Special Report: Nutritional Supplements
By Robert G. Hosey, MD, and Thomas D. Armsey, MD
Synopsis: Many nutritional agents claiming ergogenic performance-enhancing properties are presently available. Understanding their use allows the physician to provide appropriate guidance with regard to efficacy and safety.
Source: Armsey TD, Green GA. Nutrition supplements: Science vs. hype. Physician Sportsmed 1997;25(6):77-92.
Nutritional supplements continue to generate significant public interest and enormous revenues throughout the world. According to the Food and Drug Administration, the 1997 retail sale of dietary supplements generated $12.7 billion in the United States alone. This huge financial incentive, partnered with minimal federal regulation, makes this industry ripe for skepticism and corruption. Because of this, the supplement industry has developed the Council for Responsible Nutrition which selfregulates the industry and promotes legitimate scientific research of nutritional supplements. Unfortunately, these regulatory measures usually only respond to problems in the industry and do not proactively assure supplement safety. In addition, sports superstars have acknowledged the use of supplements in their training regimens, further boosting the mystique surrounding certain supplements. Combine this with advertising aimed at high school, collegiate, and recreational athletes, all eager to improve performance, and it is easy to appreciate the drive behind the increasing popularity of supplement use.
Sports medicine physicians are in an excellent position to advise athletes, coaches, and administrators about the potential benefits and risks of supplements. Therefore, physicians caring for athletes need appropriate knowledge of these "nonbanned" ergogenic aids. The purpose of this article is to review the mechanisms of action, scientific evidence of performance enhancement, and potential adverse effects of the commonly used nutritional supplements.
Creatine Monohydrate
Creatine (methylguanidine-acetic acid) is an amino acid that is found naturally in skeletal muscle and other tissues of the body. Creatine is endogenously synthesized from arginine and glycine in the liver, pancreas, and kidneys. Additional creatine is also obtained from dietary sources such as meats and fish. The majority of creatine exists as phosphocreatine (PCr) in skeletal muscle, while only approximately 25% exists as free creatine. Both creatine and PCr are involved in the production of adenosine triphosphate (ATP), the major intracellular energy compound. As a result of creatine’s involvement in "energy production" via ATP formation, its use as a potential ergogenic aid has evolved.
In 1992, investigators found that creatine supplementation increases skeletal muscle stores of PCr and free creatine. Shortly thereafter it was introduced as a potential ergogenic aid. While use among scholastic, collegiate, and professional athletes has been assumed to be "high," few studies have documented prevalence of use among these groups. However, a recent study by the NCAA revealed that 13% of intercollegiate athletes have used creatine monohydrate in the past 12 months. Additionally, in two separate single division I university settings, 41% of 219 and 28% of 750 athletes surveyed reported using creatine. Among these athletes, use was higher in males and was most prominent with football, track and field, diving, baseball, and basketball athletes.
Dosage and Mechanism of Action
Creatine is generally ingested at a loading dose of 20-25 g for 5-7 days, followed by a maintenance dose of 2 g/d. This regimen increases muscle creatine stores an average of 20%, although individual variations will occur. With cessation of supplementation, creatine stores in skeletal muscle generally return to baseline within four weeks time.
Creatine supplementation increases the bioavailability of PCr inside the skeletal muscle cell. This is thought to enhance muscle performance in two ways. First, during brief, high-intensity (anaerobic) exercise, PCr transfers its phosphate group to ADP, replenishing the available ATP to be used for energy. Second, PCr buffers the intracellular hydrogen ions that are associated with fatigue during exercise. Therefore, creatine supplementation may provide an ergogenic effect by increasing the force of muscular contraction and prolonging exercise capability.
Body Composition and Exercise Performance
Weight gain from creatine supplementation has been noted for both the loading phase and with long-term use. Weight gain has been on the order of 0.5-2.0 kg and likely results from increased body water retention. To date, creatine supplementation has not been consistently proven to result in muscle accretion. It is more likely that long-term body composition changes are the result of the athlete’s ability to perform higher intensities of weight training.
Creatine supplementation has been demonstrated to be ergogenic in repeated bouts of certain activities including weight lifting, cycling, running, rowing, and repetitive sets of muscle contractions. How this data applies to athletic performance on the field, however, has yet to be elucidated. Furthermore, creatine supplementation has no proven ergogenic ability in activities that are primarily aerobic in origin. Weight gain associated with creatine use in these endurance type athletes may offset any potential gains from creatine supplementation.
