Bioavailability and metabolism of selected cocoa bioactive compounds: A comprehensive review

References

• Actis-Goretta, L., A. Léveques, F. Giuffrida, F. Romanov-Michailidis, F. Viton, D. Barron, M. Duenas-Paton, S. Gonzalez-Manzano, C. Santos-Buelga, G. Williamson, and F. Dionisi. 2012. Elucidation of (−)-epicatechin metabolites after ingestion of chocolate by healthy humans. Free Radical Biology and Medicine 53 (4):787–95. doi: 10.1016/j.freeradbiomed.2012.05.023.
   PubMed Web of Science ®Google Scholar
• Actis-Goretta, L., A. Lèvéques, M. Rein, A. Teml, C. Schäfer, U. Hofmann, H. Li, M. Schwab, M. Eichelbaum, and G. Williamson. 2013. Intestinal absorption, metabolism, and excretion of (−)-epicatechin in healthy humans assessed by using an intestinal perfusion technique. The American Journal of Clinical Nutrition 98 (4):924–33. doi: 10.3945/ajcn.113.065789.
   PubMed Web of Science ®Google Scholar
• Adam, A., V. Crespy, M.-A. Levrat-Verny, F. Leenhardt, M. Leuillet, C. Demigné, and C. Rémésy. 2002. The bioavailability of ferulic acid is governed primarily by the food matri rather than its metabolism in intestine and liver in rats. The Journal of Nutrition 132 (7):1962–8. doi: 10.1093/jn/132.7.1962.
   PubMed Web of Science ®Google Scholar
• Ader, P., M. Blöck, S. Pietzsch, and S. Wolffram. 2001. Interaction of quercetin glucosides with the intestinal sodium/glucose co-transporter (SGLT-1). Cancer Letters 162 (2):175–80. doi: 10.1016/S0304-3835(00)00645-5.
   PubMed Web of Science ®Google Scholar
• Afoakwa, E. O., A. Paterson, M. Fowler, and A. Ryan. 2008. Flavor formation and character in cocoa and chocolate: A critical review. Critical Reviews in Food Science and Nutrition 48 (9):840–57. doi: 10.1080/10408390701719272.
   PubMed Web of Science ®Google Scholar
• Akkarachiyasit, S., P. Charoenlertkul, S. Yibchok-Anun, and S. Adisakwattana. 2010. Inhibitory activities of cyanidin and its glycosides and synergistic effect with acarbose against intestinal α-glucosidase and pancreatic α-amylase. International Journal of Molecular Sciences 11 (9):3387–96. doi: 10.3390/ijms11093387.
   PubMed Web of Science ®Google Scholar
• Andres-Lacueva, C., M. Monagas, N. Khan, M. Izquierdo-Pulido, M. Urpi-Sarda, J. Permanyer, and R. M. Lamuela-Raventtos. 2008. Flavanol and flavonol contents of cocoa powder products: Influence of manufacturing process. Journal of Agricultural and Food Chemistry 56 (9):3111–7. doi: 10.1021/jf0728754.
   PubMed Web of Science ®Google Scholar
• Appeldoorn, M. M., J. P. Vincken, A. M. Aura, P. C. Hollman, and H. Gruppen. 2009a. Procyanidin dimers are metabolized by human microbiota with 2-(3,4-dihydroxyphenyl)acetic acid and 5-(3,4-dihydroxyphenyl)-γ-valerolactone as the major metabolites. Journal of Agricultural and Food Chemistry 57 (3):1084–92. doi: 10.1021/jf803059z.
   PubMed Web of Science ®Google Scholar
• Appeldoorn, M. M., J. P. Vincken, H. Gruppen, and P. C. H. Hollman. 2009b. Procyanidin dimers A1, A2, and B2 are absorbed without conjugation or methylation from the small intestine of rats. The Journal of Nutrition 139 (8):1469–73. doi: 10.3945/jn.109.106765.
   PubMed Web of Science ®Google Scholar
• Aprotosoaie, A. C., S. V. Luca, and A. Miron. 2016. Flavor chemistry of cocoa and cocoa products – An overview. Comprehensive Reviews in Food Science and Food Safety 15 (1):73–91. doi: 10.1111/1541-4337.12180.
   PubMed Web of Science ®Google Scholar
• Aprotosoaie, A. C., A. Miron, A. Trifan, V. S. Luca, and I. I. Costache. 2016. The cardiovascular effects of cocoa polyphenols – An overview. Diseases 4 (4):39. doi: 10.3390/diseases4040039.
   Google Scholar
• Arnaud, M. J. 2011. Pharmacokinetics and metabolism of natural methylxanthines in animal and man. In Handbook of experimental pharmacology: Methylxanthines, ed. B. B. Fredholm 1st ed., 33–91. New York, NY: Springer.
   Google Scholar
• Aron, P. M., and J. A. Kennedy. 2008. Flavan-3-ols: Nature, occurrence and biological activity. Molecular Nutrition & Food Research 52 (1):79–104. doi: 10.1002/mnfr.200700137.
   PubMed Web of Science ®Google Scholar
• Baba, S., N. Osakabe, A. Yasuda, M. Natsume, T. Takizawa, T. Nakamura, and J. Terao. 2000. Bioavailability of (–)-epicatechin upon intake of chocolate and cocoa in human volunteers. Free Radical Research 33 (5):635–41. doi: 10.1080/10715760000301151.
   PubMed Web of Science ®Google Scholar
• Baba, S., N. Osakabe, M. Natsume, Y. Muto, T. Takizawa, and J. Terao. 2001. In vivo comparison of the bioavailability of (+)-catechin, (−)-epicatechin and their mixture in orally administered rats. The Journal of Nutrition 131 (11):2885–91. doi: 10.1093/jn/131.11.2885.
   PubMed Web of Science ®Google Scholar
• Badrie, N., F. Bekele, E. Sikora, and M. Sikora. 2015. Cocoa agronomy, quality, nutritional, and health aspects. Critical Reviews in Food Science and Nutrition 55 (5):620–59. doi: 10.1080/10408398.2012.669428.
   PubMed Web of Science ®Google Scholar
• Baggott, M. J., E. Childs, A. B. Hart, E. de Bruin, A. A. Palmer, J. E. Wilkinson, and H. de Wit. 2013. Psychopharmacology of theobromine in healthy volunteers. Psychopharmacology 228 (1):109–18. doi: 10.1007/s00213-013-3021-0.
   PubMed Web of Science ®Google Scholar
• Beg, M. S., S. Ahmad, K. Jan, and K. Bashir. 2017. Status, supply chain and processing of cocoa – A review. Trends in Food Science and Technology 66:108–16. doi: 10.1016/j.tifs.2017.06.007.
   Web of Science ®Google Scholar
• Belščak, A., D. Komes, D. Horzic, K. Kovačević Ganić, and D. Karlović. 2009. Comparative study of commercially available cocoa products in terms of their bioactive composition. Food Research International 42 (5–6):707–16. doi: 10.1016/j.foodres.2009.02.018.
   Web of Science ®Google Scholar
• Bernaert, H., I. Blondeel, L. Allegaert, and T. Lohmueller. 2012. Industrial treatment of cocoa in chocolate production: Health implications. In Chocolate and health, eds. R. Paoletti, A. Poli, A. Conti, and F. Visioli, 17–30. Berlin, Germany: Springer-Verlag.
   Google Scholar
• Berry, N. M., K. Davison, A. M. Coates, J. D. Buckley, and P. R. Howe. 2010. Impact of cocoa flavanol consumption on blood pressure responsiveness to exercise. British Journal of Nutrition 103:1480–4. doi: 10.1017/S0007114509993382.
   PubMed Web of Science ®Google Scholar
• Bhat, K. P. L., J. W. Kosmeder, 2nd, and J. M. Pezzuto. 2001. Biological effects of resveratrol. Antioxidants & Redox Signaling 3 (6):1041–64. doi: 10.1089/152308601317203567.
   PubMed Web of Science ®Google Scholar
• Bode, L. M., D. Bunzel, M. Huch, G. S. Cho, D. Ruhland, M. Bunzel, A. Bub, C. M. Franz, and S. E. Kulling. 2013. In vivo and in vitro metabolism of trans-resveratrol by human gut microbiota. The American Journal of Clinical Nutrition 97 (2):295–309. doi: 10.3945/ajcn.112.049379.
   PubMed Web of Science ®Google Scholar
• Borges, G., J. J. van der Hooft, and A. Crozier. 2016. A comprehensive evaluation of the [2-14C](−)-epicatechin metabolome in rats. Free Radical Biology & Medicine 99:128–38. doi: 10.1016/j.freeradbiomed.2016.08.001.
   PubMed Web of Science ®Google Scholar
• Borges, G., J. I. Ottaviani, J. J. van der Hooft, H. Schroeter, and A. Crozier. 2018. Absorption, metabolism, distribution and excretion of (−)-epicatechin: A review of recent findings. Molecular Aspects of Medicine 61:18–30. doi: 10.1016/j.mam.2017.11.002.
   PubMed Web of Science ®Google Scholar
• Boto-Ordonez, M., M. Urpi-Sarda, M. I. Queipo-Ortuno, S. Tulipani, F. J. Tinahones, and C. Andres-Lacueva. 2014. High levels of Bifidobacteria are associated with increased levels of anthocyanin microbial metabolites: A randomized clinical trial. Food & Function 5 (8):1932–8. doi: 10.1039/C4FO00029C.
   PubMed Web of Science ®Google Scholar
• Braga, A. R. C., D. C. Murador, L. M. de Souza Mesquita, and V. V. de Rosso. 2018. Bioavailability of anthocyanins: Gaps in knowledge, challenges and future research. Journal of Food Composition and Analysis 68:31–40. doi: 10.1016/j.jfca.2017.07.031.
   Web of Science ®Google Scholar
• Braune, A., and M. Blaut. 2016. Bacterial species involved in the conversion of dietary flavonoids in the human gut. Gut Microbes 7 (3):216–34. doi: 10.1080/19490976.2016.1158395.
