Introduction to Creatine

[ The Scoop ]

[ Certifcation ]

What is creatine?
Creatine, or methylguanidine-acetic acid, is a compound synthesized from the amino acids arginine, glycine, and methionine. We obtain creatine from our diet via foods such as meats and fish, and we synthesize it in the liver and pancreas. Recently, supplements of creatine monophosphate have become available. The vast majority of our bodies’ supply of creatine is in our skeletal muscle—some exists as the free molecule, but most of it binds with a phosphate group to form the high-energy compound phosphocreatine.1 Keeping a ready supply of phosphate molecules helps the body replenish its supply of its energy currency, ATP (adenosine triphosphate). As the muscle uses energy, it breaks the phosphate bonds, and converts ATP to ADP and AMP (adenosine diphosphate and monophosphate, respectively). Phosphocreatine then donates its phosphate group to these molecules to re-form the ATP. Without the presence of phosphocreatine, our muscles’ ATP supplies would be drained within only a few seconds of beginning a high-intensity activity, leaving us fatigued and unable to continue.2, 3 (Indeed, a study by Katz et al in 1986 showed that fatigue following a short-term, high-intensity exercise was more closely related to a low phosphocreatine concentration than to a high lactic acid concentration.4) Thus, creatine plays an integral role in our athletic performance. The appeal of supplementation is that, according to this pathway, more creatine would theoretically equal more readily available energy for the muscles, and therefore improved athletic performance.

Does it work?
The first hurdle in evaluating the effectiveness of creatine supplementation was ensuring that the supplements made their way into the muscle (several studies that found creatine monophosphate to have no effect on performance failed to measure whether the supplement actually increased the muscle concentration of phosphocreatine). A study conducted by Harris et al. in 1992 showed that mixed muscle phosphocreatine levels were increased by ingestion of a creatine supplement by humans.5 Then, in 1993, Greenhaff et al. showed that creatine supplementation improved performance during repeated knee extension exercises, with up to a 6% decrease in fatigue.6 Since then, studies using models involving sprint-like activities in cycling, running, and swimming have found similar results.7-10 These benefits do not translate to endurance exercises, however, probably because of the differences in the muscle types used. The muscles used for short-duration, high-intensity contractions consist mainly of Type II (“fast-twitch”) fibers. These fibers are best adapted for anaerobic (no oxygen) energy production, and are characterized by high ATPase and creatine phosphokinase activity. Conversely, the muscles used for long-term, lower-intensity contractions (such as maintaining posture, long distance running or cycling, etc.) consist mainly of Type I (“slow-twitch”) fibers. These fibers are best adapted for aerobic (oxygen-using) energy production, and are characterized by low ATPase activity and, presumably, low creatine phosphokinase activity.11

What’s the catch?
All the studies mentioned above found significant individual variation in both creatine absorption and athletic performance. It seems the lower an individual’s baseline level of creatine (“low” in this case refers to the low end of the normal spectrum; unless he/she has a genetic deficiency, a person will not be deficient in creatine), the more that person’s creatine concentration will increase as a result of supplementation, resulting in a greater observed improvement in performance.1 Also, the long-term ergogenic (performance-enhancing) effects of creatine remain unknown. Hultman et al. determined that after an initial “loading period” of 20 g/day for 6 days, a smaller dose of 2 g/day is sufficient to maintain a high concentration of total creatine in the muscle for a period of approximately 28 days.12 The effects of maintaining muscle creatine concentration beyond this point are unknown. Also, “a consistent finding from several studies is that there appears to be a definable upper limit to the intramuscular total creatine concentration of about 160 mmol/kg dry mass; once this limit is reached, further supplementation will simply result in excretion of creatine in the urine.”1 For this reason, concern about the long-term effects of creatine supplementation on renal and hepatic function remains. Side effects noted thus far include weight gain, changes in insulin production, inhibition of the body’s endogenous creatine synthesis, and gastrointestinal irritation.13

The Numbers:
Supplementary doses of creatine are usually at or around the level of daily turnover, or about 2 g/day. “In healthy athletes submitted daily to high-intensity strength or sprint training, the maximal oral creatine monohydrate supplementation should be of the order of two times the daily turnover, i.e., less than 5-6 g/day for less than two weeks, and the creatine monohydrate supplementation should be taken under appropriate medical supervision.”13 Unfortunately, consumers do not seem to be adhering to dosage recommendations: Ray et al. conducted a study on creatine use in competitive athletes, including adolescents, and found that use is widespread, and “inconsistent with optimal dosing.”14 Oral administration of more than 6 g/day is used only for clinical use, in the case of a creatine deficiency, for example. Ongoing research is exploring the potential therapeutic effects of creatine administration for patients with diseases involving problems with skeletal muscle, including Hodgkin’s disease and ALS.

Written by:
Jacqueline Munch,
UM Medical School

Reviewed for medical accuracy by:
Virginia Uhley, Ph.D., R.D.
Dept. of Integrative Medicine

Added to knowledge base:

[ References ]
  1. Casey A and Greenhaff PL. Does dietary creatine supplementation play a role in skeletal muscle metabolism and performance? American Journal of Clinical Nutrition. 72(supplement):607S-17S, 2000.

  2. Gaitanos GC et al. Human muscle metabolism during intermittent maximal exercise. Journal of Applied Physiology. 752:712-19, 1993.

  3. Bogandis GC et al. Recovery of power output and muscle metabolites following 30s of maximal sprint cycling in man. Journal of Physiology (London). 482:467-80, 1995.

  4. Katz et al. Muscle ATP turnover rate during isometric contraction in humans. Journal of Applied Physiology. 611:54-60, 1986.

  5. Harris RC et al. Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation. Clinical Science. 83:367-74, 1992.

  6. Greenhaff PL et al. Influence of oral creatine supplementation on muscle torque during repeated bouts of maximal voluntary exercise in man. Clinical Science. 84:565-71, 1993.

  7. Balsom et al. Creatine supplementation and dynamic high-intensity intermittent exercise. Scandinavian Journal of Medical Science and Sports. 3:143-9, 1993.

  8. Harris et al. The effect of oral creatine supplementation on running performance during maximal short term exercise in man. Journal of Physiology. 467:74(abstract), 1993.

  9. Birch R. et al. The influence of dietary creatine supplementation on performance during repeated bouts of maximal isokinetic cycling in man. European Journal of Applied Physiology. 69:268-70, 1994.

  10. Earnest CP et al. The effect of creatine monohydrate ingestion on anaerobic power indices, muscular strength and body composition. Acta Physiologica Scandinavica 1995; 153: 207-9.

  11. Burke RE. Motor units: anatomy, physiology, and functional organization. In: Brooks VB, ed. Handbook of physiology. Section 1: the nervous system, Vol II (1). Bethesda, MD: American Physiological Society. 345-422, 1981.

  12. Hultman et al. Muscle creatine loading in man. Journal of Applied Physiology. 811:232-7, 1996.

  13. Benzi G and Ceci A. Creatine as nutritional supplementation and medicinal product. Journal of Sports Medicine and Physical Fitness. 41(1):1-10, 2001.

  14. Ray TR et al. Use of oral creatine as an ergogenic aid for increased sports performance: perceptions of adolescent athletes. Southern Medical Journal. 94(6):608-12, 2001.
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