THE PHYSICIAN AND SPORTSMEDICINE - VOL 25 - NO. 6 - JUNE 97
In Brief: Aggressive marketing has led millions of recreational and elite athletes to use nutrition supplements in hopes of improving performance. Unfortunately, these aids can be costly and potentially harmful, and the advertised ergogenic gains are often based on little or no scientific evidence. No benefits have been convincingly demonstrated for amino acids, L-carnitine, L-tryptophan, or chromium picolinate. Creatine, beta-hydroxy-beta-methylbutyrate, and dehydroepiandrosterone (DHEA) may confer ergogenic or anabolic effects. Chromium picolinate and DHEA have adverse side effects, and the safety of the other products remains in question.
Nutrition supplements are a lucrative business in the United States. According to the Council for Responsible Nutrition (1), the retail sale of dietary supplements generated $3.3 billion in 1990, and revenues increase each year. This enormous expenditure is largely the result of aggressive advertising aimed at high school, college, and recreational athletes, all eager for anabolic-steroid-like gains through dietary aids. Riding the crest of the fitness wave, nutrition supplements appeal to millions of consumers willing to pay billions of dollars for alleged benefits that are too good to be true.
Unfortunately, these supplements are subject to little regulation by the US Food and Drug Administration (FDA). Advertised claims to the contrary, many supplements have not been subjected to the scientific scrutiny required of prescription drugs. Furthermore, given the size and continued growth of the supplement industry, the FDA will probably never be able to monitor its products effectively. The resulting lack of regulation can lead to unscrupulous advertising, impurities in manufacturing, and potentially dangerous reactions among supplement users.
Such potential outcomes obligate physicians to learn about current nutrition supplements so they can educate patients about the effects and risks of supplement use. Team physicians in particular can advise athletes, coaches, and administrators in these matters. Competing with slick advertisements and exaggerated claims can be difficult, but by using recent scientific research on commonly used supplements, their mechanisms of action, and possible adverse reactions, physicians can offer sound recommendations to patients who are either users or interested in trying these aids.
Creatine, or methylguanidine-acetic acid, is an amino acid that was first identified in 1835 by Chevreul. It is synthesized from arginine and glycine in the liver, pancreas, and kidneys and is also available in meats and fish (2). Creatine was first introduced as a potential ergogenic aid in 1993 as creatine monohydrate and is currently being used extensively by athletes throughout the United States. A National Collegiate Athletic Association (NCAA) study, publication pending, revealed that 13% of intercollegiate athletes have used creatine monohydrate in the past 12 months (Frank Uryasz, personal communication, February 1997).
According to current theory, creatine supplementation increases the bioavailability of phosphocreatine (PCr) in skeletal muscle cells. This increase is thought to enhance muscle performance in two ways. First, more available PCr allows faster resynthesis of adenosine triphosphate (ATP) to provide energy for brief, high-intensity exercise, like sprinting, jumping, or weight lifting. Second, PCr buffers the intracellular hydrogen ions associated with lactate production and muscle fatigue during exercise. Therefore, creatine supplementation may provide an ergogenic effect by increasing the force of muscular contraction and prolonging anaerobic exercise (3).
Numerous well-designed studies have demonstrated that creatine supplementation has an ergogenic potential. Greenhaff et al (4) showed that 5-day oral dosages of 20 g/day increased muscle creatine availability by 20% and significantly accelerated PCr regeneration after intense muscle contraction. Birch et al (5) and Harris et al (6), in laboratory and field studies, demonstrated significant performance enhancement in male athletes, in both brief, high-intensity work and total time to exhaustion, using creatine supplementation of 20 to 30 g/day.
Recent data reveal that the mean creatine concentration in human skeletal muscle is 125 mmole/kg-dm (dry muscle), with a normal range between 90 and 160 mmole/kg-dm (7). This wide spectrum of creatine concentration may explain why some of the published studies have not demonstrated significant ergogenic effects. In a study by Greenhaff (7), approximately half of the tested athletic subjects exhibited concentrations lower than 125 mmole/kg-dm, with strict vegetarians substantially lower. These individuals exhibited the most significant increases in muscle creatine concentration, PCr regeneration, and performance enhancement with the use of creatine. On the other hand, athletes with elevated baseline levels of creatine showed little or no ergogenic effect when tested after ingesting creatine.
While creatine use has skyrocketed, no serious side effects have been scientifically verified in subjects using relatively brief (less than 4 weeks) creatine regimens. However, there are anecdotal reports of a dramatic increase in muscle cramping associated with the use of creatine monohydrate (J. Kinderknecht, MD, personal communication, June 1996). Future research will, we hope, clarify whether these adverse reactions are caused by creatine supplementation.
Chromium is an essential trace mineral present in various foods, such as mushrooms, prunes, nuts, whole grain breads, and cereals (8). A normal American diet contains 50% to 60% of the recommended daily allowance (RDA) of chromium. It has an extremely low gastrointestinal absorption rate, so supplement manufacturers have bound chromium with picolinate (CrPic) to increase the absorption and bioavailability.
Chromium supplementation became popular after it was found that exercise increases chromium loss, raising the concern that chromium deficiency may be common among athletes (9). Chromium seems to function as a co-factor that enhances the action of insulin, especially in carbohydrate, fat, and protein metabolism. Promoters of CrPic claim it increases glycogen synthesis, improves glucose tolerance and lipid profiles, and increases amino acid incorporation in muscle.
CrPic supplementation gained scientific credence in the early 1980s when researchers demonstrated anabolic-steroid-like effects with dosages of 200 micrograms/day. Evans (10,11) and Hasten et al (12) demonstrated a decreased percentage of body fat and increased lean mass among college athletes and students who took CrPic supplements and performed resistance exercise training. However, critical analysis of these studies reveals that imprecise measurement techniques, rather than CrPic supplementation, may account for these "ergogenic" results. More recent studies by Clancy et al (13) and Hallmark et al (14), using more precise measurement techniques, failed to demonstrate any significant improvement in percent body fat, lean body mass, or strength.
Most studies of CrPic supplementation reveal no side effects except gastrointestinal intolerance with dosages of 50 to 200 micrograms/day for less than 1 month. However, anecdotal reports of serious adverse effects, including anemia (15), cognitive impairment (16), chromosome damage (17), and interstitial nephritis (18) have been reported with CrPic ingestion in increased dosages and/or durations. Therefore, the use of chromium picolinate supplementation as an ergogenic aid should be strongly discouraged and considered potentially dangerous.
Amino acids are the basic structural units of proteins, and one might expect that the more amino acids ingested, the greater the potential for building skeletal muscle. According to the 1989 RDA, an average adult must ingest 0.8 g/kg lean body mass/day of protein in order to fulfill the body's protein requirements. Athletes, however, have traditionally been assumed to need significantly more protein than the average individual, so they commonly use various protein supplements.
Theories suggest that increasing the bioavailability of amino acids promotes protein synthesis and attenuates the muscle loss that occurs during both strength and endurance exercise. These theories have gained support through scientific experimentation in protein metabolism. Fern et al (19) and Lemon et al (20) demonstrated that strength trainers increased protein synthesis with substantially increased protein ingestion during 4 weeks of resistance training. By tracking the nitrogen balance of these athletes, a new daily protein requirement (1.4 to 1.8 g/kg lean mass/day) was developed for strength athletes.
Amino acid supplementation also plays a role in endurance athletes. Lemon (21) and Gontzen et al (22) demonstrated that endurance athletes who train at moderate intensity (55% to 65% of VO2 max) and high intensity (80% of VO2 max) for more than 100 minutes significantly increase protein breakdown unless their protein intake equals 1.2 to 1.4 g/kg lean mass/day.
