From the Guidelines
For individuals with MTHFR variants, supplementation with methylfolate (L-methylfolate) at 400-1000 mcg daily may be more beneficial than standard folic acid supplements, as it can help support proper methylation pathways and reduce the risk of related health problems 1. When considering the management of MTHFR variants, it is essential to prioritize the reduction of homocysteine levels, as elevated levels are associated with an increased risk of atherosclerotic vascular disease, including stroke 1.
- The relationship between homocysteine levels and carotid IMT was eliminated after adjustment for other cardiovascular risk factors or renal function, suggesting that addressing these factors is crucial in managing MTHFR variants 1.
- Ensuring adequate vitamin B12 (methylcobalamin form, 500-1000 mcg daily) is also important, as it helps support proper methylation pathways and can reduce homocysteine levels 1.
- While MTHFR variants are common, affecting up to 40% of some populations, most people with these genetic variations remain healthy without specific intervention, and routine testing is not recommended for the general population 1. However, for individuals with certain conditions like recurrent pregnancy loss, cardiovascular disease risk factors, or specific neurological conditions, addressing potential methylation issues through appropriate supplementation may be beneficial, and supplementation with 5-MTHF may be considered, particularly in cases of increased Hcy levels due to the presence of MTHFR 677TT genotype 1.
- The body has multiple backup pathways for methylation, which is why many people with MTHFR variants never experience related health problems, and the clinical significance of MTHFR polymorphisms has been overstated in some contexts 1.
From the Research
MTHFR and Homocysteine Levels
- MTHFR mutations are associated with hyperhomocysteinemia, which is a risk factor for various health conditions, including recurrent pregnancy loss and thrombosis 2, 3, 4.
- Studies have shown that supplementation with folic acid, vitamins B6 and B12 can lower homocysteine levels in individuals with MTHFR mutations 2, 5.
- The association between MTHFR polymorphisms and homocysteine levels is influenced by dietary intake of folic acid, vitamin B12, and methionine 3, 4.
MTHFR and Pregnancy Outcomes
- MTHFR mutations are associated with recurrent pregnancy loss, and supplementation with folic acid, vitamins B6 and B12 may improve pregnancy outcomes in these individuals 2.
- A study found that supraphysiologic methylfolate, vitamins B6 and B12 supplementation in women with MTHFR mutations had a beneficial effect on pregnancy outcome 2.
MTHFR and Bone Mineral Density
- A study found that low serum folate is a significant risk factor for osteoporosis, and plasma homocysteine has a lesser effect on bone mineral density 6.
- Vitamins B12 and B6 may also have an effect on bone mineral density, albeit a weaker one than folate, by acting through homocysteine metabolism 6.
MTHFR and Renal Transplant Recipients
- Hyperhomocysteinemia is associated with chronic allograft dysfunction in renal transplant recipients, and MTHFR polymorphism may have a greater effect on homocysteine concentration than vitamin intake in these individuals 5.
- Increased folate and vitamin B6 intakes may reduce homocysteine concentrations and contribute to reducing the risk of chronic allograft dysfunction development in renal transplant recipients with normal renal function 5.