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Prepared Witness Testimony The House Committee on Energy and Commerce
Issues Relating to Ephedra-containing Dietary Supplements.
Subcommittee on Oversight and Investigations
Dr. Carlon M. Colker M.D., FACN
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®. 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®. 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®, 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® 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®, 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.
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