Docket Management
Docket: 95N-0304 - Dietary Supplements Containing Ephedrine Alkaloids
Comment Number: EC -948

Accepted - Volume 322

Comment Record
Commentor Dr. Marcellino D'Ambrosio Date/Time 2003-03-29 18:06:48
Organization Wellness Opportunities DFW
Category Dietary Supplement Industry

Comments for FDA General
Questions
1. General Comments Dear FDA officials, Following unsubstantiated and sensationalistic reports in the press attributing the tragic death of a baseball player to ephedra, we've seen many calling on the FDA to ban the sale of ephedra products (appended below is the opinion of the sports medicine faculty at Baylor regarding these allegations). Banning the sale of a substance that has been used continuously for 4,000 years and has been sold legally everywhere in the US up till now is a very drastic step. It would seem to me that such a step could be taken only if it were based on absolutely irrefutable scientific data. The problem is that there is absolutely no hard scientific data proving that ephedra products, when used as directed, have any harmful consequences at all for healthy people. In fact, the exact opposite is true. Studies by Columbia and Harvard researchers, (see www.ephedrafacts.com ) among others have shown that moderate amounts of ephedra especially when combined with moderate amounts of caffeine have extraordinary ability to help people lose excess body fat while retaining lean body mass. Obesity is the most serious health problem in the nation today with the Center for Disease Control calling it an epidemic, killing over 300,000 Americans last year alone. For the past five years, I and my wife have used a pharmaceutical grade supplement containing ephedra with superb results (BioLean, from Wellness International Network). The first three months of using this product, I lost 18 lbs which was 10% of my body weight, losing 2 inches off my waist. I've kept that weight off ever since. Besides impressive loss of body fat, the side effects of using this supplement for me, my family, and many others, have been positive--better blood lipids, enhanced energy levels, increased ability to build lean muscle mass, lower and more even blood glucose levels, relief from allergy and sinus problems. We've seen absolutely no serious adverse effects with this particular ephedra product. The reason for this is that we follow the very clear instructions on the label and discourage people from using BioLean who have a medical condition, such as hypertension, that contraindicates ephedra use. I have personally introduced this ephedra product as well as other Wellness International dietary supplements to countless people over the past four years, helping individuals lose as much as 115 lbs and keep it off. In fact much of my professional work over the past four years has been helping physicians integrate effective weight management into their practice using BioLean and other natural supplements. The results have been stellar. Are there some people who should not use ephedra supplements? Absolutely. Are there people who should not use alcohol? Absolutely. But is that reason to ban sales of alcohol? Alcoholism takes the lives of millions annually. So does tobacco. This is proven, unquestionable. Why not ban these substances? It is not simply my opinion that the case against ephedra is unproven. Rather, that is the judgment of the General Accounting Office of Congress who told the FDA that the reports of ephedra causing serious adverse effects and even death were unsubstantiated. Of all reported deaths reported, only about 10 of them appear to be remotely connected with ephedra use. Compare that with 450 deaths and over 20,000 hospitalizations last year due to acetaminophen, which is very toxic to the liver (news item appended below). Or the 100,000 deaths last year from pharmaceutical drugs (as reported in the Journal of the American Medical Association). There is an ancient Roman proverb that says abusus non tollit usus (the abuse of a thing does not take away from its [legitimate] use). By all means as Federal Regulators, it is your responsibility to prevent ephedra misuse. Proper labeling requirements to list contraindications, alert people to possible adverse effects, restrict sales to minors, etc are all very sensible proposals. Some companies, such as Wellness International, already have such labeling in place even in absence of federal regulations. But banning all products containing this substance is an irrational and indefensible move that restricts consumers rights to products that have demonstrable health benefits. I would be happy to speak to anyone from any government agency who has questions about this matter. I can be reached at 817.410.9009 x305. Thank you. Sincerely, Marcellino D'Ambrosio, Ph.D. Adjunct Professor of Theology and Ethics The International Catholic University, South Bend Indiana Co-founder of Wellness Opportunities DFW 121 Business Center, Suite 300 3801 William D. Tate Grapevine, TX 76051 817.410.9009 x305 FDA Advisors Back Stronger Acetaminophen Warning Fri Sep 20,10:25 AM ET By Ori Twersky WASHINGTON (Reuters Health) - Advisors to the US Food and Drug Administration ( news - web sites) (FDA) urged the agency on Thursday to require a stronger warning on acetaminophen product packaging to stress that misuse of the popular pain reliever can lead to liver toxicity. Acetaminophen is found in Tylenol, but is also in almost 200 different products, including cold and flu remedies. Taken by about 100 million Americans a year, acetaminophen is the most widely used nonprescription drug in the US. The FDA's