Some anthocyanins could be efficiently absorbed across the gastrointestinal mucosa: Extensive presystemic metabolism reduces apparent bioavailability

Journal of Agricultural and Food Chemistry

Volumn 62, Issue 18, 2014, Pages 3904-3911

  Fang, Jim ^a  

^a UNIVERSITY OF SASKATCHEWAN   (Canada)

Author keywords

absorption; anthocyanin; bioavailability; cyanidin 3 glucoside; first pass metabolism; pelargonidin 3 glucoside

Indexed keywords

ABSORPTION; BIOCHEMISTRY; CARBOHYDRATES; METABOLISM; PHYSIOLOGY;

4-HYDROXYBENZOIC ACIDS; BIOAVAILABILITY; CYANIDIN; ORAL ADMINISTRATION; PELARGONIDIN; PLASMA CONCENTRATION; PROTOCATECHUIC ACID; SYSTEMIC CIRCULATION;

ANTHOCYANINS;

ANTHOCYANIN;

ANIMAL; BIOAVAILABILITY; GASTROINTESTINAL TRACT; HUMAN; METABOLISM; MUCOSA;

ANIMALS; ANTHOCYANINS; BIOLOGICAL AVAILABILITY; GASTROINTESTINAL TRACT; HUMANS; MUCOUS MEMBRANE;

ANIMALIA; RATTUS;

EID: 84900314648     PISSN: 00218561     EISSN: 15205118     Source Type: Journal    
DOI: 10.1021/jf405356b     Document Type: Review

References (94)

