How are COMT and Müdigkeit related?

COMT (catechol-O-methyltransferase) degrades dopamine, norepinephrine, and epinephrine. The well-studied Val158Met variant (rs4680) alters enzyme activity: Met carriers have lower activity, leading to higher baseline dopamine levels. This has been linked to stress resilience, cognitive performance, and, in some studies, fatigue – particularly in chronic fatigue syndrome or post-exercise recovery. However, effect sizes are small, and the evidence is moderate at best. Fatigue is highly multifactorial; COMT alone explains only a tiny fraction of variance. Genetic testing can offer a clue but not a diagnosis. Lifestyle factors (sleep, diet, stress, exercise) and medical conditions (e.g., thyroid, anemia, depression) are far more influential. Individuals with persistent fatigue should seek clinical evaluation rather than rely on a single SNP.