Higher plasma quercetin levels following oral administration of an onion skin extract compared with pure quercetin dihydrate in humans
To investigate the plasma kinetics of quercetin derived from hard capsules filled with onion skin extract powder or quercetin dihydrate in humans.
In a randomized, single-blind, diet-controlled crossover study, 12 healthy subjects (six men and six women) aged 21–33 years were administered a single oral supra-nutritional dose of approximately 163 mg quercetin derived from onion skin extract powder (containing 95.3 % of total flavonoids as quercetin aglycone) or quercetin dihydrate (134 mg quercetin aglycone equivalent). Blood samples were collected before and during a 24-h period after quercetin administration. The concentrations of quercetin and its two monomethylated derivatives, isorhamnetin (3′-O-methyl quercetin), and tamarixetin (4′-O-methyl quercetin), were measured using HPLC with fluorescence detection after plasma enzymatic treatment.
The systemic availability, determined by comparing the plasma concentration–time curves of quercetin, was 4.8 times higher, and the maximum plasma concentration (Cmax) was 5.4 times higher after ingestion of the onion skin extract than after ingestion of pure quercetin dihydrate. By contrast, tmax did not differ significantly between the two formulations. The Cmax values for isorhamnetin and tamarixetin were 3.8 and 4.4 times higher, respectively, after administration of onion skin extract than after pure quercetin dihydrate. The plasma kinetics of quercetin were not significantly different in men and women.
Quercetin aglycone derived from onion skin extract powder is significantly more bioavailable than that from quercetin dihydrate powder filled hard capsules.
KeywordsQuercetin Bioavailability Onion Human study
Area under the plasma concentration–time curve
Maximum plasma concentration
Elimination rate constant
Time at maximum quercetin plasma concentration Cmax
- 2.U.S. Department of Agriculture (2013) USDA database for the flavonoid content of selected foods, release 3.1. http://www.ars.usda.gov/Services/docshtm?docid=6231
- 3.Erdman JW Jr, Balentine D, Arab L, Beecher G, Dwyer JT, Folts J, Harnly J, Hollman P, Keen CL, Mazza G, Messina M, Scalbert A, Vita J, Williamson G, Burrowes J (2007) Flavonoids and heart health: proceedings of the ILSI North America Flavonoids Workshop, May 31–June 1, 2005, Washington, DC. J Nutr 137:718S–737SGoogle Scholar
- 4.Scalbert A, Williamson G (2000) Dietary intake and bioavailability of polyphenols. J Nutr 130:2073S–2085SGoogle Scholar
- 11.Egert S, Bosy-Westphal A, Seiberl J, Kurbitz C, Settler U, Plachta-Danielzik S, Wagner AE, Frank J, Schrezenmeir J, Rimbach G, Wolffram S, Müller MJ (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 102:1065–1074CrossRefGoogle Scholar
- 13.Brüll V, Burak C, Stoffel-Wagner B, Wolffram S, Nickenig G, Muller C, Langguth P, Alteheld B, Fimmers R, Naaf S, Zimmermann BF, Stehle P, Egert S (2015) Effects of a quercetin-rich onion skin extract on 24 h ambulatory blood pressure and endothelial function in overweight-to-obese patients with (pre-)hypertension: a randomised double-blinded placebo-controlled cross-over trial. Br J Nutr 114:1263–1277CrossRefGoogle Scholar
- 15.Egert S, Wolffram S, Bosy-Westphal A, Boesch-Saadatmandi C, Wagner AE, Frank J, Rimbach G, Müller MJ (2008) Daily quercetin supplementation dose-dependently increases plasma quercetin concentrations in healthy humans. J Nutr 138:1615–1621Google Scholar