1. Basu, A.; Rhone, M.; Lyons, T. J. Berries: emerging impact on cardiovascular health Nutr. Rev. 2010, 68, 168-177
2. Giacalone, M.; Di Sacco, F.; Traupe, I.; Topini, R.; Forfori, F.; Giunta, F. Antioxidant and neuroprotective properties of blueberry polyphenols: a critical review Nutr. Neurosci. 2011, 14, 119-125
3. Tsuda, T. Dietary anthocyanin-rich plants: biochemical basis and recent progress in health benefits studies Mol. Nutr. Food Res. 2012, 56, 159-170
4. Kay, C. D.; Hooper, L.; Kroon, P. A.; Rimm, E. B.; Cassidy, A. Relative impact of flavonoid composition, dose and structure on vascular function: a systematic review of randomised controlled trials of flavonoid-rich food products Mol. Nutr. Food Res. 2012, 56, 1605-1616
5. Chen, A. Y.; Chen, Y. C. A review of the dietary flavonoid, kaempferol on human health and cancer chemoprevention Food Chem. 2013, 138, 2099-2107
6. Bhagwat, S. A.; Haytowitz, D. B.; Harnly, J.; Holden, J. M. Update of the USDA database for the flavonoid content of selected foods J. Nutr. 2005, 135, 3050s-3050s
7. Eldridge, A. L.; Haytowitz, D.; Bhagwat, S.; Gebhardt, S. E.; Holden, J. M.; Beecher, G.; Peterson, J.; Dwyer, J. T. Flavonoid content of vegetables: the USDA's Flavonoid Database FASEB J. 2003, 17, A766-A767
8. Cassidy, A.; O'Reilly, E. J.; Kay, C.; Sampson, L.; Franz, M.; Forman, J. P.; Curhan, G.; Rimm, E. B. Habitual intake of flavonoid subclasses and incident hypertension in adults Am. J. Clin. Nutr. 2011, 93, 338-347
9. Jennings, A.; Welch, A. A.; Fairweather-Tait, S. J.; Kay, C.; Minihane, A. M.; Chowienczyk, P.; Jiang, B.; Cecelja, M.; Spector, T.; Macgregor, A.; Cassidy, A. Higher anthocyanin intake is associated with lower arterial stiffness and central blood pressure in women Am. J. Clin. Nutr. 2012, 96, 781-788
10. McCullough, M. L.; Peterson, J. J.; Patel, R.; Jacques, P. F.; Shah, R.; Dwyer, J. T. Flavonoid intake and cardiovascular disease mortality in a prospective cohort of US adults Am. J. Clin. Nutr. 2012, 95, 454-464
11. Mink, P. J.; Scrafford, C. G.; Barraj, L. M.; Harnack, L.; Hong, C. P.; Nettleton, J. A.; Jacobs, D. R., Jr. Flavonoid intake and cardiovascular disease mortality: a prospective study in postmenopausal women Am. J. Clin. Nutr. 2007, 85, 895-909
12. Wedick, N. M.; Pan, A.; Cassidy, A.; Rimm, E. B.; Sampson, L.; Rosner, B.; Willett, W.; Hu, F. B.; Sun, Q.; van Dam, R. M. Dietary flavonoid intakes and risk of type 2 diabetes in US men and women Am. J. Clin. Nutr. 2012, 95, 925-933
13. Zamora-Ros, R.; Agudo, A.; Lujan-Barroso, L.; Romieu, I.; Ferrari, P.; Knaze, V.; Bueno-de-Mesquita, H. B.; Leenders, M.; Travis, R. C.; Navarro, C.; Sanchez-Cantalejo, E.; Slimani, N.; Scalbert, A.; Fedirko, V.; Hjartaker, A.; Engeset, D.; Skeie, G.; Boeing, H.; Forster, J.; Li, K.; Teucher, B.; Agnoli, C.; Tumino, R.; Mattiello, A.; Saieva, C.; Johansson, I.; Stenling, R.; Redondo, M. L.; Wallstrom, P.; Ericson, U.; Khaw, K. T.; Mulligan, A. A.; Trichopoulou, A.; Dilis, V.; Katsoulis, M.; Peeters, P. H.; Igali, L.; Tjonneland, A.; Halkjaer, J.; Touillaud, M.; Perquier, F.; Fagherazzi, G.; Amiano, P.; Ardanaz, E.; Bredsdorff, L.; Overvad, K.; Ricceri, F.; Riboli, E.; Gonzalez, C. A. Dietary flavonoid and lignan intake and gastric adenocarcinoma risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study Am. J. Clin. Nutr. 2012, 96, 1398-1408
14. Touvier, M.; Druesne-Pecollo, N.; Kesse-Guyot, E.; Andreeva, V. A.; Fezeu, L.; Galan, P.; Hercberg, S.; Latino-Martel, P. Dual association between polyphenol intake and breast cancer risk according to alcohol consumption level: a prospective cohort study Breast Cancer Res. Treat. 2012, 137, 225-236
