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Background Protein-rich foods are major parts of the human diet and are highly heterogeneous in nutrient composition and health effects. Designing healthy diets for disease prevention requires careful consideration of substituting unhealthier protein foods with healthier protein foods. Methods This was a pooled analysis of six prospective cohort studies of 29 682 US participants. Data were collected in 1985–2016. Adjusted hazard ratios (HRs) and 30-year absolute risk differences (ARDs) were calculated for the associations between simultaneous substitution of one or more animal protein foods with other animal or plant protein foods at various amounts, and incident cardiovascular disease (CVD) and all-cause mortality. Results Substituting eggs, processed meat, unprocessed red meat or poultry with nuts, whole grains, legumes or fish was associated with lower risks of incident CVD and all-cause mortality. According to different substitution amounts (varying from one serving per week to one serving per day) and different numbers of protein foods being simultaneously substituted (varying from one to four), estimates ranged between 1%: HR, 0.99 [95% confidence interval (CI), 0.98–1.00], and 54%: HR, 0.46 (0.35–0.60), lower risks on the relative scale and between 0.3%: ARD, -0.29% (-0.48% to -0.05%), and 14.0%: ARD, -13.96% (-17.29% to -9.96%) lower risks on the absolute scale. Conclusions Nuts, whole grains, legumes and fish appeared to be healthier protein sources than eggs, processed meat, unprocessed red meat and poultry for preventing incident CVD and premature death. The magnitude of lower risk for incident CVD and all-cause mortality was driven by amount and number of animal protein foods substituted.

Protein foods from animal sources, incident cardiovascular disease and all-cause mortality: a substitution analysis