Myths vs facts: VKORC1 and fatigue

The claim that VKORC1 variants directly cause fatigue is a myth. VKORC1 encodes an enzyme that recycles vitamin K, crucial for blood clotting. Its well-established role is in warfarin sensitivity. Fatigue is not a known direct phenotype of common VKORC1 polymorphisms. Rare loss-of-function mutations could theoretically lead to vitamin K deficiency and bleeding, which might cause fatigue, but this is extremely rare and not supported by population studies. Consumer DNA tests that link VKORC1 to fatigue are overstating weak mechanistic evidence. Fact: VKORC1 is a pharmacogene, not a fatigue gene. If you have unexplained fatigue, focus on iron, thyroid, sleep, and stress – not VKORC1. Evidence: mechanistic/unclear. No human-strong studies exist for this association.