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KSR Number: KSRA112065

Red and processed meat consumption and risk for all-cause mortality and cardiometabolic 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 a reduction of three servings per week of processed or unprocessed red meat may reduce all-cause mortality and cardiometabolic 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 and cardiovascular risk factors and the results of each study. In addition, no justification was provided for the choice of analysis method and 44% of the studies were not analysed.

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. Different meta-analysis methods were used but the results and GRADE assessment were based on the dose-response analysis as this was considered to be the most reliable. However, no justification was provided and 44% of the studies were excluded from this analysis. 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 55
Number of participants >4000000
Last search date April 2019
Review type Aetiological
Objective To evaluate the association between red and processed meat consumption and all-cause mortality, cardiometabolic outcomes, quality of life, and satisfaction with diet among adults.
Population Adults (>18 years of age).
Studies were excluded if >20% of the sample was younger than 18 years, had a non-cardiometabolic disease (such as cancer), or was pregnant at baseline.
Outcome All-cause mortality, cardiovascular mortality (or fatal coronary heart disease or fatal myocardial infarction [MI]), cardiovascular disease (or coronary heart disease), stroke, MI, type 2 diabetes, anemia, 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

Reduction of the intake of both, unprocessed or processed, red meat by three servings per week is associated with a lower risk for cardiometabolic outcomes. Based on guidance by the U.S. Department of Agriculture and the United Kingdom Food Agency, servings were defined as 120 g for unprocessed red meat, 50 g for processed meat, and 100 g for mixed unprocessed red and processed meat.

Unprocessed red meat intake, reduction of three servings per week:
All-cause mortality (relative risk (RR) 0.93, 95% confidence interval (CI) 0.87 to 1.00, 8 studies, n=893,436, follow-up 9 to 28 years, risk difference (RD) per 1000 persons -8, 95% CI -15 to 0, very low certainty of evidence).
Cardiovascular (CV) mortality (RR 0.90, 95% CI 0.88 to 0.91, 7 studies, n=874,896, follow-up 9 to 28 years, RD per 1000 persons -4, 95% CI -5 to -4, very low certainty of evidence).
CV disease (RR 0.95, 95% CI 0.85 to 1.06, 3 studies, n=191,803, follow-up 8 to 26 years, RD per 1000 persons -3, 95% CI -11 to 5, very low certainty of evidence).
Fatal and non-fatal stroke (RR 0.94, 95% CI 0.90 to 0.98, 6 studies, n=254,742, follow-up 12 to 26 years, RD per 1000 persons -1, 95% CI -2 to 0, low certainty of evidence).
Fatal stroke (RR 0.94, 95% CI 0.89 to 0.99, 3 studies, n=671,259, median follow-up 5.5 to 15.6 years, RD per 1000 persons not reported, very low certainty of evidence).
Fatal and non-fatal myocardial infarction (MI) (RR 0.93, 95% CI 0.87 to 0.99, 1 study, n=55,171, median follow-up 13.6 years, RD per 1000 persons -3, 95% CI -5 to 0, very low certainty of evidence).
Type 2 diabetes (RR 0.90, 95% CI 0.88 to 0.92, 6 studies, n=293,869, follow-up 5 to 28 years, RD per 1000 persons -6, 95% CI -7 to -4, low certainty of evidence).

Processed red meat intake, reduction of three servings per week:
- all-cause mortality (RR 0.92, 95% CI 0.87 to 0.96, 8 studies, n=1,241,900, follow-up 9 to 28 years, RD per 1000 persons -9, 95% CI -15 to -5, low certainty of evidence)
- CV mortality (RR 0.90, 95% CI 0.84 to 0.97, 7 studies, n=1,240,634, follow-up 9 to 28 years, RD per 1000 persons -4, 95% CI -7 to -1, very low certainty of evidence)
- CV disease (RR 0.97, 95% CI 0.87 to 1.09, 3 studies, n=200,421, follow-up 8 to 26 years, RD per 1000 persons -2, 95% CI -10 to 7, low certainty of evidence)
- fatal and non-fatal stroke (RR 0.94, 95% CI 0.90 to 0.98, 6 studies, n=254,742, follow-up 12 to 26 years, RD per 1000 persons -1, 95% CI -2 to 0, low certainty of evidence)
- fatal stroke (RR 0.95, 95% CI 0.92 to 0.98, 2 studies, n=571,378, follow-up 15 to 16 years, RD per 1000 persons not reported, very low certainty of evidence)
- fatal and non-fatal MI (RR 0.94, 95% CI 0.91 to 0.98, 1 study, n=55,171, median follow-up 13.6 years, RD per 1000 persons -2, 95% CI -3 to -1, very low certainty of evidence)
- type 2 diabetes (RR 0.78, 95% CI 0.72 to 0.84, 14 studies, n=669,530, follow-up 5 to 28 years, RD per 1000 persons -12, 95% CI -16 to -9, very low certainty of evidence)

The systematic review did not identify studies reporting on non-fatal stroke, fatal MI, quality of life, or satisfaction with diet.

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. 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 yes
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

All studies appear to have been included in the synthesis. Dose-response meta-analysis was used to calculate pooled relative risks for the association of a reduction in 3 servings per week with outcomes. If relevant data were not available then the quantity of meat intake and numbers of person-years were estimated. If analyses included 5 or more studies then the non-linear association between meat intake and cancer risk was modelled using restricted cubic splines. Random effects meta-analysis was also used to compare the lowest and highest categories of meat intake. Statistical heterogeneity was measured using the I-squared statistic but clinical heterogeneity was not discussed. Meta-regression was used to investigate the impact of risk of bias on the summary estimates. Publication bias was evaluated using the Egger test. The results of the dose-response analyses were given priority but this decision was not justified. 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

Dietary guidelines generally recommend limiting intake of red and processed meat. However, the quality of evidence implicating red and processed meat in adverse health outcomes remains unclear.To evaluate the association between red and processed meat consumption and all-cause mortality, cardiometabolic outcomes, quality of life, and satisfaction with diet among adults.EMBASE (Elsevier), Cochrane Central Register of Controlled Trials (Wiley), Web of Science (Clarivate Analytics), CINAHL (EBSCO), and ProQuest from inception until July 2018 and MEDLINE from inception until April 2019, without language restrictions, as well as bibliographies of relevant articles.Cohort studies with at least 1000 participants that reported an association between unprocessed red or processed meat intake and outcomes of interest.Teams of 2 reviewers independently extracted data and assessed risk of bias. One investigator assessed certainty of evidence, and the senior investigator confirmed the assessments.Of 61 articles reporting on 55 cohorts with more than 4 million participants, none addressed quality of life or satisfaction with diet. Low-certainty evidence was found that a reduction in unprocessed red meat intake of 3 servings per week is associated with a very small reduction in risk for cardiovascular mortality, stroke, myocardial infarction (MI), and type 2 diabetes. Likewise, low-certainty evidence was found that a reduction in processed meat intake of 3 servings per week is associated with a very small decrease in risk for all-cause mortality, cardiovascular mortality, stroke, MI, and type 2 diabetes.Inadequate adjustment for known confounders, residual confounding due to observational design, and recall bias associated with dietary measurement.The magnitude of association between red and processed meat consumption and all-cause mortality and adverse cardiometabolic outcomes is very small, and the evidence is of low certainty.None. (PROSPERO: CRD42017074074)