Creatine is an important energy substrates for the muscle and brain. Many randomized studies have provided suggestive data that creatine enhances athletic performance. Short periods of creatine supplementation does not seem to increase endurance or aerobic performance. However, much evidence indicate that creatine supplementation improves performance of repeated bouts of short and intense strength exercises. Creatine supplementation may facilitate rehabilitation of neurological conditions and muscular atrophy. One study indicated that creatine monohydrate for a week increased oxygen consumption, produced greater carbon dioxide output, and improved respiratory tidal volumes in people with spinal cord injury. Another suggested that creatine supplements retards or reverses rebuilding of atrophied muscles associated with leg casting. Creatine also has significant beneficial effects in patients who have creatine deficiency. The optimal dose and duration of creatine supplementation depends on the individual. The body synthesizes creatine and meat contains relatively high concentrations of creatine. The daily body turnover of creatine is 2-4 grams. There is no evidence that creatine intake greater than 20-30 g/day has any additional beneficial effects of creatine uptake by muscle or performance. A 5-7 days period of high-dose (20 gram/day) creatine followed by a maintainance dose of 5 grams of creatine per day during the exercise period is reasonable. Orally ingested creatine is taken up by muscle. The creatine does not appear to stimulate protein synthesis although one study suggested that the creatine may stimulate muscle satellite cells to produce more cells. The creatine is phosphorylated in the muscle. Creatine is also taken up by other tissues where it may exert a number of other effects, including improvement of oxygen consumption and reduction of blood lipids. Creatine has major effects on the brain and the heart. In patients who might be short of creatine or have a disease that reduces creatine levels, creatine supplement may have dramatic effects. Creatine and creatine analogs also have been reported to have anti-tumor effects. In particular, an analog of real-time called cyclocreatine appears to increase Na and death of tumor cells. Despite its important role in energy metabolism in many tissues, creatine supplementation has had remarkably consistent safety record. Athletes often consume 20 grams of creatine monohydrate per day for weeks, months, and even years without any well-substantiated report of adverse side-effects. Although anecdotal reports of muscle cramps and hormonal effects abound, controlled clinical studies have not reported such effects. Thus, creatine appears to be a relatively safe dietary supplement that may facilitate rehabilitation of atrophied muscles and enhance exercise therapies. Side effects are minimal perhaps because the creatine-loaded tissues do not take up additional creatine. Creatine does not affect growth hormone or other hormones and there is no convincing data that it causes kidney or liver damage.