British Journal of Nutrition

Full Papers

Metabolism and Metabolic Studies

Dose–response to 3 months of quercetin-containing supplements on metabolite and quercetin conjugate profile in adults

Lynn Cialdella-Kama1, David C. Niemana1 c1, Wei Shaa2, Mary Pat Meaneya1, Amy M. Knaba1 and R. Andrew Shanelya1

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)

Key Words:

  • Dietary supplements;
  • Flavonols;
  • Metabolic profiling;
  • Quercetin conjugates


  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