Advertisement

Bioavailability and Health Effects of Dietary Flavonols in Man

  • Peter C. H. Hollman
  • Martijn B. Katan
Conference paper
Part of the Archives of Toxicology book series (TOXICOLOGY, volume 20)

Abstract

Flavonoids are polyphenolic compounds that occur ubiquitously in foods of plant origin. Over 4000 different flavonoids have been described, and they are categorized into flavonols, flavones, catechins, flavanones, anthocyanidins, and isoflavonoids. Flavonoids have a variety of biological effects in numerous mammalian cell systems, as well as in vivo. Recently much attention has been paid to their antioxidant properties and to their inhibitory role in various stages of tumour development in animal studies.

Quercetin, the major representative of the flavonol subclass, is a strong antioxidant, and prevents oxidation of low density lipoproteins in vitro. Oxidized low density lipoproteins are atherogenic, and are considered to be a crucial intermediate in the formation of atherosclerotic plaques. This agrees with observations in epidemiological studies that the intake of flavonols and flavones was inversely associated with subsequent coronary heart disease. However, no effects of flavonols on cancer were found in these studies.

The extent of absorption of flavonoids is an important unsolved problem in judging their many alleged health effects. Flavonoids present in foods were considered non-absorbable because they are bound to sugars as β-glycosides. Only free flavonoids without a sugar molecule, the so-called aglycones were thought to be able to pass through the gut wall. Hydrolysis only occurs in the colon by microorganisms, which at the same time degrade flavonoids. We performed a study to quantify absorption of various dietary forms of quercetin. To our surprise, the quercetin glycosides from onions were absorbed far better than the pure aglycone. Subsequent pharmacokinetic studies with dietary quercetin glycosides showed marked differences in absorption rate and bioavailability. Absorbed quercetin was eliminated only slowly from the blood.

The metabolism of flavonoids has been studied frequently in various animals, but very few data in humans are available. Two major sites of flavonoid metabolism are the liver and the colonic flora. There is evidence for Omethylation, sulfation and glucuronidation of hydroxyl groups in the liver. Bacterial ring fission of flavonoids occurs in the colon. The subsequent degradation products, phenolic acids, can be absorbed and are found in urine of animals. Quantitative data on metabolism are scarce.

Keywords

Coronary Heart Disease Trolox Equivalent Antioxidant Capacity Coronary Heart Disease Mortality Dietary Flavonoid Quercetin Glycoside 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. 

Unable to display preview. 