Several factors make the amount of amino acids that athletes need less clear. Although all of the cited studies demonstrate the advisability of protein intakes higher than the current RDA, no well-designed study has yet shown that amino acid supplementation enhances performance. In addition, no scientific evidence supports protein supplementation in dosages greater than 2 g/kg lean mass/day. Finally, the improved conditioning that occurs over a 4- to 8-week training period may decrease protein breakdown, which may result in a maintenance protein requirement much closer to the current RDA.
Carnitine is a quaternary amine whose physiologically active form is beta-hydroxy-gamma-trimethylammonium butyrate. This is found in meats and dairy products and is synthesized in the human liver and kidneys from two essential amino acids, lysine and methionine. L-carnitine is thought to be ergogenic in two ways. First, by increasing free fatty acid transport across mitochondrial membranes, carnitine may increase fatty acid oxidation and utilization for energy, thus sparing muscle glycogen. Second, by buffering pyruvate, and thus reducing muscle lactate accumulation associated with fatigue, carnitine may prolong exercise.
Early studies by Gorostiaga et al (23), Wyss et al (24), and Natalie et al (25) indirectly demonstrated an ergogenic effect of this compound. These studies showed a decreased respiratory exchange ratio (RER) with L-carnitine supplementation (2 to 6 g/day) during exercise, suggesting that fatty acids rather than carbohydrates were used for energy. However, these studies had several problems in methodology, including the use of the RER as the sole measure of enhanced fatty acid oxidation. The RER is an indirect measure of lipid utilization that is influenced by many factors, such as preexercise diet, fitness level, and exercise intensity and duration (26). These confounders were not controlled and may have influenced the results.
A more controlled study by Vuchovich et al (27) avoided these problems by directly measuring muscle glycogen and lactate levels through biopsy and serum analysis. This study failed to demonstrate any glycogen-sparing effect or reductions in lactate levels while supplementing with 6 g/day of L-carnitine. Furthermore, no study to date has confirmed performance enhancement with carnitine supplementation. Finally, many currently available supplements actually contain D-carnitine, which is physiologically inactive in humans but may cause significant muscle weakness through mechanisms that deplete L-carnitine in tissues. Therefore, carnitine should not be advocated as an ergogenic supplement.
L-tryptophan, an essential amino acid, is not commercially available in its pure form but is found in many combination supplement products and reportedly remedies insomnia, depression, anxiety, and premenstrual tension (28). Athletes in the past decade have taken L-tryptophan because of its advertised ergogenic effects. The theoretical mechanism for these effects is an increase in serotonin levels in the brain; these increases produce analgesia and reduce the discomfort of prolonged muscular effort, thereby delaying fatigue. This theoretical model gained scientific credence in 1988 when Segura and Ventura (29) demonstrated a 49% increase in total exercise time to exhaustion when subjects ingested a total of 1.2 g of L-tryptophan (four 300-mg doses within 24 hours of exercise) vs placebo. Such a profound improvement in performance is difficult to imagine, and these results have never been replicated. Two larger, well-designed studies by Seltzer et al (30) and Stensrud et al (31) failed to demonstrate any improvement in subjective or objective outcome measures when supplementing with 1.2 g of L-tryptophan vs placebo. The results of these two studies are more consistent with current research data on exercise.
Physicians should be aware of two other developments that argue against supplementing with L-tryptophan. Its use has declined among elite athletes, possibly suggesting that they are recognizing its minimal ergogenic effects. More important, L-tryptophan ingestion was linked to multiple cases of eosinophilia myalgia syndrome and 32 deaths (28). Though these cases were probably due to contamination of L-tryptophan produced by one Japanese manufacturer, and not to the amino acid itself, they illustrate the quality and purity questions regarding unregulated supplements.
One of the most recent additions to the nutrition supplement market is beta-hydroxy-beta-methylbutyrate (HMB). It is a metabolite of the essential branched-chain amino acid leucine and is produced in small amounts endogenously. HMB is also found in catfish, citrus fruits, and breast milk. In the early 1980s, researchers at Iowa State University hypothesized that HMB was the bioactive component in leucine metabolism that regulates protein metabolism. The exact mechanism of this process is unknown, but promoters hypothesize that HMB regulates the enzymes responsible for protein breakdown. They propose that high HMB levels decrease protein catabolism, thereby creating a net anabolic effect.
Research in livestock (32-36) and humans seems to suggest that supplementation with HMB may increase muscle mass and strength. Nissen conducted two randomized, double-blind, placebo-controlled studies (37,38) to evaluate the ergogenic potential of HMB in exercising men. In the first study, 41 untrained subjects participated in a 4-week resistance training program. The subjects, whose diets were controlled, were given either HMB supplements of 1.5 or 3 g/day or a placebo. Those receiving HMB supplements showed significant improvements in muscle mass and strength as well as significant decreases in muscle breakdown products (3-methylhistidine and creatine phosphokinase) when compared with placebo subjects. The second study evaluated trained and untrained male subjects in a similarly designed weight training program. Relative to a placebo group, the subjects supplementing with 3 g/day demonstrated significant increases in muscle mass and one-repetition maximum bench press as well as decreases in percent body fat.
Further studies of HMB may continue to support the supplement's anabolic effects and elucidate its role in protein metabolism. No side effects of HMB supplementation have been reported, but the safety of this agent is still unknown. Therefore, it is premature to recommend its use as a safe and effective ergogenic aid.
Attention focused on dehydroepiandrosterone (DHEA) in 1996 when the FDA banned its sale and distribution for therapeutic uses until its safety and value could be reviewed. The ensuing media attention popularized this supplement, and manufacturers began selling it as a nutritional aid rather than a therapeutic drug.
DHEA was identified in 1934 as an androgen produced in the adrenal glands. It is a precursor to the endogenous production of both androgens and estrogens in primates (39). It is also available in wild yams, which are sold in many health food stores as a source of DHEA. As a precursor to androgenic steroids, DHEA may increase the production of testosterone and provide an anabolic steroid effect. Promoters claim that this compound slows the aging process and accordingly advertise it as the "fountain of youth."
Only a few randomized, double-blind, placebo-controlled studies on the effects of DHEA supplementation have been published. Two have demonstrated significant increases in androgenic steroid plasma levels, along with subjective improvements in physical and psychological well-being, while supplementing with 50 mg/day for 6 months (40) or 100 mg/day for up to 12 months (41). Whether DHEA has any effect on body composition or fat distribution is still unclear. Its effect on healthy individuals younger than 40 years old is also virtually unstudied.
DHEA users have reported few adverse effects from the supplement, but one is irreversible virilization in women, including hair loss, hirsutism, and voice deepening (42). In addition, men have reported irreversible gynecomastia, which may result from an elevation in estrogen levels. Because this supplement is so new, long-term adverse effects are unknown. Unlike most other nutrition supplements, DHEA may substantially increase the risk of uterine and prostate cancer that accompanies prolonged elevation in the levels of unopposed estrogen and testosterone. Therefore, the safety of this supplement must be questioned.
Of particular interest to competitive athletes is the effect that DHEA supplementation may have on the test used by the International Olympic Committee and NCAA in their screening for exogenous testosterone use. Using DHEA could alter the testosterone-epitestosterone ratio so it exceeds the 6:1 limit set by both groups (personal communication, Don Catlin, MD, 1997); thus DHEA users could risk disqualification from international competition.
Given the lack of evidence that DHEA enhances athletic performance and its potentially devastating adverse effects, DHEA supplementation is not recommended.
