What to watch with MTHFR and Wechseljahre?

The combination of MTHFR variants (especially rs1801133, C677T) and menopause is often linked to homocysteine and folate metabolism, but the evidence is nuanced. MTHFR polymorphisms show mostly small effect sizes in GWAS (OR 0.02–5.59) and do not directly indicate a need for supplementation. During menopause, cardiovascular risk increases, and elevated homocysteine is a moderate risk factor. However, no randomized trials demonstrate that genotype-guided folic acid or B12 supplementation reduces that risk. Many commercial tests overstate clinical relevance. A practical approach: measure fasting homocysteine (target <10 µmol/L) and ensure adequate folate, B6, and B12 from diet (leafy greens, legumes, whole grains). High-dose folic acid without medical indication is not recommended. Estrogen changes may influence homocysteine levels, but personalized supplementation based solely on MTHFR status lacks evidence. Be cautious of marketing claims that frame MTHFR as a 'master gene' for menopause.