References

  1. Aeschbacher HU, Meier H, Ruch E (1982) Nonmutagenicity in vivo of the food flavonol quercetin. Nutr Cancer 4: 90–98CrossRef
  2. Bergmark C, Wu R, de Faire U, Lefvert AK, Swedenborg J (1995) Patients with early-onset peripheral vascular disease have increased levels of autoantibodies against oxidized LDL. Arterioscler Thromb Vasc Biol 15: 441–445
  3. Block G, Patterson B, Subar A (1992) Fruit, vegetables, and cancer prevention: a review of epidemiological evidence. Nutr Cancer 18: 1–29CrossRef
  4. Goldbohm RA, van den Brandt PA, Hertog MGL, Brants HAM, van Poppel G (1995) Flavonoid intake and risk of cancer: a prospective cohort study. Am J Epidemiol 141 (Suppl): s61
  5. Griffiths LA (1982) Mammalian metabolism of flavonoids. In: The Flavonoids: Advances in Research ( Harborne J, Mabry T eds), London: Chapman and Hall, pp. 681–718
  6. Gugler R, Leschik M, Dengler HJ (1975) Disposition of quercetin in man after single oral and intravenous doses. Eur J Clin Pharmacol 9: 229–234CrossRef
  7. Hackett AM (1986) The metabolism of flavonoid compounds in mammals. In: Plant flavonoias in biology and medicine. Biochemical, pharmacological, structure-activity relationships ( Cody V, Middleton E, Harborne J eds), New York: Alan R. Liss, Inc., pp. 177–194
  8. Halliwell B (1994) Free radicals, antioxidants, and human disease: curiosity, cause, or consequence? Lancet 344: 721–724CrossRef
  9. Hertog MGL, Hollman PCH, Katan MB (1992) Content of potentially anticarcinogenic flavonoids of 28 vegetables and 9 fruits commonly consumed in the Netherlands. J Agric Food Chem 40: 2379–2383CrossRef
  10. Hertog MGL, Feskens EJM, Hollman PCH, Katan MB, Kromhout D (1993a) Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly Study. Lancet 342: 1007–1011CrossRef
  11. Hertog MGL, Hollman PCH, van de Putte B (1993b) Content of potentially anticarcinogenic flavonoids of tea infusions, wines, and fruit juices. J Agric Food Chem 41: 1242–1246
  12. Hertog MGL, Feskens EJM, Hollman PCH, Katan MB, Kromhout D (1994) Dietary flavonoids and cancer risk in the Zutphen Elderly Study. Nutr Cancer 22x: 175–184CrossRef
  13. Hertog MGL, Kromhout D, Aravanis C, Blackburn H, Buzina R, Fidanza F, Giampaoli S, Jansen A, Menotti A, Nedeljkovic S, Pekkarinen M, Simic BS, Toshima H, Feskens EJM, Hollman PCH, Katan MB (1995) Flavonoid intake and long-term risk of coronary heart disease and cancer in the Seven Countries Study. Arch Intern Med 155: 381–386CrossRef
  14. Hertog MGL, Feskens EJM, Kromhout D (1997a) Antioxidant flavonols and coronary heart disease risk: ten year follow-up of the Zutphen Elderly Study. Lancet 349: 699CrossRef
  15. Hertog MGL, Sweetnam PM, Fehily AM, Elwood PC, Kromhout D (1997b) Antioxidant flavonols and ischaemic heart disease in a Welsh population of men. The Caerphilly Study. Am J Clin Nutr 65: 1489–1494
  16. Hollman PCH, de Vries JHM, van Leeuwen SD, Mengelers MJB, Katan MB (1995) Absorption of dietary quercetin glycosides and quercetin in healthy ileostomy volunteers. Am J Clin Nutr 62: 1276–1282
  17. Hollman PCH (1997) Determinants of the absorption of the dietary flavonoid quercetin in man. Wageningen: Thesis, Agricultural University
  18. Huang M-T, Ferraro T (1992) Phenolic compounds in food and cancer prevention. In: Phenolic compounds in food and their effects on health II. Antioxidants & cancer prevention ( Huang M-T, Ho C, Lee CY eds), Washington DC: American Chemical Society, pp. 8–34CrossRef
  19. Jha P, Flather M, Lonn E, Farkouh M, Yusuf S (1995) The antioxidant vitamins and cardiovascular disease. A critical review of epidemiologic and clinical trial data. Ann Intern Med 123: 860–872
  20. Kandaswami C, Middleton E (1994) Free radical scavenging and antioxidant activity of plant flavonoids. Adv Exp Med Bio l366: 351–376
  21. Keli SO, Hertog MGL, Feskens EJM, Kromhout D (1996) Flavonoids, antioxidant vitamins and risk of stroke. The Zutphen study. Arch Intern Med 156: 637–642CrossRef
  22. Knekt P, Järvinen R, Reunanen A, Maatela J (1996) Flavonoid intake and coronary mortality in Finland: a cohort study. Br Med J 312: 478–481CrossRef
  23. Kiihnau J (1976) The flavonoids. A class of semi-essential food components: their role in human nutrition. World Rev Nutr Diet 24: 117–191
  24. MacGregor JT, Wehr CM, Manners GD, Jurd L, Minkler JL, Carrano AV (1983) In vivo exposure to plant flavonols. Influence on frequencies of micronuclei in mouse erythrocytes and sister-chromatid exchange in rabbit lymphocytes. Mutation Res 124: 255–270CrossRef
  25. Middleton E, Kandaswami C (1994) The impact of plant flavonoids on mammalian biology: implications for immunity, inflammation and cancer. In: The Flavonoids: advances in research since 1986 (Harborne JB ed), London: Chapman & Hall, pp. 619–652
  26. Ness AR, Powles JW (1997) Fruit and vegetables, and cardiovascular disease: a review Int J Epidemiol 26: 1–13
  27. Rice-Evans CA, Miller NJ (1996) Antioxidant activities of flavonoids as bioactive components of food. Biochem Soc Trans 24: 790–795
  28. Rimm EB, Katan MB, Ascherio A, Stampfer MJ, Willett WC (1996) Relation between intake of flavonoids and risk for coronary heart disease in male health professionals. Ann Intern Med 125: 384–389
  29. Salonen JT, Ylä-Herttuala S, Yamamoto R, Butler S, Korpela H, Salonen R, Nyyssönen K, Palinski W, Witztum JL (1992) Autoantibody against oxidised LDL and progression of carotid atherosclerosis. Lancet 339: 883–887CrossRef
  30. Shaikh M, Martini S, Quiney JR, Baskerville P, La Ville AE, Browse NL, Duffield R, Turner PR, Lewis B (1988) Modified plasma-derived lipoproteins in human atherosclerotic plaques. Atherosclerosis 69: 165–172CrossRef
  31. Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL (1989) Beyond cholesterol: modifications of low density lipoprotein that increase its atherogenicity. N Engl J Med 320: 915–924CrossRef
  32. Steinmetz KA, Potter JD (1991) Vegetables, fruit and cancer. I. Epidemiology. Cancer Cause Control 2: 325–357CrossRef
  33. Sugimura T, Nagao M, Matsushima T, Yahagi T, Seino Y, Shirai A, Sawamura M, Natori S, Yoshibira K, Fukuoka M, Kuroyanagi M (1977) Mutagenicity of flavone derivatives. Proc Jpn Acad 53: 194–197CrossRef
  34. Ueno I, Nakano N, Hirono I (1983) Metabolic fate of (“C]quercetin in the ACI rat. Jpn J Exp Med 53: 41–50
  35. Wattenberg LW (1992) Inhibition of carcinogenesis by minor dietary constituents. Cancer Res 52 (Suppl): 2085S - 2091S
  36. de Whalley C, Rankin SM, Hoult JRS, Jessup W, Leake DS (199o) Flavonoids inhibit the oxidative modification of low density lipoproteins by macrophages. Biochem Ph arms c of 39: 1743–1750

Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • Peter C. H. Hollman
    • 1
  • Martijn B. Katan
    • 2
  1. 1.DLO State Institute for Quality Control of Agricultural Products (RIKILT-DLO)WageningenThe Netherlands
  2. 2.Department of Human NutritionAgricultural UniversityWageningenThe Netherlands

Personalised recommendations

www.steroid-pharm.com

https://steroid-pharm.com

https://pharmacy24.com.ua