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Practicing a diverse diet may reduce chronic disease risk, but clear evidence is scarce and previous diet diversity measures rarely captured diet quality. We investigated the effect of the Healthy Food Diversity (HFD)-Index on incident type 2 diabetes (T2D), myocardial infarction (MI) and stroke among a middle-aged German population. The EPIC-Potsdam study recruited 27,548 participants from 1994 to 1998. Semiquantitative food frequency questionnaire was used to calculate the HFD-Index. Longitudinal associations of HFD-Index and verified incident diseases were investigated by multiple-adjusted Cox proportional hazards regression models. Among 26,591 participants (mean age 50.5 years, 60% women), 1537, 376 and 412 developed T2D, MI and stroke, respectively, over an average follow-up of 10.6 years. There was no association between HFD-Index and incident T2D or MI. Higher compared to lower HFD-Index was inversely associated with incident stroke in men [HR (95% CI): 0.80 (0.70, 0.92)], but positively associated with incident stroke in women [1.20 (1.01, 1.42)]. Although there was no clear association between HFD-Index and T2D or MI incidence, we found a beneficial association in men and a harmful association in women for incident stroke. We emphasised the need for further investigations on combining diet diversity and diet quality in relation to health outcomes., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Aims/hypothesis: The aim of the present study was to investigate the association between dietary exposures to dioxins, dioxin-like polychlorinated biphenyls (DL-PCBs) and non-dioxin-like polychlorinated biphenyls (NDL-PCBs) and the incidence of type 2 diabetes mellitus (T2DM) in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort., Methods: This prospective cohort study with a median 11.7 years of follow-up, included 318,416 individuals recruited in 21 centers in eight countries. Dietary intake of dioxins and PCBs was calculated by combining EPIC food consumption data with food contamination data from the European Food Safety Authority (EFSA). To identify incident cases of T2DM, a thorough review of various sources including self-reported information, linkage to primary and secondary care registers, drug registers, hospital admissions, and mortality data was conducted. Associations between dietary intake of dioxins and PCBs and T2DM were evaluated using multivariable Cox regressions., Results: Higher T2DM risk was observed for higher estimated dietary intake of non-dioxin-like PCBs (NDL-PCBs; HR per 1 SD increment = 1.03 [95 %CI 1.01;1.04], and HR (Q4 vs Q1) = 1.15 [1.08;1.22], P-trend < 0.001). The results were consistent in analyses stratified by gender, body mass index, country, median follow-up, or self-reported hypertension and hyperlipidemia, as well as when adjusting for fat intake. No consistent association was observed between dioxins+DL-PCBs intake and T2DM risk., Conclusion / Interpretation: Results obtained in this large European prospective study indicate a positive and linear association between dietary intake of NDL-PCBs and risk of T2DM. This association remained consistent across various stratified and sensitivity analyses. Further studies are warranted to better understand the biological mechanisms underlying this association., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Background: It is unknown whether the association between ultra-processed food (UPF) intake and type 2 diabetes mellitus differs from other degrees of food processing. We examined the association between degree of food processing and incident type 2 diabetes mellitus., Methods: This was a prospective cohort analysis of the European Prospective Investigation into Cancer and Nutrition (EPIC). Dietary intake was assessed at baseline using dietary questionnaires and classified according to the Nova classification into unprocessed/minimally processed food (MPF), processed culinary ingredients (PCI), processed food (PF) and UPF. Type 2 diabetes mellitus cases were verified through multiple methods. Cox regression and statistical substitution analysis was used to estimate associations between MPF + PCI, PF and UPF intake and incident type 2 diabetes mellitus. To investigate heterogeneity in the association between UPF and incident type 2 diabetes mellitus, UPF sub-group analysis was conducted. Different reference groups were used in each analysis., Findings: Over an average 10.9 years follow-up of 311,892 individuals, 14,236 type 2 diabetes mellitus cases were identified. Each 10% increment of total daily food intake from UPF (%g/day) was associated with 17% (95% confidence interval (95%CI): 1.14-1.19) higher incident type 2 diabetes mellitus. Each 10% increment in MPF + PCI or PF intake was associated with lower incident type 2 diabetes mellitus (MPF + PCI hazard ratio: 0.94 (95%CI: 0.92-0.96); PF hazard ratio: 0.92 (95%CI: 0.89-0.95)). Replacing UPF with MPF + PCI or PF was associated with lower incident type 2 diabetes mellitus. However, heterogeneity was observed across UPF sub-groups, with breads, biscuits and breakfast cereals, sweets and desserts, and plant-based alternatives associated with lower incident type 2 diabetes mellitus., Interpretation: These findings support recommendations to focus on reducing intake of specific UPF for lowering type 2 diabetes mellitus risk., Funding: International Agency for Research on Cancer., Competing Interests: SJD receives royalties from Amazon for a self-published book that mentions ultra-processed food, and payments from Red Pen Reviews. RLB is an employee of Eli Lilly and Company and reports honoraria from Novo Nordisk, Eli Lilly, Medscape, ViiV Healthcare Ltd and International Medical P and advisory board and consultancy work for Novo Nordisk, Eli Lilly, Pfizer, Gila Therapeutics Ltd, Epitomee Medical Ltd and ViiV Healthcare Ltd. All other authors declare no conflicts of interest., (© 2024 The Author(s).)

