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Anthocyanin metabolites in human urine and serum

Published online by Cambridge University Press:  09 March 2007

Colin D. Kay ,
G. Mazza ,
Bruce J. Holub  and
Jian Wang
Colin D. Kay
Affiliation:
Pacific Agri-Food Research Center, Agriculture and Agri-Food Canada, 4200 Hwy 97 Summerland, British Columbia, Canada V0H 1Z0 Department of Human Biology and Nutritional Sciences, University of Guelph, Ontario, Canada
G. Mazza*
Affiliation:
Pacific Agri-Food Research Center, Agriculture and Agri-Food Canada, 4200 Hwy 97 Summerland, British Columbia, Canada V0H 1Z0 Department of Human Biology and Nutritional Sciences, University of Guelph, Ontario, Canada
Bruce J. Holub
Affiliation:
Department of Human Biology and Nutritional Sciences, University of Guelph, Ontario, Canada
Jian Wang
Affiliation:
Calgary Laboratory, Canadian Food Inspection Agency, Calgary, Alberta, Canada
*
*Corresponding author: Dr G. (Joe) Mazza, fax +1 250 494 0755, email [email protected]
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Abstract

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In the present study we investigated the metabolic conversion of cyanidin glycosides in human subjects using solid-phase extraction, HPLC–diode array detector, MS, GC, and enzymic techniques. Volunteers consumed approximately 20 g chokeberry extract containing 1·3 g cyanidin 3-glycosides (899 mg cyanidin 3-galactoside, 321 mg cyanidin 3-arabinoside, 51 mg cyanidin 3-xyloside and 50 mg cyanidin 3-glucoside). Blood samples were drawn at 0, 0·5, 1, and 2 h post-consumption of the extract. Urine samples were also collected at 0, 4–5, and 22–24 h. We have confirmed that human subjects have the capacity to metabolise cyanidin 3-glycosides, as we observed at least ten individual anthocyanin metabolites in the urine and serum. Average concentrations of anthocyanins and anthocyanin metabolites in the urine reached levels of 17·9 (range 14·9–20·9) μmol/l within 5 h post-consumption and persisted in 24 h urine samples at levels of 12·1 (range 11·1–13·0) nmol/l. In addition, average total levels of anthocyanins and anthocyanin metabolites detected in the serum were observed at 591·7 (range 197·3–986·1) nmol/l within 2 h post-consumption. Cyanidin 3-galactoside accounted for 55·4 % (9·9 (range 7·2–12·6) μmol/l) and 66·0 % (390·6 (range 119·4–661·9) nmol/l) of the detected anthocyanins in the urine and serum samples, respectively. The metabolites were identified as glucuronide conjugates, as well as methylated and oxidised derivatives of cyanidin 3-galactoside and cyanidin glucuronide. Conjugation probably affects the biological activity of anthocyanins and these metabolic products are likely in part responsible for the reported health benefits associated with the consumption of anthocyanins.

Keywords

FlavonoidsCyanidin 3-glycosidesGlucuronideMethylated anthocyanins
Type
Research Article
Information
British Journal of Nutrition , Volume 91 , Issue 6 , June 2004 , pp. 933 - 942
Copyright
Copyright © The Nutrition Society 2004

