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

  • Lynn Cialdella-Kam (a1), David C. Nieman (a1), Wei Sha (a2), Mary Pat Meaney (a1), Amy M. Knab (a1) and R. Andrew Shanely (a1)...
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 (Q2Y= 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.

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Corresponding author
*Corresponding author: D. C. Nieman, fax +1 704 250 5409, email niemandc@appstate.edu
References
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1US Department of Agriculture, Agricultural Research Service (2011) USDA Database for the Flavonoid Content of Selected Foods, release 3.0. Nutrient Data Laboratory Home page. http://www.ars.usda.gov/nutrientdata/flav.
2Ciz M, Pavelkova M, Gallova L, et al. (2008) The influence of wine polyphenols on reactive oxygen and nitrogen species production by murine macrophages RAW 264.7. Physiol Res 57, 393402.
3Najafzadeh M, Reynolds PD, Baumgartner A, et al. (2009) Flavonoids inhibit the genotoxicity of hydrogen peroxide (H(2)O(2)) and of the food mutagen 2-amino-3-methylimadazo[4,5-f]-quinoline (IQ) in lymphocytes from patients with inflammatory bowel disease (IBD). Mutagenesis 24, 405411.
4Dias AS, Porawski M, Alonso M, et al. (2005) Quercetin decreases oxidative stress, NF-kappaB activation, and iNOS overexpression in liver of streptozotocin-induced diabetic rats. J Nutr 135, 22992304.
5Comalada M, Camuesco D, Sierra S, et al. (2005) In vivo quercitrin anti-inflammatory effect involves release of quercetin, which inhibits inflammation through down-regulation of the NF-kappaB pathway. Eur J Immunol 35, 584592.
6Comalada M, Ballester I, Bailon E, et al. (2006) Inhibition of pro-inflammatory markers in primary bone marrow-derived mouse macrophages by naturally occurring flavonoids: analysis of the structure–activity relationship. Biochem Pharmacol 72, 10101021.
7Nair MP, Mahajan S, Reynolds JL, et al. (2006) The flavonoid quercetin inhibits proinflammatory cytokine (tumor necrosis factor alpha) gene expression in normal peripheral blood mononuclear cells via modulation of the NF-kappa beta system. Clin Vaccine Immunol 13, 319328.
8Chiang LC, Chiang W, Liu MC, et al. (2003) In vitro antiviral activities of Caesalpinia pulcherrima and its related flavonoids. J Antimicrob Chemother 52, 194198.
9Chen L, Li J, Luo C, et al. (2006) Binding interaction of quercetin-3-beta-galactoside and its synthetic derivatives with SARS-CoV 3CL(pro): structure–activity relationship studies reveal salient pharmacophore features. Bioorg Med Chem 14, 82958306.
10Cushnie TP & Lamb AJ (2005) Antimicrobial activity of flavonoids. Int J Antimicrob Agents 26, 343356.
11Davis JM, Murphy EA, McClellan JL, et al. (2008) Quercetin reduces susceptibility to influenza infection following stressful exercise. Am J Physiol Regul Integr Comp Physiol 295, R505R509.
12Vrijsen R, Everaert L & Boeye A (1988) Antiviral activity of flavones and potentiation by ascorbate. J Gen Virol 69, 17491751.
13Dimova S, Mugabowindekwe R, Willems T, et al. (2003) Safety-assessment of 3-methoxyquercetin as an antirhinoviral compound for nasal application: effect on ciliary beat frequency. Int J Pharm 263, 95103.
14An D, Zhang Q, Wu S, et al. (2010) Changes of metabolic profiles in urine after oral administration of quercetin in rats. Food Chem Toxicol 48, 15211527.
15Lin JP, Yang JS, Lu CC, et al. (2009) Rutin inhibits the proliferation of murine leukemia WEHI-3 cells in vivo and promotes immune response in vivo. Leuk Res 33, 823828.
16Nair MP, Kandaswami C, Mahajan S, et al. (2002) The flavonoid, quercetin, differentially regulates Th-1 (IFNgamma) and Th-2 (IL4) cytokine gene expression by normal peripheral blood mononuclear cells. Biochim Biophys Acta 1593, 2936.
17Knekt P, Kumpulainen J, Jarvinen R, et al. (2002) Flavonoid intake and risk of chronic diseases. Am J Clin Nutr 76, 560568.
18Neuhouser ML (2004) Dietary flavonoids and cancer risk: evidence from human population studies. Nutr Cancer 50, 17.
19Erdman JW Jr, Balentine D, Arab L, et al. (2007) Flavonoids and heart health: proceedings of the ILSI North America Flavonoids Workshop, May 31–June 1, 2005, Washington, DC. J Nutr 137, 718S737S.
20Mink PJ, Scrafford CG, Barraj LM, et al. (2007) Flavonoid intake and cardiovascular disease mortality: a prospective study in postmenopausal women. Am J Clin Nutr 85, 895909.
21Davis JM, Murphy EA, Carmichael MD, et al. (2009) Quercetin increases brain and muscle mitochondrial biogenesis and exercise tolerance. Am J Physiol Regul Integr Comp Physiol 296, R1071R1077.
22Edwards RL, Lyon T, Litwin SE, et al. (2007) Quercetin reduces blood pressure in hypertensive subjects. J Nutr 137, 24052411.
