Mind the gap—deficits in our knowledge of aspects impacting the bioavailability of phytochemicals and their metabolites—a position paper focusing on carotenoids and polyphenols

Abstract

Various secondary plant metabolites or phytochemicals, including polyphenols and carotenoids, have been associated with a variety of health benefits, such as reduced incidence of type 2 diabetes, cardiovascular diseases, and several types of cancer, most likely due to their involvement in ameliorating inflammation and oxidative stress. However, discrepancies exist between their putative effects when comparing observational and intervention studies, especially when using pure compounds. These discrepancies may in part be explained by differences in intake levels and their bioavailability. Prior to exerting their bioactivity, these compounds must be made bioavailable, and considerable differences may arise due to their matrix release, changes during digestion, uptake, metabolism, and biodistribution, even before considering dose‐ and host‐related factors. Though many insights have been gained on factors affecting secondary plant metabolite bioavailability, many gaps still exist in our knowledge. In this position paper, we highlight several major gaps in our understanding of phytochemical bioavailability, including effects of food processing, changes during digestion, involvement of cellular transporters in influx/efflux through the gastrointestinal epithelium, changes during colonic fermentation, and their phase I and phase II metabolism following absorption.

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    Not in our library

97. 97.

    Kong, F., Oztop, M. H., Paul Singh, R., McCarthy, M. J., Effect of boiling, roasting and frying on disintegration of peanuts in simulated gastric environment. LWT ‐ Food Sci. Technol. 2013, 50, 32–38.

    Not in our library

98. 98.

    Flores, F. P., Singh, R. K., Kerr, W. L., Pegg, R. B. et al., Total phenolics content and antioxidant capacities of microencapsulated blueberry anthocyanins during in vitro digestion. Food Chem. 2014, 153, 272–278.

    Not in our library10.1016/j.foodchem.2013.12.063

99. 99.

    Haratifar, S., Meckling, K. A., Corredig, M., Bioefficacy of tea catechins encapsulated in casein micelles tested on a normal mouse cell line (4D/WT) and its cancerous counterpart (D/v‐src) before and after in vitro digestion. Food Funct. 2014, 5, 1160–1166.

    Not in our library10.1039/c3fo60343a

100. 100.

     Jilani, H., Cilla A., Barbera R., Hamdi, M., Impact of biosorption into Saccharomyces cerevisiae and in vitro gastrointestinal digestion on total polyphenols and antioxidant capacity of tea and olive leaves infusions. Proceedings of the 2nd International Conference on Food Digestion, 137. Proceedings of the 2nd International Conference on Food Digestion, 137 2013.

     Not in our library

101. 101.

     McDougall, G., Dobson, P., Shapiro, F., Smith, P. et al., Assessing bioavailability of soft fruit polyphenols in vitro. Acta Hort. 2007, 744, 135–148.

     Not in our library

102. 102.

     Brown, E. M., McDougall, G. J., Stewart, D., Pereira‐Caro, G. et al., Persistence of anticancer activity in berry extracts after simulated gastrointestinal digestion and colonic fermentation. PLoS One 2012, 7, e49740.

     Not in our library10.1371/journal.pone.0049740

103. 103.

     Rodriguez‐Roque, M. J., Rojas‐Grau, M. A., Elez‐Martinez, P., Martin‐Belloso, O., Changes in vitamin C, phenolic, and carotenoid profiles throughout in vitro gastrointestinal digestion of a blended fruit juice. J. Agric. Food Chem. 2013, 61, 1859–1867.

     Not in our library10.1021/jf3044204

104. 104.

     Li, H., Deng, Z., Liu, R., Loewen, S. et al., Bioaccessibility, in vitro antioxidant activities and in vivo anti‐inflammatory activities of a purple tomato (Solanum lycopersicum L.). Food Chem. 2014, 159, 353–360.

     Not in our library10.1016/j.foodchem.2014.03.023

105. 105.

     Bassolino, L., Zhang, Y., Schoonbeek, H. J., Kiferle, C. et al., Accumulation of anthocyanins in tomato skin extends shelf life. New Phytol. 2013, 200, 650–655.

