Effect of vitamin C and hesperidin on serum uric acid concentrations in healthy adults with high uric acid levels: the randomized controlled 'HesperidrinC trial'.

PURPOSE: While orange juice has been reported to decrease serum uric acid (SUA), the effects of the specific constituents hesperidin and vitamin C are not fully understood. The present study aimed to unravel their possible SUA-lowering effects. METHODS: In a randomized controlled, double-blind, two-way cross-over, two-week intervention, the effects of four orange-flavored drinks (200 mL/d) on SUA (primary outcome) were compared in 40 adults (21–78 y; BMI 17.9–41.4 kg/m2) with high SUA. One drink was a placebo; the others contained 600 mg vitamin C (VitC), 240 mg hesperidin (Hesp), or both (VitC+Hesp). Blood and urine concentrations of uric acid, vitamin C, and hesperidin metabolites were measured, along with the HOMA index as a potential confounder. RESULTS: VitC increased plasma vitamin C levels, Hesp increased urinary excretion of hesperidin metabolites, and VitC+Hesp increased both. Higher baseline plasma vitamin C levels resulted in diminished increases in vitamin C (VitC: r = -0.53; p = 0.02 and VitC+Hesp: r = -0.79; p < 0.001). Levels of SUA decreased in response to VitC and VitC+Hesp with no changes in urinary uric acid excretion (UUA) or clearance (UAC). The increase in plasma vitamin C was associated with a decrease in SUA (r = -0.25; p < 0.03) with larger effects at higher baseline SUA (r = -0.24; p = 0.03). A high HOMA index was associated with lower plasma vitamin C and elevated SUA. CONCLUSION: Vitamin C but not hesperidin decreased serum uric acid levels without affecting uric acid excretion. CLINICAL TRIALS REGISTRATION: www.clinicaltrials.gov ; NCT04316390; July 15, 2022.