Diet-Derived Phenols in Plasma and Tissues and their Implications for Health

 

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Abstract

This paper seeks to catalyse a reappraisal of the nature, fate and biological significance in humans of phenols, polyphenols and tannins (PPT) consumed in normal diets, and in particular questions the primacy of PPT radical-scavenging mechanisms for the supposed health benefits of diets rich in fruits and vegetables. PPT are classified by structure and function. Arguments are presented to show that cinnamates and derived polyphenols make significantly larger contributions to the total PPT intake than the flavonols and flavones upon which the vast majority of attention has been focussed previously. Daily intakes of total PPT may range from less than 100 mg to in excess of 2 g, and the critical importance of coffee and black tea as the major dietary sources is shown. Only some 5 % of the dietary PPT is absorbed in the duodenum, and of this only some 5 %, mainly flavanols, reaches the plasma unchanged, the balance being mammalian conjugates. Over 95 % of the intake passes to the colon and is fermented by the gut microflora. A fraction of the resulting microbial metabolites is absorbed and appears in the plasma primarily as mammalian conjugates. Even following high intakes of PPT, the plasma metabolites collectively make a very small (less than 5 %) and transient contribution to the total concentration of redox active substances in plasma. This explains the failure of most studies that sought to detect an increase in plasma antioxidant power after consuming a PPT-rich meal or supplement. The powerfully antioxidant PPT aglycones, much used in in vitro studies, do not reach the plasma. The redox potential of those unchanged PPT and PPT metabolites that reach the plasma enables them to scavenge damaging radicals, but the endogenous plasma antioxidants, especially ascorbate, are required for disposal of the resultant phenoxyl radicals. Black tea and coffee, the major sources of PPT, are poor sources of ascorbate. It is suggested that if diets rich in fruits and vegetables are health-promoting, and if these effects are due to PPT, then alternatives to radical-scavenging mechanisms must be sought. Evidence is presented to show that some mammalian metabolites of PPT may indeed be able to protect the vascular endothelium and that diets rich in PPT may in humans at normal dietary levels have the ability to protect against Type II diabetes and the metabolic syndrome through effects on glucose absorption and associated hormones. Such effects are recommended for further investigation.

References

• 1 Shahidi F, Naczk M. Food Phenolics: Sources; Chemistry; Effects; Applications. Lancaster, Pennsylvania; Technomic Publishing Inc. 1995: pp 1-321
  Google Scholar
• 2 Higdon J V, Frei B. Tea catechins and polyphenols: health effects, metabolism, and antioxidant functions.  CRC Crit Rev Food Sci Nutr. 2003;  43 89-143
  PubMedGoogle Scholar
• 3 Sesso H D, Gaziano J M, Liu S, Buring J E. Flavonoid intake and the risk of cardiovascular disease in women.  Am J Clin Nutr. 2003;  77 1400-8
  PubMedGoogle Scholar
• 4 Stewart J R, Artime M C, O'Brian C A. Resveratrol: a candidate nutritional substance for prostate cancer prevention.  J Nutr. 2003;  133 S2440-3
  PubMedGoogle Scholar
• 5 Kris-Etherton P M, Keen C L. Evidence that the antioxidant flavonoids in tea and cocoa are beneficial for cardiovascular health.  Curr Opin Lipidol. 2002;  13 41-9
  CrossrefPubMedGoogle Scholar
• 6 Arts I C, Jacobs D R, Gross M, Harnack L J, Folsom A R. Dietary catechins and cancer incidence among postmenopausal women: the Iowa Women’s Health Study (United States).  Cancer Causes Control. 2002;  13 373-82
  CrossrefPubMedGoogle Scholar
• 7 Reed J. Cranberry flavonoids, atherosclerosis and cardiovascular health.  CRC Crit Rev Food Sci Nutr. 2002;  42 301-16
  CrossrefPubMedGoogle Scholar
• 8 Sampson L, Rimm E, Hollman P C, de Vries J H, Katan M B. Flavonol and flavone intakes in US health professionals.  J Am Diet Assoc. 2002;  102 1414-20
  CrossrefPubMedGoogle Scholar
• 9 Youdim K A, Spencer J P, Schroeter H, Rice-Evans C. Dietary flavonoids as potential neuroprotectants.  Biol Chem. 2002;  383 503-19
  CrossrefPubMedGoogle Scholar
• 10 Dillard C J, German J B. Phytochemicals: nutraceuticals and human health.  J Sci Food Agric. 2000;  80 1744-56
  CrossrefPubMedGoogle Scholar
• 11 Riemersma R A, Rice-Evans C A, Tyrrell R M, Clifford M N, Lean M EJ. Tea flavonoids and cardiovascular health.  Quart J Med. 2001;  94 277-82
  PubMedGoogle Scholar
• 12 Parr A J, Bolwell G P. Phenols in the plant and in man. The potential for possible nutritional enhancement of the diet by modifying phenolic content or composition.  J Sci Food Agric. 2000;  80 985-1012
  CrossrefPubMedGoogle Scholar
• 13 Department of Health. Nutritional Aspects of the Development of Cancer. London; Her Majesty's Stationery Office 1998: pp 1-274
  Google Scholar
• 14 Ribereau-Gayon P. Plant phenolics. New York; Hafner Publishing Company 1972
  Google Scholar
• 15 Clifford M N. The health effects of tea and tea components. Appendix 1. A nomenclature for phenols with special reference to tea.  CRC Crit Rev Food Sci Nutr. 2001;  41 393-7
  PubMedGoogle Scholar
• 16 Lindsay D G, Clifford M N. Special issue devoted to critical reviews produced within the EU Concerted Action ”Nutritional Enhancement of Plant-based Food in European Trade” (NEODIET).  J Sci Food Agric. 2000;  80 793-1137
  CrossrefPubMedGoogle Scholar
• 17 Clifford M N. Chlorogenic acids and other cinnamates - nature, occurrence and dietary burden.  J Sci Food Agric. 1999;  79 362-72
  CrossrefPubMedGoogle Scholar
• 18 Clifford M N. Chlorogenic acids and other cinnamates - nature, occurrence, dietary burden, absorption and metabolism.  J Sci Food Agric. 2000;  80 1033-42
  CrossrefPubMedGoogle Scholar
• 19 Clifford M N. Miscellaneous phenols in foods and beverages - nature, occurrence and dietary burden.  J Sci Food Agric. 2000;  80 1126-37
  CrossrefPubMedGoogle Scholar