15. Basu, A.; Du, M.; Leyva, M. J.; Sanchez, K.; Betts, N. M.; Wu, M.; Aston, C. E.; Lyons, T. J. Blueberries decrease cardiovascular risk factors in obese men and women with metabolic syndrome J. Nutr. 2010, 140, 1582-1587
16. Dohadwala, M. M.; Holbrook, M.; Hamburg, N. M.; Shenouda, S. M.; Chung, W. B.; Titas, M.; Kluge, M. A.; Wang, N.; Palmisano, J.; Milbury, P. E.; Blumberg, J. B.; Vita, J. A. Effects of cranberry juice consumption on vascular function in patients with coronary artery disease Am. J. Clin. Nutr. 2011, 93, 934-940
17. Stull, A. J.; Cash, K. C.; Johnson, W. D.; Champagne, C. M.; Cefalu, W. T. Bioactives in blueberries improve insulin sensitivity in obese, insulin-resistant men and women J. Nutr. 2010, 140, 1764-1768
18. Biedermann, L.; Mwinyi, J.; Scharl, M.; Frei, P.; Zeitz, J.; Kullak-Ublick, G. A.; Vavricka, S. R.; Fried, M.; Weber, A.; Humpf, H. U.; Peschke, S.; Jetter, A.; Krammer, G.; Rogler, G. Bilberry ingestion improves disease activity in mild to moderate ulcerative colitis-an open pilot study J. Crohns Colitis 2012, 7, 271-279
19. Manach, C.; Williamson, G.; Morand, C.; Scalbert, A.; Remesy, C. Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies Am. J. Clin. Nutr. 2005, 81, 230S-242S
20. Crozier, A.; Del Rio, D.; Clifford, M. N. Bioavailability of dietary flavonoids and phenolic compounds Mol. Aspects Med. 2010, 31, 446-467
21. Kroon, P. A.; Clifford, M. N.; Crozier, A.; Day, A. J.; Donovan, J. L.; Manach, C.; Williamson, G. How should we assess the effects of exposure to dietary polyphenols in vitro? Am. J. Clin. Nutr. 2004, 80, 15-21
22. Prior, R. L.; Wu, X. L. Anthocyanins: structural characteristics that result in unique metabolic patterns and biological activities Free Radical Res. 2006, 40, 1014-1028
23. Kay, C. D. Aspects of anthocyanin absorption, metabolism and pharmacokinetics in humans Nutr. Res. Rev. 2006, 19, 137-146
24. Del Rio, D.; Rodriguez-Mateos, A.; Spencer, J. P.; Tognolini, M.; Borges, G.; Crozier, A. Dietary (poly)phenolics in human health: structures, bioavailability, and evidence of protective effects against chronic diseases Antioxid. Redox Signal. 2013, 18, 1818-1892
25. Ichiyanagi, T.; Shida, Y.; Rahman, M. M.; Hatano, Y.; Konishi, T. Bioavailability and tissue distribution of anthocyanins in bilberry (Vaccinium myrtillus L.) extract in rats J. Agric. Food Chem. 2006, 54, 6578-6587
26. Marczylo, T. H.; Cooke, D.; Brown, K.; Steward, W. P.; Gescher, A. J. Pharmacokinetics and metabolism of the putative cancer chemopreventive agent cyanidin-3-glucoside in mice Cancer Chemother. Pharmacol. 2009, 64, 1261-1268
27. Borges, G.; Roowi, S.; Rouanet, J. M.; Duthie, G. G.; Lean, M. E.; Crozier, A. The bioavailability of raspberry anthocyanins and ellagitannins in rats Mol. Nutr. Food Res. 2007, 51, 714-725
28. Matsumoto, H.; Ichiyanagi, T.; Iida, H.; Ito, K.; Tsuda, T.; Hirayama, M.; Konishi, T. Ingested delphinidin-3-rutinoside is primarily excreted to urine as the intact form and to bile as the methylated form in rats J. Agric. Food Chem. 2006, 54, 578-582
29. Felgines, C.; Talavera, S.; Gonthier, M. P.; Texier, O.; Scalbert, A.; Lamaison, J. L.; Remesy, C. Strawberry anthocyanins are recovered in urine as glucuro- and sulfoconjugates in humans J. Nutr. 2003, 133, 1296-1301
30. Felgines, C.; Texier, O.; Besson, C.; Fraisse, D.; Lamaison, J. L.; Remesy, C. Blackberry anthocyanins are slightly bioavailable in rats J. Nutr. 2002, 132, 1249-1253