Association analyses between longitudinal changes in diet quality scores (DQIs) and cardiometabolic risk remain scarce. Hence, we aimed to investigate how changes in two DQIs are associated with incident type 2 diabetes (T2D), myocardial infarction (MI) and stroke in the EPIC-Potsdam study. Changes in the Mediterranean Pyramid Score (MedPyr) and Healthy Diet Score (HDS) over 7 years from baseline (1994-1998) to follow-up 3 (2001-2005) were investigated in 23,548 middle-aged participants. Adjusted Cox Proportional Hazards Regression models were applied to investigate associations between changes in MedPyr and HDS and chronic disease incidence. More than 60% of the participants increased both DQIs more than 5%. Within a median follow-up time of 5 years 568 cases of T2D, 171 of MI, 189 of stroke were verified. An increased compared to stable MedPyr was associated with lower T2D risk (HR 0.74; 95% CI 0.59-0.92), while a decreased MedPyr was associated with higher stroke risk (HR 1.67; 95% CI 1.02-2.72). A decreased compared to stable HDS was associated with higher stroke risk (HR 1.80; 95% CI 1.02-3.20). The findings contribute further evidence on advantages of changing dietary intake towards a Mediterranean Diet. Although baseline HDS adherence was associated with T2D and stroke risk, longitudinal changes in HDS were only significantly associated with stroke risk., (© 2024. The Author(s).)

Background: Epidemiological evidence suggests that a potential association between dietary protein intake and cardiovascular disease (CVD) may depend on the protein source, that is, plant- or animal-derived, but past research was limited and inconclusive., Objectives: To evaluate the association of dietary plant- or animal-derived protein consumption with risk of CVD, and its components ischemic heart disease (IHD) and stroke., Methods: This analysis in the European Prospective Investigation into Cancer and Nutrition (EPIC)-CVD case-cohort study included 16,244 incident CVD cases (10,784 IHD and 6423 stroke cases) and 15,141 subcohort members from 7 European countries. We investigated the association of estimated dietary protein intake with CVD, IHD, and stroke (total, fatal, and nonfatal) using multivariable-adjusted Prentice-weighted Cox regression. We estimated isocaloric substitutions of replacing fats and carbohydrates with plant- or animal-derived protein and replacing food-specific animal protein with plant protein. Multiplicative interactions between dietary protein and prespecified variables were tested., Results: Neither plant- nor animal-derived protein intake was associated with incident CVD, IHD, or stroke in adjusted analyses without or with macronutrient-specified substitution analyses. Higher plant-derived protein intake was associated with 22% lower total stroke incidence among never smokers [HR 0.78, 95% confidence intervals (CI): 0.62, 0.99], but not among current smokers (HR 1.08, 95% CI: 0.83, 1.40, P-interaction = 0.004). Moreover, higher plant-derived protein (per 3% total energy) when replacing red meat protein (HR 0.52, 95% CI: 0.31, 0.88), processed meat protein (HR 0.39, 95% CI: 0.17, 0.90), and dairy protein (HR 0.54, 95% CI: 0.30, 0.98) was associated with lower incidence of fatal stroke., Conclusion: Plant- or animal-derived protein intake was not associated with overall CVD. However, the association of plant-derived protein consumption with lower total stroke incidence among nonsmokers, and with lower incidence of fatal stroke highlights the importance of investigating CVD subtypes and potential interactions. These observations warrant further investigation in diverse populations with varying macronutrient intakes and dietary patterns., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Our knowledge about the connection between protein intake and diabetes-related complications comes largely from studies among those already diagnosed with type 2 diabetes (T2D). However, there is a lack of information on whether changing protein intake after diabetes diagnosis affects complications risk. We aimed to explore the association between protein intake (total, animal, and plant) and vascular complications in incident T2D patients considering pre-diagnosis intake and changes in intake after diagnosis. This prospective cohort study included 1064 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort who developed T2D during follow-up (physician-verified). Dietary protein intake was measured with a food frequency questionnaire at baseline and follow-up. We included physician-reported incident diabetes complications (myocardial infarction, stroke, nephropathy, and neuropathy). A total of 388 participants developed complications, 82 macrovascular complications, and 343 microvascular complications. Substituting carbohydrates with protein showed a trend towards lower complications risk, although this association was not statistically significant (hazard ratio (HR) for 5% energy (E) substitution: 0.83; 95% confidence intervals (CI): 0.60-1.14). Increasing protein intake at the expense of carbohydrates after diabetes diagnosis was not associated with total and microvascular complications (HR for 5% E change substitution: 0.98; 95% CI: 0.89-1.08 and HR for 5% E change substitution: 1.02; 95% CI: 0.92-1.14, respectively). Replacing carbohydrates with protein did not elevate the risk of diabetes complications in incident T2D cases.

Background: The Mediterranean diet has been associated with lower risk of breast cancer (BC) but evidence from prospective studies on the role of Mediterranean diet on BC survival remains sparse and conflicting. We aimed to investigate whether adherence to Mediterranean diet prior to diagnosis is associated with overall and BC-specific mortality., Methods: A total of 13,270 incident breast cancer cases were identified from an initial sample of 318,686 women in 9 countries from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Adherence to Mediterranean diet was estimated through the adapted relative Mediterranean diet (arMED), a 16-point score that includes 8 key components of the Mediterranean diet and excludes alcohol. The degree of adherence to arMED was classified as low (score 0-5), medium (score 6-8), and high (score 9-16). Multivariable Cox proportional hazards models were used to analyze the association between the arMED score and overall mortality, and Fine-Gray competing risks models were applied for BC-specific mortality., Results: After a mean follow-up of 8.6 years from diagnosis, 2340 women died, including 1475 from breast cancer. Among all BC survivors, low compared to medium adherence to arMED score was associated with a 13% higher risk of all-cause mortality (HR 1.13, 95%CI 1.01-1.26). High compared to medium adherence to arMED showed a non-statistically significant association (HR 0.94; 95% CI 0.84-1.05). With no statistically significant departures from linearity, on a continuous scale, a 3-unit increase in the arMED score was associated with an 8% reduced risk of overall mortality (HR 3-unit 0.92, 95% CI: 0.87-0.97). This result sustained when restricted to postmenopausal women and was stronger among metastatic BC cases (HR 3-unit 0.81, 95% CI: 0.72-0.91)., Conclusions: Consuming a Mediterranean diet before BC diagnosis may improve long-term prognosis, particularly after menopause and in cases of metastatic breast cancer. Well-designed dietary interventions are needed to confirm these findings and define specific dietary recommendations., (© 2023. The Author(s).)