• 20 Soler-Rivas C, Espin J C, Wichers H J. Oleuropein and related compounds.  J Sci Food Agric. 2000;  80 1013-23
  CrossrefPubMedGoogle Scholar
• 21 Tomás-Barberán F A, Clifford M N. Dietary hydroxybenzoic acid derivatives - nature, occurrence and dietary burden.  J Sci Food Agric. 2000;  80 1024-32
  CrossrefPubMedGoogle Scholar
• 22 Hertog M GL, Hollman P CH, Katan M B. Content of potentially anticarcinogenic flavonoids of 28 vegetables and 9 fruits consumed in The Netherlands.  J Agr Food Chem. 1992;  40 2379-83
  CrossrefPubMedGoogle Scholar
• 23 Haslam E. Practical Polyphenolics. From structure to molecular recognition and physiological action. Cambridge; Cambridge University Press 1998: pp 1-438
  Google Scholar
• 24 Santos-Buelga C, Scalbert A. Proanthocyanidins and tannin-like compounds - nature, occurrence, dietary intake and effects on nutrition and health.  J Sci Food Agric. 2000;  80 1094-1117
  CrossrefPubMedGoogle Scholar
• 25 Clifford M N, Scalbert A. Ellagitannins - nature, occurrence and dietary burden.  J Sci Food Agric. 2000;  80 1118-25
  CrossrefPubMedGoogle Scholar
• 26 Cassidy A, Hanley B, Lamuela-Raventós R M. Isoflavones, lignans and stilbenes - origins, metabolism and potential importance to human health.  J Sci Food Agric. 2000;  80 1044-62
  CrossrefPubMedGoogle Scholar
• 27 Setchell K DR, Lawson A M, Borriello S P, Harkness R, Gordon H, Morgan D ML, Kirk D N, Adlercreutz H, Anderson L C. Lignan formation in man - microbial involvement and possible roles in relation to cancer.  Lancet. 1981;  ii 4-7
  PubMedGoogle Scholar
• 28 Diplock A T. Defence against reactive oxygen species.  Free Radic Res. 1999;  29 4637
  PubMedGoogle Scholar
• 29 Kroon P A, Clifford M N, Crozier A, Day A J, Donovan J L, Manach C, Williamson G. COMMENTARY: How should we assess the effects of exposure to dietary polyphenols in vitro .  Am J Clin Nutr. 2004;  80 15-21
  PubMedGoogle Scholar
• 30 Cameira-dos-Santos P -J, Brillouet J -M, Cheynier V, Moutounet M. Detection and partial characterisation of new anthocyanin-derived pigments in wine.  J Sci Food Agric. 1996;  70 204-8
  CrossrefPubMedGoogle Scholar
• 31 Fulcrand H, Cameira-dos-Santos P -J, Sarni-Manchado P, Cheynier V, Favre-Bonvin J. Structure of new anthocyanin-derived wine pigments.  J Chem Soc Perkin Trans. 1996;  1 735-9
  PubMedGoogle Scholar
• 32 Bakker J, Bridle P, Honda P, Kuwano H, Saito N, Terahara N, Timberlake C F. Identification of an anthocyanin occurring in some red wines.  Phytochemistry. 1997;  44 1375-82
  CrossrefPubMedGoogle Scholar
• 33 Bakker J, Timberlake C F. Isolation, identification and characterization of new color-stable anthocyanins occurring in some red wines.  J Agr Food Chem. 1997;  45 35-43
  CrossrefPubMedGoogle Scholar
• 34 Davis A L, Lewis J R, Cai Y, Powell C, Davies A P, Wilkins J PG, Pudney P, Clifford M N. A polyphenolic pigment from black tea.  Phytochemistry. 1997;  46 1397-402
  CrossrefPubMedGoogle Scholar
• 35 Fulcrand H, Benabdeljalil C, Rigaud J, Cheynier V, Moutounet M. A new class of wine pigments yielded by reaction between pyruvic acid and the grape anthocyanins.  Phytochemistry. 1998;  47 1401-7
  CrossrefPubMedGoogle Scholar
• 36 Davies A P, Goodsall C, Cai Y, Davis A L, Lewis J R, Wilkins J, Wan X, Clifford M N, Powell C, Thiru A, Safford R, Nursten H E. Black tea dimeric and oligomeric pigments - structures and formation. In: Gross GG, Hemingway RW and Yoshida T, editors Plant Polyphenols 2. Chemistry, Biology, Pharmacology, Ecology. Indian bend, Oregon, USA; Kluwer Academic 1999: pp 697-724
  Google Scholar
• 37 Vivar-Quintana A M, Santos-Buelga C, Francia-Aricha E, Rivas-Gonzalo J C. Formation of anthocyanin-derived pigments in experimental red wines.  Food Science and Technology International. 1999;  5 347-52
  PubMedGoogle Scholar
• 38 Tanaka T, Betsumiya Y, Mine C, Kouno I. Theanaphthoquinone, a novel pigment oxidatively derived from theaflavin during tea fermentation. Chem Commun 2000: 1365-6
  Google Scholar
• 39 Mateus N, Silva A M, Santos-Buelga C, Rivas-Gonzalo J C, de F V. Identification of anthocyanin-flavanol pigments in red wines by NMR and mass spectrometry.  J Agr Food Chem. 2002;  50 2110-6
  CrossrefPubMedGoogle Scholar
• 40 Mateus N, de Pascual-Teresa S, Rivas-Gonzalo J C, Santos-Buelga C, de Freitas V. Structural diversity of anthocyanin-derived pigments in port wines.  Food Chem. 2002;  76 335-42
  CrossrefPubMedGoogle Scholar
• 41 Sang S, Tian W, Meng X, Stark R E, Rosen R T, Yang C S, Ho C -T. Theadibenztropolone A, a new type pigment from enzymatic oxidation of (-)-epicatechin and (-)-epigallocatechin gallate and characterized from black tea using LC/MS/MS.  Tetrahedron Lett. 2002;  43 7129-33
  CrossrefPubMedGoogle Scholar
• 42 Kühnau J. The flavonoids. A class of semi-essential food components: their role in human nutrition.  World Rev Nutr Diet. 1976;  24 117-91
  PubMedGoogle Scholar
• 43 Knekt P, Jarvinen R, Reunanen A, Maatela J, Lunetta M, di Mauro M, Crimi S, Mughini L. Flavonoid intake and coronary mortality in Finland: a cohort study. No important differences in glycaemic responses to common fruits in type 2 diabetic patients.  Brit Med J. 1995;  12 674-8
  PubMedGoogle Scholar
• 44 Kimira M, Arai Y, Shimoi K, Watanabe S. Japanese intake of flavonoids and isoflavonoids from foods.  J Epidemiol. 1998;  8 168-5
  PubMedGoogle Scholar
• 45 Linseisen J, Radtke J, Wolfram G. Flavonoid intake of adults in a Bavarian subgroup of the National Food Consumption survey.  Z Ernährungswiss. 1997;  36 403-12
  CrossrefPubMedGoogle Scholar
• 46 Radtke J, Linseisen J, Wolfram G. Phenolic acid intake of adults in a Bavarian subgroup of the national food consumption survey.  Z Ernährungswiss. 1998;  37 190-7
  CrossrefPubMedGoogle Scholar
• 47 Hirvonen T, Pietinen P, Virtanen M, Ovaskainen M L, Hakkinen S, Albanes D, Virtamo J. Intake of flavonols and flavones and risk of coronary heart disease in male smokers.  Epidemiology. 2001;  12 62-7
  PubMedGoogle Scholar
• 48 Hirvonen T, Virtamo J, Korhonen P, Albanes D, Pietinen P. Flavonol and flavone intake and the risk of cancer in male smokers (Finland).  Cancer Causes Control. 2001;  12 789-96
