Supplements and athletes.

Annotation: No sports medicine-related subject has received more global press than dietary supplements in athletes. From the male and female high school sports, to the Olympic field and professional baseball diamond, our athletes have a problem. Long a recognized national authority on the subject of dietary supplements, Dr. Lombardo capsules current 2004 concepts.

**********

Background

Historically, supplements referred to dietary supplements which added one or more of the six essential nutrients, vitamins, minerals, carbohydrates, fats, proteins, and water to an individual's diet from a source other than food. In past times, vitamins and minerals were the most popular supplements. Most people who are presently in their fourth or fifth decade can remember the "B12 shots" and "Geritol" for fatigue, the "One-A-Day multiple vitamin", and the other popular uses of vitamins and mineral supplements in the 1950s through 70s. Athletes were not any different from the general population when it came to supplements. In addition, however, athletes desire to "get an edge" in their sports and games, and attain an advantage over their competitors. Protein powders and liquid protein, carbohydrate drinks and carbohydrate loading, rehydration products with minerals and carbohydrates in the form of sucrose and fructose, all have been introduced to the marketplace, often with athletes and obese individuals as their primary targets.

In 1994, the Dietary Supplement Health and Education Act became law. The aim of this act was to remove the obstacles presented by the regulatory control of the Food and Drug Administration (FDA) from the development and distribution of "natural" substances which could aid in the attainment and maintenance of health by Congress' constituents, the citizens of the United States. This law effectively removed supplements from the authority of the FDA, eliminated the need for research by the developer or distributor to prove the efficacy or safety of supplements, and failed to require that an independent agency be responsible for the certification of either a supplements' purity, or the amounts of the various listed ingredients that are actually present in that supplement. This is a problem for athletes who participate in sports leagues or events in which strict liability (athlete is responsible for what is in his/her body) drug programs/testing are present. Finally, the law includes plants, herbs, and their extracts. This is important in that the chemically active ingredient need not be extracted from the plant or herb, but can be synthesized in a lab, as long as it is present in a plant or herb. So are these substances really "natural"?

Two classes of supplements will be discussed in this article: anabolic agents and stimulants. These are the two classes of supplements that are predominantly used by athletes to aid in performance.

Anabolic Agents

Anabolic agents are substances that aid in the development of muscle. Anabolic means tissue-building. Dehydroepiandrosterone (DHEA) and androstenedione are precursors of testosterone that have anabolic activity. Creatine is a popular "muscle-building" substance which has become popular among athletes. For years various protein drinks, powders, and pills have been consumed by athletes to help them grow "bigger and stronger", to aid in the attainment of their ultimate goal, athletic success. Do these substances help as advertised, or is it more marketing fiction than fact?

Precursors of testosterone

Testosterone is produced in the body via a metabolic pathway, which has DHEA two steps from testosterone, and androstenedione one step from testosterone. Testosterone is a controlled drug. The distribution of testosterone is controlled and tracked by the US Drug Enforcement Administration. In many states, a physician's license is at risk for improperly prescribing testosterone or its analogs. However, DHEA and androstenedione, precursors of testosterone, which can increase testosterone levels in the body, are uncontrolled supplements. The studies which have been performed on DHEA and androstenedione have not been consistent in their results. Some have shown increases in testosterone and positive anabolic effects, while others have not. This is not unlike the contradictory studies which were performed on testosterone and the other anabolic steroids years ago. The adverse effects of lowering high-density lipoprotein-cholesterol, acne, and gynecomastia are seen with the precursors of testosterone. The testosterone/epitestosterone ratio, which is used in drug testing for identifying those who use testosterone for performance enhancement, is elevated with the use of DHEA and androstenedione. The World Anti-Doping Agency (WADA) and its US counterpart (USADA), the National Football League, and the National Collegiate Athletic Association (NCAA) ban these precursors of testosterone. It is important to remember that DHEA and androstenedione are supplements that are not controlled or certified for purity by any independent agency.