Background: Regulating meal timing may have efficacy for improving metabolic health for preventing or managing chronic disease. However, the reliability of measuring meal timing with commonly used dietary assessment tools needs characterization prior to investigating meal timing and health outcomes in epidemiologic studies., Objectives: To evaluate the reliability of estimating meal timing parameters, including overnight fasting duration, the midpoint of overnight fasting time, the number of daily eating episodes, the period with the largest percentage of daily caloric intake, and late last eating episode (> 09:00 pm) from repeated 24-h dietary recalls (24HRs)., Methods: Intraclass correlation coefficients (ICC), Light's Kappa estimates, and 95% CIs were calculated from repeated 24HR administered in 3 epidemiologic studies: The United States-based Interactive Diet and Activity Tracking in AARP (IDATA) study (n = 996, 6 24HR collected over 12-mo), German EPIC-Potsdam Validation Study (European Prospective Investigation into Cancer and Nutrition Potsdam Germany cohort) (n = 134, 12 24HR collected over 12-mo) and EPIC-Potsdam BMBF-II Study (Federal Ministry of Education and Research, "Bundesministerium für Bildung und Forschung") (n = 725, 4 24HR collected over 36 mo)., Results: Measurement reliability of overnight fasting duration based on a single 24HR was "poor" in all studies [ICC range: 0.27; 95% CI: 0.23, 0.32 - 0.46; 95% CI: 0.43, 0.50]. Reliability was "moderate" with 3 24HR (ICC range: 0.53; 95% CI: 0.47, 0.58 in IDATA, 0.62; 95% CI: 0.52, 0.69 in the EPIC-Potsdam Validation Study, and 0.72; 95% CI: 0.70-0.75 in the EPIC-Potsdam BMBF-II Study). Results were similar for the midpoint of overnight fasting time and the number of eating episodes. Reliability of measuring late eating was "fair" in IDATA (Light's Kappa: 0.30; 95% CI: 0.21, 0.39) and "slight" in the EPIC-Potsdam Validation study and the EPIC-Potsdam BMBF-II study (Light's Kappa: 0.19; 95% CI: 0.15, 0.25 and 0.09; 95% CI: 0.06, 0.12, respectively). Reliability estimates differed by sex, BMI, weekday, and season of 24HR administration in some studies., Conclusions: Our results show that ≥ 3 24HR over a 1-3-y period are required for reliable estimates of meal timing variables., (Copyright © 2023. Published by Elsevier Inc.)

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., Trial Registration: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12613000602729 https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=363860., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Authors declare support from the UK Medical Research Council, British Heart Foundation, Wellcome Trust, European Research Council, Swedish Research Council and National Institute for Health Research Cambridge Biomedical Research Centre for the submitted work. FI is a member of PLOS Medicine’s editorial board. PWF reports support for the submitted work from Novo Nordisk Foundation and consulting for Zoe Limited. JD reports grants, personal fees and non-financial support from Merck Sharp & Dohme (MSD), grants, personal fees and non-financial support from Novartis, grants from Pfizer and grants from AstraZeneca outside the submitted work. JD sits on the International Cardiovascular and Metabolic Advisory Board for Novartis (since 2010); the Steering Committee of UK Biobank (since 2011); the MRC International Advisory Group (ING) member, London (since 2013); the MRC High Throughput Science ‘Omics Panel Member, London (since 2013); the Scientific Advisory Committee for Sanofi (since 2013); the International Cardiovascular and Metabolism Research and Development Portfolio Committee for Novartis; and the Astra Zeneca Genomics Advisory Board (2018). ASB reports institutional grants outside the submitted work from AstraZeneca, Bayer, Biogen, BioMarin, Bioverativ, Novartis and Sanofi. Authors otherwise report no financial relationships with any organisations that might have an interest in the submitted work in the previous three years and no other relationships or activities that could appear to have influenced the submitted work.”, (Copyright: © 2023 Sobiecki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Inflammatory, insulin and oestrogenic pathways have been linked to breast cancer (BC). We aimed to examine the relationship between pre-diagnostic dietary patterns related to these mechanisms and BC survival., Methods: The diabetes risk reduction diet (DRRD), inflammatory score of diet (ISD) and oestrogen-related dietary pattern (ERDP) were calculated using dietary data from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Cox proportional hazards models were used to assess associations between dietary patterns and overall mortality and competing risk models for associations with BC-specific mortality., Results: We included 13,270 BC cases with a mean follow-up after diagnosis of 8.6 years, representing 2340 total deaths, including 1475 BC deaths. Higher adherence to the DRRD score was associated with lower overall mortality (HR 1-SD 0.92; 95%CI 0.87-0.96). Greater adherence to pro-inflammatory diets was borderline associated with 6% higher mortality HR 1-SD 1.06; 95%CI 1.00-1.12. No significant association with the oestrogen-related dietary pattern was observed. None of the dietary patterns were associated with BC-specific mortality., Conclusions: Greater adherence to an anti-diabetic and anti-inflammatory diet prior to diagnosis is associated with lower overall mortality among BC survivors. Long-term adherence to these dietary patterns could be a means to improve the prognosis of BC survivors., (© 2023. The Author(s).)

