From the Guidelines
MTHFR gene mutations have limited clinical significance for most people, and the latest evidence suggests that supplementation with active forms of folate, vitamin B12, and vitamin B6 may be beneficial only for individuals with elevated homocysteine levels or folate deficiency. These mutations affect the methylenetetrahydrofolate reductase enzyme, which helps convert folate to its active form and plays a role in processing homocysteine 1. The two most common variants are C677T and A1298C. For most individuals with these mutations, no specific treatment is needed unless they have elevated homocysteine levels or folate deficiency.
If homocysteine is high, supplementation with active forms of folate (methylfolate/L-methylfolate at 400-1000 mcg daily), vitamin B12 (methylcobalamin at 500-1000 mcg daily), and vitamin B6 (25-100 mg daily) may be recommended, as these supplements help support the methylation pathway that the MTHFR enzyme participates in 1. During pregnancy, women with MTHFR mutations should ensure adequate folate intake, but standard prenatal vitamins are usually sufficient. Despite marketing claims, MTHFR mutations do not require extensive supplementation or dietary changes for most people. The clinical relevance has been overstated, as these mutations are common (up to 40% of people have at least one variant) and rarely cause problems on their own. Only homozygous C677T mutations (occurring in about 10-15% of some populations) may slightly increase risk for certain conditions like venous thrombosis when other risk factors are present.
Key points to consider:
- MTHFR gene mutations are common and rarely cause problems on their own
- Elevated homocysteine levels or folate deficiency may require supplementation with active forms of folate, vitamin B12, and vitamin B6
- Standard prenatal vitamins are usually sufficient for pregnant women with MTHFR mutations
- Extensive supplementation or dietary changes are not necessary for most people with MTHFR mutations
- The latest evidence suggests that using methylcobalamin and 5-methyltetrahydrofolate instead of cyanocobalamin and folic acid may be more efficacious in preventing stroke 1.
From the Research
Clinical Implications of MTHFR Gene Mutation
The clinical implications of a Methylenetetrahydrofolate Reductase (MTHFR) gene mutation are significant and can have various effects on an individual's health. Some of the key implications include:
- Increased risk of cardiovascular disease (CVD) and stroke, as individuals with the MTHFR 677TT genotype are genetically predisposed to elevated plasma homocysteine 2
- Recurrent pregnancy loss, as MTHFR mutations and hyperhomocysteinemia are frequent features in patients with recurrent pregnancy loss 3
- Lower vitamin D levels, higher homocysteine, and natural killer (NK) cell cytotoxicities in women with MTHFR 677TT genotype 4
- Decreased MTHFR specific activity in subjects with 1298A-->C mutation, which can lead to increased homocysteine levels 5
- Importance of adequate folic acid and vitamin B12 intake during pregnancy to regulate homocysteine levels, especially in individuals with MTHFR gene mutations 6
Effects on Homocysteine Levels
The MTHFR gene mutation can affect homocysteine levels in various ways, including:
- Increased homocysteine levels in individuals with MTHFR 677TT genotype 2, 5
- Decreased homocysteine levels with folic acid, vitamin B6, and vitamin B12 supplementation 3, 6
- No significant association between MTHFR genetic polymorphisms and serum homocysteine levels in pregnant women taking folic acid supplements 6
Pregnancy Outcomes
The MTHFR gene mutation can have significant effects on pregnancy outcomes, including:
- Recurrent pregnancy loss in individuals with MTHFR mutations and hyperhomocysteinemia 3, 4
- Improved pregnancy outcomes with supraphysiologic methylfolate, vitamins B6 and B12 supplementation in women with MTHFR mutations 3
- Importance of adequate folic acid and vitamin B12 intake during pregnancy to regulate homocysteine levels and improve pregnancy outcomes 6