Creatine

Creatine is an amino acid which is synthesized in the kidneys and liver from 3 amino acids: glycine, arginine, and methionine. Creatine is also present in the diet with the consumption of meats and fish. Ninety-five percent of the body's creatine is stored in skeletal muscle. With short-burst, high-intensity activity, adenosine triphosphate (ATP) is the energy source for muscular work. The ATP loses a phosphate, becoming adenosine 5'-diphosphate (ADP), and energy is produced. To return to ATP, the phosphate is stored in the muscle as creatine phosphate (CrP). The more creatine in the muscle, the more CrP is present, and the more efficient the regeneration of ATP from ADP, resulting in more energy. This theoretically would result in an increase in performance in repetitive, short-burst, high-intensity activity. This has been the case in most studies. There is an increase in lean body mass with creatine use in most studies. No studies have shown an increase in endurance with creatine use. Adverse effects include dehydration in hot, humid environments, which may occur if care is not taken to maintain hydration. If dehydration could be a problem, one may stop the supplement in these environmental conditions, or ensure that proper hydration is maintained. Potential or theoretical adverse effects include gastrointestinal cramping and diarrhea, increase in muscle strains, liver or renal damage, but none of these have been substantiated. Many dosage regimens have been proposed, with one of the more popular being 20 g per day (5 g, 4 times per day) for 1 week, and then 2 to 5 g per day for maintenance. WADA/USADA, NFL and NCAA do not ban creatine. However, it is important to remember that creatine is a supplement that is not controlled or certified for purity by any independent agency.

Proteins

Proteins have long been known as the building blocks of muscle. Protein and amino acid supplementation has been a mainstay in the training programs of athletes for many years. There have been many studies performed on the effects on strength production of proteins and various amino acids. A few have shown some benefit with high-intensity work, but more have shown no effect. The fact that athletes have protein requirements greater than the recommended daily allowance of 0.8 g/kg has been shown. The only adverse effects of proteins and amino acids are theoretical, eg, renal damage due to overload. Protein supplements are not banned by any organization, but are also not controlled or certified for purity.

Stimulants

Stimulants are used by athletes for two reasons: to give energy, thereby fighting fatigue, and as an aid in weight loss. All stimulants when taken in a fatigued state will help an individual perform better, regardless of the task. Mental and physical tasks have both been shown to improve with the use of a stimulant when the individual is fatigued. The supplements that are stimulants to be discussed contain ephedrine, synephrine, and caffeine.

Ephedrine

Ephedrine is a sympathomimetic amine that is found naturally in Ma Huang, Sida Cordifolia, and about 40 other species of plants. Ephedrine is not a "selective stimulant", so it will exert stimulating effects on all tissue which has receptors for it. This includes the nervous system and cardiovascular system. The actions of ephedrine that are desired by athletes include increased alertness, "energy boost", assistance in weight loss, and the all-inclusive enhancement of athletic performance. Since ephedrine is a stimulant, it will combat fatigue and allow for improvement of performance when an individual is in a fatigued state. When one is not fatigued, the effects are not known. There are adverse effects associated with its use. The two main systems affected by ephedrine are the cardiovascular and neurologic. The cardiovascular effects include elevated blood pressure, cardiac arrhythmias, strokes, and myocardial infarctions. Neurologically, the effects include seizures, tremors, insomnia, irritability, and headaches. There have been a number of deaths reported that were temporally related to the use of ephedrine. Another problem with all stimulants is dependence. When a person regularly uses a stimulant, the normal state becomes the stimulated state. When the stimulant is not taken, the person does not feel "right" or "normal". Caffeine and the daily cup of coffee is the best example of this dependence. WADA/USADA, NFL, and NCAA ban ephedrine. The FDA has recently banned ephedrine. That ban will take effect this year (2004).

