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Background: High meat consumption might play a role in promoting low-grade systemic inflammation, but evidence is limited. Objectives: We examined cross-sectional associations of habitual meat consumption with serum C-reactive protein (CRP) and total white blood cell count (WBCC) in British adults. Methods: We included 403,886 men and women (aged 38–73 y) participating in the UK Biobank who provided information on meat intake (via touchscreen questionnaire) and a nonfasting blood sample at recruitment (2006–2010). For a subset of participants (∼5%), an additional blood sample was collected (median 4.4 y later). We used multivariable linear regression models to estimate associations of meat intake (total meat, unprocessed red meat, processed meat, and poultry) with logCRP and logWBCC. Results: The difference in the serum CRP (mg/L) for each 50-g/d higher intake for total meat was 11.6% (95% CI: 11.1, 12.0%), for processed meat was 38.3% (95% CI: 36.0, 40.7%), for unprocessed red meat was 14.4% (95% CI: 13.6, 15.1%), and for poultry was 12.8% (95% CI: 12.0, 13.5%). The difference in the WBCC (×10–9L) for each 50 g/d higher intake of total meat was 1.5% (95% CI: 1.4, 1.6%), for processed meat was 6.5% (95% CI: 6.1, 6.9%), for unprocessed red meat was 1.6% (95% CI: 1.4, 1.7%), and for poultry was 1.6% (95% CI: 1.4, 1.7%). All associations were attenuated after adjustment for adiposity; by 67% with BMI (in kg/m2) and by 58% with waist circumference for total meat and CRP, and by 53% and 47%, respectively, for WBCC, although associations remained statistically significant. Findings of sensitivity analyses in 15,420 participants were similar prospectively, except there were no associations between unprocessed red meat and WBCC. Conclusions: Higher meat consumption, particularly of processed meat, was positively associated with inflammatory markers in these British adults; however, the magnitudes of associations are small and predominantly due to higher adiposity.

Funding European Commission (DG-SANCO) , the International Agency for Research on Cancer (IARC) , MRC Early Career Fellowship (MR/M501669/1) ., Background Unhealthy diets, the rise of non-communicable diseases, and the declining health of the planet are highly intertwined, where food production and consumption are major drivers of increases in greenhouse gas emissions, substantial land use, and adverse health such as cancer and mortality. To assess the potential co-benefits from shifting to more sustainable diets, we aimed to investigate the associations of dietary greenhouse gas emissions and land use with all-cause and cause-specific mortality and cancer incidence rates. Methods Using data from 443 991 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, a multicentre prospective cohort, we estimated associations between dietary contributions to greenhouse gas emissions and land use and all-cause and cause-specific mortality and incident cancers using Cox proportional hazards regression models. The main exposures were modelled as quartiles. Co-benefits, encompassing the potential effects of alternative diets on all-cause mortality and cancer and potential reductions in greenhouse gas emissions and land use, were estimated with counterfactual attributable fraction intervention models, simulating potential effects of dietary shifts based on the EAT–Lancet reference diet. Findings In the pooled analysis, there was an association between levels of dietary greenhouse gas emissions and allcause mortality (adjusted hazard ratio [HR] 1·13 [95% CI 1·10–1·16]) and between land use and all-cause mortality (1·18 [1·15–1·21]) when comparing the fourth quartile to the first quartile. Similar associations were observed for cause-specific mortality. Associations were also observed between all-cause cancer incidence rates and greenhouse gas emissions, when comparing the fourth quartile to the first quartile (adjusted HR 1·11 [95% CI 1·09–1·14]) and between all-cause cancer incidence rates and land use (1·13 [1·10–1·15]); however, estimates differed by cancer type. Through counterfactual attributable fraction modelling of shifts in levels of adherence to the EAT–Lancet diet, we estimated that up to 19–63% of deaths and up to 10–39% of cancers could be prevented, in a 20-year risk period, by different levels of adherence to the EAT–Lancet reference diet. Additionally, switching from lower adherence to the EAT–Lancet reference diet to higher adherence could potentially reduce food-associated greenhouse gas emissions up to 50% and land use up to 62%. Interpretation Our results indicate that shifts towards universally sustainable diets could lead to co-benefits, such as minimising diet-related greenhouse gas emissions and land use, reducing the environmental footprint, aiding in climate change mitigation, and improving population health., European Commission European Commission Joint Research Centre, World Health Organization, UK Research & Innovation (UKRI) Medical Research Council UK (MRC) MR/M501669/1

We thank all EPIC participants and staff for their contribution to the study. We also thank staff from the EPIC-CVD coordinating centres for sample preparation and data handling. This research has been conducted using the UK Biobank Resource (application number 29916). Data on coronary artery disease have been contributed by CARDIoGRAMplusC4D investigators and have been downloaded from www.CARDIOGRAMPLUSC4D.ORG.I Sluijswas supported by a personal Dr. Dekker postdoctoral grant (2015T019) from the Netherlands Heart Foundation. NGF and FI acknowledge core Medical Research Council Epidemiology Unit support (MC_UU_12015/5) and NGF acknowledges NIHR Biomedical Research Centre Cambridge: Nutrition, Diet, and Lifestyle Research Theme (IS-BRC-1215-20014). The InterAct project was funded by the EU FP6 programme (grant number LSHM_CT_2006_037197) and provided the biomarker data in the sub-cohort that was used in the current study. These analyses were supported by Cancer Research UK (C8221/A19170). The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (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) PI13/00061 (EPIC-Granada) and PI13/01162 (EPIC-Murcia), Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, ISCIII Health Research Funds RD12/0036/0018 (cofounded by FEDER funds/European Regional Development Fund ERDF) (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skane and Vasterbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 for EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (UK). EPIC-CVD has been supported by the European Commission Framework Programme 7 (HEALTH-F2-2012-279233), the European Research Council (268834), the UK Medical Research Council (MR/L003120/1), the British Heart Foundation (RG13/13/30194 and RG/18/13/33946) and the National Institute for Health Research (Cambridge Biomedical Research Centre at the Cambridge University Hospitals NHS Foundation Trust). The MEGASTROKE project received funding from sources specified at http://www.megastroke.org/acknowledgments.html. L.E.T.V.analysed the data and drafted the manuscript. L. E. T. V., I. S. and Y. T. vdS. had access to all data for this study. L. E. T. V., I. S., Y. T. vdS., S. B., N. G. F., H. F., F. I., T. K. N., F. R., E. W., K. A., C. D., A. P. C., M. B. S., T. Y. N. T. and A. S. B. contributed to study conception, design and interpretation of data. All authors contributed to critical revision of the manuscript and approval of version to be published., Higher milk intake has been associated with a lower stroke risk, but not with risk of CHD. Residual confounding or reverse causation cannot be excluded. Therefore, we estimated the causal association of milk consumption with stroke and CHD risk through instrumental variable (IV) and gene-outcome analyses. IV analysis included 29 328 participants (4611 stroke; 9828 CHD) of the European Prospective Investigation into Cancer and Nutrition (EPIC)-CVD (eight European countries) and European Prospective Investigation into Cancer and Nutrition-Netherlands (EPIC-NL) case-cohort studies. rs4988235, a lactase persistence (LP) SNP which enables digestion of lactose in adulthood was used as genetic instrument. Intake of milk was first regressed on rs4988235 in a linear regression model. Next, associations of genetically predicted milk consumption with stroke and CHD were estimated using Prentice-weighted Cox regression. Gene-outcome analysis included 777 024 participants (50 804 cases) from MEGASTROKE (including EPIC-CVD), UK Biobank and EPIC-NL for stroke, and 483 966 participants (61 612 cases) from CARDIoGRAM, UK Biobank, EPIC-CVD and EPIC-NL for CHD. In IV analyses, each additional LP allele was associated with a higher intake of milk in EPIC-CVD (beta = 13 center dot 7 g/d; 95 % CI 8 center dot 4, 19 center dot 1) and EPIC-NL (36 center dot 8 g/d; 95 % CI 20 center dot 0, 53 center dot 5). Genetically predicted milk intake was not associated with stroke (HR per 25 g/d 1 center dot 05; 95 % CI 0 center dot 94, 1 center dot 16) or CHD (1 center dot 02; 95 % CI 0 center dot 96, 1 center dot 08). In gene-outcome analyses, there was no association of rs4988235 with risk of stroke (OR 1 center dot 02; 95 % CI 0 center dot 99, 1 center dot 05) or CHD (OR 0 center dot 99; 95 % CI 0 center dot 95, 1 center dot 03). Current Mendelian randomisation analysis does not provide evidence for a causal inverse relationship between milk consumption and stroke or CHD risk., Netherlands Heart Foundation 2015T019, UK Research & Innovation (UKRI) Medical Research Council UK (MRC), European Commission MC_UU_12015/5, NIHR Biomedical Research Centre Cambridge: Nutrition, Diet, and Lifestyle Research Theme IS-BRC-1215-20014, European Commission LSHM_CT_2006_037197, Cancer Research UK C8221/A19170, European Commission European Commission Joint Research Centre, International Agency for Research on Cancer, Danish Cancer Society, Deutsche Krebshilfe German Cancer Research Center (DKFZ) (Germany), Federal Ministry of Education & Research (BMBF), Deutsche Krebshilfe Deutsches Krebsforschungszentrum (Germany), Fondazione AIRC per la ricerca sul cancro Consiglio Nazionale delle Ricerche (CNR), Netherlands Government Netherlands Government, World Cancer Research Fund International (WCRF), Netherlands Government, Instituto de Salud Carlos III PI13/00061 PI13/01162, Junta de Andalucia Regional Government of Asturias (Spain) Regional Government of Basque Country (Spain) Regional Government of Murcia (Spain) Regional Government of Navarra (Spain), ISCIII Health Research Funds (FEDER funds/European Regional Development Fund ERDF) (Spain) RD12/0036/0018, Swedish Cancer Society Swedish Research Council County Council of Skane (Sweden) County Council of Vasterbotten (Sweden), European Commission Framework Programme 7 HEALTH-F2-2012-279233 European Research Council (ERC) European Commission 268834, UK Research & Innovation (UKRI) Medical Research Council UK (MRC) MR/L003120/1 British Heart Foundation RG13/13/30194 RG/18/13/33946 National Institute for Health Research (Cambridge Biomedical Research Centre at the Cambridge University Hospitals NHS Foundation Trust) UK Research & Innovation (UKRI) Medical Research Council UK (MRC) 1000143 MR/M012190/1 Cancer Research UK C8221/A19170 14136 C570/A16491

