. Okay. So in 6 weeks the difference between the
2, if I am reading this correctly, is about a little less than
2 pounds--a little over 2 pounds, 2\1/2\ pound difference
between the placebo group. Is that right? Am I reading this
right?
Mr. Chinery. With regard to body weight, but I think it is
also important to look at fat mass change, because ultimately
that is what most people are interested in losing. And that
number is--the differential between those two groups is much
higher there.
Mr. Walden. What is that number?
Mr. Chinery. It is 5.7 pounds from using Xenadrine without
dietary restrictions versus 1.08 pounds with the placebo.
Mr. Walden. So roughly a 4 pound difference in 6 weeks
between the two?
Mr. Chinery. A little more than four.
Mr. Walden. And from that you tell consumers in effect, or
it was being suggested you could, I guess, have 524 percent
more fat loss in the Xene group? And you are comfortable saying
that to consumers?
Mr. Chinery. Well, you know, it is a pretty significant
number and it was statistically significant, and it was
eventually accepted for publication.
Mr. Walden. Okay. This Tab 39 also has an ``hey Bob''
email. Also from Tim. It says ``Thanks for the message. I
originally thought the same thing and that Armstrong run a
comparison on lean mass changes BT groups. Unfortunately, both
groups increased lean mass from pre to post testing and
although the increase in the Xene group was 161 percent greater
than the increase in the placebo group, the diffs were not
quote/unquote statistically significant. Probably due to
variance in response. However, my opinion the effect does
warrant mentioning in the full paper.'' I mean, there he is
saying on lean mass it is not statistically significant even
though 161 percent difference.
Mr. Chinery. Correct.
Mr. Walden. Yes.
Mr. Greenwood. The time of the gentleman has expired.
Mr. Walden. Thank you, Mr. Chairman.
Mr. Greenwood. The gentleman from Illinois is recognized
for 10 minutes.
Mr. Rush. Thank you, Mr. Chairman.
I would like to go back to Mr. Schreck. Earlier, as perhaps
you heard, Mr. Vasquez testified that he was instructed in
phone calls not to use the term side effects. Can you or Mr.
Hermann comment on what policy or practice might have been in
place at the company that would have led him to make that
statement?
Mr. Hermann. No, Congressman, I am sorry. I am not familiar
with that. I do not know why that statement was made, but we
will get back to you on those policies, sir.
Mr. Rush. Mr. Schreck?
Mr. Schreck. I feel the same way. I was not part of the
company then. I had not heard that statement until this
morning, and as I have mentioned earlier, we believe in
consumer protections and I do not know where this statement
emanated from or why.
Mr. Rush. Okay. Ms. Culmo, earlier I asked a question I
would like to direct to you, since you have just recently
joined the panel, and it was when were the words ``heart attack
and stroke'' added to the label of this product and why if you
can respond to that?
Ms. Culmo. Yes, sir. The Texas Department of Health enacted
regulations that went into effect in November 1999 that
required that warning that did in fact include heart attack and
stroke. And I think there your subsequent question to that was
did Metabolife oppose that. And, yes, they did. They are on
record with that opposition.
Mr. Rush. Can you say what the record reflected as far as
the basis for their opposition?
Ms. Culmo. It was pursuant to what we call a public docket
at the Texas Department of Health. It includes all the adverse
event reports that we had received, physicians reports
published, articles, medical journal. Two medical scientific
panel reviews of the docket.
Mr. Rush. What was the gist of the basis for their
opposition, if you recall?
Ms. Culmo. The discussions were based around the fact that
it would be detrimental to sales to put something like that on
the label and that there was not adequate evidence to support
that warning.
Mr. Rush. Would either you gentlemen care to comment on
this point? Do you understand that to be an accurate
description of the position of the company with respect to this
Texas regulation?
Mr. Hermann. I am sorry, sir, that was before I joined the
company. I have no information about that.
Mr. Schreck. And I was not involved with the company at
that time. And have no knowledge of what happened in Texas at
that time.
Mr. Rush. You all do have knowledge about what happened at
the company before you joined it, I assume?
Mr. Schreck. We do have some knowledge.
Mr. Hermann. Some knowledge, yes.
Mr. Rush. Okay. Ms. Culmo, I believe there has been a
statement made earlier about Metabolife, I do not know who made
this statement, that the development of their product was
similar to--and my terminology is going to be weak here--that
the process that they followed to develop their product was
similar to the standards that would be followed in developing
similar products under the OTC monograph. Perhaps you can state
my question more competently than I did and then you can
respond?
Ms. Culmo. Yes. There were a couple of points made by some
of the panel members that I did in fact believe warranted some
clarification. And one of those was the referral to the OTC,
over-the-counter monograph of dialators and decongestants. That
is something that the industry basis the safety of their
products on. I think the clarification needs to be made that
that monograph was pursuant--it addresses a very specific
subpopulation within the general population; that is those
persons that have been diagnosed, medically diagnosed with
asthma that are to take those drug products at those
recommended doses.
It also has a warning in there that if the first dose is
not effective, within 5 minutes you are to call your medical
practitioner. It is uncommon that someone would breach the
maximum dosage that's in that monograph.
The other thing that I think is very important for people
to know is that ephedrine never had safety or efficacy studies
done. They were grandfathered into that monograph.
Mr. Rush. Okay. Would anybody on the panel like to comment
on this last particular point? Okay.
I am aware of a study done by Haller & Benowitz in December
2000 published in the New England Journal of Medicine which
examines the effects of ephedra based products on Marines at
Camp Pendleton. Is anyone on the panel familiar with that
study? Has anyone read that report in the New England Journal
of Medicine? Has anybody heard about the report? Is somebody
nodding their head? The record cannot reflect--Dr. Colker, if
you can say.
Dr. Colker. I recall reading it, but I really--the details
escape me.
Mr. Rush. Well, let me describe to you----
Dr. Colker. Help me with the question.
Mr. Rush. Let me describe to you what I think it said, and
for purposes of my question you can assume I am being accurate.
The study was based on the survey and medical data from the
First Marine Division at Camp Pendleton and found that 7
percent of Marines reported daily use of ephedra in dietary
supplements during the year 2000, and half of the Marines with
heat related injuries in 2000 in that division had used
ephedra. That is a pretty significant statistic, and I would
like to give you the chance to comment or anyone else on the
panel that would care to do so.
Dr. Colker. The way it is written, Congressman, it
certainly sounds very significant and I do not have any other
response other than to say from what I recall in general about
the study, it was an observational--it was observational data
and it was anecdotal data. I do not think it was a structured
study in anyway. And, thus, I think there is a difference.
Mr. Rush. Anyone else care to comment on that? Okay.
A question to anyone on the panel who cares to answer it.
How effective had the State laws to date in New York, Illinois,
perhaps other States, been in protecting those individuals
under 18 from buying the ephedra product?
Ms. Culmo. Congressman?
Mr. Rush. Yes, ma'am?
Ms. Culmo. I cannot comment on that. There are State
surveys that are published in public dockets where they have
done undercover buys for these products. And they are easily
accessible, and so quite frequently to persons under the age of
18.
Mr. Rush. Okay. Now, certain sporting groups, baseball and
others, have banned the use of ephedra products. Is that
correct? Can someone comment on what the basis was for the
decision to institute that ban?
Mr. Hermann. Congressman, I am not aware of what their
basis was, but we are on record of not supporting the use of
ephedra products for athletic enhancement.
Mr. Rush. So you support that ban?
Mr. Hermann. Yes, we do, Congressman.