  PubMedGoogle Scholar
• 49 Gosnay S L, Bishop J A, New S A, Catterick J, Clifford M N. Estimation of the mean intakes of fourteen classes of dietary phenolics in a population of young British women aged 20 - 30 years.  Proc Nutr Soc. 2002;  61 125A
  PubMedGoogle Scholar
• 50 Woods E, Clifford M N, Gibbs M, Hampton S, Arendt J, Morgan L. Estimation of mean intakes of 14 classes of dietary phenols in a population of male shift workers.  Proc Nutr Soc. 2003;  62 60A
  PubMedGoogle Scholar
• 51 Hertog M GL, Sweetman P M, Fehily A M, Elwood P C, Kromhout D. Antioxidant flavonols and ischaemic heart disease in a Welsh population of men: the Caerphilly Study.  Am J Clin Nutr. 1997;  65 1489-94
  PubMedGoogle Scholar
• 52 Arai Y, Watanabe S, Kimira M, Shimoi K, Mochizuki R, Kinae N. Dietary intakes of flavonols, flavones and isoflavones by Japanese women and the inverse correlation between quercetin intake and plasma LDL cholesterol concentration.  J Nutr. 2000;  130 2243-50
  PubMedGoogle Scholar
• 53 Tomás-Barberán F A, Clifford M N. Flavanones, chalcones and dihydrochalcones - nature, occurrence and dietary burden.  J Sci Food Agric. 2000;  80 1073-80
  CrossrefPubMedGoogle Scholar
• 54 Price K R, Bacon J R, Rhodes M JC. Effect of storage and domestic processing on the content and composition of flavonol glucosides in onion (Allium cepa).  J Agr Food Chem. 1997;  45 938-42
  CrossrefPubMedGoogle Scholar
• 55 Ewald C, Fjelkner-Modig S, Johanssen K, Sjöholma I, Åkesson B. Effect of processing on major flavonoids in processed onions, green beans, and peas.  Food Chem. 1999;  64 231-5
  CrossrefPubMedGoogle Scholar
• 56 Chuda Y, Suzuki M, Nagata T, Tsushida T. Contents and cooking loss of three quinic acid derivatives from Garland (Chrysanthemum coronarium L.)  J Agr Food Chem. 1998;  46 1437-9
  CrossrefPubMedGoogle Scholar
• 57 Price K R, Casuscelli F, Colquhoun I J, Rhodes M JC. Composition and content of flavonol glycosides in broccoli floreets (Brassica oleracea) and their fate during cooking.  J Sci Food Agric. 1998;  77 468-72
  CrossrefPubMedGoogle Scholar
• 58 Ioku K, Aoyama Y, Tokuno A, Terao J, Nakatani N, Takei Y. Various cooking methods and the flavonoid content in onion.  J Nutr Sci Vitaminol (Tokyo). 2001;  47 78-83
  PubMedGoogle Scholar
• 59 Brenes M, Garcia A, Dobarganes M C, Velasco J, Romero C. Influence of thermal treatments simulating cooking processes on the polyphenol content in virgin olive oil.  J Agr Food Chem. 2002;  50 5962-7
  CrossrefPubMedGoogle Scholar
• 60 Vallejo F, Tom F A, Garc C. Phenolic compound contents in edible parts of broccoli inflorescences after domestic cooking.  J Sci Food Agric. 2003;  83 1511-6
  CrossrefPubMedGoogle Scholar
• 61 Bond T A, Lewis J R, Davis A, Davies A P. Analysis and purification of catechins and their transformation products. In: Santos-Buelga C, Williamson G, editors Methods in Polyphenol Analysis. Cambridge; Royal Society of Chemistry 2003: pp 229-66
  Google Scholar
• 62 Garcia-Closas R, Gonzalez C A, Agudo A, Riboli E. Intake of specific carotenoids and flavonoids and the risk of gastric cancer in Spain.  Cancer Causes Control. 1999;  10 71-5
  CrossrefPubMedGoogle Scholar
• 63 Justesen U, Knuthsen P. Composition of flavonoids in fresh herbs and calculation of flavonoid intake by use of herbs in traditional Danish dishes.  Food Chem. 2001;  73 245-50
  CrossrefPubMedGoogle Scholar
• 64 Justesen U, Knuthsen P, Andersen N L, Leth T. Estimation of daily intake distribution of flavonols and flavanones in Denmark.  Scand J Nutr. 2000;  44 158-60
  PubMedGoogle Scholar
• 65 Keli S O, Hertog M G, Feskens E J, Kromhout D. Dietary flavonoids, antioxidant vitamins, and incidence of stroke: the Zutphen study.  Arch Intern Med. 1996;  156 637-42
  CrossrefPubMedGoogle Scholar
• 66 Knekt P, Jarvinen R, Seppanen R, Hellovaara M, Teppo L, Pukkala E, Aromaa A. Dietary flavonoids and the risk of lung cancer and other malignant neoplasms.  Am J Epid. 1997;  146 223-30
  PubMedGoogle Scholar
• 67 Knekt P, Jarvinen R, Reunanen A, Maatela J. Flavonoid intake and coronary mortality in Finland: a cohort study.  Brit Med J. 1996;  312 478-81
  PubMedGoogle Scholar
• 68 Knekt P, Isotupa S, Rissanen H, Heliovaara M, Jarvinen R, Hakkinen S, Aromaa A, Reunanen A. Quercetin intake and the incidence of cerebrovascular disease.  Eur J Clin Nutr. 2000;  54 415-7
  CrossrefPubMedGoogle Scholar
• 69 Pascual-Teresa S, Santos-Buelga C, Rivas-Gonzalo J C. Quantitative analysis of flavan-3-ols in Spanish foodstuffs and beverages.  J Agric Food Chem. 2000;  48 5331-7
  CrossrefPubMedGoogle Scholar
• 70 Arts I CW, van de Putte B, Hollman P CH. Catechin contents of foods commonly consumed in the Netherlands. 1. Fruits, vegetables, staple foods, and processed foods. J Agr Food Chem 2000: 1746-51
  Google Scholar
• 71 Arts I CW, Hollman P CH, Feskens E JM, de Mesquita B B, Kromhout D. Catechin intake is inversely associated with coronary heart disease mortality; Results from the Zutphen Elderly Study.  Circulation. 2000;  101 4
  PubMedGoogle Scholar
• 72 Stewart A J, Bozonnet S, Mullen W, Jenkins G I, Lean M E, Crozier A. Occurrence of flavonols in tomatoes and tomato-based products.  J Agr Food Chem. 2000;  48 2663-9
  CrossrefPubMedGoogle Scholar
• 73 Crozier A, Burns J, Aziz A A, Stewart A J, Rabiasz H S, Jenkins G, Edwards C A, Lean M EJ. Antioxidant flavonols from fruits, vegetables and beverages: measurement and bioavailability.  Biol Res. 2000;  33 79-88
  PubMedGoogle Scholar
• 74 Howard L R, Pandjaitan N, Morelock T, Gil M I. Antioxidant capacity and phenolic content of spinach as affected by genetics and growing season.  J Agr Food Chem. 2002;  50 5891-6
  CrossrefPubMedGoogle Scholar
• 75 Cacace J E, Mazza G. Extraction of anthocyanins and other phenolics from blackcurrants with sulfured water.  J Agr Food Chem. 2002;  50 5939-46
  CrossrefPubMedGoogle Scholar
• 76 Porteous L. Nutritional and dietary risk factors for osteoporosis: An investigation of association between diet and indices of bone health in young British women aged 25 - 30 years. B.Sc. Thesis. University of Surrey 2001
