From the Guidelines
MTHFR mutations are associated with an increased risk of stroke, and individuals with these mutations may benefit from taking methylfolate supplements and other B vitamins to lower homocysteine levels. The most recent and highest quality study, published in 2022 1, found that reduced risk of first ischemic stroke in participants with both folate and B12 below the median, particularly in methylene tetrahydrofolate reductase 677 CC carriers.
Some key points to consider:
- MTHFR mutations affect the enzyme that converts folate to its active form (methylfolate), which is essential for DNA synthesis and repair, neurotransmitter production, and homocysteine metabolism.
- Elevated homocysteine levels are associated with a 2- to 3-fold increased risk for atherosclerotic vascular disease, including stroke, as reported in a 2011 study 1.
- The B-complex vitamins pyridoxine (B6), cobalamin (B12), and folic acid lower homocysteine levels, but most trials of patients with established atherosclerotic vascular disease have found no benefit of homocysteine lowering by B complex vitamin therapy on clinical cardiovascular endpoints, as noted in a 2014 study 1.
- A 2008 study 1 suggested that it is reasonable to give folate and B vitamins to individuals with an MTHFR mutation in an effort to normalize homocysteine levels.
In terms of treatment, methylfolate (L-methylfolate) supplements, typically 400-1000 mcg daily, may be beneficial for individuals with MTHFR mutations, especially those with elevated homocysteine levels. Additional supplements like vitamin B6 (25-100 mg daily), vitamin B12 (500-1000 mcg daily), and betaine (trimethylglycine, 500-3000 mg daily) may also be helpful. Regular blood testing to monitor homocysteine levels is recommended. However, it is essential to note that most people with MTHFR mutations do not require special treatment unless they have elevated homocysteine or specific health conditions.
From the Research
Implications of MTHFR Mutation
The implications of a Methylenetetrahydrofolate Reductase (MTHFR) mutation are varied and can have significant effects on an individual's health. Some of the key implications include:
- Increased risk of cardiovascular disease due to hyperhomocysteinemia 2
- Increased risk of neurological disorders, such as neural tube defects and congenital anomalies 3, 2
- Increased risk of recurrent pregnancy loss 4
- Increased risk of cancer and neurodevelopmental disorders 2
- Folate deficiency, which can lead to a range of health issues 3, 5
Folate Supplementation
Folate supplementation is widely used to mitigate the effects of MTHFR mutations. Some key points to consider include:
- (6S)5-Methyltetrahydrofolate (5-MTHF) supplementation is preferred over folic acid for individuals with MTHFR polymorphisms, as it can bypass the block in folic acid metabolism linked to enzymatic polymorphism 3, 6
- 5-MTHF supplementation can increase plasma folate levels more effectively than folic acid, regardless of the 677C-->T mutation of the MTHFR gene 6
- Supraphysiologic methylfolate, vitamins B6 and B12 supplementation can have a beneficial effect on pregnancy outcome in women with MTHFR mutations 4
Genetic Counseling
Genetic counseling is an important aspect of managing MTHFR mutations. Some key points to consider include:
- Genetic counselors may encounter questions regarding the significance of MTHFR polymorphisms in a variety of settings, including recurrent pregnancy loss, neural tube defects, and congenital anomalies 2
- Educational resources for patients and providers are essential for ensuring that individuals with MTHFR mutations receive appropriate care and counseling 2