Mr. Rush. Okay. Comments from either of the other
principles of the companies? You support the ban as well, if
you have a position?
Mr. Occhifinto. Congressman, I do not offer my products for
the sports----
Mr. Greenwood. Bring your microphone to you.
Mr. Rush. You do not offer your products?
Mr. Occhifinto. I do not offer my products into that
marketplace.
Mr. Rush. Okay. Thank you, Mr. Chairman. Thank you.
Mr. Greenwood. Ms. Culmo, you seem to be trying to get my
attention?
Ms. Culmo. Yes, sir, if I may, there was one more point I
would like to clarify.
Mr. Greenwood. Please do.
Ms. Culmo. And there has been references to our comparison
of the statistics for aspirin and acetaminophen to poison
control centers and its numbers. I would like to point out that
one more time, specific comparison of a dietary supplements to
a drug product, those drug products are on the market on a
completely different standards and evaluations. And if in fact
they want to compare the products, dietary supplements or foods
to a drug statistics, then they should be on the market in the
same manner in which those drugs are made and available.
Mr. Greenwood. Thank you, Mr. Culmo.
The Chair would inform all of the members of the
subcommittee and the witnesses that this hearing will be over
before 7, at the latest. I know probably many of you are eager
to complete your travel plans.
Let me ask Mr. Schreck a question. I am looking at your
Metabolife 356 container and various ingredients. One of them
that I find intriguing is that it contains royal jelly. Could
you tell us what royal jelly is?
Mr. Schreck. I will have to pass that to Mr. Hermann since
he is involved in the production of the product.
Mr. Greenwood. Mr. Hermann, what is royal jelly?
Mr. Hermann. I am sorry, Chairman. I really do not know
what royal jelly is.
Mr. Greenwood. You are in charge of making the product?
Mr. Hermann. Yes, Chairman, I am. But I----
Mr. Greenwood. It seems to me then you would be in charge
of making sure that the royal jelly that gets in here is good
royal jelly and that the right amount of royal jelly gets in
here, not too much, not too little. Would that not be right?
Mr. Hermann. Absolutely, Chairman. And we do make sure that
the ingredients according to the formula are in the product.
Mr. Greenwood. So you can testify that only pure and clean
royal jelly gets in this product and that too much of it and
not too little gets into the product, is that correct?
Mr. Hermann. We set specifications for all the raw
materials that go into----
Mr. Greenwood. But you cannot tell me what royal jelly is?
Mr. Hermann. I do not have personal knowledge about what
that is, sir.
Mr. Greenwood. That is very interesting.
And who in your company could tell us what royal jelly is?
Mr. Hermann. One of our chemists or the gentleman in charge
of research and development at our laboratory.
Mr. Greenwood. What is bovine complex?
Mr. Hermann. That is a complex that came from cattle.
Mr. Greenwood. Okay. Do you know what part of the cow it
comes from?
Mr. Hermann. Not specifically, no sir, I do not.
Mr. Greenwood. But you are in charge of making sure that
whatever piece of a cow goes into this capsule is good for
people, not bad for people, right?
Mr. Hermann. Congressman, I am in charge of manufacturing
the product according to the requirements of our formula and
making sure that we follow that formula----
Mr. Greenwood. Okay. So when----
Mr. Hermann [continuing]. Other than that the company will
discern whether or not those products are----
Mr. Greenwood [continuing]. You make sure that the right
amount of bovine complex gets in here, how do you do that?
Mr. Hermann. Through various analytical methods, sir.
Mr. Greenwood. Okay. So when you're analyzing your bovine
complex, how do you analyze your bovine complex?
Mr. Hermann. Sir, I am not a scientist. I do not know the
process that is taken to do that. However, we do have batch
records that support analysis of our product throughout the
entire system. We do not just make one test. We test raw
materials when they come into our facility to make sure they
meet our specifications and then in every step through the
manufacturing process we will pull samples. Once it is mixed
and before it is tableted, and then after it is tableted to
make sure that it does--that the ingredients that are listed on
the label are in the product in accordance with what the label
says is in the product, sir.
Mr. Greenwood. So all you know is that some barrels of
stuff come in that say bovine complex and you know how many
grams or ounces or pounds or what of bovine complex goes into a
batch of Metabolife, but you have no clue as to what--whether
that's cow ears, nose, throats, brain, testicles? You do not
know what part of the cow goes into this thing?
Mr. Hermann. Sir, not myself personally. I have people that
report to me who do have the specialties and do know that.
The bovine complex, I do believe--well, I do know this: It
is no longer in our product. It was removed from the product.
Mr. Greenwood. Do you know why that is?
Mr. Hermann. Pardon me?
Mr. Greenwood. Do you know why you removed the bovine
complex?
Mr. Hermann. It was removed from the product about a year
ago, about the same time when all the publicity on Mad Cow
Disease in Europe. We felt that it was--after reviewing the
formula with various scientists, we determined that it could be
removed from the product without changing performances of the
formula.
Mr. Greenwood. That's funny. Then one would wonder why it
went in to begin with.
Mr. Hermann. I do not know that, sir.
Mr. Greenwood. Do not know that either. Okay.
I would appreciate it if you would have your scientists
inform the committee as to what royal jelly is and what
constituted the bovine complex that you used to put in the
product.
Mr. Hermann. We would be more than happy to do that.
Mr. Greenwood. Thank you.
Mr. Occhifinto, I am going to return to you?
Is it Occhifinto or Occhifinto?
Mr. Occhifinto. Occhifinto.
Mr. Greenwood. Occhifinto. And you will need to pull your
microphone.
You stated in your June 5, 2003 letter to the committee
that Stacker 2 Lite has less ephedra than other of your
products, is that not right?
Mr. Occhifinto. Yes.
Mr. Greenwood. Okay. You also agree that your various
ephedra-containing products such as Yellow Jackets or Yellow
Swarm, Black Beauty, Stacker 2, Midnight Stallion have other
active ingredients besides ephedrine and caffeine? They have
other active ingredients?
Mr. Occhifinto. There is other herbs in those products. I
do not know whether you would consider them active ingredients.
There are other herbs in those formulations.
Mr. Greenwood. Okay. And can you tell us what some of them
are?
Mr. Occhifinto. There is--I believe there's maybe ginseng
in some of those formulas, green tea, cola nut. That is all I
remember off hand.
Mr. Greenwood. I thought you were the developer of the
formula?
Mr. Occhifinto. I am the developer of the formula, but they
have been developed over the years. I do not remember every
ingredient and why I put it in there when we did the
development work on it.
Mr. Greenwood. Really? Is bitter orange, citrus auranthium,
is that in the product?
Mr. Occhifinto. Yes, I believe it is in maybe 1 or 2 of
those products.
Mr. Greenwood. Okay. And what made you decide you wanted to
put that in there?
Mr. Occhifinto. It was a popular supplement that was coming
out to replace ephedra on the market a couple of years ago.
Mr. Greenwood. Okay. Is it a stimulant?
Mr. Occhifinto. I believe so.
Mr. Greenwood. Is it standardized for cenefrene, which is a
stimulant?
Mr. Occhifinto. I am not sure of the pharmacological--what
it pharmacologically does and what I have read about it, I
believe it is a slight stimulant.
Mr. Greenwood. Ms. Culmo, do you know what citrus
auranthium, bitter orange does, what the impact of that is?
Ms. Culmo. Yes.
Mr. Greenwood. Could you tell us?