     Not in our library10.1111/nph.12524

106. 106.

     McDougall, G. J., Kulkarni, N. N., Stewart, D., Current developments on the inhibitory effects of berry polyphenols on digestive enzymes. Biofactors 2008, 34, 73–80.

     Not in our library10.1002/biof.5520340108

107. 107.

     Arranz, S., Silvan, J. M., Saura‐Calixto, F., Nonextractable polyphenols, usually ignored, are the major part of dietary polyphenols: a study on the Spanish diet. Mol. Nutr. Food Res. 2010, 54, 1646–1658.

     Not in our library10.1002/mnfr.200900580

108. 108.

     Maeda‐Yamamoto, M., Ema, K., Tokuda, Y., Monobe, M. et al., Effect of green tea powder (Camellia sinensis L. cv. Benifuuki) particle size on O‐methylated EGCG absorption in rats; The Kakegawa Study. Cytotechnology 2011, 63, 171–179.

     Not in our library10.1007/s10616-010-9331-8

109. 109.

     McClements, D. J., Decker, E. A., Park, Y., Controlling lipid bioavailability through physicochemical and structural approaches. Crit. Rev. Food Sci. Nutr. 2009, 49, 48–67.

     Not in our library10.1080/10408390701764245

110. 110.

     Bravo, L., Polyphenols: chemistry, dietary sources, metabolism, and nutritional significance. Nutr. Rev. 1998, 56, 317–333.

     Not in our library10.1111/j.1753-4887.1998.tb01670.x

111. 111.

     Anderson, J. M., Van Itallie, C. M., Physiology and function of the tight junction. Cold Spring Harb. Perspect. Biol. 2009, 1, a002584.

     Not in our library10.1101/cshperspect.a002584

112. 112.

     Miranda, L., Deusser, H., Evers, D., The impact of in vitro digestion on bioaccessibility of polyphenols from potatoes and sweet potatoes and their influence on iron absorption by human intestinal cells. Food Funct. 2013, 4, 1595–1601.

     Not in our library10.1039/c3fo60194c

113. 113.

     Perez‐Jimenez, J., AZ‐Rubio, M. E., Saura‐Calixto, F., Non‐extractable polyphenols, a major dietary antioxidant: occurrence, metabolic fate and health effects. Nutr. Res. Rev. 2013, 26, 118–129.

     Not in our library10.1017/s0954422413000097

114. 114.

     Chitchumroonchokchai, C., Failla, M. L., Hydrolysis of zeaxanthin esters by carboxyl ester lipase during digestion facilitates micellarization and uptake of the xanthophyll by Caco‐2 human intestinal cells. J. Nutr. 2006, 136, 588–594.

     Not in our library10.1093/jn/136.3.588

115. 115.

     Andre, C. M., Greenwood, J. M., Walker, E. G., Rassam, M. et al., Anti‐inflammatory procyanidins and triterpenes in 109 apple varieties. J. Agric. Food Chem. 2012, 60, 10546–10554.

     Not in our library10.1021/jf302809k

116. 116.

     Bohn, T., Tian, Q., Chitchumroonchokchai, C., Failla, M. L. et al., Supplementation of test meals with fat‐free phytosterol products can reduce cholesterol micellarization during simulated digestion and cholesterol accumulation by Caco‐2 cells. J. Agric. Food Chem. 2007, 55, 267–272.

     Not in our library10.1021/jf061829l

117. 117.

     Parker, R. S., Absorption, metabolism, and transport of carotenoids. FASEB J. 1996, 10, 542–551.

     Not in our library

118. 118.

     Sy, C., Gleize, B., Dangles, O., Landrier, J. F. et al., Effects of physicochemical properties of carotenoids on their bioaccessibility, intestinal cell uptake, and blood and tissue concentrations. Mol. Nutr. Food Res. 2012, 56, 1385–1397.

     Not in our library10.1002/mnfr.201200041

119. 119.

