The Effects of Creatine Supplementation Among Athletes and Bodybuilders

Creatine is popular as an ergogenic (tends to increase work) aid although limited evidence supports benefits only in high-intensity, short-term exercise. Potential renal effects with long-term use are of concern. For starters, creatine is a nitrogenous amine found in animal products. Omnivores ingest about 1 g daily. Creatine can also be formed in the liver, kidney, and pancreas from glycine, arginine, and methionine. Creatine comprises 0.3% to 0.5% of muscle weight. Most creatine in muscle is in the form of phosphocreatine and about 40% in the form of free creatine. Food sources: Meat, fish and other animal products Main Function Creatine is an important source of energy for muscle contraction because it can undergo both rapid and reversible phosphorylation. Phosphorylation of creatine, catalyzed by creatine kinase, forms phosphocreatine; during dephosphorylation, a phosphate group is donated to ADP forming ATP. This phosphorylation-dephosphorylation reaction provides phosphate for performing high-intensity, short-duration physical activity. Three days of creatine ingestion increases total body water and intracellular fluid volumes without affecting extracellular fluid volumes. Clinical Trials With regard to Ergogenics, creatine research is characterized by many small laboratory studies and very few field studies. Evidence is mixed on the effect of creatine in short-term, high-intensity exercise, and negative trials predominate for other ergogenic effects. A review of creatine supplementation in exercise identified 31 trials of creatine monohydrate supplements on short-term (meaning less that 30 seconds) high-intensity performance, thought to be dependent on endogenous levels of ATP and phosphocreatine. Twenty-two of these trials were randomized, double-blind and placebo controlled, but all were very small (the largest enrolled 36 participants; two-thirds enrolled fewer than 20 participants). Most trials used doses of 20 to 25 g/day. Most of these trials indicated a positive ergogenic effect; however, only 9 of 22 randomized double-blind placebo controlled trials showed a benefit. Fourteen trials of creatine monophosphate in high-intensity, more prolonged, predominantly anaerobic exercise tests were identified. Nine were randomized, double-blind, placebo-controlled trials. The largest trial enrolled only 32 participants, and only three trials enrolled more than 20 people. Most used doses of creatine > 20/day. Five of 14 trials showed a positive ergogenic effect; only two of nine randomized double-blind placebo-controlled trials showed a benefit. Six of these studies were field studies. None of the studies that examined creatine supplementation in swim performance found any benefit. In 12 female runners, creatine supplementation (20g/day x 5 days) did not improve 700-m run time. A single-blind study of creatine supplementation in 10 trained middle distance runners reported a significant benefit. Studies in aerobic exercise performance tests (>150 seconds, testing primarily aerobic glycolysis) are even less impressive. Only two of eight studies of creatine monohydrate supplementation (most used 20g/day) in aerobic exercise performance tests found a benefit of creatine. Of the five randomized double-blind, placebo-controlled trials, only one found a benefit. Only one of five of the field trials found a benefit; one of the field reports found that creatine impaired performance in a forest terrain run. Effects on Body Mass Of 19 publications (including 21 groups) that recorded effects on body mass, increased body mass was noted in 13/21 groups. Short-term supplementation may increase both total body mass and lean body mass (at least in males); however, most of the increased body mass may be due to water retention. Chronic heart failure A double-blind, placebo-controlled trial in 17 males with congestive heart failure tested the effects of creatine 20 g/day x 10 days. There was no effect on ejection fraction; however, compared with the placebo group, creatine increased performance in knee extensor exercise, cycle ergometry, and peak torque. Another study found that creatine supplementation (5 g 4x/day x 5 days) in 20 male congestive heart failure patients increased skeletal muscle endurance and decreased abnormal skeletal muscle metabolic response to exercise in a forearm model of muscle metabolism. Neuromuscular diseases A double-blind, placebo-controlled crossover trial of creatine monohydrate (20g/day x 4 weeks) in 16 patients with chronic progressive external ophthalmoplegia or mitochondrial myopathy found no significant effects of creatine on exercise performance, eye movement, or activities of daily life. A double-blind, placebo-controlled crossover clinical study of creatine (20 g/day) in 36 patient with muscular dystrophies tested the effects of creatine monohydrate (20 g/day x 8 weeks) and found a small but significant improvement in muscle strength and daily life activities. A single-blind study in 21 patients with a variety of neuromuscular diseases gave participants placebo for 11 days, then creatine monohydrate (10 g once a day x 5 days, then 5 g once a day x 5 to 7 days). Compared with baseline, creatine but not placebo improved isometric and isokinetic knee strength, handgrip strength, and dorsiflexion ankle strength over baseline. Adverse Reactions Renal Impairment Creatine breaks down to creatinine, and those with impaired renal function should not supplement with creatine. In addition, long-term studies on the renal effects of creatinine have not been performed. A 25-year old man with focal segmental glomerulosclerosis had maintained normal renal function for years on cyclosporine; renal function deteriorated after starting creatine supplementation. One month after discontinuing creatine, his renal function tests normalized. In clinical trials, no adverse effects have been associated with creatine supplementation of up to 30 g/day for 1 week or up to 3 g/day for 6 weeks. A double-blind, placebo-controlled, 12-week study that included 34 participants tested the effects of creatine monohydrate. Pooled data showed no significant changes in total protein, serum creatinine, bilirubin, blood urea nitrogen, or liver enzymes. However, when results were broken down by sex, there was a significant increase in serum creatine phosphokinase (CPK) in men and a significant increase in serum BUN in women at the end of the study. Both abnormalities returned to normal at a follow-up visit 1 month after the study ended. Drug Interactions Caffeine appears to eliminate any ergogenic effect of creatine. Concurrent use with potentially nephrotoxic drugs should be avoided. Common Dosage Forms 20 to 25 g (0.2 g/kg/day) x 5 days, then maintenance dose of 2 to 4 g/day, is the most commonly tested regimen in clinical trials. However, 3 g/day x 28 days achieves similar intracellular creatine levels, and maintenance doses above 2 g/day (0.03 g/kg/day) appear to have no additional benefit. Is it legal to use creatine supplementation in athletic competition? Yes, it is an allowable substance. References: 1. Williams MH. Creatine supplementation and exercise performance. 2. Lind MC. Nutritional biochemistry and metabolism, with clinical applications. 3. Benzi G. Pharmacol Res 4. Gordon A. Cardiovasc Res 5. Andrews R. European Heart Journal 6. Klopstock T. A placebo-controlled crossover trial in mitochondrial diseases. Neurology. 7. Pritchard NR. Renal dysfunction accompanying oral creatine supplements. 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