MTHFR current research and risks

Impaired production of glutathione, which is the body’s most intracellular anti-oxidant,
contributes to tissue injury in inflammatory bowel disease (IBD) (1)
This cellular injury predisposes individuals to an increased risk of colorectal cancer (2).

How can we increase our glutathione levels?

Homocysteine is an amino acid that your body makes from another amino acid called methionine. You obtain methionine from many of the protein-dense foods that you eat on a regular basis, such as sunflower seeds, eggs, and fish.

Normally, homocysteine found in your blood gets converted into two substances called SAMe (S-adenosyl methionine) and glutathione. Both SAMe and glutathione have health-promoting effects. Specifically, SAMe helps to prevent depression, arthritis, and liver damage. Glutathione is a powerful antioxidant and detoxifying agent that helps to slow down aging.

Conversion of homocysteine to SAMe requires the following nutrients:

Folate, Vitamin B12, Vitamin B2, Zinc, TMG (trimethylglycine – from choline), Magnesium

Conversion of homocysteine to glutathione requires the following nutrients:

Vitamin B6, Vitamin B2, Zinc

When your body does not efficiently convert homocysteine into SAMe and glutathione, the amount of homocysteine in your blood rises.

Put another way, you want your body to efficiently convert homocysteine into SAMe and glutathione.

The Evidence

A  meta-analysis conducted in suggests that MTHFR A1298C polymorphism is associated with increased cervical cancer and lymphoma risk in Asians, however found MTHFR A1298C polymorphism is associated with decreased colorectal cancer risk in Asians (3).  Conflicting evidence however, found across various racial–ethnic groups opposing findings in subgroups, such as Hispanic, Turkey, Romania, Croatia, Hungary, Portugal, Mexico, Brazil, U.S. Hawai’i, Taiwan, India, and Egypt.  (4)

The methylenetetrahydrofolate reductase gene (MTHFR) is one of the most investigated of the genes associated with various chronic human diseases through the mechanism of epigenetics. The mechanism of low folate levels, regulated by MTHFR, is well documented in various subtypes along with associations with cancer and a plethora of major cardiovascular and neurodevelopmental diseases associated with high homocysteine levels. (4) with research concluding that lowering homocysteine levels lowers the risk of ischaemic heart disease, deep vein thrombosis and stroke. (5)


Homocysteine is a common amino acid (one of the building blocks that make up proteins) found in the blood.  High levels of homocysteine are related to the early development of heart and blood vessel disease. In fact, it is considered an independent risk factor for heart disease. High homocysteine is associated with low levels of vitamin B6, B12, and folate and renal disease.  This is particularly evident in the vegan or vegetarian population. (6)

How can we lower homocysteine?

Riboflavin, or B2 a yellow vitamin of the B complex which is essential for metabolic energy production. It is present in many foods, especially milk, liver, eggs, and green vegetables, and is also synthesized by the intestinal flora. Research shows that Riboflavin has the potential to lower homocysteine. (7)

Folate, B12 and B6. Research supports the use of Folic Acid and B12 to lower homocysteine levels, but in this meta-analysis there was no evidence to support B6. (8)

Food. Vitamin B12 is naturally found in animal products, including fishmeatpoultryeggsmilk, and milk products. Vitamin B12 is generally not present in plant foods.

Folic Acid, a vitamin of the B complex found especially in leafy green vegetables, liver, and kidney

The richest sources of vitamin B6 include fishbeef liver and other organ meats, potatoes and other starchy vegetables, and fruit (other than citrus). In the United States, adults obtain most of their dietary vitamin B6 from fortified cereals, beefpoultry, starchy vegetables, and some non-citrus fruits

Oysters contain more zinc per serving than any other food, but red meat andpoultry provide the majority of zinc in the  diet. Other good food sources include beans, nuts, seeds, especially pepitas and certain types of seafood










  1. Sido B, Hack V, Hochlehnert A, Lipps H, Herfarth C, Dröge W. Impairment of intestinal glutathione synthesis in patients with inflammatory bowel disease. Gut 1998;42(4):485.
  2. Kim ER, Chang DK. Colorectal cancer in inflammatory bowel disease: The risk, pathogenesis, prevention and diagnosis. World Journal of Gastroenterology : WJG 2014;20(29):9872-81.
  3. Zhu XL, Liu ZZ, Yan SX, Wang W, Chang RX, Zhang CY, et al. Association between the MTHFR A1298C polymorphism and risk of cancer: evidence from 265 case-control studies. Mol Genet Genomics 2016;291(1):51-63.
  4. Shiao SPK, Yu CH. Meta-Prediction of MTHFR Gene Polymorphism Mutations and Associated Risk for Colorectal Cancer. Biological Research for Nursing 2016;18(4):357.
  5. Wald DS, Law M, Morris JK. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. Bmj 2002;325(7374):1202.
  6. Kajanachumpol S, Atamasirikul K, Tantibhedhyangkul P. C677T methylenetetrahydrofolate reductase and plasma homocysteine levels among Thai vegans and omnivores. Int J Vitam Nutr Res 2013;83(2):86-91.
  7. McNulty H, Dowey LRC, Strain JJ, Dunne A, Ward M, Molloy AM, et al. Riboflavin Lowers Homocysteine in Individuals Homozygous for the <em>MTHFR</em> 677C→T Polymorphism. Circulation 2006;113(1):74.
  8. Trialists’Collaboration HL. Dose-dependent effects of folic acid on blood concentrations of homocysteine: a meta-analysis of the randomized trials. The American journal of clinical nutrition 2005;82(4):806-12.