Millions of people rely on dietary supplements for everything from enhancing their sex lives to improving their athletic performances. There is essentially no systematic regulation of the dietary supplement industry, so there is no guarantee that a given supplement will live up to its claims. More important, there is no guarantee that any supplement is safe. At the Gatorade Sports Science Institute, we asked a panel of experts to discuss the relative safety of dietary supplements. Each of these ex‚Ē¨¬°perts—Priscilla Clarkson, PhD; Ellen Coleman, MPH, MA, RD; and Chris Rosen‚Ē¨¬°bloom, PhD, RD, LD—has authored num‚Ē¨¬°er‚Ē¨¬°ous publications and given many public presentations on various sports nutrition topics—including dietary supplements. Their comments should be carefully weighed by athletes and nonathletes alike who may be considering the use of a dietary supplement.

Which dietary supplements do you think have the most potential for harm? What is the evidence that each of them might be potentially dangerous?

Coleman: I think the riskiest of the popular supplements are herbs that contain ephe‚Ē¨¬°drine, e.g., Ma Huang (Chinese Ephedra, Ephedra Sinica), Mormon Tea and Sida Cordifolia. Ephedrine is structurally similar to the amphetamines and increases heart rate and blood pressure. The adverse effects of ephedrine range from heart attack, stroke, seizures, psychosis and death to less serious but nevertheless wor‚Ē¨¬°risome effects such as dizziness, headache, tremor, nervousness, gastrointestinal distress, irregular heartbeat and heart palpitations. In susceptible persons, serious adverse effects can occur with low doses. Combining caffeine (from coffee, Guarana or Kola nut) with ephedrine-containing products, e.g., the “ephedrine-caffeine-aspirin stack,” greatly increases the potential for adverse effects of ephedrine. Two years ago Haller and Benowitz reviewed records from 140 ephedra users who experienced complications (heart attack, stroke, seizure and death) between 1997 and 1999. The researchers found that one-third of the patients’ complications were “definitely or probably” caused by ephedra use and another third of the problems were “possibly” caused by ephedra. They noted that most of the people studied were healthy young people, some of whom had been taking ephedra for only a few days. The National Collegiate Athletic Asso‚Ē¨¬°ciation (NCAA), the International Olym‚Ē¨¬°pic Committee (IOC) and the National Football League (NFL) have banned the use of ephedrine.

Androstenedione is another risky supplement. It is a “prohormone” steroid that can be converted to testosterone and is marketed as a supplement that can increase muscle mass and strength. But these effects were not confirmed in a study by King and colleagues, who evaluated the effects of androstenedione supplementation (300 milligrams [mg] per day) in untrained men during 8 weeks of resistance training. There were no differences in serum testosterone, muscle size and strength, or body composition between the androstenedione group and the placebo group. However, the androstenedione group had decreases in HDL cholesterol and increases in serum estrogen levels, which may have adverse health consequences during long-term supplementation. The NCAA, IOC and NFL all ban androstenedione.

Yohimbine, another risky supplement, is extracted from yohimbe bark. It supposedly increases serum testosterone levels (thereby increasing muscle mass), decreases body fat and serves as an aphrodisiac; none of these effects has yet been substantiated. Reported side effects from yohimbe use include minor complaints such as headaches, anxiety and psychological tension, plus more serious effects such as high blood pressure, elevated heart rate, heart palpitations and hallucinations. Anyone who uses yohimbine should be careful to avoid all tyramine-containing foods, e.g., red wine, liver and cheese, and nasal decongestants or diet aids containing phenylpropanolamine, all of which could contribute to dangerous blood pressure fluctuations.

Clarkson: Ephedrine would be at the top of my list of popular risky supplements, too. Of the 140 adverse reactions between 1997 and 1999 that Ellen described, 10 resulted in death and 13 resulted in permanent disability. However, judging the relative risk of weight loss supplements containing the ephedrine-caffeine-aspirin stack may depend on whether or not the person is obese. This combination of drugs is a moderately effective weight loss agent because it can speed up metabolism and decrease appetite. In obese people, the risks associated with obesity possibly outweigh the risks of taking the drugs, but in some‚Ē¨¬°one who is overweight but not obese, the risk of taking these drugs almost certainly outweighs the weight loss benefits.

