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

Piyapat Rattanasuwan; Prem Lertpongpipat; Natthapat Hiranchatchawal; Konwalin Wannaphueak; Sakonwan Pounghom; Parinya Thongkhao-on; Matchuda Suwanthai; Duangthip Sompradee; Auiporn Saithongdee; Churdsak Jaikang; Preechaya Tajai

doi:10.5599/admet.2740

Authors

Piyapat Rattanasuwan Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand https://orcid.org/0009-0003-0026-6722
Prem Lertpongpipat Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand https://orcid.org/0009-0000-1326-4791
Natthapat Hiranchatchawal Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand https://orcid.org/0009-0002-4792-3278
Konwalin Wannaphueak Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand https://orcid.org/0009-0004-9448-1702
Sakonwan Pounghom Hua Hin Hospital, Prachuap Khiri Khan 77110, Thailand https://orcid.org/0009-0006-1036-5910
Parinya Thongkhao-on Hua Hin Hospital, Prachuap Khiri Khan 77110, Thailand https://orcid.org/0009-0006-7277-8008
Matchuda Suwanthai Hua Hin Hospital, Prachuap Khiri Khan 77110, Thailand https://orcid.org/0009-0004-7689-7464
Duangthip Sompradee Hua Hin Hospital, Prachuap Khiri Khan 77110, Thailand https://orcid.org/0009-0005-8219-712X
Auiporn Saithongdee Hua Hin Hospital, Prachuap Khiri Khan 77110, Thailand https://orcid.org/0009-0006-7919-7329
Churdsak Jaikang Department of Forensic Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand https://orcid.org/0000-0002-9262-0404
Preechaya Tajai Department of Forensic Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand https://orcid.org/0000-0002-8706-4976

DOI:

https://doi.org/10.5599/admet.2740

Keywords:

Biomarker, drug interaction, 1H-NMR-based metabolomics, Metabolites, personalized anticoagulant

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.

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