   PubMed Web of Science ®Google Scholar
• Briz, M. R. M., B. S. Ruiz, and L. Bravo-Clemente. 2017. Methylxanthines: Dietary sources, bioavailability, and health benefits. In Fruit and vegetable phytochemicals: Chemistry and human health, ed. E. M. Yahia, 2nd ed., 183–97. Hoboken, NJ: John Wiley & Sons Ltd.
   Google Scholar
• Brown, V. A., K. R. Patel, M. Viskaduraki, J. A. Crowell, M. Perloff, T. D. Booth, G. Vasilinin, A. Sen, A. M. Schinas, G. Piccirilli, et al. 2010. Repeat dose study of the cancer chemopreventive agent resveratrol in healthy volunteers: Safety, pharmacokinetics, and effect on the insulin-like growth factor axis. Cancer Research 70 (22):9003–11. doi: 10.1158/0008-5472.
   PubMed Web of Science ®Google Scholar
• Carbonell-Capella, J. M., M. Buniowska, F. J. Barba, M. J. Esteve, and A. Frígola. 2014. Analytical methods for determining bioavailability and bioaccessibility of bioactive compounds from fruits and vegetables: A review. Comprehensive Reviews in Food Science and Food Safety 13 (2):155–71. doi: 10.1111/1541–4337.12049.
   PubMed Web of Science ®Google Scholar
• Cardona, F., C. Andres-Lacueva, S. Tulipani, F. J. Tinahones, and M. I. Queipo-Ortuno. 2013. Benefits of polyphenols on gut microbiota and implications in human health. Journal of Nutritional Biochemistry 24 (8):1415–22. doi: 10.1016/j.jnutbio.2013.05.001.
   PubMed Web of Science ®Google Scholar
• Cassidy, A., and A. M. Minihane. 2017. The role of metabolism (and the microbiome) in defining the clinical efficacy of dietary flavonoids. The American Journal of Clinical Nutrition 105 (1):10–22. doi: 10.3945/ajcn.116.136051.
   Google Scholar
• Castell, M., F. J. Pérez-Cano, and J. F. Bisson. 2013. Clinical benefits of cocoa: An overview. In Chocolate in health and nutrition, eds. R. Watson, V. R. Preedy, and S. Zibadi, 265–76. New York, Heidelberg, Dordrecht London: Humana Press.
   Google Scholar
• Castello, F., G. Costabile, L. Bresciani, M. Tassotti, D. Naviglio, D. Luongo, P. Ciciola, M. Vitale, C. Vetrani, G. Galaverna., et al. 2018. Bioavailability and pharmacokinetic profile of grape pomace phenolic compounds in humans. Archives of Biochemistry and Biophysics 646:1–9. doi: 10.1016/j.abb.2018.03.021.
   PubMed Web of Science ®Google Scholar
• Chachay, V. S., C. M. J. Kirkpatrick, I. J. Hickman, M. Ferguson, J. B. Prins, and J. H. Martin. 2011. Resveratrol – Pills to replace a healthy diet? British Journal of Clinical Pharmacology 72 (1):27–38. doi: 10.1111/j.1365-2125.2011.03966.x.
   PubMed Web of Science ®Google Scholar
• Cifuentes-Gomez, T., A. Rodriguez-Mateos, I. Gonzalez-Salvador, M. E. Alañon, and J. P. Spencer. 2015. Factors affecting the absorption, metabolism, and excretion of cocoa flavanols in humans. Journal of Agricultural and Food Chemistry 63 (35):7615–23. doi: 10.1021/acs.jafc.5b00443.
   PubMed Web of Science ®Google Scholar
• Cooper, K. A., J. L. Donovan, A. L. Waterhouse, and G. Williamson. 2008. Cocoa and health: A decade of research. British Journal of Nutrition 99 (1):1–11. doi: 10.1017/S0007114507795296.
   PubMed Web of Science ®Google Scholar
• Counet, C., D. Callemien, and S. Collin. 2006. Chocolate and cocoa: New sources of trans-resveratrol and trans-piceid. Food Chemistry 98 (4):649–57. doi: 10.1016/j.foodchem.2005.06.030.
   Web of Science ®Google Scholar
• Crozier, A., D. Del Rio, and M. N. Clifford. 2010. Bioavailability of dietary flavonoids and phenolic compounds. Molecular Aspects of Medicine 31 (6):446–67. doi: 10.1016/j.mam.2010.09.007.
   PubMed Web of Science ®Google Scholar
• Crozier, A. 2013. Absorption, metabolism, and excretion of (–)-epicatechin in humans: An evaluation of recent findings. The American Journal of Clinical Nutrition 98 (4):861–2. doi: 10.3945/ajcn.113.072009.
   PubMed Web of Science ®Google Scholar
• Czank, C., A. Cassidy, Q. Zhang, D. J. Morrison, T. Preston, P. A. Kroon, N. P. Botting, and C. D. Kay. 2013. Human metabolism and elimination of the anthocyanin, cyanidin-3-glucoside: A 13C-tracer study. The American Journal of Clinical Nutrition 97 (5):995–1003. doi: 10.3945/ajcn.112.049247.
   PubMed Web of Science ®Google Scholar
• Day, A. J., F. Mellon, D. Barron, G. Sarrazin, M. R. Morgan, and G. Williamson. 2001. Human metabolism of dietary flavonoids: Identification of plasma metabolites of quercetin. Free Radical Research 35 (6):941–52. doi: 10.1080/10715760100301441.
   PubMed Web of Science ®Google Scholar
• Day, A. J., J. M. Gee, M. S. DuPont, I. T. Johnson, and G. Williamson. 2003. Absorption of quercetin-3-glucoside and quercetin-4′-glucoside in the rat small intestine: The role of lactase phlorizin hydrolase and the sodium-dependent glucose transporter. Biochemical Pharmacology 65 (7):1199–206. doi: 10.1016/S0006-2952(03)00039-X.
   PubMed Web of Science ®Google Scholar
• D’Archivio, M., C. Filesi, R. Varì, B. Scazzocchio, and R. Masella. 2010. Bioavailability of the polyphenols: Status and controversies. International Journal of Molecular Sciences 11 (4):1321–42. doi: 10.3390/ijms11041321.
   PubMed Web of Science ®Google Scholar
• De Araujo, Q. R., J. N. Gattward, S. Almoosawi, Md Silva, P. A. 2. Dantas, and Q. R. De Araujo Júnior. 2016. Cocoa and human health: From head to foot – A review. Critical Reviews in Food Science and Nutrition 56 (1):1–12. doi: 10.1080/10408398.2012.657921.
   PubMed Web of Science ®Google Scholar
• Del Rio, D., A. Rodriguez-Mateos, J. P. Spencer, M. Tognolini, G. Borges, and A. Crozier. 2013. Dietary (poly)phenolics in human health: Structures, bioavailability, and evidence of protective effects against chronic diseases. Antioxidants & Redox Signaling 18 (14):1818–92. doi: 10.1089/ars.2012.4581.
   PubMed Web of Science ®Google Scholar
• Delmas, D., B. Jannin, and N. Latruffe. 2005. Resveratrol: Preventing properties against vascular alterations and ageing. Molecular Nutrition & Food Research 49 (5):377–95. doi: 10.1002/mnfr.200400098.
   PubMed Web of Science ®Google Scholar
• Deprez, S., I. Mila, J. F. Huneau, D. Tome, and A. Scalbert. 2001. Transport of proanthocyanidin dimer, trimer, and polymer across monolayers of human intestinal epithelial caco-2 cells. Antioxidants & Redox Signaling 2001 (3):957–67. doi: 10.1089/152308601317203503.
   Google Scholar
• Donovan, J. L., V. Crespy, M. Oliveira, K. A. Cooper, B. B. Gibson, and G. Williamson. 2006. (+)-catechin is more bioavailable than (−)-catechin: Relevance to the bioavailability of catechin from cocoa. Free Radical Research 40 (10):1029–34. doi: 10.1080/10715760600868545.
   PubMed Web of Science ®Google Scholar
• Dorenkott, M. R., L. E. Griffin, K. M. Goodrich, K. A. Thompson-Witrick, G. Fundaro, L. Ye, J. R. Stevens, M. Ali, S. F. O’Keefe, M. W. Hulver, and A. P. Neilson. 2014. Oligomeric cocoa procyanidins possess enhanced bioactivity compared to monomeric and polymeric cocoa procyanidins for preventing the development of obesity, insulin resistance, and impaired glucose tolerance during high-fat feeding. Journal of Agricultural and Food Chemistry 62 (10):2216–27. doi: 10.1021/jf500333y.
   PubMed Web of Science ®Google Scholar
• Edwards, C. A., J. Havlik, W. Cong, W. Mullen, T. Preston, D. J. Morrison, and E. Combet. 2017. Polyphenols and health: Interactions between fibre, plant polyphenols and the gut microbiota. Nutrition Bulletin 2 (4):356–60. doi: 10.1111/nbu.12296.
   Google Scholar
• Ellam, S., and G. Williamson. 2013. Cocoa and human health. Annual Review of Nutrition 33 (1):105–28. doi: 10.1146/annurev-nutr-071811-150642.
   PubMedGoogle Scholar
• Elwers, S., A. Zambrano, C. Rohsius, and R. Lieberei. 2009. Differences between the content of phenolic compounds in criollo, forastero and trinitario cocoa seed (Theobroma cacao L.). European Food Research and Technology 229 (6):937–48. doi: 10.1007/s00217-009-1132-y.
   Web of Science ®Google Scholar
• Engemann, A., F. Hubner, S. Rzeppa, and H. U. Humpf. 2012. Intestinal metabolism of two A-type procyanidins using the pig cecum model: Detailed structure elucidation of unknown catabolites with Fourier transform mass spectrometry (FTMS). Journal of Agricultural and Food Chemistry 60 (3):749–57. doi: 10.1021/jf203927g.