Ms. Culmo. Citrus aurantium also contains the active
ingredient epinephrine. It is the one that Dr. Woosley alluded
to earlier that it is believed also has cardiac stimulant
activity.
Mr. Greenwood. Okay. And can you comment on what you think
the impact of that would be to combine that with ephedrine and
perhaps caffeine?
Ms. Culmo. Well, the concern has been anytime you combine
these stimulants, you obviously are going to have an increased
effect of all of them.
Mr. Greenwood. An added effect, cumulative effect of more
than one stimulant?
Ms. Culmo. Definitely.
Mr. Greenwood. Okay. Thank you.
Back to you, Mr. Occhifinto. All your products do not have
the same exact formulation, do they?
Mr. Occhifinto. No, they do not.
Mr. Greenwood. Okay. For example, your Stacker 2 product is
not formulated identical to Black Beauty, which is now known as
Midnight Stallion and Black Beauty/Midnight Stallion did not
have the same amount of ephedra and caffeine as Yellow Jacket
or Yellow Swarm do, is that right?
Mr. Occhifinto. Congressman, I did not hear the last part
of the question.
Mr. Greenwood. I am saying that your different products,
Stacker 2 has a different amount of ephedra than does Midnight
Stallion, and that is different than Yellow Jackets or Yellow
Swarm?
Mr. Occhifinto. I believe at this time that most, except
for our Stacker Lite product and figure free products have the
same amount of ephedra in the formulas.
Mr. Greenwood. As of when? You say ``now you think they are
the same?'' Because I am aware that we have consumer complaints
that were sent to your company that lists Black Beauty as
having 25 milligrams of ephedra and 200 milligrams of caffeine
per pill, Yellow Jackets 30 milligrams of ephedra 300
milligrams of caffeine per pill. So was that the case before
you changed? Did they have different dosages?
Mr. Occhifinto. I do not know what you are referencing
there. Most of our formulas were for 25 milligrams--equivalent
to 25 milligrams from the ephedra source. Or if it was Stacker
Lite, it was 1\1/2\ milligrams of ephedrine.
Mr. Greenwood. But you never intentionally had different
levels of ephedra for a different level for Black Stallion than
for Yellow Swarm, or whatever it is?
Mr. Occhifinto. We have been in this business for a long
time. The formulas have changed from time-to-time to meet
different requirements for different States. I do not know
which formulas you are referring to. I know that most of ours
are standardized to 25 milligrams ephedrine, and the amounts of
caffeine or what usually varies.
Mr. Greenwood. What is your understanding of the OTC
monograph concerning the maximum amount of ephedrine and
caffeine that a person should ingest during a 24 hour period?
Mr. Occhifinto. I do not know what the maximum is of
caffeine, but I believe it's 160 milligrams of ephedra.
Mr. Greenwood. Is the maximum that a person should ingest
in a day?
Mr. Occhifinto. I believe so.
Mr. Greenwood. Okay. I just want to go back to one point
that we were discussing earlier. When I asked you about
documentation of your formula, virtually none of which you have
supplied to this committee, you said well we supplied the
formula cards. Okay.
The question that I was really trying to get at is
documents that would educate us as to what process you went
through in developing the formula. In other words, are there no
documents in your company that would represent a description of
how your company came to choose the particular formulas that it
ultimately uses?
Mr. Occhifinto. That is true, Congressman.
Mr. Greenwood. And how would that be? It just came straight
out of your head?
Mr. Occhifinto. The formulas were developed by referencing
herbal books, magazines, what was on the market, what could be
sold and how the product would work after it was formulated.
Mr. Greenwood. Okay. So you used these references and then
told your company to manufacture per these specifications and
just handed them a book or handed them a magazine article? Is
that how you did it?
Mr. Occhifinto. No. Extrapolated that information and wrote
formula cards that are followed to make sure that the product
got----
Mr. Greenwood. So you went straight from the reference to
the formula card without any other intervening documents or
paperwork that you----
Mr. Occhifinto. There really was nothing generated for
that.
Mr. Greenwood. Okay.
Mr. Occhifinto. We really went straight from there and
formulated the products.
Mr. Greenwood. Okay. Can you tell us, what reference would
you have used to formulate Yellow Jacket, for instance? And yet
what is now called Yellow Swarm. Where did you turn to find
that formula?
Mr. Occhifinto. Well, the formula for the ephedra and the
caffeine is pretty much standard in the industry, not to go
over 26 milligrams of ephedrine. Now the rest of the components
in it we are just using research documents. We have a library
of herbal books and just look through those books to find
complimentary herbs.
Mr. Greenwood. Okay. When you renamed Yellow Jacket to
Yellow Swarm, you increased the ephedrine and you added another
ingredient, correct?
Mr. Occhifinto. Chairman, I do not remember what the other
ingredient that I added to it. If you are talking about an--we
increased the ephedra 10 milligrams, which would be the
equivalent of one milligram of ephedra in it. And the only
reason we did that is to standardize our formulas so they all
were 25 milligrams of ephedrine.
Mr. Greenwood. Okay. Did you take out citrus aurantium at
that time?
Mr. Occhifinto. I do not recall.
Mr. Greenwood. Okay. There is a stunning lack of
information among some of you on this panel as to what is
contained in the products you sell.
The Chair recognizes the gentlelady from Colorado.
Ms. DeGette. Mr. Chairman, I have no further questions.
I would like to thank you for holding this hearing and say
how much I look forward to the hearing tomorrow. And also to
note that I share your extreme concern over the fact that
people are marketing what are called dietary supplements which
are clearly having an adverse health effect on Americans and
which are not, apparently, controlled in any way.
And furthermore, how we have a bunch of people in this
industry, this is only one product, ephedra. And we have a
bunch of people who are making pills they do not even know what
is in them, they do not have Ph.D, like Dr. Boozer, they do not
have even college degrees. And I think that this is an area--I
know from my own personal experience that my friends are
increasingly interested in herbal supplements. I think this is
an area that this committee has to put continuing attention to.
And I am really interested to hear what the regulators say
tomorrow. So thank you for holding this hearing.
Mr. Greenwood. Thank the gentlelady for her many hours of
participation.
The gentleman from Oregon is recognized for 10 minutes.
Mr. Walden. Thank you very much, Mr. Chairman.
Mr. Conklin, when you approached Dr. Armstrong about
speaking out on behalf of your product, what was his response?
Mr. Conklin. I am sorry, sir. Could you please repeat that?
Mr. Walden. I am sorry. When you approached Dr. Armstrong
about speaking out on behalf of your product, what was his
response?
Mr. Conklin. At first he was hesitant. He said he was not
good in front of a camera.
Mr. Walden. Would you say he was cooperative in nature but
just hesitant?
Mr. Conklin. He eventually became cooperative, but he was
hesitant because he was, we will call it camera shy.
Mr. Walden. So it was camera shy, it was not about not
wanting to be associated with the percentage claims versus the
actual number claims?
Mr. Conklin. Well, the initial comments from him were that
he is not good in front of a camera.
Mr. Walden. Initial comments? Did he ever express to you
any hesitation about the use of percentages in the advertising?
Mr. Conklin. Yes, sir, he did. Initially as I have seen
with various scientists and research scientists, they do not
like to express anything in percentages or in any other means.
They are very scientific and they stay away from anything that
has to do with advertising.
Mr. Walden. Is not Dr. Zigginfuss a scientist?
Mr. Conklin. He is a research scientist, yes.
Mr. Walden. He seems to be a real advocate for using these
percentages, is he not?
Mr. Conklin. Well, there are some that are. There are some
that are not.