  Google Scholar
• 77 Bennett G. Food choices, dietary patterns and circulation adaptation in shift workers: an investigation into the possible impact on coronary heart disease risk. B.Sc. Thesis. University of Surrey 2001
  Google Scholar
• 78 Paul N. Do eating patterns and post-prandial hormonal and metabolic markers vary significantly according to shift type and circadian status in swing shift workers in the offshore oil industry. B.Sc. Thesis. University of Surrey 2001
  Google Scholar
• 79 Balentine D A, Wiseman S A, Bouwens C M. The chemistry of tea flavonoids.  CRC Crit Rev Food Sci Nutr. 1997;  37 693-704
  PubMedGoogle Scholar
• 80 Clifford M N. Tea. In: Ranken MD, Kill RC and Baker CJG, editors Food Industries Manual. 24th edition London; Blackie 1997: pp 379-95
  Google Scholar
• 81 Harbowy M E, Balentine D A. Tea Chemistry.  CRC Crit Rev Plant Sci. 1997;  16 415-80
  PubMedGoogle Scholar
• 82 Olthof M R, Hollman P C, Buijsman M N, van Amelsvoort J M, Katan M B. Chlorogenic acid, quercetin-3-rutinoside and black tea phenols are extensively metabolized in humans.  J Nutr. 2003;  133 1806-14
  CrossrefPubMedGoogle Scholar
• 83 Nardini M, Cirillo E, Natella F, Scaccini C. Absorption of phenolic acids in humans after coffee consumption.  J Agr Food Chem. 2002;  50 5735-41
  CrossrefPubMedGoogle Scholar
• 84 Lee M -J, Wang Z -Y, Li H, Chen L, Sun Y, Gobbo S, Balentine D A, Yang C S. Analysis of plasma and urinary tea polyphenols in human subjects.  Cancer Epidemiol Biomarkers Prev. 1995;  4 393-9
  PubMedGoogle Scholar
• 85 Hollman P C, Katan M B. Health effects and bioavailability of dietary flavonols.  Free Radic Res. 1999;  31 Suppl S75-80
  PubMedGoogle Scholar
• 86 Olthof M R, Hollman P C, Vree T B, Katan M B. Bioavailabilities of quercetin-3-glucoside and quercetin-4′-glucoside do not differ in humans.  J Nutr. 2000;  130 1200-3
  PubMedGoogle Scholar
• 87 Hollman P CH, van Trijp J M, Buysman M N, van der Gaag M S, Mengelers M J, de Vries J HM, Katan M B. Relative bioavailability of the antioxidant quercetin from various foods in man.  FEBS Lett. 1997;  418 152-6
  CrossrefPubMedGoogle Scholar
• 88 Walle T, Walle U K, Halushka P V. Carbon dioxide is the major metabolite of quercetin in humans.  J Nutr. 2001;  131 2648-52
  CrossrefPubMedGoogle Scholar
• 89 Krishnamurty H G, Cheng K J, Jones G A, Simpson F J, Watkin J E. Identification of products produced by the anaerobic degradation of rutin and related flavonoids by Butyrivibrio sp. C3.  Can J Microbiol. 1970;  16 759-67
  PubMedGoogle Scholar
• 90 Scheline R R. The metabolism of (+)-catechin to hydroxyphenylvaleric acids by the intestinal microflora.  Biochim Biophys Acta. 1970;  222 228-30
  PubMedGoogle Scholar
• 91 Scheline R R. Mammalian Metabolism of Plant Xenobiotics. London; Academic Press 1978: pp 1-502
  Google Scholar
• 92 Griffiths L A. Mammalian metabolism of flavonoids. In: Harborne JB, Mabry TJ, editors The Flavonoids: Advances in Research. London; Chapman and Hall 1982: pp 681-718
  Google Scholar
• 93 Groenewoud G, Hundt H KL. The microbial metabolism of (+)-catechins to two novel diarylpropan-2-ol metabolites in vitro .  Xenobiotica. 1984;  14 711-7
  PubMedGoogle Scholar
• 94 Bokkenheuser V D, Shackleton C H, Winter J. Hydrolysis of dietary flavonoid glycosides by strains of intestinal Bacteroides from humans.  Biochem J. 1987;  248 953-6
  PubMedGoogle Scholar
• 95 Sawai Y, Kohsaka K, Nishiyama Y, Ando K. Serum concentrations of rutoside metabolites after oral administration of a rutoside formulation to humans.  Arzneimittel-Forsch. 1987;  37 729-32
  PubMedGoogle Scholar
• 96 Bokkenheuser V D, Winter J. Hydrolysis of flavonoids by human intestinal bacteria.  Progress in Clinical & Biological Research. 1988;  280 143-5
  PubMedGoogle Scholar
• 97 Winter J, Moore L H, Dowell V R, Bokkenheuser V D. C-ring cleavage of flavonoids by human intestinal bacteria.  Appl Environ Microbiol. 1989;  55 1203-8
  PubMedGoogle Scholar
• 98 Coldham N G, King L J, Macpherson D D, Sauer M J. Biotransformation of genistein in the rat: elucidation of metabolite structure by product ion mass fragmentology.  J Steroid Biochem Mol Biol. 1999;  70 169-84
  CrossrefPubMedGoogle Scholar
• 99 Schneider H, Schwiertz A, Collins M D, Blaut M. Anaerobic transformation of quercetin-3-glucoside by bacteria from the human intestinal tract.  Arch Microbiol. 1999;  171 81-091
  CrossrefPubMedGoogle Scholar
• 100 Simmering R, Kleessen B, Blaut M. Quantification of the flavonoid-degrading bacterium Eubacterium ramulus in human fecal samples with a species-specific oligonucleotide hybridization probe.  Appl Environ Microbiol. 1999;  65 3705-9
  PubMedGoogle Scholar
• 101 Deprez S, Brezillon C, Rabot S, Philippe C, Mila I, Lapierre C, Scalbert A. Polymeric proanthocyanidins are catabolized by human colonic microflora into low-molecular-weight phenolic acids.  J Nutr. 2000;  130 2733-8
  CrossrefPubMedGoogle Scholar
• 102 Justesen U, Arrigoni E, Larsen B R, Amado R. Degradation of flavonoid glycosides and aglycones during in vitro fermentation with human faecal flora.  Lebensm Wiss Technol. 2000;  33 424-30
  CrossrefPubMedGoogle Scholar
• 103 Clifford M N, Copeland E L, Bloxsidge J P, Mitchell L A. Hippuric acid is a major excretion product associated with black tea consumption.  Xenobiotica. 2000;  30 317-26
  CrossrefPubMedGoogle Scholar
• 104 Li C, Lee M -J, Sheng S, Meng X, Prabhu S, Winnik B, Huang B, Chung J Y, Yan S, Ho C -T, Yang C S. Structural identification of two metabolites of catechins and their kinetics in human urine and blood after tea ingestion.  Chem Res Toxicol. 2000;  13 177-84
  CrossrefPubMedGoogle Scholar
• 105 Schneider H, Blaut M. Anaerobic degradation of flavonoids by Eubacterium ramulus .  Arch Microbiol. 2000;  173 71-5
  CrossrefPubMedGoogle Scholar
• 106 Schneider H, Simmering R, Hartmann L, Blaut M. Degradation of quercetin-3-glucoside in gnotobiotic rats associated with human intestinal bacteria.  J Appl Microbiol. 2000;  89 1027-37
  CrossrefPubMedGoogle Scholar
