{"doi":"10.1016/j.tjnut.2024.11.004","title":"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":"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. 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. We used untargeted proton nuclear magnetic resonance spectroscopy ( 1 H 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 1 H 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. We characterized 11 1 H 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/m 2 ; 95% CI: −1.62, −0.78; P < 0.0001). These associations were, to a large extent, explained by urinary citrate excretion. We identified 1 H 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.","journal":"Journal of Nutrition","year":2024,"id":450943,"datarank":0.25613487816046004,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.014719191295344965,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.014719191295344965,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":4,"citers_with_citation_signal":2,"citers_with_endowment":2,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.92,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT00005271"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":892044,"name":"Elena Chekmeneva","orcid":"0000-0003-1807-2398","position":1,"is_corresponding":false},{"id":37775,"name":"Linda Van Horn","orcid":"0000-0002-1362-5806","position":2,"is_corresponding":false},{"id":37769,"name":"Queenie Chan","orcid":"0000-0001-9278-230X","position":3,"is_corresponding":false},{"id":37779,"name":"Martha L. Daviglus","orcid":"0000-0002-6791-8727","position":4,"is_corresponding":false},{"id":285388,"name":"Gary Frost","orcid":"0000-0003-0529-6325","position":5,"is_corresponding":false},{"id":302125,"name":"Elaine Holmes","orcid":"0000-0002-0556-8389","position":6,"is_corresponding":false},{"id":65491,"name":"Timothy M. D. Ebbels","orcid":"0000-0002-3372-8423","position":7,"is_corresponding":false},{"id":37768,"name":"Paul Elliott","orcid":"0000-0002-7511-5684","position":8,"is_corresponding":false},{"id":425774,"name":"Linda M. Oude Griep","orcid":"0000-0001-7697-7473","position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":null,"created_at":"2026-07-19T02:02:28.969209Z","pmid":"39536968","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}