Medications Legal Performance Enhancing Agents
| 05 August 2009
More than ever before, young high school and college athletes are being pressured to excel in sports. The combination of peer pressure, future financial rewards, and aggressive marketing has created significant interest in the use of performance enhancing substances in young athletes looking for that “extra edge” in their sport.
When sports heroes such as Mark McGwire, Shannon Sharpe and Dante Bichette publicly support the use of agents such as creatine (and androstenedione in McGwire’s case), everyone takes notice. These substances are touted by the manufacturers as being safe, legal, and effective. When patients ask for advice on these agents, we need to be well informed; otherwise they will obtain their information from other (usually less-reliable) sources. The most obvious questions to be answered are how safe and how effective are they?
One might also wonder why some of these substances are “legal” ie. can be obtained without a prescription. The FDA was mandated by the federal Food, Drug, and Cosmetic Act of 1938 to insure the safety and efficacy of prescription drugs. In following the FDA’s regulations, drug manufacturers are required to prove the safety and efficacy of the drug before marketing the drug.
In 1994, an interesting turn of events occurred. The health-food industry spearheaded a bill called the Dietary Supplement Health and Education Act 0f 1994 (DSHEA) which altered the FDA’s ability to regulate products listed as “dietary supplements”. The result was that hundreds of previously restricted substances such as steroid precursors and creatine became available over the counter. Under these new regulations, any “natural” substance can be marketed as a dietary supplement with claims that it improves health. Scientific studies indicating efficacy and safety are not necessary for dietary supplements. DSHEA approaches safety for dietary supplements in a manner completely opposite to that of FDA drug approval. The burden of proof is on the FDA to prove that a product is unsafe before it can be removed from the marketplace.
Regulations such as this are good for business, but not good for ensuring safe supplements. There are now over 600 dietary supplement manufacturers in the United States, producing over 4,000 products with sales in excess of 4 billion dollars. The FDA is clearly not capable of monitoring this volume of substances. Therefore, the ultimate responsibility for the safety of these products is now in the hands of the consumer. BUYER BEWARE!! Now more than ever, we need to be able to make informed decisions regarding the use of dietary supplements.
Performance-enhancing substances can be categorized into 4 different types, based on their effects on the body:
1) Stimulants- ephedrine, caffeine, ginseng.
2) Hormone enhancing- DHEA, tribulus, androstenedione, norandrostenedione
3) Amino acids and proteins- creatine, whey protein, lysine, arginine, ornithine.
4) Vitamins and Minerals- chromium picolinate.
Each of these substances need to be evaluated individually in terms of risks vs. benefits. In this article, we will focus our attention on creatine and androstenedione ---two substances which have been in the press recently due to Mark McGwire’s claims of performance enhancement with these agents.
Creatine
General- Creatine is an amino acid which serves as the phosphate donor in the phosphorylation of ADP to ATP. The normal daily requirement of creatine is about 2 g, half of which is obtained through a normal diet, the rest synthesized in the liver, pancreas, and kidneys. 95% of the creatine is stored in skeletal muscle, with a total pool of about 120 g in a 70 kg individual.
Typical Dosage-20-25 g/d for 5-7 d then 2-25 g/d thereafter.
Cost- $5 - $60 / month depending on dose and supplier.
Proposed Mechanism of Action- Consuming the above dose results in 15-30% increase in total creatine. Increased creatine pool results in increased ATP synthesis. Note- 20-30% of individuals do not respond to creatine supplementation.
Effects on Performance- No improvements in aerobic fitness. Benefits are only seen in high intensity, intermittent activities. Over 25 studies have been done, with the vast majority showing improvements in strength, power, and sprint performance of 5 - 15%. Improvements in performance are most likely due to a combination of better metabolic efficiency and enhanced quality of training.
Adverse Effects- There are no long term ( > one year) studies available. Current studies have not demonstrated any adverse effects other than weight gain and dehydration with short term use (under 4 weeks) in young healthy athletes. Anecdotal reports include rash, muscle cramping, dyspnea, vomiting, diarrhea, anxiety, fatigue, migraine, myopathy, polymyositis, seizures, and atrial fibrillation. No long term studies have been done.
