The Southern European Atlantic diet and all-cause and cause-specific mortality: a European multicohort study.

AIMS: The Southern European Atlantic diet (SEAD) is the traditional dietary pattern of northwestern Spain and northern Portugal, but it may resemble that of central, eastern, and western European countries. The SEAD has been found associated with lower risk of myocardial infarction and mortality in older adults, but it is uncertain whether this association also exists in other European populations and if it is similar as that found in its countries of origin. METHODS AND RESULTS: We conducted a prospective analysis of four cohorts with 35 917 subjects aged 18-96 years: ENRICA (Spain), HAPIEE (Czechia and Poland), and Whitehall II (United Kingdom). The SEAD comprised fresh fish, cod, red meat and pork products, dairy, legumes and vegetables, vegetable soup, potatoes, whole-grain bread, and moderate wine consumption. Associations were adjusted for sociodemographic variables, energy intake, lifestyle, and morbidity. After a median follow-up of 13.6 years (range = 0-15), we recorded 4 973 all-cause, 1 581 cardiovascular, and 1 814 cancer deaths. Higher adherence to the SEAD was associated with lower mortality in the pooled sample. Fully adjusted hazard ratios and 95% confidence interval per 1-standard deviation increment in the SEAD were 0.92 (0.89, 0.95), 0.91 (0.86, 0.96), and 0.94 (0.89, 0.99) for all-cause, cardiovascular, and cancer mortality, respectively. The association of the SEAD with all-cause mortality was not significantly different between countries [Spain = 0.93 (0.88, 0.99), Czechia = 0.94 (0.89,0.99), Poland = 0.89 (0.85, 0.93), United Kingdom = 0.98 (0.89, 1.07); P for interaction = 0.16]. CONCLUSION: The SEAD was associated with lower all-cause, cardiovascular, and cancer mortality in southern, central, eastern, and western European populations. Associations were of similar magnitude as those found for existing healthy dietary patterns.

In this study of 35 917 subjects from southern, central, eastern, and western European countries, the Southern European Atlantic diet (traditional dietary pattern of northwestern Spain and northern Portugal) was associated with lower 13.6-year mortality from any cause, cardiovascular disease, and cancer. The associations of the Southern European Atlantic diet with lower mortality were not significantly different between countries (Spain, Czechia, Poland, and the United Kingdom). Study associations were similar as those found for existing healthy dietary patterns, suggesting that rather different diets could confer comparable benefits on health.

Adherence to the EAT-Lancet reference diet is associated with a reduced risk of incident cancer and all-cause mortality in UK adults.

Food systems have been identified as significant contributors to the global environmental emergency. However, there is no universally agreed-upon definition of what constitutes a planetary healthy, sustainable diet. In our study, we investigated the association between the EAT-Lancet reference diet, a diet within the planetary boundaries, and incident cancer, incident major cardiovascular events, and all-cause mortality. Higher adherence to the EAT-Lancet reference diet was associated with lower incident cancer risk (hazard ratio [HR]continuous: 0.99; 95% confidence interval [CI]: 0.98-0.99]) and lower all-cause mortality (HR continuous: 0.98; 95% CI: 0.98-0.99), while mostly null associations were detected for major cardiovascular event risk (HR continuous: 1.00; 95% CI: 0.98-1.01). Stratified analyses using potentially modifiable risk factors led to similar results. Our findings, in conjunction with the existing literature, support that adoption of the EAT-Lancet reference diet could have a benefit for the prevention of non-communicable diseases.

Associations of intakes of total protein, protein from dairy sources, and dietary calcium with risks of colorectal, breast, and prostate cancer: a prospective analysis in UK Biobank.

