F(2)-isoprostanes are recently described prostaglandin F isomers produced by cyclooxygenase-independent free radical peroxidation of arachidonic acid. Their quantification in plasma and urine is a sensitive and specific indicator of lipid peroxidation and, hence, of oxidative stress in vivo. Some components of garlic are known to possess antioxidant properties. Thus, we have investigated the effect of dietary supplementation with aged garlic extract (AGE; Kyolic; Wakunaga of America, Mission Viejo, CA) on the plasma and urine concentrations of the F(2)-isoprostane 8-iso-prostaglandin F(2 alpha) (8-iso-PGF(2 alpha)). Because smokers are exposed to increased oxidative stress, this study was performed in both smoking and nonsmoking subjects. Plasma and urine concentrations of 8-iso-PGF(2 alpha) in nonsmoking individuals were 1.25 +/- 0.19 nmol/L and 272 +/- 53 pmol/mmol of creatinine, respectively. In age- and sex-matched smokers, plasma and urine concentrations of 8-iso-PGF(2 alpha) were 58% and 85% higher, respectively. Dietary supplementation with AGE for 14 d reduced plasma and urine concentrations of 8-iso-PGF(2 alpha) by 29% and 37% in nonsmokers and by 35% and 48% in smokers. Fourteen days after cessation of dietary supplementation, plasma and urine concentrations of 8-iso-PGF(2 alpha) returned to values not different from those before ingestion of AGE in both groups. Thus, dietary supplementation with AGE may be useful in reducing oxidative stress in humans.