   PubMed Web of Science ®Google Scholar
• Etcheverry, P., M. A. Grusak, and L. E. Fleige. 2012. Application of in vitro bioaccessibility and bioavailability methods for calcium, carotenoids, folate, iron, magnesium, polyphenols, zinc, and vitamins B6, B12, D, and E. Frontiers in Physiology 3:317. doi: 10.3389/fphys.2012.00317.
   PubMed Web of Science ®Google Scholar
• Etxeberria, U., A. Fernandez-Quintela, F. I. Milagro, L. Aguirre, J. A. Martinez, and M. P. Portillo. 2013. Impact of polyphenols and polyphenol-rich dietary sources on gut microbiota composition. Journal of Agricultural and Food Chemistry 61 (40):9517–33. doi: 10.1021/jf402506c.
   PubMed Web of Science ®Google Scholar
• Fang, J. 2014. Bioavailability of anthocyanins. Drug Metabolism Reviews 46 (4):508–20. doi: 10.3109/03602532.2014.978080.
   PubMed Web of Science ®Google Scholar
• Faria, A., D. Pestana, D. Teixeira, P. O. Couraud, I. Romero, B. Weksler, V. de Freitas, N. Mateus, and C. Calhau. 2011. Insights into the putative catechin and epicatechin transport across blood-brain barrier. Food & Function 2 (1):39–44. doi: 10.1039/C0FO00100G.
   PubMed Web of Science ®Google Scholar
• Faria, A., I. Fernandes, S. Norberto, N. Mateus, and C. Calhau. 2014. Interplay between anthocyanins and gut microbiota. Journal of Agricultural and Food Chemistry 62 (29):6898–902. doi: 10.1021/jf501808a.
   PubMed Web of Science ®Google Scholar
• Felgines, C., S. Talavéra, M.-P. Gonthier, O. Texier, A. Scalbert, J.-L. Lamaison, and C. Rémésy. 2003. Strawberry anthocyanins are recovered in urine as glucuro- and sulfoconjugates in humans. The Journal of Nutrition 133 (5):1296–301. doi: 10.1093/jn/133.5.1296.
   PubMed Web of Science ®Google Scholar
• Fernandez, K., and J. Labra. 2013. Simulated digestion of proantho-cyanidins in grape skin and seed extracts and the effects of diges-tion on the angiotensin I-converting enzyme (ACE) inhibitoryactivity. Food Chemistry 139:196–202. doi: 10.1016/j.foodchem.2013.01.021.
   PubMed Web of Science ®Google Scholar
• Fernández-García, E., I. Carvajal-Lérida, and A. Pérez-Gálvez. 2009. In vitro bioaccessibility assessment as a prediction tool of nutritional efficiency. Nutrition Research 29 (11):751–60. doi: 10.1016/j.nutres.2009.09.016.
   PubMed Web of Science ®Google Scholar
• Ferri, C., G. Desideri, L. Ferri, I. Proietti, S. Di Agostino, L. Martella, F. Mai, P. Di Giosia, and D. Grassi. 2015. Cocoa, blood pressure, and cardiovascular health. Journal of Agricultural and Food Chemistry 63 (45):9901–9. doi: 10.1021/acs.jafc.5b01064.
   PubMed Web of Science ®Google Scholar
• Fulda, S. 2010. Resveratrol and derivatives for the prevention and treatment of cancer. Drug Discovery Today 15 (17–18):757–65. doi: 10.1016/j.drudis.2010.07.005.
   PubMed Web of Science ®Google Scholar
• Fogliano, V., M. L. Corollaro, P. Vitaglione, A. Napolitano, R. Ferracane, F. Travaglia, M. Arlorio, A. Costabile, A. Klinder, and G. Gibson. 2011. In vitro bioaccessibility and gut biotransformation of polyphenols present in the water-insoluble cocoa fraction. Molecular Nutrition & Food Research 55 (S1):S44–S55. doi: 10.1002/mnfr.201000360.
   PubMedGoogle Scholar
• Franco, R., A. Oñatibia-Astibia, and E. Martínez-Pinilla. 2013. Health benefits of methylxanthines in cacao and chocolate. Nutrients 5 (10):4159–73. doi: 10.3390/nu5104159.
   PubMed Web of Science ®Google Scholar
• Gallo, M., G. Vinci, G. Graziani, C. De Simone, and P. Ferranti. 2013. The interaction of cocoa polyphenols with milk proteins studied by proteomic techniques. Food Research International 54 (1):406–15. doi: 10.1016/j.foodres.2013.07.011.
   Web of Science ®Google Scholar
• Gardea, A. A., M. L. García-Bañuelos, J. A. Orozco-Avitia, E. Sánchez-Chávez, B. Sastré-Flores, and G. Ávila-Quezada. 2017. Cacao (Theobroma cacao L.). In Fruit and vegetable phytochemicals: Chemistry and human health, ed. E. M. Yahia, 2nd ed., 921–40. Hoboken, NJ: John Wiley & Sons Ltd.
   Google Scholar
• Gonthier, M.-P., M.-A. Verny, C. Besson, C. Rémésy, and A. Scalbert, 2003. Chlorogenic acid bioavailability largely depends on its metabolism by the gut microflora in rats. The Journal of Nutrition 133 (6):1853–9. doi: 10.1093/jn/133.6.1853.
   PubMed Web of Science ®Google Scholar
• Goodrich, K. M., M. R. Dorenkott, L. Ye, S. F. O’Keefe, M. W. Hulver, and A. P. Neilson. 2014. Dietary supplementation with cocoa flavanols does not alter Colon tissue profiles of native flavanols and their microbial metabolites established during habitual dietary exposure in C57BL/6J mice. Journal of Agricultural and Food Chemistry 62 (46):11190–9. doi: 10.1021/jf503838q.
   PubMed Web of Science ®Google Scholar
• Garcia-Aloy, M., R. Llorach, M. Urpi-Sarda, O. Jáuregui, D. Corella, M. Ruiz-Canela, J. Salas-Salvadó, M. Fitó, E. Ros, R. Estruch, and C. Andres-Lacueva. 2015. A metabolomics-driven approach to predict cocoa product consumption by designing a multimetabolite biomarker model in free-living subjects from the PREDIMED study. Molecular Nutrition & Food Research 59 (2):212–20. doi: 10.1002/mnfr.201400434.
   PubMed Web of Science ®Google Scholar
• Grassi, D., G. Desideri, and C. Ferri. 2010. Blood pressure and cardiovascular risk: What about cocoa and chocolate? Archives of Biochemistry and Biophysics 501 (1):112–5. doi: 10.1016/j.abb.2010.05.020.
   PubMed Web of Science ®Google Scholar
• Han, S. J., S. N. Ryu, H. T. Trinh, E. H. Joh, S. Y. Jang, M. J. Han, and D. H. Kim. 2009. Metabolism of cyanidin-3-O-beta-D-glucoside isolated from black colored rice and its antiscratching behavioral effect in mice. Journal of Food Science 74:253–8. doi: 10.1111/j.1750-3841.2009.01327.x.
   Web of Science ®Google Scholar
• Heleno, S. A., A. Martins, M. J. R. P. Queiroz, and I. C. F. R. Ferreira. 2015. Bioactivity of phenolic acids: Metabolites versus parent compounds: A review. Food Chemistry 173:501–13. doi: 10.1016/j.foodchem.2014.10.057.
   PubMed Web of Science ®Google Scholar
• Hollman, P. C. H., J. M. P. van Trijp, M. N. C. P. Buysman, M. S. V.D. Gaag, M. J. B. Mengelers, J. H. M. de Vries, and M. B. Katan. 1997. Relative bioavailability of the antioxidant flavonoid quercetin from various foods in man. FEBS Letters 418 (1–2):152–6. doi: 10.1016/S0014-5793(97)01367-7.
   PubMed Web of Science ®Google Scholar
• Holst, B., and G. Williamson. 2008. Nutrients and phytochemicals: From bioavailability to bioefficacy beyond antioxidants. Current Opinion in Biotechnology 19 (2):73–82. doi: 10.1016/j.copbio.2008.03.003.
   PubMed Web of Science ®Google Scholar
• Holt, R. R., S. A. Lazarus, M. C. Sullards, Q. Y. Zhu, D. D. Schramm, J. F. Hammerstone, C. G. Fraga, H. H. Schmitz, and C. L. Keen. 2002. Procyanidin dimer B2 [epicatechin-(4β-8)-epicatechin] in human plasma after the consumption of a flavanol-rich cocoa. The American Journal of Clinical Nutrition 76 (4):798–804. doi: 10.1093/ajcn/76.4.798.
   PubMed Web of Science ®Google Scholar
• Hodgson, J. M., L. W. Morton, I. B. Puddey, L. J. Beilin, and K. D. Croft. 2000. Gallic acid metabolites are markers of black tea intake in humans. Journal of Agricultural and Food Chemistry 48 (6):2276–80. doi: 10.1021/jf000089s.
   PubMed Web of Science ®Google Scholar
• Hurst, W. J., J. A. Glinski, K. B. Miller, J. Apgar, M. H. Davey, and D. A. Stuart. 2008. Survey of the trans-resveratrol and trans-piceid content of cocoa-containing and chocolate products. Journal of Agricultural and Food Chemistry 56 (18):8374–8. doi: 10.1021/jf801297w.
   PubMed Web of Science ®Google Scholar
• Jang, S., J. Sun, P. Chen, S. Lakshman, A. Molokin, J. M. Harnly, B. T. Vinyard, J. F. Urban, Jr., and C. D. Davis, G. Solano-Aguilar. 2016. Flavanol-enriched cocoa powder alters the intestinal microbiota, tissue and fluid metabolite profiles, and intestinal gene expression in pigs. The Journal of Nutrition 146 (4):673–80. doi: 10.3945/jn.115.222968.
   PubMed Web of Science ®Google Scholar
• Jailani, F., and G. Williamson. 2014. Effect of edible oils on quercetin, kaempferol and galangin transport and conjugation in the intestinal Caco-2/HT29-MTX co-culture model. Food & Function 5 (4):653–62. doi: 10.1039/c3fo60691k.