23Egert S, Bosy-Westphal A, Seiberl J, et al. (2009) Quercetin reduces systolic blood pressure and plasma oxidised low-density lipoprotein concentrations in overweight subjects with a high-cardiovascular disease risk phenotype: a double-blinded, placebo-controlled cross-over study. Br J Nutr 102, 10651074.
24Knab AM, Shanely RA, Henson DA, et al. (2011) Influence of quercetin supplementation on disease risk factors in community-dwelling adults. J Am Diet Assoc 111, 542549.
25Egert S, Wolffram S, Bosy-Westphal A, et al. (2008) Daily quercetin supplementation dose-dependently increases plasma quercetin concentrations in healthy humans. J Nutr 138, 16151621.
26Shanely RA, Knab AM, Nieman DC, et al. (2010) Quercetin supplementation does not alter antioxidant status in humans. Free Radic Res 44, 224231.
27Loke WM, Hodgson JM, Proudfoot JM, et al. (2008) Pure dietary flavonoids quercetin and ( − )-epicatechin augment nitric oxide products and reduce endothelin-1 acutely in healthy men. Am J Clin Nutr 88, 10181025.
28Egert S, Boesch-Saadatmandi C, Wolffram S, et al. (2010) Serum lipid and blood pressure responses to quercetin vary in overweight patients by apolipoprotein E genotype. J Nutr 140, 278284.
29Boots AW, Drent M, de Boer VC, et al. (2011) Quercetin reduces markers of oxidative stress and inflammation in sarcoidosis. Clin Nutr 30, 506512.
30Zulyniak MA & Mutch DM (2011) Harnessing metabolomics for nutrition research. Curr Pharm Biotechnol 12, 10051015.
31Bakker GC, van Erk MJ, Pellis L, et al. (2010) An antiinflammatory dietary mix modulates inflammation and oxidative and metabolic stress in overweight men: a nutrigenomics approach. Am J Clin Nutr 91, 10441059.
32de Boer VC, Dihal AA, van der Woude H, et al. (2005) Tissue distribution of quercetin in rats and pigs. J Nutr 135, 17181725.
33Loke WM, Proudfoot JM, McKinley AJ, et al. (2008) Quercetin and its in vivo metabolites inhibit neutrophil-mediated low-density lipoprotein oxidation. J Agric Food Chem 56, 36093615.
34Santos MR, Rodriguez-Gomez MJ, Justino GC, et al. (2008) Influence of the metabolic profile on the in vivo antioxidant activity of quercetin under a low dosage oral regimen in rats. Br J Pharmacol 153, 17501761.
35Mullen W, Edwards CA & Crozier A (2006) Absorption, excretion and metabolite profiling of methyl-, glucuronyl-, glucosyl- and sulpho-conjugates of quercetin in human plasma and urine after ingestion of onions. Br J Nutr 96, 107116.
36Egert S, Wolffram S, Schulze B, et al. (2012) Enriched cereal bars are more effective in increasing plasma quercetin compared with quercetin from powder-filled hard capsules. Br J Nutr 107, 539546.
37Hodge A, Patterson AJ, Brown WJ, et al. (2000) The Anti Cancer Council of Victoria FFQ: relative validity of nutrient intakes compared with weighed food records in young to middle-aged women in a study of iron supplementation. Aust N Z J Public Health 24, 576583.
38Heinz SA, Henson DA, Nieman DC, et al. (2010) A 12-week supplementation with quercetin does not affect natural killer cell activity, granulocyte oxidative burst activity or granulocyte phagocytosis in female human subjects. Br J Nutr 104, 849857.
39Root MM, McGinn MC, Nieman DC, et al. (2012) Combined fruit and vegetable intake is correlated with improved inflammatory and oxidant status from a cross-sectional study in a community setting. Nutrients 4, 2941.
40Qiu Y, Cai G, Su M, et al. (2009) Serum metabolite profiling of human colorectal cancer using GC-TOFMS and UPLC-QTOFMS. J Proteome Res 8, 48444850.
41Qiu Y, Cai G, Su M, et al. (2010) Urinary metabonomic study on colorectal cancer. J Proteome Res 9, 16271634.
42Wishart DS, Knox C, Guo AC, et al. (2009) HMDB: a knowledgebase for the human metabolome. Nucleic Acids Res 37, D603D610.
43Mimurai T, Yazaki K, Sawaki K, et al. (2005) Hydroxyl radical scavenging effects of guaiacol used in traditional dental pulp sedation: reaction kinetic study. Biomed Res 26, 139145.
44Kanehisa M, Goto S, Furumichi M, et al. (2010) KEGG for representation and analysis of molecular networks involving diseases and drugs. Nucleic Acids Res 38, D355D360.
45Stipanuk MH & Ueki I (2011) Dealing with methionine/homocysteine sulfur: cysteine metabolism to taurine and inorganic sulfur. J Inherit Metab Dis 34, 1732.
46Quash G & Fournet G (2009) Methionine-derived metabolites in apoptosis: therapeutic opportunities for inhibitors of their metabolism in chemoresistant cancer cells. Curr Med Chem 16, 36863700.
47Lodi F, Jimenez R, Moreno L, et al. (2009) Glucuronidated and sulfated metabolites of the flavonoid quercetin prevent endothelial dysfunction but lack direct vasorelaxant effects in rat aorta. Atherosclerosis 204, 3439.
48Bieger J, Cermak R, Blank R, et al. (2008) Tissue distribution of quercetin in pigs after long-term dietary supplementation. J Nutr 138, 14171420.
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