Supplemental creatine may decrease serum homocysteine and abolish the homocysteine 'gender gap' by suppressing endogenous creatine synthesis.

Creatine synthesis is responsible for the large majority of the methyl group transfers in normal hepatic metabolism, and is significantly greater in men than in women. Since methyl group depletion impairs the efficiency of homocysteine disposal, it is believed that the comparatively high rate of creatine synthesis in men is primarily responsible for the 'gender gap' in homocysteine levels. Adequate supplemental intakes of creatine can suppress creatine synthesis by inhibiting expression of the enzyme arginine-glycine transamidase. Thus, it is proposed that creatine supplementation may represent a practical strategy for decreasing plasma homocysteine levels.