Background: Food processing has been hypothesised to play a role in cancer development; however, data from large-scale epidemiological studies are scarce. This study investigated the association between dietary intake according to amount of food processing and risk of cancer at 25 anatomical sites using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) study., Methods: This study used data from the prospective EPIC cohort study, which recruited participants between March 18, 1991, and July 2, 2001, from 23 centres in ten European countries. Participant eligibility within each cohort was based on geographical or administrative boundaries. Participants were excluded if they had a cancer diagnosis before recruitment, had missing information for the NOVA food processing classification, or were within the top and bottom 1% for ratio of energy intake to energy requirement. Validated dietary questionnaires were used to obtain information on food and drink consumption. Participants with cancer were identified using cancer registries or during follow-up from a combination of sources, including cancer and pathology centres, health insurance records, and active follow-up of participants. We performed a substitution analysis to assess the effect of replacing 10% of processed foods and ultra-processed foods with 10% of minimally processed foods on cancer risk at 25 anatomical sites using Cox proportional hazard models., Findings: 521 324 participants were recruited into EPIC, and 450 111 were included in this analysis (318 686 [70·8%] participants were female individuals and 131 425 [29·2%] were male individuals). In a multivariate model adjusted for sex, smoking, education, physical activity, height, and diabetes, a substitution of 10% of processed foods with an equal amount of minimally processed foods was associated with reduced risk of overall cancer (hazard ratio 0·96, 95% CI 0·95-0·97), head and neck cancers (0·80, 0·75-0·85), oesophageal squamous cell carcinoma (0·57, 0·51-0·64), colon cancer (0·88, 0·85-0·92), rectal cancer (0·90, 0·85-0·94), hepatocellular carcinoma (0·77, 0·68-0·87), and postmenopausal breast cancer (0·93, 0·90-0·97). The substitution of 10% of ultra-processed foods with 10% of minimally processed foods was associated with a reduced risk of head and neck cancers (0·80, 0·74-0·88), colon cancer (0·93, 0·89-0·97), and hepatocellular carcinoma (0·73, 0·62-0·86). Most of these associations remained significant when models were additionally adjusted for BMI, alcohol and dietary intake, and quality., Interpretation: This study suggests that the replacement of processed and ultra-processed foods and drinks with an equal amount of minimally processed foods might reduce the risk of various cancer types., Funding: Cancer Research UK, l'Institut National du Cancer, and World Cancer Research Fund International., Competing Interests: Declaration of interests We declare no competing interests., (© 2023 World Health Organization; licensee Elsevier. This is an Open Access article published under the CC BY NC ND 3.0 IGO license which permits users to download and share the article for non-commercial purposes, so long as the article is reproduced in the whole without changes, and provided the original source is properly cited. This article shall not be used or reproduced in association with the promotion of commercial products, services, or any entity. There should be no suggestion that WHO endorses any specific organisation, products, or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL.)

Background: Frailty development is partly dependent on multiple factors like low levels of nutrients and high levels of oxidative stress (OS) and inflammation potentially leading to a muscle-catabolic state. Measures of specific biomarker patterns including nutrients, OS and inflammatory biomarkers as well as muscle related biomarkers like 3-methylhistidine (3MH) may improve evaluation of mechanisms and the complex networks leading to frailty., Methods: In 220 multi-morbid patients (≥ 60 years), classified as non-frail (n = 104) and frail (n = 116) according to Fried's frailty criteria, we measured serum concentrations of fat-soluble micronutrients, amino acids (AA), OS, interleukins (IL) 6 and 10, 3MH (biomarker for muscle protein turnover) and serum spectra of fatty acids (FA). We evaluated biomarker patterns by principal component analysis (PCA) and their cross-sectional associations with frailty by multivariate logistic regression analysis., Results: Two biomarker patterns [principal components (PC)] were identified by PCA. PC1 was characterized by high positive factor loadings (FL) of carotenoids, anti-inflammatory FA and vitamin D 3 together with high negative FL of pro-inflammatory FA, IL6 and IL6/IL10, reflecting an inflammation-related pattern. PC2 was characterized by high positive FL of AA together with high negative FL of 3MH-based biomarkers, reflecting a muscle-related pattern. Frail patients had significantly lower factor scores than non-frail patients for both PC1 [median: -0.27 (interquartile range: 1.15) vs. 0.27 (1.23); P = 0.001] and PC2 [median: -0.15 (interquartile range: 1.13) vs. 0.21 (1.38); P = 0.002]. Patients with higher PC1 or PC2 factor scores were less likely to be frail [odds ratio (OR): 0.62, 95% CI: 0.46-0.83, P = 0.001 for PC1; OR: 0.64, 95% CI: 0.48-0.86, P = 0.003 for PC2] compared with patients with lower PC1 or PC2 factor scores. This indicates that increasing levels of anti-inflammatory biomarkers and increasing levels of muscle-anabolic biomarkers are associated with a reduced likelihood (38% and 36%, respectively) for frailty. Significant associations remained after adjusting the regression models for potential confounders., Conclusions: We conclude that two specific patterns reflecting either inflammation-related or muscle-related biomarkers are both significantly associated with frailty among multi-morbid patients and that these specific biomarker patterns are more informative than single biomarker analyses considering frailty identification., (© 2022 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Objectives: We explored the prospective associations between adherence to a priori chosen dietary patterns, including EAT-Lancet (EAT-L) and Mediterranean (tMDS) diet with long-term inflammatory responses in a German population sample., Design and Setting: Prospective cohort study., Participants: A subsample of 636 predominantly healthy participants from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study who were on average 51-years old at baseline., Measurements: Data was collected repeatedly between 1994/1998 - 2013. At baseline (1994/1998) and 6.8-years later (2001/2005), EAT-L and tMDS scores were derived from available food frequency questionnaires. Stable high, stable low, increasing, and decreasing adherence to EAT-L and tMDS were defined as scoring above/below baseline median at baseline and 6.8-years later. Long-term chronic inflammation was assessed based on the average values of repeated measurements of two inflammatory biomarkers - chemerin and high-sensitivity C-reactive protein (hs-CRP) - in plasma samples collected between 2010/2012 and 2013. Multivariable linear regression analysis adjusted for socio-demographic and lifestyle factors at baseline and in 2010/2012 was used to assess the association between diet adherence and long-term hs-CRP and chemerin concentrations., Results: Stable high or increasing adherence to EAT-L diet compared to stable low adherence was associated with slight reduction of long-term chemerin concentrations on the long run (stable high: -4.4%; increasing: -4.0%), not reaching statistical significance. Increasing adherence to tMDS compared to stable low adherence was also associated with a minor reduction in chemerin concentrations (-3.6%). Decreasing adherence to tMDS compared stable high adherence was associated with 2.7% higher chemerin. The associations were even less pronounced when hs-CRP was used as an outcome., Conclusions: Adherence to healthy and sustainable dietary patterns defined using existing definitions for EAT-L and tMDS were associated with minor and not statistically significant reduction in the concentrations of inflammatory biomarkers on the long run. More research is needed to explore whether following these diets may represent a suitable approach for targeted prevention in the general population., Competing Interests: None.