   PubMed Web of Science ®Google Scholar
• Jalil, A. M., and A. Ismail. 2008. Polyphenols in cocoa and cocoa products: Is there a link between antioxidant properties and health? Molecules 13 (9):2190–219. molecules. doi: 10.3390/molecules13092190.
   PubMed Web of Science ®Google Scholar
• Jamar, G., D. Estadella, and L. P. Pisani. 2017. Contribution of anthocyanin-rich foods in obesity control through gut microbiota interactions. Biofactors 43 (4):507–16. doi: 10.1002/biof.1365.
   PubMed Web of Science ®Google Scholar
• Jerkovic, V., M. Bröhan, E. Monnart, F. Nguyen, S. Nizet, and S. Collin. 2010. Stilbenic profile of cocoa liquors from different origins determined by RP-HPLC-APCI(+)-MS/MS. Detection of a new resveratrol hexoside. Journal of Agricultural and Food Chemistry 58 (11):7067–74. doi: 10.1021/jf101114c.
   PubMed Web of Science ®Google Scholar
• Kaliora, A. C., P. T. Kanellos, and N. Kalogeropoulos. 2013. Gallic acid bioavailability in humans. In Handbook on gallic acid, eds. M. A. Thompson and P. B. Collins, 301–12. Hauppauge, NY: Nova Science Publishers, Inc.
   Google Scholar
• Kaulmann, A., and T. Bohn. 2016. Bioactivity of polyphenols: Preventive and adjuvant strategies toward reducing inflammatory bowel diseases-promises, perspectives, and pitfalls. Oxidative Medicine and Cellular Longevity 2016:9346470. doi: 10.1155/2016/9346470.
   PubMed Web of Science ®Google Scholar
• Karakaya, S. 2004. Bioavailability of phenolic compounds. Critical Reviews in Food Science and Nutrition 44 (6):453–64. doi: 10.1080/10408690490886683.
   PubMed Web of Science ®Google Scholar
• Kay, C. D., G. Mazza, B. J. Holub, and J. Wang. 2004. Anthocyanin metabolites in human urine and serum. British Journal of Nutrition 91 (6):933–42. doi: 10.1079/BJN20041126.
   PubMed Web of Science ®Google Scholar
• Keogh, J. B., J. McInerney, and P. M. Clifton. 2007. The effect of milk protein on the bioavailability of cocoa polyphenols. Journal of Food Science 72 (3):S230–S233. doi: 10.1111/j.1750-3841.2007.00314.x.
   PubMed Web of Science ®Google Scholar
• Kern, S. M., N. R. Bennett, P. W. Needs, F. A. Mellon, P. A. Kroon, and M. T. Garcia-Conesa. 2003. Characterization of metabolites of hydroxycinnamates in the in vitro model of human small intestinal epithelium caco-2 cells. Journal of Agricultural and Food Chemistry 51 (27):7884–91. doi: 10.1021/jf030470n.
   PubMed Web of Science ®Google Scholar
• Khoo, C., and M. Falk. 2014. Cranberry polyphenols: Effects on cardiovascular risk factors. In Polyphenols in human health and disease, eds. R. R. Watson, V. R. Preedy and S. Zibadi, 1049–65. Cambridge, MA: Academic Press.
   Google Scholar
• Kofink, M., M. Papagiannopoulos, and R. Galensa. 2007. (−)-Catechin in cocoa and chocolate: Occurence and analysis of an atypical flavan-3-ol enantiomer. Molecules 12 (7):1274–88. doi: 10.3390/12071274.
   PubMed Web of Science ®Google Scholar
• Kongor, J. E., M. Hinneh, D. V. de Walle, E. O. Afoakwa, P. Boeckx, and K. Dewettinck. 2016. Factors influencing quality variation in cocoa (Theobroma cacao) bean flavor profile – A review. Food Research International 82:44–52. doi: 10.1016/j.foodres.2016.01.012.
   Web of Science ®Google Scholar
• Konishi, Y., Z. Zhao, and M. Shimizu. 2006. Phenolic acids are absorbed from the rat stomach with different absorption rates. Journal of Agricultural and Food Chemistry 54 (20):7539–43. doi: 10.1021/jf061554+.
   PubMed Web of Science ®Google Scholar
• Kothe, L., B. F. Zimmermann, and R. Galensa. 2013. Temperature influences epimerization and composition of flavanol monomers, dimers and trimers during cocoa bean roasting. Food Chemistry 141 (4):3656–63. doi: 10.1016/j.foodchem.2013.06.049.
   PubMed Web of Science ®Google Scholar
• Kris-Etherton, P. M., and C. L. Keen. 2002. Evidence that the antioxidant flavonoids in tea and cocoa are beneficial for cardiovascular health. Current Opinion in Lipidology 13 (1):41–9. doi: 10.1097/00041433-200202000-00007.
   PubMed Web of Science ®Google Scholar
• la Porte, C., N. Voduc, G. Zhang, I. Seguin, D. Tardiff, N. Singhal, and D. W. Cameron. 2010. Steady-State pharmacokinetics and tolerability of trans-resveratrol 2000 mg twice daily with food, quercetin and alcohol (ethanol) in healthy human subjects. Clinical Pharmacokinetics 49 (7):449–54. doi: 10.2165/11531820-000000000-00000.
   PubMed Web of Science ®Google Scholar
• Labib, S., A. Erb, M. Kraus, T. Wickert, and E. Richling. 2004. The pig caecum model: A suitable tool to study the intestinal metabolism of flavonoids. Molecular Nutrition & Food Research 48 (4):326–32. doi: 10.1002/mnfr.200400022.
   PubMed Web of Science ®Google Scholar
• Lafay, S., and A. Gil-Izquierdo. 2008. Bioavailability of phenolic acids. Phytochemistry Reviews 7 (2):301–11. doi: 10.1007/s11101-007-9077-x.
   Google Scholar
• Larrosa, M., C. Luceri, E. Vivoli, C. Pagliuca, M. Lodovici, G. Moneti, and P. Dolara. 2009. Polyphenol metabolites from colonic microbiota exert antiinflammatory activity on different inflammation models. Molecular Nutrition & Food Research 53 (8):1044–54. doi: 10.1002/mnfr.200800446.
   PubMed Web of Science ®Google Scholar
• Latif, R. 2013. Health benefits of cocoa. Current Opinion in Clinical Nutrition & Metabolic Care 16 (6):669–74. doi: 10.1097/MCO.0b013e328365a235.
   PubMed Web of Science ®Google Scholar
• Lechtenberg, M., K. Henschel, U. Liefländer-Wulf, B. Quandt, and A. Hensel. 2012. Fast determination of N-phenylpropenoyl-L-amino acids (NPA) in cocoa samples from different origins by ultra-performance liquid chromatography and capillary electrophoresis. Food Chemistry 135 (3):1676–84. doi: 10.1016/j.foodchem.2012.06.006.
   PubMed Web of Science ®Google Scholar
• Lecumberri, E., R. Mateos, M. Izquierdo-Pulido, P. Rupérez, L. Goya, and L. Bravo. 2007. Dietary fibre composition, antioxidant capacity and physico-chemical properties of a fibre-rich product from cocoa (Theobroma cacao L.). Food Chemistry 104 (3):948–54. doi: 10.1016/j.foodchem.2006.12.054.
   Web of Science ®Google Scholar
• Lima, L. J. R., M. H. Almeida, M. J. R. Nout, and M. H. Zwietering. 2011. Theobroma cacao L., “the food of the gods”: Quality determinants of commercial cocoa beans, with particular reference to the impact of fermentation. Critical Reviews in Food Science and Nutrition 51 (8):731–61. doi: 10.1080/10408391003799913.
   PubMed Web of Science ®Google Scholar
• Llorach, R., M. Urpi-Sarda, O. Jauregui, M. Monagas, and C. Andres-Lacueva. 2009. An LC-MS-based metabolomics approach for exploring urinary metabolome modifications after cocoa consumption. Journal of Proteome Research 8 (11):5060–8. doi: 10.1021/pr900470a.
   PubMed Web of Science ®Google Scholar
• Llorach-Asunción, R., O. Jauregui, M. Urpi-Sardaa, and C. Andres-Lacueva. 2010. Methodological aspects for metabolome visualization and characterization. A metabolomic evaluation of the 24 h evolution of human urine after cocoa powder consumption. Journal of Pharmaceutical and Biomedical Analysis 51 (2):373–81. doi: 10.1016/j.jpba.2009.06.033.
   PubMed Web of Science ®Google Scholar
• Lau-Cam, C. A. 2013. The absorption, metabolism, and pharmacokinetics of chocolate polyphenols, in chocolate. In Health and nutrition, eds. R. R. Watson, V. R. Preedy, and S. Zibadi, 201–46. Totowa, NJ: Humana Press.
   Google Scholar
• Maier-Salamon, A., M. Bohmdorfer, T. Thalhammer, T. Szekeres, and W. Jaeger. 2011. Hepatic glucuronidation of resveratrol: Interspecies comparison of enzyme kinetic profiles in human, mouse, rat, and dog. Drug Metabolism and Pharmacokinetics 26 (4):364–73. doi: 10.2133/dmpk.DMPK-11-RG-006.
   PubMed Web of Science ®Google Scholar
• Madyastha, K. M., and G. R. Sridhar. 1998. A novel pathway for the metabolism of caffeine by a mixed culture consortium. Biochemical and Biophysical Research Communications 249 (1):178–81. doi: 10.1006/bbrc.1998.9102.
   PubMed Web of Science ®Google Scholar
• Mandel, H. G. 2002. Update on caffeine consumption, disposition and action. Food and Chemical Toxicology 40 (9):1231–4. doi: 10.1016/S0278-6915(02)00093-5.
   PubMed Web of Science ®Google Scholar
• Marques, C., I. Fernandes, S. Norberto, C. Sá, D. Teixeira, V. de Freitas, N. Mateus, C. Calhau, and A. Faria. 2016. Pharmacokinetics of blackberry anthocyanins consumed with or without ethanol: A randomized and crossover trial. Molecular Nutrition & Food Research 60 (11):2319–30. doi: 10.1002/mnfr.201600143.
