Isocaloric substitution of animal protein with plant protein and its impact on all-cause, cardiovascular, and cancer mortality: A systematic review and meta-analysis
Abstract
BACKGROUND AND AIMS
Epidemiological evidence indicates that isocaloric substitution of animal-protein sources with plant-protein sources may reduce all-cause mortality (ACM), cardiovascular mortality (CVM), and cancer mortality (CM). However, the impact of substituting different proportions of animal-protein with plant-protein remains unclear. This systematic review and meta-analysis aimed to evaluate the effects of isocaloric substitution of animal-protein with plant-protein at two levels-3% and 5% of total caloric value (TCV)-on ACM, CVM and CM, and to assess whether these effects differ between substitution levels.
METHODS
Three databases-PubMed, Embase and Web of Science-were systematically searched up to December 2025. Prospective observational studies with multivariable adjustment evaluating isocaloric substitution of 3% and 5% of animal-protein with plant-protein on ACM, CVM and CM were included. Risk of bias was assessed using ROBINS-E. Hazard ratios (HR) for mortality outcomes were pooled using a random-effects model, with heterogeneity assessed with Tau2, Chi2 and I2., Statistical analysis was performed using Review Manager 5.4.
RESULTS
Nine cohort studies including 1,036,799 participants and 19, 904,866 person-years of follow-up were analyzed. Pooled results from studies examining 3% and 5% substitution of TCV from animal-protein with plant-protein significantly reduced ACM (HR 0.91; 95% CI 0.87-0.94; p < 0.00001; I2 = 77%) with no significant difference between…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 1,036,799 participants or records.
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