• 107 Jenkins D I, Wolever T M, Taylor R H. Glycaemic index of foods: a physiological basis for carbohydrate exchange.  Am J Clin Nutr. 1981;  34 362-6
  PubMedGoogle Scholar
• 108 Couteau D, McCartney A L, Gibson G R, Williamson G, Faulds C B. Isolation and characterization of human colonic bacteria able to hydrolyse chlorogenic acid.  J Appl Microbiol. 2001;  90 873-881
  CrossrefPubMedGoogle Scholar
• 109 Olthof M R. Bioavailability of flavonoids and cinnamic acids and their effect on plasma homocysteine in humans. PhD Thesis. Wageningen University 2001: pp 136
  Google Scholar
• 110 Olthof M R, Hollman P CH, Katan M B. Chlorogenic acid and caffeic acid are absorbed in humans.  J Nutr. 2001;  131 66-71
  CrossrefPubMedGoogle Scholar
• 111 Aura A M, O'Leary K A, Williamson G, Ojala M, Bailey M, Puupponen-Pimia R, Nuutila A M, Oksman-Caldentey K M, Poutanen K. Quercetin derivatives are deconjugated and converted to hydroxyphenylacetic acids but not methylated by human fecal flora in vitro .  J Agr Food Chem. 2002;  50 1725-30
  CrossrefPubMedGoogle Scholar
• 112 Schoefer L, Mohan R, Braune A, Birringer M, Blaut M. Anaerobic C-ring cleavage of genistein and daidzein by Eubacterium ramulus.  FEMS Microbiol Lett. 2002;  208 197-202
  CrossrefPubMedGoogle Scholar
• 113 Braune A, Gutschow M, Engst W, Blaut M. Degradation of quercetin and luteolin by Eubacterium ramulus .  Appl Environ Microbiol. 2001;  67 5558-67
  CrossrefPubMedGoogle Scholar
• 114 Wang L Q, Meselhy M R, Li Y, Nakamura N, Min B S, Qin G W, Hattori M. The heterocyclic ring fission and dehydroxylation of catechins and related compounds by Eubacterium sp. strain SDG-2, a human intestinal bacterium.  Chem Pharm Bull. 2001;  49 1640-3
  CrossrefPubMedGoogle Scholar
• 115 Hur H, Rafii F. Biotransformation of the isoflavonoids biochanin A, formononetin, and glycitein by Eubacterium limosum .  FEMS Microbiol Lett. 2000;  192 21-5
  CrossrefPubMedGoogle Scholar
• 116 Wang L Q, Meselhy M R, Li Y, Qin G W, Hattori M. Human intestinal bacteria capable of transforming secoisolariciresinol diglucoside to mammalian lignans, enterodiol and enterolactone.  Chem Pharm Bull. 2000;  48 1606-10
  CrossrefPubMedGoogle Scholar
• 117 Barcenilla A, Pryde S E, Martin J C, Duncan S H, Stewart C S, Henderson C, Flint H J. Phylogenetic relationships of butyrate-producing bacteria from the human gut.  Appl Environ Microbiol. 2000;  66 1654-61
  CrossrefPubMedGoogle Scholar
• 118 Takanaga H, Tamai I, Tsuji A. pH-dependent and carrier-mediated transport of salicylic acid across Caco-2 cells.  J Pharm Pharmacol. 1994;  46 567-70
  PubMedGoogle Scholar
• 119 Tsuji A, Takanaga H, Tamai I, Terasaki T. Transcellular transport of benzoic acid across Caco-2 cells by a pH-dependent and carrier-mediated transport mechanism.  Pharm Res. 1994;  11 30-7
  CrossrefPubMedGoogle Scholar
• 120 Tamai I, Takanaga H, Maeda H, Yabuuchi H, Sai Y, Suzuki Y, Tsuji A. Intestinal brush-border membrane transport of monocarboxylic acids mediated by proton-coupled transport and anion antiport mechanisms.  J Pharm Pharmacol. 1997;  49 108-12
  PubMedGoogle Scholar
• 121 Konishi Y, Shimizu M. Transepithelial transport of ferulic acid by monocarboxylic acid transporter in Caco-2 cell monolayers.  Biosci Biotechnol Biochem. 2003;  67 856-62
  CrossrefPubMedGoogle Scholar
• 122 Konishi Y, Kobayashi S, Shimizu M. Transepithelial transport of p-coumaric acid and gallic acid in Caco-2 cell monolayers.  Biosci Biotechnol Biochem. 2003;  67 2317-24
  CrossrefPubMedGoogle Scholar
• 123 Baba S, Osakabe N, Yasuda A, Natsume M, Takizawa T, Nakamura T, Terao J. Bioavailability of (-)-epicatechin upon intake of chocolate and cocoa in human volunteers.  Free Radic Res. 2000;  33 635-41
  PubMedGoogle Scholar
• 124 Bell J RC, Donovan J L, Wong R, Waterhouse A L, German J B, Walzem R L, Kasim-Karakas S E. (+)-Catechin in human plasma after ingestion of a single serving of reconstituted red wine.  Am J Clin Nutr. 2000;  71 103-8
  PubMedGoogle Scholar
• 125 Hollman P CH, van der Gaag M S, Mengelers M JB, van Trijp J MP, de Vries J HM, Katan M B. Absorption and disposition kinetics of the dietary antioxidant quercetin in man.  Free Radic Biol Med. 1996;  21 703-7
  CrossrefPubMedGoogle Scholar
• 126 Holt R R, Lazarus S A, Sullards M C, Zhu Q Y, Schramm D D, Hammerstone J F, Fraga C G, Schmitz H H, Keen C L. Procyanidin dimer B2 [epicatechin-(4beta-8)-epicatechin] in human plasma after the consumption of a flavanol-rich cocoa.  Am J Clin Nutr. 2002;  76 798-804
  CrossrefPubMedGoogle Scholar
• 127 Kimura M, Umegaki K, Kasuya Y, Sugisawa A, Higuchi M. The relation between single/double or repeated tea catechin ingestions and plasma antioxidant activity in humans.  Eur J Clin Nutr. 2002;  56 1186-93
  CrossrefPubMedGoogle Scholar
• 128 McAnlis G T, McEneny J, Pearce J, Young I S. Absorption and antioxidant effects of quercetin from onions, in man.  Eur J Clin Nutr. 1999;  53 92-6
  CrossrefPubMedGoogle Scholar
• 129 van het Hof K, Wiseman S A, de Boer H, Weststrate N LJ, Tijburg L. Bioavailability and antioxidant activity of tea polyphenols in humans. In: Amadó R, Andersson H, Bardócz S and Serra F, editors COST 916 Bioactive plant cell wall components in mutrition and health. Polyphenols in food. Luxembourg; EC 1998: 115
  Google Scholar
• 130 Wang J F, Schramm D D, Holt R R, Ensunsa J L, Fraga C G, Schmitz H H, Keen C L. A dose-response effect from chocolate consumption on plasma epicatechin and oxidative damage.  J Nutr. 2000;  130 2115S-9
  PubMedGoogle Scholar
• 131 Manach C, Morand C, Gil-Izquierdo A, Bouteloup-Demange C, Remesy C. Bioavailability in humans of the flavanones hesperidin and narirutin after the ingestion of two doses of orange juice.  Eur J Clin Nutr. 2003;  57 235-42
  CrossrefPubMedGoogle Scholar
• 132 Yang C S, Lee M J, Chen L. Human salivary tea catechin levels and catechin esterase activities: implication in human cancer prevention studies.  Cancer Epidemiology, Biomarkers & Prevention. 1999;  8 83-9
  PubMedGoogle Scholar
• 133 Meng X, Lee M J, Li C, Sheng S, Zhu N, Sang S, Ho C T, Yang C S. Formation and identification of 4′-O-methyl-(-)-epigallocatechin in humans.  Drug Metab Dispos. 2001;  29 789-93
