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Quercetin supplementation results in a variable plasma quercetin response in humans. The purpose of this study was to determine whether this variance is related to gender, age, body mass index (BMI), and other demographic and lifestyle factors.Subjects (N= 1002, ages 18–85 years, 60% female and 40% male) were recruited from the community and randomized to one of three groups, with supplements administered using double-blinded procedures: Q-500 (500 mg/day), Q-1000 (1000 mg/day), or placebo. Subjects ingested two soft chew supplements twice daily during the 12-week study. Fasting blood samples were obtained pre- and post-study, analyzed for plasma quercetin, and then compared between and within groups by gender, age group (<40, 40–59, and ≥60 years), BMI (<25, 25–29.9, and ≥30 kg/m2), self-reported physical fitness level, and diet intake (food group servings).Quercetin supplementation over 12 weeks caused a significant increase in overnight-fasted plasma quercetin, with a net increase of 332± 21.0 and 516± 30.8 μg/l for Q-500 and Q-1000 compared with 53.6 ± 6.4 μg/l for placebo (interaction effect, P<0.001). The increase in plasma quercetin was highly variable within each quercetin supplementation group, but was unrelated to age, gender, BMI, fitness levels, or diet intake.In summary, quercetin supplementation in doses of 500 and 1000 mg/day caused large but highly variable increases in plasma quercetin that were unrelated to demographic or lifestyle factors.