Effects of Bioactive Compound Supplementation on Insulin Resistance and Systemic Inflammation in Overweight and Obese Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background/objectives: Obesity is characterized by chronic low-grade inflammation and insulin resistance. This systematic review and meta-analysis evaluated oral supplementation with curcumin, green tea extract, resveratrol and omega-3 fatty acids on homeostatic model assessment of insulin resistance (HOMA-IR) and C-reactive protein (CRP) in adults with overweight or obesity. Methods: PubMed and Scopus were searched on 22 July 2026 for randomized controlled trials (RCTs) of isolated oral supplementation versus placebo or control, lasting ≥4 weeks, in adults with BMI ≥25.0 kg/m2 without type 2 diabetes. Risk of bias was assessed with RoB 2 and certainty of evidence with GRADE. Random-effects meta-analyses were performed separately for each compound and biomarker, using mean difference (MD). Results: Fifty-nine RCTs (3263 participants) were included (omega-3: 23; curcumin: 13; green tea: 13; resveratrol: 10). Most trials had some concerns or high risk of bias. Only curcumin significantly reduced HOMA-IR (MD = −0.30 [−0.53, −0.07], p = 0.019; moderate certainty), with low heterogeneity. Green tea extract yielded a non-significant CRP reduction (MD = −0.43 mg/L [−0.87, 0.02], p = 0.057; low certainty) with substantial heterogeneity. Resveratrol and omega-3 showed no significant effect on either outcome (low certainty). Significant heterogeneity was observed in five of eight analyses. Conclusions: Curcumin may modestly improve insulin resistance in this population, potentially as a complementary strategy in obesity management. Green tea’s anti-inflammatory effect requires confirmation. Heterogeneous formulations and doses, small samples and risk of bias limit interpretation; future RCTs should use standardized formulations with documented bioavailability.