Although some of the supplements discussed here may have benefits, physicians should remain skeptical about the use of any supplement. The purity of agents available to consumers is in doubt, as we have seen with L-tryptophan. The Medical Letter, for example, analyzed several commercial preparations of melatonin and found unidentifiable impurities in four of six samples (43). The supplements used for the research reported in this review were pure, but consumers in the largely unregulated marketplace cannot be assured of that same purity in the products they buy.
Table 1. Daily Dose Costs of Various Nutrition Supplements Used by Athletes. Creatine
Chromium 200 mg/day: $0.43/day L-Carnitine 2.0 g/day: $2.67/day Beta-Hydroxy-Beta-Methylbutrate
Dehydroepiandrosterone
L-Tryptophan Currently unavailable in pure form due to federal regulation Sources: National Supplement Association and General Nutrition Centers |
There is also the issue of cost (tables 1 and 2). At current rates, doses of the supplements discussed range as high as $7.20/day, the cost of a loading dose of creatine (20 to 30 g/day). It makes little sense to invest in supplements that offer minimal or no benefit, especially for athletic departments in this era of shrinking budgets.
Table 2. Protein Supplements Cost Comparison: Daily Cost of 2 g Protein/kg for a 70-kg Individual Brand name protein powder: $9.80/day ($0.07/g protein) Generic Protein Powder: $2.80/day ($0.02/g protein) Tuna: $2.80/day ($0.02/g protein) Source: National Supplement Association |
The key word in nutrition supplements is nutrition. NCAA guidelines state that "there are no shortcuts to sound nutrition, and the use of suspected or advertised ergogenic aids may be detrimental and will, in most instances, provide no competitive advantage (44)." Physicians need to educate athletes, parents, coaches, trainers, and athletic administrators in sound dietary practices or see to it that a nutrition professional does so. Then nutrition supplements can be put in proper perspective, and decisions regarding their use can be based on proper scientific study and proven benefit to the individual.
Dr Armsey is a clinical instructor and sports medicine fellow, and Dr Green is a clinical associate professor in the Department of Family Medicine at the University of California, Los Angeles, Medical Center. Address correspondence to Gary A. Green, MD, University of California, Los Angeles, Medical Center, Box 951683, Los Angeles, CA 90095-1683; e-mail to ggreen@fammed.medsch.ucla.edu.
THE PHYSICIAN AND SPORTSMEDICINE - VOL 26 - NO. 5 - MAY 98
When you're used to being active, there's nothing worse than being pinned down by a recurring upset stomach or cold. You might assume you have a virus, but sometimes these recurrences can be signs of food allergies or, more likely, food intolerances.
Although you might include yourself in the 1 out of 4 people in the United States who believe they have food allergies, only about 1 or 2 in 100 are actually allergic to foods like cow's milk, eggs, seafood, nuts, beans, and wheat.
Someone who has a true food allergy has an abnormal or exaggerated immune-system response to specific proteins found in foods. (The body's immune system normally fights disease.)
Symptoms. Allergy symptoms vary from person to person, but they can be traced to the action of antibodies that normally fight bacteria and viruses. In some people, these antibodies attach to substances in foods, causing a release of chemicals such as histamine that trigger allergy symptoms.
Symptoms can range from annoying to life-threatening and can include rash, hives, itchy skin or eyes, swelling of the lips, mouth, tongue, face, or throat, sneezing, coughing, wheezing, stuffy or runny nose, abdominal pain, bloating or gas, nausea and vomiting, and diarrhea. They typically appear within 24 hours of eating and can last 48 to 72 hours or, in some cases, longer.
Food allergies can also provoke anaphylactic shock, an uncommon but life-threatening reaction that includes a sharp drop in blood pressure and difficulty breathing caused by swelling of the tongue and throat. The drop in blood pressure can cause shaking, sweating, difficulty focusing, and fainting. If this reaction happens, immediate medical attention is necessary.
Allergy tests. It's difficult to diagnose food allergies. The best-known procedure is the skin test, in which various food proteins are injected under the skin. Visible bumps indicate a positive test, but false positives occur up to 60% of the time, so you can't count on a positive test's accuracy. You can usually count on a negative test (no visible bumps) to mean you have no allergy.
Blood testing for food allergies is expensive and difficult to interpret. A board-certified allergist will provide the most accurate results.
A "food challenge" reveals an allergy when a reaction occurs after the suspect food is eaten. This testing should also be done by an expert allergist to ensure accuracy and safety in case a reaction becomes life-threatening.
Minimizing responses. If you have food allergies, there's not much you can do to eliminate them--you simply need to avoid the triggering foods. But research involving babies whose parents were prone to allergies suggests that you may be able to help young children avoid some allergy-related problems. It may help if moms avoid eggs, nuts, and shellfish during the last 3 months of pregnancy and while breast feeding, and withhold these foods from kids until they turn 2 (1).
Rather than being the result of a food allergy, your symptoms following a meal are most likely an intolerance. Intolerance or sensitivity is not the same as the immune response of an allergy. Instead, you may have deficiencies in digestive enzymes or responses to chemicals in foods.
Lactose intolerance. The most common gastrointestinal sensitivity is to lactose, a sugar found in milk. From 70% to 100% of blacks, Asians, and Native Americans have some lactose intolerance (2). Among Europeans, the prevalence varies from 1% to 5% in northerners to 60% to 90% in Mediterranean populations.
The inability to digest lactose is caused by the body's insufficient production of lactase, the enzyme required for lactose digestion. The result can be uncomfortable bloating, gas, and diarrhea after consuming lactose-containing foods. Symptoms can range from mild to extremely painful and can occur within minutes or hours after ingesting large amounts of lactose.
Avoiding foods that contain lactose may seem like a simple solution, but the outcome may be less than desirable. Dairy foods, which all contain lactose, may not be easy to eliminate from your diet if you enjoy them. It may not be easy to avoid the many foods that have milk products as ingredients, either. In addition, dairy foods provide the nutrients calcium, riboflavin, and protein. For practical solutions, see "Lactose Tolerance," below.
Fructose sensitivity. Hundreds of other substances can cause reactions. One of these is fructose (fruit sugar). Mild fructose intolerance is not uncommon, and its symptoms of stomach and intestinal cramps become very noticeable during exercise. Severe symptoms include vomiting, weakness, dizziness, hunger, headaches, jaundice, and abnormal sweating. Drinking sweetened soda, fruit juices, and other high-fructose beverages is most likely to bring on symptoms.
Fructose is found in thousands of sweetened food products. Many sports drinks contain it. As long as fructose is not the sole or the first sweetening ingredient listed, there is usually not enough to cause a problem. If you're sensitive to fructose, you should avoid large amounts, especially before exercise.
Amine sensitivity. Foods that contain amines also can cause reactions. The most notorious amine is monosodium glutamate, or MSG, a flavor enhancer. Glutamate is also found in tomatoes, bananas, avocados, oranges, mushrooms, chocolate, wine, and Parmesan cheese. Amines can cause irritation of the skin, mouth, throat, stomach, and bowels, as well as hives, swelling, mouth ulcers, nausea, stomach cramps, diarrhea, lethargy, and headaches.
MSG is common in soups, Chinese food, and prepared food, so read labels carefully if you have an amine sensitivity.
Whether your problem is allergy or intolerance, your discomfort may be intolerable. If you find that you must eliminate an entire food group from your diet to get relief, contact a registered dietitian to learn how to healthfully modify your diet to stay well and symptom-free.
If you are lactose intolerant, here are a few helpful ways to get the health benefits of dairy products and minimize discomfort:
Remember, you, your physician, and your nutritionist need to work together to discuss nutrition concerns. The above information is not intended as a substitute for appropriate medical treatment
Dr Kleiner is a private nutrition consultant to athletes in the Seattle area. She is a member of the American College of Sports Medicine; a member of the American Dietetic Association and its practice group, Sports and Cardiovascular Nutritionists (SCAN); and a fellow of the American College of Nutrition.
