Journal Title (Medline/Pubmed accepted abbreviation): Br J Nutr
Page numbers: 849-857
Background: The most prominent flavonoids in fruits and vegetables are flavonols, of which quercetin is the most commonly consumed in the human diet. Quercetin is a strong antioxidant with anti-inflammatory, antimicrobial, and immune-modulating properties. Total dietary flavonol intake estimates for US adults range from 13 to 22 mg/day, with quercetin representing about 75% of the total intake. Despite earlier concerns, long-term supplementation with high-doses of quercetin has not been linked to any adverse effects in rodents or human subjects. Moreover, epidemiologic studies have positively correlated flavonoid intake with deceased incidence of chronic heart disease and some common human cancers.
Hypothesis: The authors hypothesized that long-term supplementation with high doses of quercetin would positively affect innate immune function and reduce expression of markers of inflammation in adult human subjects.
Subjects: 120 healthy, Caucasian, adult female subjects from the general population (age 30 to 79 yr; mean body mass index [BMI] > 25.0 kg/m2) participated in the study.
Experimental design: Randomized, double-blind, placebo-controlled
Treatments and protocol:Subjects were randomized to 1 of 3 treatment groups: 500 mg aglycone quercetin/day (Q-500; n = 38), 1,000 mg aglycone quercetin/day (Q-1,000; N = 40), or placebo (n = 42). Aglycone quercetin is water soluble. Subjects ingested 2 soft chew supplements twice daily during the 12-week study period. Fasting blood samples were obtained pre- and post-study and were analyzed for plasma quercetin, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and leucocyte subset cell counts. Blood samples from a subset of patients were analyzed for natural killer cell activity (NKCA) and lymphocyte subsets (n = 74), and granulocyte oxidative burst activity (GOBA) and phagocytosis (n = 64). There was some overlap between the cohorts: 18 subjects were tested for both NKCA and GOBA/phagocytosis.
- There were no significant correlations between subject age and any of the pre-study measures of innate immune function (P > .4) or inflammation (P > .2).
- Compared with placebo, 12 weeks of quercetin supplementation (Q-500 and Q-1,000) caused
- A significant increase in plasma quercetin levels (P < .001).
- No significant effects on plasma concentrations of leukocytes (P = .306), lymphocytes (P = .867) neutrophils (P = .193), IL-6 (P = .812), or TNF-α (P = .208).
- For all subjects, there was a positive correlation between BMI and IL-6 (r = 0.23; P = .010).
- No significant effects on GOBA (P = .602) or phagocytosis (P = .990).
- For all subjects, GOBA increased pre- to post-supplementation (P < .001).
- No significant effect on NKCA (P = .696)
- For all subjects, NKCA tended to increase pre- to post-supplementation; however, this apparent time effect did not reach significance (P = .163).
- For all subjects, there was a positive correlation between NKCA and self-reported physical fitness level (r = 0.24; P = .032), and a negative correlation between NKCA and BMI (r = –0.25; P = .035) and body fat percentage (r = –0.38; P = .001).
The current study demonstrated that quercetin supplementation (Q-500 and Q-1,000) increased plasma quercetin levels but had no influence on measures of innate immune function or inflammation in community-dwelling adult females. Subjects tended to be overweight individuals (mean BMI > 25.0 kg/m2) with mean plasma IL-6 and TNF-α concentrations that were slightly elevated (but within normal limits) compared with those reported for lean women. As such, the lack of quercetin-related effects on inflammation in this study could be because subjects were already within normal limits of the outcome measures. Additionally, supplementation with aglycone quercetin may lack an anti-inflammatory or immunomodulatory effect in humans because of its reduced bioavailability or its metabolic transformation in vivo. A growing body of evidence suggests that a mixed flavonoid approach to modifying innate immunity is more effective than supplementation with a pure flavonoid. Future research will determine if the immunomodulatory effects of quercetin can be enhanced through the addition of other flavonoids (eg, epigallocatechin 3-gallate) or food components.