  PubMedGoogle Scholar
• 134 Caccetta R A, Croft K D, Beilin L J, Puddey I B. Ingestion of red wine significantly increases plasma phenolic acid concentrations but does not acutely affect ex vivo lipoprotein oxidizability.  Am J Clin Nutr. 2000;  71 67-74
  PubMedGoogle Scholar
• 135 Carbonneau M A, Leger C L, Monnier L, Bonnet C, Michel F, Fouret G, Dedieu F, Descomps B. Supplementation with wine phenolic compounds increases the antioxidant capacity of plasma and vitamin E of low-density lipoprotein without changing the lipoprotein Cu(2+)-oxidizability: possible explanation by phenolic location.  Eur J Clin Nutr. 1997;  51 682-90
  CrossrefPubMedGoogle Scholar
• 136 Conquer J A, Maiani G, Azzini E, Raguzzini A, Holub B J. Supplementation with quercetin markedly increases plasma quercetin concentration without effect on selected risk factors for heart disease in healthy subjects.  J Nutr. 1998;  128 593-7
  PubMedGoogle Scholar
• 137 Eccleston C, Baoru Y, Tahvonen R, Kallio H, Rimbach G H, Minihane A M. Effects of an antioxidant-rich juice (sea buckthorn) on risk factors for coronary heart disease in humans.  J Nutr Biochem. 2002;  13 346-54
  PubMedGoogle Scholar
• 138 Ghiselli A, Natella F, Guidi A, Montanari L, Fantozzi P, Scaccini C. Beer increases plasma antioxidant capacity in humans.  J Nutr Biochem. 2000;  11 76-80
  PubMedGoogle Scholar
• 139 Hodgson J M, Puddey I B, Croft K D, Burke V, Mori T A, Caccetta R A, Beilin L J. Acute effects of ingestion of black and green tea on lipoprotein oxidation.  Am J Clin Nutr. 2000;  71 1103-7
  PubMedGoogle Scholar
• 140 Hodgson J M, Puddey I B, Croft K D, Mori T A, Rivera J, Beilin L J. Isoflavonoids do not inhibit in vivo lipid peroxidation in subjects with high-normal blood pressure.  Atherosclerosis. 1999;  145 167-72
  CrossrefPubMedGoogle Scholar
• 141 Leenen R, Roodenburg A J, Tijburg L B, Wiseman S A. A single dose of tea with or without milk increases plasma antioxidant activity in humans.  Eur J Clin Nutr. 2000;  54 87-92
  CrossrefPubMedGoogle Scholar
• 142 Mathur S, Devaraj S, Grundy S M, Jialal I. Cocoa products decrease low density lipoprotein oxidative susceptibility but do not affect biomarkers of inflammation in humans.  J Nutr. 2002;  132 3663-7
  PubMedGoogle Scholar
• 143 Mazza G, Kay C D, Cottrell T, Holub B J. Absorption of anthocyanins from blueberries and serum antioxidant status in human subjects.  J Agr Food Chem. 2002;  50 7731-7
  CrossrefPubMedGoogle Scholar
• 144 Mitchell J H, Collins A R. Effects of a soy milk supplement on plasma cholesterol levels and oxidative DNA damage in men - a pilot study.  Eur J Nutr. 1999;  38 143-8
  CrossrefPubMedGoogle Scholar
• 145 Nakagawa K, Ninomiya M, Okubo T, Aoi N, Juneja L R, Kim M, Yamanaka K, Miyazawa T. Tea catechin supplementation increases antioxidant capacity and prevents phospholipid hydroperoxidation in plasma of humans.  J Agr Food Chem. 1999;  47 3967-73
  CrossrefPubMedGoogle Scholar
• 146 Natella F, Belelli F, Gentili V, Ursini F, Scaccini C. Grape seed proanthocyanidins prevent plasma postprandial oxidative stress in humans.  J Agr Food Chem. 2002;  50 7720-5
  CrossrefPubMedGoogle Scholar
• 147 Nigdikar S V, Williams N R, Griffin B A, Howard A N. Consumption of red wine polyphenols reduces the susceptibility of low-density lipoproteins to oxidation in vivo .  Am J Clin Nutr. 1998;  68 258-65
  PubMedGoogle Scholar
• 148 O'Byrne D J, Devaraj S, Grundy S M, Jialal I. Comparison of the antioxidant effects of Concord grape juice flavonoids alpha-tocopherol on markers of oxidative stress in healthy adults.  Am J Clin Nutr. 2002;  76 1367-74
  PubMedGoogle Scholar
• 149 Pedersen C B, Kyle J, Jenkinson A M, Gardner P T, McPhail D B, Duthie G G. Effects of blueberry and cranberry juice consumption on the plasma antioxidant capacity of healthy female volunteers.  Eur J Clin Nutr. 2000;  54 405-8
  CrossrefPubMedGoogle Scholar
• 150 Princen H M, van Duyvenvoorde W, Buytenhek R, Blonk C, Tijburg L B, Langius J A, Meinders A E, Pijl H. No effect of consumption of green and black tea on plasma lipid and antioxidant levels and on LDL oxidation in smokers.  Arterioscler Thromb Vasc Biol. 1998;  18 833-41
  PubMedGoogle Scholar
• 151 Rein D, Lotito S, Holt R R, Keen C L, Schmitz H H, Fraga C G. Epicatechin in human plasma: In vivo determination and effect of chocolate consumption on plasma oxidation status.  J Nutr. 2000;  130 2109S-14
  PubMedGoogle Scholar
• 152 Serafini M, Maiani G, Ferro-Luzzi A. Alcohol-free red wine enhances plasma antioxidant capacity in humans.  J Nutr. 1998;  128 1003-7
  PubMedGoogle Scholar
• 153 Simonetti P, Ciappellano S, Gardana C, Bramati L, Pietta P. Procyanidins from Vitis vinifera seeds: in vivo effects on oxidative stress.  J Agr Food Chem. 2002;  50 6217-21
  CrossrefPubMedGoogle Scholar
• 154 Stein J H, Keevil J G, Wiebe D A, Aeschlimann S, Folts J D. Purple grape juice improves endothelial function and reduces the susceptibility of LDL cholesterol to oxidation in patients with coronary artery disease.  Circulation. 1999;  100 1050-5
  PubMedGoogle Scholar
• 155 Tikkanen M J, Wahala K, Ojala S, Vihma V, Adlercreutz H. Effect of soybean phytoestrogen intake on low density lipoprotein oxidation resistance.  Proc Natl Acad Sci USA. 1998;  95 3106-10
  CrossrefPubMedGoogle Scholar
• 156 van den Berg R, van Vliet T, Broekmans W MR, Cnubben N HP, Vaes W HJ, Roza L, Haenen G RMM, Bast A, van den Berg H. A vegetable/fruit concentrate with high antioxidant capacity has no effect on biomarkers of antioxidant status in male smokers.  J Nutr. 2001;  131 1714-22
  PubMedGoogle Scholar
• 157 Wan Y, Vinson J A, Etherton T D, Proch J, Lazarus S A, Kris-Etherton P M. Effects of cocoa powder and dark chocolate on LDL oxidative susceptibility and prostaglandin concentrations in humans.  Am J Clin Nutr. 2001;  74 596-602
  PubMedGoogle Scholar
• 158 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 antioxidative status.  Am J Clin Nutr. 1999;  69 87-94
  PubMedGoogle Scholar