BACKGROUND: Evidence concerning intakes of protein or sources of dairy protein and risks of colorectal, breast, and prostate cancers is inconclusive. METHODS: Using a subsample of UK Biobank participants who completed ≥2 (maximum of 5) 24-h dietary assessments, we estimated intakes of total protein, protein from total dairy products, milk, and cheese, and dietary calcium in 114,217 participants. Hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using multivariable-adjusted Cox regression. RESULTS: After a median of 9.4 years of follow-up, 1193 colorectal, 2024 female breast, and 2422 prostate cancer cases were identified. There were inverse associations of total dairy protein, protein from milk, and dietary calcium intakes with colorectal cancer incidence (HRQ4 vs Q1:0.80, 95% CI: 0.67-0.94; 0.79, 0.67-0.94; 0.71, 0.58-0.86, respectively). We also observed positive associations of milk protein and dietary calcium with prostate cancer risk (HRQ4 vs Q1:1.12, 1.00-1.26 and 1.16, 1.01-1.33, respectively). No significant associations were observed between intake of dairy protein and breast cancer risk. When insulin-like growth factor-I concentrations measured at recruitment were added to the multivariable-adjusted models, associations remained largely unchanged. Analyses were also similar when looking at total grams of dairy products, milk, and cheese. CONCLUSION: Further research is needed to understand the mechanisms underlying the relationships of dairy products with cancer risk and the potential roles of dietary protein and calcium.

Vegans, vegetarians, fish-eaters and meat-eaters in the UK show discrepant environmental impacts.

Modelled dietary scenarios often fail to reflect true dietary practice and do not account for variation in the environmental burden of food due to sourcing and production methods. Here we link dietary data from a sample of 55,504 vegans, vegetarians, fish-eaters and meat-eaters with food-level data on greenhouse gas emissions, land use, water use, eutrophication risk and potential biodiversity loss from a review of 570 life-cycle assessments covering more than 38,000 farms in 119 countries. Our results include the variation in food production and sourcing that is observed in the review of life-cycle assessments. All environmental indicators showed a positive association with amounts of animal-based food consumed. Dietary impacts of vegans were 25.1% (95% uncertainty interval, 15.1-37.0%) of high meat-eaters (≥100 g total meat consumed per day) for greenhouse gas emissions, 25.1% (7.1-44.5%) for land use, 46.4% (21.0-81.0%) for water use, 27.0% (19.4-40.4%) for eutrophication and 34.3% (12.0-65.3%) for biodiversity. At least 30% differences were found between low and high meat-eaters for most indicators. Despite substantial variation due to where and how food is produced, the relationship between environmental impact and animal-based food consumption is clear and should prompt the reduction of the latter.

The Southern European Atlantic diet and depression risk: a European multicohort study.

The Southern European Atlantic diet (SEAD) is the traditional dietary pattern of north-western Spain and northern Portugal, but it may resemble that of other European countries. The SEAD has been found associated with lower risk for myocardial infarction and mortality. Since dietary patterns may also influence mental health, we examined the association between the SEAD and depression risk in southern, central, eastern, and western European populations. We conducted a prospective analysis of five cohorts (13,297 participants aged 45-92 years, free of depression at baseline): Seniors-ENRICA-1 and Seniors-ENRICA-2 (Spain), HAPIEE (Czechia and Poland), and Whitehall-II (United Kingdom). The SEAD comprised cod, other fresh fish, red meat and pork products, dairy, legumes and vegetables, vegetable soup, potatoes, whole-grain bread, and moderate wine consumption. Depression at follow-up was defined according to presence of depressive symptoms (based on available scales), use of prescribed antidepressants, inpatient admissions, or self-reported diagnosis. Associations were adjusted for sociodemographic, lifestyle, and dietary variables. During a median follow-up of 3.9 years (interquartile range 3.4-4.9), there were 1437 new depression cases. Higher adherence to the SEAD was associated with lower depression risk in the pooled sample. Individual food groups showed a similar tendency, albeit non-significant. The fully adjusted odds ratio (95% confidence interval) per 1-standard deviation increment in the SEAD was 0.91 (0.86, 0.96). This association was rather consistent across countries [Spain = 0.86 (0.75, 0.99), Czechia = 0.86 (0.75, 0.99), Poland = 0.97 (0.89, 1.06), United Kingdom = 0.85 (0.75, 0.97); p for interaction = 0.24], and was of similar magnitude as that found for existing healthy dietary patterns. In conclusion, the SEAD was associated with lower depression risk across European populations. This may support the development of mood disorder guidelines for Southern European Atlantic regions based on their traditional diet, and for central, eastern, and western European populations based on the SEAD food groups that are culturally rooted in these places.

