What role does COMT play in fatigue?

COMT (catechol-O-methyltransferase) breaks down dopamine and other catecholamines. The common Val158Met variant (rs4680) alters enzyme activity: Val (high activity) and Met (low activity). This affects dopamine levels in the prefrontal cortex, influencing cognition, mood, and fatigue. Some observational and GWAS studies suggest that Met carriers may be more prone to fatigue, especially in chronic fatigue syndrome or after exercise, due to altered stress and dopamine regulation. However, the evidence is moderate and inconsistent. Many other factors – sleep, nutrition, stress, and underlying health conditions – are more impactful. Consumer genetic tests often overstate the role of single genes. A COMT test alone cannot predict or diagnose fatigue. If you experience persistent tiredness, consult a healthcare professional for a comprehensive evaluation.