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THE PHYSICIAN AND SPORTSMEDICINE - VOL 26 - NO. 6 - JUNE 2021


Creatine Supplements Face Scrutiny

When three college wrestlers died last fall after using severe weight-cutting practices, medical authorities wondered if the use of creatine supplements might have played a role. Analyses so far have not implicated the substance in those episodes, and no clear evidence of harmful side effects of creatine use has yet emerged elsewhere.

Still, as creatine loading has spread from elite settings to high school locker rooms in recent years, questions about safety have been asked more and more often. And as experts await the results of long-term studies, they don't all agree on what to tell patients about creatine use.

A Creatine Profile

Athletes use over-the-counter synthetic creatine monohydrate supplements in attempts to improve performance and build muscle. Sales of creatine are expected to reach $200 million this year (1).

Creatine, an amino acid, is stored in muscle as phosphocreatine. During intense exercise, phosphocreatine breaks down into creatine and phosphate, releasing energy that regenerates adenosine triphosphate (ATP), which in turn fuels muscle contractions (2). The normal daily requirement for creatine is about 2 g for a 70-kg person; about half comes from animal protein in the diet, and the other half is synthesized by the body. A half-pound of raw meat contains about 1 g of creatine.

Several studies have shown that short-term creatine supplementation increases phosphocreatine stores in muscle by 10% to 40% (3). Gains in muscle mass are thought to occur from fluid retention (4) and/or stimulation of protein synthesis (5-7). Creatine supplementation may allow athletes to maintain greater training volumes, which may promote muscle hypertrophy; however, the mechanism is not fully understood (2,3). Creatine is available in powders, pills, gum, candy, and liquid.

Athletes generally take a loading dosage of 20 to 25 g per day (split into 3 or 4 doses) for the first 5 to 7 days, followed by a maintenance dosage of 2 to 5 g per day. Recent reports (8,9) suggest that taking large amounts of glucose with creatine may increase the amount of creatine taken up by muscles.

Interest in creatine supplements has spread beyond the playing field, says Richard B. Kreider, PhD, associate professor and assistant chair in the Department of Human Movement Sciences and Education at the University of Memphis. Creatine is being studied as a therapy to reverse muscle wasting in patients after they have heart surgery and to improve exercise capacity in patients who have chronic heart failure (10,11). "Creatine supplements may also help AIDS and HIV-positive patients reduce muscle wasting," Kreider says. Creatine has also been used to treat certain congenital metabolism errors in infants (12).

Are the Benefits Real?

Several studies (13-15) have shown that creatine improves performance in repeated bouts of high-intensity strength work and repeated sprints. But its effects on single sprint activities are equivocal (13,14,16-18), and it does not appear to enhance endurance exercise (16). Jeff S. Volek, MS, RD, a doctoral student in the sports medicine laboratory in the Department of Kinesiology at Pennsylvania State University in University Park, has been involved in creatine research since 1995 (19). "In acute studies—looking at the effects of a creatine loading regimen—our results confirm the positive effect on performance and increased body mass, increased fat-free mass, and increased strength," Volek says.

On the basis of several research studies and his own observations, says Kreider, the effects of creatine supplementation are impressive and occur very fast. "Athletes can gain 1 to 3 lb the first week," he says. "Then at 2 weeks, there are significant increases in lean mass—in the 4- to 5-lb range above baseline. At 6 weeks, there's an average 10-lb gain in lean mass." Strength gains are equally dramatic, he says.

In one study (15), college football players who took creatine supplements for 28 days during resistance and agility training had significant gains in fat- and bone-free mass when compared with players who took a placebo. An analysis of the literature on creatine (3) states that short-term creatine use increases total body mass by 0.7 to 1.6 kg.

Not all studies have confirmed the ergogenic effects of creatine supplementation, however. An analysis of the studies (2) suggests that individuals may vary in their response to creatine and that supplementation appears to be less effective under certain circumstances—for example, when doses of less than 20 g per day are used for 5 days or less and when low doses are used without an initial loading period.

Mark S. Juhn, DO, a sports medicine physician in the Department of Family Medicine at the University of Washington in Seattle, says that claims for creatine's ergogenic effect can be misleading. It's clear that creatine is ergogenic for subjects doing repeated bouts of stationary cycling in a lab, he says, but the jury is still out regarding single-burst exercise. Furthermore, he says the studies on running and swimming are less consistent in their conclusions, possibly because the weight gain slows athletes down. Juhn says studies involving athletes in competition are lacking, and athletes may not obtain the effects they want.

Juhn has informally surveyed athletes who have tried creatine. "Football players thought it was helpful, but there were plenty of other athletes who said it slowed them down—probably because of the weight gain," he says.

Kreider says about 80% of creatine studies have reported an ergogenic effect. "Nearly all of the 19 studies to be reported at this year's American College of Sports Medicine meeting will report a benefit," he says.

