Effects of combined training on inflammatory biomarkers in middle-aged and older adults: a systematic review and meta-analysis

Chronic low-grade inflammation is a key factor in aging and age-related diseases. With population aging, effective anti-inflammatory interventions were increasingly needed. Combined aerobic and resistance training (CART) has emerged as a promising non-pharmacological approach; however, its effects on inflammatory biomarkers in middle-aged and older adults remained unclear. This study aimed to evaluate the effects of CART on inflammatory biomarkers and to identify potential moderating factors using a meta-analysis. Following PRISMA 2020 guidelines, we conducted a systematic review registered in PROSPERO (CRD420251120740). We searched PubMed, Web of Science, the Cochrane Library, and EBSCOhost from inception to September 2025. Standardized mean differences (Hedges’ g) were calculated using random-effects models. Subgroup and meta-regression analyses were performed to examine potential moderators, including body mass index (BMI), age, and intervention duration. All analyses were performed in R (v4.2.0). Study quality was assessed using RoB 2 and the PEDro scale, and the certainty of evidence was evaluated using the GRADE approach. Nineteen trials ( n = 756) were included. CART significantly reduced IL-6 (Hedges’ g = − 0.66, 95% CI − 1.11 to − 0.22; p = 0.003) and TNF-α (Hedges’ g = − 0.90, 95% CI − 1.77 to − 0.03; p = 0.042); CART was also associated with a possible increase in IL-10; however, the evidence was very uncertain because this finding was based on only four studies with substantial heterogeneity (Hedges’ g = 1.80, 95% CI 0.02 to 3.57; I² = 88.7%; prediction interval − 4.45 to 8.04). The effects on CRP (Hedges’ g = − 0.24, 95% CI − 0.77 to 0.28; p = 0.366) and hs-CRP (Hedges’ g = − 0.32, 95% CI − 0.66 to 0.02; p = 0.063) were not statistically significant. Exploratory analyses suggested that BMI may be associated with the effects of CART on TNF-α and IL-6; however, these findings were inconsistent across categorical subgroup analyses and continuous meta-regression models and should be interpreted with caution. The overall certainty of evidence was rated as low to very low across all outcomes. CART may be associated with reductions in pro-inflammatory cytokines and a possible increase in IL-10 in middle-aged and older adults. However, the certainty of evidence is low to very low and heterogeneity is substantial; evidence for CRP and hs-CRP remains inconclusive. BMI-related findings are exploratory and should be interpreted cautiously. Although CART may be associated with improvements in some inflammatory biomarkers, the certainty of evidence is low to very low and the findings remain exploratory. Larger, well-designed randomized controlled trials are needed before firm conclusions can be drawn regarding its anti-inflammatory effects and clinical relevance. CRD420251120740.