Hesperidin supplementation has no effect on blood glucose control: a systematic review and meta-analysis of randomized controlled clinical trials.

Systematic review and meta-analysis of randomized controlled clinical trials in adults older than 18 years. Included populations ranged from healthy overweight or obese adults to patients with metabolic syndrome or type 2 diabetes, with trials conducted in Iran, Germany, Spain, France, and Italy.

Hesperidin was evaluated in 6 randomized trials using oral daily dosing of 450 mg/day to 500 mg/day for 3 to 8 weeks in most studies, with two crossover beverage trials using hesperidin-containing juice or beverage formulations. Individual active-arm sample sizes were not reported; the review pooled 318 participants across 3 crossover and 3 parallel trials.

Hesperidin supplementation did not improve blood glucose control or insulin sensitivity versus placebo/control. Pooled random-effects analyses showed no significant effect on fasting blood glucose (WMD -1.10 mg/dL, 95% CI -3.79 to 1.57; P = .844), HbA1c (WMD -0.04%, 95% CI -0.14 to 0.04; P = .321), HOMA-IR (WMD 0.117, 95% CI -0.06 to 0.29; P = .208), or QUICKI (WMD 0.135, 95% CI -0.13 to 0.39; P = .319). Heterogeneity was low for fasting blood glucose, HbA1c, and HOMA-IR (I2 = 0% for each) but extreme for QUICKI (I2 = 99.7%). The authors concluded that hesperidin does not show a confirmed benefit for glycemic control in humans and that longer, higher-quality trials, especially in type 2 diabetes, are needed.

Only 6 trials were included, and several outcomes were informed by very few studies (HbA1c n = 2, HOMA-IR n = 3, QUICKI n = 2). Interventions were short and heterogeneous in design, population, and formulation, including both crossover and parallel trials. Individual active-arm sample sizes and adverse events were not reported, and QUICKI showed very high heterogeneity, limiting confidence in precision and generalizability.