a1 Human Performance Laboratory, North Carolina Research Campus, Appalachian State University, 600 Laureate Way, Kannapolis, NC, USA
a2 UNC Charlotte, Bioinformatics Services Division, Kannapolis, NC, USA
Quercetin, a flavonol in fruits and vegetables, has been demonstrated to have antioxidant, anti-inflammatory and immunomodulating influences. The purpose of the present study was to determine if quercetin, vitamin C and niacin supplements (Q-500 = 500 mg/d of quercetin, 125 mg/d of vitamin C and 5 mg/d of niacin; Q-1000 = 1000 mg/d of quercetin, 250 mg/d of vitamin C and 10 mg/d of niacin) would alter small-molecule metabolite profiles and serum quercetin conjugate levels in adults. Healthy adults (fifty-eight women and forty-two men; aged 40–83 years) were assigned using a randomised double-blinded placebo-controlled trial to one of three supplement groups (Q-1000, Q-500 or placebo). Overnight fasted blood samples were collected at 0, 1 and 3 months. Quercetin conjugate concentrations were measured using ultra-performance liquid chromatography (UPLC)-MS/MS, and metabolite profiles were measured using two MS platforms (UPLC-quadrupole time-of-flight MS (TOFMS) and GC-TOFMS). Statistical procedures included partial least square discriminant analysis (PLS-DA) and linear mixed model analysis with repeated measures. After accounting for age, sex and BMI, quercetin supplementation was associated with significant shifts in 163 metabolites/quercetin conjugates (false discovery rate, P< 0·05). The top five metabolite shifts were an increase in serum guaiacol, 2-oxo-4-methylthiobutanoic acid, allocystathionine and two bile acids. Inflammatory and oxidative stress metabolites were not affected. PLS-DA revealed a clear separation only between the 1000 mg/d and placebo groups (Q 2 Y= 0·763). The quercetin conjugate, isorhamnetin-3-glucuronide, had the highest concentration at 3 months followed by quercetin-3-glucuronide, quercetin-3-sulphate and quercetin diglucuronide. In human subjects, long-term quercetin supplementation exerts disparate and wide-ranging metabolic effects and changes in quercetin conjugate concentrations. Metabolic shifts were apparent at the 1000 mg/d dose; further research is required to understand the health implications of these shifts.
(Received April 10 2012)
(Revised August 03 2012)
(Accepted August 12 2012)
(Online publication November 14 2012)
Abbreviations: DHMRI, David H. Murdock Research Institute; ESI, electrospray ionisation; FDR, false discovery rate; IR-3-GlcUA, isorhamnetin-3-glucuronide; MTOB, 4-methylthio-2-oxo-butaroic acid; PLS-DA, partial least square discriminant analysis; Q-500, 500, 125 and 5 mg/d of quercetin, vitamin C and niacin supplementation, respectively; Q-1000, 1000, 250, 10 mg/d of quercetin, vitamin C and niacin supplementation, respectively; QTOFMS, quadrupole time-of-flight MS; TOFMS, time-of-flight MS; UPLC, ultra-performance liquid chromatography