Metabolic insights into the warfarin-mango interaction: A pilot study integrating clinical observations and metabolomics.

Abstract

Background and purpose: Warfarin is a widely prescribed oral anticoagulant for the prevention and treatment of thromboembolic events, frequently used in patients with atrial fibrillation. However, its effectiveness is often challenged by a narrow therapeutic range and significant inter-patient variability in dosage requirements and treatment responses. Drug interactions remain a critical concern, as they heighten the risk of supratherapeutic anticoagulation. Reports of interactions between warfarin and mango have documented cases of elevated international normalized ratio (INR) following mango consumption, although the underlying molecular mechanisms remain unclear.

Experimental approach: This study investigates the molecular basis of the warfarin-mango interaction using proton nuclear magnetic resonance (¹H-NMR)-based metabolomics. In a pre-post design study, plasma samples were collected from patients on long-term warfarin therapy (>6 months) who exhibited supratherapeutic INR levels after consuming mango. After a two-week discontinuation of mango consumption, additional plasma samples were collected once INR levels returned to the therapeutic range.

Key results and conclusion: This is the first study to utilize ¹H-NMR metabolomics to explore warfarin-mango interactions, integrating clinical observations with metabolic insights. Findings suggest that a reduction in glycerol 3-phosphate may impair glycolysis, disrupting platelet activation and contributing to the elevated INR levels observed in all patients. These results underscore the potential for ¹H-NMR metabolomics to elucidate drug-food interactions, advancing personalized anticoagulant management and improving patient safety.