Plant-versus animal-derived protein and nutritional, cardiometabolic, and inflammatory outcomes in middle-aged and older adults: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Interest in plant-derived proteins and cardiometabolic health is growing, yet evidence directly comparing plant- and animal-derived protein intake in middle-aged and older adults remains inconsistent. AIMS: This systematic review and meta-analysis evaluated the effects of plant-versus animal-derived protein interventions on nutritional status, cardiometabolic health, and inflammatory outcomes in adults aged ≥50 years. METHODS: PubMed, Scopus, Google Scholar, and ClinicalTrials.gov were searched for randomized controlled trials (RCTs) published between January 2000 and August 2025. Eligible studies included adults aged ≥50 years, intervention durations of >1 month, and direct comparisons between plant- and animal-derived protein interventions. Random-effects meta-analyses were performed, and risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Exploratory subgroup analyses were conducted according to daily plant- and animal-protein intake, using 27 g/day as the data-derived median for both protein sources; intervention duration, using 12 weeks as the data-derived median; sex composition; and the presence or absence of an exercise intervention. RESULTS: Twenty-nine RCTs involving 2363 participants were included; 61.3% of participants were female, with 1174 assigned to animal-protein group and 1189 to plant-protein group. Most trials compared soy-based protein interventions with dairy-derived proteins; 25 of the 29 (86%) included RCTs used soy as the plant-protein source, and 23 of 29 (79%) evaluated purified protein isolates or isolate-based products rather than whole foods. Seven trials included an exercise intervention. Pooled analyses showed no significant differences between plant- and animal-protein interventions on body composition, including lean mass and handgrip strength, and on most blood indices. A marginal reduction in total cholesterol (T-CHOL) favored plant protein with substantial between-study heterogeneity (Hedges' g = -0.31, 95% CI: -0.62 to -0.00; I2 = 86.20%). Exploratory analyses suggested that plant protein favored T-CHOL among comparisons with plant-protein intake <27 g/day, animal-protein intake <27 g/day, or no exercise intervention. Conversely, diastolic blood pressure (DBP) favored animal protein among comparisons with animal-protein intake <27 g/day. Findings were accompanied by increased heterogeneity. CONCLUSIONS: Plant- and animal-derived protein interventions produced generally similar effects on nutritional, cardiometabolic, and inflammatory outcomes in adults aged ≥50 years. However, the predominance of soy-based isolates and dairy-derived comparators, together with substantial between-study heterogeneity, limits the certainty and generalizability of the findings. The results should be interpreted as evidence from controlled protein-source interventions rather than as evidence of equivalence between whole-food plant and animal protein substitutions. Further RCTs evaluating diverse whole-protein foods within protein-adequate, isocaloric, and nutritionally well-characterized dietary patterns are warranted. PROSPERO REGISTRATION ID: CRD420261304953.