31. Nemeth, K.; Plumb, G. W.; Berrin, J.-G.; Juge, N.; Jacob, R.; Naim, H. Y.; Williamson, G.; Swallow, D. M.; Kroon, P. A. Deglycosylation by small intestinal epithelial cell β-glucosidases is a critical step in the absorption and metabolism of dietary flavonoid glycosides in humans Eur. J. Nutr. 2003, 42, 29-42
32. Vitaglione, P.; Donnarumma, G.; Napolitano, A.; Galvano, F.; Gallo, A.; Scalfi, L.; Fogliano, V. Protocatechuic acid is the major human metabolite of cyanidin-glucosides J. Nutr. 2007, 137, 2043-2048
33. Chen, W.; Wang, D.; Wang, L. S.; Bei, D.; Wang, J.; See, W. A.; Mallery, S. R.; Stoner, G. D.; Liu, Z. Pharmacokinetics of protocatechuic acid in mouse and its quantification in human plasma using LC-tandem mass spectrometry J. Chromatogr., B: Anal. Technol. Biomed. Life Sci. 2012, 908, 39-44
34. Azzini, E.; Vitaglione, P.; Intorre, F.; Napolitano, A.; Durazzo, A.; Foddai, M. S.; Fumagalli, A.; Catasta, G.; Rossi, L.; Venneria, E.; Raguzzini, A.; Palomba, L.; Fogliano, V.; Maiani, G. Bioavailability of strawberry antioxidants in human subjects Br. J. Nutr. 2010, 104, 1165-1173
35. Shargel, L.; Yu, A. B. C.; Wu-Pong, S. Applied Biopharmaceutics & Pharmacokinetics, 6 th ed.; McGraw-Hill: New York, 2012.
36. He, J.; Wallace, T. C.; Keatley, K. E.; Failla, M. L.; Giusti, M. M. Stability of black raspberry anthocyanins in the digestive tract lumen and transport efficiency into gastric and small intestinal tissues in the rat J. Agric. Food Chem. 2009, 57, 3141-3148
37. Talavera, S.; Felgines, C.; Texier, O.; Besson, C.; Gil-Izquierdo, A.; Lamaison, J. L.; Remesy, C. Anthocyanin metabolism in rats and their distribution to digestive area, kidney, and brain J. Agric. Food Chem. 2005, 53, 3902-3908
38. Faria, A.; Pestana, D.; Azevedo, J.; Martel, F.; de Freitas, V.; Azevedo, I.; Mateus, N.; Calhau, C. Absorption of anthocyanins through intestinal epithelial cells-putative involvement of GLUT2 Mol. Nutr. Food Res. 2009, 53, 1430-1437
39. Steinert, R. E.; Ditscheid, B.; Netzel, M.; Jahreis, G. Absorption of black currant anthocyanins by monolayers of human intestinal epithelial Caco-2 cells mounted in ussing type chambers J. Agric. Food Chem. 2008, 56, 4995-5001
40. Yi, W.; Akoh, C. C.; Fischer, J.; Krewer, G. Absorption of anthocyanins from blueberry extracts by Caco-2 human intestinal cell monolayers J. Agric. Food Chem. 2006, 54, 5651-5658
41. Jakesevic, M.; Xu, J.; Aaby, K.; Jeppsson, B.; Ahrne, S.; Molin, G. Effects of bilberry (Vaccinium myrtillus) in combination with lactic acid bacteria on intestinal oxidative stress induced by ischemia-reperfusion in mouse J. Agric. Food Chem. 2013, 61, 3468-3478
42. Jurgonski, A.; Juskiewicz, J.; Zdunczyk, Z. An anthocyanin-rich extract from Kamchatka honeysuckle increases enzymatic activity within the gut and ameliorates abnormal lipid and glucose metabolism in rats Nutrition 2013, 29, 898-902
43. Mallery, S. R.; Budendorf, D. E.; Larsen, M. P.; Pei, P.; Tong, M.; Holpuch, A. S.; Larsen, P. E.; Stoner, G. D.; Fields, H. W.; Chan, K. K.; Ling, Y.; Liu, Z. Effects of human oral mucosal tissue, saliva, and oral microflora on intraoral metabolism and bioactivation of black raspberry anthocyanins Cancer Prev. Res. (Phila.) 2011, 4, 1209-1221
44. Berrin, J. G.; McLauchlan, W. R.; Needs, P.; Williamson, G.; Puigserver, A.; Kroon, P. A.; Juge, N. Functional expression of human liver cytosolic β-glucosidase in Pichia pastoris. Insights into its role in the metabolism of dietary glucosides Eur. J. Biochem. 2002, 269, 249-258