Mark S. Juhn, DO
THE PHYSICIAN AND SPORTSMEDICINE - VOL 27 - NO. 5 - MAY 1999
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In Brief: Many athletes--especially those participating in sports that emphasize strength--are taking oral creatine. Creatine supplements appear to enhance performance in repeated short bursts of stationary cycling and weight lifting, but the data on running, swimming, and single cycle sprints are not convincing of an ergogenic effect. Commonly reported side effects include muscle cramping, GI disturbances, and renal dysfunction, but creatine's effect on the heart, brain, reproductive organs, and other organs has yet to be determined. Comprehensive studies with larger samples and crossover design are needed. If patients decide to take oral creatine, physicians need to provide guidance for proper dosing as well as education about potential harmful effects.
Consumption of synthetically manufactured creatine by athletes and bodybuilders attempting to enhance athletic performance has become very popular. A surge in use began in 1992, when Harris et al (1) showed that oral supplementation with high doses of creatine resulted in a 20% increase in skeletal muscle creatine concentration. Although no claims could be made with regard to its effect on athletic performance, companies were quick to market the ergogenic potential of this legal substance. Creatine is not banned by the National Collegiate Athletic Association or the International Olympic Committee.
Creatine is a nitrogenous amino acid compound found naturally in skeletal muscle, heart, brain, testes, retina, and other tissues (2), In skeletal muscle, approximately one-fourth exists as free creatine and three-fourths as phosphocreatine (PCr) (3,4). Creatine is synthesized primarily by the liver, kidneys, and pancreas at a rate of 1 to 2 g/day (3-5). An additional 1 to 2 g/day is obtained in the diet, mainly from fish and meats (3,6). Excretion of creatine by the kidneys at a rate of 1 to 2 g/day is via irreversible conversion to creatinine in skeletal muscle (3). The reader should use caution not to confuse creatine with creatinine.
Total creatine is the sum of free creatine and phosphocreatine (PCr). Both types play important roles in anaerobic adenosine triphosphate (ATP) production during maximal anaerobic burst-type exercise via the creatine kinase system (4,7) (figure 1: not shown). Creatine and PCr exist in a reversible equilibrium in skeletal muscle (4,7,8). During intense muscle contraction, the flux in the forward direction increases, which rapidly produces more ATP for energy, anaerobically (4,7,9). The PCr reaction contributes significantly to ATP resynthesis for about 10 to 20 seconds of maximal exercise. This is followed by a proportionate increase in other pathways of ATP resynthesis, such as anaerobic glycolysis or aerobic oxidation of carbohydrate and fat (9).
Creatine supplementation can increase muscle PCr concentration by 6% to 16% (1,10-14), theoretically enhancing ATP turnover during maximal exercise. Additionally, creatine supplementation may enhance resynthesis of PCr during rest periods between repeated short bouts of exercise (15), though a recent study (14) did not support this theory. There is also some evidence that prolonged creatine supplementation increases myofibrillar protein synthesis, which results in muscle accretion (16,17), a controversial topic that will be discussed later.
In summary then, oral creatine supplementation may be ergogenic for the following reasons:
It should be noted that the PCr reaction is anaerobic (4,7), meaning that oral creatine supplementation is potentially ergogenic only for activity that has a high anaerobic component, not for endurance activity (18,19). The possibility exists, however, that creatine may be ergogenic for endurance events that involve intermittent bursts of anaerobic activity.
The typical creatine supplementation protocol begins with a loading dose of 20 g/day (or 0.3 g/kg) for 5 days, followed by a "maintenance" dose of 2 g/day (or 0.03 g/kg) (12), though the maintenance dose is often unnecessarily exceeded (20). Although a 5-day loading period is typical, 2 days of loading has been shown to yield similar muscle creatine concentration and performance results (14). Without loading, 3 g/day for 28 days results in muscle creatine concentrations similar to 5 days of loading (12).
A study by Green et al (21) found that the addition of a carbohydrate solution (90 g four times daily during the loading phase) further enhanced the increase in muscle creatine concentration relative to taking creatine alone. Based on this study, the combination of creatine with sports drinks has become popular.
It is important to note, however, that skeletal muscle has a creatine storage capacity of 150 to 160 mmol/kg (normal is 125 mmol/kg) (1,10), which makes oversupplementation futile. This is important information for those who think that more is better. Any excess creatine ingestion will not further increase muscle creatine but will simply increase urinary creatine and creatinine excretion.
Muscle concentrations of creatine and PCr return to baseline levels approximately 28 days after discontinuing creatine supplementation (13,22).
In controlled laboratory studies, oral creatine supplementation has been shown to be ergogenic in repeated stationary cycling sprints (23-28), weight lifting (13,26,27,29), repetitive sets of muscle contractions such as knee extensions (14,30), and kayak ergometry (31). However, the media and even some in the scientific community often extrapolate these studies to a much broader generalization regarding athletic performance, seemingly omitting mention of many studies that do not demonstrate an ergogenic effect. This can be misleading for the athlete and clinician alike.
Common misconceptions. There are two common misconceptions about creatine's ergogenic potential. The first is a gross generalization that creatine supplementation is ergogenic for all types of "sprinting," including running, swimming, and cycling. The fact is, the literature has shown reasonable support for an ergogenic benefit only in repeated bouts of stationary cycling sprints in a laboratory setting (table 1) (23-28). And unanimity is lacking even here, as there are several studies (22,32-34) of repeated cycling sprints that did not demonstrate an ergogenic effect.
| Table 1. Effect of Oral Creatine Supplementation on Specific Activities | ||
| Activity | Summary of Studies | Comments |
| Stationary cycling sprints | Several studies support an ergogenic effect in repeated sprints but are not convincing for single sprints | Field studies with bicycles on a track are needed to simulate actual competition |
| Running sprints (repeated or single) | Conflicting results regarding performance enhancement | Speculation is that weight gain offsets any potential benefit |
| Swimming sprints (repeated or single) | Conflicting results regarding performance enhancement | Speculation is that weight gain offsets any potential benefit |
| Weight lifting | Some evidence of an ergogenic effect | Whether creatine supplementation truly increases muscle synthesis is being investigated. Creatine-induced weight gain may make true double-blindness difficult to achieve |
As for creatine's effect on running sprints and swimming sprints (35), more studies (36-40) have demonstrated no benefit with supplementation than have demonstrated a benefit (41). (Some studies produced mixed results: Both Bosco et al (42) and Peyrebrune et al (43) found one protocol to show no benefit and one protocol to show a benefit, while Grindstaff et al (44) found no benefit in two swimming heats and some benefit in one.)
It is speculated that the weight gain from water retention that occurs with creatine supplementation (12,13) may impede performance in runners and swimmers. The effect of weight gain on performance may not be as significant in a weight-supported activity such as stationary cycling or weight lifting. Also, the cycling studies are performed on stationary cycle ergometers, not on bicycles on a track or road. This has led some to question whether creatine is truly ergogenic outside of a laboratory. In general, the vague term "sprinting" should be avoided when discussing creatine's ergogenic potential.
The second common misconception is that creatine supplementation is beneficial in a single timed event, such as a single sprint. The fact is that, even with stationary cycling, creatine has not been shown to enhance single-event performance (25,45-47). Again, the strongest support for the ergogenic potential of creatine supplementation is in repeated maximal bursts of activity, specifically 6- to 30-second bouts of stationary cycling with 20 seconds to 5 minutes of rest between bouts (23-28). However, some multiple-bout studies (24,25,27) did demonstrate an improvement in the first bout, which can be construed as single-bout performance.