Mr. Walden. Yes. But he was actually more in your marketing
side of promoting this than the research side, is that right as
a consultant?
Mr. Conklin. Well, he was hired as a consultant to contract
other research institutions to do studies on Xenadrine.
Mr. Walden. Well, was he not also trying to nudge Dr.
Armstrong to come out with the right data in the abstracts and
how he used the data?
Mr. Conklin. Well, that would not be accurate. He was--Dr.
Armstrong, though the data existed, did not present that data.
So Dr. Zigginfuss spoke with him in order to get him to present
the data that was obtained from the study.
Mr. Walden. Or present it in a way that would be more
favorable for marketing purposes?
Mr. Conklin. Well, I mean, the results were such that, you
know if a statistician were to I guess work on them
mathematically the percentages would be correct. And I guess
through his discussions with Dr. Armstrong they both came to
that conclusion or Dr. Armstrong came to that conclusion.
Mr. Walden. Okay. Regarding the advertising, what role do
you play in the advertising?
Mr. Conklin. My role is to work with athletes and/or
celebrities who endorse the product.
Mr. Walden. Okay. And do you then actually produce the ads,
do you write the scripts, do you hire the production firm? How
does all that--do you play a role in all of that?
Mr. Conklin. No, sir, I do not.
Mr. Walden. You do not? So you do not line up people to
speak on camera and that sort of thing?
Mr. Conklin. I do not do what?
Mr. Walden. Line up people to speak on camera? You do not
make those decisions or recommendations of who should be on
camera, who should not in your advertising, the marketing?
Mr. Conklin. Well, if we have plans where we going to do
someone for a commercial or something like that, then I would
look for people who have achieved success with the product or
celebrities or athletes to go on a commercial or we will say in
front of the camera.
Mr. Walden. Okay. Because I was just looking at an email
that you had sent to Bob C, Tab 43. It sure sounds like when I
have done ads, kind of the person that produces them.
``Armstrong was not being cooperative as far as interviews or
locating test subjects. I finally talked him into giving a one
liner off camera that can be worked into the VNR as a quote
from the author. We can than--'' although I know you mean
then--``include interviews from Zig, Calman and/or Colker. Zig
can use the angle that he has reviewed several studies and this
one kicks ass. You get the point. Colker and Calman can use the
angle that this study yielded--'' and it goes on and on and on.
To me that sounds like you are kind of scripting out how to
do the ad. It is not a bad thing. I am just trying to figure
out what your role is.
Mr. Conklin. Well I guess my role could be putting projects
together. And in this case, it was a video news release of VNR.
Mr. Walden. Yes.
Mr. Conklin. And I was----
Mr. Walden. So this was a new release trying to work the
press on the results. Is that what a VNR is?
Mr. Conklin. Right. Correct. Yes.
Mr. Walden. Okay. Go to Tab 5 if you would, and there is an
email from Kelly Conklin to John Jay Murphy, dated November 19,
2002.
``John, thanks for the kind words. I left there with a good
impression of you. Also I have a training video that we may be
doing in the near future, may want to include you. Can you get
ripped in case this thing goes through in a couple of weeks? If
it does not, no harm done.'' What is ``ripped?''
Mr. Conklin. Well, that is a common term used amongst
athletes to show muscularity, low body fat.
Mr. Walden. Okay. And why would you tell him to get ripped
in case this thing goes through in a couple of weeks? Did you
want him to look buff, is that a term similar to--synonymous
with ripped? I am not an athlete.
Mr. Conklin. I guess ripped is more specific to showing
muscle definition. Buff might be muscular.
Mr. Walden. All right. I am learning as we go here.
So you wanted him to get ripped so he would look good on
camera. Was John Jay Murphy somebody who was going to use your
product or testify on camera that he was a user of your product
and had gotten results?
Mr. Conklin. Actually, he was a success story who had sent
photographs to me after he achieved the success on Xenadrine.
And we were contemplating the other training video, and he was
one of the potential candidates to be used in that. And, of
course, if he is going to be on a video, we would like him to
look good.
Mr. Walden. Yes. Okay.
Mr. Conklin. Now this is sometime after he had originally
gotten through the transformation process.
Mr. Walden. How long was he on your product?
Mr. Conklin. He was very short term, but I am not quite
sure, sir.
Mr. Walden. How much weight did he lose? How much fat did
he lose?
Mr. Conklin. Once I am not--I do no recall. There were so
many that I do not specifically recall his weight or his fat
loss.
Mr. Walden. I see. If you could supply that for the
committee at some point, it would be helpful.
Mr. Conklin. Yes, sir.
Mr. Walden. We are trying to figure out, you know, how
accurate the claims were here.
And so he is a real person, he gets ripped. You want him to
look his best on camera. Obviously, to put the best face on
your product?
Mr. Conklin. That is correct.
Mr. Walden. Or best abs or whatever it is he is putting on
your product.
Mr. Conklin. Well, this is, like I said, sometime after he
had sent his photographs to me. So I did not know what kind of
shape that he was in.
Mr. Walden. All right. So you remember he sent the photos,
but you do not recall but you will supply for us how much
weight he lost that he attributes to your product?
Mr. Conklin. I do not remember, sir.
Mr. Walden. No, but you will supply it for us?
Mr. Conklin. Yes.
Mr. Walden. Did any physician like Dr. Colker ever evaluate
these success stories to ascertain their veracity?
Dr. Colker, I mean, were you using success stories in
advertising, did you take a look at them and say they meet some
criteria?
Dr. Colker. No, I did not.
Mr. Walden. Anybody in the company do that to verify that
these were real success stories? Mr. Conklin?
Mr. Conklin. We got signed affidavits, sworn affidavits
from the people.
Mr. Walden. Okay.
Mr. Conklin. Attesting to their weight loss.
Mr. Walden. All right. So nobody checked beyond that? They
just told you. And how much did they get paid? What do you pay
somebody to come in that looks ripped?
Mr. Conklin. Well, they do not get paid if they just send
photographs in, it is if they are used in any advertising.
Mr. Walden. Yes. If they are used in a video that you do,
what do you pay them generally?
Mr. Conklin. For an ad, I believe a couple thousand
dollars.
Mr. Walden. Really?
Mr. Conklin. Yes.
Mr. Walden. So there is a real incentive. But so they just
can sign an affidavit that says I swear I took whatever it is
and look at me now, and you use them and nobody checks? There
is no controlled study, is that right, no control on this?
Mr. Conklin. Well these----
Mr. Walden. They just tell you they took it? No doctor
reviews it?
Mr. Conklin. Well, these were photographs that we received
after he had made his transformation. So----
Mr. Walden. But in general. Have anybody in any of your
videos, do you do any kind of quality control to make sure they
are telling you the truth?
Mr. Conklin. We look into it.
Mr. Walden. Who looks into it?
Mr. Conklin. I would look into it. I would--they would send
typically a letter with their photographs outlining their
progress and then they would sign a sworn affidavit.
Mr. Walden. Do you do any kind of blood tests to make sure
they are not on steroids rather than ephedra/caffeine products?
Mr. Conklin. No. We do not do blood tests.
Mr. Walden. How do you know then? I mean----
Mr. Conklin. Well, I believe----
Mr. Walden [continuing]. With any certainty?
Mr. Conklin. I believe in the agreement that they sign they
are swearing that they have not used any other illicit drugs or
any drugs otherwise.
Mr. Walden. But you do not do any blood tests to check?
Mr. Conklin. No, sir, we do not.
Mr. Walden. Huh. All right. All right. Well, interesting.