Searching for Side Effects

The Centers for Disease Control and Prevention in Atlanta analyzed the wrestlers' deaths and did not implicate creatine use as a contributing factor (20). The US Food and Drug Administration said it would investigate creatine's possible role in the deaths, but has not yet issued a report.

The only documented side effect of creatine supplementation appears to be weight gain, says Kreider. He says unpublished anecdotal reports about side effects have linked creatine use to muscle strains or pulls, muscle cramps, and renal failure. "Perception isn't always reality. We shouldn't be alarming the public until we see the research," he adds.

Juhn says that though anecdotal reports don't prove side effects, they shouldn't be ignored. He says his main concerns are the long-term effects of creatine use on the kidney and liver—the kidney because it must clear higher levels of creatinine and the liver because it, along with the pancreas and kidneys, stops making endogenous creatine during supplementation.

A 1997 study (21) showed that short-term creatine use (20 g per day for 5 days) did not increase markers of renal stress in five healthy men. A recent case report (22) described a 25-year-old male soccer player who developed renal dysfunction while taking creatine supplements. The patient was being treated for prior focal segmental glomerulosclerosis. He had not exceeded recommended doses. His renal function returned when he stopped taking the creatine supplements.

Juhn also cites studies from the 1970s (23,24) that recognized a possible connection between creatine use and cardiac muscle hypertrophy. "Perhaps this is another reason why we need to be more cautious, especially before recommending long-term supplementation," he says.

Researchers say athletes and their physicians should be aware that the long-term side effects of creatine supplementation have not been studied. Until more is known, says Kreider, anyone who advises athletes about creatine use should offer clear guidelines about dosages to reduce the chances of excessive use.

Volek says he and his colleagues will soon be launching a long-term study of side effects. "We're going to look at metabolic, renal, cardiovascular, and endocrinologic indices—in heat conditions," he says. Anecdotal reports suggest that creatine may exacerbate dehydration, particularly in heat conditions. However, Volek believes long-term side effects are unlikely. "A healthy person should not have any problem with creatine. It's a low-molecular-weight compound that is excreted in the kidney by simple diffusion," he says. "In the maintenance phase, people take the amount of creatine generally found in the diet."

What to Tell Patients

When fielding questions from patients, parents, and coaches, Kreider refers them to reviews that summarize research on creatine.

Physicians should ask patients how much creatine they are taking, say Kreider, Volek, and Juhn. Volek recommends the dosages that have been studied so far: a loading dosage of 20 g to 25 g of creatine per day for 5 or 6 days, followed by a maintenance dosage of 2 to 5 g per day. Juhn advises athletes to account for their body weight when determining a dosage—0.3 g/kg/day of the supplement for loading, then 0.03 g/kg/day for maintenance.

Volek says megadoses do not correlate with greater muscle gains. "There's a limit to how much creatine muscles can take on, and taking larger doses is just creating very expensive urine," he says. Patients should be advised to stop taking creatine if they experience any unusual symptoms, Kreider says. If questions concern a younger athlete, the athlete and parents should be aware that no studies have looked at short-term or long-term effects on growth or health in children or adolescents, according to William O. Roberts, MD, a family physician at MinnHealth SportsCare in White Bear Lake, Minnesota, and an editorial board member of The Physician and Sportsmedicine.

Dietary supplements are not required by current law to meet FDA safety standards. "Always suggest that patients demand a purity test from supplement manufacturers," Kreider says.

Juhn says he advises athletes not to take creatine. "Anyone involved in sports medicine knows that athletes are willing to take some risk for that extra edge, even if it's unproven in actual competition," he says. "But as a physician, I have trouble recommending a non-FDA controlled supplement to people who are perfectly healthy to begin with." However, he will work with and monitor those who insist on using creatine supplements. Juhn keeps the following caveats in mind when treating such patients:

  • Tell them that creatine may or may not improve their performance, that they will gain weight, and that side effects are not well known;
  • Take a thorough medical history;
  • Monitor them with kidney and liver function tests and cardiac exams; and
  • Ensure that they're taking the generally accepted dose.

Roberts adds that athletes should avoid creatine use when dehydration is a concern, such as during heat exposure, during double-session practices, and while making weight in wrestling.

Ethical Issues

Creatine is not structurally or functionally related to anabolic steroids, and creatine supplements are not banned by the International Olympic Committee or the National Collegiate Athletic Association. But creatine use still carries a stigma, says Volek. "I don't think it should be banned, and if it was, it would be difficult to detect—it would require a muscle biopsy," he adds.

Kreider rejects the idea that creatine use gives athletes an unfair advantage. "Creatine use is based on the same principle as carbohydrate loading," he says.

Juhn wonders whether creatine use will prompt athletes to consider other ergogenic aids. Creatine's availability could reduce interest in anabolic steroids, but it could generate interest in other nutrition supplements, he speculates.

Kreider and Volek believe that scientific and public interest in creatine supplementation will continue to build. "I think creatine is here to stay," says Volek. "It works, and people can actually see and feel results. It's been studied for 5 or 6 years, and there's still a lot of public and scientific interest in it."

