Orange juice–derived flavanone and phenolic metabolites do not acutely affect cardiovascular risk biomarkers: a randomized, placebo-controlled, crossover trial in men at moderate risk of cardiovascular disease

Randomized, placebo-controlled, crossover trial conducted in the United Kingdom in healthy nonsmoking men at moderate cardiovascular disease risk. Men were aged 51 to 69 years, with mean age 61 years and absolute CVD risk 15.8% (range 10-20%); for each active intervention period, 16 participants were randomized and 14 completed.

Participants received a single oral dose of either 767 mL orange juice providing 320 mg hesperidin or a dose-matched 320 mg hesperidin supplement; both interventions were matched for vitamin C and sugars and were compared with control in a crossover design. Outcomes were assessed 5 hours after dosing.

A single dose of orange juice increased circulating flavanone and phenolic metabolites, but neither orange juice nor hesperidin improved cardiovascular risk biomarkers over 5 hours. Total plasma flavanone metabolites were higher after orange juice than control (1.75 ± 0.35 mmol/L), and total phenolics were also higher (13.27 ± 2.22 mmol/L). Hesperidin metabolites after the hesperidin supplement did not differ from control (P = 0.9), and plasma vitamin C increased similarly after all interventions. No significant differences were seen for endothelial function, blood pressure, arterial stiffness, cardiac autonomic function, platelet activation, or NADPH oxidase gene expression, and no serious adverse events were reported.

The trial was small, with only 14 completers per active intervention period, and it assessed only acute effects after a single dose. The 5-hour follow-up may have been too short to detect cardiovascular changes, and findings from middle-aged to older men at moderate CVD risk may not generalize to women or other populations.