45. Talavera, S.; Felgines, C.; Texier, O.; Besson, C.; Manach, C.; Lamaison, J.-L.; Remesy, C. Anthocyanins are efficiently absorbed from the small intestine in rats J. Nutr. 2004, 134, 2275-2279
46. Woodward, G. M.; Needs, P. W.; Kay, C. D. Anthocyanin-derived phenolic acids form glucuronides following simulated gastrointestinal digestion and microsomal glucuronidation Mol. Nutr. Food Res. 2011, 55, 378-386
47. Russell, W. R.; Scobbie, L.; Labat, A.; Duthie, G. G. Selective bio-availability of phenolic acids from Scottish strawberries Mol. Nutr. Food Res. 2009, 53 (Suppl. 1) S85-S91
48. Guo, X.; Chen, X.; Li, L.; Shen, Z.; Wang, X.; Zheng, P.; Duan, F.; Ma, Y.; Bi, K. LC-MS determination and pharmacokinetic study of six phenolic components in rat plasma after taking traditional Chinese medicinal-preparation: Guanxinning lyophilized powder for injection J. Chromatogr., B: Anal. Technol. Biomed. Life Sci. 2008, 873, 51-58
49. Talavera, S.; Felgines, C.; Texier, O.; Besson, C.; Lamaison, J. L.; Remesy, C. Anthocyanins are efficiently absorbed from the stomach in anesthetized rats J. Nutr. 2003, 133, 4178-4182
50. Stalmach, A.; Edwards, C. A.; Wightman, J. D.; Crozier, A. Gastrointestinal stability and bioavailability of (poly)phenolic compounds following ingestion of Concord grape juice by humans Mol. Nutr. Food Res. 2012, 56, 497-509
51. Bermudez-Soto, M. J.; Tomas-Barberan, F. A.; Garcia-Conesa, M. T. Stability of polyphenols in chokeberry (Aronia melanocarpa) subjected to in vitro gastric and pancreatic digestion Food Chem. 2007, 102, 865-874
52. Passamonti, S.; Vrhovsek, U.; Vanzo, A.; Mattivi, F. The stomach as a site for anthocyanins absorption from food FEBS Lett. 2003, 544, 210-213
53. Vanzo, A.; Terdoslavich, M.; Brandoni, A.; Torres, A. M.; Vrhovsek, U.; Passamonti, S. Uptake of grape anthocyanins into the rat kidney and the involvement of bilitranslocase Mol. Nutr. Food Res. 2008, 52, 1106-1116
54. Fernandes, I.; de Freitas, V.; Reis, C.; Mateus, N. A new approach on the gastric absorption of anthocyanins Food Funct. 2012, 3, 508-516
55. Gonzalez-Barrio, R.; Edwards, C. A.; Crozier, A. Colonic catabolism of ellagitannins, ellagic acid, and raspberry anthocyanins: in vivo and in vitro studies Drug Metab. Dispos. 2011, 39, 1680-1688
56. Fleschhut, J.; Kratzer, F.; Rechkemmer, G.; Kulling, S. E. Stability and biotransformation of various dietary anthocyanins in vitro Eur. J. Nutr. 2006, 45, 7-18
57. Perez-Vicente, A.; Gil-Izquierdo, A.; Garcia-Viguera, C. In vitro gastrointestinal digestion study of pomegranate juice phenolic compounds, anthocyanins, and vitamin C J. Agric. Food Chem. 2002, 50, 2308-2312
58. Kahle, K.; Kraus, M.; Scheppach, W.; Ackermann, M.; Ridder, F.; Richling, E. Studies on apple and blueberry fruit constituents: do the polyphenols reach the colon after ingestion? Mol. Nutr. Food Res. 2006, 50, 418-423
59. Talavera, S.; Felgines, C.; Texier, O.; Besson, C.; Manach, C.; Lamaison, J. L.; Remesy, C. Anthocyanins are efficiently absorbed from the small intestine in rats J. Nutr. 2004, 134, 2275-2279
60. Frank, T.; Netzel, M.; Strass, G.; Bitsch, R.; Bitsch, I. Bioavailability of anthocyanidin-3-glucosides following consumption of red wine and red grape juice Can. J. Physiol. Pharmacol. 2003, 81, 423-435
61. Mazza, G.; Kay, C. D.; Cottrell, T.; Holub, B. J. Absorption of anthocyanins from blueberries and serum antioxidant status in human subjects J. Agric. Food Chem. 2002, 50, 7731-7737
62. Aura, A. M.; Martin-Lopez, P.; O'Leary, K. A.; Williamson, G.; Oksman-Caldentey, K. M.; Poutanen, K.; Santos-Buelga, C. In vitro metabolism of anthocyanins by human gut microflora Eur. J. Nutr. 2005, 44, 133-142
