Abstract

BACKGROUND Hesperidin (a flavanone found in citrus fruits) supplementation is suggested to inversely affect inflammation; however, clinical trials have led to inconsistent results. OBJECTIVE To examine the effect of hesperidin supplementation on inflammatory markers using systematic review and meta-analysis of randomized controlled clinical trials (RCTs). PATIENT AND METHODS Online databases including PubMed, Scopus, ISI Web of Science, and Google Scholar were searched up to December 2018. A random-effects model was used to compare the mean changes in the inflammatory markers between hesperidin supplemented and control subjects. RESULTS Six eligible RCTs with 296 participants were included in the systematic review. The meta-analysis revealed that hesperidin significantly reduces Vascular Cell Adhesion Molecule 1 (VCAM-1) levels [weighted mean difference (WMD) = -22.81 ng/L, P = 0.041, n = 3]. No considerable changes was observed for serum C-reactive protein (CRP) levels (WMD = -0.69 mg/L, P = 0.079, n = 5); the subgroup analysis showed a significant reduction in studies with a parallel design (WMD = -0.72 mg/L, P = 0.024, n = 3), and studies with more than 4 weeks of follow-up (WMD = -0.76 mg/L, P = 0.020, n = 2). Hesperidin supplementation had no signification effect on circulating E-selectin, interleukin 6, and Intercellular Adhesion Molecule 1 (ICAM-1) levels. CONCLUSION The present study suggests that although hesperidin supplementation significantly improves VCAM-1 levels; however, other inflammatory markers might not be affected. Further high-quality systematic reviews exploring the effect of hesperidin particularly on VCAM-1, ICAM-1, E-selectin, and interleukin 6 are still needed to confirm these results.