References

  1. Bramberger M: The magic potion. Sports Illus 192021;88(16):58-65
  2. Kreider RB: Creatine, the next ergogenic supplement? Sportscience Training and Technology. Internet Society for Sports Science. Available at: https://www.sportsci.org/traintech/creatine/rbk.html. Accessed May 5, 192021
  3. Kreider RB: Creatine supplement: analysis of ergogenic value, medical safety, and concerns. Journal of Exercise Physiology Online 192021;1(1). Available at: https://www.css.edu/users/tboone2/asep/jan3.htm. Accessed May 5, 192021
  4. Balsom PD, Soderlund B, Ekblom B: Creatine in humans with special reference to creatine supplementation. Sports Med 1994;18(4):268-280
  5. Bessman SP, Savabi F: The role of the phosphocreatine energy shuttle in exercise and muscle hypertrophy, in: Taylor AW, Gollnick PD, Green HJ (eds), International Series on Sport Sciences: Biochemistry of Exercise VII. Champaign, IL, Human Kinetics, 120218, vol 19, pp 167-178
  6. Ingwall JS: Creatine and the control of muscle-specific protein synthesis in cardiac and skeletal muscle. Circ Res 1976;38(5 suppl 1):I115-I123
  7. Sipila I, Rapola J, Simell O, et al: Supplementary creatine as a treatment for gyrate atrophy of the choroid and retina. N Engl J Med 120211;304(5):867-870
  8. Green A, Sewell D, Simpson L, et al: Creatine ingestion augments muscle creatine uptake and glycogen synthesis during carbohydrate feeding in man (abstract). J Physiol 1996;491:63
  9. Green AL, Simpson EJ, Littlewood JJ, et al: Carbohydrate ingestion augments creatine retention during creatine feeding in humans. Acta Physiol Scand 1996;158(2):195-202
  10. Pauletto P, Strumia E: Clinical experience with creatine phosphate therapy, in Conway M, Clark JF (eds): Creatine and Creatine Phosphate: Scientific and Clinical Perspectives. San Diego, Academic Press, 1996, pp 185-12021
  11. Gordon A, Hultman E, Kaijser L, et al: Creatine supplementation in chronic heart failure increases skeletal muscle creatine phosphate and muscle performance. Cardiovasc Res 1995;30(3):413-418
  12. Stockler S, Hanefeld F, Frahm J: Creatine replacement therapy in guanidinoacetate methyltransferase deficiency, a novel inborn error or metabolism. Lancet 1996;348(9030):789-790
  13. Almada A, Kreider R, Ferreira M, et al: Effects of calcium-HMB supplementation with or without creatine during training on strength and sprint capacity, abstract. FASEB J 1997;11:A374
  14. Earnest CP, Snell PG, Rodriguez R, et al: The effect of creatine monohydrate ingestion on anaerobic power indices, muscular strength and body composition. Acta Physiol Scand 1995;153(2):207-209
  15. Kreider RB, Ferreira M, Wilson M, et al: Effects of creatine supplementation on body composition, strength, and sprint performance. Med Sci Sports Exerc 192021;30(1):73-82
  16. Burke LM, Pyne DB, Telford RD: Effect or oral creatine supplementation on single-effort sprint performance in elite swimmers. Int J Sports Nutr 1996;6(3):222-233
  17. Dawson B, Cutler M, Moody A, et al: Effects of oral creatine loading on single and repeated maximal short sprints. Aust J Sci Med Sports 1995;27(3):56-61
  18. Redondo DR, Dowling EA, Graham BL, et al: The effect of oral creatine monohydrate supplementation on running velocity. Int J Sports Nutr 1996;6(3):213-221
  19. Volek JS, Kraemer WJ, Bush JA, et al: Creatine supplementation enhances muscular performance during high-intensity resistance exercise. J Am Diet Assoc 1997;97(7):765-770
  20. Hyperthermia and dehydration-related deaths associated with intentional rapid weight loss in three collegiate wrestlers—North Carolina, Wisconsin, and Michigan, November-December 1997. MMWR 192021;47(6):105-108
  21. Poortmans JR, Auquier H, Renaut V, et al: A Effect of short-term creatine supplementation on renal responses in men. Eur J Appl Physiol 1997;76(6):566-567
  22. Pritchard NR, Kalra PA: Renal dysfunction accompanying oral creatine supplements, letter. Lancet 192021;351(9111):1252-1253
  23. Ingwall JS, Morales MF, Stockdale FE, et al: Creatine: a possible stimulus for skeletal and cardiac muscle hypertrophy. Recent Adv Stud Cardiac Struct Metab 1975;8:467-481
  24. Ingwall JS: Creatine and the control of muscle-specific protein synthesis in cardiac and skeletal muscle. Circ Res 1976;38(5 suppl 1):I115-I123

Lisa Schnirring
Minneapolis


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