Effect of the MTHFR 677C/T polymorphism on homocysteinemia in response to creatine supplementation: a case study

Creatine (Cr) is recommended as a dietary supplement especially for athletes but its therapeutic potential is also discussed. It is assumed that human body uses Cr for the formation of phosphocreatine, which is necessary for muscular work as a source of energy. Production of Cr in a body is closely connected to methionine cycle where guanidinoacetate (GAA) is in a final step methylated from S-adenosylmethionine (SAM). Increased availability of SAM for phosphatidylcholine (PC) and sarcosine synthesis can potentially stimulate endogenous production of betaine a thus methylation of homocysteine (HCy) to form methionine. Our subject who was methylenetetrahydrofolate reductase (MTHFR) 677TT homozygote lowered plasma HCy from 33.3 micromol/l to 17.1 micromol/l following one-month Cr supplementation (5 g/day) opposite to 677CC and CT genotypes whose HCy levels tended to increase (but still in normal ranges). We suppose that Cr supplementation stimulates pathways leading to production of sarcosine which can serve to regenerate tetrahydrofolate (THF) to form 5,10-methylene-THF. This could potentially increase MTHFR enzyme activity which may later result in increased HCy methylation. Cr supplementation significantly effects metabolism of one carbon unit and potentially lower body´s demands for methyl groups. This could be beneficial as in the case of reduced enzyme activity such as MTHFR 677C/T polymorphism.