Skip to main content

Human Metabolism of Dietary Quercetin Glycosides

  • Chapter
Plant Polyphenols 2

Part of the book series: Basic Life Sciences ((BLSC,volume 66))

Abstract

Flavonoids, along with other phytochemicals, are thought to have a role in reducing the risk of chronic diseases such as coronary heart disease and cancers.1,2 Fruits and vegetables undoubtedly afford some protection against these diseases,3 but the effects of individual compounds that may play a role is unclear. Evidence has been accumulating from both in vivo and in vitro studies that flavonoids have biological activity that may be beneficial. They are good antioxidants and can act by scavenging free radicals, chelation of metal ions or inhibiting lipid peroxidation,4 and they can inhibit platelet aggregation.5 Flavonols also have the ability to induce phase II detoxification enzymes6 and have been shown to inhibit the growth of certain human cancer cells such as those of the colon,7 ovary,8 and gastrointestinal tract.9

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Middleton, E.; Kandaswami, C. The impact of plant flavonoids on mammalian biology: implications for immunity, inflammation and cancer. In: Harborne, J.B. (ed.) The flavonoids: advances in research since 1986. Chapman and Hall, London p. 619 (1994).

    Google Scholar 

  2. Huang, M.-T.; Ferraro, T. Phenolic compounds in food and cancer prevention. In: Huang, M.-T.; Ho, C.-T.; Lee, C.Y. (eds.) Phenolic compounds in food and their effects on health II. American Chemical Society, Washington, DC. p. 8 (1992).

    Chapter  Google Scholar 

  3. Block G.; Patterson B.; Subar A. Fruit, vegetables and cancer prevention: a review of the epidemiological evidence. Nutr. Cancer 18:1 (1992).

    Article  PubMed  CAS  Google Scholar 

  4. Cotelle N.; Bernier J.-L.; Catteau J.-P.; Pommery J.; Wallet J.-C.; Gaydou E.M. Antioxidant properties of hydroxy-flavones. Free Rad. Biol. Med. 20:35 (1996).

    Article  PubMed  CAS  Google Scholar 

  5. Tzeng S.H.; Ko W.C.; Ko F.N.; Teng C.M. Inhibition of platelet aggregation by some flavonoids. Thromb. Res. 64:91 (1991).

    Article  PubMed  CAS  Google Scholar 

  6. Uda Y.; Price K.R.; Williamson G.; Rhodes M.J.C. Induction of the anticarcinogenic marker enzyme quinone reductase in murine hepatoma cells in vitro by flavonoids. Cancer Lett. 120:213 (1997).

    Article  PubMed  CAS  Google Scholar 

  7. Ranelletti F.O.; Ricci R.; Larocca L.M. Growth inhibitory effects of quercetin and presence of estrogen binding sites in human colon cancer cell lines and primary colorectal tumours. Int. J. Cancer 50:486 (1992).

    Article  PubMed  CAS  Google Scholar 

  8. Scambia G.; Ranelletti F.O.; Panici P.B.; Piantelli M.; Bonanno G.; Devincenzo R.; Ferrandina G.; Rumi C.; Larocca L.M.; Mancuso S. Inhibitory effects of quercetin on OVCA-433 cells and presence of type II oestrogen binding sites in primary ovarian tumours and cultured cells. Brit. J. Cancer 62:942 (1990).

    Article  PubMed  CAS  Google Scholar 

  9. Yoshida M.; Sakai T.; Hosokawa N.; Marui N.; Matsumoto K.; Fujioka A.; Nishino H.; Aoika A. The effect of quercetin on cell cycle progression and growth of human gastric cancer cells. FEBS Lett. 260:10 (1990).

    Article  PubMed  CAS  Google Scholar 

  10. Rice-Evans C.A.; Miller N.J.; Paganga G. Structure—antioxidant activity relationships of flavonoids and phenolic acids. Free Rad. Biol. Med. 20:933 (1996).

    Article  PubMed  CAS  Google Scholar 

  11. Fossen T.; Pedersen A.T.; Andersen O.M. Flavonoids from red onion (Allium Capa). Phytochemistry 47:281 (1998).

    Article  CAS  Google Scholar 

  12. Kühnau, J. The flavonoids: a class of semi-essential food components: their role in human nutrition. Wld. Rev. Nutr. Diet 24:117 (1976).

