Methylenetetrahydrofolate reductase (MTHFR) is one of the most important enzymes in human physiology, deficiencies in production or function of this enzyme have been associated with increased risk of different diseases.
These defects relate to MTHFR are very common, though they vary enormously between ethnic groups and regions.
Put most simply, MTHFR is an important enzyme in the pathway that convert folate into the activated form, 5-MTHF or 5-methyltetrahydrofolate. Though this reaction plays a part in many biochemical cycle, it is probably best-known in the context of breaking down the amino acid homocysteine. This process produces methionine and eventually S-Adenosylmethionine (SAMe), a crucial DNA methylator.
Emerging science of nutrigenomics indicates that some individuals, due to their unique genetic patterns and expression, have polymorphic forms of this enzyme and do not produce adequate or effective MTHFR.
Cutting edge scientific research is shed light how much the MTHFR polymorphism is implicated in chronic disease states and how folate nutrition may contribute to replace adequate methylation and overall health.
Several evidences highlight the advantages of the supplementation of reduced folate (such as Quatrefolic®) vs folic acid.
Quatrefolic® is the glucosamine salt of (6S)-5-methyltetrahydrofolate and is structurally analogous to the reduced and active form of folic acid so Quatrefolic® completely bypasses the "damaged" MTHFR conversion step and delivers a "finished" folate the body can immediately use.
The inability of a part of world's population to assimilate and metabolize folic acid from food or supplements may jeopardize their health and increase the risk of adverse health outcomes as recent study as shows.
New link of MTHFR Gene Mutations and health
Neural Tube Defects
In a meta-analysis Tsang et al., assessed the association between MTHFR C677T genotypes and blood folate concentrations among healthy women between 12-49 y, finding a consistent low folate concentration with this polymorphism that could have a major risk to have a child with neural-tube defects.
Jadavji et al., highlighted that genetic or nutritional disturbances in one-carbon metabolism, with associated hyperhomocysteinemia, can result in complex disorders including pregnancy complications and neuropsychiatric diseases. Maternal MTHFR deficiency resulted in short-term memory impairment in offspring. These dams had elevated levels of plasma homocysteine when compared with wild-type dams.
Gong et al., performed a meta-analysis of published case-control studies to re-examine the role of Methylenetetrahydrofolate reductase (MTHFR) polymorphism as a risk factor for male infertility. Results indicated that the MTHFR polymorphism is associated with an increased risk of male infertility.
Varicose vein disease and its thrombotic complications.
As reported by Fernandez-Peralta et al., alterations in the enzyme function (as seen in gene polymorphic variants) could lead to elevated levels of homocysteine, free radical formation, and endothelial damage. This could potentially suggests that there may be a link between MTHFR in the pathogenesis of varicose vein disease and its thrombotic complications.
Besides many evidences had showed a role of disturbed folate metabolism in increasing risk for autism, with methylenetetrahydrofolate reductase (MTHFR) being a pivotal enzyme controlling it. Scientific data provided by Meguid et al., supports an increased risk for ASD in association with MTHFR 1298 AC/CC polymorphism and hence a role of folate/methylation cycle disturbances is suspected in autism.