Nonprescription Drugs Advisory Committee expressed almost unanimous support for an immediate change to the drug's labeling, citing concerns about consumers who use the product inappropriately. The FDA convened Thursday's advisory panel as part of an ongoing review of over-the-counter drugs that began in 1988. On Friday, the panel will consider whether warnings on other popular nonprescription pain relievers, including ibuprofen, provide adequate information about possible gastrointestinal side effects. US regulators have discussed and debated acetaminophen's possible liver toxicity since 1977. The purpose of Thursday's meeting was to revisit the issue in light of recent data suggesting that additional measures might be needed to prevent unintentional overdoses. Overdoses are the most often cited cause of acetaminophen-associated liver toxicity. According to federal figures, acetaminophen overdoses lead to about 56,000 emergency room visits, 26,000 hospitalizations and 450 deaths a year. Although the majority of the events are suicide-related, FDA officials said during Thursday's meeting that about 13,000 of the emergency room visits, 2,200 of the hospitalizations and 100 of the deaths are apparently unintentional. Causes include inadvertent use of multiple acetaminophen-containing products at the same time and the misinformed belief that larger doses will lead to faster relief, the FDA officials said. Advisory panel members recommended adoption of a label that more clearly outlines the possible effects of an overdose and points out the presence of acetaminophen in products such as cough and cold medications. We don't want to make Tylenol look like a dangerous drug, said panel member Dr. Nathaniel Katz, an anesthesiologist in New Rochelle, New York. Still, it seems to me that someone buying something in the supermarket should know what's in it. The FDA is not required to follow its advisors' recommendations, but it often does so. If the agency does require stronger labels, it will have the support of some industry members. McNeil Consumer, the Johnson & Johnson subsidiary that makes Tylenol, already has proposed the adoption of a label cautioning that inappropriate use could lead to liver toxicity. McNeil Vice President Dr. Anthony R. Temple told Reuters Health the firm has been encouraging other manufacturers to adopt the new label on a voluntary basis. It would certainly help if the FDA finalized a rule, he said. But both McNeil and the FDA stressed that unintentional overdoses and liver toxicity are rare events given the number of users of acetaminophen. The agency continues to believe that acetaminophen is a safe and effective OTC analgesic that benefits tens of millions of consumers every year, the FDA said. The Alleged Role of Ephedra in the Death of a Professional Baseball Player http://www3.baylor.edu/HHPR/ESNL/EphedraStatement.htm Richard B. Kreider, Ph.D., FACSM, EPC, FASEP Mike Greenwood, PhD, CSCS*D Lori Greenwood, PhD, ATC, LAT Exercise & Sport Nutrition Lab Center for Exercise, Nutrition & Preventive Health Research Baylor University February 21, 2003 As active researchers in the area of exercise physiology, sport nutrition, strength and conditioning, and sports medicine, we would like to make the following comment and observations regarding the current controversy about the supposed link of ephedra supplementation to the tragic death of Baltimore Orioles pitcher Steve Bechler due to multiple organ failure, as a result of heat stroke, on Feb.17, 2003. Heat stroke fatalities are preventable if proper screening, conditioning, acclimatization, and precautions are employed to ensure that athletes train safely in hot and humid environments. The local coroner and members of Orioles management have suggested that Mr. Bechler’s death was related and/or caused by the possible consumption of a dietary supplement containing the herb ephedra. These reports have caused a flurry of reports in the media questioning the safety of ephedra supplementation and calls to ban the use of ephedra in Major League Baseball and/or sale of ephedra in over the counter dietary supplements. At this point, toxicology reports have yet to confirm that Mr. Bechler had taken an ephedra supplement prior to practice. Clinical studies published in peer-reviewed journals have indicated that ephedrine and herbal ephedra supplementation can significantly promote weight loss with no major side effects in overweight but otherwise healthy individuals. There is also evidence that taking ephedra and caffeine during training may help promote greater fat loss. Most studies show that ephedra or ephedrine has no ergogenic benefit in and of itself. Claims that ephedra is a “performance enhancing substance” is not supported by the scientific literature. However, there is data showing that caffeine has ergogenic value and that there may be some ergogenic value of ingesting supplements that have ephedra and caffeine. Many over-the-counter medications (e.g., cold medications) contain ephedrine alkaloids (e.g., pseudoephedrine, etc.) at higher concentrations than found in nutritional supplements containing ephedra. Closer examination of contributing factors related to Mr. Bechler’s death reveals that even if Mr. Bechler did consume the supplement, it was probably the least of the contributing factors leading to his death—and it may not have been a factor at all. According to reports in the media, Mr. Bechler had the following risk factors for heat stroke: a prior history of heat illness episodes while in high school - which heightens the probability of reoccurring incidents; a family history of