(P13-004-25) Examining the Impact of Isocaloric Substitution of Animal Protein With Plant Protein All-Cause, Cardiovascular, and Cancer Mortality: A Systematic Review and Meta-Analysis

Objectives: This systematic review and meta-analysis aimed to evaluate the effect and difference in isocaloric substitution of 3% and 5% of total caloric value (TCV) of animal proteins (AP) with plant proteins (PP) on all-cause mortality (ACM) as primary outcome, cardiovascular mortality (CVM) and cancer mortality (CM) as secondary outcomes.

Methods: Three databases (PubMed, Embase and Web Of Science) were systematically searched from inception to November 2024 for prospective cohort studies evaluating the effects of the isocaloric substitution of 3% and 5% of AP with PP on mortality outcomes in adults (≥18 years old). Hazards ratio with their 95% confidence intervals (CIs) were estimated using a random-effects method.

Heterogeneity was assessed using Tau², Chi² and I² statistics. Subgroup analyses were performed to determine differences between both isocaloric substitution rates for each outcome assessed. Sensitivity analyses were conducted to evaluate the robustness of the summary estimates. The quality of the evidence was assessed using the Nutri-Grade approach.

Results: Ten cohort studies with 1,074,032 participants and 20,202,634 person-years were included. Substituting 3% and 5% of the TCV from AP with PP significantly reduced ACM (HR 0.88; 95% CI 0.85-0.91; p< 0.00001; I²=79%) with no significant differences between both replacement percentages in the subgroup test (p=0.55). CVM was significantly reduced for both 3% (HR 0.88; 95% CI 0.84-0.92; p< 0.00001; I²=24%) and 5% (HR 0.77; 95% CI 0.69-0.85; p< 0.00001; I²=0%). Significant differences were observed when comparing both percentages on CVM (p=0.01). The substitution of AP for PP was associated with a significantly reduction in CM (HR 0.95; 95% CI 0.91-0.99; p=0.01; I²=51%) with no significant differences between both replacement percentages in the subgroup test (p=0.41). 

Conclusions: Isocaloric substitution of animal proteins with plant proteins significantly reduces ACM, CVM and CM. We found a particularly notable benefit on cardiovascular mortality and an amplified effect when increasing the percentage of substitution from 3% to 5%. This highlights the potential of increasing the substitution of animal proteins with plant proteins in the diet to improve cardiovascular health.

Funding Sources: The study received no specific funding from any public, commercial, or non-profit funding agency.