How are MTHFR and fatigue related?

The provided context does not contain direct information on the relationship between MTHFR and fatigue. In consumer DNA testing, MTHFR variants (especially C677T) are frequently marketed as a cause of fatigue via impaired methylation and elevated homocysteine. However, the evidence is mixed: some small studies suggest a link, but larger meta-analyses and systematic reviews do not confirm a strong causal effect. Fatigue is highly multifactorial (sleep, nutrition, stress, hormones, physical activity). Genetic testing for MTHFR alone has limited clinical utility for fatigue management. Caveat: Do not self-prescribe high-dose folate or methyl donors without medical guidance; measuring homocysteine levels is more actionable. Evidence grade: unclear.