Evidence check: VKORC1 in the context of fatigue

VKORC1 encodes the vitamin K epoxide reductase complex subunit 1, a key enzyme in the vitamin K cycle. It is best known for its role in warfarin sensitivity: certain variants (e.g., rs9923231) significantly affect dosing requirements. However, a direct link between VKORC1 variants and fatigue is not well established in the scientific literature. Indirectly, altered vitamin K metabolism could influence coagulation or bone health, potentially affecting energy levels, but this remains speculative. In nutrigenetics, VKORC1 is discussed mainly in the context of blood clotting and bone density, not fatigue. Therefore, testing VKORC1 alone is not clinically useful for evaluating tiredness. The evidence level is 'mechanistic' or 'unclear'. For persistent fatigue, a comprehensive medical workup (iron, thyroid, sleep, etc.) is recommended rather than genetic testing for this single gene.