The Methylene Tetrahydrofolate Reductase (MTHFR) isoform challenge. High doses of folic acid are not a suitable option compared to 5 Methyltetrahydrofolate treatment

Abstract

Methylene Tetrahydofolate Reductase (MTHFR) is an enzyme participating to the " folic acid cycle " which is linked to the one carbon cycle (1-CC). These combined metabolic cycles are involved in methylation, a major biochemical process. Methylation is performed on lipids, proteins and DNA. DNA methylation is involved in major cellular processes such as gene transcription, genomic imprinting and epigenesis. MTHFR have several genetic isoforms: the most common are C677T and A1298C, both of them are frequent and negatively affect the methylation process, as they impair the formation of the metabolically active folate 5MTHF (Methylene tetrahydrofolate) . This biochemical deficiency alters strongly fertility through a deleterious impact on gamete quality. We discuss here the necessity of testing the MTHFR in case of long lasting impaired fertility and repeat miscarriages. We present also our preliminary data associated with literature data indicating that high doses of Folic acid, a synthetic compound, are not a reasonable option. These patients must be treated with 5MTHF, associated with a support of the 1-CC a in order to back up the methylation process.