The concept of plant-based diets has become popular due to the purported benefits for both human health and environmental impact. Although “plant-based” is sometimes used to indicate omnivorous diets with a relatively small component of animal foods, here we take it to mean either vegetarian (plant-based plus dairy products and/or eggs) or vegan (100% plant-based). Important characteristics of plant-based diets which would be expected to be beneficial for long-term health are low intakes of saturated fat and high intakes of dietary fibre, whereas potentially deleterious characteristics are the risk of low intakes of some micronutrients such as vitamin B12, vitamin D, calcium and iodine, particularly in vegans. Vegetarians and vegans typically have lower body mass index, serum low-density lipoprotein (LDL) cholesterol and blood pressure than comparable regular meat-eaters, as well as lower bone mineral density. Vegetarians in the EPIC-Oxford study have a relatively low risk of ischaemic heart disease, diabetes, diverticular disease, kidney stones, cataracts and possibly some cancers, but a relatively high risk of stroke (principally haemorrhagic stroke) and bone fractures, in comparison with meat-eaters. Vegans in EPIC-Oxford have a lower risk of diabetes, diverticular disease and cataracts and a higher risk of fractures, but for other conditions there are insufficient data to draw conclusions. Overall, the health of people following plant-based diets appears to be generally good, with advantages but also some risks, and the extent to which the risks may be mitigated by optimal food choices, fortification and supplementation is not yet known.

Industrial foods have been associated with increased risks of several chronic conditions. We investigated the relationship between the degree of food processing and risks of Crohn's disease (CD) and ulcerative colitis (UC) in the European Prospective Investigation into Cancer and Nutrition cohort.Analyses included 413,590 participants (68.6% women; mean baseline age, 51.7 y) from 8 European countries. Dietary data were collected at baseline from validated country-specific dietary questionnaires. Associations between proportions of unprocessed/minimally processed and ultraprocessed food intake and CD and UC risks were estimated using Cox models to obtain hazard ratios (HRs) and 95% CIs. Models were stratified by center, age, and sex, and adjusted for smoking status, body mass index, physical activity, energy intake, educational level, and alcohol consumption.During a mean follow-up period of 13.2 years, 179 incident cases of CD and 431 incident cases of UC were identified. The risk of CD was lower in people consuming high proportions of unprocessed/minimally processed foods (adjusted HR for the highest vs lowest quartile: 0.57; 95% CI, 0.35-0.93; P trend.01), particularly fruits and vegetables (adjusted HRs, 0.54; 95% CI, 0.34-0.87 and 0.55; 95% CI, 0.34-0.91, respectively). There was no association between unprocessed/minimally processed food intake and the risk of UC. No association was detected between ultraprocessed food consumption and CD or UC risks.In the European Prospective Investigation into Cancer and Nutrition cohort, consumption of unprocessed/minimally processed foods was associated with a lower risk of CD. No association between UC risk and food processing was found.

Background:Exposure to higher levels of melatonin may be associated with lower breast cancer risk, but epidemiologic evidence has been limited. We examined the relationship in a case–control study nested within the Diagnostisch Onderzoek Mammacarcinoom (DOM) study and conducted a meta-analysis of prospective studies.Methods:Concentrations of 6-sulfatoxymelatonin (aMT6s) in prediagnostic first morning urine voids were measured in 274 postmenopausal women diagnosed with breast cancer and 274 matched controls from the DOM study. Conditional logistic regression models were used to estimate multivariable adjusted ORs of breast cancer for thirds of aMT6s. Meta-analysis of this and previous prospective studies of urinary melatonin with breast cancer risk estimated the inverse-variance weighted averages of study-specific log RRs of breast cancer for the highest versus lowest levels of aMT6s.Results:In the DOM study, the ORs of breast cancer for the middle and highest versus lowest thirds of aMT6s were 0.70 [95% confidence interval (CI), 0.45–1.09] and 0.72 (95% CI, 0.44–1.19), respectively. In the meta-analysis of the DOM study with six previous studies (2,296 cases), RR of breast cancer for the highest versus lowest levels of aMT6s was 0.87 (95% CI, 0.76–1.01).Conclusions:Results from the DOM study, together with the published prospective data, do not support a strong association of melatonin with breast cancer risk.Impact:This study adds to the relatively scarce prospective data on melatonin in relation to breast cancer risk. The totality of the prospective evidence does not clearly show an association between melatonin and breast cancer risk, but further data are needed to be able to exclude a modest association.

Background: Circulating insulin-like growth factor-I (IGF-I) is associated with the risk of several cancers. Dietary protein intake, particularly dairy protein, may increase circulating IGF-I; however, associations with different protein sources, other macronutrients, and fibre are inconclusive. Aim: To investigate the associations between intake of protein, macronutrients and their sources, fibre, and alcohol with serum IGF-I concentrations. Methods: A total of 11,815 participants from UK Biobank who completed ≥4 24-hour dietary assessments and had serum IGF-I concentrations measured at baseline were included. Multivariable linear regression was used to assess the cross-sectional associations of macronutrient and fibre intake with circulating IGF-I concentrations. Results: Circulating IGF-I concentrations were positively associated with intake of total protein (per 2.5% higher energy intake: 0.56 nmol/L, (95% confidence interval: 0.47, 0.66)), milk protein: 1.20 nmol/L (0.90, 1.51), and yogurt protein: 1.33 nmol/L (0.79, 1.86), but not with cheese protein: -0.07 nmol/L (-0.40, 0.25). IGF-I concentrations were also positively associated with intake of fibre (per 5 gram/day higher intake: 0.46 nmol/L (0.35, 0.57)) and starch from wholegrains (Q5 vs. Q1: 1.08 nmol/L (0.77, 1.39)), and inversely associated with alcohol consumption (>40 g/day vs Conclusions: These results show differing associations with IGF-I concentrations depending on the source of dairy protein, with positive associations with milk and yogurt protein but no association with cheese protein. The positive association of fibre and starch from wholegrains with IGF-I warrants further investigation.

BackgroundRed and processed meat has been consistently associated with risk for colorectal cancer, but evidence for other cancer sites is limited and few studies have examined the association between poultry intake and cancer risk. We examined associations between total meat, red meat, processed meat and poultry intake and incidence for 20 common cancer sites.Methods and FindingsWe analysed data from 475,023 participants (54% women) in UK Biobank. Participants were aged 37-73 years and cancer free at baseline. Information on meat consumption was based on a touchscreen questionnaire completed at baseline covering type and frequency of meat intake. Diet intake was re-measured a minimum of three times in a subsample (15%) using a web-based 24h dietary recall questionnaire. Multivariable-adjusted Cox proportional hazards models were used to determine the association between baseline meat intake and cancer incidence. Trends in risk across baseline meat intake categories were calculated by assigning a mean value to each category using estimates from the re-measured meat intakes. During a mean follow-up of 6.9 years, 28,955 participants were diagnosed with a malignant cancer. Total, red and processed meat intakes were each positively associated with risk of colorectal cancer (e.g. hazard ratio (HR) per 70 g/day higher intake of red and processed meat combined 1.31, 95%-confidence interval (CI) 1.14-1.52).Red meat intake was positively associated with breast cancer (HR per 50 g/day higher intake 1.12, 1.01-1.24) and prostate cancer (1.15, 1.03-1.29). Poultry intake was positively associated with risk for cancers of the lymphatic and hematopoietic tissues (HR per 30g/day higher intake 1.16, 1.03-1.32). Only the associations with colorectal cancer were robust to Bonferroni correction for multiple comparisons. Study limitations include unrepresentativeness of the study sample for the UK population, low case numbers for less common cancers and the possibility of residual confounding.ConclusionsHigher intakes of red and processed meat were associated with a higher risk of colorectal cancer. The observed positive associations of red meat consumption with breast and prostate cancer, and poultry intake with cancers of the lymphatic and hematopoietic tissues, require further investigation.

