Does vitamin D interact with warfarin (Coumadin)?

Vitamin D and Warfarin Interaction

Vitamin D supplements do not significantly interact with warfarin at standard supplementation doses, but high levels of vitamin D may potentially increase bleeding risk in warfarin-treated patients. 1

Mechanism of Action and Potential Interaction

• Warfarin works by inhibiting vitamin K-dependent clotting factors (II, VII, IX, X) through inhibition of the vitamin K epoxide reductase (VKORC1) enzyme complex, preventing the regeneration of vitamin K1 epoxide 2, 3
• Unlike vitamin K, which directly counteracts warfarin's anticoagulant effect, vitamin D operates through different physiological pathways and does not directly interfere with warfarin's mechanism of action 2, 3
• Vitamin D may have mild anticoagulant properties of its own, which could potentially enhance warfarin's effect rather than reduce it 4

Clinical Evidence on Vitamin D and Warfarin

• A retrospective study found a weak but statistically significant positive correlation between vitamin D levels and warfarin sensitivity index (WSI), suggesting patients with higher vitamin D levels may require slightly lower warfarin doses to achieve therapeutic anticoagulation 4
• A 2019 study observed that patients on warfarin with vitamin D levels ≥30-100 ng/ml had higher rates of major gastrointestinal bleeding compared to those with lower vitamin D levels, suggesting a potential additive anticoagulant effect 1
• This contrasts with vitamin K, which directly counteracts warfarin's effect and can significantly reduce INR when consumed in varying amounts 2

Clinical Management Recommendations

• Standard vitamin D supplementation (typically 600-2000 IU daily) does not require adjustment of warfarin dosing or additional INR monitoring 4
• Unlike vitamin K intake, which must be kept consistent to maintain stable anticoagulation, vitamin D supplementation does not require the same level of dietary restriction 2
• Monitor for potential increased bleeding risk in patients with high vitamin D levels (≥30 ng/ml) who are also taking warfarin 1
• Be aware that multivitamin supplements containing both vitamin D and small amounts of vitamin K (even as low as 25 μg) may affect warfarin anticoagulation, particularly in patients with vitamin K deficiency 5

Important Warfarin Interactions to Consider

• Medications that significantly interact with warfarin include antibiotics (trimethoprim-sulfamethoxazole, metronidazole), which inhibit clearance of S-warfarin and potentiate warfarin's effect 2
• Amiodarone inhibits metabolic clearance of both S- and R-isomers of warfarin, significantly potentiating anticoagulation 2
• Barbiturates, rifampicin, and carbamazepine increase hepatic clearance of warfarin, reducing its anticoagulant effect 2
• Dietary vitamin K from green vegetables or supplements can significantly counteract warfarin's effect by providing substrate for the warfarin-insensitive pathway 2
• Maintaining consistent vitamin K intake is more important for stable anticoagulation than restricting vitamin D 2

Common Pitfalls and Caveats

• Do not confuse vitamin D with vitamin K when counseling patients on dietary restrictions while taking warfarin 2
• Be aware that patients with vitamin K deficiency (approximately 12% of anticoagulated patients) may be particularly sensitive to even small amounts of vitamin K in multivitamins that also contain vitamin D 5
• Consider monitoring vitamin D levels in patients with unexplained warfarin resistance or sensitivity, as vitamin D status might affect warfarin maintenance dose requirements 4
• Remember that while standard vitamin D supplementation is generally safe with warfarin, very high levels of vitamin D may potentially increase bleeding risk 1