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KSR Number: KSRA112063

Patterns of red and processed meat consumption and risk for cardiometabolic and cancer outcomes: a systematic review and meta-analysis of cohort studies

Risk of Bias Assessment

Overall summary: Risk of bias unclear

Bottom Line

Evidence from observational studies shows that dietary patterns lower in red and processed meat may result in very small reductions in all-cause and cardiometabolic diseases and mortality and cancer morbidity and mortality. However, the estimated lifetime effects of exposure are very small, the overall certainty of evidence is low or very low, and a causal relationship has not been established. There was a lack of information about other cancer or cardiovascular risk factors and the results of each study. Furthermore, there is some concern regarding the similarity of the pooled studies.

Risk of Bias Assessment

Overall summary Risk of bias unclear

Unclear

It was unclear why the review was restricted to studies of more than 1000 participants. Baseline study characteristics regarding cancer risk were not reported. Some analyses used multivariate methods (factor or principal component analyses) to establish dietary patterns prior to meta-analysis and full details of the methods and results were not reported. Some analyses had high statistical heterogeneity and the pooled results may not be reliable.

A. Did the interpretation of findings address all of the concerns identified in Domains 1 to 4? Probably no
B. Was the relevance of identified studies to the review's research question appropriately considered? Probably yes
C. Did the reviewers avoid emphasizing results on the basis of their statistical significance? Probably yes
Risk of bias in the review Unclear

Details of Review

Number of studies 70
Number of participants > 6000000
Last search date April 2019
Review type Aetiological
Objective To evaluate the association between dietary patterns that are lower versus higher in red and processed meat intake and the risk for cardiometabolic and cancer outcomes.
Population Adults (>18 years of age) with or without cardiometabolic conditions but without cancer or any infectious or chronic non-cardiometabolic conditions.

Studies were excluded if >20% of the sample was pregnant or had a chronic health condition other than cardiometabolic diseases without these conditions being reported separately.
Outcome Major cardiometabolic morbidity and mortality; incidence of mortality associated with gastrointestinal, breast, gynaecologic, and prostate cancer; quality of life; and satisfaction with diet.
Study design Cohort studies with more than 1000 participants.
Reference standard NA
Exposure Consumption of red meat or processed meat.
PP factor Consumption of red meat or processed meat.

Results

Dietary patterns lower in red and processed meat intake are associated with a lower risk of overall mortality (relative risk [RR] 0.87, 95% confidence interval [CI] 0.82 to 0.92, 24 studies; 15 fewer deaths per 1000 people) and cardiovascular mortality (RR 0.86, 95% CI 0.79 to 0.94, 25 studies; 6 fewer death per 1000 people) compared to those with a higher intake. Both estimates were based on very low certainty evidence.

Dietary patterns lower in red and processed meat intake were also associated with lower risks of nonfatal stroke (RR 0.86, 95% CI 0.81 to 0,92, 2 studies; 3 fewer events) and type 2 diabetes (RR 0.76, 95% CI 0.68 to 0.86, 14 studies, 13 fewer events). There was no evidence of an association between meat pattern intake and stroke (fatal and non-fatal), fatal stroke, myocardial infarction, cardiovascular disease (fatal and non-fatal) and nonfatal cardiovascular disease although these results were based on very low or low certainty evidence.

For cancer outcomes, dietary patterns lower in red and processed meat were associated with lower risks of gallbladder cancer (RR 0.36, 95% CI 0.20 to 0.62, 1 study; 1 fewer cancer); any cancer (RR 0.90, 95% CI 0.86 to 0.94, 4 studies; 18 fewer cancers); and deaths from any cancer (RR 0.89, 95% CI 0.83 to 0.96, 18 studies; 12 fewer deaths) or pancreatic cancer (RR 0.44, 95% CI 0.26 to 0.76, 1 study; 2 fewer cancers). There was no evidence of an association between meat pattern intake and incidence of or death from breast, colorectal, endometrial, oesophageal, extrahepatic, liver, ovarian, prostate, stomach or uterine cancers although again all results were based on very low or low certainty evidence.

Full Risk of Bias Assessment

The research objective was clearly stated. The reported inclusion criteria were broadly appropriate, however, the authors did not provide the reasoning for their choice of minimum sample size (n=1000), however, this was considered to be appropriate for the study objective. No language or publication status restrictions were applied.

1.1 Did the review adhere to pre-defined objectives and eligibility criteria? Yes
1.2 Were the eligibility criteria appropriate for the review question? Probably yes
1.3 Were eligibility criteria unambiguous? Yes
1.4 Were all restrictions in eligibility criteria based on study characteristics appropriate (e.g. date, sample size, study quality, outcomes measured)? Probably yes
1.5 Were any restrictions in eligibility criteria based on sources of information appropriate (e.g. publication status or format, language, availability of data)? Yes
Concerns regarding specification of study eligibility criteria Low

MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, CINAHL and ProQuest were searched from inception to July 2018 and update searches were undertaken (MEDLINE only) to April 2019. In addition, trial registries (ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform Search Portal), bibliographies of included articles, and relevant literature reviews were screened for additional articles. The search strategies used for each database were published in full (supplementary material) and appeared adequate. No date or language limitations were applied. Two reviewers independently assessed studies for inclusion and any disagreements were resolved through discussion or consultation with a third reviewer.