Synephrine

Synephrine is a sympathomimetic amine that is also found naturally in Citrus aurantium. Popularly known as bitter orange, it is known as zhi shi in traditional Chinese medicine. Synephrine is more selective than ephedrine in its stimulating effects, and does not carry the cardiovascular and extreme neurologic negative actions of ephedrine. The effects desired by athletes are similar to those for ephedrine: increased alertness, combating fatigue, increasing metabolic rate for weight loss, and overall for increasing energy levels. Synephrine is considered a mild stimulant and has been reported to have minimal to no cardiovascular side effects, and fewer neurologic problems. WADA/USADA and NCAA ban synephrine. As with all other supplements, the concern for levels of ingredients present in the supplement and purity of the supplement is applicable to synephrine, as with all supplements.

Caffeine

Caffeine is a trimethylxanthine and has stimulant properties. Caffeine is found in coffee, tea, and soda drinks such as colas and Mountain Dew. A similar substance, guaranine, is found naturally in the guarana plant. The desired effects of caffeine include fighting fatigue, increased energy levels, and increases in metabolism of fatty acids, elevated metabolic rate, and increasing force of muscle contraction. The stimulant effects of caffeine will make it effective for enhancing performance in a fatigued state. The increased metabolism of free fatty acids has been proven and is useful in endurance events. Adverse effects of caffeine include cardiac arrhythmias (usually supraventricular in origin), insomnia, tremors, and headache. The potential for developing dependence to stimulants is especially true for caffeine. There are many people who cannot function until they have had their coffee in the morning. Again, the normal state has become the caffeinated state. WADA/USADA and NCAA ban caffeine above a cutoff level. This level is reached when 800 to 1,000 mg of caffeine is ingested. When caffeine is included as one ingredient of a multi-ingredient supplement, the concern remains for the level of the caffeine, and purity of the supplement.

Vitamins and minerals

Historically, the dietitians and nutritionists have taught that there is not a need in the United States to supplement one's dietary intake of vitamins and minerals. Avoidance of deficiency states was the goal when it came to these essential nutrients. There was no advantage to ingesting larger-than-necessary amounts, other than to produce "expensive urine". There have been those who argue that increased levels of some of the vitamins and minerals result in more optimal function and enhanced performance. These beliefs have not been substantiated in the literature. Diets that limit the food intake from one or more of the nutrient groups--low carbohydrate, low fat, etc--can affect the amount of vitamins and minerals available from dietary sources. These diets all suggest the addition of vitamins and minerals to be certain that the appropriate amounts of these are present. The trace minerals, zinc and magnesium, have been reported to be lacking in some athletes. One popular performance enhancer is "ZMA", zinc monomethionine aspartate plus magnesium aspartate and vitamin [B.sub.6]. The use of this is based on a belief that people, including athletes, have a deficiency of the trace metals zinc and magnesium. There has been some research on this supplement, but not an abundance of it.

Summary

Supplements have become a staple with athletes. Athletes take supplements to enhance their performance through replenishment of real and perceived deficiencies, anabolic action of stimulants, increased energy and alertness, and for weight control. Physicians who deal with athletes should be aware of the supplements being utilized by athletes, the athletes' desired effects and the efficacy of the supplement, the adverse effects, and whether the supplement is banned by leagues or organizations in which the athletes are competing. For those athletes who are regularly drug tested for performance enhancers, it is important to remember that one cannot be 100% sure that any supplement will not result in a positive drug test, because there is no independent agency certifying purity.

Good people do not need laws to tell them to act responsibly, while bad
people will find a way around the laws.
--Plato

Accepted May 21, 2004.

Suggested Readings

* Juhn MS. Popular sports supplements and ergogenic aids. Sports Med 2003;333:921-939.

* Kraemer WJ, Volek JS. Creatine supplementation: its role in human performance. Clin Sports Med 1999;18:651-666.

* Kreider RB. Effects of creatine supplementation on performance and training adaptations. Mol Cell Biochem 2003;244:89-94.

* Preuss HG, DiFerdinando D, Bagchi M, et al. Citrus aurantium as a thermogenic, weight reduction replacement for ephedra: an overview. J Med 2002;33:247-264.

John A. Lombardo, MD

From the Sports Medicine Center, Ohio State University, Columbus, OH.

Reprint requests to John A. Lombardo, MD, Sports Medicine Center, Ohio State University, 2050 Kenny Road, Columbus, OH 43221.