Dietary intake of total, heme and non-heme iron and the risk of colorectal cancer in a European prospective cohort study.

BACKGROUND: Iron is an essential micronutrient with differing intake patterns and metabolism between men and women. Epidemiologic evidence on the association of dietary iron and its heme and non-heme components with colorectal cancer (CRC) development is inconclusive. METHODS: We examined baseline dietary questionnaire-assessed intakes of total, heme, and non-heme iron and CRC risk in the EPIC cohort. Sex-specific multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were computed using Cox regression. We modelled substitution of a 1 mg/day of heme iron intake with non-heme iron using the leave one-out method. RESULTS: Of 450,105 participants (318,680 women) followed for 14.2 ± 4.0 years, 6162 (3511 women) developed CRC. In men, total iron intake was not associated with CRC risk (highest vs. lowest quintile, HRQ5vs.Q1:0.88; 95%CI:0.73, 1.06). An inverse association was observed for non-heme iron (HRQ5vs.Q1:0.80, 95%CI:0.67, 0.96) whereas heme iron showed a non-significant association (HRQ5vs.Q1:1.10; 95%CI:0.96, 1.27). In women, CRC risk was not associated with intakes of total (HRQ5vs.Q1:1.11, 95%CI:0.94, 1.31), heme (HRQ5vs.Q1:0.95; 95%CI:0.84, 1.07) or non-heme iron (HRQ5vs.Q1:1.03, 95%CI:0.88, 1.20). Substitution of heme with non-heme iron demonstrated lower CRC risk in men (HR:0.94; 95%CI: 0.89, 0.99). CONCLUSIONS: Our findings suggest potential sex-specific CRC risk associations for higher iron consumption that may differ by dietary sources.

Antibody levels following vaccination against SARS-CoV-2: associations with post-vaccination infection and risk factors in two UK longitudinal studies.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody levels can be used to assess humoral immune responses following SARS-CoV-2 infection or vaccination, and may predict risk of future infection. Higher levels of SARS-CoV-2 anti-Spike antibodies are known to be associated with increased protection against future SARS-CoV-2 infection. However, variation in antibody levels and risk factors for lower antibody levels following each round of SARS-CoV-2 vaccination have not been explored across a wide range of socio-demographic, SARS-CoV-2 infection and vaccination, and health factors within population-based cohorts. Methods: Samples were collected from 9361 individuals from TwinsUK and ALSPAC UK population-based longitudinal studies and tested for SARS-CoV-2 antibodies. Cross-sectional sampling was undertaken jointly in April-May 2021 (TwinsUK, N=4256; ALSPAC, N=4622), and in TwinsUK only in November 2021-January 2022 (N=3575). Variation in antibody levels after first, second, and third SARS-CoV-2 vaccination with health, socio-demographic, SARS-CoV-2 infection, and SARS-CoV-2 vaccination variables were analysed. Using multivariable logistic regression models, we tested associations between antibody levels following vaccination and: (1) SARS-CoV-2 infection following vaccination(s); (2) health, socio-demographic, SARS-CoV-2 infection, and SARS-CoV-2 vaccination variables. Results: Within TwinsUK, single-vaccinated individuals with the lowest 20% of anti-Spike antibody levels at initial testing had threefold greater odds of SARS-CoV-2 infection over the next 6-9 months (OR = 2.9, 95% CI: 1.4, 6.0), compared to the top 20%. In TwinsUK and ALSPAC, individuals identified as at increased risk of COVID-19 complication through the UK 'Shielded Patient List' had consistently greater odds (two- to fourfold) of having antibody levels in the lowest 10%. Third vaccination increased absolute antibody levels for almost all individuals, and reduced relative disparities compared with earlier vaccinations. Conclusions: These findings quantify the association between antibody level and risk of subsequent infection, and support a policy of triple vaccination for the generation of protective antibodies. Funding: Antibody testing was funded by UK Health Security Agency. The National Core Studies program is funded by COVID-19 Longitudinal Health and Wellbeing - National Core Study (LHW-NCS) HMT/UKRI/MRC ([MC_PC_20030] and [MC_PC_20059]). Related funding was also provided by the NIHR 606 (CONVALESCENCE grant [COV-LT-0009]). TwinsUK is funded by the Wellcome Trust, Medical Research Council, Versus Arthritis, European Union Horizon 2020, Chronic Disease Research Foundation (CDRF), Zoe Ltd and the National Institute for Health Research (NIHR) Clinical Research Network (CRN) and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust in partnership with King's College London. The UK Medical Research Council and Wellcome (Grant ref: [217065/Z/19/Z]) and the University of Bristol provide core support for ALSPAC.