Is Mr. Murphy a friend of yours from the gym?
Mr. Conklin. No, he is not.
Mr. Walden. He is not? Huh. All right.
What is his profession?
Mr. Conklin. He is a medical doctor.
Mr. Walden. Mr. Murphy is a medical doctor?
Mr. Conklin. Yes, he is.
Mr. Walden. Okay. Does he do any kind of body building or
is he a professional body builder as well?
Mr. Conklin. I do not believe he's a body builder, no.
Mr. Walden. Okay. Does he have an agent?
Mr. Conklin. I am not sure.
Mr. Walden. Maybe somebody named Michael Snell? Does that
name ring a bell?
Mr. Conklin. Michael Snell may have been the person who
sent his photographs originally to me, yes.
Mr. Walden. Would a person who send somebody else's photos
usually be considered an agent?
Mr. Conklin. Not always. Sometimes they are a friend of
theirs. Sometimes they call themselves an agent when, in fact,
they are just a friend whose----
Mr. Walden. Do you enter into an agreement with Mr. Snell,
has your company ever done that?
Mr. Conklin. I do not believe so, no. It was directly with
John Murphy.
Mr. Walden. Okay. All right.
Did Cytodyne ever hire people to gain and then lose weight
for the purposes of advertising? Mr. Chinery.
Mr. Chinery. No, sir.
Mr. Walden. Okay. Did not Cytodyne's choice of models come
into question in a recent California suit, Park v. Cytodyne?
Mr. Chinery. In that case there was one witness who had
changed his testimony, actually testified completely
inconsistent with his sworn statements that he had provided to
the company earlier. And in that testimony he said for the
first time he told the company that he had gained weight prior
to starting his after program.
Mr. Walden. Did your company have the raw data to show that
in fact his affidavit was not right?
Mr. Chinery. I am not sure what you mean by the raw data.
Mr. Walden. Did you have the actual data, his amount of fat
loss?
Mr. Chinery. That would be based upon the affidavit that he
provided to the company, which was a sworn affidavit, sworn
under penalty of perjury.
Mr. Walden. And what you are telling me if I understand it
right is that he lied in that affidavit to your company? Is
that what you are saying?
Mr. Chinery. That is my belief, yes.
Mr. Walden. In fact, did not the judge in that case state,
and I quote: ``Since both Mr. Chinery and Mr. Conklin were
aware of the inconsistent information, the claims in
advertising regarding a hired model's fat loss and muscle mass
gain are evidence of defendant's willingness to stretch the
truth to make its product appear to be more effective than it
actually was.'' That is a quote from the judge.
Mr. Chinery. I believe that was his own opinion on that.
But I strongly disagree with it.
Mr. Walden. How long was that trial?
Mr. Chinery. I believe it was between 6 or 7 weeks.
Mr. Walden. Okay. Look at Tab 2. We have an email here
where ABC Channel 7 New York contacted you about your product
in April 2001. You referred the reporter to Dr. Colker so that
she could hear from ``an independent research scientist that is
one of the foremost authorities in the world on ephedrine.''
But before you gave the reporter Dr. Colker's contact
information you quote ``went over with him'' so that ``he is
clear that he is not to mention our company and is an
independent researcher.''
Do you make it a habit to not disclose all pertinent
information to the press or the public when the spotlight is on
your company?
Mr. Conklin. So is that directed to me? That would be on my
email?
Mr. Walden. It is your email. Yes, I am sorry. Yes. Yes. To
Bob C.
Mr. Conklin. Okay. In that case----
Mr. Walden. I want to make sure you have it. Tab 2. Okay.
Mr. Conklin. This is Dr. Colker who, as he has on several
other occasions, spoken as an independent researcher not on
behalf of the company.
Mr. Walden. Okay. But if I read this right, I thought you
referred this to the reporter so that she could hear from an
independent research scientist. Yet, did not Dr. Colker do work
for your company? Was he not on a retainer?
Mr. Conklin. Yes, sir, he was, but he was not an employee.
And----
Mr. Walden. Well, what's the difference between somebody on
a retainer and somebody who is an employee? Is that--it seems
to me that if I am on a retainer, I am not as independent as if
I am not either an employee or on a retainer.
Mr. Conklin. Well, he has done consulting and he still may
for other companies other than Cytodyne.
Mr. Walden. But he was on Cytodyne's cost of doing
business, right? How much were you paying him, Mr. Chinery, do
you know at that time, 2001?
Mr. Chinery. I believe at that time it was in the range of
around $5,000 per month.
Mr. Walden. $5,000 a month? On a retainer? And yet Mr.
Conklin, I guess, tells the press here that he is independent.
Do you believe him to have been independent?
Mr. Greenwood. This will have to be the gentleman's last
question.
Mr. Walden. Oh, I am sorry.
Mr. Chinery. In a certain capacity, yes. Because Dr. Colker
has done a lot of research for a lot of other companies and
other products, and we do consider him an expert on the subject
of dietary supplements.
Mr. Walden. Mr. Chairman, could I just ask one question of
Dr. Colker?
Mr. Greenwood. Quickly.
Mr. Walden. Do you consider yourself independent when you
are paid $5,000 a month by a company?
Dr. Colker. I did.
Mr. Greenwood. It is all the independence money can buy.
The Chair recognizes himself quickly for two questions
directed to Metabolife officials.
Metabolife officials have repeatedly said that they are
interested in both consumers' health and in mandatory reporting
of adverse events to FDA, yet the company did not voluntarily
send to FDA copies of adverse event reports until August 2002.
Why not?
Mr. Hermann. Congressman, I do not know the reasons
specifically of why those were not turned over until last year.
Mr. Greenwood. Okay. Do you know, Mr. Schreck?
Mr. Schreck. I have no idea why they were not turned over
prior to 2002.
Mr. Greenwood. Okay. With that, would you please respond to
this committee in writing on answer to that question, which is,
and we will be happy to provide you with a copy of it,
Metabolife officials have repeatedly said they are interested
in both the consumers' health and in mandatory reporting of
adverse events to the FDA, yet the company did not voluntarily
send to FDA copies of adverse events reports until August 2002.
And we would like to know why not.
Let me ask you one final question before we end the
hearing. Dr. Steven Heymsfield has testified that he was
involved in two studies of ephedra conducted by ST&T on behalf
of Metabolife. After Dr. Heymsfield declined to provide a
statement that would benefit Metabolife in a civil lawsuit the
company had filed, Dr. Heymsfield said the company terrorized
him, told him that ``they were at war'' according to an
interview that the doctor had with the Department of Health and
Human Services. He reported that the consequences of
Metabolife's actions almost ended his career.
Dr. Heymsfield also told his interviewers at HHS that
although he was never requested by Metabolife to alter his
data, he was encouraged to adjust his interpretation of that
data.
Mr. Schreck, you were not an employee of Metabolife at that
time, were you?
Mr. Schreck. No, I was not.
Mr. Greenwood. Okay. Even so, how does Dr. Heymsfield's
story reflect upon your company's tactics in trying to obtain
scientific results to boost your claim that Metabolife 356 is
safe?
Mr. Schreck. Well, without previously seeing a document
that you are talking about----
Mr. Greenwood. Look at Tab 104, please.
Mr. Schreck. I'm sorry.
Mr. Greenwood. Turn to Tab 104.
Mr. Schreck. Thank you. Is there a specific section of 104
you would want us to look at?
Mr. Greenwood. Page 8.
Mr. Schreck. Page 8?