• 159 Lotito S B, Frei B. Relevance of apple polyphenols as antioxidants in human plasma: contrasting in vitro and in vivo effects.  Free Radic Biol Med. 2004;  36 201-11
  PubMedGoogle Scholar
• 160 Jovanovic S V, Steenken S, Hara Y, Simic M G. Reduction potentials of flavonoid and model phenoxyl radicals. Which ring in flavonoids is responsible for antioxidant activity?.  J Chem Soc Perkin Trans. 1996;  2 2497-504
  PubMedGoogle Scholar
• 161 Jovanovic S V, Hara Y, Steenken S, Simic M G. Antioxidant potential of gallocatechins. A pulse radiolysis and laser photolysis study.  J Am Chem Soc. 1995;  117 9881-8
  CrossrefPubMedGoogle Scholar
• 162 Jovanovic S V, Steenken S, Tosic M, Marjanovic B, Simic M G. Flavonoids as antioxidants.  J Am Chem Soc. 1994;  116 4846-51
  CrossrefPubMedGoogle Scholar
• 163 Steenken S, Neta P. One-electron redox potentials of phenols. Hydroxy and amino-phenols and related compounds of biological interest. J Phys Chem 1982: 3661-7
  Google Scholar
• 164 Ferry D R, Smith A, Malkhandi J, Fyfe D W, deTakats P G, Anderson D, Baker J, Kerr D J. Phase I clinical trial of the flavonoid quercetin: pharmacokinetics and evidence for in vivo tyrosine kinase inhibition.  Clin Cancer Res. 1996;  2 659-68
  PubMedGoogle Scholar
• 165 Ayrton A D, Lewis D FV, Walker R, Ioannides C. Antimutagenicity of ellagic acid toward the food mutagen IQ: investigations into the possible mechanisms of action.  Food Chem Toxicol. 1992;  30 289-95
  PubMedGoogle Scholar
• 166 Hirose Y, Tanaka T, Kawamori T, Ohnishi M, Makita H, Mori H, Satoh K, Hara A. Chemoprevention of urinary-bladder carcinogenesis by the natural phenolic compound protocatechuic acid in rats.  Carcinogen. 1995;  16 2337-42
  PubMedGoogle Scholar
• 167 Shirai M, Moon J H, Tsushida T, Terao J. Inhibitory effect of a quercetin metabolite, quercetin 3-O-β-D-glucuronide, on lipid peroxidation in liposomal membranes.  J Agr Food Chem. 2001;  49 5602-8
  CrossrefPubMedGoogle Scholar
• 168 Terao J, Murota K, Moon J -H. Quercetin glucosides as dietary antioxidants in blood plasma: modulation of their function by metabolic conversion. In: Yoshikawa T, Toyokuni Y, Yamamoto Y and Naito Y, editors Free radicals in chemistry, biology and medicine. London; OIAC International 2000: pp 462-75
  Google Scholar
• 169 Liao K, Yin M. Individual and combined antioxidant effects of seven phenolic agents in human erythrocyte membrane ghosts and phosphatidylcholine liposome systems: importance of the partition coefficient.  J Agr Food Chem. 2000;  48 2266-70
  CrossrefPubMedGoogle Scholar
• 170 Finch S, Doyle W, Lowe C, Bates C J, Prentice A, Smithers G, Clarke P C. National Diet and Nutrition Survey. People aged 65 years and over. London; The Stationery Office 1998
  Google Scholar
• 171 Sauberlich H E. Human requirements and needs. Vitamin C status: methods and findings.  Ann NY Acad Sci. 1975;  258 438-50
  PubMedGoogle Scholar
• 172 Yoshizumi M, Tsuchiya K, Suzaki Y, Kirima K, Kyaw M, Moon J H, Terao J, Tamaki T. Quercetin glucuronide prevents VSMC hypertrophy by angiotensin II via the inhibition of JNK and AP-1 signaling pathway.  Biochem Biophys Res Commun. 2002;  293 1458-65
  CrossrefPubMedGoogle Scholar
• 173 Nees S, Weiss D R, Reichenbach-Klinke E, Rampp F, Heilmeier B, Kanbach J, Esperester A. Protective effects of flavonoids contained in the red vine leaf on venular endothelium against the attack of activated blood components in vitro .  Arzneimittel-Forsch. 2003;  53 33-41
  PubMedGoogle Scholar
• 174 Terao J, Yamaguchi S, Shirai M, Miyoshi M, Moon J H, Oshima S, Inakuma T, Tsushida T, Kato Y. Protection by quercetin and quercetin 3-O-β-d-glucuronide of peroxynitrite-induced antioxidant consumption in human plasma low-density lipoprotein.  Free Radic Res. 2001;  35 925-31
  PubMedGoogle Scholar
• 175 Day A J, Bao Y, Morgan M RA, Williamson G. Conjugation position of quercetin glucuronides and effect on biological activity.  Free Radic Biol Med. 2000;  29 1234-43
  CrossrefPubMedGoogle Scholar
• 176 Thompson L U, Yoon J H, Jenkins D J, Wolever T M, Jenkins A L. Relationship between polyphenol intake and blood glucose response of normal and diabetic individuals.  Am J Clin Nutr. 1984;  39 745-51
  PubMedGoogle Scholar
• 177 Gin H, Rigalleau V, Caubet O, Masquelier J, Aubertin J. Effects of red wine, tannic acid, or ethanol on glucose tolerance in non-insulin-dependent diabetic patients and on starch digestibility in vitro .  Metabolism. 1999;  48 1179-83
  CrossrefPubMedGoogle Scholar
• 178 Johnston K L, Clifford M N, Morgan L M. Coffee acutely modifies gastrointestinal hormone secretion and glucose tolerance in humans: glycemic effects of chlorogenic acid and caffeine.  Am J Clin Nutr. 2003;  78 728-33
  PubMedGoogle Scholar
• 179 Johnston K L, Clifford M N, Morgan L M. Possible role for apple juice phenolic compounds in the acute modification of glucose tolerance and gastrointestinal hormone secretion in humans.  J Sci Food Agric. 2002;  82 1800-5
  CrossrefPubMedGoogle Scholar
• 180 Coutinho M, Gerstein H C, Wang Y, Yusef S. The relationship between glucose and incident cardiovascular events: a metaregression analysis of published data from 20 studies of 95,783 individuals followed for 12.4 years.  Diabetes Care. 1999;  22 233-40
  CrossrefPubMedGoogle Scholar
• 181 van Dam R M, Feskens E J. Coffee consumption and risk of type 2 diabetes mellitus.  Lancet. 2002;  360 1477-8
  CrossrefPubMedGoogle Scholar
• 182 Facchini F S, Saylor K L. A low-iron-available, polyphenol-enriched, carbohydrate-restricted diet to slow progression of diabetic nephropathy.  Diabetes. 2003;  52 1204-9
  PubMedGoogle Scholar
• 183 Hara Y, Honda M. The inhibition of a-amylase by tea polyphenols.  Agric Biol Chem. 1990;  54 1939-45
  PubMedGoogle Scholar
• 184 Matsumoto N, Ishigaki F, Ishigaki A, Iwashina H, Hara Y. Reduction of blood-glucose levels by tea catechin.  Biosci Biotechnol Biochem. 1993;  57 525-7
  PubMedGoogle Scholar
• 185 Matsui T, Ebuchi S, Kobayashi M, Fukui K, Sugita K, Terahara N, Matsumoto K. Anti-hyperglycemic effect of diacylated anthocyanin derived from Ipomoea batatas cultivar Ayamurasaki can be achieved through the α-glucosidase inhibitory action.  J Agr Food Chem. 2002;  50 7244-8