sudden death following exercise (his half-brother died of an aneurysm at the age of 20 after overheating from playing baseball); a history of hypertension and liver problems; he had not eaten solid food for a day or two, in an apparent attempt to lose weight; he was apparently not adequately acclimatized to training in the heat and humidity of South Florida; it appeared that he was wearing two or three layers of clothing during workouts, again, in an attempt to lose weight; he was overweight and did not have a high enough fitness level to make it through conditioning drills; and, he was allowed to exercise until he collapsed with a core temperature reportedly of 106° F before being removed from the field. It has been extensively documented that untrained, overweight, and unacclimatized people who perform excessive exercise in heat/humidity are at great risk of heat illness and heat stroke—particularly if they have become dehydrated and are trying to lose weight quickly. These pre-existing conditions raise serious questions as to the appropriate medical screening, conditioning, and supervision of Mr. Bechler participating in spring conditioning drills as follows: Were team athletic trainers and conditioning specialists aware of Mr. Bechler’s prior history of heat illness or stroke? If they were aware, why weren’t additional exercise precautions taken to ensure that he was adequately trained, acclimatized, hydrated, and fed prior to his participation in intense conditioning drills? Media reports indicate that Mr. Bechler had a prior history of reporting to camp overweight and out of shape. If this is the case, was Mr. Bechler given appropriate training and dietary counseling and/or placed on a pre-camp conditioning and nutrition program to make sure he reported in good condition? Excess body fat is a major liability when exercising in hot/humid climates because it increases the insulation properties of the body which in turn reduces the amount of body heat that can be released through perspiration. Fatal heat strokes occur 3.5 more times in obese populations than any other population. Why didn’t pre-participation medical screening identify the risk factors to heat stroke described above? Complete pre-participation exercise stress tests and/or fitness/sprint tests would have indicated that Mr. Bechler was not in sufficient physical condition to perform intense training. Further, that he was not adequately acclimatized to exercise in the heat. According to media reports, Orioles coaches knew that his conditioning was “not good”. If this is the case, then how was he allowed to participate in intense conditioning training? Medical screening should have also revealed a history of hypertension and liver problems. These are all contraindications to performing excessive exercise particularly in hot/humid environments. Where was the supervision to notice signs of heat illness in Mr. Bechler? Media reports indicate that he was dizzy, he was only able to perform 60% of the conditioning drills, and that he collapsed on the field. These are all signs and symptoms of heat intolerance and/or heat illness. It is the responsibility of athletic trainers and strength and conditioning specialists to make sure that athletes safely engage in physical activity. If athletes are showing signs of abnormal responses to exercise, it is the responsibility of coaches, team physicians, athletic trainers and/or strength and conditioning specialists to pull the athlete out of conditioning drills – not the athletes. Did the athletic trainers, team physicians, and/or strength and conditioning specialists know that Mr. Bechler evidently was not eating solid food? Training camp is not an appropriate time for athletes to diet. Allowing athletes to train when they are dehydrated and/or not well fed is dangerous. Athletes who report to camp overweight should be given proper nutritional counseling about safe and effective ways to lose weight. Team physicians , athletic trainers, and strength and conditioning coaches should know what supplements athletes are taking so they can counsel them about whether or not they are safe, legal, effective, and/or appropriate to take at a given time during training. In this case, a supplement bottle was purportedly found in Mr. Belcher’s locker yet team officials were supposedly unaware of him taking supplements. This is troubling given that he had pre-existing medical conditions that were contraindicated for use of the purported supplement. The supposed link that ephedra supplementation caused or contributed to heat stroke does not make sense from a physiological standpoint for the following reasons: Some of Mr. Bechler’s teammates claimed that he usually took three supplement capsules (1.5 servings) in the morning. According to that product’s label, that would have provided 30 mg of herbal ephedra. This is one third of the dose shown in long-term clinical trials to be safe. There is no scientific or medical evidence to indicate that ephedra/caffeine supplementation significantly increases thermal stress (increases core temperature 2-3 degrees above normal) during exercise, that it promotes dehydration, or increases the incidence of heat illness. The thermogenic effects of ephedra and caffeine are relatively small, typically increasing resting caloric expenditure by 5-10 kcals per hour. One oral dose of ephedra/caffeine usually lasts less than 3 hours. Therefore, the total caloric (i.e., heat) load would be 15 – 30 calories in a 2-3 hour period following ingestion of one serving of an ephedra containing supplement. While this may be sufficient to promote