Vaccination against the virus that causes COVID-19 triggers the body to produce antibodies that help fight future infections. But some people generate more antibodies after vaccination than others. People with lower levels of antibodies are more likely to get COVID-19 in the future. Identifying people with low antibody levels after COVID-19 vaccination is important. It could help decide who receives priority for future vaccination. Previous studies show that people with certain health conditions produce fewer antibodies after one or two doses of a COVID-19 vaccine. For example, people with weakened immune systems. Now that third booster doses are available, it is vital to determine if they increase antibody levels for those most at risk of severe COVID-19. Cheetham et al. show that a third booster dose of a COVID-19 vaccine boosts antibodies to high levels in 90% of individuals, including those at increased risk. In the experiments, Cheetham et al. measured antibodies against the virus that causes COVID-19 in 9,361 individuals participating in two large long-term health studies in the United Kingdom. The experiments found that UK individuals advised to shield from the virus because they were at increased risk of complications had lower levels of antibodies after one or two vaccine doses than individuals without such risk factors. This difference was also seen after a third booster dose, but overall antibody levels had large increases. People who received the Oxford/AstraZeneca vaccine as their first dose also had lower antibody levels after one or two doses than those who received the Pfizer/BioNTech vaccine first. Positively, this difference in antibody levels was no longer seen after a third booster dose. Individuals with lower antibody levels after their first dose were also more likely to have a case of COVID-19 in the following months. Antibody levels were high in most individuals after the third dose. The results may help governments and public health officials identify individuals who may need extra protection after the first two vaccine doses. They also support current policies promoting booster doses of the vaccine and may support prioritizing booster doses for those at the highest risk from COVID-19 in future vaccination campaigns.

Intakes of major food groups in China and UK: results from 100,000 adults in the China Kadoorie biobank and UK biobank.

PURPOSE: Different populations may exhibit differences in dietary intakes, which may result in heterogeneities in diet-disease associations. We compared intakes of major food groups overall, by sex, and by socio-economic status (SES) (defined as both education and income), between participants in the China Kadoorie Biobank (CKB) and the UK Biobank (UKB). METHODS: Data were from ~ 25,000 CKB participants who completed a validated interviewer-administered computer-based questionnaire (2013-2014) and ~ 74,000 UKB participants who completed ≥ 3 web-based 24-h dietary assessments (2009-2012). Intakes of 12 major food groups and five beverages were harmonized and compared between the cohorts overall, by sex and by SES. Multivariable-adjusted linear regression examined the associations between dietary intakes and body mass index (BMI) in each cohort. RESULTS: CKB participants reported consuming more rice, eggs, vegetables, soya products, and less wheat, other staple foods (other than rice and wheat), fish, poultry, all dairy products, fruit, and beverages compared to UKB participants. Red meat intake was similar in both cohorts. Having a higher SES was generally associated with a higher consumption of foods and beverages in CKB, whereas in UKB dietary intakes differed more by education and income, with a positive association observed for meat and income in both UKB and CKB but an inverse association observed for education in UKB. Associations of dietary intakes with BMI varied between the two cohorts. CONCLUSION: The large differences in dietary intakes and their associations with SES and BMI could provide insight into the interpretation of potentially different diet-disease associations between CKB and UKB.