Purpose: Chronic inflammation is thought to initiate or promote differentiated thyroid cancer (DTC) and previous studies have shown that diet can modulate this inflammatory process. We aimed to evaluate the association of several dietary scores reflecting the inflammatory potential of the diet with DTC risk., Methods: Within the EPIC cohort, 450,063 participants were followed during a mean period of 14 years, and 712 newly incident DTC cases were identified. Associations between four dietary inflammatory scores [the dietary inflammatory index (DII ® ) and two energy-adjusted derivatives (the E-DII r and the E-DII d ), and the Inflammatory Score of the Diet (ISD)] and DTC risk were evaluated in the EPIC cohort using multivariable Cox regression models., Results: Positive associations were observed between DTC risk and the DIIs (HR for 1 SD increase in DII: 1.11, 95%CI: 1.01, 1.23, similar results for its derivatives), but not with the ISD (HR for 1 SD increase: 1.04, 95% CI 0.93, 1.16)., Conclusion: Diet-associated inflammation, as estimated by the DII and its derivatives, was weakly positively associated with DTC risk in a European adult population. These results suggesting that diet-associated inflammation acts in the etiology of DTC need to be validated in independent studies., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Purpose: In several studies, exploratory dietary patterns (DP), derived by principal component analysis, were inversely or positively associated with incident type 2 diabetes (T2D). However, findings remained study-specific, inconsistent and rarely replicated. This study aimed to investigate the associations between DPs and T2D in multiple cohorts across the world., Methods: This federated meta-analysis of individual participant data was based on 25 prospective cohort studies from 5 continents including a total of 390,664 participants with a follow-up for T2D (3.8-25.0 years). After data harmonization across cohorts we evaluated 15 previously identified T2D-related DPs for association with incident T2D estimating pooled incidence rate ratios (IRR) and confidence intervals (CI) by Piecewise Poisson regression and random-effects meta-analysis., Results: 29,386 participants developed T2D during follow-up. Five DPs, characterized by higher intake of red meat, processed meat, French fries and refined grains, were associated with higher incidence of T2D. The strongest association was observed for a DP comprising these food groups besides others (IRR pooled per 1 SD = 1.104, 95% CI 1.059-1.151). Although heterogeneity was present (I 2  = 85%), IRR exceeded 1 in 18 of the 20 meta-analyzed studies. Original DPs associated with lower T2D risk were not confirmed. Instead, a healthy DP (HDP1) was associated with higher T2D risk (IRR pooled per 1 SD = 1.057, 95% CI 1.027-1.088)., Conclusion: Our findings from various cohorts revealed positive associations for several DPs, characterized by higher intake of red meat, processed meat, French fries and refined grains, adding to the evidence-base that links DPs to higher T2D risk. However, no inverse DP-T2D associations were confirmed., (© 2022. The Author(s).)

Previously, the attempt to compile German dietary guidelines into a diet score was predominantly not successful with regards to preventing chronic diseases in the EPIC-Potsdam study. Current guidelines were supplemented by the latest evidence from systematic reviews and expert papers published between 2010 and 2020 on the prevention potential of food groups on chronic diseases such as type 2 diabetes, cardiovascular diseases and cancer. A diet score was developed by scoring the food groups according to a recommended low, moderate or high intake. The relative validity and reliability of the diet score, assessed by a food frequency questionnaire, was investigated. The consideration of current evidence resulted in 10 key food groups being preventive of the chronic diseases of interest. They served as components in the diet score and were scored from 0 to 1 point, depending on their recommended intake, resulting in a maximum of 10 points. Both the reliability (r = 0.53) and relative validity (r = 0.43) were deemed sufficient to consider the diet score as a stable construct in future investigations. This new diet score can be a promising tool to investigate dietary intake in etiological research by concentrating on 10 key dietary determinants with evidence-based prevention potential for chronic diseases.