EPIC-CVD was supported by the European Commission Framework Programme 7 (HEALTH-F2-2012-279233), and the European Research Council (268834). The coordinating center was supported by core funding from the: United Kingdom MRC (G0800270; MR/L003120/1), British Heart Foundation (BHF) (SP/09/002; RG13/13/30194; RG/18/13/33946), and National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre (BRC) (BRC-1215-20014).* The establishment of the study subcohort was supported by the European Union Sixth Framework Programme (grant LSHM_CT_ 2006_037197 to the InterAct project) and the MRC Epidemiology Unit (grant MC_UU_00006/1). The coordination of EPIC is financially supported by International Agency for Research on Cancer and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, which has additional infrastructure support provided by NIHR Imperial BRC. The national cohorts are supported by: Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (France); German Cancer Aid, German Cancer Research Center, German Institute of Human Nutrition Potsdam-Rehbruecke, Federal Ministry of Education and Research (Germany); Associazione Italiana per la Ricerca sul Cancro--AIRC--Italy, Compagnia di SanPaolo and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports, Netherlands Cancer Registry, LK Research Funds, Dutch Prevention Funds, Zorg Onderzoek Nederland, World Cancer Research Fund, Statistics Netherlands (the Netherlands); Health Research Fund-Instituto de Salud Carlos III, Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skane and Vasterbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C8221/A29017 to EPIC-Oxford), MRC (1000143 to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford) (United Kingdom). EPIC-Greece was supported by the Hellenic Health Foundation (Greece). M.S., N.J.W., N.G.F., and F.I. acknowledge support from MRC Epidemiology Unit (MC_UU_ 00006/1 and MC_UU_00006/3). N.J.W. and N.G.F. acknowledge support from NIHR* Cambridge BRC: Nutrition, Diet, and Lifestyle Research Theme (IS-BRC-1215--20014) and NGF is a NIHR Senior Investigator Award holder. M.S. was also supported by BHF for part of this work while working in the BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom. R. Z.-R. thanks the "Miguel Servet" program (CP15/00100) from the Institute of Health Carlos III (co-funded by the European Social Fund--European Social Fund Investing in Your Future). A.W. was supported by a BHF-Turing Cardiovascular Data Science Award and by the European Commission-Innovative Medicines Initiative (BigData@Heart).R.C.was funded by a MRC-Newton project grant to study genetic risk factors of cardiovascular disease among Southeast Asian people and the Academy of Sciences Malaysia (grant no. MR/P013880/1) and a United Kingdom Research and Innovation-Global Challenges Research Fund Project Grant to study risk factors of noncommunicable diseases in Bangladesh. J.D. holds a BHF Professorship and a NIHR Senior Investigator Award. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy, or views of the International Agency for Research on Cancer/World Health Organization. The funders of the study had no role in study design, data collection, analysis, data interpretation, or writing of the article, or in the decision to submit for publication. M.S. had full access to all the data in the study, and M.S. and N.G.F. had final responsibility for the decision to submit for publication., BACKGROUND: There is controversy about associations between total dietary fatty acids, their classes (saturated fatty acids [SFAs], monounsaturated fatty acids, and polyunsaturated fatty acids), and risk of coronary heart disease (CHD). Specifically, the relevance of food sources of SFAs to CHD associations is uncertain. METHODS AND RESULTS: We conducted a case-cohort study involving 10 529 incident CHD cases and a random subcohort of 16 730 adults selected from a cohort of 385 747 participants in 9 countries of the EPIC (European Prospective Investigation into Cancer and Nutrition) study. We estimated multivariable adjusted country-specific hazard ratios (HRs) and 95% CIs per 5% of energy intake from dietary fatty acids, with and without isocaloric macronutrient substitutions, using Prentice-weighted Cox regression models and pooled results using random-effects meta-analysis. We found no evidence for associations of the consumption of total or fatty acid classes with CHD, regardless of macronutrient substitutions. In analyses considering food sources, CHD incidence was lower per 1% higher energy intake of SFAs from yogurt (HR, 0.93 [95% CI, 0.88–0.99]), cheese (HR, 0.98 [95% CI, 0.96–1.00]), and fish (HR, 0.87 [95% CI, 0.75–1.00]), but higher for SFAs from red meat (HR, 1.07 [95% CI, 1.02–1.12]) and butter (HR, 1.02 [95% CI, 1.00–1.04]). CONCLUSIONS: This observational study found no strong associations of total fatty acids, SFAs, monounsaturated fatty acids, and polyunsaturated fatty acids, with incident CHD. By contrast, we found associations of SFAs with CHD in opposite directions dependent on the food source. These findings should be further confirmed, but support public health recommendations to consider food sources alongside the macronutrients they contain, and suggest the importance of the overall food matrix., European Commission Framework Programme 7 HEALTH-F2-2012-279233, European Research Council (ERC), European Commission 268834, UK Research & Innovation (UKRI), Medical Research Council UK (MRC) G0800270 MR/L003120/1, British Heart Foundation SP/09/002 RG13/13/30194 RG/18/13/33946, National Institute for Health Research (NIHR) BRC-1215-20014, European Commission LSHM_CT_ 2006_037197, Medical Research Council UK (MRC) MC_UU_ 00006/1 MC_UU_00006/3, International Agency for Research on Cancer, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Danish Cancer Society, Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (France), German Cancer Aid, German Cancer Research Center, German Institute of Human Nutrition Potsdam, Rehbruecke, Federal Ministry of Education and Research (Germany), Fondazione AIRC per la ricerca sul cancro, Compagnia di San Paolo, Dutch Ministry of Public Health, Welfare and Sports, Netherlands Cancer Registry, LK Research Funds, Dutch Prevention Funds, Zorg Onderzoek Nederland, World Cancer Research Fund International (WCRF), Netherlands Government, Instituto de Salud Carlos III, Junta de Andalucia, Regional Government of Asturias, Basque Government, Regional Government of Murcia, Regional Government of Navarra, Catalan Institute of Oncology (Spain), Swedish Cancer Society, County Council of Skane (Sweden), County Council of Vasterbotten (Sweden), Cancer Research UK 14136 C8221/A29017, Medical Research Council UK (MRC) 1000143 MR/M012190/1, Hellenic Health Foundation (Greece), NIHR* Cambridge BRC: Nutrition, Diet, and Lifestyle Research Theme IS-BRC-1215-20014, British Heart Foundation, Institute of Health Carlos III (European Social Fund-European Social Fund Investing in Your Future) CP15/00100, BHF-Turing Cardiovascular Data Science Award, European Commission-Innovative Medicines Initiative (BigData@Heart), MRC-Newton project grant MR/P013880/1, United Kingdom Research and Innovation-Global Challenges Research Fund, NIHR Senior Investigator Award

Background: Short or long sleep duration has been associated with some major chronic diseases, but whether disease-related blood biomarkers vary according to habitual sleep duration is unclear. This cross-sectional study aimed to assess blood biomarker levels in relation to total sleep duration. Methods: The analysis includes 459,796 white British adults aged 40-69 during 2006-2010 in UK Biobank. At recruitment, blood samples and self-reported information on total sleep duration were collected from participants. A panel of blood biomarkers were measured. Using linear regression, we estimated geometric mean concentrations of blood biomarkers and mean ratio of ApoB/ApoA1 by sleep duration adjusted for sex, age at data collection, time of blood collection, and lifestyle covariates. Results: Percentage differences in the concentrations of most biomarkers by sleep duration were modest. The largest differences were for C-reactive protein (CRP, an inflammatory biomarker) and gamma glutamyltransferase (GGT, a liver function biomarker), and the differences were markedly attenuated after multivariable-adjustment. The multivariable-adjusted geometric means of CRP and of GGT were 14% and 14% higher in 9 hours vs 7-8 hours of sleep, respectively. Conclusion: In white British adults, most blood biomarker levels varied only modestly with sleep duration and the remaining associations may be due to residual confounding.

Background Previous studies suggest that different foods rich in saturated fatty acids (SFA), particularly meat and dairy, have diverging directions of association with risks of total cardiovascular disease (CVD) and CVD subtypes.(1,2) Purpose To investigate the associations between SFA from different dietary sources and risks of total CVD, ischaemic heart disease (IHD), and stroke. Methods We analysed data on 114,285 UK Biobank participants who had completed ≥2 24-h dietary assessments and were free of CVD at the date of the latest 24-h dietary assessment. Risks of incident (non-fatal and fatal) total CVD, IHD and stroke by intakes of SFA from different sources were estimated using multivariable Cox regressions. Additional models assessed the role of body mass index (BMI) and low-density lipoprotein cholesterol (LDL-C) as potential mediators. We also estimated the associations between modelled isoenergetic substitution of 5% energy from SFA from meat with SFA from dairy, polyunsaturated fatty acids, monounsaturated fatty acids, carbohydrates from whole grains and carbohydrates from fruit and vegetables, and risk of CVD outcomes. A false discovery rate controlling procedure was used to account for multiple testing. Results Over a median 8.5 years of follow-up, there were 4,365, 3,394, and 1,041 cases of total CVD, IHD and stroke, respectively. There were no significant associations between total SFA intake and CVD outcomes. SFA from meat was positively associated with total CVD (hazard ratio for each 5% of energy, 1.19; 95% CI, 1.05–1.35) and IHD (1.21; 1.05–1.39) risk independently of lifestyle and cardiovascular risk factors. However, the estimates were attenuated and non-significant for both total CVD (1.11; 0.98–1.26) and IHD (1.12; 0.97–1.29) after adjustment for BMI. SFA from dairy was inversely associated with IHD risk (0.89; 0.82–0.96) in the multivariable model, however this finding was also attenuated after adjustment for BMI and did not pass correction for multiple testing (0.91; 0.84 to 0.98). Modelled replacement of 5% of energy from SFA from meat with carbohydrates from whole grains or carbohydrates from fruit and vegetables were associated with lower risk of stroke in the multivariable model (0.86; 0.78–0.94 & 0.86; 0.78–0.95, respectively) and the model adjusted for BMI and LDL-C (0.87; 0.79–0.96 & 0.86; 0.78–0.95, respectively). Conclusion(s) SFA from meat was associated with a higher risk of total CVD and IHD, while SFA from dairy was associated with lower risk of IHD, although BMI seemed to account for a large proportion of these associations. It is possible that diverging associations of SFA from different sources with CVD risk may explain the overall null association with total SFA observed in this study and some previous observational studies. Randomised controlled trials are needed to confirm whether replacing SFA from meat by carbohydrate from wholegrains or fruit and vegetables may be beneficial in reducing stroke risk. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Clarendon Fund and Jesus College Clarendon Old Members' AwardJesus College Graduate Scholarship

