Myths vs facts: COMT and Müdigkeit

COMT (catechol-O-methyltransferase) degrades dopamine and norepinephrine. The common rs4680 (Val158Met) variant alters enzyme activity: Met/Met carriers have slower COMT, leading to higher baseline catecholamine levels. Some studies link Met/Met to increased stress sensitivity and fatigue, especially in chronic fatigue conditions. However, effects are small, inconsistent, and not clinically predictive. Fatigue is multifactorial (sleep, stress, diet, exercise, other genes). A standalone COMT test does not provide actionable guidance. Direct-to-consumer tests often overstate its role. Evidence: mixed, based on small studies with replicated but weak associations. No RCTs demonstrate causality.