     Lesser, S., Cermak, R., Wolffram, S., Bioavailability of quercetin in pigs is influenced by the dietary fat content. J. Nutr. 2004, 134, 1508–1511.

     Not in our library10.1093/jn/134.6.1508

120. 120.

     Chitchumroonchokchai, C., Riedl, K. M., Suksumrarn, S., Clinton, S. K. et al., Xanthones in mangosteen juice are absorbed and partially conjugated by healthy adults. J. Nutr. 2012, 142, 675–680.

     Not in our library10.3945/jn.111.156992

121. 121.

     Bohn, T., Blackwood, M., Francis, D., Tian, Q. et al., Bioavailability of phytochemical constituents from a novel soy fortified lycopene rich tomato juice developed for targeted cancer prevention trials. Nutr. Canc. 2013, 65, 919–929.

     Not in our library10.1080/01635581.2011.630156

122. 122.

     Thomson, A. B., Jarocka‐Cyrta, E., Faria, J., Wild, G. E., Small bowel review–Part II. Can. J. Gastroenterol. 1997, 11, 159–165.

     Not in our library10.1155/1997/536830

123. 123.

     Han, X., Shenemail, T., Hongxiang L., Dietary polyphenols and their biological significance. Int. J. Mol. Sci. 2007, 8, 950–988.

     Not in our library

124. 124.

     Manach, C., Scalbert, A., Morand, C., Remesy, C. et al., Polyphenols: food sources and bioavailability. Am. J. Clin. Nutr. 2004, 79, 727–747.

     Not in our library10.1093/ajcn/79.5.727

125. 125.

     Kern, S. M., Bennett, R. N., Needs, P. W., Mellon, F. A. et al., Characterization of metabolites of hydroxycinnamates in the in vitro model of human small intestinal epithelium caco‐2 cells. J. Agric. Food Chem. 2003, 51, 7884–7891.

     Not in our library10.1021/jf030470n

126. 126.

     Granado‐Lorencio, F., Olmedilla‐Alonso, B., Herrero‐Barbudo, C., Blanco‐Navarro, I. et al., In vitro bioaccessibility of carotenoids and tocopherols from fruits and vegetables. Food Chem. 2007, 102, 641–648.

     Not in our library10.1021/jf070301t

127. 127.

     Cai, K., Bennick, A., Effect of salivary proteins on the transport of tannin and quercetin across intestinal epithelial cells in culture. Biochem. Pharmacol. 2006, 72, 974–980.

     Not in our library10.1016/j.bcp.2006.06.026

128. 128.

     Singh, H., Ye, A., Structural and biochemical factors affecting the digestion of protein‐stabilized emulsions. Curr. Opin. Colloid Interface Sci. 2013, 18, 360–370.

     Not in our library

129. 129.

     Bitsch, R., Netzel, M., Frank, T., Strass, G. et al., Bioavailability and biokinetics of anthocyanins from red grape juice and red wine. J. Biomed. Biotechnol. 2004, 2004, 293–298.

     Not in our library10.1155/s1110724304403106

130. 130.

     Biehler, E., Hoffmann, L., Krause, E., Bohn, T., Divalent minerals decrease micellarization and uptake of carotenoids and digestion products into Caco‐2 cells. J. Nutr. 2011, 141, 1769–1776.

     Not in our library10.3945/jn.111.143388

131. 131.

     Lai, S. K., Wang, Y. Y., Wirtz, D., Hanes, J., Micro‐ and macrorheology of mucus. Adv. Drug Deliv. Rev. 2009, 61, 86–100.

     Not in our library10.1016/j.addr.2008.09.012

132. 132.

     Dunnhaupt, S., Barthelmes, J., Hombach, J., Sakloetsakun, D. et al., Distribution of thiolated mucoadhesive nanoparticles on intestinal mucosa. Int. J. Pharm. 2011, 408, 191–199.

     Not in our library10.1016/j.ijpharm.2011.01.060

133. 133.

     Menard, S., Cerf‐Bensussan, N., Heyman, M., Multiple facets of intestinal permeability and epithelial handling of dietary antigens. Mucosal. Immunol 2010, 3, 247–259.