I also agree with Ellen that androstenedione and other so-called “prohormones” are potentially dangerous, especially if used for a prolonged period and in high doses.
Although not very popular, there are even more dangerous supplements on the market, like those that contain gamma butyrolactone (GBL), gamma hydroxybutyric acid (GHB) and 1,4 butanediol (BD). Such supplements are illegally marketed, unapproved drugs and have been associated with serious illnesses and deaths.
Rosenbloom: Products containing ephedra also concern me. Ephedra is found in at least 25 over-the-counter dietary supplements, and many of them don’t identify ephedra by name as the stimulant in the product. So, even if an athlete is aware that ephedra is a potentially dangerous substance and is banned by a sport-governing body, the athlete may not know that a product promoted to boost energy contains ephedra. And while the supplement manufacturers who do identify ephedra as an active ingredient warn athletes not to take more than the recom‚Ē¨¬°‚Ē¨¬°mended dose, the potential for overuse is great. I have heard athletes say that because they are bigger and have more lean tissue than the “average” person, they need more of a supplement to get the desired effect.

I also fear that the rising use of prohormones, especially by young athletes, will result in many adverse effects. A survey by Blue Cross and Blue Shield conducted in 2001 showed that andro‚Ē¨¬°‚Ē¨¬°‚Ē¨¬°stene‚Ē¨¬°dione, creatine and ephedra were the three most popular supplements with teenage athletes, with close to a million teens taking sports supplements.
Supplements that contain kava may also be risky. The U.S. Food and Drug Admin‚Ē¨¬°istration (FDA) recently advised consumers of the potential risk of severe liver injury associated with the use of kava-containing dietary supplements. Kava (Piper methysticum) is an herb included in supplements purported to promote relaxation, to reduce sleeplessness and to relieve menopausal symptoms. Whether or not kava actually does any of these things has not been adequately substantiated. Regulatory agencies in Europe have warned consumers about the potential risks of kava use and in some cases have removed kava-containing products from the marketplace. Kava-containing products have been associated with hepatitis, cirrhosis and liver failure in over 25 reports of adverse events in other countries. Four of these patients required liver transplants. In the United States, the FDA has received a report of a previously healthy young female who required liver transplantation, as well as several reports of liver-related injuries associated with the use of kava.

Are there some dietary supplements that are probably safe and effective if consumed according to the manufacturers’ instructions but are likely to be harmful if the consumer ingests substantially more of the products than is recommended?

Clarkson: A good example is the traditional use of vitamin and mineral supplements. While the recommended doses can improve a deficiency resulting from a poor diet, megadoses can have toxic effects. For instance, iron deficiency can negatively affect an athlete’s endurance performance, and this deficiency can be improved by taking an iron supplement, which will also improve performance. However, taking megadoses (10 times the recommended level) of iron can create imbalances in other minerals—particularly copper, because high iron intake affects copper absorption. Moreover, research has shown that high levels of iron in the body increase the risk of cardiovascular disease. Thus, taking an iron supplement for a long period of time could result in cardiovascular disease later in life.

Rosenbloom: I think creatine and protein supplements probably fit into this category, too. Creatine has been around long enough that if there were serious risks to health they should have surfaced by now. However, I would caution athletes about using more than the suggested amounts and inform them that a “loading” phase is probably not needed. It also seems likely that well-trained athletes whose protein intakes are less than about 2.8 grams (g) of protein per kilogram (kg) of body weight per day (~1.3 g/pound daily) will not harm the function of their kidneys, although higher protein intakes may. √Ē√á‚ĖĎ

Coleman: Caffeine and ginkgo biloba come to mind. Caffeine seems to improve endurance performance with minimal side effects when used in doses of 6 mg/kg (3 mg/pound) or less. Higher doses more often resulted in dizziness, headache, insomnia and gastrointestinal distress. Also, the use of doses greater than 6 mg/kg is progressively more likely to cause excretion of caffeine in the urine that would lead to a positive doping test according to the rules of the IOC, which considers urinary caffeine levels above 12 micrograms per milliliter to be evidence of doping.

