By Karin Krisher of DaVinci Labs
Single-nucleotide polymorphisms (SNPs) in the MTHFR gene are quite prevalent; by some estimates, up to 40 percent of people have some mutation in this gene.[1] A great number of variants of this gene have been identified, though some are more thoroughly researched than others. Ultimately, SNPs in the gene that code the enzyme methylenetetrahydrofolate reductase mean that the enzyme produced will display decreased activity, a difference that can have far-reaching effects on health.
This article will examine ways in which the consequent impaired conversion of 5,10-methylenetetrahydrofolate to active form of folate (5-MTHF) a methyl donor, can affect various aspects of biological wellness.[2]

  1. You may be down in the dumps

Folate is necessary for the body to properly synthesize serotonin, epinephrine and dopamine. Active folate, 5-MTHF, is involved in homocysteine remethylation and the creation of methionine. SAM-e, a methyl donor itself, is a metabolite of methionine. When 5-MTHF is not present, the disease process of depression may result, due to a decrease in both SAMe and neurotransmitter levels in cerebrospinal fluid.[3]
Folate metabolism and methylation are intimately linked. BH4, a cofactor essential to the formation of serotonin, norepinephrine and dopamine, is dependent on folate metabolism – meaning we know of at least two ways impaired folate metabolism and/or lack of active folate may impact mood.

  1. Your heart may suffer

When folate conversion and methylation are impaired, the resulting impaired ability to recycle homocysteine can give rise to a multitude of health concerns, one of the most well-known of which is cardiovascular disease. Hyperhomocysteinemia’s connection to CVD is oft-debated, but it is clear, at least, that homocysteine is an independent risk factor for atherosclerosis.[4]

  1. Mental illness can emerge

One of the two most well known variants of MTHFR, C677T, is significantly associated with schizophrenia and bipolar disorder, as well as unipolar depressive disorder, while the other, called A1298C, is associated with bipolar disorder only. Interestingly, research suggests that people with C677T SNP and elevated serum homocysteine are at increased risk for schizophrenia.[5]

  1. You may seriously lack energy

The methylation reactions facilitated by the health of our folate cycles are necessary for forming energy. For example, as we know, coenzyme Q10 is critical to our body’s energy production process, through its role in the mitochondrial respiratory chain. The synthesis of CoQ10 requires adequate levels of some substances in the methylation pathway – specifically, SAMe, which is generated within the methylation cycle. Impaired folate metabolism can affect adequate levels of SAMe, leading to concerns about energy production.

  1. You may not be able to eliminate toxins or “bad” metabolites

Because part of our detoxification process involves attaching toxins to methionine prior to elimination, a sufficient level of methionine is required. The conjugation process that is methylation occurs in every cell to help our bodies eliminate excess neurotransmitters, hormones and homocysteine. SAMe is also an important part of this process, as it helps the body produce methyl-based substances.
In those with insufficient methylation capabilities due to MTHFR mutations, detoxification processes can be hindered. It is common for heavy metal elimination to suffer, which can lead to behavioral concerns, fatigue, and more.[6]
Whatever the MTHFR SNP may be, the effects on health can be monumental. Specifically, folate metabolism and methylation may be impaired – thus contributing to the impairment of a variety of bodily functions. Patients should address MTHFR mutations with a health care professional in order to optimize diet and supplement regimens for sufficient methylation.
[1] Stein, Traci. A Genetic Mutation That Can Affect Mental & Physical Health. Psychology Today. September 5, 2014.
[2] Genetics Home Reference: MTHFR. U.S. National Library of Medicine. Published September 28, 2015. Accessed September 30, 2015.
[3] Miller AL. The methylation, neurotransmitter, and antioxidant connections between folate and depression. Altern Med Rev. 2008;13(3):216-26. Available at:
[4] Pang X, Liu J, Zhao J, Mao J, Zhang X, Feng L et al.. Homocysteine induces the expression of C – reactive protein via NMDAr-ROS-MAPK-NF-κB signal pathway in rat vascular smooth muscle cells. Atherosclerosis. 2014; 236:73-81.
[5] DiLuglio, BE. Understanding MTHFR Genetic Mutation. PreviMedica. 2015. Available at: Accessed October 1, 2015.
[6] Things that Plague Us: Heavy Metals. MTHFR Living. 2014. Available at: Accessed October 1, 2015.

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.