   PubMed Web of Science ®Google Scholar
• Martínez-López, S., B. Sarriá, M. Gómez-Juaristi, L. Goya, R. Mateos, and L. Bravo-Clemente. 2014. Theobromine, caffeine, and theophylline metabolites in human plasma and urine after consumption of soluble cocoa products with different methylxanthine contents. Food Research International 63:446–55. doi: 10.1016/j.foodres.2014.03.009.
   Web of Science ®Google Scholar
• Massot-Cladera, M., A. Costabile, C. E. Childs, P. Yaqoob, A. Franch, M. Castell, and F. J. Perez-Cano. 2015. Prebiotic effects of cocoa fibre on rats. Journal of Functional Foods 19:341–52. doi: 10.1016/j.jff.2015.09.021.
   Web of Science ®Google Scholar
• Mena, P., I. A. Ludwig, V. B. Tomatis, A. Acharjee, L. Calani, A. Rosi, F. Brighenti, S. Ray, J. L. Griffin, L. J. Bluck, and D. Del Rio. 2018. Inter-individual variability in the production of flavan-3-ol colonic metabolites: Preliminary elucidation of urinary metabotypes. European Journal of Nutrition. doi: 10.1007/s00394-018-1683-4.
   Web of Science ®Google Scholar
• Mena, P., L. Bresciani, N. Brindani, I. A. Ludwig, G. Pereira-Caro, D. Angelino, R. Llorach, L. Calani, F. Brighenti, M. N. Clifford, et al. 2019. Phenyl-γ-valerolactones and phenylvaleric acids, the main colonic metabolites of flavan-3-ols: Synthesis, analysis, bioavailability, and bioactivity. Natural Product Reports. doi: 10.1039/c8np00062j.
   PubMed Web of Science ®Google Scholar
• Mennen, L. I., D. Sapinho, H. Ito, S. Bertrais, P. Galan, S. Hercberg, and A. Scalbert. 2006. Urinary flavonoids and phenolic acids as biomarkers of intake for polyphenol-rich foods. British Journal of Nutrition 96 (1):191–8. doi: 10.1079/BJN20061808.
   PubMed Web of Science ®Google Scholar
• Milenkovic, D., C. Morand, A. Cassidy, A. Konic-Ristic, F. Tomás-Barberán, J. M. Ordovas, P. Kroon, R. De Caterina, and A. Rodriguez-Mateos. 2017. Interindividual variability in biomarkers of cardiometabolic health after consumption of major Plant-Food bioactive compounds and the determinants involved. Advances in Nutrition (Bethesda, Md.) 8 (4):558–70. doi: 10.3945/an.116.013623.
   PubMed Web of Science ®Google Scholar
• Minekus, M. 2015. The TNO Gastro-Intestinal Model (TIM). In The impact of food bioactives on health, eds. K. Verhoeckx, P. Cotter, I. López-Expósito, C. Kleiveland, T. L. A. Mackie, T. Requena, D. Swiatecka, and H. Wichers, 37–46. Cham, Heidelberg, New York, Dordrecht, London: Springer.
   Google Scholar
• Mitchell, L. E. S., M. Slettenaar, N. Vd Meer, C. Transler, L. Jans, F. Quadt, and M. Berry. 2011. Differential contributions of theobromine and caffeine on mood, psychomotor performance and blood pressure. Physiology & Behavior 104 (5):816–22. doi: 10.1016/j.physbeh.2011.07.027.
   PubMed Web of Science ®Google Scholar
• Mojzer, E. B., M. K. Hrnčič, M. Škerget, Ž. Knez, and U. Bren. 2016. Polyphenols: Extraction methods, antioxidative action, bioavailability and anticarcinogenic effects. Molecules 21 (7):901–39. doi: 10.3390/molecules21070901.
   Web of Science ®Google Scholar
• Monagas, M., M. Urpi-Sarda, F. Sánchez-Patán, R. Llorach, I. Garrido, C. Gómez-Cordovés, C. Andres-Lacueva, and B. Bartolomé. 2010. Insights into the metabolism and microbial biotransformation of dietary flavan-3-ols and the bioactivity of their metabolites. Food & Function 1 (3):233–53. doi: 10.1039/c0fo00132e.
   PubMed Web of Science ®Google Scholar
• Monteiro, J., M. Alves, P. Oliveira, and B. Silva. 2016. Structure-bioactivity relationships of methylxanthines: Trying to make sense of all the promises and the drawbacks. Molecules 21 (8):974. doi: 10.3390/molecules21080974.
   Web of Science ®Google Scholar
• Morais, C. A., V. V. de Rosso, D. Estadella, and L. P. Pisani. 2016. Anthocyanins as inflammatory modulators and the role of the gut microbiota. Journal of Nutritional Biochemistry 33:1–7. doi: 10.1016/j.jnutbio.2015.11.008.
   PubMed Web of Science ®Google Scholar
• Mullen, W., G. Borges, J. L. Donovan, C. A. Edwards, M. Serafini, M. E. Lean, and A. Crozier. 2009. Milk decreases urinary excretion but not plasma pharmacokinetics of cocoa flavan-3-ol metabolites in humans. The American Journal of Clinical Nutrition 89 (6):1784–91. doi: 10.1007/s002280050205.
   PubMed Web of Science ®Google Scholar
• Mumford, G. K., N. L. Benowitz, S. M. Evans, B. J. Kaminski, K. L. Preston, C. A. Sannerud, K. Silverman, and R. R. Griffiths. 1996. Absorption rate of methylxanthines following capsules, cola and chocolate. European Journal of Clinical Pharmacology 51 (3–4):319–25. doi: 10.1007/s002280050205.
   PubMed Web of Science ®Google Scholar
• Murota, K., Y. Nakamura, and M. Uehara. 2018. Flavonoid metabolism: The interaction of metabolites and gut microbiota. Bioscience, Biotechnology, and Biochemistry 82 (4):600–10. doi: 10.1080/09168451.2018.1444467.
   PubMed Web of Science ®Google Scholar
• Nardini, M., F. Natella, C. Scaccini, and A. Ghiselli. 2006. Phenolic acids from beer are absorbed and extensively metabolized in humans. Journal of Nutritional Biochemistry 17 (1):14–22. doi: 10.1016/j.jnutbio.2005.03.026.
   PubMed Web of Science ®Google Scholar
• Nehlig, A. 2013. The neuroprotective effects of cocoa flavanol and its influence on cognitive performance. British Journal of Clinical Pharmacology 75 (3):716–27. doi: 10.1111/j.1365-2125.2012.04378.x.
   PubMed Web of Science ®Google Scholar
• Neilson, A. P., J. C. George, E. M. Janle, R. D. Mattes, R. Rudolph, N. V. Matusheski, and M. G. Ferruzzi. 2009. Influence of chocolate matrix composition on cocoa flavan-3-ol bioaccessibility in vitro and bioavailability in humans. Journal of Agricultural and Food Chemistry 57 (20):9418–26. doi: 10.1021/jf902919k.
   PubMed Web of Science ®Google Scholar
• Neilson, A. P., and M. G. Ferruzzi. 2011. Influence of formulation and processing on absorption and metabolism of flavan-3-ols from tea and cocoa. Annual Review of Food Science and Technology 2 (1):125–51. doi: 10.1146/annurev-food-022510-133725.
   PubMedGoogle Scholar
• Nemeth, K., G. W. Plumb, J. G. Berrin, N. Juge, R. Jacob, H. Y. Naim, G. Williamson, D. M. Swallow, and P. A. Kroon. 2003. Deglycosylation by small intestinal epithelial cell beta-glucosidases is a critical step in the absorption and metabolism of dietary flavonoid glycosides in humans. European Journal of Nutrition 42 (1):29–42. doi: 10.1007/s00394-003-0397-3.
   PubMed Web of Science ®Google Scholar
• Oleaga, C., C. J. Ciudad, M. Izquierdo-Pulid, and V. Noé. 2013. Cocoa flavanol metabolites activate HNF-3β, Sp1, and NFY-mediated transcription of apolipoprotein AI in human cells. Molecular Nutrition & Food Research 57 (6):986–95. doi: 10.1002/mnfr.201200507.
   PubMed Web of Science ®Google Scholar
• Olivas-Aguirre, F. J., J. Rodrigo-García, N. D. Martínez-Ruiz, A. I. Cárdenas-Robles, S. O. Mendoza-Díaz, E. Álvarez-Parrilla, G. A. González-Aguilar, L. A. de la Rosa, A. Ramos-Jiménez, and A. Wall-Medrano. 2016. Cyanidin-3-O-glucoside: Physical-chemistry, foodomics and health effects. Molecules 21 (9):1264. doi: 10.3390/molecules21091264.
   Web of Science ®Google Scholar
• Olthof, M. R., P. C. Hollman, T. B. Vree, and M. B. Katan. 2000. Bioavailabilities of quercetin-3-glucoside and quercetin-4´-glucoside do not differ in humans. The Journal of Nutrition 130 (5):1200–3. doi: 10.1093/jn/130.5.1200.
   PubMed Web of Science ®Google Scholar
• Ortega, N., M.-P. Romero, A. Macià, J. Reguant, N. Anglès, J.-R. Morelló, and M.-J. Motilva. 2008. Obtention and characterization of phenolic extracts from different cocoa sources. Journal of Agricultural and Food Chemistry 56 (20):9621–7. doi: 10.1021/jf8014415.90/molecules21091264.
   PubMed Web of Science ®Google Scholar
• Oracz, J., E. Nebesny, and D. Żyżelewicz. 2015. Changes in the flavan-3-ols, anthocyanins, and flavanols composition of cocoa beans of different Theobroma cacao L. groups affected by roasting conditions. European Food Research and Technology 241 (5):663–81. doi: 10.1007/s00217-015-2494-y.
   Web of Science ®Google Scholar
• Oracz, J., D. Zyzelewicz, and E. Nebesny. 2015. The content of polyphenolic compounds in cocoa beans (Theobroma cacao L.), depending on variety, growing region, and processing operations: A review. Critical Reviews in Food Science and Nutrition 55 (9):1176–92. doi: 10.1080/10408398.2012.686934.