Mr. Greenwood. Yes.
Mr. Schreck. There is no page numbers on the bottom of
this, so I will count them out.
Mr. Greenwood. Well, I will tell you what I am going to do,
Mr. Schreck. You are the new CEO. You are telling us you do not
know anything about this. What I would like to ask you to do is
to go back to your company and you conduct an investigation
within your company. And I would like you to find out whether
in fact who was involved in these contacts with Dr. Heymsfield
and whether or not he was encouraged to adjust his
interpretation of that data and at your leisure take a look at
that tab, review it and interview individuals at your company
and provide this committee with a response as to what you found
out. Would you do that for us, sir?
Mr. Schreck. Yes.
Mr. Greenwood. And would you also do that, you have also
indicated in response to my previous question that you do not
know why it is that the company waited until August to send
these adverse event reports to the FDA. I would like you to
also find that out for us.
Mr. Schreck. Yes.
Mr. Greenwood. Do an investigation, ask your people and get
back to us in writing. Would you do that, sir?
Mr. Schreck. Yes, Mr. Chairman.
Mr. Greenwood. Thank you.
It has been a long day, a very, very long day for all of
you. I thank all of our witnesses for their patience and
forbearance.
I thank our members for theirs as well.
And this hearing is adjourned.
[Whereupon, at 7 p.m., the subcommittee was adjourned.]
[Additional material submitted for the record follows:]
Michael M. Baden, M.D.
New York, New York 10019
17 July 2003
Honorable James C. Greenwood
Chairman, Subcommittee on Oversight and Investigations
Committee on Energy and Commerce
U.S. House of Representatives
Washington, D.C. 20515-6115
Re: Death of Steven Bechler
Dear Chairman Greenwood: I have been retained by Arent Fox,
attorneys for Cytodyne Technologies, to review and evaluate the death
of Mr. Steven Bechler. I am the former Chief Medical Examiner of the
City of New York, and I was the chief forensic pathologist for the
United States House of Representatives Select Committee on
Assassinations that investigated the deaths of President John F.
Kennedy and of Dr. Martin Luther King Jr. from 1977 to 1979.
I have reviewed the autopsy report and Broward County Medical
Examiner's Investigative Report; the toxicology reports of Broward
County, National Medical Services and Aegis Analytical Laboratories;
literature relied upon by Chief Medical Examiner Dr. Joshua Perper;
transcripts and video of Dr. Perper's press conferences; the Rand
Report on Ephedra and Ephedrine prepared for the U. S. Department of
Health and Human Services of February, 2003; the Cytodyne Technologies
responses to Congressman W.J. ``Billy'' Tauziri s requests for
information about Xenadrine RFA1 dated March 14 and March 25, 2003; the
Florida District Medical Examiners Office reports of past heat stroke
deaths in their jurisdictions; and a February 19, 2003 ESPN article
entitled ``Family: Bechler had heatstroke while in high school'' in
which the decedent's mother is quoted as saying that her son had had
two prior episodes of heat stroke while playing baseball in high school
when he was 16 and 17 years old. The above were forwarded to me for
review by Arent Fox. I have also spoken to Dr. Perper by telephone
about this death.
I have not had access to the EMTFire Rescue records of February 16,
the North Ridge Medical Center Hospital records of February 16 and 17,
past medical records, the autopsy microscopic slides and photographs,
and the interviews of the witnesses to Mr. Bechler's collapse and
initial treatment.
Mr. Bechler was 23 years old and overweight when he arrived in
Florida for spring training in February of 2003. His weight was listed
as 249 pounds; in 1998 it had been 190 pounds. A routine physical
examination after arriving at training camp showed his blood pressure
to be extremely high, at 150/112. It later dropped to ``150/92''; his
pulse was very rapid at 96 beats per minute. He was known to have a
history of untreated high blood pressure and of liver disease. His
liver function tests were abnormal and it had been previously
documented that he had a fatty liver, possibly caused by his obesity.
His very high blood pressure readings alone upon arriving at the
training camp as well as his increased weight and liver disease, in my
opinion, should have caused delay of his exercise training until he was
further evaluated medically.
On February 15, Mr. Bechler participated in the morning training
exercise but was unable to complete the final run, didn't feel good and
went home. On February 16, with the outdoor temperature at 85
Fahrenheit and the humidity at 75%, he again could not complete the
final run, but this time, he fell to the ground, could not stand up,
vomited and was noted by the Assistant Trainer to be hot. He was taken
to the training room, given oxygen by mask and cooled with ice packs
behind his neck. He was unable to drink offered fluids. His temperature
was found to be 106 and his blood pressure was 160/90, with rapid
pulse and rapid breathing. Fire Rescue was called at 11:39 a.m. It is
not clear from the records presently available to me how much time
elapsed after Mr. Bechler's collapse on the field until Fire Rescue was
called. When Rescue arrived, Mr. Bechler was ``unresponsive,'' his
pulse was extremely rapid at 210, incompatible with proper functioning
of the heart; his blood pressure was listed as ``160/p,'' which
indicates shock; and his respirations were extremely rapid at 36 beats
per minute. Intravenous fluids and Narcan were administered; Narcan is
the specific antidote for a narcotic drug overdose such as from heroin,
morphine or oxycodone. He did not respond. He vomited ``large amounts''
requiring suctioning en route to North Ridge Hospital, where he arrived
at 12:23 p.m. His temperature was 108 degrees and a diagnosis was made
of heat stroke. He remained comatose, developed severe multiple organ
failure and was pronounced dead 23 hours after admission to the
hospital.
The autopsy report confirmed that Mr. Bechler was markedly obese
with a scale weight at the medical examiner's office of 320 pounds 71
pounds more than listed by the team trainer two days earlier. His
height is mistakenly listed in the autopsy report as 62 inches.
Assuming that his proper height is 6 feet 2 inches, as is indicated in
press reports, Mr. Bechler's Body Mass Index (BMI) would be 41,
establishing him as morbidly obese. The autopsy also showed that his
abdominal fat pad the panniculus adiposis was 4 cm thick, consistent
with his weight of 320 pounds, and confirmed that he had a fatty liver.
His heart was enlarged to 450 grams. He had heart and kidney disease
due to the harmful effects of untreated high blood pressure.
Toxicologic testing showed the presence of ephedrine, a weightreducing
drug, and twice the normal amount of DHEA, a naturally occurring
steroid, also available as a dietary supplement because it is believed
by some to enhance athletic performance and to help in losing weight.
It is of interest that Dr. Perper states in his report that in 2001 one
of Mr. Bechler's physicians had told him to avoid steroid supplements
and alcohol consumption. Review of medical records is needed to
determine why this warning was necessary.
The ephedrine level in Mr. Bechler's blood continued to rise for
three hours after he collapsed and while he was in the hospital, which
Dr. Perper stated in his March 13 report indicated that much of the
ephedrine taken by Mr. Bechler ``was still in an absorption stage''
when he arrived at the hospital. This means that at the time that Mr.
Bechler collapsed from heat stroke much of the ephedrine he had
swallowed was still in his stomach and had not yet entered his
bloodstream and, therefore could not have produced any harmful
physiologic effects; the unabsorbed ephedrine and the ephedrine in Mr.
Bechler's vomitus could not have caused or contributed to Mr. Bechler's
death. Dr. Perper, however, had publicly committed himself at a press
conference on February 18, the day of the autopsy, stating that
Xenadrine had been found in Mr. Bechler's baseball locker, that it
contains ephedrine and that the ephedrine significantly contributed to
Mr. Bechler's death from heat stroke this conclusion was reached before
toxicologic and microscopic studies were completed and before full
medical information could be obtained.