- 16.Boesch-Saadatmandi C, Egert S, Schrader C, Coumol X, Barouki R, Muller MJ, Wolffram S, Rimbach G (2010) Effect of quercetin on paraoxonase 1 activity-studies in cultured cells, mice and humans. J Physiol Pharmacol 61:99–105Google Scholar
- 18.Olthof MR, Hollman PC, Vree TB, Katan MB (2000) Bioavailabilities of quercetin-3-glucoside and quercetin-4′-glucoside do not differ in humans. J Nutr 130:1200–1203Google Scholar
- 19.Hollman PC, de Vries JH, van Leeuwen SD, Mengelers MJ, Katan MB (1995) Absorption of dietary quercetin glycosides and quercetin in healthy ileostomy volunteers. Am J Clin Nutr 62:1276–1282Google Scholar
- 20.Wiczkowski W, Romaszko J, Bucinski A, Szawara-Nowak D, Honke J, Zielinski H, Piskula MK (2008) Quercetin from shallots (Allium cepa L. var. aggregatum) is more bioavailable than its glucosides. J Nutr 138:885–888Google Scholar
- 23.Bieger J, Cermak R, Blank R, de Boer VC, Hollman PC, Kamphues J, Wolffram S (2008) Tissue distribution of quercetin in pigs after long-term dietary supplementation. J Nutr 138:1417–1420Google Scholar
- 24.Sun SS, Chumlea WC, Heymsfield SB, Lukaski HC, Schoeller D, Friedl K, Kuczmarski RJ, Flegal KM, Johnson CL, Hubbard VS (2003) Development of bioelectrical impedance analysis prediction equations for body composition with the use of a multicomponent model for use in epidemiologic surveys. Am J Clin Nutr 77:331–340Google Scholar
- 25.Bruno RS, Leonard SW, Park SI, Zhao Y, Traber MG (2006) Human vitamin E requirements assessed with the use of apples fortified with deuterium-labeled alpha-tocopheryl acetate. Am J Clin Nutr 83:299–304Google Scholar
- 27.Zamora-Ros R, Forouhi NG, Sharp SJ, Gonzalez CA, Buijsse B, Guevara M, van der Schouw YT, Amiano P, Boeing H, Bredsdorff L, Fagherazzi G, Feskens EJ, Franks PW, Grioni S, Katzke V, Key TJ, Khaw KT, Kuhn T, Masala G, Mattiello A, Molina-Montes E, Nilsson PM, Overvad K, Perquier F, Redondo ML, Ricceri F, Rolandsson O, Romieu I, Roswall N, Scalbert A, Schulze M, Slimani N, Spijkerman AM, Tjonneland A, Tormo MJ, Touillaud M, Tumino R, van der AD, van Woudenbergh GJ, Langenberg C, Riboli E, Wareham NJ (2014) Dietary intakes of individual flavanols and flavonols are inversely associated with incident type 2 diabetes in European populations. J Nutr 144:335–343CrossRefGoogle Scholar
- 30.Manach C, Williamson G, Morand C, Scalbert A, Remesy C (2005) Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. Am J Clin Nutr 81:230S–242SGoogle Scholar
- 31.Williamson G, Manach C (2005) Bioavailability and bioefficacy of polyphenols in humans. II. Review of 93 intervention studies. Am J Clin Nutr 81:243S–255SGoogle Scholar
- 32.Manach C, Scalbert A, Morand C, Remesy C, Jimenez L (2004) Polyphenols: food sources and bioavailability. Am J Clin Nutr 79:727–747Google Scholar
- 37.de Boer VC, Dihal AA, van der WH, Arts IC, Wolffram S, Alink GM, Rietjens IM, Keijer J, Hollman PC (2005) Tissue distribution of quercetin in rats and pigs. J Nutr 135:1718–1725Google Scholar
- 38.Zhu BT, Ezell EL, Liehr JG (1994) Catechol-O-methyltransferase-catalyzed rapid O-methylation of mutagenic flavonoids. Metabolic inactivation as a possible reason for their lack of carcinogenicity in vivo. J Biol Chem 269:292–299Google Scholar
- 39.Saha S, Hollands W, Needs PW, Ostertag LM, de Roos B, Duthie GG, Kroon PA (2012) Human O-sulfated metabolites of (−)-epicatechin and methyl-(−)-epicatechin are poor substrates for commercial aryl-sulfatases: implications for studies concerned with quantifying epicatechin bioavailability. Pharmacol Res 65:592–602CrossRefGoogle Scholar