2.1 Did the search include an appropriate range of databases/electronic sources for published and unpublished reports? Probably yes
2.2 Were methods additional to database searching used to identify relevant reports? Probably yes
2.3 Were the terms and structure of the search strategy likely to retrieve as many eligible studies as possible? Probably yes
2.4 Were restrictions based on date, publication format, or language appropriate? Yes
2.5 Were efforts made to minimise error in selection of studies? Yes
Concerns regarding methods used to identify and/or select studies Low

Two reviewers independently extracted data from included studies, using a predefined data extraction form, and any disagreements were resolved through discussion or consultation with a third reviewer. The risk of bias of included studies was assessed using a modified version of the Clinical Advances through Research and Information Technology risk of bias tool. Risk of bias was assessed independently by two reviewers and any disagreements were resolved through discussion or consultation with a third reviewer; studies were considered to have high risk of bias if two or more of the seven items were classified as high risk after consensus. The criteria considered are relevant for aetiological studies but do not provide a comprehensive assessment. Some details of the included studies (e.g. participant age at baseline, gender distribution, duration of follow-up) were reported as supplementary material, however, no information was provided about other potential cancer risk factors (e.g. family history, genetic markers; smoking, weight) although adjustment for other risk factors formed part of the risk of bias assessment.

3.1 Were efforts made to minimise error in data collection? Yes
3.2 Were sufficient study characteristics considered for both review authors and readers to be able to interpret the results? Probably no
3.3 Were all relevant study results collected for use in the synthesis? Probably yes
3.4 Was risk of bias (or methodological quality) formally assessed using appropriate criteria? Probably no
3.5 Were efforts made to minimise error in risk of bias assessment? Yes
Concerns regarding methods used to collect data and appraise studies Unclear

If studies evaluated multiple dietary patterns factor or principal components analysis was used to analyse those patterns with highest factor loadings. Otherwise the lowest category of red or processed meat consumption was compared to the highest category of meat consumption. The Hartung-Knapp-Sidik-Jonkman model was used to perform meta-analyses comparing the lowest and highest categories of meat consumption. A DerSimonian and Laird random effects model was used a sensitivity analysis. Statistical heterogeneity was evaluated with the I-squared statistic but there was no discussion of clinical heterogeneity. Subgroup analyses were used to explore risk of bias (low versus high) and methods of defining dietary patterns. Individual study results were not presented.

4.1 Did the synthesis include all studies that it should? Probably yes
4.2 Were all pre-defined analyses reported or departures explained? Probably yes
4.3 Was the synthesis appropriate given the degree of similarity in the research questions, study designs and outcomes across included studies? Probably no
4.4 Was between-study variation minimal or addressed in the synthesis? Probably no
4.5 Were the findings robust, e.g. as demonstrated through funnel plot or sensitivity analyses? Probably yes
4.6 Were biases in primary studies minimal or addressed in the synthesis? Probably yes
Concerns regarding synthesis and findings Unclear

Abstract

Background: Studying dietary patterns may provide insights into the potential effects of red and processed meat on health outcomes. Purpose(s): To evaluate the effect of dietary patterns, including different amounts of red or processed meat, on all-cause mortality, cardiometabolic outcomes, and cancer incidence and mortality. Data Sources: Systematic search of MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, CINAHL, Web of Science, and ProQuest Dissertations & Theses Global from inception to April 2019 with no restrictions on year or language. Study Selection: Teams of 2 reviewers independently screened search results and included prospective cohort studies with 1000 or more participants that reported on the association between dietary patterns and health outcomes. Data Extraction: Two reviewers independently extracted data, assessed risk of bias, and evaluated the certainty of evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria. Data Synthesis: Eligible studies that followed patients for 2 to 34 years revealed low- to very-low-certainty evidence that dietary patterns lower in red and processed meat intake result in very small or possibly small decreases in all-cause mortality, cancer mortality and incidence, cardiovascular mortality, nonfatal coronary heart disease, fatal and nonfatal myocardial infarction, and type 2 diabetes. For all-cause, cancer, and cardiovascular mortality and incidence of some types of cancer, the total sample included more than 400 000 patients; for other outcomes, total samples included 4000 to more than 300 000 patients. Limitation(s): Observational studies are prone to residual confounding, and these studies provide low- or very-low-certainty evidence according to the GRADE criteria. Conclusion(s): Low- or very-low-certainty evidence suggests that dietary patterns with less red and processed meat intake may result in very small reductions in adverse cardiometabolic and cancer outcomes. Primary Funding Source: None (PROSPERO: CRD42017074074)