Methylenetetrahydrofolate reductase (MTHFR) is a gene that is responsible for producing an enzyme that converts folic acid to methylfolate, a bioavailable form of vitamin B9. Nutrient deficiencies of Vitamin B6, B12, and folate increase homocysteine levels which cause inflammation in the body. The ability of this gene to turn this switch on or off is crucial for the production of glutathione, the body’s most important antioxidant.
Glutathione plays a major role in the body’s detoxification of harmful, disease causing toxins. When the body’s ability to produce glutathione is decreased, secondary to genetic mutations like an MTHFR mutation, the disease process is enhanced due to the build-up of toxicity in the body. Disorders such as autism, ADHD, autoimmune diseases, multiple sclerosis, fibromyalgia, heart disease, addiction, miscarriages, and neural tube defects have been linked to MTHFR mutations. Mutations in MTHFR may lead to a condition called homocystinuria, a disorder where there are abnormal levels of homocysteine and methionine in the body which may lead to eye problems, cognitive issues, abnormal blood clotting, skeletal and congenital heart abnormalities.
Glutathione’s key role is the maintenance of intracellular redox balance (oxidation-reduction) and the detoxification of xenobiotics (a chemical or substance foreign to the body). A defective MTHFR gene creates a vulnerability to disease processes as detoxification is impaired, leaving the body more susceptible to oxidative stress, and less tolerant of toxins such as heavy metals.
In children with ASD, the heterozygous allele frequency occurred in 56% of children, whereby the frequency was significantly lower in the control group (41%). This could indicate that there is a genomic vulnerability in the folate pathway to environmental risk factors. Although a review of the research indicates conflicting analysis, some studies show an association exists between MTHFR polymorphisms and an increased risk of ASD, suggesting the modulating role of folate may be affected by the MTHFR genotype. Another study suggests that the enhanced maternal folate status before and during pregnancy may alter natural selection by increasing survival rates of fetuses who have an MTHFR mutation. Presumably, infants with an MTHFR polymorphism cannot maintain the higher folate status after birth, affecting neurodevelopment from the inability to detoxify environmental toxins. For example, individuals with ASD have been shown to have higher levels of heavy metals in their blood, leading researchers to believe that the MTHFR polymorphisms may be partly responsible for increasing their toxicity. While an association is likely, it is unlikely that this mutation is solely responsible for complex neurodevelopmental disorders and more probable that influencing co-factors exist.