a gradual weight loss (if one took 2-3 servings per day for 2-6 months), it would have minimal, if any, affects of core body temperature. In contrast, athletes commonly expend 600-1,200 kcals per hour during intense exercise or 1,800 – 3,600 calories during an intense 3 hour practice. The thermal load of exercise generally increases core body temperature by 2-3 degrees when properly regulated. The primary way heat from exercise is dissipated is through evaporation of sweat. Exercise in humid environments decreases the ability of sweat to evaporate making it more difficult to regulate body temperature. When the humidity is very high (i.e., > 70%), sweat may not fully evaporate which increases susceptibility to heat disorders. Humidity is higher in morning and evening hours. This is the primary rationale why intense exercise should be avoided during humid conditions and/or additional precautions should be employed to supervise athletes training or performing in hot/humid environments. The media scare linking Mr. Bechler’s heatstroke death with ephedra places emphasis on the unknown (pending toxicology results), and ignores known and obvious contributing factors already detailed here. Unfortunately, these media reports may mislead some to conclude that simply prohibiting athletes from taking ephedra supplements will eliminate the risk of heat fatalities. Instead, we should be stressing the importance of properly educating athletes, coaches and athletic trainers about the risks of training in hot and humid environments when participants are poorly conditioned, have not acclimatized to the heat and humidity, have engaged in dehydration practices, have medical histories that should have raised warning flags, and have not been sufficiently supervised. It seems that Major League Baseball and others want to blame ephedra for the death of Mr. Bechler, rather than admit that they may have been negligent in screening, conditioning, and supervising their athletes. The tragedy is that if Mr. Bechler had been properly screened and conditioned; if he had acclimatized properly to high heat and humidity conditions; if he had been adequately supervised; and if he had been properly educated about diet, weight loss, and the use of dietary supplements, he may be alive today. In our view, this is another example of poor supervision and screening of athletes and not an issue of inappropriate use of a dietary supplement. Tips to Prevent Heat Illness and Stroke in Athletes Conduct a comprehensive medical examination to examine past history and risk factors to heat illness. Make sure the athlete is adequately trained to participate in high intensity exercise prior to the start of conditioning. Acclimatize the athlete to training in hot/humid environments by beginning with brief and low intensity exercise sessions and progressing up to longer and more intense training sessions during the first few days of training. Make sure the athlete is eating a healthy and nutritious diet and is well-hydrated prior to the start of each practice. Monitor ambient environmental conditions (temperature, humidity, heat index, etc) and adjust workout intensity, duration, and frequency as necessary to reduce risk to athletes. Monitor pre- and post practice weight changes. Ingest 3 cups of water or sports drink for every pound lost during practice. Do not allow athletes who lost more than 3% of their body weight to practice again until their weight is up to acceptable ranges. Do not allow athletes to wear excessive clothing which can impede sweat evaporation and therefore reduce cooling. Provide frequent and planned water/sports drink breaks during practice. Ensure that the athlete drinks 1-2 cups of water or sports drink every 15-20 minutes during exercise in the heat/humidity. Watch for signs of heat illness including cramping, dry mouth, fatigue, dizziness, loss of concentration, palor, vomiting, cessation of sweating, dry and hot skin, and inability to maintain exercise workloads. Do not excessively train athletes in hot/humid environments. The higher the intensity of training, the greater amount of heat produced. This means that if it is very hot/humid, practices should be rescheduled and/or involve less intense training. Athletes should be pulled from conditioning drills if they are unable to perform them and not allowed to train until they collapse. Provide appropriate medical supervision at a supervisor to athlete ratio that will allow signs and symptoms of heat illness to be immediately recognized. Provide prompt medical care when signs are observed of abnormal responses to exercise in the heat. Have emergency procedures well defined so that prompt medical attention can be provided in the event heat illness is observed. Prof. Richard Kreider, a specialist in exercise physiology and sport nutrition, is chairman of the Department of Health, Human Performance and Recreation at Baylor University. He founded the Exercise & Sport Nutrition Lab, the Center for Exercise, Nutrition, and Preventive Health Research, and is president of the American Society of Exercise Physiologists. Prof. Mike Greenwood, a specialist in strength and conditioning and former NCAA Division I Baseball Coach, is Professor of Musculoskeletal Physiology and Nutrition in the Department of Health, Human Performance and Recreation at Baylor University. Prof. Lori Greenwood, a certified athletic trainer and sports medicine specialist, is Associate Professor and Director of the Graduate Athletic Training and Sports Medicine Program in the Department of Health, Human Performance and Recreation at Baylor University.




EC -948