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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

Authors: Linda M Oude Griep; Elena Chekmeneva; Linda Van Horn; Queenie Chan; Martha L Daviglus; Gary Frost; Elaine Holmes; +2 Authors

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

Abstract

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.

Keywords

Male, Adult, cardiovascular disease risk factors, urinary metabolites, blood pressure, body mass index, Blood Pressure, Middle Aged, Diet, Cross-Sectional Studies, 24-h dietary recalls, Cardiovascular Diseases, Heart Disease Risk Factors, fruit and vegetables, Fruit, Vegetables, Metabolome, Humans, Female, Genomics, Proteomics, and Metabolomics, Biomarkers, Aged

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
1
Average
Average
Average
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