Background: Food biodiversity, encompassing the variety of plants, animals, and other organisms consumed as food and drink, has intrinsic potential to underpin diverse, nutritious diets and improve Earth system resilience. Dietary species richness (DSR), which is recommended as a crosscutting measure of food biodiversity, has been positively associated with the micronutrient adequacy of diets in women and young children in low- and middle-income countries (LMICs). However, the relationships between DSR and major health outcomes have yet to be assessed in any population., Methods and Findings: We examined the associations between DSR and subsequent total and cause-specific mortality among 451,390 adults enrolled in the European Prospective Investigation into Cancer and Nutrition (EPIC) study (1992 to 2014, median follow-up: 17 years), free of cancer, diabetes, heart attack, or stroke at baseline. Usual dietary intakes were assessed at recruitment with country-specific dietary questionnaires (DQs). DSR of an individual's yearly diet was calculated based on the absolute number of unique biological species in each (composite) food and drink. Associations were assessed by fitting multivariable-adjusted Cox proportional hazards regression models. In the EPIC cohort, 2 crops (common wheat and potato) and 2 animal species (cow and pig) accounted for approximately 45% of self-reported total dietary energy intake [median (P10-P90): 68 (40 to 83) species consumed per year]. Overall, higher DSR was inversely associated with all-cause mortality rate. Hazard ratios (HRs) and 95% confidence intervals (CIs) comparing total mortality in the second, third, fourth, and fifth (highest) quintiles (Qs) of DSR to the first (lowest) Q indicate significant inverse associations, after stratification by sex, age, and study center and adjustment for smoking status, educational level, marital status, physical activity, alcohol intake, and total energy intake, Mediterranean diet score, red and processed meat intake, and fiber intake [HR (95% CI): 0.91 (0.88 to 0.94), 0.80 (0.76 to 0.83), 0.69 (0.66 to 0.72), and 0.63 (0.59 to 0.66), respectively; PWald < 0.001 for trend]. Absolute death rates among participants in the highest and lowest fifth of DSR were 65.4 and 69.3 cases/10,000 person-years, respectively. Significant inverse associations were also observed between DSR and deaths due to cancer, heart disease, digestive disease, and respiratory disease. An important study limitation is that our findings were based on an observational cohort using self-reported dietary data obtained through single baseline food frequency questionnaires (FFQs); thus, exposure misclassification and residual confounding cannot be ruled out., Conclusions: In this large Pan-European cohort, higher DSR was inversely associated with total and cause-specific mortality, independent of sociodemographic, lifestyle, and other known dietary risk factors. Our findings support the potential of food (species) biodiversity as a guiding principle of sustainable dietary recommendations and food-based dietary guidelines., Competing Interests: The authors have declared that no competing interests exist.

Background: There is a worldwide shift towards increased consumption of ultra-processed foods (UPF) with concurrent rising prevalence of obesity. We examined the relationship between the consumption of UPF and weight gain and risk of obesity., Methods: This prospective cohort included 348 748 men and women aged 25-70 years. Participants were recruited between 1992 and 2000 from 9 European countries in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Two body weight measures were available, at baseline and after a median follow-up time of 5 years. Foods and drinks were assessed at baseline by dietary questionnaires and classified according to their degree of processing using NOVA classification. Multilevel mixed linear regression was used to estimate the association between UPF consumption and body weight change (kg/5 years). To estimate the relative risk of becoming overweight or obese after 5 years we used Poisson regression stratified according to baseline body mass index (BMI)., Results: After multivariable adjustment, higher UPF consumption (per 1 SD increment) was positively associated with weight gain (0·12 kg/5 years, 95% CI 0·09 to 0·15). Comparing highest vs. lowest quintile of UPF consumption was associated with a 15% greater risk (95% CI 1·11, 1·19) of becoming overweight or obese in normal weight participants, and with a 16% greater risk (95% CI 1·09, 1·23) of becoming obese in participants who were overweight at baseline., Conclusions: These results are supportive of public health campaigns to substitute UPF for less processed alternatives for obesity prevention and weight management., Competing Interests: Conflict of interest None of the authors declared a conflict of interest., (Copyright © 2021. Published by Elsevier Ltd.)

The aim of this study was to assess the ability of the FFQ to describe reliable and valid dietary pattern (DP) scores. In a total of 134 participants of the European Prospective Investigation into Cancer and Nutrition-Potsdam study aged 35-67 years, the FFQ was applied twice (baseline and after 1 year) to assess its reliability. Between November 1995 and March 1997, twelve 24-h dietary recalls (24HDR) as reference instrument were applied to assess the validity of the FFQ. Exploratory DP were derived by principal component analyses. Investigated predefined DP were the Alternative Healthy Eating Index (AHEI) and two Mediterranean diet indices. From dietary data of each FFQ, two exploratory DP were retained, but differed in highly loading food groups, resulting in moderate correlations (r 0·45-0·58). The predefined indices showed higher correlations between the FFQ (r(AHEI) 0·62, r(Mediterranean Diet Pyramid Index (MedPyr)) 0·62 and r(traditional Mediterranean Diet Score (tMDS)) 0·51). From 24HDR dietary data, one exploratory DP retained differed in composition to the first FFQ-based DP, but showed similarities to the second DP, reflected by a good correlation (r 0·70). The predefined DP correlated moderately (r 0·40-0·60). To conclude, long-term analyses on exploratory DP should be interpreted with caution, due to only moderate reliability. The validity differed extensively for the two exploratory DP. The investigated predefined DP showed a better reliability and a moderate validity, comparable to other studies. Within the two Mediterranean diet indices, the MedPyr performed better than the tMDs in this middle-aged, semi-urban German study population.