Ephedra refers to a species of plants, which includes the Chinese
herb ma huang, which contain ephedrine, a pharmacologically active drug
used as a nasal decongestant, as a bronchodilator and to raise low
blood pressure, and is similar to epinephrine (adrenaline), which is a
normal body hormone. It is also used to lose weight. The terms ephedra
and ephedrine are often used interchangeably.
At the March 13 press conference, Dr. Perper acknowledged that he
knew of no prior instance in which ephedrine had caused a death from
heat stroke. He also stated that no other drugs were found in Mr.
Bechler's blood on admission to the hospital, despite the toxicologic
finding of increased DHEA, which is not present in Xenadrine.
During that same press conference, Dr. Perper referred to the Rand
Report. The Rand Report found no evidence not a single case in an
extensive review of the literature and of reported adverse effects,
that ephedrine had caused any heat stroke deaths. Similarly, Cytodyne,
in its responses to Congressman Tauzin, Chairman of the House Committee
on Energy and Commerce, documented that it had had no reports of
Xenadrine RFA1 causing a death from heat stroke after more than 2
billion capsules had been sold. A MEDLINE search of the National
Library of Medicine's database of scientific articles in 4,500
biomedical journals worldwide since the 1960's, showed not a single
report linking ephedra or ephedrine to heat stroke. The Physician's
Desk Reference (PDR) does not list heat stroke as an adverse effect of
ephedrine.
Dr. Perper specifically referred to an editorial by neurosurgeon
Dr. Julian Bailes, published in the Journal of Neurosurgery in 2002, as
of particular importance in his reaching the conclusion that ephedrine
was a significant factor in causing Mr. Bechler's death. However, Dr.
Bailes does not describe or refer to a single instance in which
ephedrine caused a heat stroke death. He merely cites statistics in
which heat stroke deaths among football nationwide were 4.4 per year
between 1965 and 1974, 1.7 per year between 1975 and 1984, 0.6 per year
between 1985 and 1994 and were back to 4 deaths per year between 1995
and 2000. Not one of these deaths was linked to ephedra. However, Dr.
Baffles proposed that since there was an increase in the use of dietary
supplements and of ephedrinelike compounds between 1995 and 2000, they
might be the cause of the slight increase in heat stroke deaths.
Correlation is not causation. This is pure speculation by Dr. Baffles
and is not a basis upon which a medical examiner can make a cause of
death determination.
A number of Letters to the Editor written in response to Dr.
Baffles' editorial in that same Journal disagreed strongly with Dr.
Baffles' opinion that ephedra causes or contributes to heat stroke.
One, signed by 12 sports medicine specialists, exercise physiologists,
neuroscientists, and researchers from around this country and England
cited 66 references and concluded that obesity was the most important
risk factor in causing heat stroke: ``According to the National Center
for Catastrophic Sport Injury Research statistics, most heatrelated
deaths in recent years have occurred in individuals who weigh more than
250 pounds, with many athletes weighing more than 300 pounds.'' The
authors also stated that there was no evidence that ephedra increased
the risk of heat intolerance or of heat stroke.
Dr. Bailes, in responding to these critical letters, conceded that
many factors could contribute to heat stroke. ``These multiple other
factors,'' he wrote, ``include the relative dehydration of the athlete
before participation, heat acclimatization, the amount of heat and
humidity exposure, the intensity of exercise, the design of the
athlete's clothing and/or uniform, fluid replacement, the athlete's
underlying medical or cardiac structure, the simultaneous ingestions of
substances or medications that may interact, excessive dosages, genetic
disposition, medical management and other possible variables.'' At the
time of his collapse, Mr. Bechler had not yet had the ability to
acclimatize to the Florida weather; he was suddenly attempting to
exercise intensively; he had severely impaired underlying medical and
cardiac ``structure'' with known liver and heart disease and high blood
pressure, and had had an extremely high blood pressure reading of 150/
112, without further evaluation and treatment, just before engaging in
intense exercise; there may have been a delay in appropriate medical
management; and there is a history that Mr. Bechler had experienced
prior heat strokes.
Mr. Bechler's obesity is of particular concern. Dr. Perper assured
me that the medical examiner's body scale is accurate and that Mr.
Bechler weighed 320 pounds when he was brought there. Mr. Bechler was
much more overweight, with attendant increased health risks, than the
trainers realized. The 70 pound weight discrepancy cannot be explained
by excess hospital fluid administration in the 23 hours he lay in the
hospital; it would require delivery of more than three pounds of fluid
per hour without any hospital personnel realizing that there was
something wrong, while continuously adding intravenous bags. Further,
the autopsy showed no evidence of such extreme overhydration in the
body tissues or in the body cavities.
I agree with Dr. Perper that the cause of Mr. Bechler's death was
heat stroke. However, I disagree as to the cause of this heat stroke.
Mr. Bechler's poor health, vigorous exercise in hot, muggy weather,
severe obesity, abnormal fatty liver, untreated high blood pressure,
and enlarged heart are competent factors in and of themselves to be
causes of heat stroke. The coincidental toxicologic finding of
ephedrine, which is not known to produce heat stroke, in my opinion
should not have been linked to the death by the medical examiner just
as the medical examiner did not link the finding of the increased level
of DHEA to his death.
It is my opinion, to a reasonable degree of medical certainty,
based on all of the materials I have thus far reviewed, on my training
and on my 43 years experience as a medical examiner, that Mr. Bechler
died of a heat stroke precipitated by his morbid obesity, high blood
pressure and heart disease, adverse weather conditions, physical
exertion, and inadequate screening, monitoring and medical supervision;
that Xenadrine did not cause or contribute to Mr. Bechler's death; and
that proper and prompter treatment with intravenous fluids and cold
wraps immediately after he collapsed but was still conscious may have
prevented Mr. Bechler's death.
My opinions are subject to modification when more information,
including Fire Rescue and medical records, become available.
Yours very truly,
Michael M. Baden, M.D.
Sworn to before me this 18th day of July, 2003
JANET AMERASINGHE, LICENSE NO. 01AM4789617, QUALIFIED IN NEW YORK
COUNTY COMMISSION EXPIRES 6/30/2007
______
Metabolife Response to Committee Questions
As requested by members of the House Committee on Energy and
Commerce, Subcommittee on Oversight and Investigations in its hearing
on ephedra on July 23, 2003, Metabolife International, Inc., submits
the following supplemental written statement.
Metabolife believes that labeling is the key to informed consumer
choices. Appropriate labels can adequately inform consumers about
ephedra products and their use. There are benefits and risks that
accompany the use of all products. Consumers can make informed choices
about whether a product is right for them when they have access to
complete, accurate, and science-based information about how to use the
product safely as well as information on the product's benefits and
risks. For these reasons, Metabolife supports the FDA's proposed
labeling requirement for supplements containing ephedra.
Metabolife's label has evolved over time, in part due to changing
state law requirements. In November 1999, the Metabolife 356 label was
changed to include the language ``Exceeding recommended serving may
cause serious adverse health effects including heart attack and
stroke.'' This label change was made to comply with the requirements of
the Texas Ephedra Rule, effective November 1, 1999. (Texas
Administrative Code, Title 25, Part 1, Chapter 229, Subchapter Y, Rule
229.462(2)). Metabolife generally supported the regulatory and
legislative efforts in Texas, including a ban on the sale of ephedra
products to minors, even though, based on the best available science,
Metabolife does not believe that a causal connection has been
established between the use of its products taken as directed and
certain outcomes required to be placed on its label.
