# Warfarin-Durian interaction: A case study bridging clinical outcomes and metabolic profiling through metabolomics

## TL;DR

This study shows that eating durian can increase the blood-thinning effect of warfarin, potentially raising bleeding risk, and uses metabolomics to explain the mechanism.

## Contribution

First use of metabolomics to investigate the warfarin-durian interaction and identify metabolic biomarkers.

## Key findings

- Durian consumption significantly increased INR in warfarin-treated patients.
- Sulfur-containing compounds like hydrogen sulfide and trimethylsulfonium were biomarkers of durian exposure.
- Metabolomic disruptions in purine metabolism and the TCA cycle were observed in the interaction group.

## Abstract

Warfarin-food interactions present significant challenges in achieving optimal anticoagulation; however, comprehensive research remains limited. This preliminary study explores possible mechanisms underlying the effects of durian consumption on warfarin efficacy, based on clinical observations of international normalized ratio (INR). A cross-sectional study was conducted in patients undergoing warfarin therapy who exhibited INR exceeding the therapeutic range after repeated durian consumption (one to three pieces per day for five days to one month). Plasma samples were analyzed using proton nuclear magnetic resonance (1H NMR)-based metabolomics to identify metabolic alterations. Patients who consumed durian exhibited a statistically significant increase in INR (3.93 ± 0.60) compared to the control group (2.48 ± 0.32, p = 0.0003). Sulfur-containing compounds were biomarkers of durian exposure, with hydrogen sulfide, trimethylsulfonium, and thiosulfate significantly increased in the warfarin-durian interaction group (p < 0.05). Metabolomic analysis revealed significant disruptions in purine metabolism and the tricarboxylic acid (TCA) cycle, with adenylosuccinic acid and fumaric acid identified as key biomarkers. The reduction in adenylosuccinic acid suggests impaired purine metabolism, while the increase in fumaric acid indicates TCA cycle dysregulation. This study is the first to utilize metabolomics to investigate warfarin-durian interactions, integrating clinical and metabolic insights, and highlights the potential of metabolomics in drug-food interaction research and patient safety.

•This is the first study to employ metabolomics in investigating the warfarin-durian interaction.•Durian consumption may increase the risk of bleeding in patients taking warfarin.•Sulfur-containing metabolites are potential exposure biomarkers of durian consumption.•Metabolomics reveals disruptions in purine metabolism and the TCA cycle during the warfarin-durian interaction.•1H NMR metabolomics holds promise for providing a more comprehensive understanding of drug-food interactions.

This is the first study to employ metabolomics in investigating the warfarin-durian interaction.

Durian consumption may increase the risk of bleeding in patients taking warfarin.

Sulfur-containing metabolites are potential exposure biomarkers of durian consumption.

Metabolomics reveals disruptions in purine metabolism and the TCA cycle during the warfarin-durian interaction.

1H NMR metabolomics holds promise for providing a more comprehensive understanding of drug-food interactions.