Patterns of Red and Processed Meat Consumption and Risk for Cardiometabolic and Cancer Outcomes

Observational studies have reported higher incidence of all-cause mortality, cardiometabolic diseases, and cancer outcomes in people who consume greater quantities of red meat (16). Consequently, most guidelines from national and international agencies recommend limiting intake of red and processed meat (79). However, additional scrutiny of the evidence to determine the extent to which current recommendations are justified is warranted, particularly given the possible methodological limitations of systematic reviews to date (for example, the lack of consideration of the overall certainty of evidence) and other confounding factors (10, 11). Foods and nutrients are not consumed in isolation, and their effects may differ depending on the totality of one's diet and how dietary habits change over time. Moreover, interventions focusing on modification of intake of particular foods or nutrients require compensatory changes in other dietary components. Nevertheless, most nutritional epidemiologic research since the 1970s has focused on the effects of individual foods or nutrients (12). Given the potential for interaction, an increasingly common alternative to focusing on individual foods or nutrients is to examine the effects of dietary patterns on health outcomes (13). Two approaches are commonly used to define dietary patterns: data-driven methods, including factor analysis or principal-components analysis, or a priori approaches that use diet indices or scores based on dietary recommendations or characteristics. This review was done to inform recommendations on red and processed meat intake from the NutriRECS (Nutritional Recommendations) consortium (14). We conducted 4 additional systematic reviews addressing evidence from randomized trials on the effect of red meat consumption on health outcomes (15), observational evidence on the association between red and processed meat consumption and cardiometabolic outcomes (16), observational evidence on the association between red and processed meat consumption and cancer outcomes (17), and qualitative and quantitative evidence on public values and preferences regarding meat consumption (18). We used the results of these to develop guideline recommendations on red and processed meat consumption (19). In this article, we report the results of a systematic review addressing the association between dietary patterns that are lower versus higher in red and processed meat intake and the risk for cardiometabolic and cancer outcomes. Methods This article complies with the recommendations of PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) (20). We registered the protocol in PROSPERO (CRD42017074074) on 10 August 2017. Data Sources and Searches With assistance from an experienced librarian, we developed a comprehensive search strategy for 5 databases: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, Web of Science, and CINAHL. We searched each database without restrictions on year or language of publication from inception to 8 July 2018, with an updated search of MEDLINE through to April 2019 (Supplement Table 1). In addition, we searched the following gray literature sources: ProQuest Dissertations & Theses Global (1989 to 2018), trial registries (ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform Search Portal), bibliographies of included articles, and relevant literature reviews. This search strategy informed all supporting NutriRECS reviews on red and processed meat (1517) except the one addressing public values and preferences (18). Supplement. Supplementary Material Study Selection We included cohort studies with 1000 or more participants that reported an association between dietary patterns and 1 or more of our outcomes of interest in adults with or without cardiometabolic conditions but without cancer or any infectious or chronic noncardiometabolic conditions. We excluded studies that did not report the quantity of consumption of red and processed meat across categories of dietary habits. Red meat was defined as mammalian meat, and processed meat was defined as white or red meat preserved by smoking, curing, salting, or adding preservatives (21). We assumed serving sizes of 120 g for unprocessed red meat, 50 g for processed meat, and 100 g for mixed unprocessed red and processed meat. These were selected to be comparable to serving sizes used in other systematic reviews and to reflect those used by the U.S. Department of Agriculture and the U.K. Food Standards Agency (47). We also included studies comparing vegetarians with nonvegetarians. When more than 1 eligible article reported on the same exposure and cohort and addressed the same outcome, we included only results from the article with the longest follow-up. If the duration of follow-up was the same across articles, we included the article with the largest number of participants, resulting in each unique cohort study as the unit of analysis. The panel for the NutriRECS guideline on red and processed meat, which comprised members of the public and clinicians, including dietitians, epidemiologists, and methodologists, selected the outcomes of interest for this systematic review (14, 22). These included major cardiometabolic morbidity and mortality; incidence of or mortality associated with gastrointestinal, breast, gynecologic, and prostate cancer; quality of life; and satisfaction with diet. Reviewers conducted pilot screening exercises and received detailed instructions for each item before screening. Pairs of reviewers independently screened titles and abstracts in duplicate and reviewed the full-text articles of those found to be potentially eligible. Reviewers resolved disagreements by discussion or, if necessary, by third-party adjudication. Data Extraction and Risk-of-Bias Assessment Reviewers conducted calibration exercises and worked in duplicate to independently extract data. We used a standardized, piloted data abstraction form. The reviewers resolved disagreements by discussion or, if necessary, by third-party adjudication involving a senior investigator. We extracted the following information from each study: setting, number of participants at baseline and follow-up, age, sex, method of diet assessment, dietary pattern data (intake of red and processed meat), type of cancer or cardiometabolic disease, years of follow-up, and effect estimates and corresponding 95% CIs. Reviewers, independently and in duplicate, assessed risk of bias of each eligible study by using a modified version of the CLARITY (Clinical Advances Through Research and Information Translation) instrument (23, 24), with omission of 1 item related to co-interventions that was not relevant to our review (Supplement Table 3). We rated each item as having definitely low, probably low, probably high, or definitely high risk of bias. We adapted item 2 (assessment of exposure) to address the validity of dietary measures. For example, if a study measured diet at least once every 5 years using a food-frequency questionnaire validated against a weighted food record for red and processed meat, it was deemed to have definitely low risk of bias for this item. We also adapted item 4 (adjustment for prognostic factors) on the basis of established prognostic factors for each outcome of interest. Consultation with research methodologists and nutrition researchers confirmed the appropriateness of the instrument and informed criteria to evaluate each item. We considered each item to be equally important. Risk of bias was evaluated at the outcome level and not the study level. We considered studies that were rated to have high risk of bias on 2 or more of the 7 domains to have high overall risk of bias. Although this threshold is arbitrary, it represents a compromise between excessive stringency and leniency and facilitates subgroup analysis by providing an approximately even division between studies at higher versus lower risk of bias. Data Synthesis and Analysis The lowest category (for example, tertiles or quartiles) of adherence to dietary patterns high in red and processed meat was compared with the highest category as a proxy to determine the dietary patterns lower versus higher in red and processed meat consumption. When a single study investigated multiple dietary patterns, our analysis focused on the one with the greatest difference in red or processed meat intake between the lowest and highest categories. In studies that investigated multiple dietary patterns, we used factor analysis or principal-component analysis to analyze the patterns with the highest factor loadings for red meat, processed meat, or both. Using the HartungKnappSidikJonkman model (25, 26) and a DerSimonianLaird random-effects model as a sensitivity analysis (27), we conducted meta-analyses comparing the lowest and highest categories of intake. For studies in which the outcomes of interest were reported stratified by participant characteristics (for example, sex) with no overlap in participants or events across strata, we meta-analyzed across subgroups. We calculated the risk difference by multiplying the pooled effect estimate from our meta-analyses by the baseline risk for cancer incidence or mortality, which was based on GLOBOCAN cumulative lifetime risks (28, 29). For cardiometabolic disease, data from the Emerging Risk Factors Collaboration (30) provided the baseline risk to calculate risk differences over 10.8 years. We conducted subgroup analyses for each outcome based on our assessment of overall risk of bias for each study. When we found a statistically significant subgroup effect based on risk of bias, we present results for studies with low risk of bias. We also conducted a subgroup analysis based on the methods for defining dietary patterns. Certainty of Evidence One investigator assessed the certainty of evidence as high, moderate, low, or very low for each outcome using th