Drug Guide


By Anthony McDaniel, M.D.

Creatine is a nitrogenous organic acid that occurs naturally in vertebrates and helps to supply energy to all cells in the body, primarily muscle, by increasing the formation of Adenosine triphosphate (ATP). Creatine was identified in 1832 when Michel Eugène Chevreul discovered it as a component of skeletal muscle, which he later named creatine after the Greek word for meat. In solution, creatine is in equilibrium with creatinine. Creatine supplements are sometimes used by athletes, bodybuilders, and others who wish to gain muscle mass, typically consuming 2 to 3 times the amount that could be obtained from a very-high-protein diet. A survey of long-time use gives the creatine content of several foods. The Mayo Clinic states that creatine has been associated with asthmatic symptoms and warns against consumption by persons with known allergies.

While there was once some concern that creatine supplementation could affect hydration status and heat tolerance and lead to muscle cramping and diarrhea, recent studies have shown these concerns to be unfounded. There is less concern today than there used to be about possible kidney damage from creatine, although there are reports of kidney damage, such as interstitial nephritis; patients with kidney disease should avoid use of this supplement. In similar manner, liver function may be altered, and caution is advised in those with underlying liver disease although studies have shown little or no adverse impact on kidney or liver function from oral creatine supplementation. In theory, creatine may alter the activities of insulin. Caution is advised in patients with diabetes or hypoglycemia, and in those taking drugs, herbs, or supplements that affect blood sugar. Serum glucose levels may need to be monitored by a health-care professional, and medication adjustments may be necessary.

Long-term administration of large quantities of creatine is reported to increase the production of formaldehyde, which has the potential to cause serious unwanted side-effects. However, this risk is largely theoretical because urinary excretion of formaldehyde, even under heavy creatine supplementation, does not exceed normal limits. Extensive research over the last decade has shown that oral creatine supplementation at a rate of 5 to 20 grams per day appears to be very safe and largely devoid of adverse side-effects while at the same time, effectively improving the physiological response to resistance exercise, increasing the maximal force production of muscles in both men and women. A placebo-controlled double-blind experiment found that vegetarians who took 5 grams of creatine per day for six weeks showed a significant improvement on two separate tests of fluid intelligence, Raven's Progressive Matrices, and the backward digit span test from the WAIS. The treatment group was able to repeat longer sequences of numbers from memory and had higher overall IQ scores than the control group. The researchers concluded that "supplementation with creatine significantly increased intelligence compared with placebo." A subsequent study found that creatine supplements improved cognitive ability in the elderly. A study on young adults (0.03 g/kg/day for six weeks, e.g., 2 g/day for 150-pound individual) failed, however, to find any improvements.

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