Associations between food group intakes and circulating insulin-like growth factor-I in the UK Biobank: a cross-sectional analysis.

PURPOSE: Circulating insulin-like growth factor-I (IGF-I) concentrations have been positively associated with risk of several common cancers and inversely associated with risk of bone fractures. Intakes of some foods have been associated with increased circulating IGF-I concentrations; however, evidence remains inconclusive. Our aim was to assess cross-sectional associations of food group intakes with circulating IGF-I concentrations in the UK Biobank. METHODS: At recruitment, the UK Biobank participants reported their intake of commonly consumed foods. From these questions, intakes of total vegetables, fresh fruit, red meat, processed meat, poultry, oily fish, non-oily fish, and cheese were estimated. Serum IGF-I concentrations were measured in blood samples collected at recruitment. After exclusions, a total of 438,453 participants were included in this study. Multivariable linear regression was used to assess the associations of food group intakes with circulating IGF-I concentrations. RESULTS: Compared to never consumers, participants who reported consuming oily fish or non-oily fish ≥ 2 times/week had 1.25 nmol/L (95% confidence interval:1.19-1.31) and 1.16 nmol/L (1.08-1.24) higher IGF-I concentrations, respectively. Participants who reported consuming poultry ≥ 2 times/week had 0.87 nmol/L (0.80-0.94) higher IGF-I concentrations than those who reported never consuming poultry. There were no strong associations between other food groups and IGF-I concentrations. CONCLUSIONS: We found positive associations between oily and non-oily fish intake and circulating IGF-I concentrations. A weaker positive association of IGF-I with poultry intake was also observed. Further research is needed to understand the mechanisms which might explain these associations.

Meat consumption and risk of ischemic heart disease: A systematic review and meta-analysis.

There is uncertainty regarding the association between unprocessed red and processed meat consumption and the risk of ischemic heart disease (IHD), and little is known regarding the association with poultry intake. The aim of this systematic review and meta-analysis was to quantitatively assess the associations of unprocessed red, processed meat, and poultry intake and risk of IHD in published prospective studies. We systematically searched CAB Abstract, MEDLINE, EMBASE, Web of Science, bioRxiv and medRxiv, and reference lists of selected studies and previous systematic reviews up to June 4, 2021. All prospective cohort studies that assessed associations between 1(+) meat types and IHD risk (incidence and/or death) were selected. The meta-analysis was conducted using fixed-effects models. Thirteen published articles were included (ntotal = 1,427,989; ncases = 32,630). Higher consumption of unprocessed red meat was associated with a 9% (relative risk (RR) per 50 g/day higher intake, 1.09; 95% confidence intervals (CI), 1.06 to 1.12; nstudies = 12) and processed meat intake with an 18% higher risk of IHD (1.18; 95% CI, 1.12 to 1.25; nstudies = 10). There was no association with poultry intake (nstudies = 10). This study provides substantial evidence that unprocessed red and processed meat, though not poultry, might be risk factors for IHD.

Risk of cancer in regular and low meat-eaters, fish-eaters, and vegetarians: a prospective analysis of UK Biobank participants.