BackgroundFollowing a vegetarian diet has become increasingly popular and some evidence suggests that being vegetarian may be associated with a lower risk of cancer overall. However, for specific cancer sites, the evidence is limited.AimTo assess the associations of vegetarian and non-vegetarian diets with risks of all cancer, colorectal cancer, postmenopausal breast cancer, and prostate cancer, and to explore the role of potential mediators between these associations.MethodsWe conducted a prospective analysis of 472,377 UK Biobank participants who were free from cancer at recruitment. Participants were categorised into regular meat-eaters (n=247,571), low meat-eaters (n=205,385), fish-eaters (n=10,696), and vegetarians (n=8,685) based on dietary questions completed at recruitment. Multivariable-adjusted Cox regressions were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for all cancer incidence and separate cancer sites across diet groups.ResultsAfter an average follow-up of 11.4 years, 54,961 incident cancers were identified, including 5,882 colorectal, 7,537 postmenopausal breast, 9,501 prostate cancer cases. Compared with regular meat-eaters, being a low meat-eater, fish-eater, or vegetarian were all associated with a lower risk of all cancer (HR: 0.98, 95% CI: 0.96-1.00; 0.90, 0.84-0.96; 0.86, 0.80-0.93, respectively). Being a low meat-eater was associated with a lower risk of colorectal cancer in comparison to regular meat-eaters (0.91, 0.86-0.96); there was heterogeneity in this association by sex (p=0.007), with an inverse association across diet groups in men, but not in women. Vegetarian postmenopausal women had a lower risk of breast cancer (0.82, 0.68-0.99), which was attenuated and non-significant after adjusting for body mass index (BMI; 0.87, 0.72-1.05); in mediation analyses, BMI was found to possibly mediate the observed association. In men, being a fish-eater or a vegetarian was inversely associated with prostate cancer risk (0.80, 0.65-0.99 and 0.69, 0.54-0.89, respectively).ConclusionLow and non-meat-eaters had a lower risk of being diagnosed with cancer in comparison to regular meat-eaters. We also found that low meat-eaters had a lower risk of colorectal cancer, vegetarian women had a lower risk of postmenopausal breast cancer, and vegetarians and fish-eaters had a lower risk of being diagnosed with prostate cancer. The lower risk of colorectal cancer in low meat-eaters is consistent with previous evidence suggesting an adverse impact of meat intake. The lower risk of postmenopausal breast cancer in vegetarian women may be explained by their lower BMI. It is not clear whether the other differences observed, for all cancers and for prostate cancer, reflect any causal relationships or are or due to other factors such as residual confounding or differences in cancer detection.

BackgroundWhile there is strong epidemiological evidence that circulating insulin-like growth factor-I (IGF-I) is associated with a higher risk of several cancers, little is known about its association with non-cancer outcomes. We investigated associations of circulating IGF-I with risk of 25 common conditions, other than cancer, in a large British cohort.MethodsStudy participants were 318 749 middle-aged adults enrolled in the UK Biobank Study. Serum IGF-I concentration was measured in samples collected at baseline (2006-2010), and re-measured in 12 334 participants after an average of 4.3 years. We followed-up participants over an average of 11.5 years by linking to hospital admissions and mortality registries. Multivariable-adjusted Cox regressions estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between circulating IGF-I and 25 common conditions, using the repeated IGF-I measurements to correct for regression dilution bias.ResultsAfter correction for multiple testing (PConclusionsHigher IGF-I concentration might be associated with the risk for several conditions, but genetic studies are needed to clarify which associations may be causal.Key messagesEvidence on the association between circulating insulin-like growth factor-I (IGF-I) and risk of many common, non-cancer health outcomes in the general population is relatively limited.This study used an outcome-wide approach to prospectively examine associations of circulating IGF-I with risk of 25 common conditions in a large, prospective cohort of over 300,000 UK adults.Our study showed that circulating IGF-I is associated with risks of several common diseases and conditions; IGF-I was positively associated with carpal tunnel syndrome and inversely associated with varicose veins, cataracts, diabetes, and iron deficiency anaemia.Further research is needed to evaluate whether these differences in risk may reflect causal relationships.

Background: There may be differences in hematological parameters between meat-eaters and vegetarians.Objective: The aim of this study was to perform cross-sectional analyses of hematological parameters by diet group in a large cohort in the United Kingdom.Methods: A complete blood count was carried out in all UK Biobank participants at recruitment (2006–2010). We examined hemoglobin, red and white blood cell counts, and platelet counts and volume in regular meat eaters (>3 times/wk of red/processed meat consumption, n = 212,831), low meat eaters (n = 213,092), poultry eaters (n = 4815), fish eaters (n = 10,042), vegetarians (n = 6548), and vegans (n = 398) of white ethnicity and meat eaters (n = 3875) and vegetarians (n = 1362) of British Indian ethnicity.Results: In both white and British Indian populations, compared with regular meat eaters (or meat eaters in Indians), the other diet groups had up to 3.7% lower age-adjusted hemoglobin concentrations (difference not significant in white vegan women) and were generally more likely to have anemia (e.g., 8.7% of regular meat eaters compared with 12.8% of vegetarians in white premenopausal women; P < 0.05 after Bonferroni correction). In the white population, compared with regular meat eaters, all other diet groups had lower age- and sex-adjusted total white cells, neutrophils, lymphocytes, monocytes, and eosinophils (P-heterogeneity < 0.001 for all), but basophil counts were similar across diet groups; in British Indians, there was no significant difference in any of the white blood cell counts by diet group. Compared with white regular meat eaters, the low meat eaters, poultry eaters, fish eaters, and vegans had significantly lower platelet counts and higher platelet volume, whereas vegetarians had higher counts and lower volume. Compared with British Indian meat eaters, vegetarians had higher platelet count and lower volume.Conclusions: In the UK Biobank, people with low or no red meat intake generally had lower hemoglobin concentrations and were slightly more likely to be anemic. The lower white blood cell counts observed in low and non-meat eaters, and differences in mean platelet counts and volume between diet groups, warrant further investigation. This observational study was registered at http://www.isrctn.com/ as ISRCTN10125697.

Supplemental Digital Content is available in the text., Objective: Macronutrients may relate differently with serum lipids depending on their source, and understanding this relationship is important for cardiovascular disease prevention. We aimed to investigate the associations between macronutrients and macronutrients from different sources with serum lipids in UK Biobank. Approach and Results: Serum lipids were obtained from serum collected at baseline in 24 639 participants with diet assessed using ≥2 twenty-four–hour dietary assessments completed at baseline and during follow-up. Multivariable linear regressions were conducted to calculate geometric mean concentrations of serum lipids by quintiles of macronutrients. We modeled the association between isoenergetic substitution of 5% energy intake from saturated fatty acids (SFA) with other macronutrients and serum lipids. Free sugar intake was positively associated with triglycerides (0.15 mmol/L geometric mean difference between highest and lowest quintile of intake [95% CI, 0.12–0.17 mmol/L]), whereas nonfree sugar intake was inversely associated with triglycerides (−0.08 [−0.10 to −0.05]). SFA intake was positively associated with LDL-C (low-density lipoprotein cholesterol; 0.17 [0.13–0.20]), omega-3 fatty acid intake was inversely associated with triglycerides (−0.15 [−0.17 to −0.12]). Modeled substitution of SFA with polyunsaturated fatty acids was associated with lower total cholesterol, LDL-C, and triglycerides. Conclusions: The relationship between carbohydrates and triglycerides may depend on their quality, and reducing free sugar intake may be important in cardiovascular disease prevention. Consistent with previous studies, SFA intake is associated with LDL-C and substitution of SFA intake with polyunsaturated fatty acids intake may be associated with a more favorable serum lipid profile.

