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The MedLey trial was funded by a National Health and Medical Research Council Grant (#APP1050949 to KJM). The InterAct project was funded by the EU FP6 programme (grant number LSHM_CT_2006_037197 to NJW). Biomarker measurements for carotenoids were funded jointly by the InterAct project, the EPIC-CVD project, and the MRC Cambridge Initiative (RG71466 and SJAH/004 to NJW, NGF, JD, AB). EPIC-CVD has been supported by the UK Medical Research Council (MR/L003120/1 to ASB and JD), the British Heart Foundation (RG/13/13/30194 and RG/18/13/33946 to ASB and JD), the European Commission Framework Programme 7 (HEALTH -F2-2012-279233 to ASB and JD), the European Research Council (268834 to ASB and JD), and the National Institute for Health Research (NIHR; Cambridge Biomedical Research Centre at the Cambridge University Hospitals NHS Foundation Trust, BRC-1215-20014 to ASB and JD). This work was also supported by Health Data Research UK (to ASB and JD), which is funded by the UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, Department of Health and Social Care (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), and Wellcome. The coordination of EPIC is financially supported by the International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by: Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Ge'ne'rale de l'Education Nationale, Institut National de la Sante' et de la Recherche Me'dicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany); Associazione Iblea Ricerca Epidemiologica (A.I.R.E. - ONLUS) Ragusa, Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di San Paolo, National Research Council and Sicilian Regional Government (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands~Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS) -Instituto de Salud Carlos III (ISCIII), Regional Governments of Andaluci'a, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology -ICO (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skane and Vasterbotten (Sweden); Cancer Research UK (14136 to NJW; C8221/A29017), Medical Research Council (1000143 to NJW; MR/M012190/1) (United Kingdom). JGS was supported by the MRC PhD studentship. NJW, NGF, and FI acknowledge funding from the Medical Research Council Epidemiology Unit (MC_UU_00006/1, MC_UU_00006/3); and NJW, NGF and AK from the NIHR Cambridge Biomedical Research Centre (IS-BRC-1215-20014; NIHR203312). NGF and JD are NIHR Senior Investigators. JD holds a British Heart Foundation Professorship. MBS acknowledges funding from the Federal Ministry of Education and Research and the State of Brandenburg (DZD grant 82DZD03D03). JSZ has received funding from Westlake University (No YSYY0209) and European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 701708. PWF has received funding from Novo Nordisk, Swedish Diabetes Association, Swedish Heart-Lung Foundation, European Research Council. ER has received funding from Imperial College Biomedical Research Centre. The funders of the studies had no role in the study design, data collection, data analysis, data interpretation, or report preparation. Trial Australian., Background Self-reported adherence to the Mediterranean diet has been modestly inversely associated with incidence of type 2 diabetes (T2D) in cohort studies. There is uncertainty about the validity and magnitude of this association due to subjective reporting of diet. The association has not been evaluated using an objectively measured biomarker of the Mediterranean diet. Methods and findings We derived a biomarker score based on 5 circulating carotenoids and 24 fatty acids that discriminated between the Mediterranean or habitual diet arms of a parallel design, 6-month partial-feeding randomised controlled trial (RCT) conducted between 2013 and 2014, the MedLey trial (128 participants out of 166 randomised). We applied this biomarker score in an observational study, the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study, to assess the association of the score with T2D incidence over an average of 9.7 years of follow-up since the baseline (1991 to 1998). We included 22,202 participants, of whom 9,453 were T2D cases, with relevant biomarkers from an original case-cohort of 27,779 participants sampled from a cohort of 340,234 people. As a secondary measure of the Mediterranean diet, we used a score estimated from dietary-self report. Within the trial, the biomarker score discriminated well between the 2 arms; the cross-validated C-statistic was 0.88 (95% confidence interval (CI) 0.82 to 0.94). The score was inversely associated with incident T2D in EPIC-InterAct: the hazard ratio (HR) per standard deviation of the score was 0.71 (95% CI: 0.65 to 0.77) following adjustment for sociodemographic, lifestyle and medical factors, and adiposity. In comparison, the HR per standard deviation of the self-reported Mediterranean diet was 0.90 (95% CI: 0.86 to 0.95). Assuming the score was causally associated with T2D, higher adherence to the Mediterranean diet in Western European adults by 10 percentiles of the score was estimated to reduce the incidence of T2D by 11% (95% CI: 7% to 14%). The study limitations included potential measurement error in nutritional biomarkers, unclear specificity of the biomarker score to the Mediterranean diet, and possible residual confounding. Conclusions These findings suggest that objectively assessed adherence to the Mediterranean diet is associated with lower risk of T2D and that even modestly higher adherence may have the potential to reduce the population burden of T2D meaningfully., EU FP6 programme LSHM_CT_2006_037197, European Commission Framework Programme 7 HEALTH-F2-2012-279233, European Research Council (ERC), World Health Organization, Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), Catalan Institute of Oncology - ICO (Spain), Spanish Government 701708, Marie Curie Actions 701708, European Union's Horizon 2020, Marie Sklodowska-Curie 701708

Background and Aims We aimed to investigate the association between protein intake and risk of inflammatory bowel disease [IBD] in the European Prospective Investigation into Cancer and Nutrition. Methods A total of 413 593 participants from eight European countries were included. Dietary data were collected at baseline from validated food frequency questionnaires. Dietary data were calibrated to correct errors in measures related to each country-specific questionnaire. Associations between proteins [total, animal, and vegetable] or food sources of animal proteins, and IBD risk were estimated by Cox proportional hazard models. Results After a mean follow-up of 16 years, 177 patients with Crohn’s disease [CD] and 418 with ulcerative colitis [UC], were identified. There was no association between total protein, animal protein, or vegetable protein intakes and CD or UC risks. Total meat and red meat intakes were associated with UC risk (hazard ratio [HR] for the 4th vs 1st quartile = 1.40, 95% confidence interval [CI] = 0.99-1.98, p-trend = 0.01; and 1.61, 95% CI = 1.10-2.36, p-trend = 0.007, respectively]. There was no association between other food sources of animal protein [processed meat, fish, shellfish, eggs, poultry] and UC. We found no association between food sources of animal proteins and CD risk. Conclusions Meat and red meat consumptions are associated with higher risks of UC. These results support dietary counselling of low meat intake in people at high-risk of IBD.

Background Randomised trials of vitamin D supplementation for cardiovascular disease and all-cause mortality have generally reported null findings. However, generalisability of results to individuals with low vitamin D status is unclear. We aimed to characterise dose-response relationships between 25-hydroxyvitamin D (25[OH]D) concentrations and risk of coronary heart disease, stroke, and all-cause mortality in observational and Mendelian randomisation frameworks. Methods Observational analyses were undertaken using data from 33 prospective studies comprising 500 962 individuals with no known history of coronary heart disease or stroke at baseline. Mendelian randomisation analyses were performed in four population-based cohort studies (UK Biobank, EPIC-CVD, and two Copenhagen population-based studies) comprising 386 406 middle-aged individuals of European ancestries, including 33 546 people who developed coronary heart disease, 18 166 people who had a stroke, and 27 885 people who died. Primary outcomes were coronary heart disease, defined as fatal ischaemic heart disease (International Classification of Diseases 10th revision code I20-I25) or non-fatal myocardial infarction (I21-I23); stroke, defined as any cerebrovascular disease (I60-I69); and all-cause mortality. Findings Observational analyses suggested inverse associations between incident coronary heart disease, stroke, and all-cause mortality outcomes with 25(OH)D concentration at low 25(OH)D concentrations. In population-wide genetic analyses, there were no associations of genetically-predicted 25(OH)D with coronary heart disease, stroke, or all-cause mortality. However, for the participants with vitamin D deficiency (25[OH]D concentration Interpretation Stratified Mendelian randomisation analyses suggest a causal relationship between 25(OH)D concentrations and mortality for individuals with low vitamin D status. Our findings have implications for the design of vitamin D supplementation trials, and potential disease prevention strategies. Funding British Heart Foundation, Medical Research Council, National Institute for Health Research, Health Data Research UK, Cancer Research UK, and International Agency for Research on Cancer.

Objectives To examine differences in health-related behaviours such as screening or testing for cancer, use of hormone replacement therapy (HRT) and use of other medications in different diet groups. Design We studied 31 260 participants across four diet groups (18 155 meat eaters, 5012 fish eaters, 7179 vegetarians, 914 vegans) in the UK EPIC-Oxford cohort. Information was collected in 5-year (around 2000–2003) or 10-year (around 2007) follow-up questionnaires regarding participation in breast screening, cervical screening, prostate-specific antigen (PSA) testing, use of HRT and use of medications for the past 4 weeks. Using Poisson regression, we estimated the prevalence ratios (PR) for each behaviour across people of different diet groups, using meat eaters as the reference group. Results Compared with meat eaters, vegetarian (PR: 0.94, 95% CI 0.89 to 0.98) and vegan (PR: 0.82, 95% CI 0.71 to 0.95) women reported lower participation in breast screening, and vegetarian men were less likely to report PSA testing (PR: 0.82, 95% CI 0.71 to 0.96). No differences were observed among women for cervical screening. In women, all non-meat-eating groups reported lower use of HRT compared with meat eaters (P heterogeneity