63. Hanske, L.; Engst, W.; Loh, G.; Sczesny, S.; Blaut, M.; Braune, A. Contribution of gut bacteria to the metabolism of cyanidin 3-glucoside in human microbiota-associated rats Br. J. Nutr. 2013, 109, 1433-1441
64. He, J.; Magnuson, B. A.; Giusti, M. M. Analysis of anthocyanins in rat intestinal contents-impact of anthocyanin chemical structure on fecal excretion J. Agric. Food Chem. 2005, 53, 2859-2866
65. Sanchez-Patan, F.; Cueva, C.; Monagas, M.; Walton, G. E.; Gibson, G. R.; Quintanilla-Lopez, J. E.; Lebron-Aguilar, R.; Martin-Alvarez, P. J.; Moreno-Arribas, M. V.; Bartolome, B. In vitro fermentation of a red wine extract by human gut microbiota: changes in microbial groups and formation of phenolic metabolites J. Agric. Food Chem. 2012, 60, 2136-2147
66. Hidalgo, M.; Oruna-Concha, M. J.; Kolida, S.; Walton, G. E.; Kallithraka, S.; Spencer, J. P.; de Pascual-Teresa, S. Metabolism of anthocyanins by human gut microflora and their influence on gut bacterial growth J. Agric. Food Chem. 2012, 60, 3882-3890
67. Forester, S. C.; Waterhouse, A. L. Identification of Cabernet Sauvignon anthocyanin gut microflora metabolites J. Agric. Food Chem. 2008, 56, 9299-9304
68. Gill, C. I.; McDougall, G. J.; Glidewell, S.; Stewart, D.; Shen, Q.; Tuohy, K.; Dobbin, A.; Boyd, A.; Brown, E.; Haldar, S.; Rowland, I. R. Profiling of phenols in human fecal water after raspberry supplementation J. Agric. Food Chem. 2010, 58, 10389-10395
69. Jimenez-Giron, A.; Queipo-Ortuno, M. I.; Boto-Ordonez, M.; Munoz-Gonzalez, I.; Sanchez-Patan, F.; Monagas, M.; Martin-Alvarez, P. J.; Murri, M.; Tinahones, F. J.; Andres-Lacueva, C.; Bartolome, B.; Moreno-Arribas, M. V. Comparative study of microbial-derived phenolic metabolites in human feces after intake of gin, red wine, and dealcoholized red wine J. Agric. Food Chem. 2013, 61, 3909-3915
70. Keppler, K.; Humpf, H. U. Metabolism of anthocyanins and their phenolic degradation products by the intestinal microflora Bioorg. Med. Chem. 2005, 13, 5195-5205
71. Gonzalez-Barrio, R.; Borges, G.; Mullen, W.; Crozier, A. Bioavailability of anthocyanins and ellagitannins following consumption of raspberries by healthy humans and subjects with an ileostomy J. Agric. Food Chem. 2010, 58, 3933-3939
72. Borges, G.; Lean, M. E.; Roberts, S. A.; Crozier, A. Bioavailability of dietary (poly)phenols: a study with ileostomists to discriminate between absorption in small and large intestine Food Funct. 2013, 4, 754-762
73. Wu, X.; Pittman, H. E., 3rd; Prior, R. L. Fate of anthocyanins and antioxidant capacity in contents of the gastrointestinal tract of weanling pigs following black raspberry consumption J. Agric. Food Chem. 2006, 54, 583-589
74. Wu, X.; Pittman, H. E., 3rd; McKay, S.; Prior, R. L. Aglycones and sugar moieties alter anthocyanin absorption and metabolism after berry consumption in weanling pigs J. Nutr. 2005, 135, 2417-2424
75. Czank, C.; Cassidy, A.; Zhang, Q.; Morrison, D. J.; Preston, T.; Kroon, P. A.; Botting, N. P.; Kay, C. D. Human metabolism and elimination of the anthocyanin, cyanidin-3-glucoside: a (13)C-tracer study Am. J. Clin. Nutr. 2013, 97, 995-1003
76. Felgines, C.; Krisa, S.; Mauray, A.; Besson, C.; Lamaison, J. L.; Scalbert, A.; Merillon, J. M.; Texier, O. Radiolabelled cyanidin 3- O -glucoside is poorly absorbed in the mouse Br. J. Nutr. 2010, 103, 1738-1745
