What are the implications of a Methionine Synthase (MTR) mutation?

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Last updated: April 23, 2025View editorial policy

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From the Research

For individuals with MTHFR mutations, supplementation with methylfolate, vitamin B12, and possibly vitamin B6 is recommended to reduce homocysteine levels and alleviate related health issues, as supported by the most recent and highest quality study 1. The MTHFR gene produces an enzyme involved in processing folate and regulating homocysteine levels, with common variants C677T and A1298C reducing enzyme efficiency by 30-70% depending on the number of copies of the mutation.

  • The most common variants are C677T and A1298C, which can reduce enzyme efficiency by 30-70% depending on whether you have one copy (heterozygous) or two copies (homozygous) of the mutation.
  • For most people with MTHFR mutations, no specific treatment is needed unless they have elevated homocysteine levels or folate-related health issues.
  • If treatment is necessary, it typically involves taking methylfolate (400-1000 mcg daily) instead of regular folic acid, along with vitamin B12 (methylcobalamin form, 500-1000 mcg daily) and possibly vitamin B6 (25-100 mg daily), as shown in a study where supplementation induced a decrease in homocysteine from 19.4±5.3μmol/L to 6.9±2.2μmol/L after folate supplementation (p<0.05) 2. These methylated forms of vitamins bypass the enzymatic defect, and their effectiveness in reducing homocysteine levels has been demonstrated in various studies, including one that found a statistically significant decrease in homocysteine levels in groups treated with vitamins B6, B12, and/or folic acid compared to controls, with a mean decline of homocysteine concentration of 31.9% in the intervention arms 3. While some practitioners recommend extensive supplementation protocols, most medical geneticists and hematologists consider these unnecessary for most people with MTHFR variants, as the mutations are extremely common (up to 40% of people have at least one variant) and usually don't cause health problems unless combined with other genetic or environmental factors 4. However, in cases where MTHFR mutations are associated with elevated homocysteine levels, supplementation with methylfolate, vitamin B12, and possibly vitamin B6 can help alleviate related health issues, such as impaired folate metabolism and vitamin B deficiency, which have been linked to an increased risk of certain diseases, including multiple sclerosis 1. Overall, the available evidence suggests that supplementation with methylfolate, vitamin B12, and possibly vitamin B6 can be an effective way to reduce homocysteine levels and alleviate related health issues in individuals with MTHFR mutations, and this approach is supported by the most recent and highest quality study 1.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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