AbstractObjectiveTo examine the associations of vegetarianism with risks of ischaemic heart disease and stroke.DesignProspective cohort study.SettingThe EPIC-Oxford study, a cohort in the United ...Kingdom with a large proportion of non-meat eaters, recruited across the country between 1993 and 2001.Participants48 188 participants with no history of ischaemic heart disease, stroke, or angina (or cardiovascular disease) were classified into three distinct diet groups: meat eaters (participants who consumed meat, regardless of whether they consumed fish, dairy, or eggs; n=24 428), fish eaters (consumed fish but no meat; n=7506), and vegetarians including vegans (n=16 254), based on dietary information collected at baseline, and subsequently around 2010 (n=28 364).Main outcome measuresIncident cases of ischaemic heart disease and stroke (including ischaemic and haemorrhagic types) identified through record linkage until 2016.ResultsOver 18.1 years of follow-up, 2820 cases of ischaemic heart disease and 1072 cases of total stroke (519 ischaemic stroke and 300 haemorrhagic stroke) were recorded. After adjusting for sociodemographic and lifestyle confounders, fish eaters and vegetarians had 13% (hazard ratio 0.87, 95% confidence interval 0.77 to 0.99) and 22% (0.78, 0.70 to 0.87) lower rates of ischaemic heart disease than meat eaters, respectively (P<0.001 for heterogeneity). This difference was equivalent to 10 fewer cases of ischaemic heart disease (95% confidence interval 6.7 to 13.1 fewer) in vegetarians than in meat eaters per 1000 population over 10 years. The associations for ischaemic heart disease were partly attenuated after adjustment for self reported high blood cholesterol, high blood pressure, diabetes, and body mass index (hazard ratio 0.90, 95% confidence interval 0.81 to 1.00 in vegetarians with all adjustments). By contrast, vegetarians had 20% higher rates of total stroke (hazard ratio 1.20, 95% confidence interval 1.02 to 1.40) than meat eaters, equivalent to three more cases of total stroke (95% confidence interval 0.8 to 5.4 more) per 1000 population over 10 years, mostly due to a higher rate of haemorrhagic stroke. The associations for stroke did not attenuate after further adjustment of disease risk factors.ConclusionsIn this prospective cohort in the UK, fish eaters and vegetarians had lower rates of ischaemic heart disease than meat eaters, although vegetarians had higher rates of haemorrhagic and total stroke.
Numerous epidemiological studies have investigated the role of blood lipids in prostate cancer (PCa) risk, though findings remain inconclusive to date. The ongoing research has mainly involved ...observational studies, which are often prone to confounding. This study aimed to identify the relationship between genetically predicted blood lipid concentrations and PCa.
Data for low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides (TG), apolipoprotein A (apoA) and B (apoB), lipoprotein A (Lp(a)), and PCa were acquired from genome-wide association studies in UK Biobank and the PRACTICAL consortium, respectively. We used a two-sample summary-level Mendelian randomisation (MR) approach with both univariable and multivariable (MVMR) models and utilised a variety of robust methods and sensitivity analyses to assess the possibility of MR assumptions violation. No association was observed between genetically predicted concentrations of HDL, TG, apoA and apoB, and PCa risk. Genetically predicted LDL concentration was positively associated with total PCa in the univariable analysis, but adjustment for HDL, TG, and Lp(a) led to a null association. Genetically predicted concentration of Lp(a) was associated with higher total PCa risk in the univariable (ORweighted median per standard deviation (SD) = 1.091; 95% CI 1.028 to 1.157; P = 0.004) and MVMR analyses after adjustment for the other lipid traits (ORIVW per SD = 1.068; 95% CI 1.005 to 1.134; P = 0.034). Genetically predicted Lp(a) was also associated with advanced (MVMR ORIVW per SD = 1.078; 95% CI 0.999 to 1.163; P = 0.055) and early age onset PCa (MVMR ORIVW per SD = 1.150; 95% CI 1.015,1.303; P = 0.028). Although multiple estimation methods were utilised to minimise the effect of pleiotropy, the presence of any unmeasured pleiotropy cannot be excluded and may limit our findings.
We observed that genetically predicted Lp(a) concentrations were associated with an increased PCa risk. Future studies are required to understand the underlying biological pathways of this finding, as it may inform PCa prevention through Lp(a)-lowering strategies.
It has been proposed that night shift work could increase breast cancer incidence. A 2007 World Health Organization review concluded, mainly from animal evidence, that shift work involving circadian ...disruption is probably carcinogenic to humans. We therefore aimed to generate prospective epidemiological evidence on night shift work and breast cancer incidence.
Overall, 522 246 Million Women Study, 22 559 EPIC-Oxford, and 251 045 UK Biobank participants answered questions on shift work and were followed for incident cancer. Cox regression yielded multivariable-adjusted breast cancer incidence rate ratios (RRs) and 95% confidence intervals (CIs) for night shift work vs no night shift work, and likelihood ratio tests for interaction were used to assess heterogeneity. Our meta-analyses combined these and relative risks from the seven previously published prospective studies (1.4 million women in total), using inverse-variance weighted averages of the study-specific log RRs.
In the Million Women Study, EPIC-Oxford, and UK Biobank, respectively, 673, 28, and 67 women who reported night shift work developed breast cancer, and the RRs for any vs no night shift work were 1.00 (95% CI = 0.92 to 1.08), 1.07 (95% CI = 0.71 to 1.62), and 0.78 (95% CI = 0.61 to 1.00). In the Million Women Study, the RR for 20 or more years of night shift work was 1.00 (95% CI = 0.81 to 1.23), with no statistically significant heterogeneity by sleep patterns or breast cancer risk factors. Our meta-analysis of all 10 prospective studies included 4660 breast cancers in women reporting night shift work; compared with other women, the combined relative risks were 0.99 (95% CI = 0.95 to 1.03) for any night shift work, 1.01 (95% CI = 0.93 to 1.10) for 20 or more years of night shift work, and 1.00 (95% CI = 0.87 to 1.14) for 30 or more years.
The totality of the prospective evidence shows that night shift work, including long-term shift work, has little or no effect on breast cancer incidence.
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).
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.
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).
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.
We aimed to investigate the causal effect of circulating uric acid concentrations on type 2 diabetes risk. A Mendelian randomization study was performed using a genetic score with 24 uric ...acid-associated loci. We used data of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study, comprising 24,265 individuals of European ancestry from eight European countries. During a mean (SD) follow-up of 10 (4) years, 10,576 verified incident case subjects with type 2 diabetes were ascertained. Higher uric acid was associated with a higher diabetes risk after adjustment for confounders, with a hazard ratio (HR) of 1.20 (95% CI 1.11, 1.30) per 59.48 µmol/L (1 mg/dL) uric acid. The genetic score raised uric acid by 17 µmol/L (95% CI 15, 18) per SD increase and explained 4% of uric acid variation. By using the genetic score to estimate the unconfounded effect, we found that a 59.48 µmol/L higher uric acid concentration did not have a causal effect on diabetes (HR 1.01 95% CI 0.87, 1.16). Including data from the Diabetes Genetics Replication And Meta-analysis (DIAGRAM) consortium, increasing our dataset to 41,508 case subjects with diabetes, the summary odds ratio estimate was 0.99 (95% CI 0.92, 1.06). In conclusion, our study does not support a causal effect of circulating uric acid on diabetes risk. Uric acid-lowering therapies may therefore not be beneficial in reducing diabetes risk.
There is limited prospective evidence on possible differences in fracture risks between vegetarians, vegans, and non-vegetarians. We aimed to study this in a prospective cohort with a large ...proportion of non-meat eaters.
In EPIC-Oxford, dietary information was collected at baseline (1993-2001) and at follow-up (≈ 2010). Participants were categorised into four diet groups at both time points (with 29,380 meat eaters, 8037 fish eaters, 15,499 vegetarians, and 1982 vegans at baseline in analyses of total fractures). Outcomes were identified through linkage to hospital records or death certificates until mid-2016. Using multivariable Cox regression, we estimated the risks of total (n = 3941) and site-specific fractures (arm, n = 566; wrist, n = 889; hip, n = 945; leg, n = 366; ankle, n = 520; other main sites, i.e. clavicle, rib, and vertebra, n = 467) by diet group over an average of 17.6 years of follow-up.
Compared with meat eaters and after adjustment for socio-economic factors, lifestyle confounders, and body mass index (BMI), the risks of hip fracture were higher in fish eaters (hazard ratio 1.26; 95% CI 1.02-1.54), vegetarians (1.25; 1.04-1.50), and vegans (2.31; 1.66-3.22), equivalent to rate differences of 2.9 (0.6-5.7), 2.9 (0.9-5.2), and 14.9 (7.9-24.5) more cases for every 1000 people over 10 years, respectively. The vegans also had higher risks of total (1.43; 1.20-1.70), leg (2.05; 1.23-3.41), and other main site fractures (1.59; 1.02-2.50) than meat eaters. Overall, the significant associations appeared to be stronger without adjustment for BMI and were slightly attenuated but remained significant with additional adjustment for dietary calcium and/or total protein. No significant differences were observed in risks of wrist or ankle fractures by diet group with or without BMI adjustment, nor for arm fractures after BMI adjustment.
Non-meat eaters, especially vegans, had higher risks of either total or some site-specific fractures, particularly hip fractures. This is the first prospective study of diet group with both total and multiple specific fracture sites in vegetarians and vegans, and the findings suggest that bone health in vegans requires further research.
Vegetarians and others who do not eat meat have been observed to have lower incidence rates than meat eaters of some chronic diseases, but it is unclear whether this translates into lower mortality.
...The purpose of this study was to describe mortality in vegetarians and comparable nonvegetarians in a large United Kingdom cohort.
The study involved a pooled analysis of data from 2 prospective studies that included 60,310 persons living in the United Kingdom, comprising 18,431 regular meat eaters (who ate meat ≥5 times/wk on average), 13,039 low (less-frequent) meat eaters, 8516 fish eaters (who ate fish but not meat), and 20,324 vegetarians (including 2228 vegans who did not eat any animal foods). Mortality by diet group for each of 18 common causes of death was estimated with the use of Cox proportional hazards models.
There were 5294 deaths before age 90 in >1 million y of follow-up. There was no significant difference in overall (all-cause) mortality between the diet groups: HRs in low meat eaters, fish eaters, and vegetarians compared with regular meat eaters were 0.93 (95% CI: 0.86, 1.00), 0.96 (95% CI: 0.86, 1.06), and 1.02 (95% CI: 0.94, 1.10), respectively; P-heterogeneity of risks = 0.082. There were significant differences in risk compared with regular meat eaters for deaths from circulatory disease higher in fish eaters (HR: 1.22; 95% CI: 1.02, 1.46); malignant cancer lower in fish eaters (HR: 0.82; 95% CI: 0.70, 0.97), including pancreatic cancer lower in low meat eaters and vegetarians (HR: 0.55; 95% CI: 0.36, 0.86 and HR: 0.48; 95% CI: 0.28, 0.82, respectively) and cancers of the lymphatic/hematopoietic tissue lower in vegetarians (HR: 0.50; 95% CI: 0.32, 0.79); respiratory disease lower in low meat eaters (HR: 0.70; 95% CI: 0.53, 0.92); and all other causes lower in low meat eaters (HR: 0.74; 95% CI: 0.56, 0.99). Further adjustment for body mass index left these associations largely unchanged.
United Kingdom-based vegetarians and comparable nonvegetarians have similar all-cause mortality. Differences found for specific causes of death merit further investigation.
The incidence of acute myeloid leukaemia (AML) increases with age and mortality exceeds 90% when diagnosed after age 65. Most cases arise without any detectable early symptoms and patients usually ...present with the acute complications of bone marrow failure
. The onset of such de novo AML cases is typically preceded by the accumulation of somatic mutations in preleukaemic haematopoietic stem and progenitor cells (HSPCs) that undergo clonal expansion
. However, recurrent AML mutations also accumulate in HSPCs during ageing of healthy individuals who do not develop AML, a phenomenon referred to as age-related clonal haematopoiesis (ARCH)
. Here we use deep sequencing to analyse genes that are recurrently mutated in AML to distinguish between individuals who have a high risk of developing AML and those with benign ARCH. We analysed peripheral blood cells from 95 individuals that were obtained on average 6.3 years before AML diagnosis (pre-AML group), together with 414 unselected age- and gender-matched individuals (control group). Pre-AML cases were distinct from controls and had more mutations per sample, higher variant allele frequencies, indicating greater clonal expansion, and showed enrichment of mutations in specific genes. Genetic parameters were used to derive a model that accurately predicted AML-free survival; this model was validated in an independent cohort of 29 pre-AML cases and 262 controls. Because AML is rare, we also developed an AML predictive model using a large electronic health record database that identified individuals at greater risk. Collectively our findings provide proof-of-concept that it is possible to discriminate ARCH from pre-AML many years before malignant transformation. This could in future enable earlier detection and monitoring, and may help to inform intervention.
Human metabolism is influenced by dietary factors and lifestyle, environmental, and genetic factors; thus, men who exclude some or all animal products from their diet might have different metabolic ...profiles than meat eaters.
We aimed to investigate differences in concentrations of 118 circulating metabolites, including acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexose, and sphingolipids related to lipid, protein, and carbohydrate metabolism between male meat eaters, fish eaters, vegetarians, and vegans from the Oxford arm of the European Prospective Investigation into Cancer and Nutrition.
In this cross-sectional study, concentrations of metabolites were measured by mass spectrometry in plasma from 379 men categorized according to their diet group. Differences in mean metabolite concentrations across diet groups were tested by using ANOVA, and a false discovery rate-controlling procedure was used to account for multiple testing. Principal component analysis was used to investigate patterns in metabolic profiles.
Concentrations of 79% of metabolites differed significantly by diet group. In the vast majority of these cases, vegans had the lowest concentration, whereas meat eaters most often had the highest concentrations of the acylcarnitines, glycerophospholipids, and sphingolipids, and fish eaters or vegetarians most often had the highest concentrations of the amino acids and a biogenic amine. A clear separation between patterns in the metabolic profiles of the 4 diet groups was seen, with vegans being noticeably different from the other groups because of lower concentrations of some glycerophospholipids and sphingolipids.
Metabolic profiles in plasma could effectively differentiate between men from different habitual diet groups, especially vegan men compared with men who consume animal products. The difference in metabolic profiles was mainly explained by the lower concentrations of glycerophospholipids and sphingolipids in vegans.
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