Because the evidence does not strongly support an ergogenic effect of oral creatine on single-sprint activity and because most competition involves single timed events rather than repetitive burst activity, some have expressed skepticism that creatine can truly help athletic performance. The argument can be made, however, that athletes in sports such as football, which involves repeated bursts of maximal exercise, may gain an ergogenic effect from creatine supplementation. On the other hand, players need to consider the possible detriment of weight gain, though some athletes may find the weight gain desirable, depending on the sport and position they play.
Conflicting results. The variable results in creatine studies are difficult to explain but may be due to study design, author bias, or subject variability. Very few studies incorporated a crossover design, in which the control group becomes the experimental group and vice versa after a washout period. Crossover designs reduce the sample size required and reduce the chances of a type 2 statistical error (an acceptance of the null hypothesis when in fact it is false).
Author bias may also contribute to the different conclusions seen. According to disclosure statements accompanying the articles, several studies were funded by grants from sport supplement companies or have one or more authors who serve as consultants for such companies (26,27,44). Such affiliations would, of course, not affect results, but they may unintentionally influence the discussion and ultimately the authors' conclusions. Finally, a simple yet very plausible hypothesis to explain conflicting study results is subject variability.
Creatine supplementation results in weight gain, from 0.5 to 1.6 kg during the 5-day loading phase (15,25,26,29,32,33,38,47), and even more with prolonged use (13,27). The weight gain is initially due to water retention (12,13). After 1 year of use, muscle accretion may occur (17), although this is unproved and still under study.
Several studies (13,26,27,29) have demonstrated an ergogenic effect of creatine supplementation in weight lifting. Weight gain, however, is noted even after 1 to 2 days of creatine loading, which is too short a time for appreciable muscle accretion to occur. Furthermore, it is possible that despite investigators' efforts to maintain double-blindness, the weight gain experienced by those in the creatine group can result in a placebo effect of feeling "stronger."
Further study is needed to determine if oral creatine supplementation per se enhances muscle accretion and truly increases strength. However, even without muscle accretion, the ergogenic effect observed may be due to enhanced ATP turnover as discussed previously.
Adverse effects of oral creatine supplementation have not been extensively studied, though concerns have been prevalent in the media and training rooms. In the United States, creatine is considered a dietary supplement. Therefore, in accordance with the Dietary Supplement Health and Education Act of 1994 (48), claims regarding performance and safety do not need to be substantiated by the US Food and Drug Administration (FDA).
Muscle cramping. It is common to hear reports from athletic trainers about muscle cramping or strains in athletes taking creatine. Since water retention occurs with creatine supplementation (12,13), it is speculated that this effect increases skeletal muscle compartment pressure, leading to the risk of muscle dysfunction. In some studies that have evaluated performance (11,13,14,27,44), none of the subjects experienced muscle cramping. However, such studies had sample sizes of 25 or fewer, which is suboptimal for comprehensive statistical analysis.
To elaborate, if a side effect is present in 50% of an experimental group versus 30% of a control group, and the researcher wishes to achieve a statistical significance level of 0.05 with 80% power, then a sample size of 146 (73 in each group) is needed (49). The sample size required is much larger if 90% power is the goal, or if the difference between groups is less, such as 40% versus 30%.
In one survey of 52 male collegiate athletes (20), muscle cramping was reported by 25% of those who took creatine. However, this was not a controlled study, and, in most cases, such complaints did not cause the athlete voluntarily to stop taking creatine. While theoretical concerns and anecdotal reports abound, randomized double-blind studies with larger numbers of subjects and crossover design are needed to more accurately assess this controversial aspect.
Gastrointestinal effects. Diarrhea and gastrointestinal pain have also been reported anecdotally. Authors of several performance studies (11,13,14,27,44) noted that none of their subjects experienced gastrointestinal symptoms of any kind, but, again, sample sizes were extremely small (fewer than 12 in the experimental group). Since the average diet includes 1 to 2 g of creatine daily, it may be reasonable to assume that a loading dose of 20 g daily for 5 days is excessive for some people's digestive systems.
Renal dysfunction. Anecdotal reports and two published case reports (50,51) of renal dysfunction in subjects taking creatine have raised concern about the effects of creatine supplementation on the kidneys. Short-term (5-day) creatine supplementation does not appear to impair function in the healthy kidney (52). However, supplementation significantly increases the urinary creatine excretion rate, as much as 90-fold during the loading phase (13,52), and whether this has long-term adverse effects is unclear. Urinary creatinine also increases, but to a much lesser degree (12-14,53). Currently, creatine supplementation should not be used by people with preexisting renal disease or by those with a potential for renal dysfunction (eg, those who have diabetes).
Dehydration. There is anecdotal concern that the water retention resulting from creatine supplementation can increase the risk of dehydration via fluid shifts into the skeletal muscle cells (intracellular water retention). While an increased risk of dehydration has not been proven, most creatine manufacturers advocate proper hydration while taking creatine, theoretically to reduce this chance.
Creatine is naturally found in many other places in the body, including the heart, brain, and testicles (2). The fact that possible side effects in these areas receive less attention than muscle cramping and gastrointestinal effects is surprising and of concern. It is unknown, for example, what effect oral creatine supplementation has on creatine concentration in the heart, brain, and reproductive organs. Furthermore, oral creatine supplementation results in the attenuation or suppression of endogenous creatine synthesis by the liver (13), and the long-term effects of this on the liver or other organ systems are not known. In addition, creatine is found and synthesized in the testes (54,55), and animal studies have shown that creatine is involved in sperm metabolism (56).
Other potential areas of concern have been addressed in a recent critical review (57), which is summarized in table 2 (not shown) (2,11-13,17,27,38,52,53,55,56,58-64). One notable area that remains unstudied is the pediatric population, perhaps the most susceptible population when it comes to ergogenics and athletic performance. Clearly, human studies evaluating the effects of oral creatine supplementation beyond just muscle cramping and diarrhea are indicated.
The FDA has officially logged 32 complaints regarding people who used creatine (65). These complaints include seizure, cardiac arrhythmia, cardiomyopathy, deep venous thrombosis, rhabdomyolysis, and death. Thus far, no conclusions linking these reports to creatine supplementation have been made. A well-publicized case series of three wrestlers who died after taking severe dehydration measures implicated creatine as a contributor, but this claim was not supported by an investigation by the Centers for Disease Control and Prevention (66). In addition, ethical and legal issues need to be resolved (see "Creatine: Ethical and Medicolegal Issues," below).
Physicians will continue to encounter patients who insist on using creatine. When this occurs, informing patients of the following would be a reasonable start:
It is up to the physician whether or not to monitor patients with regular laboratory tests. A baseline set of renal and liver function lab values would be advisable, as would a screening physical examination.
There is evidence that oral creatine supplementation enhances performance in repeated short bouts of stationary cycling in a laboratory setting. The most accepted hypothesis is that enhanced ATP turnover as a result of greater muscle PCr concentration after supplementation enhances muscle contractility. However, the data on creatine supplementation and single sprints of any kind do not support an ergogenic effect. Additionally, the evidence that creatine improves running and swimming performance is not convincing, perhaps because of weight gain from water retention. Also, it remains to be seen if long-term creatine supplementation enhances muscle accretion. Finally, creatine has not been shown to be ergogenic outside the laboratory setting.
Commonly reported adverse effects of creatine supplementation include muscle cramping and gastrointestinal disturbances, but studies with larger sample sizes are needed to identify the scope of the problem. The greater concern lies in the unknown effects of creatine supplementation on various organ systems, particularly the kidneys, liver, heart, brain, and reproductive organs.
Though physicians can educate patients about oral creatine use, the decision on supplementation will ultimately be made by the patient. Physicians, though, can provide valuable guidance.
