Pomegranate juice consumption reduces oxidative stress, atherogenic modifications to LDL, and platelet aggregation: studies in humans and in atherosclerotic apolipoprotein E–deficient mice

Abstract

Background: Dietary supplementation with nutrients rich in antioxidants is associated with inhibition of atherogenic modifications to LDL, macrophage foam cell formation, and atherosclerosis. Pomegranates are a source of polyphenols and other antioxidants. Objective: We analyzed, in healthy male volunteers and in atherosclerotic apolipoprotein E–deficient (E⁰) mice, the effect of pomegranate juice consumption on lipoprotein oxidation, aggregation, and retention; macrophage atherogenicity; platelet aggregation; and atherosclerosis. Design: Potent antioxidative effects of pomegranate juice against lipid peroxidation in whole plasma and in isolated lipoproteins (HDL and LDL) were assessed in humans and in E⁰ mice after pomegranate juice consumption for ≤2 and 14 wk, respectively. Results: In humans, pomegranate juice consumption decreased LDL susceptibility to aggregation and retention and increased the activity of serum paraoxonase (an HDL-associated esterase that can protect against lipid peroxidation) by 20%. In E⁰ mice, oxidation of LDL by peritoneal macrophages was reduced by up to 90% after pomegranate juice consumption and this effect was associated with reduced cellular lipid peroxidation and superoxide release. The uptake of oxidized LDL and native LDL by mouse peritoneal macrophages obtained after pomegranate juice administration was reduced by 20%. Finally, pomegranate juice supplementation of E⁰ mice reduced the size of their atherosclerotic lesions by 44% and also the number of foam cells compared with control E⁰ mice supplemented with water. Conclusion: Pomegranate juice had potent antiatherogenic effects in healthy humans and in atherosclerotic mice that may be attributable to its antioxidative properties.