References

Andriambeloson, E, Magnier, C, Haan-Archipoff, G, Lobstein, A, Anton, R, Beretz, A, Stoclet, JC & Andriantsitohaina, R (1998) Natural dietary polyphenolic compounds cause endothelium-dependent vasorelaxation in rat thoracic aorta. J Nutr 128, 2324–2333.CrossRefGoogle ScholarPubMed
Buset, H & Scheline, RR (1980) Disposition of [2-14C]flavone in the rat. Acta Pharm Suec 17, 157–165.Google Scholar
Chandra, A, Rana, J & Li, Y (2001) Separation, identification, quantification and method validation of anthocyanins in botanical supplement raw material by HPLC and HPLC-MS. J Agric Food Chem 49, 3515–3521.CrossRefGoogle ScholarPubMed
Day, AJ, Bao, Y, Morgan, MRA & Williamson, G (2000) Conjugation position of quercetin glucuronides and effect on biological activity. Free Radic Biol Med 29, 1234–1243.CrossRefGoogle ScholarPubMed
Day, AJ & Williamson, G (2001) Biomarkers for exposure to dietary flavonoids: a review of the current evidence for identification of quercetin glycosides in plasma. Br J Nutr 86, Suppl. 1, S105–S110.CrossRefGoogle ScholarPubMed
Donovan, JL, Crespy, V, Manach, C, Morand, C, Besson, C, Scalbert, A & Rémésy, C (2001) Catechin is metabolised by both the small intestine and liver of rats. J Nutr 131, 1753–1757.CrossRefGoogle Scholar
Doostdar, H, Burke, MD & Mayer, RT (2000) Bioflavonoids: selective substrates and inhibitors for cytochrome P450 CYP1A and CYP1B1. Toxicology 144, 31–38.CrossRefGoogle ScholarPubMed
Dutton, GJ (1980) Glucuronidation of Drugs and Other Compounds. Boca Raton, FL: CRC Press.Google Scholar
Felgines, C, Talavera, S, Gonthier, MP, Texier, O, Scalbert, A, Lamaison, JL & Remesy, C (2003) Strawberry anthocyanins are recovered in urine as glucuro- and sulfoconjugates in humans. J Nutr 133, 1296–1301.CrossRefGoogle ScholarPubMed
Gao, L & Mazza, G (1994) A rapid method for complete characterization of simple and acylated anthocyanins by high performance liquid chromatography and capillary gas liquid chromatography. J Agric Food Chem 42, 118–125.CrossRefGoogle Scholar
Griffiths, LA (1982) Mammalian metabolism of flavonoids. In The Flavonoids: Advances in Research, pp.681–718 [Mabry, T and Harborne, J, editors]. London: Chapman & Hall.CrossRefGoogle Scholar
Harborne, JB (1958) Spectral methods of characterizing anthocyanins. Biochem J 70, 22–28.CrossRefGoogle ScholarPubMed
Holder, CL, Churchwell, MI & Doerge, DR (1999) Quantification of soy isoflavones, genistein and daidzein, and conjugates in rat blood using LC/ES-MS. J Agric Food Chem 47, 3764–3770.CrossRefGoogle ScholarPubMed
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, 1276–1282.CrossRefGoogle ScholarPubMed
Hollman, PC & Katan, MB (1998) Absorption, metabolism and bioavailability of flavonoids. In Flavonoids in Health and Disease, pp.483–522 [Rice-Evans, CA and Packer, L, editors]. NewYork: Marcel Dekker, Inc.Google Scholar
Kamei, H, Kojima, T, Hasegawa, M, Koide, T, Umeda, T, Yukawa, T & Terabe, K (1995) Suppression of tumor cell growth by anthocyanins in vitro. Cancer Invest 13, 590–594.CrossRefGoogle ScholarPubMed
Kuhnle, G, Spencer, JP, Chowrimootoo, G, Schroeter, H, Debnam, ES, Srai, SK, Rice-Evans, C & Hahn, U (2000) Resveratrol is absorbed in the small intestine as resveratrol glucuronide. Biochem Biophys Res Commun 272, 212–217.CrossRefGoogle ScholarPubMed
Laitinen, M & Watkins, JB (1986) Mucosal biotransformations. In Gastrointestinal Toxicology, pp.169–192 [Rozman, K and Hänninen, O, editors]. New York: Elsevier.Google Scholar
Laplaud, PM, Lelubre, A & Chapman, MJ (1997) Antioxidant action of Vaccinium myrtillus extract on human low density lipoproteins in vitro: initial observations. Fundam Clin Pharmacol 11, 35–40.CrossRefGoogle ScholarPubMed
Mazza, G (2000) Health aspects of natural colors.In Natural Food Colorants: Science and Technology, pp. 289–314 [Lauro, GJ and Francis, FJ, editors]. New York: Marcel Dekker, Inc.Google Scholar
