Is MTHFR useful for fatigue?

Whether MTHFR is useful for fatigue cannot be clearly answered from the available evidence. MTHFR encodes an enzyme in folate metabolism. Variants like C677T are commonly highlighted in direct-to-consumer DNA tests and linked to vague symptoms such as fatigue. However, the evidence for a causal role is weak: most studies are associative, effect sizes are small, and fatigue is multifactorial (sleep, nutrition, stress, medical conditions). A positive MTHFR result alone does not justify supplementation with methylfolate or other nutrients without confirmed deficiency (e.g., via blood tests). Self-supplementation can mask B12 deficiency or cause other risks. The provided context contains no specific studies on MTHFR and fatigue. Therefore, the clinical utility for fatigue is unclear. Evidence: unclear. Sources: none provided.