BACKGROUND: Following 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. Our aim was to 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. METHODS: We 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 = 8685) 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. RESULTS: After an average follow-up of 11.4 years, 54,961 incident cancers were identified, including 5882 colorectal, 7537 postmenopausal breast, and 9501 prostate cancers. 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); however, 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 associated with a lower risk of prostate cancer (0.80, 0.65-0.99 and 0.69, 0.54-0.89, respectively). CONCLUSION: 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 due to other factors such as residual confounding or differences in cancer detection.

Higher Meat Intake Is Associated with Higher Inflammatory Markers, Mostly Due to Adiposity: Results from UK Biobank.

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.

Circulating insulin-like growth factor-I and risk of 25 common conditions: outcome-wide analyses in the UK Biobank study.

While 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. Study 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. After correction for multiple testing (P < 0.002), IGF-I was positively associated with carpal tunnel syndrome (HR per 5 nmol/l higher concentration = 1.12, 95% CI 1.08-1.16), and inversely associated with varicose veins (0.90, 0.85-0.95), cataracts (0.97, 0.95-0.99), diabetes (0.92, 0.90-0.95), and iron deficiency anaemia (0.90, 0.86-0.93). The associations for cataracts and diabetes attenuated when restricted to cases diagnosed after five or more years of follow-up, suggesting that these associations were likely affected by reverse causality. Higher IGF-I concentration might be associated with the risk for several conditions, but genetic studies are needed to clarify which associations may be causal.

Co-benefits from sustainable dietary shifts for population and environmental health: an assessment from a large European cohort study.

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 all-cause 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. FUNDING: European Commission (DG-SANCO), the International Agency for Research on Cancer (IARC), MRC Early Career Fellowship (MR/M501669/1).

Associations of circulating insulin-like growth factor-I with intake of dietary proteins and other macronutrients.

BACKGROUND & AIMS: 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. 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-h 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 g/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 <1 g/day: -1.36 nmol/L (-1.00, -1.71)). 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 intake but no association with cheese protein. The positive association of fibre and starch from wholegrains with IGF-I warrants further investigation.

Association between change in cardiovascular risk scores and future cardiovascular disease: analyses of data from the Whitehall II longitudinal, prospective cohort study.

BACKGROUND: Evaluation of cardiovascular disease risk in primary care, which is recommended every 5 years in middle-aged and older adults (typical age range 40-75 years), is based on risk scores, such as the European Society of Cardiology Systematic Coronary Risk Evaluation (SCORE) and American College of Cardiology/American Heart Association Atherosclerotic Cardiovascular Disease (ASCVD) algorithms. This evaluation currently uses only the most recent risk factor assessment. We aimed to examine whether 5-year changes in SCORE and ASCVD risk scores are associated with future cardiovascular disease risk. METHODS: We analysed data from the Whitehall II longitudinal, prospective cohort study for individuals with no history of stroke, myocardial infarction, coronary artery bypass graft, percutaneous coronary intervention, definite angina, heart failure, or peripheral artery disease. Participants underwent clinical examinations in 5-year intervals between Aug 7, 1991, and Dec 6, 2016, and were followed up for incident cardiovascular disease until Oct 2, 2019. Levels of, and 5-year changes in, cardiovascular disease risk were assessed using the SCORE and ASCVD risk scores and were analysed as predictors of cardiovascular disease. Harrell's C index, continuous net reclassification improvement, the Akaike information criterion, and calibration analysis were used to assess whether incorporating change in risk scores into a model including only a single risk score assessment improved the predictive performance. We assessed the levels of, and 5-year changes in, SCORE and ASCVD risk scores as predictors of cardiovascular disease and disease-free life-years using Cox proportional hazards and flexible parametric survival models. FINDINGS: 7574 participants (5233 [69·1%] men, 2341 [30·9%] women) aged 40-75 years were included in analyses of risk score change between April 24, 1997, and Oct 2, 2019. During a mean follow-up of 18·7 years (SD 5·5), 1441 (19·0%; 1042 [72·3%] men and 399 [27·7%] women) participants developed cardiovascular disease. Adding 5-year change in risk score to a model that included only a single risk score assessment improved model performance according to Harrell's C index (from 0·685 to 0·690, change 0·004 [95% CI 0·000 to 0·008] for SCORE; from 0·699 to 0·700, change 0·001 [0·000 to 0·003] for ASCVD), the Akaike information criterion (from 17 255 to 17 200, change -57 [95% CI -97 to -13] for SCORE; from 14 739 to 14 729, change -10 [-28 to 7] for ASCVD), and the continuous net reclassification index (0·353 [95% CI 0·234 to 0·447] for SCORE; 0·232 [0·030 to 0·344] for ASCVD). Both favourable and unfavourable changes in SCORE and ASCVD were associated with cardiovascular disease risk and disease-free life-years. The associations were seen in both sexes and all age groups up to the age of 75 years. At the age of 45 years, each 2-unit improvement in risk scores was associated with an additional 1·3 life-years (95% CI 0·4 to 2·2) free of cardiovascular disease for SCORE and an additional 0·9 life-years (95% CI 0·5 to 1·3) for ASCVD. At age 65 years, this same improvement was associated with an additional 0·4 life-years (95% CI 0·0 to 0·7) free of cardiovascular disease for SCORE and 0·3 life-years (95% CI 0·1 to 0·5) for ASCVD. These models were developed into an interactive calculator, which enables estimation of the number of cardiovascular disease-free life-years for an individual as a function of two risk score measurements. INTERPRETATION: Changes in the SCORE and ASCVD risk scores over time inform cardiovascular disease risk prediction beyond a single risk score assessment. Repeat data might allow more accurate cardiovascular risk stratification and strengthen the evidence base for decisions on preventive interventions. FUNDING: UK Medical Research Council, British Heart Foundation, Wellcome Trust, and US National Institute on Aging.