    Google Scholar 

  13. Hertog M.G.L.; Hollman P.C.H.; Katan M.B.; Kromhout D. Intake of potentially anticarcinogenic flavonoids and their determinants in adults in The Netherlands. Nutr. Cancer 20:21 (1993).

    Article  PubMed  CAS  Google Scholar 

  14. Herrmann K. Flavonols and flavones in food plant: a review. J. Food Tech. 11:433 (1976).

    Article  CAS  Google Scholar 

  15. Hertog M.G.L.; Kromhout D.; Aravanis C.; Blackburn H.; Buzina R.; Fidanza F.; Giampaoli S.; Jansen A.; Menotti A.; Nedeljkovic S.; Pekkarinen M.; Simic B.S.; Toshima H.; Feskens E.J.M.; Hollman P.C.H.; Katan M.B. Flavonoid intake and long-term risk of coronary heart disease and cancer in the seven countries study. Arch. Intern. Med. 155:381 (1995).

    Article  PubMed  CAS  Google Scholar 

  16. Hertog M.G.L.; Hollman P.C.H.; Katan M.B. Content of potentially anticarcinogenic flavonoids of 28 vegetables and 9 fruits commonly consumed in The Netherlands. J. Agric. Food Chem. 40:2379 (1992).

    Article  CAS  Google Scholar 

  17. Price K.R.; Rhodes M.J.C.; Barnes K.A. Flavonol glycoside content and composition of tea infusions made from commercially available teas and tea products. J. Agric. Food Chem. 46:2517 (1998).

    Article  CAS  Google Scholar 

  18. Hertog M.G.; Feskens E.J.M.; Hollman P.C.H.; Katan M.B.; Kromhout D. Dietary antioxidant flavonoids and risk of coronary heart disease: The Zutphen Elderly Study. The Lancet 342:1007 (1993).

    Article  CAS  Google Scholar 

  19. Knekt P.; Jarvinen R.; Reunanen A.; Maatela J. Flavonoid intake and coronary mortality in Finland: a cohort study. BMJ 312:478 (1996).

    Article  PubMed  CAS  Google Scholar 

  20. Keli S.O.; Hertog M.G.L.; Feskens E.J.M.; Kromhout D. Dietary flavonoids, antioxidant vitamins, and incidence of stroke. Arch. Intern. Med. 156:637 (1996).

    Article  PubMed  CAS  Google Scholar 

  21. Rimm E.B.; Katan M.B.; Ascherio A.; Stampfer M.J.; Willett W.C. Relation between intake of flavonoids and risk for coronary heart disease in male health professionals. Ann. Intern. Med. 125:384 (1996).

    PubMed  CAS  Google Scholar 

  22. Hertog M.G.L.; Sweetnam P.M.; Fehily A.M.; Elwood P.C.; Kromhout D. Antioxidant flavonols and ischemic heart disease in a Welsh population of men: the Caerphilly study. Am. J. Clin. Nutr. 65:1489 (1997).

    PubMed  CAS  Google Scholar 

  23. Hertog G.L.; Feskens E.J.M.; Kromhout D. Antioxidant flavonols and coronary heart disease risk. The Lancet 349:699 (1997).

    Article  CAS  Google Scholar 

  24. van het Hof K.H.; Kivits G.A.A.; Weststrate J.A.; Tijburg L.B.M. Bioavailability of catechins from tea: the effect of milk. Eur. J. Clin. Nutr. 52:356 (1998).

    Article  Google Scholar 

  25. Price K.R.; Casuscelli F.; Colquhoun I.J.; Rhodes M.J.C. Composition and content of flavonol glycosides in broccoli florets (Brassica olearacea) and their fate during cooking. J. Sci. Food Agric. 77:468 (1998).

    Article  CAS  Google Scholar 

  26. Price K.R.; Bacon J.R.; Rhodes M.J.C. Effect of storage and domestic processing on the content and composition of flavonol glucosides in onion (Allium cepa). J. Agric. Food Chem. 45:938 (1997).

    Article  CAS  Google Scholar 

  27. Price K.R.; Colquhoun I.J.; Barnes K.A.; Rhodes M.J.C. The composition and content of flavonol glycosides in green beans and their fate during processing. J. Agric. Food Chem. 48:4898 (1998).