Background There is limited prospective evidence on the association between meat consumption and many common, non-cancerous health outcomes. We examined associations of meat intake with risk of 25 common conditions (other than cancer). Methods We used data from 474,985 middle-aged adults recruited into the UK Biobank study between 2006 and 2010 and followed up until 2017 (mean follow-up 8.0 years) with available information on meat intake at baseline (collected via touchscreen questionnaire), and linked hospital admissions and mortality data. For a large sub-sample (~ 69,000), dietary intakes were re-measured three or more times using an online, 24-h recall questionnaire. Results On average, participants who reported consuming meat regularly (three or more times per week) had more adverse health behaviours and characteristics than participants who consumed meat less regularly, and most of the positive associations observed for meat consumption and health risks were substantially attenuated after adjustment for body mass index (BMI). In multi-variable adjusted (including BMI) Cox regression models corrected for multiple testing, higher consumption of unprocessed red and processed meat combined was associated with higher risks of ischaemic heart disease (hazard ratio (HRs) per 70 g/day higher intake 1.15, 95% confidence intervals (CIs) 1.07–1.23), pneumonia (1.31, 1.18–1.44), diverticular disease (1.19, 1.11–1.28), colon polyps (1.10, 1.06–1.15), and diabetes (1.30, 1.20–1.42); results were similar for unprocessed red meat and processed meat intakes separately. Higher consumption of unprocessed red meat alone was associated with a lower risk of iron deficiency anaemia (IDA: HR per 50 g/day higher intake 0.80, 95% CIs 0.72–0.90). Higher poultry meat intake was associated with higher risks of gastro-oesophageal reflux disease (HR per 30 g/day higher intake 1.17, 95% CIs 1.09–1.26), gastritis and duodenitis (1.12, 1.05–1.18), diverticular disease (1.10, 1.04–1.17), gallbladder disease (1.11, 1.04–1.19), and diabetes (1.14, 1.07–1.21), and a lower IDA risk (0.83, 0.76–0.90). Conclusions Higher unprocessed red meat, processed meat, and poultry meat consumption was associated with higher risks of several common conditions; higher BMI accounted for a substantial proportion of these increased risks suggesting that residual confounding or mediation by adiposity might account for some of these remaining associations. Higher unprocessed red meat and poultry meat consumption was associated with lower IDA risk.

This is a pre-copyedited, author-produced version of an article accepted for publication in The American Journal of Clinical Nutrition following peer review. The version of record, Zamora-Ros, R., Lujan-Barroso, L., Achaintre, D., Franceschi, S., Kyrø, C., Overvad, K., ... Agudo, A. (2020). Blood polyphenol concentrations and differentiated thyroid carcinoma in women from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. American Journal of Clinical Nutrition, 113(1), 162-171, is available online at: https://doi.org/10.1093/ajcn/nqaa277. Background - Polyphenols are natural compounds with anticarcinogenic properties in cellular and animal models, but epidemiological evidence determining the associations of these compounds with thyroid cancer (TC) is lacking. Objectives - The aim of this study was to evaluate the relations between blood concentrations of 36 polyphenols and TC risk in EPIC (the European Prospective Investigation into Cancer and Nutrition). Methods - A nested case–control study was conducted on 273 female cases (210 papillary, 45 follicular, and 18 not otherwise specified TC tumors) and 512 strictly matched controls. Blood polyphenol concentrations were analyzed by HPLC coupled to tandem MS after enzymatic hydrolysis. Results - Using multivariable-adjusted conditional logistic regression models, caffeic acid (ORlog2: 0.55; 95% CI: 0.33, 0.93) and its dehydrogenated metabolite, 3,4-dihydroxyphenylpropionic acid (ORlog2: 0.84; 95% CI: 0.71, 0.99), were inversely associated with differentiated TC risk. Similar results were observed for papillary TC, but not for follicular TC. Ferulic acid was also inversely associated only with papillary TC (ORlog2: 0.68; 95% CI: 0.51, 0.91). However, none of these relations was significant after Bonferroni correction for multiple testing. No association was observed for any of the remaining polyphenols with total differentiated, papillary, or follicular TC. Conclusions - Blood polyphenol concentrations were mostly not associated with differentiated TC risk in women, although our study raises the possibility that high blood concentrations of caffeic, 3,4-dihydroxyphenylpropionic, and ferulic acids may be related to a lower papillary TC risk.

Background Prior research suggested a differential association of 25-hydroxyvitamin D (25(OH)D) metabolites with type 2 diabetes (T2D), with total 25(OH)D and 25(OH)D3 inversely associated with T2D, but the epimeric form (C3-epi-25(OH)D3) positively associated with T2D. Whether or not these observational associations are causal remains uncertain. We aimed to examine the potential causality of these associations using Mendelian randomisation (MR) analysis. Methods and findings We performed a meta-analysis of genome-wide association studies for total 25(OH)D (N = 120,618), 25(OH)D3 (N = 40,562), and C3-epi-25(OH)D3 (N = 40,562) in participants of European descent (European Prospective Investigation into Cancer and Nutrition [EPIC]–InterAct study, EPIC-Norfolk study, EPIC-CVD study, Ely study, and the SUNLIGHT consortium). We identified genetic variants for MR analysis to investigate the causal association of the 25(OH)D metabolites with T2D (including 80,983 T2D cases and 842,909 non-cases). We also estimated the observational association of 25(OH)D metabolites with T2D by performing random effects meta-analysis of results from previous studies and results from the EPIC-InterAct study. We identified 10 genetic loci associated with total 25(OH)D, 7 loci associated with 25(OH)D3 and 3 loci associated with C3-epi-25(OH)D3. Based on the meta-analysis of observational studies, each 1–standard deviation (SD) higher level of 25(OH)D was associated with a 20% lower risk of T2D (relative risk [RR]: 0.80; 95% CI 0.77, 0.84; p < 0.001), but a genetically predicted 1-SD increase in 25(OH)D was not significantly associated with T2D (odds ratio [OR]: 0.96; 95% CI 0.89, 1.03; p = 0.23); this result was consistent across sensitivity analyses. In EPIC-InterAct, 25(OH)D3 (per 1-SD) was associated with a lower risk of T2D (RR: 0.81; 95% CI 0.77, 0.86; p < 0.001), while C3-epi-25(OH)D3 (above versus below lower limit of quantification) was positively associated with T2D (RR: 1.12; 95% CI 1.03, 1.22; p = 0.006), but neither 25(OH)D3 (OR: 0.97; 95% CI 0.93, 1.01; p = 0.14) nor C3-epi-25(OH)D3 (OR: 0.98; 95% CI 0.93, 1.04; p = 0.53) was causally associated with T2D risk in the MR analysis. Main limitations include the lack of a non-linear MR analysis and of the generalisability of the current findings from European populations to other populations of different ethnicities. Conclusions Our study found discordant associations of biochemically measured and genetically predicted differences in blood 25(OH)D with T2D risk. The findings based on MR analysis in a large sample of European ancestry do not support a causal association of total 25(OH)D or 25(OH)D metabolites with T2D and argue against the use of vitamin D supplementation for the prevention of T2D., Using both observational and genetic analyses, Ju-Sheng Zheng and colleagues investigate the relationship between vitamin D metabolites and type 2 diabetes among European individuals., Author summary Why was this study done? There is ongoing uncertainty on whether the body’s vitamin D status indicated by blood 25-hydroxyvitamin D (25(OH)D) is relevant to the prevention of type 2 diabetes. There are conflicting findings from observational studies and a limited number of randomised controlled trials. Prior research did not distinguish between different metabolites of total 25(OH)D, including 25(OH)D3 and C3-epi-25(OH)D3, an isomer of 25(OH)D3. It is not clear whether the associations of 25(OH)D metabolites with type 2 diabetes are causal, with conflicting findings from prior Mendelian randomisation studies of total 25(OH)D and no previous Mendelian randomisation studies appraising 25(OH)D metabolites. What did the researchers do and find? The current research compared observational estimates of the association between 25(OH)D metabolites and incident type 2 diabetes with Mendelian randomisation estimates based on genetic instruments. Using multiple data sources, we performed genome-wide association studies among 120,618 individuals for total 25(OH)D, and among 40,562 individuals for the other vitamin D metabolites. Among participants of European descent, 10 genetic loci were identified for total 25(OH)D, 7 loci for 25(OH)D3 and 3 loci for C3-epi-25(OH)D3. In meta-analysis of observational studies, we found that each 1–standard deviation higher level of total 25(OH)D was associated with 20% lower risk of type 2 diabetes. The result was similar for 25(OH)D3, but for C3-epi-25(OH)D3, a positive association with type 2 diabetes was found. With up to 80,983 type 2 diabetes cases and 842,909 controls, we assessed the association of genetically predicted differences in total 25(OH)D and its metabolites with type 2 diabetes. Neither genetically predicted higher total 25(OH)D level nor genetically predicted higher levels of 25(OH)D metabolites were significantly associated with type 2 diabetes. What do these findings mean? There were conflicting findings for a link with type 2 diabetes for the observational analysis of biochemically measured 25(OH)D metabolites versus the genetically predicted levels of these metabolites. The null findings based on Mendelian randomisation analysis indicate that blood levels of 25(OH)D or its metabolites are not likely to be causal factors for the development of type 2 diabetes. The current findings together with other evidence from randomised controlled trials do not support the use of vitamin D supplementation for the prevention of type 2 diabetes.