Ginkgo biloba appears to be effective in treating ailments associated with decreased cerebral blood flow, particularly in older individuals. Ginkgo enhances blood flow to the brain by promoting vasodilation. For the elderly, ginkgo may improve con‚Ē¨¬°centration and memory, absent-mindedness, headaches and tinnitus (ringing in the ears). It may also aid leg circulation. Very large doses may cause restlessness, diarrhea, nausea and vomiting. Ginkgo can act as a blood thinner and may be contraindicated when an individual is using anticoagulant drugs (e.g., Coumadin or aspirin) or dietary supplements such as vitamin E or fish oil, which also have anticoagulant properties.

Do dietary supplements sometimes contain substances not listed on the package that might cause an athlete who used the supplements to fail a drug test for sport competition?

Rosenbloom: Oh yes! Trace contamination of androstenedione and norandrostenedione supplements was found in one study to be sufficient to cause positive urine tests for 19-norandrosterone. In another report, it was shown that several prohormone supplements contained substances that were not indicated on the label, and two products claiming to be “mental enhancers” contained ephedra that was not indicated on the label. And, of course, there is always the possible waste of money when purchasing supplements—some products don’t contain any active ingredients.

Coleman: I’d like to expand on Chris’s response with a few details of the studies she mentioned. Researchers from the UCLA Olympic Analytical Labora‚Ē¨¬°‚Ē¨¬°tory found that men who took either 100 or 300 mg of androstenedione for 1 week tested positive for 19-norandrosterone, a metabolic byproduct of nandrolone. The researchers also found that some brands of androstenedione were grossly mislabeled with respect to potency and purity and contained the illegal anabolic steroid, testosterone. In another report, Kamber and colleagues found different substances than indicated on the labels, including testosterone, in seven out of 17 prohormone products. In two out of seven “mental enhancer” products, the authors found caffeine and ephedrine that were not clearly declared on the labels. One pro‚Ē¨¬°duct contained a high enough concentration of ephedrine that an athlete would fail a doping test if only one capsule was consumed just before competition.

Clarkson: Because dietary supplements are not regulated by the FDA, there is no guarantee that what is stated on the label is actually in the supplement. In addition to the scientific articles mentioned by Chris and Ellen, there are many other anecdotal reports in which athletes who have tested positive for drugs claimed that the banned substance was not listed on the label of a supposedly legal supplement they had been using.

What tips do you have for increasing the confidence of the consumer that a given dietary supplement actually contains the appropriate amounts of the ingredients listed on the package and only those ingredients?

Coleman: The USP (United States Pharmacopoeia) designation on the label of a vitamin/mineral supplement indicates that the product passes tests for dissolution, disintegration, potency and purity. Nationally known food and drug manufacturers generally make supplements under the strict quality control procedures they already have in place. Supplement Watch (www.supplementwatch.com) and Consumer Lab (www.consumerlab.com) provide independent test results and information to help people evaluate and select dietary supplements. Products that pass Consumer Lab’s testing are eligible to bear the CL Seal of Approval.

Clarkson: The more reputable the company, the more likely the supplement contains what it is purported to contain. Still, there is no guarantee.
Rosenbloom: I think Ellen’s advice to check the Consumer Lab evaluation is on target, but as Priscilla suggested, athletes should know it is a “buyer beware” market when it comes to supplements.

Priscilla Clarkson, PhD, FACSM, is professor of exercise science at the University of Massachusetts in Amherst, Massachusetts.
Ellen Coleman, MPH, MA, RD, is a sports nutritionist at The Sports Clinic in Riverside, California.
Christine Rosenbloom, PhD, RD, LD, is associate professor of nutrition at Georgia State University in Atlanta, Georgia.

Editor’s Note: This article was excerpted with permission from the Gatorade Sports Science Institute’s Sports Science Exchange Roundtable 48 (Vol. 13 [2002], No. 2).