    Article  Google Scholar 

  28. Crozier A.; Lean M.E.J.; McDonald M.S.; Black C. Quantitative analysis of the flavonoid content of commercial tomatoes, onions, lettuce, and celery. J. Agric. Food Chem. 45:590 (1997).

    Article  CAS  Google Scholar 

  29. Tsushida T.; Suzuki M. Content of flavonoid glucosides and some properties of enzymes metabolizing the glucoside in onion. Nippon Shokuhin Kagaku Kaishi 43:642 (1996).

    Article  CAS  Google Scholar 

  30. Price K.R.; Rhodes M.J.C. Analysis of the major flavonol glycosides present in four varieties of onion and changes in composition resulting from autolysis. J. Sci. Food Agric. 74:331 (1997).

    Article  CAS  Google Scholar 

  31. McDonald M.S.; Hughes M.; Burns J.; Lean M.E.J.; Matthews D.; Crozier A. Survey of the free and conjugated myricetin and quercetin content of red wines of different geographical origins. J. Agric. Food Chem. 46:368 (1998).

    Article  PubMed  CAS  Google Scholar 

  32. Hollman, P.C.H. Determinants of the absorption of the dietary flavonoid quercetin in man. Ph.D Thesis, Wageningen Agricultural University, The Netherlands (1997).

    Google Scholar 

  33. Hollman P.C.H.; de Vries J.H.M.; van Leeuwen S.D.; Mengelers M.J.B.; Katan M.B. Absorption of dietary quercetin glycosides and quercetin in healthy ileostomy volunteers. Am. J. Clin. Nutr. 62:1276 (1995).

    PubMed  CAS  Google Scholar 

  34. Hollman P.C.H.; van Trijp J.M.P.; Buysman M.N.C.P. Fluorescence detection of flavonols in HPLC by postcolumn chelation with aluminium. Anal. Chem. 68:3511 (1996).

    Article  PubMed  CAS  Google Scholar 

  35. Hollman P.C.H.; Gaag M.V.D.; Mengelers M.J.B.; van Trijp J.M.P.; de Vries J.H.M.; Katan M.B. Absorption and disposition kinetics of the dietary antioxidant quercetin in man. Free Rad. Biol. Med. 21:703 (1996).

    Article  PubMed  CAS  Google Scholar 

  36. Hollman P.C.H.; Van Trijp, J.M.P.; Buysman M.N.C.P.; Gaag M.S.; Mengelers M.J.B.; de Vries J.H.M.; Katan M.B. Relative bioavailablity of the antioxidant quercetin from various foods in man. FEBS Lett. 418:152 (1997).

    Article  PubMed  CAS  Google Scholar 

  37. de Vries J.H.M.; Hollman P.C.H.; Meyboom S.; Buysman M.N.C.P.; Zock P.L.; van Staveren W.A.; Katan M.B. Plasma concentrations and urinary excretion of the antioxidant flavonols quercetin and kaempferol as biomarkers for dietary intake. Am. J. Clin. Nutr. 68:60 (1998).

    PubMed  Google Scholar 

  38. Janseen P.L.T.M.; Mensink R.P.; Cox F.J.J.; Harryvan J.L.; Hovenier R.; Hollman P.C.H.; Katan M.B. Effects of the flavonoids quercetin and apigenin on hemostasis in healthy volunteers: results from an in vitro and a dietary supplement study. Am. J. Clin. Nutr. 67:255 (1998).

    Google Scholar 

  39. Nielsen, S.E. Metabolism and biomarker studies of dietary flavonoids. Ph.D thesis, Danish Veterinary and Food Administration, Denmark (1998).

    Google Scholar 

  40. Young J.F.; Nielsen S.E.; Haraldsdottir J.; Daneshvar B.; Lauridsen S.T.; Knuthsen P.; Crozier A.; Sandstrom B.; Dragsted L.O. Effect of fruit juice intake on urinary quercetin excretion and biomarkers of antioxidant status. Am. J. Clin. Nutr. 69:87 (1999).

    PubMed  CAS  Google Scholar 

  41. Gee J.M.; DuPont M.S.; Rhodes M.J.C; Johnson I.T. Quercetin glucosides interact with the intestinal glucose transport pathway. Free Rad. Biol. Med. 25:19 (1998).