77. Hassimotto, N. M.; Genovese, M. I.; Lajolo, F. M. Absorption and metabolism of cyanidin-3-glucoside and cyanidin-3-rutinoside extracted from wild mulberry (Morus nigra L.) in rats Nutr. Res. (N.Y.) 2008, 28, 198-207
78. Wu, X.; Cao, G.; Prior, R. L. Absorption and metabolism of anthocyanins in elderly women after consumption of elderberry or blueberry J. Nutr. 2002, 132, 1865-1871
79. Tian, Q.; Giusti, M. M.; Stoner, G. D.; Schwartz, S. J. Urinary excretion of black raspberry (Rubus occidentalis) anthocyanins and their metabolites J. Agric. Food Chem. 2006, 54, 1467-1472
80. Felgines, C.; Talavera, S.; Texier, O.; Gil-Izquierdo, A.; Lamaison, J.-L.; Remesy, C. Blackberry anthocyanins are mainly recovered from urine as methylated and glucuronidated conjugates in humans J. Agric. Food Chem. 2005, 53, 7721-7727
81. Kay, C. D.; Mazza, G. J.; Holub, B. J. Anthocyanins exist in the circulation primarily as metabolites in adult men J. Nutr. 2005, 135, 2582-2588
82. Ichiyanagi, T.; Shida, Y.; Rahman, M. M.; Hatano, Y.; Konishi, T. Extended glucuronidation is another major path of cyanidin 3- O -β- d -glucopyranoside metabolism in rats J. Agric. Food Chem. 2005, 53, 7312-7319
83. Ichiyanagi, T.; Rahman, M. M.; Kashiwada, Y.; Ikeshiro, Y.; Shida, Y.; Hatano, Y.; Matsumoto, H.; Hirayama, M.; Tsuda, T.; Konishi, T. Absorption and metabolism of delphinidin 3- O -β- d -glucopyranoside in rats Free Radical Biol. Med. 2004, 36, 930-937
84. 14C]protocatechuic acid in the rat. Aromatic dehydroxylation J. Pharm. Pharmacol. 1968, 20, 610-618
85. Bub, A.; Watzl, B.; Heeb, D.; Rechkemmer, G.; Briviba, K. Malvidin-3-glucoside bioavailability in humans after ingestion of red wine, dealcoholized red wine and red grape juice Eur. J. Nutr. 2001, 40, 113-120
86. Charron, C. S.; Kurilich, A. C.; Clevidence, B. A.; Simon, P. W.; Harrison, D. J.; Britz, S. J.; Baer, D. J.; Novotny, J. A. Bioavailability of anthocyanins from purple carrot juice: effects of acylation and plant matrix J. Agric. Food Chem. 2009, 57, 1226-1230
87. 14C-labeled grape polyphenols in the periphery and the central nervous system following oral administration J. Med. Food 2010, 13, 926-933
88. Milbury, P. E.; Cao, G.; Prior, R. L.; Blumberg, J. Bioavailablility of elderberry anthocyanins Mech. Ageing Dev. 2002, 123, 997-1006
89. Cai, H.; Thomasset, S. C.; Berry, D. P.; Garcea, G.; Brown, K.; Steward, W. P.; Gescher, A. J. Determination of anthocyanins in the urine of patients with colorectal liver metastases after administration of bilberry extract Biomed. Chromatogr. 2011, 25, 660-663
90. Felgines, C.; Talavera, S.; Texier, O.; Gil-Izquierdo, A.; Lamaison, J. L.; Remesy, C. Blackberry anthocyanins are mainly recovered from urine as methylated and glucuronidated conjugates in humans J. Agric. Food Chem. 2005, 53, 7721-7727
91. Miyazawa, T.; Nakagawa, K.; Kudo, M.; Muraishi, K.; Someya, K. Direct intestinal absorption of red fruit anthocyanins, cyanidin-3-glucoside and cyanidin-3,5-diglucoside, into rats and humans J. Agric. Food Chem. 1999, 47, 1083-1091
92. Andlauer, W.; Stumpf, C.; Frank, K.; Furst, P. Absorption and metabolism of anthocyanin cyanidin-3-glucoside in the isolated rat small intestine is not influenced by ethanol Eur. J. Nutr. 2003, 42, 217-223
93. Tsuda, T.; Horio, F.; Osawa, T. Absorption and metabolism of cyanidin 3- O -β- d -glucoside in rats FEBS Lett. 1999, 449, 179-182
94. Dreiseitel, A.; Oosterhuis, B.; Vukman, K. V.; Schreier, P.; Oehme, A.; Locher, S.; Hajak, G.; Sand, P. G. Berry anthocyanins and anthocyanidins exhibit distinct affinities for the efflux transporters BCRP and MDR1 Br. J. Pharmacol. 2009, 158, 1942-1950