OBJECTIVE There is sparse evidence for the association of suitable food substitutions for red and processed meat on the risk of type 2 diabetes. We modeled the association between replacing red and processed meat with other protein sources and the risk of type 2 diabetes and estimated its population impact. RESEARCH DESIGN AND METHODS The European Prospective Investigation into Cancer (EPIC)-InterAct case cohort included 11,741 individuals with type 2 diabetes and a subcohort of 15,450 participants in eight countries. We modeled the replacement of self-reported red and processed meat with poultry, fish, eggs, legumes, cheese, cereals, yogurt, milk, and nuts. Country-specific hazard ratios (HRs) for incident type 2 diabetes were estimated by Prentice-weighted Cox regression and pooled using random-effects meta-analysis. RESULTS There was a lower hazard for type 2 diabetes for the modeled replacement of red and processed meat (50 g/day) with cheese (HR 0.90, 95% CI 0.83–0.97) (30 g/day), yogurt (0.90, 0.86–0.95) (70 g/day), nuts (0.90, 0.84–0.96) (10 g/day), or cereals (0.92, 0.88–0.96) (30 g/day) but not for replacements with poultry, fish, eggs, legumes, or milk. If a causal association is assumed, replacing red and processed meat with cheese, yogurt, or nuts could prevent 8.8%, 8.3%, or 7.5%, respectively, of new cases of type 2 diabetes. CONCLUSIONS Replacement of red and processed meat with cheese, yogurt, nuts, or cereals was associated with a lower rate of type 2 diabetes. Substituting red and processed meat by other protein sources may contribute to the prevention of incident type 2 diabetes in European populations.

Study Objectives To investigate the association between sleep duration and breast cancer incidence, we examined the association in a large UK prospective study and conducted a meta-analysis of prospective studies. Methods In the Million Women Study, usual sleep duration over a 24-h period was collected in 2001 for 713,150 participants without prior cancer, heart problems, stroke, or diabetes (mean age = 60 years). Follow-up for breast cancer was by record linkage to national cancer registry data for 14.3 years on average from the 3-year resurvey. Cox regression models yielded multivariable-adjusted breast cancer relative risks (RR) and 95% confidence intervals (CIs) for sleep duration categories. Published prospective studies of sleep duration and breast cancer risk were included in a meta-analysis, which estimated the inverse-variance weighted average of study-specific log RRs for short and for long versus average duration sleep. Results After excluding the first 5 years to minimize reverse causation bias in the Million Women Study, 24,476 women developed breast cancer. Compared with 7–8 h of sleep, the RRs for 9 h of sleep were 1.01 (95% CI, 0.95–1.07), 0.99 (0.96–1.03), 1.01 (0.96–1.06), and 1.03 (0.95–1.12), respectively. In a meta-analysis of 14 prospective studies plus the Million Women Study, including 65,410 breast cancer cases, neither short (RR < 7 h = 0.99 [0.98–1.01]) nor long (RR > 8 h = 1.01 [0.98–1.04]) versus average duration sleep was associated with breast cancer risk. Conclusions The totality of the prospective evidence does not support an association between sleep duration and breast cancer risk.

Several studies have reported associations of hypertension with cancer, but not all results were conclusive. We examined the association of systolic (SBP) and diastolic (DBP) blood pressure with the development of incident cancer at all anatomical sites in the European Prospective Investigation into Cancer and Nutrition (EPIC). Hazard ratios (HRs) (95% confidence intervals) were estimated using multivariable Cox proportional hazards models, stratified by EPIC-participating center and age at recruitment, and adjusted for sex, education, smoking, body mass index, physical activity, diabetes and dietary (in women also reproductive) factors. The study included 307,318 men and women, with an average follow-up of 13.7 (standard deviation 4.4) years and 39,298 incident cancers. We confirmed the expected positive association with renal cell carcinoma: HR = 1.12 (1.08-1.17) per 10 mm Hg higher SBP and HR = 1.23 (1.14-1.32) for DBP. We additionally found positive associations for esophageal squamous cell carcinoma (SCC): HR = 1.16 (1.07-1.26) (SBP), HR = 1.31 (1.13-1.51) (DBP), weaker for head and neck cancers: HR = 1.08 (1.04-1.12) (SBP), HR = 1.09 (1.01-1.17) (DBP) and, similarly, for skin SCC, colon cancer, postmenopausal breast cancer and uterine adenocarcinoma (AC), but not for esophageal AC, lung SCC, lung AC or uterine endometroid cancer. We observed weak inverse associations of SBP with cervical SCC: HR = 0.91 (0.82-1.00) and lymphomas: HR = 0.97 (0.93-1.00). There were no consistent associations with cancers in other locations. Our results are largely compatible with published studies and support weak associations of blood pressure with cancers in specific locations and morphologies.

Aim To investigate the associations between major foods and dietary fibre with subtypes of stroke in a large prospective cohort. Methods and results We analysed data on 418 329 men and women from nine European countries, with an average of 12.7 years of follow-up. Diet was assessed using validated country-specific questionnaires which asked about habitual intake over the past year, calibrated using 24-h recalls. Multivariable-adjusted Cox regressions were used to estimate hazard ratios (HRs) for ischaemic and haemorrhagic stroke associated with consumption of red and processed meat, poultry, fish, dairy foods, eggs, cereals, fruit and vegetables, legumes, nuts and seeds, and dietary fibre. For ischaemic stroke (4281 cases), lower risks were observed with higher consumption of fruit and vegetables combined (HR; 95% CI per 200 g/day higher intake, 0.87; 0.82–0.93, P-trend Conclusion Risk of ischaemic stroke was inversely associated with consumption of fruit and vegetables, dietary fibre, and dairy foods, while risk of haemorrhagic stroke was positively associated with egg consumption. The apparent differences in the associations highlight the importance of examining ischaemic and haemorrhagic stroke subtypes separately.

Objective To investigate the association of plasma vitamin C and carotenoids, as indicators of fruit and vegetable intake, with the risk of type 2 diabetes. Design Prospective case-cohort study. Setting Populations from eight European countries. Participants 9754 participants with incident type 2 diabetes, and a subcohort of 13 662 individuals from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort of 340 234 participants: EPIC-InterAct case-cohort study. Main outcome measure Incident type 2 diabetes. Results In a multivariable adjusted model, higher plasma vitamin C was associated with a lower risk of developing type 2 diabetes (hazard ratio per standard deviation 0.82, 95% confidence interval 0.76 to 0.89). A similar inverse association was shown for total carotenoids (hazard ratio per standard deviation 0.75, 0.68 to 0.82). A composite biomarker score (split into five equal groups), comprising vitamin C and individual carotenoids, was inversely associated with type 2 diabetes with hazard ratios 0.77, 0.66, 0.59, and 0.50 for groups 2-5 compared with group 1 (the lowest group). Self-reported median fruit and vegetable intake was 274 g/day, 396 g/day, and 508 g/day for participants in categories defined by groups 1, 3, and 5 of the composite biomarker score, respectively. One standard deviation difference in the composite biomarker score, equivalent to a 66 (95% confidence interval 61 to 71) g/day difference in total fruit and vegetable intake, was associated with a hazard ratio of 0.75 (0.67 to 0.83). This would be equivalent to an absolute risk reduction of 0.95 per 1000 person years of follow up if achieved across an entire population with the characteristics of the eight European countries included in this analysis. Conclusions These findings indicate an inverse association between plasma vitamin C, carotenoids, and their composite biomarker score, and incident type 2 diabetes in different European countries. These biomarkers are objective indicators of fruit and vegetable consumption, and suggest that diets rich in even modestly higher fruit and vegetable consumption could help to prevent development of type 2 diabetes.

Background Although lifestyle factors have been studied in relation to individual non-communicable diseases (NCDs), their association with development of a subsequent NCD, defined as multimorbidity, has been scarcely investigated. The aim of this study was to investigate associations between five lifestyle factors and incident multimorbidity of cancer and cardiometabolic diseases. Methods In this prospective cohort study, 291,778 participants (64% women) from seven European countries, mostly aged 43 to 58 years and free of cancer, cardiovascular disease (CVD), and type 2 diabetes (T2D) at recruitment, were included. Incident multimorbidity of cancer and cardiometabolic diseases was defined as developing subsequently two diseases including first cancer at any site, CVD, and T2D in an individual. Multi-state modelling based on Cox regression was used to compute hazard ratios (HR) and 95% confidence intervals (95% CI) of developing cancer, CVD, or T2D, and subsequent transitions to multimorbidity, in relation to body mass index (BMI), smoking status, alcohol intake, physical activity, adherence to the Mediterranean diet, and their combination as a healthy lifestyle index (HLI) score. Cumulative incidence functions (CIFs) were estimated to compute 10-year absolute risks for transitions from healthy to cancer at any site, CVD (both fatal and non-fatal), or T2D, and to subsequent multimorbidity after each of the three NCDs. Results During a median follow-up of 11 years, 1910 men and 1334 women developed multimorbidity of cancer and cardiometabolic diseases. A higher HLI, reflecting healthy lifestyles, was strongly inversely associated with multimorbidity, with hazard ratios per 3-unit increment of 0.75 (95% CI, 0.71 to 0.81), 0.84 (0.79 to 0.90), and 0.82 (0.77 to 0.88) after cancer, CVD, and T2D, respectively. After T2D, the 10-year absolute risks of multimorbidity were 40% and 25% for men and women, respectively, with unhealthy lifestyle, and 30% and 18% for men and women with healthy lifestyles. Conclusion Pre-diagnostic healthy lifestyle behaviours were strongly inversely associated with the risk of cancer and cardiometabolic diseases, and with the prognosis of these diseases by reducing risk of multimorbidity.

