Effects of hesperidin supplementation on inflammation and oxidative stress in overweight or obese individuals: a systematic review and meta-analysis of randomized controlled trials.

This study aimed to evaluate, through a systematic review and meta-analysis of randomized controlled trials (RCTs), the effects of hesperidin and hesperidin-containing citrus interventions on biomarkers of inflammation, oxidative stress, and endothelial function in overweight or obese individuals. Two authors independently searched PubMed, Web of Science, Embase, Scopus, and the Cochrane Library from inception to April 4, 2026. Methodological quality was assessed using the Cochrane Risk of Bias 2 tool (RoB 2), and certainty of evidence was evaluated with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Heterogeneity was assessed using Cochran's Q test and the I-square (I 2) statistic, and fixed- or random-effects models were applied as appropriate. Most continuous outcomes were pooled as mean differences (MDs) with 95% confidence intervals (CIs), whereas total antioxidant capacity (TAC) was pooled as standardized mean differences (SMDs; Hedges' g) due to inconsistent assay methods. Sixteen RCTs involving 845 participants were included. Compared with placebo or control, hesperidin-related interventions reduced C-reactive protein/high-sensitivity C-reactive protein (CRP/hsCRP) (MD: -0.43 mg/L, 95% CI: -0.68, -0.17, P = 0.001; GRADE = moderate), tumor necrosis factor-alpha (TNF-α) (MD: -2.84 pg/mL, 95% CI: -4.81, -0.86, P = 0.005; GRADE = very low), and vascular cell adhesion molecule-1 (VCAM-1) (MD: -27.16 ng/mL, 95% CI: -50.13, -4.19, P = 0.020; GRADE = very low), with no significant effects on interleukin-6 (IL-6), TAC, or intercellular adhesion molecule-1 (ICAM-1). Malondialdehyde (MDA) and superoxide dismutase (SOD) were reported narratively in single studies. Current randomized evidence suggests that hesperidin-related interventions are associated with a modest reduction in CRP/hsCRP, representing the most consistent biomarker signal to date. Evidence for TNF-α and VCAM-1 remains very low in certainty, and findings for IL-6, oxidative stress markers, and ICAM-1 remain inconclusive. Marked between-study differences in intervention matrix, design structure, and reporting methods preclude dose- or matrix-specific recommendations at present. Further high-quality randomized trials with longer follow-up, standardized biomarker assessment, and better characterization of formulations are needed.