What role does COMT play in weight loss?

COMT (catechol-O-methyltransferase) breaks down catecholamines like dopamine and adrenaline. The common Val158Met polymorphism alters enzyme activity: the Met variant leads to higher dopamine levels, which may increase reward-driven eating and appetite. Some studies link the Met allele to higher BMI and difficulty losing weight, but the effect is modest and inconsistent. Direct-to-consumer DNA tests often report this variant, but its predictive power for weight loss is weak. COMT interacts with many other genes and lifestyle factors; it is not a standalone determinant. Current evidence is mixed—mostly from observational and candidate-gene studies—so it should be interpreted cautiously. For weight management, a holistic approach including diet, exercise, sleep, and stress is far more impactful than any single gene variant. Evidence: mixed (human association studies, no strong clinical trials).