  CrossrefPubMedGoogle Scholar
• 186 Kawabata J, Mizuhata K, Sato E, Nishioka T, Aoyama Y, Kasai T. 6-hydroxyflavonoids as α-glucosidase inhibitors from marjoram (Origanum majorana) leaves.  Biosci Biotechnol Biochem. 2003;  67 445-7
  CrossrefPubMedGoogle Scholar
• 187 Hilt P, Schieber A, Yildirim C, Arnold G, Klaiber I, Conrad J, Beifuss U, Carle R. Detection of phloridzin in strawberries (Fragaria x ananassa Duch.) by HPLC-PDA-MS/MS and NMR spectroscopy.  J Agr Food Chem. 2003;  51 2896-9
  CrossrefPubMedGoogle Scholar
• 188 Nakazawa F. Influence of phloridzin on intestinal absorption.  Tohoku J Exptl Med. 1922;  3 288-94
  PubMedGoogle Scholar
• 189 Alvarado F. Hypothesis for the interaction of phlorizin and phloretin with membrane carriers for sugars.  Biochim Biophys Acta. 1967;  135 483-95
  PubMedGoogle Scholar
• 190 Alvarado F, Crane R K. Phlorizin as a competitive inhibitor of the active transport of sugars by hamster small intestine.  Biochim Biophys Acta. 1962;  56 170-2
  CrossrefPubMedGoogle Scholar
• 191 Crane R K. Intestinal absorption of sugars.  Phys Rev. 1960;  40 789-825
  PubMedGoogle Scholar
• 192 Welsch C A, Lachance P A, Wasserman B P. Dietary phenolic compounds: Inhibition of Na⁺-dependent d-glucose uptake in rat intestinal brush border membrane vesicles.  J Nutr. 1989;  119 1698-1704
  PubMedGoogle Scholar
• 193 Kobayashi Y, Suzuki M, Satsu H, Arai S, Hara Y, Suzuki K, Miyamoto Y, Shimizu M. Green tea polyphenols inhibit the sodium-dependent glucose transporter of intestinal epithelial cells by a competitive mechanism.  J Agr Food Chem. 2000;  48 5618-23
  CrossrefPubMedGoogle Scholar
• 194 Noteborn H PJM, Jansen E, Benito S, Mengelers M JB. Oral absorption and metabolism of quercetin and sugar-conjugated derivatives in specific transport systems.  Cancer Lett. 1997;  114 175-7
  CrossrefPubMedGoogle Scholar
• 195 Walgren R A, Walle U K, Walle T. Transport of quercetin and its glucosides across human intestinal epithelial Caco-2 cells.  Biochem Pharmacol. 1998;  55 1721-7
  CrossrefPubMedGoogle Scholar
• 196 Gee J M, DuPont M S, Rhodes M JC, Johnson I T. Quercetin glucosides interact with the intestinal glucose transport pathway.  Free Radic Biol Med. 1998;  25 19-25
  CrossrefPubMedGoogle Scholar
• 197 Walgren R A, Lin J T, Kinne R K, Walle T. Cellular uptake of dietary flavonoid quercetin 4′-β-glucoside by sodium-dependent glucose transporter SGLT1.  J Pharmacol Exp Ther. 2000;  294 837-43
  PubMedGoogle Scholar
• 198 Walgren R A, Karnaky K J Jr., Lindenmayer G E, Walle T. Efflux of dietary flavonoid quercetin 4′-beta-glucoside across human intestinal Caco-2 cell monolayers by apical multidrug resistance-associated protein-2.  J Pharmacol Exp Ther. 2000;  294 830-6
  PubMedGoogle Scholar
• 199 Song J, Kwon O, Chen S, Daruwala R, Eck P, Park J B, Levine M. Flavonoid inhibition of sodium-dependent vitamin C transporter 1 (SVCT1) and glucose transporter isoform 2 (GLUT2), intestinal transporters for vitamin C and glucose.  J Biol Chem. 2002;  277 15 252-60
  PubMedGoogle Scholar
• 200 Wolffram S, Block M, Ader P. Quercetin-3-glucoside is transported by the glucose carrier SGLT1 across the brush border membrane of rat small intestine.  J Nutr. 2002;  132 630-5
  PubMedGoogle Scholar
• 201 Deutsch J C, SanthoshKumar C R. Quantitation of homogentisic acid in normal human plasma.  J Chromatogr B Biomed Appl. 1996;  667 147-51
  PubMedGoogle Scholar
• 202 Deutsch J C. Determination of p-hydroxyphenylpyruvate, p-hydroxyphenyllactate and tyrosine in normal human plasma by gas chromatography-mass spectrometry isotope-dilution assay.  J Chromatogr B. 1997;  690 1-6
  PubMedGoogle Scholar
• 203 Heinecke J W. Tyrosyl radical production by myeloperoxidase: a phagocyte pathway for lipid peroxidation and dityrosine cross-linking of proteins.  Toxicology. 2002;  177 11-22
  CrossrefPubMedGoogle Scholar
• 204 Gregory J R, Collins D L, Davies P SW, Hughes J M, Clarke P C. National Diet and Nutrition Survey. Children aged one and a half years to four and a half years. London; HMSO 1995
  Google Scholar
• 205 Gregory J, Lowe S, Bates C J, Prentice A, Jackson L V, Smithers G, Wenlock R, Farron M. National Diet and Nutrition Survey. Young people aged 4 to 18 years. London; The Stationery Office 2000
  Google Scholar
• 206 Halliwell B, Gutteridge J M. Free Radicals in Biology and Medicine. 3th edition Oxford; Oxford University Press 1999
  Google Scholar
• 207 Jovanovic S V, Hara Y, Steenken S, Simic M G. Antioxidant potential of theaflavins. a pulse radiolysis study.  J Am Chem Soc. 1997;  119 5337-43
  CrossrefPubMedGoogle Scholar
• 208 Buettner G R. The pecking order of free radicals and antioxidants: lipid peroxidation, alpha-tocopherol, and ascorbate.  Arch Biochem Biophys. 1993;  300 535-43
  CrossrefPubMedGoogle Scholar
• 209 Jovanovic S V, Steenken S, Boone C W, Simic M G. H-atom transfer is a preferred antioxidant mechanism of curcumin.  J Am Chem Soc. 1999;  121 9677-81
  CrossrefPubMedGoogle Scholar
• 210 Steenken S, Neta P. Electron transfer rates and equilibria between substituted phenoxide ions and phenoxyl radicals.  J Phys Chem. 1979;  83 1134-7
  CrossrefPubMedGoogle Scholar
• 211 Jovanovic S V, Tosic M, Simic M G. Use of Hammett correlation and σ⁺ for calculation of one-electron redox potentials of antioxidants.  J Phys Chem. 1991;  95 10 824-7
  PubMedGoogle Scholar
• 212 Koppenol W H. Oxyradical reactions: from bond-dissociation energies to reduction potentials.  FEBS Lett. 1990;  264 165-7
  CrossrefPubMedGoogle Scholar
• 213 Jovanovic S V, Jankovic I, Josimovic L. Electron transfer reactions of alkyl peroxy radicals.  J Am Chem Soc. 1992;  114 9018-21
  CrossrefPubMedGoogle Scholar
• 214 Jones D P, Carlson J L, Mody V C, Cai J, Lynn M J, Sternberg P. Redox state of glutathione in human plasma.  Free Radic Biol Med. 2000;  28 625-35
  CrossrefPubMedGoogle Scholar

M. N. Clifford

Centre for Nutrition & Food Safety

School of Biomedical & Molecular Sciences

University of Surrey

Guildford

Surrey GU2 7XH

UK

Fax: +44-1483-300374

Email: M.Clifford@Surrey.ac.uk