Background: Trans fatty acids (TFAs) have been hypothesised to influence breast cancer risk. However, relatively few prospective studies have examined this relationship, and well-powered analyses according to hormone receptor-defined molecular subtypes, menopausal status, and body size have rarely been conducted., Methods: In the European Prospective Investigation into Cancer and Nutrition (EPIC), we investigated the associations between dietary intakes of TFAs (industrial trans fatty acids [ITFAs] and ruminant trans fatty acids [RTFAs]) and breast cancer risk among 318,607 women. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models, adjusted for other breast cancer risk factors., Results: After a median follow-up of 8.1 years, 13,241 breast cancer cases occurred. In the multivariable-adjusted model, higher total ITFA intake was associated with elevated breast cancer risk (HR for highest vs lowest quintile, 1.14, 95% CI 1.06-1.23; P trend = 0.001). A similar positive association was found between intake of elaidic acid, the predominant ITFA, and breast cancer risk (HR for highest vs lowest quintile, 1.14, 95% CI 1.06-1.23; P trend = 0.001). Intake of total RTFAs was also associated with higher breast cancer risk (HR for highest vs lowest quintile, 1.09, 95% CI 1.01-1.17; P trend = 0.015). For individual RTFAs, we found positive associations with breast cancer risk for dietary intakes of two strongly correlated fatty acids (Spearman correlation r = 0.77), conjugated linoleic acid (HR for highest vs lowest quintile, 1.11, 95% CI 1.03-1.20; P trend = 0.001) and palmitelaidic acid (HR for highest vs lowest quintile, 1.08, 95% CI 1.01-1.16; P trend = 0.028). Similar associations were found for total ITFAs and RTFAs with breast cancer risk according to menopausal status, body mass index, and breast cancer subtypes., Conclusions: These results support the hypothesis that higher dietary intakes of ITFAs, in particular elaidic acid, are associated with elevated breast cancer risk. Due to the high correlation between conjugated linoleic acid and palmitelaidic acid, we were unable to disentangle the positive associations found for these fatty acids with breast cancer risk. Further mechanistic studies are needed to identify biological pathways that may underlie these associations.

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., (Copyright © American Society for Nutrition 2019.)

Besides a priori approaches, using previous knowledge about food characteristics, exploratory dietary pattern (DP) methods, using data at hand, are commonly applied. This systematic literature review aimed to identify exploratory methods on DP in pan-European studies and to inform the development of the DEterminants of DIet and Physical ACtivity (DEDIPAC) toolbox of methods suitable for use in future European studies. The search was conducted in three databases on prospective studies in healthy, free-living people across the whole life span. To identify validated DP methods, an additional search without regional restrictions was conducted. Studies including at least two European countries were retained. The search resulted in six pan-European studies applying principal component/factor analysis (PC/FA) (n 5) or cluster analysis (n 2). The criteria to retain PC/factors ranged from the application of the eigenvalue>1 criterion, the scree plot and/or the interpretability criterion. Furthermore, seven validation studies were identified: DP, derived by PC/FA (n 6) or reduced rank regression (RRR) (n 1) were compared using dietary information from FFQ (n 6) or dietary history (n 1) as study instrument and dietary records (n 6) or 24-h dietary recalls (n 1) as reference. The correlation coefficients for the derived DP ranged from modest to high. To conclude, PC/FA was predominantly applied using the eigenvalue criterion and scree plot to retain DP, but a better description of the applied criteria is highly recommended to enable a standardised application of the method. Research gaps were identified for the methods cluster analysis and RRR, as well as for validation studies on DP.

Background: The Mediterranean Diet (MedDiet) has been acknowledged as a healthy diet. However, its relation with risk of major chronic diseases in non-Mediterranean countries is inconclusive. The Nordic diet is proposed as an alternative across Northern Europe, although its associations with the risk of chronic diseases remain controversial. We aimed to investigate the association between the Nordic diet and the MedDiet with the risk of chronic disease (type 2 diabetes (T2D), myocardial infarction (MI), stroke, and cancer) in the EPIC-Potsdam cohort., Methods: The EPIC-Potsdam cohort recruited 27,548 participants between 1994 and 1998. After exclusion of prevalent cases, we evaluated baseline adherence to a score reflecting the Nordic diet and two MedDiet scores (tMDS, reflecting the traditional MedDiet score, and the MedPyr score, reflecting the MedDiet Pyramid). Cox regression models were applied to examine the association between the diet scores and the incidence of major chronic diseases., Results: During a follow-up of 10.6 years, 1376 cases of T2D, 312 of MI, 321 of stroke, and 1618 of cancer were identified. The Nordic diet showed a statistically non-significant inverse association with incidence of MI in the overall population and of stroke in men. Adherence to the MedDiet was associated with lower incidence of T2D (HR per 1 SD 0.93, 95% CI 0.88-0.98 for the tMDS score and 0.92, 0.87-0.97 for the MedPyr score). In women, the MedPyr score was also inversely associated with MI. No association was observed for any of the scores with cancer., Conclusions: In the EPIC-Potsdam cohort, the Nordic diet showed a possible beneficial effect on MI in the overall population and for stroke in men, while both scores reflecting the MedDiet conferred lower risk of T2D in the overall population and of MI in women.

Background: Previously, a "purchase" pattern (rich in vegetable oil, manufactured foods, red meat and poultry, fruits, and vegetables) was identified among adults in urban Ghana and was inversely associated with T2D, while a "traditional" pattern (rich in fish, palm oil, plantain, green-leafy vegetables, beans, garden egg, fermented maize products,) increased the odds of T2D. To investigate, if specific fatty acids (FAs), partly reflecting the intakes of certain food groups and cooking methods, might explain the observed diet-disease relationships, serum phospholipid fatty acid profiles were characterized and their relationships with blood lipids that are common risk factors for T2D were analyzed., Methods: The relative proportions of 28 FAs (%) in 653 Ghanaians without T2D were measured by gas chromatography. In a cross-sectional analysis, the associations of FAs with dietary patterns and with serum lipids that are likely involved in T2D development were investigated. The FAs distributions across dietary pattern scores were examined. Standardized beta coefficients (β) were calculated for the associations of dietary pattern scores (per 1 standard deviation (SD) increase) with FAs. Across the tertiles of selected diet-related FAs, adjusted means of serum triglycerides, cholesterol, HDL-cholesterol and LDL-cholesterol were calculated., Results: In this mainly female (76%), middle-aged (mean age: 46.4, SD: 15.3 years) and predominately overweight study population (mean body mass index: 25.8, SD: 5.4 kg/m 2 ), saturated FAs (SFAs) contributed 52% to total serum FAs, n-6 polyunsaturated FAs (PUFAs) 27%, monounsaturated FAs 12%, n-3 PUFAs 9% and trans FAs (TFAs) <1%. The "purchase" pattern was related to lower proportions of n-3 PUFAs (β per 1 score SD: -0.25, p < 0.0001), but higher proportions of linoleic acid (LA) (β per 1 score SD: 0.24, p < 0.0001). The "traditional" pattern was characterized by lower proportions of arachidic acid (β per 1 score SD: -0.10, p = 0.001). LA was inversely associated with triglycerides, but positively with HDL-cholesterol and LDL-cholesterol., Conclusions: In this Ghanaian population, serum FA profiles reflected the intake of key components of dietary patterns, such as fish and vegetable oil. FAs from manufactured foods (SFAs) and deep-fried meals (TFAs) did not contribute to the observed associations between dietary patterns and T2D. Still, LA might partly explain the health-beneficial effect of the "purchase" pattern.

Background: Different methodologic approaches for constructing dietary patterns and differences in their composition limit conclusions on healthful patterns for diabetes prevention. Objective: We summarized evidence from prospective studies that examined associations of dietary patterns with type 2 diabetes by considering different methodologic approaches. Methods: The literature search (MEDLINE and Web of Science) identified prospective studies (cohorts or trials) that associated dietary patterns with diabetes incidence in nondiabetic and apparently healthy participants. We summarized evidence by meta-analyses and distinguished different methodologic approaches. Results: The search resulted in 48 articles comprising 16 cohorts. Adherence to the Mediterranean diet (RR for comparing extreme quantiles: 0.87; 95% CI: 0.82, 0.93), Dietary Approaches to Stop Hypertension (DASH) (RR: 0.81; 95% CI: 0.72, 0.92), and Alternative Healthy Eating Index (AHEI) (RR: 0.79; 95% CI: 0.69, 0.90) was associated with significant risk reductions of incident diabetes. Patterns from exploratory factor and principal component analyses characterized by red and processed meat, refined grains, high-fat dairy, eggs, and fried products ("mainly unhealthy") were positively associated with diabetes (RR: 1.44; 95% CI: 1.27, 1.62), whereas patterns characterized by vegetables, legumes, fruits, poultry, and fish ("mainly healthy") were inversely associated with diabetes (RR: 0.84; 95% CI: 0.77, 0.91). Reduced rank regression (RRR) used diabetes-related biomarkers to identify patterns. These patterns were characterized by high intakes of refined grains, sugar-sweetened soft drinks, and processed meat and were all significantly associated with diabetes risk. Conclusions: Our meta-analysis suggests that diets according to the Mediterranean diet, DASH, and AHEI have a strong potential for preventing diabetes, although they differ in some particular components. Exploratory dietary patterns were grouped based on concordant food groups and were significantly associated with diabetes risk despite single-component foods having limited evidence for an association. Still, they remain population-specific observations. Consistent positive associations with diabetes risk were observed for 3 RRR patterns., Competing Interests: 2: Author disclosures: F Jannasch, J Kröger, and MB Schulze, no conflicts of interest., (© 2017 American Society for Nutrition.)

Reduced rank regression (RRR) is an innovative technique to establish dietary patterns related to biochemical risk factors for type 2 diabetes, but has not been applied in sub-Saharan Africa. In a hospital-based case-control study for type 2 diabetes in Kumasi (diabetes cases, 538; controls, 668) dietary intake was assessed by a specific food frequency questionnaire. After random split of our study population, we derived a dietary pattern in the training set using RRR with adiponectin, HDL-cholesterol and triglycerides as responses and 35 food items as predictors. This pattern score was applied to the validation set, and its association with type 2 diabetes was examined by logistic regression. The dietary pattern was characterized by a high consumption of plantain, cassava, and garden egg, and a low intake of rice, juice, vegetable oil, eggs, chocolate drink, sweets, and red meat; the score correlated positively with serum triglycerides and negatively with adiponectin. The multivariate-adjusted odds ratio of type 2 diabetes for the highest quintile compared to the lowest was 4.43 (95% confidence interval: 1.87-10.50, p for trend < 0.001). The identified dietary pattern increases the odds of type 2 diabetes in urban Ghanaians, which is mainly attributed to increased serum triglycerides.