Frequency of Use- NCAA poll indicates over 30% of college athletes use it. A players poll estimates 60% of Major League baseball players use it.
Legal Issues- Non-prescription. Not FDA approved. Not banned by International Olympic Committee or any other athletic association. American College of Sports Medicine has no position papers on creatine but calls for further research.
Androstenedione (Andro)
General- Androstenedione is an androgen, normally produced by the gonads and adrenal glands in small amounts. It has little intrinsic activity, but is converted to testosterone and has therefore been termed a “prohormone” by manufacturers. Commercially, it is derived from either meat products or pine pollen and is advertised as being legal and natural.
Typical Dosage- Manufacturers recommend 50mg BID. Many athletes consume much higher doses. It is common practice to use along with other types of steroids (termed stacking).
Cost- $20 - $90 / month depending on dose and supplier.
Mechanism of Action- Converted to testosterone in the liver. One 100mg dose has been shown to elevate blood testosterone 200-600%. Elevated testosterone results in an anabolic state with increases in lean body mass, nitrogen retention, and muscle growth.
Effects on Performance- No studies are available for androstenedione. The conclusion of the American College of Sports Medicine is that the use of anabolic androgenic steroids by experienced weight lifters often results in strength gains and increases in lean body mass. The improvements are usually small. No improvements in aerobic fitness have been shown.
Adverse Effects- No studies are available for androstenedione. Common sense dictates they should be the same as for other anabolic steroids which increase testosterone levels. These include numerous effects on the liver, cardiovascular and reproductive systems. The most serious include peliosis hepatis, liver tumors, and possible prostatic cancer risk. In children, early closure of growth plates is a concern.
Frequency of Use- Unknown, but sales are around $5 million / year.
Legal Issues-Non prescription. Not FDA approved. Banned by International Olympic Committee, NCAA, NFL, but not by Major League Baseball, the National Basketball Association, or the National Hockey League.
Conclusion
Based on available literature, both creatine and androstenedione both seem to improve anaerobic sports performance by different mechanisms in certain situations. The most significant factor is most likely enhanced strength training which leads to increased strength and power. There are no aerobic improvements with either agent. Based on this information alone, many athletes will choose to supplement with one or both of these agents in spite of the risks involved. As physicians, the best approach in dealing with athletes is not to be judgmental, but rather be a source of reliable information, and let the athlete make their own decision. Some issues to discuss openly with our patients include:
1) Androstenedione has many more known risks than does creatine. It is currently banned by most athletic organizations, and will likely be banned by all in the future. This is an anabolic steroid.
2) East German athletes have been using androstenedione since the 1980's, some are suing their coaches and doctors over long- term side effects.
3) Currently, minimal adverse effects have been reported with creatine, but no long term studies have been done. If athletes elect to use it, they will be the guinea pigs.
4) Remind patients, “natural” does not mean safe.
5) The benefits from either agent is minimal—so unless there is an obvious and important reason to improve performance by a small amount, the risks outweighs the benefits.
6) If an athlete elects to use these agents, they need closer medical surveillance with more frequent routine check-ups, lab work, prostate exams, etc.
7) Remind athletes that 99% of their performance is related to natural ability and training, and not supplements.
8) At least 3 college wrestlers have died using creatine–most likely due to dehydration.
9) The truth is that nobody knows the long term effects of taking these substances.
10) The purity of most of these dietary substances is not monitored, and can be quite variable.
References
Kreider, R.B. Creatine supplementation: analysis of ergogenic value, medical safety, and concerns, Journal of Exercise Physiology, April, 1998.
Schnirring, L., Androstenedione et al: Nonprescription Steroids, The Physician and Sportsmedicine, vol 26, No. 11 Nov. 1998.
The Medical Letter, November 6, 1998, Creatine and Androstenedione–two “Dietary Supplements”.
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