The mean Cr concentration in human skeletal muscle is approximately 125 mmol/kg-dm with a "normal range" of 90-160 mmol/kg-dm. Approximately half of athletic subjects will exhibit concentrations lower than 125 mmole/kg-dm, with women and strict vegetarians substantially lower. Those individuals with skeletal muscle concentrations of ([Cr] < 125) are likely to exhibit the most significant increases in muscle Cr concentration, PCr resynthesis, and performance enhancement with the use of creatine supplementation. Athletes with levels of Cr at the higher end of the normal range are more apt to show little or no ergogenic effect from creatine supplementation. This wide spectrum of Cr concentrations in athletes may explain many of the conflicting results in the literature.
Side Effects
No deleterious side effects have been consistently documented in subjects using short-term creatine supplementation. However, there have been anecdotal reports of creatine causing nausea/vomiting, hypertension, renal dysfunction, muscle cramping, and dehydration. While there is a lack of scientific evidence to implicate creatine supplementation as a health risk, this does not necessarily equate with safety of the supplement. As creatine is a relatively new supplement, the long-term effects and, perhaps, even some of the short-term effects of creatine supplementation remain unknown.
Chromium Picolinate
Chromium is an essential trace mineral present in various foods, such as mushrooms, prunes, nuts, whole grain breads, and cereals. It has been found that the intake of chromium in the general population is less than the recommended daily amounts. Chromium by itself has a low gastrointestinal absorption rate. As a result, three molecules of picolinic acid are often added to increase the absorption and bioavailability and produce the supplement chromium picolinate (CrPic).
Mechanism of Action
Chromium supplementation became popular after it was found that exercise increases chromium loss, raising the concern that chromium deficiency may be prevalent among active individuals. Chromium seems to function as a co-factor that potentiates the action of insulin in carbohydrate, fat, and protein metabolism. Promoters of CrPic claim it increases glycogen synthesis, improves glucose tolerance and lipid lipoprotein profiles, and increases lean body mass.
Body Composition and Exercise Performance
Early on, CrPic supplementation seemed to hold some promise as an ergogenic aid. Decreased percent body fat and increased lean mass were found in collegiate athletes and students performing resistance training and taking 200 mcg per day of CrPic. Critical analysis of these studies, however, reveals that imprecise measurement techniques may have accounted for these "ergogenic" results. More recent studies using precise measurement techniques have failed to demonstrate any significant improvement in percent body fat, lean body mass, or strength. Therefore, the current consensus of the scientific community is that CrPic is ineffective as an ergogenic aid.
Side Effects
Most of the studies involving CrPic have been short-term studies and have revealed no major side effects. However, when supplemented at doses of 50-400 mcg per day, CrPic has been implicated in precipitating adverse events including anemia and cognitive impairment. Therefore, with a limited scientific rationale as an ergogenic aid and the noted potential adverse effects, CrPic supplementation should be discouraged.
Beta-Hydroxy-beta-Methylbutyrate
One of the most recent additions to the nutritional supplement armamentarium is beta-hydroxy-beta-methylbutyrate (HMB). HMB is a metabolite of the essential branched-chain amino acid, leucine, and is produced in small amounts endogenously. HMB is also found in various food sources, such as catfish, citrus fruits, and breast milk. In the early 1980s, HMB was studied as a repartitioning agent in livestock because of its ability to promote lean muscle mass without the use of anabolic hormones.
Mechanism of Action
HMB seems to be unique in regards to its mechanism of action. It has been hypothesized that HMB is an anti-catabolic agent that results in a decrease in protein breakdown. Although the exact mechanism of action is currently unknown, promoters suggest that HMB regulates the enzymes responsible for protein or muscle breakdown, decreasing protein (muscle) catabolism, thereby creating a net anabolic effect. By minimizing protein breakdown, HMB, when combined with a resistance-training program, may cause an increase in muscle mass and strength.
Body Composition and Exercise Performance
Scientific research in livestock and humans seems to suggest that supplementation with HMB may, in fact, increase lean muscle mass and strength. Nissen has conducted randomized, double-blinded, placebo-controlled studies to evaluate the ergogenic potential of HMB in exercising males. In the first study, 41 untrained subjects participated in a four-week-structured resistance-training program. This study demonstrated statistically significant improvements in lean muscle mass and strength as well as significant decreases in muscle breakdown products (3-methylhistidine and creatine phosphokinase) while supplementing a controlled diet with 1.5 or 3.0 g HMB/d vs. controls. The second study evaluated both trained and untrained male subjects in a similarly designed weight training program. Both groups demonstrated statistically significant increases in lean muscle mass and one-repetition maximum bench press with a coincident decrease in percent body fat vs. controls with the use of 3.0 g HMB/d.