    Article  PubMed  CAS  Google Scholar 

  42. Paganga G.; Rice-Evans C. The identification of flavonoids as glycosides in human plasma. FEBS Lett. 401:78 (1997).

    Article  PubMed  CAS  Google Scholar 

  43. Frank, H.K. Dictionary of food microbiology. Technonomic Publishing Company, Lancaster, USA (1992).

    Google Scholar 

  44. Hackett, A.M. The metabolism of flavonoid compounds in mammals. In: Cody, V.; Middleton, E.; Harborne, J.B. (eds.) Plant flavonoids in biology and medicine: biochemical, pharmological and structure-activity relationships. Alan Liss Inc., New York p. 177 (1986).

    Google Scholar 

  45. Mizuma T.; Ohta K.; Hayashi M.; Awazu S. Comparitive study of active absorption by the intestine and disposition of anomers of sugar-conjugated compounds. Biochem. Pharm. 45:1520 (1993).

    Article  PubMed  CAS  Google Scholar 

  46. Day A.J.; DuPont M.S.; Ridley S.; Rhodes M.; Rhodes M.J.C.; Morgan M.R.A.; Williamson G. Deglycosylation of flavonoid and isoflavonoid glycosides by human small intestine and liver β-glucosidase activity. FEBS Lett. 436:71 (1998).

    Article  PubMed  CAS  Google Scholar 

  47. Daniels L.B.; Coyle P.J.; Chiao Y.-B.; Glew R.H. Purification and characterization of a cytosolic broad specificity beta-glucosidase from human liver. J. Biol. Chem. 256:13004 (1981).

    PubMed  CAS  Google Scholar 

  48. Leese H.J.; Semenza G. On the identity between the small intestinal enzymes phlorizin hydrolase and glycosylceramidase. J. Biol. Chem. 248:8170 (1973).

    PubMed  CAS  Google Scholar 

  49. Baba S.; Furuta T.; Horie M.; Nakagawa H. Studies on drug metabolism by use of isotopes XXVI: Determination of urinary metaboiltes of rutin in humans. J. Pharm. Sci. 70:780 (1981).

    Article  PubMed  CAS  Google Scholar 

  50. Baba S.; Furuta T.; Fujioka M.; Goromaru T. Studies in drug metabolism by use of isotopes XXVII. Urinary metabolites of rutin in rats and the role of intestinal microflora in the metabolism of rutin. J. Pharm. Sci. 72:1155 (1983).

    Article  PubMed  CAS  Google Scholar 

  51. Booth A.N.; Murray C.W.; Jones F.T.; DeEds F. The metabolic fate of rutin and quercetin in the animal body. J. Biol. Chem. 223:251 (1956).

    PubMed  CAS  Google Scholar 

  52. Petrakis P.L.; Kallianos A.G.; Wender S.H.; Shetlar M.R. Metabolic studies of quercetin labeled with 14C. Arch. Biochem. Biophys. 85:264 (1959).

    Article  PubMed  CAS  Google Scholar 

  53. Sawai Y.; Kohsaka K.; Nishiyama Y.; Ando K. Serum concentrations of rutinoside metabolites after oral administration of a rutoside formulation to humans. Drug Res. 37:729 (1987).

    CAS  Google Scholar 

  54. Ueno I.; Nakano N.; Hirono I. Metabolic fate of 14C quercetin in the A.C.I, rat. Jpn. J. Exp. Med. 53:41 (1983).

    PubMed  CAS  Google Scholar 

  55. Nielsen, S.E.; Breinholt, V.; Justesen, U.; Cornett, C.; Dragsted, L.O. In vitro biotransformation of flavonoids by rat liver microsomes. Xenobiotic 28:389 (1998).

    Article  CAS  Google Scholar 

  56. Nielsen S.E.; Kall M.; Justesen U.; Schou A.; Dragsted L.O. Human absorption and excretion of flavonoids after broccoli consumption. Cancer Lett. 114:173 (1997).

    Article  PubMed  CAS  Google Scholar 

  57. Ameer B.; Weintraub R.A.; Johnson J.V.; Yost R.A.; Rouseff R.L. Flavanone absorption after naringin, hesperidin, and citrus administration. Clin. Pharm. Ther. 60:34 (1996).