Background: A detailed description of anthropometric and physiologic characteristics of persons in different diet groups is lacking Objective: We aimed to perform cross-sectional analyses of diet group with anthropometric and physiologic characteristics in a large cohort in the United Kingdom. Design: The UK Biobank recruited ∼500,000 middle-aged participants throughout the United Kingdom in 2006–2010. Anthropometric indexes (height, weight, waist and hip circumference, body composition) and other physiologic characteristics (heel bone mineral density, grip strength, blood pressure, pulse rate) were measured following standardized protocols. We estimated the age-adjusted means of each characteristic in 6 diet groups (198,166 regular meat eaters, 199,784 low meat eaters, 4381 poultry eaters, 9674 fish eaters, 6366 vegetarians, and 378 vegans) in white women and men, and in 2 diet groups (3322 meat eaters and 1186 vegetarians) in British Indian women and men. Results: In white women, after adjustment for age and compared with regular meat eaters, non–red meat eaters had lower adiposity (e.g., 4.5% lower body fat in vegan women) and lower systolic and diastolic blood pressure (−4.2 and −3.3 mm Hg, respectively), and generally lower heel bone mineral density t-score (−0.26). Patterns of differences by diet group were similar in white men. In the Indian population, compared with meat eaters, vegetarian women were shorter (−1.1 cm) and had lower lean mass (−0.5 kg), and both vegetarian women and men had lower grip strength (−1.3 and −1.4 kg, respectively). No significant differences in the other characteristics were observed. Conclusions: Differences in anthropometric and physiologic characteristics were observed across diet groups in white participants, but fewer differences were observed in British Indian participants. The observed differences may be important as intermediate markers of long-term health in different diet groups. This observational study was registered at http://www.isrctn.com/ as ISRCTN10125697.

Introduction: Beverage consumption is a modifiable risk factor for type 2 diabetes (T2D), but there is insufficient evidence to inform the suitability of substituting 1 type of beverage for another. Objective: The aim of this study was to estimate the risk of T2D when consumption of sugar-sweetened beverages (SSBs) was replaced with consumption of fruit juice, milk, coffee, or tea. Methods: In the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study of 8 European countries (n = 27,662, with 12,333 cases of incident T2D, 1992-2007), beverage consumption was estimated at baseline by dietary questionnaires. Using Prentice-weighted Cox regression adjusting for other beverages and potential confounders, we estimated associations of substituting 1 type of beverage for another on incident T2D. Results: Mean +/- SD of estimated consumption of SSB was 55 +/- 105 g/d. Means +/- SDs for the other beverages were as follows: fruit juice, 59 +/- 101 g/d; milk, 209 +/- 203 g/d; coffee, 381 +/- 372 g/d; and tea, 152 +/- 282 g/d. Substituting coffee for SSBs by 250 g/d was associated with a 21% lower incidence of T2D (95% CI: 12%, 29%). The rate difference was -12.0 (95% CI: -20.0, -5.0) per 10,000 person-years among adults consuming SSBs >= 250 g/d (absolute rate = 48.3/10,000). Substituting tea for SSBs was estimated to lower T2D incidence by 22% (95% CI: 15%, 28%) or -11.0 (95% CI:-20.0, -2.6) per 10,000 person-years, whereas substituting fruit juice or milk was estimated not to alter T2D risk significantly. Conclusions: These findings indicate a potential benefit of substituting coffee or tea for SSBs for the primary prevention of T2D and may help formulate public health recommendations on beverage consumption in different populations., The InterAct project was funded by the EU FP6 program (LSHM_CT_2006_037197). InterAct investigators acknowledge funding from the following agencies: Medical Research Council Epidemiology Unit Core Support (MC_UU_12015/1, MC_UU_12015/5); National Institute for Health Research, Biomedical Research Centre Cambridge: Nutrition, Diet, and Lifestyle Research Theme (IS-BRC-1215-20014); the German Federal Ministry of Education and Research, the German Center for Diabetes Research, the State of Brandenburg, Germany; Netherlands Agency grant IGE05012 and an Incentive Grant from the Board of the University Medical Center Utrecht (Netherlands); Dutch Ministry of Public Health, Welfare, and Sports, Netherlands Cancer Registry, LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund, and Statistics Netherlands; Swedish Research Council, Novo Nordisk, Swedish Heart Lung Foundation, and Swedish Diabetes Association; Danish Cancer Society; Deutsche Krebshilfe; Associazione Italiana per la Ricerca sul Cancro; Asturias Regional Government; Navarra Regional Government, Health Research Fund of the Spanish Ministry of Health; CIBER Epidemiologia y Salud Publica, Spain; Murcia Regional Government (grant 6236); and AIRE-ONLUS Ragusa, AVIS-Ragusa, and Sicilian Regional Government.

Purpose:Advanced glycation end products (AGEs) can be formed in foods by the reaction of reducing sugars with proteins, and have been shown to induce insulin resistance and obesity in experimental studies. We examined the association between dietary AGEs intake and changes in body weight in adults over an average of 5years of follow-up. Methods:A total of 255,170 participants aged 25–70years were recruited in ten European countries (1992–2000) in the PANACEA study (Physical Activity, Nutrition, Alcohol, Cessation of smoking, Eating out of home in relation to Anthropometry), a sub-cohort of the EPIC (European Prospective Investigation into Cancer and Nutrition). Body weight was measured at recruitment and self-reported between 2 and 11years later depending on the study center. A reference database for AGEs was used containing UPLC–MS/MS-measured Nε-(carboxymethyl)-lysine (CML), Nε-(1-carboxyethyl)-lysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) in 200 common European foods. This reference database was matched to foods and decomposed recipes obtained from country-specific validated dietary questionnaires in EPIC and intake levels of CEL, CML, and MG-H1 were estimated. Associations between dietary AGEs intake and body weight change were estimated separately for each of the three AGEs using multilevel mixed linear regression models with center as random effect and dietary AGEs intake and relevant confounders as fixed effects. Results:A one-SD increment in CEL intake was associated with 0.111kg (95% CI 0.087–0.135) additional weight gain over 5years. The corresponding additional weight gain for CML and MG-H1 was 0.065kg (0.041–0.089) and 0.034kg (0.012, 0.057), respectively. The top six food groups contributing to AGEs intake, with varying proportions across the AGEs, were cereals/cereal products, meat/processed meat, cakes/biscuits, dairy, sugar and confectionary, and fish/shellfish. Conclusion:In this study of European adults, higher intakes of AGEs were associated with marginally greater weight gain over an average of 5years of follow-up.

Background High carbohydrate intake raises blood triglycerides, glucose, and insulin; reduces HDLs; and may increase risk of coronary heart disease (CHD). Epidemiological studies indicate that high dietary glycemic index (GI) and glycemic load (GL) are associated with increased CHD risk. Objectives The aim of this study was to determine whether dietary GI, GL, and available carbohydrates are associated with CHD risk in both sexes. Methods This large prospective study—the European Prospective Investigation into Cancer and Nutrition—consisted of 338,325 participants who completed a dietary questionnaire. HRs with 95% CIs for a CHD event, in relation to intake of GI, GL, and carbohydrates, were estimated using covariate-adjusted Cox proportional hazard models. Results After 12.8 y (median), 6378 participants had experienced a CHD event. High GL was associated with greater CHD risk [HR 1.16 (95% CI: 1.02, 1.31) highest vs. lowest quintile, p-trend 0.035; HR 1.18 (95% CI: 1.07, 1.29) per 50 g/day of GL intake]. The association between GL and CHD risk was evident in subjects with BMI (in kg/m2) ≥25 [HR: 1.22 (95% CI: 1.11, 1.35) per 50 g/d] but not in those with BMI Conclusions This large pan-European study provides robust additional support for the hypothesis that a diet that induces a high glucose response is associated with greater CHD risk.

Background: Cardiometabolic benefits of the Mediterranean diet have been recognized, but underlying mechanisms are not fully understood. Objectives: We aimed to investigate how the Mediterranean diet could influence circulating metabolites and how the metabolites could mediate the associations of the diet with cardiometabolic risk factors. Methods: Among 10,806 participants (58.9% women, mean age = 48.4 y) in the Fenland Study (2004–2015) in the United Kingdom, we assessed dietary consumption with FFQs and conducted a targeted metabolomics assay for 175 plasma metabolites (acylcarnitines, amines, sphingolipids, and phospholipids). We examined cross-sectional associations of the Mediterranean diet score (MDS) and its major components with each metabolite, modeling multivariable-adjusted linear regression. We used the regression estimates to summarize metabolites associated with the MDS into a metabolite score as a marker of the diet. Subsequently, we assessed how much metabolite subclasses and the metabolite score would mediate the associations of the MDS with circulating lipids, homeostasis model assessment of insulin resistance (HOMA-IR), and other metabolic factors by comparing regression estimates upon adjustment for the metabolites. Results: Sixty-six metabolites were significantly associated with the MDS (P ≤ 0.003, corrected for false discovery rate) (Spearman correlations, r: −0.28 to +0.28). The metabolite score was moderately correlated with the MDS (r = 0.43). Of MDS components, consumption of nuts, cereals, and meats contributed to variations in acylcarnitines; fruits, to amino acids and amines; and fish, to phospholipids. The metabolite score was estimated to explain 37.2% of the inverse association of the MDS with HOMA-IR (P for mediation < 0.05). The associations of the MDS with cardiometabolic factors were estimated to be mediated by acylcarnitines, sphingolipids, and phospholipids. Conclusions: Multiple metabolites relate to the Mediterranean diet in a healthy general British population and highlight the potential to identify a set of biomarkers for an overall diet. The associations may involve pathways of phospholipid metabolism, carnitine metabolism, and development of insulin resistance and dyslipidemia.