There is concern that the "win at all costs" attitude has become too prevalent in today's sports-oriented society. Adolescents are the most easily influenced age-group, yet they are the least studied with respect to sport supplementation. Regardless of whether creatine is ergogenic or not, does its prevalent use send the wrong message? Would the use of creatine and other supplements steer athletes away from the most reliable and safe method of enhancing performance, namely practice and dedicated training?
Medicolegal concerns are being addressed at the high school and college level. For example, several institutions have abandoned the practice of freely distributing creatine in training rooms for fear of potential litigation should adverse effects occur in a student-athlete. Medicolegally, physicians are advised to let athletes decide for themselves to take creatine or not. However, physicians can educate athletes to help them make informed decisions.
It should not be forgotten that although the term "athlete" is often used in sports medicine, every athlete cared for is also a patient.
Dr Juhn is an attending physician in the Family Medicine Clinic and Sports Medicine Clinic at the University of Washington's Hall Health Primary Care Center in Seattle. He is also a clinical instructor in the Department of Family Medicine at the University of Washington School of Medicine. Address correspondence to Mark S. Juhn, DO, Hall Health Primary Care Sports Medicine Center, University of Washington, Box 354410, Seattle, WA 98195-4410.
THE PHYSICIAN AND SPORTSMEDICINE - VOL 26 - NO. 7 - JULY 98
Once upon a time, eggs were considered a "breakfast of champions." Just about every active, hard-working person enjoyed them fried, scrambled, poached, or even raw in eggnog and protein drinks. Then, Americans became cholesterol-conscious and began to substitute bagels, cereal, and other high-carbohydrate, low-cholesterol breakfast foods.
Today, active people may welcome the news that eggs have less cholesterol than originally thought (210 milligrams, not 275), that dietary cholesterol may be of less importance than thought earlier in heart disease, and that eggs are an excellent source of high-quality protein that's low in saturated fat. Although eggs are being revisited, you may still question their role in your food plan. Any way you look at it, 210 milligrams of cholesterol is still the better part of the 300-milligram daily limit recommended by the American Heart Association (AHA).
When high blood cholesterol was first linked to heart disease, we were urged to cut back on cholesterol-rich foods such as eggs and other animal foods. But saturated fat likely plays a larger role than cholesterol in heart disease. Thus, eggs themselves may be less of a concern than saturated fat in the grease in which they were fried, and in the accompanying bacon, buttered toast, and greasy hash browns (table 1: not shown).
In addition, not everyone's blood cholesterol levels respond to changes in dietary cholesterol. According to a study by H. Gylling and others published in 1997, about 85% of us are "nonresponders" whose blood cholesterol will stay the same even if we reduce our intake of eggs and other cholesterol-rich foods. This inherited trait underscores the importance of identifying people with high cholesterol levels who are responders so they can modify their diets.
Egg advocates can point out research that suggests there is no relationship between egg consumption and heart disease. Japan, for example, has the highest per-capita egg consumption, at 6.3 eggs per person per week, and the lowest rate of heart disease.
But egg opponents can refer to research published in the American Journal of Clinical Nutrition that suggests that reducing dietary cholesterol can result in slightly lower blood cholesterol. For some people who are at high risk of heart disease, this means that trading a daily two-egg breakfast for cereal could result in a 9-milligram drop in blood cholesterol.
All of this conflicting research calls for individualized dietary recommendations. A one-diet-fits-all approach clearly does not work when it comes to heart health.
If you have high cholesterol and your doctor recommends you reduce your dietary cholesterol, you can enjoy egg alternatives. For example, the egg industry offers cholesterol-free egg substitutes such as Egg Beaters, which are primarily egg whites with vegetable oil, coloring, and flavoring added to simulate the yolk. In addition, egg industry researchers have learned that when hens are fed flaxseed, a source of the omega-3 fatty acids also found in fish, this beneficial fat shows up in the yolks. One of these eggs may have as much omega-3 as a 4-ounce serving of tuna.
To use fewer cholesterol-rich egg yolks, you can use an egg alternative, or two egg whites in place of one whole egg. Or, if a recipe calls for two eggs, you could substitute one whole egg and two egg whites.
The properties that make eggs life-sustaining for little chicks also make them a nutrient-dense food for humans. A whole egg is not only a good source of 6 grams of the high- quality protein that helps to build muscles, but the yolk is also rich in iron, zinc, B vitamins including folic acid, and vitamins D and E. The egg white is almost pure protein, with water. Many protein powders include egg protein (albumin) because it contains all the essential amino acids needed to build new proteins.
Note that while egg whites contain complete protein, one egg white offers only about 3 grams of protein, in contrast to 26 grams in a 4-ounce serving of tuna or 30 in a cooked 4-ounce chicken breast. Hence, two scrambled egg whites or an egg-white omelet adds relatively little protein to the day's intake.
If you're wondering if you need eggs for protein, be aware that most active people can get plenty of protein without eating eggs. But since many active people eat too little fiber and fruit, swapping or alternating eggs with fruit-topped bran cereal at breakfast is a healthful move.
In the egg debate, most medical professionals still take a conservative stand. The AHA, for example, continues to recommend limiting eggs to four yolks per week (or one yolk per week if your blood cholesterol levels are high) including those used in cooking. Egg whites can be used freely.
You might want to personalize that recommendation. If your family history includes long, active lives and if your blood cholesterol is low, you can likely eat a few more yolks per week. Poached eggs on toast or a vegetable-filled omelet are nutrient-dense, healthy breakfast choices and can be balanced with fruit or juice for fiber and vitamin C. But if your family is riddled with heart disease and early heart-attack deaths, you might want to remain cautious about your cholesterol intake. Bran cereal with low-fat milk and a banana might be the better breakfast bet.
Poultry is a major carrier of salmonella bacteria. These bacteria, which reside in the hens' intestines, can be passed along in eggs. They are commonly found in eggs with cracked shells, so avoid using eggs that have cracks. But beware--salmonella has also been found in whole eggs. Cooking destroys these bacteria, but be sure to cook eggs until the white is set and the yolk is firm. You should also avoid eating raw cookie dough or using raw eggs in protein drinks. (Milk powder gives a similar protein boost.) Wash your hands well after handling eggs.
Remember: You, your physician, and your nutritionist need to work together to discuss nutrition concerns. The above information is not intended as a substitute for appropriate medical treatment.
THE PHYSICIAN AND SPORTSMEDICINE - VOL 25 - NO. 4 - APRIL 97
In Brief: Athletes at all levels explore ergogenic aids. Testosterone and growth hormone are still abused and difficult to detect. Single doses of albuterol or salmeterol do not seem ergogenic, but questions remain about prolonged dosing and about other beta2 agonists. Caffeine can be ergogenic for prolonged or brief exertion. Creatine supplementation is legal and in vogue among strength and power athletes. Not all studies agree, but creatine seems ergogenic for repeated brief bouts of intense exercise. Ergogenic aids pose vexing questions for athletes, physicians, and society.
The Olympic motto is Citius, Altius, Fortius--swifter, higher, stronger. Maybe, at least in the strength and power sports, we should add fraudator, the Latin word for deceiver. In spite of increasingly sophisticated drug testing at the Olympics, suspicions of the use of illegal ergogenic aids are stronger than ever. Proof of cheating is often lacking, but by all appearances, the suspicions are well-founded. In a never-ending game of cat and mouse, athletes who cheat seem always one step ahead of those who try to catch them (1).