Mazza, G, Kay, C, Cottrell, T & Holub, B (2002) Absorption of anthocyanins from blueberries and serum antioxidant status in humans. J Agric Food Chem 50, 7731–7737.CrossRefGoogle Scholar
Miyazawa, T, Nakagawa, K, Kudo, M, Muraishi, K & Someya, K (1999) Direct intestinal absorption of red fruit anthocyanins, cyanidin-3-glucoside and cyanidin-3,5-diglucoside, into rats and humans. J Agric Food Chem 47, 1083–1091.CrossRefGoogle ScholarPubMed
Mizuma, T, Ohta, K & Awazu, S (1994) The beta-anomeric and glucose preferences of glucose transport carrier for intestinal active absorption of monosaccharide conjugates. Biochim Biophys Acta 1200, 117–122.CrossRefGoogle ScholarPubMed
Mülleder, U, Murkovic, M & Pfannhauser, W (2002) Urinary excretion of cyanidin glycosides. J Biochem Biophys Methods 53, 61–66.CrossRefGoogle ScholarPubMed
Murkovic, M, Adam, U & Pfannhauser, W (2000) Analysis of anthocyane glycosides in human serum. Fresenius J Anal Chem 366, 379–381.CrossRefGoogle ScholarPubMed
Okushio, K, Suzuki, M, Matsumoto, N, Nanjo, F & Hara, Y (1999) Identification of (-)-epicatechin metabolites and their metabolic fate in the rat. Drug Metab Dispos 27, 309–316.Google ScholarPubMed
Oliveira, EJ, Watson, DG & Grant, MH (2002) Metabolism of quercetin and kaempferol by rat hepatocytes and the identification of flavonoid glycosides in human plasma. Xenobiotica 32, 279–287.CrossRefGoogle ScholarPubMed
Parthasarathy, S, Khan-Merchant, N, Penumetcha, M & Santanam, N (2001) Oxidative stress in cardiovascular disease. J Nucl Cardiol 8, 379–389.CrossRefGoogle ScholarPubMed
Piskula, MK & Terao, J (1998) Accumulation of (-)-epicatechin metabolites in rat plasma after oral administration and distribution of conjugation enzymes in rat tissues. J Nutr 128, 1172–1178.CrossRefGoogle ScholarPubMed
Rozman, K (1986) Fecal excretion of toxic substances. In Gastrointestinal Toxicology 119–145 [Rozman, K and Hänninen, O, editors]. New York: Elsevier.Google Scholar
Spencer, JP, Chowrimootoo, G, Choudhury, R, Debnam, ES, Srai, SK & Rice-Evans, C (1999) The small intestine can both absorb and glucuronidate luminal flavonoids. FEBS Lett 458, 224–230.CrossRefGoogle ScholarPubMed
Suda, I, Oki, T, Masuda, M, Nishiba, Y, Furuta, S, Matsugano, K, Sugita, K & Terahara, N (2002) Direct absorption of acylated anthocyanin in purple-fleshed sweet potato in rats. J Agric Food Chem 50, 1672–1676.CrossRefGoogle Scholar
Trevithick, JR & Mitton, KP (1999) Antioxidants and diseases of the eye. In Antioxidant Status, Diet, Nutrition, and Health, pp. 545– 566 [Papus, AM, editors]. NewYork: CRC Press.Google Scholar
Tsuda, T, Horio, F & Osawa, T (1999) Absorption and metabolism of cyanidin 3-O-beta-D-glucoside in rats. FEBS Lett 449, 179–182.CrossRefGoogle ScholarPubMed
Walle, T, Otake, Y, Walle, UK & Wilson, FA (2000) Quercetin glucosides are completely hydrolyzed in ileostomy patients before absorption. J Nutr 130, 2658–2661.CrossRefGoogle ScholarPubMed
Wermeille, M, Turin, E & Griffiths, LA (1983) Identification of the major urinary metabolites of (+)-catechin and 3-O- methyl-(+)-catechin in man. Eur J Drug Metab Pharmacokinet 8, 77–84.CrossRefGoogle Scholar
Williamson, G, Day, AJ, Plumb, GW & Couteau, D (2000) Human metabolic pathways of dietary flavonoids and cinnamates. Biochem Soc Trans 28, 16–22.CrossRefGoogle ScholarPubMed
Wolffram, S, Weber, T, Grenacher, B & Scharrer, E (1995) A Na(+)-dependent mechanism is involved in mucosal uptake of cinnamic acid across the jejunal brush border in rats. J Nutr 125, 1300–1308.Google Scholar
Wu, X, Cao, G & Prior, RL (2002) Absorption and metabolism of anthocyanins in elderly women after consumption of elderberry or blueberry. J Nutr 132, 1865–1871.Google ScholarPubMed