How are ADH1B and fatigue related?

ADH1B encodes alcohol dehydrogenase, which metabolizes ethanol to acetaldehyde. Certain variants (e.g., ADH1B*2, rs1229984) increase enzyme activity, leading to higher acetaldehyde levels after drinking. This causes flushing, nausea, headache, and can contribute to fatigue, especially during hangovers. The link to fatigue is indirect: it is primarily a consequence of alcohol consumption and its metabolites, not a direct genetic effect on energy levels. Additionally, ADH1B variants are associated with altered alcohol dependence risk, which may affect sleep and overall tiredness. Evidence is moderate (GWAS, population studies), but effect sizes on general fatigue without alcohol are small. A DNA test can indicate this predisposition, but persistent fatigue requires medical evaluation beyond genetics.