Circulating metabolomic signatures of ultra-processed and minimally processed food intake and risk of cardiovascular disease and type 2 diabetes: 20-year follow-up in the Whitehall II cohort.

Mengmei E Wang, Annie Britton, Michail Katsoulis, Kiara Chang, Eszter P Vamos, Clare H Llewellyn

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Article in BMC medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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Mengmei E WangResearch Department of Epidemiology and Public Health, University College London, London, UK. mengmei.wang.21@ucl.ac.uk.

Annie BrittonResearch Department of Epidemiology and Public Health, University College London, London, UK.

Michail KatsoulisUnit for Lifelong Health and Ageing, University College London, London, UK.

Kiara ChangPublic Health Policy Evaluation Unit, School of Public Health, Imperial College London, London, UK.

Eszter P VamosPublic Health Policy Evaluation Unit, School of Public Health, Imperial College London, London, UK.

Clare H LlewellynResearch Department of Behavioural Science and Health, University College London, London, UK.

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Abstract

backgroundHigher intakes of ultra-processed food (UPF) and minimally processed food (MPF) are linked to increased and decreased cardiometabolic risks, respectively, though mechanisms underlying these associations remain less understood. We aimed to identify metabolomic signatures associated with UPF and MPF intakes, examine their prospective associations with cardiovascular disease (CVD) and type 2 diabetes (T2D), and quantify their mediation of processing-disease associations.

methodsIn the Whitehall II cohort, UPF and MPF intakes in 6010 participants were derived using the Nova classification from 127-item food frequency questionnaires administered at phases 3 and 5 (1991-1994, 1997-1999), averaged across phases. Fasting plasma samples were analysed for 233 metabolites using nuclear magnetic resonance (NMR) spectroscopy. Metabolomic signatures for UPF and MPF intake were derived using elastic net regression. Cox models examined associations between metabolomic signatures and incident CVD and T2D. Mediation analyses quantified the proportion explained by metabolomic signatures.

resultsWe identified metabolomic signatures for UPF (34 metabolites) and MPF (50 metabolites). The UPF signature correlated positively with pro-inflammatory and atherogenic metabolites and inversely with omega-3 fatty acids and high-density lipoproteins; the MPF signature showed the opposite pattern. 1094 CVD and 853 T2D events occurred over 20 and 18 years median follow-up, respectively. Comparing the highest to lowest tertile, higher UPF signature scores were associated with greater risk of (hazard ratio [HR] = 1.19; 95% confidence interval [CI] 1.02-1.39) and T2D (HR = 1.20; 95% CI 1.03-1.42), whereas higher MPF signature scores were inversely associated with these outcomes (CVD: HR = 0.81; 95% CI 0.69-0.94; T2D: HR = 0.60; 95% CI 0.48-0.73). Associations between the signatures and outcomes were robust to additional adjustment for UPF or MPF intake. The signatures mediated 42.8-51.1% of processing-disease associations (51.1% for UPF-CVD, 46.6% for MPF-CVD, 42.8% for UPF-T2D, and 47.8% for MPF-T2D; all p < 0.05).

conclusionsMetabolomic signatures of UPF and MPF intake showed opposing associations with CVD and T2D risk, partially mediating these processing-disease associations. These findings suggest biological pathways linking UPF intake to adverse cardiometabolic outcomes, though the unexplained proportion indicates additional mechanisms may contribute.

Indexed as

Cardiovascular DiseasesDiabetes Mellitus, Type 2MetabolomeAdultCohort StudiesFemaleFollow-Up StudiesHumansMaleMetabolomicsMiddle AgedProspective StudiesRisk FactorsCardiovascular diseaseMetabolic diseasesMetabolomicsMinimally processed foodsNutritional epidemiologyType 2 diabetesUltra-processed foods

Identifiers

PMID42482054

DOI10.1186/s12916-026-05081-7

PMCPMC13632048

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