Whereas meat consumption is commonly considered a risk factor for cardiovascular and metabolic diseases, our findings indicate that the effects and magnitudes may vary depending on both the type of meat consumed and the outcome considered. This first systematic review and meta-analysis of these relationships, including 1,218,380 individuals from 10 countries on 4 continents with 23,889 cases of CHD, 2,280 cases of stroke, and 10,797 cases of diabetes, provides the most robust and reliable evidence to-date of how unprocessed red and processed meat consumption may influence risk of cardiometabolic diseases. Consumption of processed meats was associated with significantly higher incidence of both CHD and diabetes, with 42% and 19% higher risk, respectively, per 50 g serving/day. In contrast, consumption of unprocessed red meats was not associated with CHD and was associated with a nonsigificant trend toward higher risk of diabetes. Associations were intermediate for total meat intake.
Our extensive search of multiple databases and direct contact with authors resulted in the identification of 17 prospective cohorts and 3 case-control studies; no RCTs were identified that evaluated effects of red, processed, or total meat consumption on CVD or diabetes events. This is not surprising considering that trials of such effects can be very challenging and costly to conduct, with limitations of nonblinding and noncompliance over the long periods of time required to detect clinical endpoints. In this setting, the best available evidence is derived from long-term prospective cohorts of disease endpoints such as those identified here, although such studies can be limited by misclassification and residual confounding. Retrospective case-control studies may have additional potential limitations (e.g., recall and selection bias).
Thus, each of these individual studies have potential limitations, and our findings should be interpreted in that context. On the other hand, this represents the most complete worldwide evidence to-date of the potential effects of red and processed meat consumption on incidence of CHD, stroke, and diabetes. We also performed multiple sensitivity analyses to evaluate the extent to which our findings might vary depending on underlying study design (cohort vs. case-control), presence or absence of prespecified analyses, geographic region (e.g., US vs. other), overrepresentation of one large study, or identified other sources of heterogeneity. Generally, findings were consistent in each of these sensitivity analyses and similar to the overall pooled results. Thus, although limitations of the individual studies should not be ignored, our results provide the best current evidence for how red, processed, and total meat consumption relate to CHD, stroke, and diabetes and highlight specific gaps in knowledge that are essential for policy decisions relating to these important diet-disease relationships.
For example, our findings of different relationships of red vs. processed meat consumption with incident CHD and diabetes events support the need to better characterize which particular components of meats may increase cardiometabolic risk. At least in the US, where most of the studies were performed, processed meats contain, on average, similar saturated fat and lower cholesterol and iron compared with red meats, suggesting that differences in these constituents may not account for different associations with disease risk. Other constituents may be relevant in determining health effects. In particular, the observed substantially higher sodium and nitrate preservative levels in processed meats could plausibly contribute to increased CVD and diabetes risk and account, at least in part, for the present findings. Dietary sodium significantly increases blood pressure(30
), and habitual consumption may also worsen arterial compliance and promote vascular stiffness(33
). Nitrates and their byproducts (e.g., peroxynitrite) experimentally promote atherosclerosis and vascular dysfunction(34
), reduce insulin secretion(35
), and impair glucose tolerance(36
),while streptozotocin, a nitrosamine-related compound, is a known diabetogenic compound(37
). In observational studies in children, nitrites and nitrous compounds are associated with type 1 diabetes(38
), and nitrite concentrations in adults have been used as a biomarker of endothelial dysfunction(40
) and impaired insulin response(41
). Differences in types of foods commonly replaced when individuals consume red vs. processed meats could also partly account for their different associations with risk.