   PubMed Web of Science ®Google Scholar
• Ostertag, L. M., P. A. Kroon, S. Wood, G. W. Horgan, E. Cienfuegos-Jovellanos, S. Saha, G. G. Duthie, and B. de Roos. 2013. Flavan-3-ol-enriched dark chocolate and white chocolate improve acute measures of platelet function in a gender-specific way – A randomized-controlled human intervention trial. Molecular Nutrition & Food Research 57 (2):191–202. doi: 10.1002/mnfr.201200283.
   PubMed Web of Science ®Google Scholar
• Ottaviani, J. I., T. Y. Momma, C. Heiss, C. Kwik-Uribe, H. Schroeter, and C. L. Keen. 2011. The stereochemical configuration of flavanols influences the level and metabolism of flavanols in humans and their biological activity in vivo. Free Radical Biology and Medicine 50 (2):237–44. doi: 10.1016/j.freeradbiomed.2010.11.005.
   PubMed Web of Science ®Google Scholar
• Ottaviani, J. I., T. Y. Momma, G. K. Kuhnle, C. L. Keen, and H. Schroeter. 2012a. Structurally related (−)-epicatechin metabolites in humans: Assessment using de novo chemically synthesized authentic standards. Free Radical Biology & Medicine 52 (8):1403–12. doi: 10.1016/j.freeradbiomed.2011.12.010.
   PubMed Web of Science ®Google Scholar
• Ottaviani, J. I., C. Kwik-Uribe, C. L. Keen, and H. Schroeter. 2012b. Intake of dietary procyanidins does not contribute to the Pool of circulation flavanols in humans. The American Journal of Clinical Nutrition 95 (4):851–8. doi: 10.3945/ajcn.111.028340.
   PubMed Web of Science ®Google Scholar
• Ottaviani, J. I., G. Borges, T. Y. Momma, J. P. Spencer, C. L. Keen, A. Crozier, and H. Schroeter. 2016. The metabolome of [2-14C](−)-epicatechin in humans: Implications for the assessment of efficacy, safety, and mechanisms of action of polyphenolic bioactives. Scientific Reports 6:29034. doi: 10.1038/srep29034.
   PubMed Web of Science ®Google Scholar
• Ottaviani, J. I., C. Heiss, J. P. E. Spencer, M. Kelm, and H. Schroeter. 2018. Recommending flavanols and procyanidins for cardiovascular health: Revisited. Molecular Aspects of Medicine 61:63–75. doi: 10.1016/j.mam.2018.02.001.
   PubMed Web of Science ®Google Scholar
• Ou, K., S. S. Percival, T. Zou, C. Khoo, and L. Gu. 2012. Transport of cranberry A-type procyanidin dimers, trimers, and tetramers across monolayers of human intestinal epithelial caco-2 cells. Journal of Agricultural and Food Chemistry 60 (6):1390–6. doi: 10.1021/jf2040912.
   PubMed Web of Science ®Google Scholar
• Ou, K., P. Sarnoski, K. R. Schneider, K. Song, C. Khoo, and L. Gu. 2014. Microbial catabolism of procyanidins by human gut microbiota. Molecular Nutrition & Food Research 58 (11):2196–205. doi: 10.1002/mnfr.201400243.
   PubMed Web of Science ®Google Scholar
• Ozdal, T., D. Sela, J. Xiao, D. Boyacioglu, F. Chen, and E. Capanoglu. 2016. The reciprocal interactions between polyphenols and gut microbiota and effects on bioaccessibility. Nutrients 8 (2):78. doi: 10.3390/nu8020078.
   PubMed Web of Science ®Google Scholar
• Quiroz-Reyes, C. N., and V. Fogliano. 2018. Design cocoa processing towards healthy cocoa products: The role of phenolics and melanoidins. Journal of Functional Foods 45:480–90. doi: 10.1016/j.jff.2018.04.031.
   Web of Science ®Google Scholar
• Panoutsopoulos, G. I., D. Kouretas, and C. Beedham. 2004. Contribution of aldehyde oxidase, xanthine oxidase, and aldehyde dehydrogenase on the oxidation of aromatic aldehydes. Chemical Research in Toxicology 17 (10):1368–76. doi: 10.1021/tx030059u.
   PubMed Web of Science ®Google Scholar
• Pasinetti, G. M., R. Singh, S. Westfall, F. Herman, J. Faith, and L. Ho. 2018. The role of the gut microbiota in the metabolism of polyphenols as characterized by gnotobiotic mice. Journal of Alzheimer’s Disease 63 (2):409–21. doi: 10.3233/JAD-171151.
   PubMed Web of Science ®Google Scholar
• Passamonti, S., U. Vrhovsek, A. Vanzo, and F. Mattivi. 2003. The stomach as a site for anthocyanins absorption from food. FEBS Letters 544 (1–3):210–3. doi: 10.1016/S0014-5793(03)00504-0.
   PubMed Web of Science ®Google Scholar
• Pastoriza, S., C. Delgado-Andrade, A. Haro, and J. A. Rufián-Henares. 2011. A physiologic approach to test the global antioxidant response of foods. The GAR method. Food Chemistry 129 (4):1926–32. doi: 10.1016/j.foodchem.2011.06.009.
   Web of Science ®Google Scholar
• Pedan, V., N. Fischer, K. Bernath, T. Hühn, and S. Rohn. 2017. Determination of oligomeric proanthocyanidins and their antioxidant activity from different chocolate manufacturing stages using the NP-HPLC-online DPPH methodology. Food Chemistry 214:523–32. doi: 10.1016/j.foodchem.2016.07.094.
   PubMed Web of Science ®Google Scholar
• Perez-Jimenez, J., M. E. Dıaz-Rubio, and F. Saura-Calixto. 2013. Nonextractable polyphenols, a major dietary antioxidant: Occurrence, metabolic fate and health effects. Nutrition Research Reviews 26:118–29. doi: 10.1017/S0954422413000097.
   PubMed Web of Science ®Google Scholar
• Petersen, B., S. Egert, A. Bosy-Westphal, M. J. Müller, S. Wolffram, E. M. Hubbermann, G. Rimbach, and K. Schwarz. 2016. Bioavailability of quercetin in humans and the influence of food matrix comparing quercetin capsules and different apple sources. Food Research International 88 (Pt A):159–65. doi: 10.1016/j.foodres.2016.02.013.
   PubMedGoogle Scholar
• Poquet, L., M. N. Clifford, and G. Williamson. 2008. Transport and metabolism of ferulic acid through the colonic epithelium. Drug Metabolism & Disposition (1):190–197. doi: 10.1124/dmd.107.017558.
   Google Scholar
• Ptolemy, A. S., E. Tzioumis, A. Thomke, S. Rifai, and M. Kellogg. 2010. Quantification of theobromine and caffeine in saliva, plasma and urine via liquid chromatography–tandem mass spectrometry: A single analytical protocol applicable to cocoa intervention studies. Journal of Chromatography B 878 (3–4):409–16. doi: 10.1016/j.jchromb.2009.12.019.
   PubMed Web of Science ®Google Scholar
• Rauf, A., M. Imran, M. S. Butt, M. Nadeem, D. G. Peters, and M. S. Mubarak. 2018. Resveratrol as an anti-cancer agent: A review. Critical Reviews in Food Science and Nutrition 58 (9):1428–47. doi: 10.1080/10408398.2016.1263597.
   PubMed Web of Science ®Google Scholar
• Rein, D., S. Lotito, R. R. Holt, C. L. Keen, H. H. Schmitz, and C. G. Fraga. 2000. Epicatechin in human plasma: In vivo determination and effect of chocolate consumption on plasma oxidation status. The Journal of Nutrition 130 (8):2109S–14S. doi: 10.1093/jn/130.8.2109S.
   PubMed Web of Science ®Google Scholar
• Rein, M. J., M. Renouf, C. Cruz-Hernandez, L. Actis-Goretta, S. K. Thakkar, and M. da Silva Pinto. 2013. Bioavailability of bioactive food compounds: A challenging journey to bioefficacy. British Journal of Clinical Pharmacology 75 (3):588–602. doi: 10.1111/j.1365-2125.2012.04425.x.
   PubMed Web of Science ®Google Scholar
• Richelle, M., I. Tavazzi, M. Enslen, and E. A. Offord. 1999. Plasma kinetics in man of epicatechin from black chocolate. European Journal of Clinical Nutrition 53 (1):22–6. doi: 10.1038/sj.ejcn.1600673.
   PubMed Web of Science ®Google Scholar
• Rios, L. Y., Bennett, R. N., Lazarus, S. A., Rémésy, C., Scalbert, A., and G. Williamson. 2002. Cocoa procyanidins are stable during gastric transit in humans. The American Journal of Clinical Nutrition 76 (5): 1106–1110. doi: 10.1093/ajcn/76.5.1106.
   PubMed Web of Science ®Google Scholar
• Rios, L. Y., M.-P. Gonthier, C. Rémésy, I. Mila, C. Lapierre, S. A. Lazarus, G. Williamson, and A. Scalbert. 2003. Chocolate intake increases urinary excretion of polyphenol-derived phenolic acids in healthy human subjects. The American Journal of Clinical Nutrition 77 (4):912–8. doi: 10.1093/ajcn/77.4.912.
   PubMed Web of Science ®Google Scholar
• Rocha-González, H. I., M. Ambriz-Tututi, and V. Granados-Soto. 2008. Resveratrol: A natural compound with pharmacological potential in neurodegenerative diseases. CNS Neuroscience & Therapeutics 14 (3):234–47. doi: 10.1111/j.1755-5949.2008.00045.x.
   PubMed Web of Science ®Google Scholar
• Rodriguez-Mateos, A., D. Vauzour, C. G. Krueger, D. Shanmuganayagam, J. Reed, L. Calani, P. Mena, D. Del Rio, and A. Crozier. 2014. Bioavailability, bioactivity and impact on health of dietary flavonoids and related compounds: An update. Archives of Toxicology 88 (10):1803–53. doi: 10.1007/s00204-014-1330-7.