Importance: Soft drinks are frequently consumed, but whether this consumption is associated with mortality risk is unknown and has been understudied in European populations to date. Objective: To examine the association between total, sugar-sweetened, and artificially sweetened soft drink consumption and subsequent total and cause-specific mortality. Design, Setting, and Participants: This population-based cohort study involved participants (n = 451 743 of the full cohort) in the European Prospective Investigation into Cancer and Nutrition (EPIC), an ongoing, large multinational cohort of people from 10 European countries (Denmark, France, Germany, Greece, Italy, the Netherlands, Norway, Spain, Sweden, and the United Kingdom), with participants recruited between January 1, 1992, and December 31, 2000. Excluded participants were those who reported cancer, heart disease, stroke, or diabetes at baseline; those with implausible dietary intake data; and those with missing soft drink consumption or follow-up information. Data analyses were performed from February 1, 2018, to October 1, 2018. Exposure: Consumption of total, sugar-sweetened, and artificially sweetened soft drinks. Main Outcomes and Measures Total mortality and cause-specific mortality. Hazard ratios (HRs) and 95% CIs were estimated using multivariable Cox proportional hazards regression models adjusted for other mortality risk factors. Results: In total, 521 330 individuals were enrolled. Of this total, 451 743 (86.7%) were included in the study, with a mean (SD) age of 50.8 (9.8) years and with 321 081 women (71.1%). During a mean (range) follow-up of 16.4 (11.1 in Greece to 19.2 in France) years, 41 693 deaths occurred. Higher all-cause mortality was found among participants who consumed 2 or more glasses per day (vs consumers of

ObjectiveTo examine the associations of vegetarianism with risks of ischaemic heart disease and stroke.DesignProspective cohort study.SettingThe EPIC-Oxford study, a cohort in the United Kingdom with a large proportion of non-meat eaters, recruited across the country between 1993 and 2001.Participants48 188 participants with no history of ischaemic heart disease, stroke, or angina (or cardiovascular disease) were classified into three distinct diet groups: meat eaters (participants who consumed meat, regardless of whether they consumed fish, dairy, or eggs; n=24 428), fish eaters (consumed fish but no meat; n=7506), and vegetarians including vegans (n=16 254), based on dietary information collected at baseline, and subsequently around 2010 (n=28 364).Main outcome measuresIncident cases of ischaemic heart disease and stroke (including ischaemic and haemorrhagic types) identified through record linkage until 2016.ResultsOver 18.1 years of follow-up, 2820 cases of ischaemic heart disease and 1072 cases of total stroke (519 ischaemic stroke and 300 haemorrhagic stroke) were recorded. After adjusting for sociodemographic and lifestyle confounders, fish eaters and vegetarians had 13% (hazard ratio 0.87, 95% confidence interval 0.77 to 0.99) and 22% (0.78, 0.70 to 0.87) lower rates of ischaemic heart disease than meat eaters, respectively (PConclusionsIn this prospective cohort in the UK, fish eaters and vegetarians had lower rates of ischaemic heart disease than meat eaters, although vegetarians had higher rates of haemorrhagic and total stroke.

Background Population-specificity of exploratory dietary patterns limits their generalizability in investigations with type 2 diabetes incidence. Objective The aim of this study was to derive country-specific exploratory dietary patterns, investigate their association with type 2 diabetes incidence, and replicate diabetes-associated dietary patterns in other countries. Methods Dietary intake data were used, assessed by country-specific questionnaires at baseline of 11,183 incident diabetes cases and 14,694 subcohort members (mean age 52.9 y) from 8 countries, nested within the European Prospective Investigation into Cancer and Nutrition study (mean follow-up time 6.9 y). Exploratory dietary patterns were derived by principal component analysis. HRs for incident type 2 diabetes were calculated by Prentice-weighted Cox proportional hazard regression models. Diabetes-associated dietary patterns were simplified or replicated to be applicable in other countries. A meta-analysis across all countries evaluated the generalizability of the diabetes-association. Results Two dietary patterns per country/UK-center, of which overall 3 dietary patterns were diabetes-associated, were identified. A risk-lowering French dietary pattern was not confirmed across other countries: pooled HRFrance per 1 SD: 1.00; 95% CI: 0.90, 1.10. Risk-increasing dietary patterns, derived in Spain and UK-Norfolk, were confirmed, but only the latter statistically significantly: HRSpain: 1.09; 95% CI: 0.97, 1.22 and HRUK-Norfolk: 1.12; 95% CI: 1.04, 1.20. Respectively, this dietary pattern was characterized by relatively high intakes of potatoes, processed meat, vegetable oils, sugar, cake and cookies, and tea. Conclusions Only few country/center-specific dietary patterns (3 of 18) were statistically significantly associated with diabetes incidence in this multicountry European study population. One pattern, whose association with diabetes was confirmed across other countries, showed overlaps in the food groups potatoes and processed meat with identified diabetes-associated dietary patterns from other studies. The study demonstrates that replication of associations of exploratory patterns with health outcomes is feasible and a necessary step to overcome population-specificity in associations from such analyses.

IntroductionDifferences in health outcomes between meat-eaters and non-meat-eaters might relate to differences in dietary intakes between these diet groups. We assessed intakes of major protein-source foods and other food groups in six groups of meat-eaters and non-meat-eaters participating in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Oxford study.Materials and methodsData were from 30, 239 participants who answered four questions regarding their consumption of meat, fish, dairy or eggs and completed a food frequency questionnaire (FFQ) in 2010. Participants were categorized as regular meat-eaters (> 50 grams of total/any meat per day: n = 12,997); low meat-eaters (< 50 grams of total/any meat per day: n = 4,650); poultry-eaters (poultry but no red meat: n = 591); fish-eaters (no meat but consumed fish: n = 4,528); vegetarians (no meat or fish: n = 6,672); and vegans (no animal products: n = 801). FFQ foods were categorised into 45 food groups. Analysis of variance was used to test for differences between age-adjusted mean intakes of each food group by diet group.ResultsWe found that regular meat-eaters, vegetarians and vegans, respectively, consumed about a third, quarter and a fifth of their total energy intake from high protein-source foods. Compared with regular meat-eaters, low and non-meat-eaters consumed higher amounts of high-protein meat alternatives (soy, legumes, pulses, nuts, seeds) and other plant-based foods (whole grains, vegetables, fruits) and lower amounts of refined grains, fried foods, alcohol, and sugar-sweetened beverages.DiscussionOverall, our results suggest that there were large differences in the amounts and types of protein-rich and other foods eaten by regular, low and non-meat-eaters. These findings provide insight into potential nutritional explanations for differences in health outcomes between diet groups.

ObjectiveTo test whether diets achieving recommendations from the UK’s Scientific Advisory Committee on Nutrition (SACN) were associated with higher monetary costs in a nationally representative sample of UK adults.DesignA cross-sectional study linking 4 d diet diaries in the National Diet and Nutrition Survey (NDNS) to contemporaneous food price data from a market research firm. The monetary cost of diets was assessed in relation to whether or not they met eight food- and nutrient-based recommendations from SACN. Regression models adjusted for potential confounding factors. The primary outcome measure was individual dietary cost per day and per 2000 kcal (8368 kJ).SettingUK.SubjectsAdults (n 2045) sampled between 2008 and 2012 in the NDNS.ResultsOn an isoenergetic basis, diets that met the recommendations for fruit and vegetables, oily fish, non-milk extrinsic sugars, fat, saturated fat and salt were estimated to be between 3 and 17 % more expensive. Diets meeting the recommendation for red and processed meats were 4 % less expensive, while meeting the recommendation for fibre was cost-neutral. Meeting multiple targets was also associated with higher costs; on average, diets meeting six or more SACN recommendations were estimated to be 29 % more costly than isoenergetic diets that met no recommendations.ConclusionsFood costs may be a population-level barrier limiting the adoption of dietary recommendations in the UK. Future research should focus on identifying systems- and individual-level strategies to enable consumers achieve dietary recommendations without increasing food costs. Such strategies may improve the uptake of healthy eating in the population.

The Mediterranean diet has been linked to a number of health benefits, including reduced mortality risk and lower incidence of cardiovascular disease. Definitions of the Mediterranean diet vary across some settings, and scores are increasingly being employed to define Mediterranean diet adherence in epidemiological studies. Some components of the Mediterranean diet overlap with other healthy dietary patterns, whereas other aspects are unique to the Mediterranean diet. In this forum article, we asked clinicians and researchers with an interest in the effect of diet on health to describe what constitutes a Mediterranean diet in different geographical settings, and how we can study the health benefits of this dietary pattern. Electronic supplementary material The online version of this article (doi:10.1186/1741-7015-12-112) contains supplementary material, which is available to authorized users.