Prospective analyses of testosterone and sex hormone-binding globulin with the risk of 19 types of cancer in men and postmenopausal women in UK Biobank.

We investigated the associations of estimated free and total circulating testosterone and sex hormone-binding globulin (SHBG) with cancer risk in men and postmenopausal women, using a pan-cancer approach, including 19 cancers in UK Biobank. Risk was estimated using multivariable-adjusted Cox regression in up to 182 608 men and 122 112 postmenopausal women who were cancer-free at baseline. Participants diagnosed with cancer within 2 years of baseline were excluded. Hazard ratios (HRs) and confidence intervals (CIs) were corrected for regression dilution bias using repeat measurements. We accounted for multiple testing using the false discovery rate. In men, higher free testosterone was associated with higher risks of melanoma and prostate cancer (HR per 50 pmol/L increase = 1.35, 95% CI 1.14-1.61 and 1.10, 1.04-1.18, respectively). Higher total testosterone was associated with an elevated risk of liver cancer (HR per 5 nmol/L = 2.45, 1.56-3.84), and higher SHBG was associated with a higher risk of liver cancer (HR per 10 nmol/L = 1.56, 1.31-1.87) and a lower risk of prostate cancer (0.93, 0.91-0.96); the associations with liver cancer were partially attenuated after excluding men diagnosed within 4.7 years from baseline. In postmenopausal women, free and total testosterone and SHBG were associated with risks of endometrial (HR per 10 pmol/L = 1.59, 1.32-1.90; HR per 0.5 nmol/L = 1.34, 1.18-1.52 and HR per 25 nmol/L = 0.78, 0.67-0.91, respectively) and breast cancer (1.32, 1.22-1.43; 1.24, 1.17-1.31 and 0.88, 0.83-0.94, respectively). We report a novel association of free testosterone with malignant melanoma in men, and confirm known associations between testosterone and risks for prostate, breast and endometrial cancers. The association with liver cancer in men may be attributable to reverse causation.

Meat consumption and risk of 25 common conditions: outcome-wide analyses in 475,000 men and women in the UK Biobank study.

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.