   PubMed Web of Science ®Google Scholar
• Rodriguez-Mateos, A., T. Cifuentes-Gomez, I. Gonzalez-Salvador, J. I. Ottaviani, H. Schroeter, M. Kelm, C. Heiss, and J. P. E. Spencer. 2015. Influence of age on the absorption, metabolism, and excretion of cocoa flavanols in healthy subjects. Molecular Nutrition & Food Research 59 (8):1504–12. doi: 10.1002/mnfr.201500091.
   PubMed Web of Science ®Google Scholar
• Rodriguez, A., A. Costa-Bauza, C. Saez-Torres, D. Rodrigo, and F. Grases. 2015. HPLC method for urinary theobromine determination: Effect of consumption of cocoa products on theobromine urinary excretion in children. Clinical Biochemistry 48 (16–17):1138–43. doi: 10.1016/j.clinbiochem.2015.06.022.
   PubMed Web of Science ®Google Scholar
• Rotches-Ribalta, M., C. Andres-Lacueva, R. Estruch, E. Escribano, and M. Urpi-Sarda. 2012. Pharmacokinetics of resveratrol metabolic profile in healthy humans after moderate consumption of red wine and grape extract tablets. Pharmacological Research 66 (5):375–82. doi: 10.1016/j.phrs.2012.08.001.
   PubMed Web of Science ®Google Scholar
• Roura, E., C. Andrés-Lacueva, O. Jauregui, E. Badía, R. Estruch, M. Izquierdo-Pulido, and R. M. Lamuela-Raventós. 2005. Rapid liquid chromatography tandem mass spectrometry assay to quantify plasma (−)-epicatechin metabolites after ingestion of a standard portion of coca beverage in humans. Journal of Agricultural and Food Chemistry 53 (16):6190–4. doi: 10.1021/jf050377u.
   PubMed Web of Science ®Google Scholar
• Roura, E., M. P. Almajano, M. L. Bilbao, C. Andrés-Lacueva, R. Estruch, and R. M. Lamuela-Raventós. 2007a. Human urine: Epicatechin metabolites and antioxidant activity after cocoa beverage intake. Free Radical Research 41 (8):943–9. doi: 10.1080/10715760701435236.
   PubMed Web of Science ®Google Scholar
• Roura, E., C. Andrés-Lacueva, R. Estruch, M. L. Mata-Bilbao, M. Izquierdo-Pulido, A. L. Waterhouse, and R. M. Lamuela-Raventós. 2007b. Milk does not affect the bioavailability of cocoa powder flavonoid in healthy human. Annals of Nutrition and Metabolism 51 (6):493–8. doi: 10.1159/000111473.
   PubMed Web of Science ®Google Scholar
• Roura, E., C. Andrés-Lacueva, R. Estruch, M. L. Mata-Bilbao, M. Izquierdo-Pulido, and M. Lamuela-Raventós. 2008. The effects of milk as a food matrix for polyphenols on the excretion profile of cocoa (−)-epicatechin metabolites in healthy human subjects. British Journal of Nutrition 100 (4):846–51. ( doi: 10.1017/S0007114508922534.
   PubMed Web of Science ®Google Scholar
• Ross, J. A., and C. M. Kasum. 2002. Dietary flavonoids: Bioavailability, metabolic effects, and safety. Annual Review of Nutrition 22 (1):19–34. doi: 10.1146/annurev.nutr.22.111401.144957.
   PubMed Web of Science ®Google Scholar
• Rusconi, M., and A. Conti. 2010. Theobroma cacao L., the food of the goods: Ascientific approach beyond myths and claims. Pharmacological Research 61 (1):5–13. doi: 10.1016/j.phrs.2009.08.008.
   PubMed Web of Science ®Google Scholar
• Salvador, I., A. P. Massarioli, A. P. Silva, H. Malaguetta, P. S. Melo, and S. M. Alencar. 2018. Can we conserve trans-resveratrol content and antioxidant activity during industrial production of chocolate? Journal of the Science of Food and Agriculture 99 (1):83–9. doi: 10.1002/jsfa.9146.
   PubMed Web of Science ®Google Scholar
• Sánchez-Rabaneda, F., O. Jáuregui, I. Casals, C. Andrés-Lacueva, M. Izquierdo-Pulido, and R. M. Lamuela-Raventós. 2003. Liquid chromatographic/electrospray ionization tandem mass spectrometric study of the phenolic composition of cocoa (Theobroma cacao). Journal of Mass Spectrometry 38 (1):35–42. doi: 10.1002/jms.395.
   PubMed Web of Science ®Google Scholar
• Sansone, R., J. I. Ottaviani, A. Rodriguez-Mateos, Y. Heinen, D. Noske, J. P. Spencer, A. Crozier, M. W. Merx, M. Kelm, H. Schroeter, and C. Heiss. 2017. Methylxanthines enhance the effects of cocoa flavanols on cardiovascular function: Randomized, double-masked controlled studies. The American Journal of Clinical Nutrition 105 (2):352–60. doi: 10.3945/ajcn.116.140046.
   PubMed Web of Science ®Google Scholar
• Santos-Buelga, C., and A. Scalbert. 2000. Proanthocyanidins and tannin-like compounds-nature, occurrence, dietary intake and effects on nutrition and health. Journal of the Science of Food and Agriculture 80 (7):1094–117. doi: 10.1002/(sici)1097-0010(20000515)80:7 < 1094::aid-jsfa569 > 3.0.co;2-1.
   Web of Science ®Google Scholar
• Serafini, M., R. Bugianesi, G. Maiani, S. Valtuena, S. De Santis, and A. Crozier. 2003. Plasma antioxidants from chocolate. Nature 424 (6952):1013. doi: 10.1038/4241013a.
   PubMedGoogle Scholar
• Sergides, C., M. Chirilă, L. Silvestro, D. Pitta, and A. Pittas. 2016. Bioavailability and safety study of resveratrol 500 mg tablets in healthy male and female volunteers. Experimental and Therapeutic Medicine 11 (1):164–70. doi: 10.3892/etm.2015.2895.
   PubMed Web of Science ®Google Scholar
• Serra, A., A. Macià, M.-P. Romero, N. Anglés, J.-R. Morelló, and M.-J. Motilva. 2011. Metabolic pathways of the colonic metabolism of procyanidins (monomers and dimers) and alkaloids. Food Chemistry 126 (3):1127–37. doi: 10.1016/j.foodchem.2010.11.145.
   Web of Science ®Google Scholar
• Shahrzad, S., K. Aoyagi, A. Winter, A. Koyama, and I. Bitsch. 2001. Pharmacokinetics of gallic acid and its relative bioavailability from tea in healthy humans. The Journal of Nutrition 131 (4):1207–10. doi: 10.1093/jn/131.4.1207.
   PubMed Web of Science ®Google Scholar
• Schneider, H., R. Simmering, L. Hartmann, H. Pforte, and M. Blaut. 2000. Degradation of quercetin-3-glucoside in gnotobiotic rats associated with human intestinal bacteria. Journal of Applied Microbiology 89 (6):1027–37. doi: 10.1046/j.1365-2672.2000.01209.x.
   PubMed Web of Science ®Google Scholar
• Schramm, D. D., M. Karim, H. R. Schrader, R. R. Holt, N. J. Kirkpatrick, J. A. Polagruto, J. L. Ensunsa, H. H. Schmitz, and C. L. Keen. 2003. Food effects on the absorption and pharmacokinetics of cocoa flavanols. Life Science 73 (7):857–69. doi: 10.1016/S0024-3205(03)00373-4.
   PubMed Web of Science ®Google Scholar
• Smith, D. S. 2013. Benefits of flavanol-rich cocoa-derived products for mental well-being: A review. Journal of Functional Foods 5 (1):10–5. doi: 10.1016/j.jff.2012.09.002.
   Web of Science ®Google Scholar
• Smith, J. H. 2011. Theobromine and the pharmacology of cocoa. In Handbook of experimental pharmacology: Methylxanthines, ed. B. B. Fredholm, 1st ed., 201–34. New York, NY: Springer.
   Google Scholar
• Sokolov, A. N., M. A. Pavlova, S. Klosterhalfen, and P. Enck. 2013. Chocolate and the brain: Neurobiological impact of cocoa flavanols on cognition and behavior. Neuroscience & Biobehavioral Reviews 37 (10):2445–53. doi: 10.1016/j.neubiorev.2013.06.013.
   PubMed Web of Science ®Google Scholar
• Stoupi, S., G. Williamson, F. Viton, D. Barron, L. J. King, J. E. Brown, and M. N. Clifford. 2010. In vivo bioavailability, absorption, excretion, and pharmacokinetics of [14C] procyanidin B2 in male rats. Drug Metabolism & Disposition 38 (2):287–91. doi: 10.1124/dmd.109.030304.
   PubMed Web of Science ®Google Scholar
• Spencer, J. P., F. Chaudry, A. S. Pannala, S. K. Srai, E. Debnam, and C. Rice-Evans. 2000. Decomposition of cocoa procyanidins in the gastric milieu. Biochemical and Biophysical Research Communications 272 (1):236–41. doi: 10.1006/bbrc.2000.2749.
   PubMed Web of Science ®Google Scholar
• Spencer, J. P., H. Schroeter, B. Shenoy, S. K. Srai, E. S. Debnam, and C. Rice-Evans. 2001a. Epicatechin is the primary bioavailable form of the procyanidin dimers B2 and B5 after transfer across the small intestine. Biochemical and Biophysical Research Communications 285 (3):588–93. doi: 10.1006/bbrc.2001.5211.
   PubMed Web of Science ®Google Scholar
• Spencer, J. P., H. Schroeter, A. J. Crossthwaithe, G. Kuhnle, R. J. Williams, and C. Rice-Evans. 2001b. Contrasting influences of glucuronidation and O-methylation of epicatechin on hydrogen peroxide-induced cell death in neurons and fibroblasts. Free Radical Biology & Medicine 31 (9):1139–46. doi: 10.1016/S0891-5849(01)00704-3.