Attempts to enhance athletic performance are not new. The Olympic Games date back 2,700 years, so trickery in sport likely dates back at least that long. Ancient Greek Olympians ate mushrooms to win. Aztec athletes ate the human heart. In the late 1800s, European cyclists took heroin, cocaine "speedballs," and ether-soaked sugar tablets. The winner of the 1904 Olympic marathon, Tom Hicks, took strychnine and brandy during the race. The winner of the 1920 Olympic 100-m dash, Charlie Paddock, drank sherry with raw egg before the race. In the 1960 Olympics, Danish cyclist Knut Jensen died in the road race from taking amphetamine. In the 1967 Tour de France, famed British cyclist Tommy Simpson died, also from amphetamine (1).
Deaths like Simpson's and other drug-related sports incidents led the International Olympic Committee to begin Olympic drug testing for stimulants in 1968 (2). Since then, Olympic testing has expanded and struggled to stem a rising tide of drug use. We have witnessed waves of use that included stimulants, anabolic steroids, beta2 agonists, hormones, and now the rumored testosterone patches. We have seen the diluting and "masking" of drugs. Among athletes caught for drug use, we have seen creative excuses and maneuvers, including claims of sabotage. And athletes continue to explore legal drugs and nutrients, such as asthma medications, caffeine, and creatine.
Drug use, though, is not limited to Olympic or elite athletes. Many adolescent athletes--boys more than girls--try anabolic steroids (3,4). A recent study (5) explores the efficacy of a "testosterone boost" for normal young men who stay fit by lifting weights. Another (6) probes the potential of growth hormone as a "rejuvenator" for older men who want to stay active. Athletes at all levels--some asthmatic and some not--want to know if asthma medications improve performance. Caffeine is widely used as an ergogenic by community runners, cyclists, and triathletes. Judging from sports-related magazines and newsletters, creatine is popular among collegiate and community strength and power athletes. Given these trends, a review of the history and state of the art in ergogenics is in order.
In the 1956 World Games in Moscow, US physician John Ziegler saw Soviet athletes using testosterone. To level the playing field for Western athletes, Ziegler helped develop the anabolic steroid Dianabol as an alternative to testosterone. Dianabol soon became the rage, and athletes used huge doses. Ziegler realized he had created a monster, a fact he regretted the rest of his life (1).
Other anabolic steroids followed, and athletes began "stacking" them in cycles tailored by steroid gurus. Steroid-using athletes grew stronger, but serious side effects included unhealthy cholesterol profiles, heart attack, stroke, liver tumors, and prostate problems (3). Mood changes were also seen. Some reports suggested that large doses of anabolic steroids tended to make men irritable and moody at best, and at worst, raging, murderous, and suicidal. In a noteworthy study (7) of 20 normal men, modest doses of methyltestosterone evoked both positive moods (euphoria, energy) and negative moods (irritability, hostility). Three (15%) of these men developed, respectively, mania, hypomania, and depression.
When sports scientists began studying the effects of steroids on performance, they lost credibility with steroid-abusing athletes by arguing that anabolic steroids did not increase strength. In time, analysis of many studies convinced even the skeptics that anabolic steroids did enhance strength, especially in athletes who trained hard on them (8). Now the pendulum has swung further toward proving steroids as strength-enhancers: A placebo-controlled study (5) of 43 normal young men has increased interest in testosterone by showing that, in only 10 weeks, weight-lifting men injected with testosterone increased muscle mass by an average of 13 lb and bench pressed an extra 48 lb.
Female athletes, more than male athletes, are likely to gain a competitive edge by using male hormones, which give females more muscle, less fat, narrower hips, and higher hematocrits. Anabolic steroids turned East German female swimmers into "lumbering beauties" who won Olympic medals during the 1970s and 1980s (Sports Illustrated. October 16, 1995:84; Time. August 5, 1996:45). China followed suit. Between 1992 and 1994, Chinese women came out of obscurity to set world records in swimming and running. Then officials sprang urine tests on the athletes, and from 1993 to 1994, found that 11 Chinese stars, including seven female swimmers, were on dihydrotestosterone (Sports Illustrated. October 16, 1995:84; Time. August 5, 1996:45). In 1996, rumors suggested that some female Olympians used testosterone patches in training; experts say that tiny amounts of testosterone (as from skin patches) are difficult to detect but can measurably boost strength and speed in women (Time. August 5, 1996:45).
Experts also think that some male Olympians are using testosterone (2) but cannot accurately determine the extent because of imprecise testing. The new high-resolution mass spectrometer first used at the 1996 Olympics is highly sensitive to traces of most anabolic steroids, but cannot tell synthetic testosterone from the natural kind. Because natural testosterone levels vary widely in men, high readings alone prove little, so the ratio of testosterone to a key metabolite, epitestosterone (T/E ratio), is used to determine a positive test. This ratio is about 1 in most men, rarely greater than 3 (recent alcohol use may raise it to 2 to 3), and very rarely greater than 6. (The blanket use of this number is complicated by the fact that 1 in 2,000 men is apparently deficient in an enzyme that produces epitestosterone, and this deficiency could abnormally raise the T/E ratio.) Olympic testers call a test positive only if the ratio is greater than 6. This offers room to dope with testosterone up to the cutoff of 6, or to "raise the denominator" by taking epitestosterone, as some male athletes may be doing. Olympic officials soon hope to have a test that detects synthetic testosterone, which changes carbon isotope ratios in urine. The test will measure the ratio of carbon 13 to carbon 12 in urinary testosterone (2).
The situation of recombinant human growth hormone (hGH) seems similar to that of anabolic steroids in the early years of their use. Scientists report that hGH may not increase effective strength or performance, but some athletes, convinced it works, use it. For example, two recent studies (9,10) suggest no performance benefit from hGH. When 16 untrained men underwent a 12-week muscle-building program, receiving either hGH or placebo, the hGH increased fat-free mass and total body water, but not muscle protein synthesis, muscle size, or strength. With hGH use, insulin action was slightly impaired, and two of the men contracted carpal tunnel syndrome. When seven trained weight lifters were given hGH for 2 weeks as they continued training, the hGH did not increase the rate of muscle protein synthesis or reduce the rate of whole-body protein breakdown.
The early interest in hGH as a "rejuvenator" is fading. Now a 6-month, controlled, randomized, double-blind study (6) of hGH in healthy older men (mean age 75 years) reports slight improvements in body composition (decrease in fat mass, increase in lean mass), but no increase in strength, endurance, or cognitive function.
No test can now detect abuse of hGH, but Olympic scientists vow to perfect one by the Sydney Olympics in 2000. This test will focus on blood markers (hGH itself and insulin-like growth-factor-binding proteins), and so calls for a change in Olympic policy, which now permits testing only of urine.
Beta2 agonists (clenbuterol, terbutaline, albuterol, salmeterol) are not anabolic steroids but are potentially anabolic, and so their systemic use is banned. Yet in the 1992 Olympics, two athletes tested positive for clenbuterol.
Studies show that clenbuterol affects animals in different ways. It increases muscle mass and cuts fat in livestock and in laboratory animals, mainly from a selective hypertrophy of skeletal muscles. It can retard muscle wasting in denervated rodents. Research also suggests that, although clenbuterol increases muscle mass in rodents, it decreases the oxidative potential of those same muscles, perhaps by decreasing the expression of the beta2 adrenergic receptors or by preferentially increasing nonmitochondrial proteins. As a result, clenbuterol decreases endurance running in rodents. This decrease in performance, however, can be offset, in mice at least, by an exercise regimen (11).
No human studies are available on whether clenbuterol can increase strength or power, yet some athletes are using clenbuterol without proof of its effectiveness or safety. Strength athletes use it along with steroids, or after they stop steroids, to retard loss of muscle and "strip" fat to "define" muscles. Some athletes note troubling tachycardia while on clenbuterol; others have stopped taking it because of tremor. Two European bodybuilders on clenbuterol died suddenly, but it's unclear whether the drug contributed to their deaths (12).