Therefore, HMB supplementation (dosages of 1.5-3.0 g/d) has been shown to augment resistance-training programs in novice and experienced male subjects with regard to muscle mass, strength, and percent body fat, presumably by decreasing muscle catabolism. Further studies regarding this supplement may continue to support these anabolic, "steroid-like" effects, as well as elucidate the role of HMB in protein metabolism.
Side Effects
Currently, there are no reported sideeffects of HMB supplementation, but the safety profile of this agent is still unknown. Also, there are no corroborating studies to prove that HMB is an effective ergogenic aid. Therefore, it is premature to recommend HMB supplementation as a safe and effective ergogenic aid.
Dehydroepiandrosterone
In 1996, the FDA banned the sale and distribution of dehydroepiandrosterone (DHEA) for therapeutic purposes until the safety and efficacy profiles could be reviewed. Although this action was instituted to decrease the availability of this agent, the ensuing media attention served to popularize this supplement. Currently, by avoiding therapeutic claims, manufacturers are still able to sell DHEA as a nutritional supplement. DHEA was discovered in 1934 to be an androgenic hormone produced in the adrenal glands. It is a precursor to the production of both androgens and estrogens in primates. It is also available exogenously in wild yams which are sold in many health food stores as a source of DHEA.
The current theoretical action of DHEA stems from the fact that as a precursor to androgenic steroids, it may increase the production of testosterone and provide an "anabolic steroid effect." Promoters also claim that DHEA slows the aging process and advertise it as the "fountain of youth."
Body Composition and Exercise Performance
Only a few randomized, double-blinded, placebo-controlled studies have been published on the effects of DHEA supplementation. 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/d for six months or 100 mg/d for 12 months. Whether DHEA has any effect on body composition or fat distribution is still unclear. The effect of DHEA on healthy individuals younger than 40 years of age is also unknown and virtually unstudied.
Side Effects
Few consumer complaints have been reported as to the adverse effects of DHEA. The most concerning are the irreversible virilizing effects seen in women, including hair loss, hirsutism, and voice deepening. Males have also reported irreversible gynecomastia with DHEA use which may occur from an elevation in estrogen levels. Because the current scientific knowledge is inadequate, long-term adverse effects are unknown. Therefore, the safety of this "hormone replacement" therapy must be queried prior to its medical endorsement. Unlike most other nutritional supplements, DHEA may substantially increase the risk of uterine and prostate cancer that accompanies prolonged elevated levels of unopposed estrogen and testosterone.
Also of interest to competitive athletes, DHEA supplementation may alter the testosterone/epitestosterone ratio to levels that exceed the 6:1 ratio used by the International Olympic Committee (IOC) and National Collegiate Athletic Association (NCAA) to screen for exogenous testosterone use and, thus, may create a risk for disqualification from international competition. Due to the lack of clinical evidence that DHEA enhances performance in athletes, as well as the potentially devastating adverse effects associated with its use, DHEA supplementation should not be endorsed by the medical community.
| Table: Cost Comparison | |
| Creatine |
20-25 g/d (loading dose): $7.20/d for one week 2 g/d (maintenance dose): $3.60/d |
| Chromium | 200 mcg/d: $0.43/d |
| HMB |
3.0 g/d: $3.48/d 1.5 g/d: $1.74/d |
| DHEA |
50 mg/d: $0.67/d 100 mg/d: $1.34/d |
| National Supplement Association and General Nutrition Centers | |
Conclusion
This article presents information regarding several popular nutritional supplements and their use as ergogenic aids. Although some of these supplements may have potential benefits, it is important to mention the NCAA guidelines which state, "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."
The skepticism over nutritional supplements is due to a number of factors. As mentioned in this article, there is a paucity of properly performed scientific research to support a positive effect for many of these substances. In addition, the lack of rigorous FDA regulation may lead to impurities in the preparation of supplements as has already been documented in a number of investigative reports. Finally, the cost of nutritional supplements must be addressed. The Table demonstrates the considerable financial burden that is created by these often unproven ergogenic aids. In an era of shrinking athletic department budgets, it makes little sense to invest in nutritional supplements which offer little or no benefit to the athlete. Therefore, decisions regarding the use of nutritional supplements should only be made on the basis of proper scientific study and proven benefit to the patient.
Selected References
1. Kraemer WJ, Volek JS. Creatine supplementation: Its role in human performance. Clin Sports Med 1999;18(3):651-666.
2. Armsey TD, Green GA. Nutrition supplements: Science vs. hype. Physician Sportsmed 1997;25(6).
3. Lefavi RG. Sizing up a few supplements. Physician Sportsmed 1992;20(3):190.
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