   PubMed Web of Science ®Google Scholar
• Stahl, W., H. van den Berg, J. Arthur, A. Bast, J. Dainty, R. M. Faulks, C. Gärtner, G. Haenen, P. Hollman, B. Holst, et al. 2002. Bioavailability and metabolism. Molecular Aspects of Medicine 23 (1–3):39–100. doi: 10.1016/S0098-2997(02)00016-X.
   PubMed Web of Science ®Google Scholar
• Stark, T., R. Lang, D. Keller, A. Hensel, and T. Hofmann. 2008. Absorption of N-phenylpropenoyl-L-amino acids in healthy humans by oral administration of cocoa (Theobroma cacao). Molecular Nutrition & Food Research 52 (10):1201–14. doi: 10.1002/mnfr.200700447.
   PubMed Web of Science ®Google Scholar
• Tomas-Barberan, F. A., E. Cienfuegos-Jovellanos, A. Marín, B. Muguerza, A. Gil-Izquierdo, B. Cerda, P. Zafrilla, J. Morillas, J. Mulero, A. Ibarra, et al. 2007. A new process to develop a cocoa powder with higher flavonoid monomer content and enhanced bioavailability in healthy humans. Journal of Agricultural and Food Chemistry 55 (10):3926–35. doi: 10.1021/jf070121j.
   PubMed Web of Science ®Google Scholar
• Torres-Moreno, M., A. Tarrega, E. Costell, and C. Blanch. 2012. Dark chocolateacceptability: Influence of cocoa origin and processing conditions. Journal of the Science of Food and Agriculture 92 (2):404–11. doi: 10.1002/jsfa.4592.
   PubMed Web of Science ®Google Scholar
• Trost, K., M. M. Ulaszewska, J. Stanstrup, D. Albanese, C. De Filippo, K. M. Tuohy, F. Natella, C. Scaccini, and F. Mattivi. 2018. Host: Microbiome co-metabolic processing of dietary polyphenols – An acute, single blinded, cross-over study with different doses of apple polyphenols in healthy subjects. Food Research International 112:108–28. doi: 10.1016/j.foodres.2018.06.016.
   PubMed Web of Science ®Google Scholar
• Tsai, H. Y., C. T. Ho, and Y. K. Chen. 2017. Biological actions and molecular effects of resveratrol, pterostilbene, and 3′-hydroxypterostilbene. Journal of Food and Drug Analysis 25 (1):134–47. doi: 10.1016/j.jfda.2016.07.004.
   PubMed Web of Science ®Google Scholar
• Urpi-Sarda, M., M. Monagas, K. Nasiruddin, R. M. Lamuela-Raventos, C. Santos-Buelga, E. Sacanella, M. Castell, J. Permanyer, and C. Andres-Lacueva. 2009. Epicatechin, procyanidins, and phenolic microbial metabolites after cocoa intake in humans and rats. Analytical and Bioanalytical Chemistry 394 (6):1545–56. doi: 10.1007/s00216-009-2676-1.
   PubMed Web of Science ®Google Scholar
• Urpi-Sarda, M., R. Llorach, N. Khan, M. Monagas, M. Rotches-Ribalta, R. Lamuela-Raventos, R. Estruch, F. J. Tinahones, and C. Andres-Lacueva. 2010. Effect of milk on the urinary excretion of microbial phenolic acids after cocoa powder consumption in humans. Journal of Agricultural and Food Chemistry 58 (8):4706–11. doi: 10.1021/jf904440h.
   PubMed Web of Science ®Google Scholar
• Visioli, F., H. Bernaert, R. Corti, C. Ferri, S. Heptinstall, E. Molinari, A. Poli, M. Serafini, H. J. Smit, J. A. Vinson, et al. 2009. Chocolate, lifestyle, and health. Critical Reviews in Food Science and Nutrition 49 (4):299–312. doi: 10.1080/10408390802066805.
   PubMed Web of Science ®Google Scholar
• Visioli, F., C. A. De La Lastra, C. Andres-Lacueva, M. Avira, C. Calhau, A. Cassano, M. D'Archivio, A. Faria, G. Favé, V. Fogliano, et al. 2011. Polyphenols and human health: A prospectus. Critical Reviews in Food Science and Nutrition 51 (6):524–46. doi: 10.1080/10408391003698677.
   PubMed Web of Science ®Google Scholar
• Vitaglione, P., R. B. Lumaga, R. Ferracane, S. Sellitto, J. R. Morelló, J. R. Miranda, E. Shimoni, and V. Fogliano. 2013. Human bioavailability of flavanols and phenolic acids from cocoa-nut creams enriched with free or microencapsulated cocoa polyphenols. British Journal of Nutrition 109 (10):1832–43. doi: 10.1017/S0007114512003881.
   PubMed Web of Science ®Google Scholar
• Vuong, Q. 2014. Epidemiological evidence linking tea consumption to human health: A review. Critical Reviews in Food Science and Nutrition 54 (4):523–36. doi: 10.1080/10408398.2011.594184.
   PubMed Web of Science ®Google Scholar
• Walgren, R. A., J.-T. Lin, K.-H. Kinne, and T. Walle. 2000. Cellular uptake of dietary flavonoid quercetin-4′-β-glucoside by sodium-dependent glucose transporter SGLT1. Journal of Pharmacology and Experimental Therapeutics 294 (3):837–43.
   PubMed Web of Science ®Google Scholar
• Walle, T., F. Hsieh, M. H. DeLegge, J. E. Oatis, Jr., and U. K. Walle. 2004. High absorption but very low bioavailability of oral resveratrol in humans. Drug Metabolism & Disposition 32 (12):1377–82. doi: 10.1124/dmd.104.000885.
   PubMed Web of Science ®Google Scholar
• Wang, P., and S. Sang. 2018. Metabolism and pharmacokinetics of resveratrol and pterostilbene. Biofactors 44 (1):16–25. doi: 10.1002/biof.1410.
   PubMed Web of Science ®Google Scholar
• Williamson, G., and M. N. Clifford. 2017. Role of the small intestine, Colon and microbiota in determining the metabolic fate of polyphenols. Biochemical Pharmacology 139:24–39. doi: 10.1016/j.bcp.2017.03.012.
   PubMed Web of Science ®Google Scholar
• Williamson, G., C. D. Kay, and A. Crozier. 2018. The bioavailability, transport, and bioactivity of dietary flavonoids: A review from a historical perspective. Comprehensive Reviews in Food Science and Food Safety 17 (5):1054–112. doi: 10.1111/1541-4337.12351.
   PubMed Web of Science ®Google Scholar
• Wenzel, E., T. Soldo, H. Erbersdobler, and V. Somoza. 2005. Bioactivity and metabolism of trans-resveratrol orally administered to Wistar rats. Molecular Nutrition & Food Research 49 (5):482–94. doi: 10.1002/mnfr.200500003.
   PubMed Web of Science ®Google Scholar
• Wiczkowski, W., E. Romaszko, and M. K. Piskula. 2010. Bioavailability of cyanidin glycosides from natural chokeberry (Aronia melanocarpa) juice with dietary-relevant dose of anthocyanins in humans. Journal of Agricultural and Food Chemistry 58 (23):12130–6. doi: 10.1021/jf102979z.
   PubMed Web of Science ®Google Scholar
• Wiese, S., T. Esatbeyoglu, P. Winterhalter, H. P. Kruse, S. Winkler, A. Bub, and S. E. Kulling. 2015. Comparative biokinetics and metabolism of pure monomeric, dimeric, and polymeric flavan-3-ols: A randomized cross-over study in humans. Molecular Nutrition & Food Research 59 (4):610–21. doi: 10.1002/mnfr.201400422.
   PubMed Web of Science ®Google Scholar
• Wilson, P.K. 2012. Chocolate as medicine: A changing framework of evidence throughout history. In Chocolate and health, eds. R., Paoletti, A. Poli, A. Conti, and F. Visioli, 1–16. Milano, Italia: Springer Verlag Italia.
   Google Scholar
• Wollgast, J., and E. Anklam. 2000. Review on polyphenols in Theobroma cacao: Changes in composition during the manufacture of chocolate and methodology for identification and quantification. Food Research International 33 (6):423–47. doi: 10.1016/S0963-9969(00)00068-5.
   Web of Science ®Google Scholar
• Wu, X., G. Cao, and R. L. Prior. 2002. Absorption and metabolism of anthocyanins in elderly women after consumption of elderberry or blueberry. The Journal of Nutrition 132 (7):1865–71. doi: 10.1093/jn/132.7.1865.
   PubMed Web of Science ®Google Scholar
• Xie, L., S. G. Lee, T. M. Vance, Y. Wang, B. Kim, J.-Y. Lee, O. K. Chun, and B. W. Bolling. 2016. Bioavailability of anthocyanins and colonic polyphenol metabolites following consumption of aronia berry extract. Food Chemistry 211 (15):860–8. doi: 10.1016/j.foodchem.2016.05.122.
   PubMedGoogle Scholar
• Yuan, S., X. Li, Y. Jin, and J. Lu. 2017. Chocolate consumption and risk of coronary heart disease, stroke, and diabetes: A meta-analysis of prospective studies. Nutrients 9 (7):688. doi: 10.3390/nu9070688.
   PubMed Web of Science ®Google Scholar
• Yi, W., C. C. Akoh, J. Fischer, and G. Krewer. 2006. Absorption of anthocyanins from blueberry extracts by caco-2 human intestinal cell monolayers. Journal of Agricultural and Food Chemistry 54 (15):5651–8. doi: 10.1021/jf0531959.
   PubMed Web of Science ®Google Scholar
• Zumdick, S., A. Deters, and A. Hensel. 2012. In vitro intestinal transport of oligomeric procyanidins (DP 2 to 4) across monolayers of Caco-2 cells. Fitoterapia 83 (7):1210–7. doi: 10.1016/j.fitote.2012.06.013.
   PubMed Web of Science ®Google Scholar