Effects of whey and soy protein supplementation on inflammatory cytokines in older adults: a systematic review and meta-analysis

Systematic review and meta-analysis of 31 studies involving 3274 participants, with 1611 in intervention arms and 1663 in comparators. The population was older adults, generally about 50 to 80 years old, including healthy participants and people with sarcopenia, pre-frailty, obesity, type 2 diabetes, hypercholesterolemia, hypothyroidism, prostate cancer, and other chronic diseases.

Included trials evaluated isolated whey protein or soy protein supplementation, usually taken orally once daily for 6 weeks to 24 weeks, with doses ranging from 15 g/d to 52 g/d. Several soy protocols also added isoflavones, ranging from 2 mg to 160 mg daily, and some whey protocols included milk protein comparators within the active intervention descriptions.

Overall, whey and soy protein showed modest, biomarker-specific anti-inflammatory effects rather than broad reductions across all markers. Whey protein was associated with lower IL-6 overall (MD -0.79 pg/ml, 95% CI -1.15 to -0.42), while effects on CRP, hs-CRP, and TNF-alpha were not statistically clear. Soy protein was associated with a reduction in TNF-alpha (MD -0.16 pg/mL, 95% CI -0.26 to -0.05), and adding isoflavones further lowered TNF-alpha (MD -0.20, 95% CI -0.31 to -0.08) but increased CRP in one subgroup analysis (MD 0.53, 95% CI 0.12 to 0.94). Benefits appeared more evident in older adults with sarcopenia or pre-frailty, in those with BMI at least 25 kg/m2, and with longer or more specific regimens.

Results were limited by substantial heterogeneity for several outcomes, especially whey IL-6 and CRP and soy CRP and hs-CRP. The included trials varied widely in dose, duration, protein source, isoflavone content, and participant health status, which weakens direct comparability and limits generalizability. Many subgroup findings were based on small samples and should be interpreted cautiously.