title: Dose-response to 3 months of quercetin-containing supplements on metabolite and quercetin conjugate profile in adults.
abstract: 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.
authors.affiliation: Human Performance Laboratory, North Carolina Research Campus, Appalachian State University, 600 Laureate Way, Kannapolis, NC, USA.
authors.forename: Lynn
authors.initials: L
authors.lastname: Cialdella-Kam
authors.forename: David C
authors.initials: DC
authors.lastname: Nieman
authors.forename: Wei
authors.initials: W
authors.lastname: Sha
authors.forename: Mary Pat
authors.initials: MP
authors.lastname: Meaney
authors.forename: Amy M
authors.initials: AM
authors.lastname: Knab
authors.forename: R Andrew
authors.initials: RA
authors.lastname: Shanely
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000975:Antioxidants / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009525:Niacin / Q000008:administration & dosage / Q000493:pharmacokinetics; D011794:Quercetin / Q000008:administration & dosage* / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D009525:Niacin; D011794:Quercetin; D001205:Ascorbic Acid