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A Metabolome Wide Association Study of Fruit and Vegetable Consumption and Associations with Cardiovascular Disease Risk Factors: The International Study of Macro-/Micronutrients and Blood Pressure (INTERMAP) Study
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A Metabolome Wide Association Study of Fruit and Vegetable Consumption and Associations with Cardiovascular Disease Risk Factors: The International Study of Macro-/Micronutrients and Blood Pressure (INTERMAP) Study

Linda M Oude Griep, Elena Chekmeneva, Linda Van Horn, Queenie Chan, Martha L Daviglus, Gary Frost, Elaine Holmes, Timothy MD Ebbels and Paul Elliott
The Journal of nutrition, Vol.155(1), pp.122-131
2024
DOI: https://doi.org/10.1016/j.tjnut.2024.11.004
PMID: 39536968
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CC BY V4.0,  Open Access

Abstract

24-h dietary recalls Biomarkers blood pressure body mass index cardiovascular disease risk factors fruit and vegetables urinary metabolites
Background Epidemiologic evidence linking blood pressure (BP) and body weight-lowering effects with fruit and vegetable consumption mostly relies on self-reported dietary assessment prone to misreport and under- or overestimation of relationships. Objectives We aimed to characterize objective 24-h urinary metabolites and a derived metabolite score associated with fruit and vegetable intake and assessed their associations with BP and BMI, with validation across cohorts. Methods We used untargeted proton nuclear magnetic resonance spectroscopy (1H NMR) of 2 timed repeated 24-h urine collections from free-living participants from the US (n = 2032) and the UK (n = 449) of the cross-sectional International Study of Macro-/Micronutrients and Blood Pressure (INTERMAP). We evaluated correlations between fruit and vegetable intake assessed by 24-h dietary recalls with 7100 1H NMR features, adjusted for confounders and multiple testing. We related identified metabolites and a metabolite score with BP and BMI using extensively adjusted multiple linear regression models. Results We characterized 11 1H NMR-derived 24-h urinary metabolites related to fruit and vegetable intake, reproducible across multiple 24-h urine collections of both cohorts. Proline betaine, citrate, N-methylproline, scyllo-inositol, 2-hydroxy-2-(4-methyl cyclohex-3-en-1-yl) propoxyglucuronide, and proline were associated with fruit intake, specifically with Rutaceae intake, whereas S-methyl-L-cysteine sulfoxide and S-methyl-L-cysteine sulfoxide metabolite were associated with Brassicaceae intake. The metabolite score, explaining 39.8% of fruit and vegetable intake, was inversely associated with systolic BP [−1.65 mmHg; 95% confidence interval (CI): −2.68, −0.62; P < 0.002] and BMI (−1.21 kg/m2; 95% CI: −1.62, −0.78; P < 0.0001). These associations were, to a large extent, explained by urinary citrate excretion. Conclusions We identified 1H NMR-derived urinary metabolites associated with fruit and vegetable consumption, consistent and reproducible between urine collections and across populations. A higher fruit and vegetable-related metabolite score showed associations with lower systolic BP and BMI, mainly mediated by citrate, but would need confirmation in further studies.

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