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Creatine Supplementation Lowers Homocysteine in MTHFR Case

Creatine supplementation produces unique effects on homocysteine in individuals with MTHFR polymorphism, lowering plasma homocysteine levels instead of raising them in this case study. This is relevant to the methylation cycle and thus to glaucoma, as discussed in other artlcles on FitEyes.

Physiol Res. 2013 Dec 20;62(6):721-9. Epub 2013 Jul 17.

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 creatine for the formation of phosphocreatine, which is necessary for muscular work as a source of energy.

Production of creatine 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 (aka trimethyl-glycine or TMG) a thus methylation of homocysteine (HCy) to form methionine.

NOTE: This is part of what we have been callling the methylation cycle.

Our subject was methylenetetrahydrofolate reductase (MTHFR) 677TT homozygote (two MHTFR C677T SNPs). Creatine lowered the subject's plasma homocysteine from 33.3 micromol/l to 17.1 micromol/l following one-month creatine supplementation (5 g/day). This is the opposite to 677CC (no mutation) and CT (single SNP) genotypes whose plasma homocysteine levels tended to increase (but remain in normal ranges) with creatine supplementation.

We suppose that creatine 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 homocysteine methylation (forming methionine and thus lowering plasma homocysteine).


Creatine supplementation significantly affects metabolism of one carbon units* 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.

* one carbon metabolism refers to what we are calling the methylation cycle. Methyl groups are one carbon units (CH3).

PMID: 23869894

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