Our study had several strengths. We reviewed multiple databases broadly and systematically for all investigations of meat consumption and incidence of CHD, stroke, or diabetes, making it likely that we identified all major published reports. Multiple authors were directly contacted and clarified findings or provided additional data, minimizing both misclassification and effects of publication bias. Study inclusion/exclusion and data extraction were performed independently and in duplicate by two investigators, increasing validity of results. Studies were identified from the US, Europe, Asia, and Australia, increasing generalizability. Large numbers of disease endpoints were identified, providing substantial statistical power to detect clinically meaningful associations. We used generalized least squares models for trend estimation, that explicitly assesses dose-response rather than simply categorical comparisons. We carefully identified and separately evaluated red, processed, and total meat consumption; in particular, relatively few prior reports have separately considered unprocessed red meats. Indeed, several key reports on “red meat” consumption included processed meats in this category(3
), limiting inference on effects of unprocessed red meats alone. For example, a systematic review by the World Cancer Research Fund and American Institute for Cancer Research concluded that both “red” and processed meat consumption increased colorectal cancer(24
); however, “red” meats in several of the included studies were the sum of unprocessed and processed meats. Interestingly, their identified relationship of “red” (commonly total, i.e., unprocessed red plus processed) meat intake with colorectal cancer (22% higher risk per 100 g/day) was approximately half that as for processed meat alone (46% higher risk per 100 g/day), consistent with our results that much of the association between total meat intake and CHD and diabetes may result from effects of processed meats.
Potential limitations should also be considered. As with all meta-analyses, analyses were restricted to available published and unpublished data. Most of these studies did not separately assess extensive details about specific subcategories of deli meats consumed. Processed meats may have included small amounts of processed poultry, which could theoretically have smaller effects and cause underestimation of effects of processed red meats. We did not have data on cooking methods that could alter health effects of red or processed meats(42
). Both red and processed meats represent somewhat heterogeneous categories, and thus our findings should be interpreted as the average overall association rather than the particular effect of one specific subtype of such meats. This interpretation would be similar, for example, to analyses or meta-analyses of effects of other classes of dietary factors, such as fruits, vegetables, fish, whole grains, alcohol, etc. A recent meta-analysis of relationships between meat consumption and diabetes has been reported(45
); this study also found higher risk with processed meat intake, but included crude (unadjusted) risk estimates and also did not separately evaluate unprocessed red meats.
All studies were observational, and residual confounding by imprecisely or unmeasured factors cannot be excluded. In particular, several studies did not adjust for other dietary habits or socioeconomic status. Thus, associations of processed meat consumption with diabetes or CHD could relate to generally less healthy diet or lifestyle, rather than causal effects of processed meats. Conversely, most studies adjusted for at least several major demographics and other risk factors; the reported potential confounding factors related to red vs. processed meat consumption were similar, yet only the latter was related to risk; and specific ingredients in processed meats (e.g., salt, other preservatives) provide biologic plausibility for the observed relationships. Several studies adjusted for factors that could be either confounders or intermediates in the causal pathway, that could potentially attenuate the observed risk estimates between meat consumption and disease risk. We standardized all servings to 100 g for red and total meat and 50 g for processed meat, and risks could vary when serving sizes are lower or higher. Representative nutrient and preservative data were available only for the US, and such values should be considered illustrative rather than definitive for other countries. Too few studies were present to formally exclude publication bias with sufficient statistical power. On the other hand, our extensive direct contact with multiple authors and inclusion of unpublished findings minimizes the potential impact of publication bias. Notably, if publication bias were present, it might cause overestimation of harmful associations between processed meats and diabetes or CHD (i.e., identified harmful associations might more likely be published), but would unlikely contribute to null associations between red meats and CHD or diabetes or between meats and stroke (i.e., publication bias is unlikely to favor reporting of null associations).
Our findings demonstrate that consumption of processed meat in particular is associated with incidence of CHD and diabetes, highlighting the importance of separate consideration of health effects, underlying mechanisms, and policy implications of different types of processed vs. unprocessed meats. Our findings also identify critical gaps in our understanding of how meat consumption influences cardiometabolic risk, including potential effects of red meat consumption on diabetes or CHD; of any meat consumption on stroke risk; and of specific ingredients that could be underlying these relationships. Based on our evaluation of average nutrient and preservative contents of red and processed meats, constituents in meats other than fats may be especially relevant to health effects. Based on this systematic review and meta-analysis of all available data, future research should carefully distinguish between different types of meats, and policy measures for improving cardiometabolic health should focus particularly on reducing processed meat consumption, including consideration of recommendations for specific quantitative limits. These findings are particularly timely to current efforts to update the US Dietary Guidelines for Americans that are also often a reference for other countries around the world.