Evidence check: COMT in the context of fatigue

COMT (catechol-O-methyltransferase) degrades catecholamines such as dopamine and norepinephrine. The Val158Met polymorphism (rs4680) alters enzyme activity: the Met variant results in slower breakdown, the Val variant in faster breakdown. This can theoretically influence energy levels, stress response, and cognitive performance – and thus indirectly relate to fatigue. However, the evidence for a direct link between COMT variants and clinical fatigue is weak. Most studies are mechanistic or show small effects in specific subgroups (e.g., after sleep deprivation). Fatigue is multifactorial (sleep, nutrition, stress, hormones, inflammation). Direct-to-consumer tests often overstate clinical relevance. A COMT finding alone does not justify specific therapy. A holistic assessment using biomarkers (e.g., cortisol, vitamin D, inflammatory markers) and lifestyle analysis is more appropriate.