A similar quandary exists for albuterol (salbutamol), legal only in inhaled form for exercise-induced asthma. In a 3-week study (13) of a slow-release oral form of albuterol, it seemed to increase, though inconsistently, the voluntary strength of young men. A study (14) in which healthy young men took oral albuterol (4 mg four times daily for 6 weeks) suggests that resistance exercise may augment any strength gain from albuterol. In two other studies (15,16), however, long-acting inhaled salmeterol had no ergogenic effect on maximal or endurance cycling in asthmatic men, or on anaerobic cycling or peak leg torque in nonasthmatic men. For now, all long-acting beta2 agonists are banned, but some authors are calling for legalizing salmeterol for asthmatic athletes (16).
Whether the legal inhaled form of albuterol is ergogenic remains controversial. As reviewed in four recent studies (17-20), the weight of evidence suggests that single doses of albuterol are not ergogenic for asthmatic or nonasthmatic athletes. Two early studies in cyclists suggested that albuterol was ergogenic, but their design has been faulted, and six other studies (three in cyclists, two in runners, one in power athletes) found no immediate ergogenic effect for albuterol on either power or endurance. Researchers do caution, however, that albuterol is conceivably ergogenic at higher or prolonged dosage (20).
In spite of the confusing research picture regarding albuterol, the peculiar epidemic of "asthma" among elite athletes suggests that they think albuterol is ergogenic. The declared prevalence of exercise-induced asthma (EIA) among American Olympians shot up from just over 10% at the 1984 Summer Games to nearly 60% at the 1994 Winter Games (P.Z. Pearce, MD, personal communication, 1994). Though some of this increase could be ascribed to the contribution of cold weather to EIA, the size of the increase suggests that more and more Olympians want to be "approved" to use albuterol in order to level the playing field.
Caffeine is a legal drug (to a urine level of 12 micrograms/mL) that can be ergogenic for both elite and recreational athletes. Recent controlled studies find that moderate doses of caffeine (3 to 6 mg/kg) ingested 1 hour before exercise enhance endurance performance at legal urine levels. In one study (21) of trained runners, a high caffeine dose (9 mg/kg) before "race-pace" exercise increased endurance running time and cycling time an astonishing 44% and 51%, respectively. How caffeine does this is unclear, but a metabolic action is most likely involved, in that caffeine increases plasma free fatty acid levels and muscle triglyceride use, while sparing muscle glycogen use early in exercise. In addition, increases in plasma epinephrine usually occur, but are not essential to the endurance enhancing effect of caffeine (22).
Recent research suggests caffeine is also ergogenic for exercise lasting 20 minutes or less. Caffeine can enhance performance in a 20-minute swim, a 100-m swim trial, a 1500-m treadmill run, and brief bursts of all-out cycling (22). Any ergogenic effect in these efforts is surely not from muscle glycogen sparing, because the exercise is too brief. Rather, it probably stems from an effect on the brain (decreasing perceived exertion or increasing motor-unit recruitment) or from a direct effect on skeletal muscle (22).
The ergogenic effects of caffeine vary greatly, but are most predictable in trained athletes who habitually use caffeine. Few studies, however, have been done in the field, so the extent of caffeine's ergogenic effects during competition remains unclear. In a recent controlled field study, caffeine did not improve performance in a 21-km road race in hot, humid conditions (23).
Creatine, a natural substance found in raw meat and fish, locates in muscles and is critical for high-intensity muscle contractions. Creatine supplementation, a legal practice, was first used by British sprinters and hurdlers in the 1992 Olympics (24). Current reports in sports-related newsletters (25,26) affirm that the use of creatine is widespread among elite and collegiate athletes, including weight lifters, power athletes, sprinters, and football players. One report states, "It is not unusual for trainers at almost every level to keep creatine in stock and dispense it to athletes (26)."
Creatine binds phosphate to form creatine phosphate. During brief, intense, anaerobic actions, like sprinting, jumping, or weight lifting, creatine phosphate regenerates adenosine triphosphate (ATP) to provide the energy necessary for muscle contractions. The aim of supplemental creatine is to increase resting levels of creatine phosphate so as to regenerate more ATP and sustain a high power output, thus delaying fatigue and improving performance. Creatine also helps buffer the lactic acid that accumulates in muscles during intense exercise.
The estimated daily need for creatine in humans is about 2 g, whereas the daily intake from meat or fish is about l g in the average American diet. The body makes up the deficit by producing creatine in the liver, kidney, and pancreas, using as precursors glycine and arginine. When dietary supply is low, the body steps up its production of creatine, but may not completely compensate, especially among vegetarians, who have a reduced body creatine pool (27-31).
Creatine stores vary greatly among individuals, and apart from diet, the reasons are unclear. Athletes with low stores might be most apt to benefit from supplementation. Muscle creatine levels increase an average of 20% after 6 days of supplementing at 20 g/day ("rapid creatine loading"). These higher levels can be maintained by ingesting 2 g/day thereafter. A similar, but slower, 20% rise in muscle creatine levels occurs by ingesting 3 g/day for 1 month, the "no-load" method (31).
Creatine is available commercially, but is classified as a nutritional supplement, not a drug, so its purity is not guaranteed. Twenty grams per day is a high dosage, since 20 g is the amount in 10 lb of raw steak. Yet other than a small weight gain (perhaps from a gain in muscle water that accompanies the creatine), there seem to be few short-term side effects, although some observers say high doses promote dehydration and possibly muscle cramping. Creatine is degraded to creatinine and eliminated in the urine. Questions remain about the potential long-term effects on muscles, specifically the heart, and on the kidneys (24).
Growing evidence suggests that creatine can improve performance in repeated bouts of all-out strength work or sprinting--whether pedaling or running (27-29,32). If further studies confirm this research, it has practical implications for some team sports and for many track and field events. Not all studies, however, are positive. A study (30) of untrained men, for example, shows no ergogenic effect in single 15-second bouts of cycle sprinting. This "negative" study, however, does not refute the "positive" studies, because the trend of findings in this area is that total work improves not in the first bout of sprinting, but in the later bouts of a series of consecutive efforts.
Other negative studies are appearing. In one (33) using videotaping, creatine had no effect on the runner's speed at any point during a 60-m sprint. In another study (34), creatine did not improve sprint performance in competitive swimmers. Finally, creatine supplementation does not--nor would it be expected to--benefit aerobic performance, such as a 6-km cross-country running race, and perhaps because of the weight gain, it may actually slow distance running (35).
It is a sad commentary on human nature and society that so much effort is spent trying to detect and deter drug abuse among athletes. But a big-money, winning-is-everything mentality grips much of our social life. Since sport mirrors society, the field of competition is a stage where athletes enact social values. And if winning is everything, some athletes may try anything to win.
The problem is not just how to keep young, sometimes impulsive athletes alive and well while preserving their liberty to do what they please with their bodies. The larger problem for the athlete and society is this: When one athlete decides to use drugs to win, that action presents peers with a vexing dilemma. They remain free to choose whether or not to break the rules as their competitor is doing, but they are no longer free to pursue their dream secure in the faith that the best athlete will win (2). So they are forced to face this troubling question: What price glory?
Dr Eichner is professor of medicine in the Department of Medicine at the University of Oklahoma Health Sciences Center, Oklahoma City. He is a fellow of the American College of Sports Medicine and an editorial board member of The Physician and Sportsmedicine. Address correspondence to E. Randy Eichner, MD, Section of Hematology/Oncology, Dept of Medicine, University of Oklahoma Health Sciences Center, Box 26901, Oklahoma City, OK 73190; e-mail to ereichner@aol.com.