Myths vs facts: CYP1A2 and fatigue

Myth vs. facts: CYP1A2 and fatigue. A common myth is that carrying the slow CYP1A2 variant (e.g., rs551 C allele) directly causes fatigue or poor caffeine tolerance. The evidence is moderate and context-dependent. CYP1A2 is the main enzyme metabolizing caffeine. Slow metabolizers indeed have higher caffeine levels after consumption, which can disrupt sleep and lead to fatigue if caffeine intake is high. However, the effect on everyday fatigue is small and confounded by tolerance, sleep hygiene, and total caffeine intake. Some studies suggest slow metabolizers with high coffee intake have increased risk of hypertension, but direct causal links to fatigue are not robustly established. A DNA test alone cannot diagnose fatigue. Evidence grade: human-moderate. Safety note: persistent fatigue should be evaluated by a physician.