    Article  CAS  Google Scholar 

  58. Manach C.; Morand C.; Demigne C.; Texier O.; Regerat F.; Remesy C. Bioavailability of rutin and quercetin in rats. FEBS Lett. 409:12 (1997).

    Article  PubMed  CAS  Google Scholar 

  59. Manach C.; Morand C.; Texier O.; Favier M.L.; Agullo G.; Demigune C.; Regerat F.; Remesy C. Quercetin metabolites in plasma of rats fed diets containing rutin or quercetin. J. Nutr. 125:1911 (1995).

    PubMed  CAS  Google Scholar 

  60. Manach C.; Texier O.; Regerat F.; Agullo G.; Demigne C.; Remesy C. Dietary quercetin is recovered in rat plasma as conjugated derivates of isorhamnetin and quercetin. Nutr. Biochem. 7:375 (1996).

    Article  CAS  Google Scholar 

  61. Zhu B.T.; Ezell E.L.; Liehr J.G. Catechol-o-methyltransferase catalyzed rapid o-methylation of mutagenic flavonoids. J. Biol. Chem. 269:292 (1994).

    PubMed  CAS  Google Scholar 

  62. Manach C.; Morand C.; Crespy V.; Demigne C.; Texier O.; Regerat F.; Remesy C. Quercetin is recovered in human plasma as conjugated derivatives which retain antioxi-dant properties. FEBS Letters 426:331 (1998).

    Article  PubMed  CAS  Google Scholar 

  63. Smith, R.L. The excretory function of bile. Chapman and Hall, London (1973).

    Google Scholar 

  64. Gibson, G.G.; Skett, P. (eds.) Factors affecting drug metabolism: internal factors. In: Introduction to drug metabolism. Blackie Academic and Professional, London p. 107 (1994).

    Google Scholar 

  65. Sfakianos J.; Coward L.; Kirk M.; Barnes S. Intestinal uptake and bilary excretion of the isoflavone genistein in rats. J. Nutr. 127:1260 (1997).

    PubMed  CAS  Google Scholar 

  66. Boutin, J.A.; Meunier, F.; Lambert, P.-H.; Hennig, P.; Bertin, D.; Serkiz, B.; Volland, J.-P In vivo and in vitro glucuronidation of the flavonoid diosmetin in rats. Drug Met. Dispostion 21:1157 (1993).

    CAS  Google Scholar 

  67. Mizuma T.; Ohta K.; Awazu S. The β-anomeric and glucose preferences of glucose transport carrier for intestinal active absorption of monosaccharide conjugates. Biochim. Biophys. Acta. 1200:117 (1994).

    Article  PubMed  CAS  Google Scholar 

  68. Mizuma T.; Awazu S. Intestinal Na+/glucose cotransporter mediated transport of glucose conjugate formed from disaccharide conjugate. Biochim. Biophys. Acta. 1379:1 (1998).

    Article  PubMed  CAS  Google Scholar 

  69. Piskula M.K.; Terao J. Accumulation of (−)-epicatechin metabolites in rat plasma after oral administration and distribution of conjugated enzymes in rat tissues. J. Nutr. 128:1172 (1998).

    PubMed  CAS  Google Scholar 

  70. Crespy, V.; Manach, C.; Morand, C.; Besson, C.; Demigne, C.; Remesy, C. Intestinal absorption and metabolism of quercetin. In: Polyphenol communications 98, XIXth International conference on polyphenols. Lille, France p. 75 (1998).

    Google Scholar 

  71. Stocker, R.; Frei, B. Endogenous antioxidant defenses in human blood plasma. In: Sies, H. (ed.) Oxidative stress: oxidants and antioxidants, Academic Press, London p. 213 (1991).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1999 Kluwer Academic / Plenum Publishers, New York

About this chapter

Cite this chapter

Day, A.J., Williamson, G. (1999). Human Metabolism of Dietary Quercetin Glycosides. In: Gross, G.G., Hemingway, R.W., Yoshida, T., Branham, S.J. (eds) Plant Polyphenols 2. Basic Life Sciences, vol 66. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4139-4_22

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-4139-4_22

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-0-306-46218-4

  • Online ISBN: 978-1-4615-4139-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics