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Dietary protein intake and all-cause and cause-specific mortality: results from the Rotterdam Study and a meta-analysis of prospective cohort studies.

ABSTRACT: Evidence for associations between long-term protein intake with mortality is not consistent. We aimed to examine associations of dietary protein from different sources with all-cause and cause-specific mortality. We followed 7786 participants from three sub-cohorts of the Rotterdam Study, a population-based cohort in the Netherlands. Dietary data were collected using food-frequency questionnaires at baseline (1989-1993, 2000-2001, 2006-2008). Deaths were followed until 2018. Associations were examined using Cox regression. Additionally, we performed a highest versus lowest meta-analysis and a dose-response meta-analysis to summarize results from the Rotterdam Study and previous prospective cohorts. During a median follow-up of 13.0 years, 3589 deaths were documented in the Rotterdam Study. In this cohort, after multivariable adjustment, higher total protein intake was associated with higher all-cause mortality [e.g. highest versus lowest quartile of total protein intake as percentage of energy (Q4 versus Q1), HR = 1.12 (1.01, 1.25)]; mainly explained by higher animal protein intake and CVD mortality [Q4 versus Q1, CVD mortality: 1.28 (1.03, 1.60)]. The association of animal protein intake and CVD was mainly contributed to by protein from meat and dairy. Total plant protein intake was not associated with all-cause or cause-specific mortality, mainly explained by null associations for protein from grains and potatoes; but higher intake of protein from legumes, nuts, vegetables, and fruits was associated with lower risk of all-cause and cause-specific mortality. Findings for total and animal protein intake were corroborated in a meta-analysis of eleven prospective cohort studies including the Rotterdam Study (total 64,306 deaths among 350,452 participants): higher total protein intake was associated with higher all-cause mortality [pooled RR for highest versus lowest quantile 1.05 (1.01, 1.10)]; and for dose-response per 5 energy percent (E%) increment, 1.02 (1.004, 1.04); again mainly driven by an association between animal protein and CVD mortality [highest versus lowest, 1.09 (1.01, 1.18); per 5 E% increment, 1.05 (1.02, 1.09)]. Furthermore, in the meta-analysis a higher plant protein intake was associated with lower all-cause and CVD mortality [e.g. for all-cause mortality, highest versus lowest, 0.93 (0.87, 0.99); per 5 E% increment, 0.87 (0.78, 0.98), for CVD mortality, highest versus lowest 0.86 (0.73, 1.00)]. Evidence from prospective cohort studies to date suggests that total protein intake is positively associated with all-cause mortality, mainly driven by a harmful association of animal protein with CVD mortality. Plant protein intake is inversely associated with all-cause and CVD mortality. Our findings support current dietary recommendations to increase intake of plant protein in place of animal protein.Clinical trial registry number and website NTR6831, https://www.trialregister.nl/trial/6645.

SUBMITTER: Chen Z

PROVIDER: S-EPMC7250948 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background: The association between α-linolenic acid (ALA) and mortality is inconsistent and has not been summarized systematically. Objective: The purpose was to conduct a meta-analysis that synthesized the results of prospective cohort studies to investigate associations between ALA intake and mortality. Methods: We conducted a comprehensive search on PubMed, Embase, and Web of Science databases on May 1, 2021, for relevant prospective cohort studies which reported associations of ALA (assessed by dietary surveys and/or ALA concentrations in body tissues) with mortality from all-cause, cardiovascular disease (CVD), and other diseases. Multivariable-adjusted relative risks (RRs) were pooled by a random or fixed-effects model. Results: A total of 34 prospective cohort studies, of which 17 reported dietary ALA intake, 14 for ALA biomarkers, and the remaining 3 reported both of intake and biomarkers. The studies included 6,58,634 participants, and deaths were classified into all-cause mortality (56,898), CVD mortality (19,123), and other diseases mortality (19,061). Pooled RRs of ALA intake were 0.93 (95% CI: 0.86, 1.01, I 2 = 71.2%) for all-cause mortality, 0.90 (95% CI: 0.83, 0.98, I 2 = 22.1%) for CVD mortality, and 0.94 (95% CI: 0.83, 1.06, I 2 = 73.3%) for other diseases mortality. The two-stage random-effects dose-response analysis showed a linear relationship between dietary ALA intake and CVD-mortality and each 0.5% energy increment of ALA intake was associated with a 5% lower risk of CVD-mortality (RR: 0.95; 95% CI: 0.90, 1.00). Pooled RRs per SD increment of ALA biomarkers were 0.99 (95% CI: 0.96, 1.01, I 2 = 27%) for all-cause mortality, 1.00 (95% CI: 0.98, 1.03, I 2 = 0%) for CVD mortality and 0.98 (95% CI: 0.95, 1.01, I 2 = 0%) for other diseases mortality. Conclusions: This meta-analysis summarizing the available prospective cohort studies indicated that ALA intake was associated with reduced risk of mortality, especially CVD mortality. Our findings suggest that ALA consumption may be beneficial for death prevention. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO; identifier: CRD42021264532.

Project description:BACKGROUND:Low carbohydrate diets, which restrict carbohydrate in favour of increased protein or fat intake, or both, are a popular weight-loss strategy. However, the long-term effect of carbohydrate restriction on mortality is controversial and could depend on whether dietary carbohydrate is replaced by plant-based or animal-based fat and protein. We aimed to investigate the association between carbohydrate intake and mortality. METHODS:We studied 15?428 adults aged 45-64 years, in four US communities, who completed a dietary questionnaire at enrolment in the Atherosclerosis Risk in Communities (ARIC) study (between 1987 and 1989), and who did not report extreme caloric intake (<600 kcal or >4200 kcal per day for men and <500 kcal or >3600 kcal per day for women). The primary outcome was all-cause mortality. We investigated the association between the percentage of energy from carbohydrate intake and all-cause mortality, accounting for possible non-linear relationships in this cohort. We further examined this association, combining ARIC data with data for carbohydrate intake reported from seven multinational prospective studies in a meta-analysis. Finally, we assessed whether the substitution of animal or plant sources of fat and protein for carbohydrate affected mortality. FINDINGS:During a median follow-up of 25 years there were 6283 deaths in the ARIC cohort, and there were 40?181 deaths across all cohort studies. In the ARIC cohort, after multivariable adjustment, there was a U-shaped association between the percentage of energy consumed from carbohydrate (mean 48·9%, SD 9·4) and mortality: a percentage of 50-55% energy from carbohydrate was associated with the lowest risk of mortality. In the meta-analysis of all cohorts (432?179 participants), both low carbohydrate consumption (<40%) and high carbohydrate consumption (>70%) conferred greater mortality risk than did moderate intake, which was consistent with a U-shaped association (pooled hazard ratio 1·20, 95% CI 1·09-1·32 for low carbohydrate consumption; 1·23, 1·11-1·36 for high carbohydrate consumption). However, results varied by the source of macronutrients: mortality increased when carbohydrates were exchanged for animal-derived fat or protein (1·18, 1·08-1·29) and mortality decreased when the substitutions were plant-based (0·82, 0·78-0·87). INTERPRETATION:Both high and low percentages of carbohydrate diets were associated with increased mortality, with minimal risk observed at 50-55% carbohydrate intake. Low carbohydrate dietary patterns favouring animal-derived protein and fat sources, from sources such as lamb, beef, pork, and chicken, were associated with higher mortality, whereas those that favoured plant-derived protein and fat intake, from sources such as vegetables, nuts, peanut butter, and whole-grain breads, were associated with lower mortality, suggesting that the source of food notably modifies the association between carbohydrate intake and mortality. FUNDING:National Institutes of Health.