Metabolife established its consumer information line as a means for
its customers to ask general questions about the proper use of its
products and assist them with their weight loss questions. Between 1997
and 2002, only about 3 of every 100 calls pertained to health related
issues. Moreover, based on the GAO's count, only about 6 out of every
1000 of these health related calls pertained to significant health
allegations, such as stroke or heart attack. It is Metabolife's policy
to tell customers who report a negative experience with the product to
discontinue product use and consult a physician.
Employees who staff the consumer information line have been advised
that Metabolife is a dietary supplement company and not a drug company,
and that terms like ``side effect'' are not applicable to Metabolife
356 because they imply that it is a drug. This is supported by
Stedman's Medical Dictionary, 26th Edition, where the definition of
``side effect'' is: ``A result of drug or other therapy in addition to
or in extension of the desired therapeutic effect; usually but not
necessarily, connoting an undesirable effect. Although technically the
therapeutic effect carried beyond the desired limit (e.g., a hemorrhage
from an anticoagulant) is a s.e., the term more often refers to
pharmacologic results of therapy unrelated to the usual objective
(e.g., a development of signs of Cushing's syndrome with steroid
therapy).''
Metabolife supports mandatory reporting to the FDA of serious or
significant anecdotal health-related consumer complaints based on
criteria and definitions to be established by the FDA and industry that
are consistent and understandable, together with an objective standard
and appropriate method of evaluation by industry and the FDA. To this
end, in early 2002, Metabolife, through its regulatory counsel,
retained Life Sciences Research Office (``LSRO''), a private, non-
profit organization, to undertake a review of non-adverse event
reporting systems, such as Metabolife's call line, as well as existing
adverse event reporting models, and make recommendations regarding an
adverse event collection and reporting system appropriate for dietary
supplement products. LSRO was established in 1962 by the Federation of
American Societies for Experimental Biology and is known and respected
for studying fundamental problems in biomedicine, healthcare,
nutrition, food safety, and the environment, including for various
government agencies. LSRO's reports are independent in nature and
developed in a transparent process. Although the LSRO report will not
necessarily reflect the views of Metabolife on the issue, we believe
that the report, which is expected to be available in the Fall of 2003,
will be an important contribution to the development of a responsible,
reliable industry-wide reporting system.
Metabolife has provided the FDA with unredacted call records based
upon assurances under federal law that personal information will not be
made public. It is this concern for the privacy interests of its
customers that has guided the Company in dealing with requests for
production of its call records.
Metabolife has taken proactive steps to ensure that Metabolife 356
actually contains what the label says it contains. Despite the fact
that the FDA has yet to issue a final rule establishing Good
Manufacturing Practices (``GMPs'') for dietary supplements, Metabolife
has implemented quality control procedures, such as voluntary batch-
testing of each lot of ephedra-containing product, that meet or exceed
GMPs for food. Metabolife urges the FDA to require such stringent GMPs
for all manufacturers of dietary supplements. Metabolife discontinued
the inclusion of bovine complex as an ingredient in Metabolife in
approximately July 2002. Bovine complex consists of a combination of
ovary, orchic, uterus and prostate glands of a cow. This ingredient was
included in the formula because it provides beneficial amino acids.
Metabolife removed bovine complex from the Metabolife 356 formula
because of publicity surrounding issues with Mad Cow Disease in other
countries. While Metabolife continues to believe the bovine complex is
a safe and healthy addition to the formula, it was removed because it
was not an essential ingredient in the formula and removing the
ingredient would not alter the effectiveness of the product.
Among other ingredients, Metabolife 356 contains royal jelly, a
thick, milky-white, creamy liquid secreted by the hypopharyngeal glands
of nurse bees. Commonly found in dietary supplements, royal jelly is a
very rich source of proteins and contains eight essential amino acids,
carbohydrates, and beneficial lipids, including the important fatty
acids sterols and phosphorous compounds as well as acetylcholine.
During the hearing a question arose regarding Metabolife's
interaction with Dr. Heymsfield. As reflected in the FDA interview
cited below, the Company did not seek to have Dr. Heymsfield alter or
adjust scientific data concerning Metabolife 356. Dr. Heymsfield was
involved in two studies concerning ephedra dietary supplements: an
eight-week study and a six-month study. With regard to the eight week
study, Dr. Heymsfield told FDA investigators ``No requests were made to
change data or comments regarding adverse events.'' See FDA Memorandum
of Interview, Oct. 18, 2001, p. 3.
With regard to the six month study, Dr. Heymsfield ``re-iterated a
number of times that he was never requested by Metabolife to alter or
adjust data, . . .'' Id. at 8. The FDA Interview Memorandum contains a
vague allegation that ``he was encouraged (pushed) to adjust his
interpretation of the data,'' but does not explain what is meant by
this. Other portions of the Interview Memorandum indicate that he did
not have access to the relevant data to provide any interpretation of
it. According to the FDA Interview Memorandum, ``he did not see any
patients, he did not review any charts, the study results were not
shared or discussed with him and he was not a co-author of any abstract
or presentation of study results.'' See id at 4. Also, according to the
Interview Memorandum, Dr. Heymsfield indicated that he ``was not
informed of any adverse events that occurred during the second study,
and raw or summary data were not shared with or evaluated by him.'' Id.
at 5. The six-month study was supervised by the principal investigator,
Dr. Carol Boozer. The Interview Memorandum reflects that Dr. Heymsfield
stated that ``Dr. Boozer does have a lot of scientific integrity.'' See
id. at 8.
According to a Washington Post story, Dr. Heymsfield said that ``he
wouldn't hesitate to recommend a patient trying Metabolife as long as
he knew the patient didn't suffer from high blood pressure, heart
disease, or other maladies mentioned in the warning label.'' See
Charles Babcock, ``Stimulant Propels Diet Empire,'' Washington Post,
May 24, 1999, Section A.
______
Prepared Statement of the American College of Obstetricians and
Gynecologists
The American College of Obstetricians and Gynecologists and its
46,000 partners in women's health care, thanks Chairman Greenwood,
Ranking Member Deutsch, and the entire Committee for holding this
important hearing concerning ephedra and its use in dietary
supplements. As physicians dedicated to improving women's healthcare,
we are particularly concerned with the effects ephedra has on the life
and reproductive health of women. We believe that there are many
unknown risks for women, especially pregnant women, who may use these
supplements, and believe it is appropriate for Congress to seriously
consider measures to ensure the safety of products that can be bought
so easily over the counter.
Increasingly, evidence points to the serious adverse effects
associated with ephedra use. It has been reported that individuals
using these products have suffered heart attacks, strokes, seizures and
even death. Even more troubling to ACOG Fellows, is the potential for
damage to pregnant women using ephedra and the effects its use may have
on a fetus. The FDA has already stated that pregnant women should avoid
the use of dietary supplements with ephedrine alkaloids, and the
effects of these substances on fetuses are undetermined.
Women often take ephedra for weight loss although current evidence
does not support its effectiveness. Thus, they are exposing themselves
and, should they become pregnant, their fetus, to unknown effects. It
is estimated that almost 50 percent of pregnancies are unplanned, so
even if warnings are given, many women will have already used ephedra
before they know they are pregnant.
As members of the Coalition for Anabolic Steroid Precursor and
Ephedra Regulation (CASPR), we support efforts to regulate products
containing steroid precursors and products containing ephedra. Members
of CASPR include phys |