Project description:BackgroundCurrent evidence on associations between intakes of linoleic acid (LA), the predominant n-6 (ω-6) fatty acid, and mortality is inconsistent and has not been summarized by a systematic review and meta-analysis.ObjectiveThe aim was to perform a systematic review and meta-analysis of prospective cohort studies to examine associations between LA intake and mortality.MethodsWe conducted a comprehensive search of MEDLINE and EMBASE databases through 31 July 2019 for prospective cohort studies reporting associations of LA (assessed by dietary surveys and/or LA concentrations in adipose tissue or blood compartments) with mortality from all causes, cardiovascular disease (CVD), and cancer. Multivariable-adjusted RRs were pooled using random-effects meta-analysis.ResultsThirty-eight studies reporting 44 prospective cohorts were identified; these included 811,069 participants with dietary intake assessment (170,076 all-cause, 50,786 CVD, and 59,684 cancer deaths) and 65,411 participants with biomarker measurements (9758 all-cause, 6492 CVD, and 1719 cancer deaths). Pooled RRs comparing extreme categories of dietary LA intake (high vs low) were 0.87 (95% CI: 0.81, 0.94; I2 = 67.9%) for total mortality, 0.87 (95% CI: 0.82, 0.92; I2 = 3.7%) for CVD mortality, and 0.89 (95% CI: 0.85, 0.93; I2 = 0%) for cancer mortality. Pooled RRs for each SD increment in LA concentrations in adipose tissue/blood compartments were 0.91 (95% CI: 0.87, 0.95; I2 = 64.1%) for total mortality, 0.89 (95% CI: 0.85, 0.94; I2 = 28.9%) for CVD mortality, and 0.91 (95% CI: 0.84, 0.98; I2 = 26.3%) for cancer mortality. Meta-regressions suggested baseline age and dietary assessment methods as potential sources of heterogeneity for the association between LA and total mortality.ConclusionsIn prospective cohort studies, higher LA intake, assessed by dietary surveys or biomarkers, was associated with a modestly lower risk of mortality from all causes, CVD, and cancer. These data support the potential long-term benefits of PUFA intake in lowering the risk of CVD and premature death.

Project description:ObjectiveThis systematic review and meta-analysis of prospective cohort studies examined the associations between egg and dietary cholesterol intake and the risk of mortality from all causes, including cardiovascular disease (CVD) and cancer.MethodsWe searched PubMed, Scopus, ISI Web of Knowledge, and Google Scholar until April 2021, as well as references to the relevant articles retrieved. Random-effects models were used to calculate summary relative risk (RR) and 95% confidence intervals (CIs) for the highest vs. lowest categories of egg and dietary cholesterol intake. Also, linear and non-linear dose-response analyses were conducted to examine the dose-response relationships.ResultsWe included 55 studies, comprising data from 2,772,486 individuals with 228,425, 71,745, and 67,211 cases of all-cause, CVD, and cancer mortality, respectively. Intake of each additional egg per day was associated with a 7% higher risk of all-cause (1.07, 95% CI: 1.02-1.12, I2 = 84.8%) and a 13% higher risk of cancer mortality (1.13, 95% CI: 1.06-1.20, I2 = 54.2%), but was not associated with CVD mortality (1.00, 95% CI: 0.92-1.09, I2 = 81.5%). Non-linear analyses showed increased risks for egg consumption of more than 1.5 and 0.5 eggs/day, respectively. Each 100 mg/day increment in dietary cholesterol intake was associated with a 6% higher risk of all-cause mortality (1.06, 95% CI: 1.03-1.08, I2 = 34.5%) and a 6% higher risk of cancer mortality (1.06, 95% CI: 1.05-1.07, I2 = 0%), but was not associated with CVD mortality (1.04, 95% CI: 0.99-1.10, I2 = 85.9%). Non-linear analyses demonstrated elevated risks of CVD and cancer mortality for intakes more than 450 and 250 mg/day, respectively.Conclusions and relevanceHigh-dietary intake of eggs and cholesterol was associated with all-cause and cancer mortality. Little evidence for elevated risks was seen for intakes below 0.5 egg/day or 250 mg/day of dietary cholesterol. Our findings should be considered with caution because of small risk estimates and moderate between-study heterogeneity.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=252564, PROSPERO, identifier: CRD42021252564.

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Dietary protein intake and all-cause and cause-specific mortality: results from the Rotterdam Study and a meta-analysis of prospective cohort studies.

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