     Not in our library10.1038/mi.2010.5

134. 134.

     Rogoll, D., Bergmann, H., Hellenschmidt, D., Heinze, J. et al., Influence of apple polyphenols on the intestinal barrier in a colonic cell model. J. Appl. Bot. Food Qual. 2010, 83, 110–117.

     Not in our library

135. 135.

     Ulluwishewa, D., Anderson, R. C., McNabb, W. C., Moughan, P. J. et al., Regulation of tight junction permeability by intestinal bacteria and dietary components. J. Nutr. 2011, 141, 769–776.

     Not in our library10.3945/jn.110.135657

136. 136.

     Appeldoorn, M. M., Vincken, J. P., Gruppen, H., Hollman, P. C., Procyanidin dimers A1, A2, and B2 are absorbed without conjugation or methylation from the small intestine of rats. J. Nutr. 2009, 139, 1469–1473.

     Not in our library10.3945/jn.109.106765

137. 137.

     Shoji, T., Masumoto, S., Moriichi, N., Akiyama, H. et al., Apple procyanidin oligomers absorption in rats after oral administration: analysis of procyanidins in plasma using the porter method and high‐performance liquid chromatography/tandem mass spectrometry. J. Agric. Food Chem. 2006, 54, 884–892.

     Not in our library10.1021/jf052260b

138. 138.

     Chhabra, R. S., Intestinal absorption and metabolism of xenobiotics. Environ. Health Perspect. 1979, 33, 61–69.

     Not in our library10.1289/ehp.793361

139. 139.

     Estudante, M., Morais, J. G., Soveral, G., Benet, L. Z., Intestinal drug transporters: an overview. Adv. Drug Deliv. Rev. 2013, 65, 1340–1356.

     Not in our library10.1016/j.addr.2012.09.042

140. 140.

     Li, Y., Paxton, J. W., The effects of flavonoids on the ABC transporters: consequences for the pharmacokinetics of substrate drugs. Exp. Opin. Drug Metab. Toxicol. 2013, 9, 267–285.

     Not in our library10.1517/17425255.2013.749858

141. 141.

     Reboul, E., Thap, S., Tourniaire, F., Andre, M. et al., Differential effect of dietary antioxidant classes (carotenoids, polyphenols, vitamins C and E) on lutein absorption. Br. J. Nutr. 2007, 97, 440–446.

     Not in our library10.1017/s0007114507352604

142. 142.
     Absorption of Vitamin A and Carotenoids by the Enterocyte: Focus on Transport Proteins · 2013

     No notice
143. 143.

     Schramm, D. D., Karim, M., Schrader, H. R., Holt, R. R. et al., Food effects on the absorption and pharmacokinetics of cocoa flavanols. Life Sci. 2003, 73, 857–869.

     Not in our library10.1016/s0024-3205(03)00373-4

144. 144.

     Paine, M. F., Fisher, M. B., Immunochemical identification of UGT isoforms in human small bowel and in caco‐2 cell monolayers. Biochem. Biophys. Res. Commun. 2000, 273, 1053–1057.

     Not in our library10.1006/bbrc.2000.3064

145. 145.

     Chen, G., Zhang, D., Jing, N., Yin, S. et al., Human gastrointestinal sulfotransferases: identification and distribution. Toxicol. Appl. Pharmacol. 2003, 187, 186–197.

     Not in our library10.1016/s0041-008x(02)00073-x

146. 146.

     Shoba, G., Joy, D., Joseph, T., Majeed, M. et al., Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med. 1998, 64, 353–356.

     Not in our library10.1055/s-2006-957450

147. 147.

     Kaulmann, A., Bohn, T., Carotenoids, inflammation and oxidative stress – implications in cellular signalling pathways. Nutr. Res. 2014, 34, 907–929.

     Not in our library10.1016/j.nutres.2014.07.010

148. 148.

     van de Wetering, K., Burkon, A., Feddema, W., Bot, A. et al., Intestinal breast cancer resistance protein (BCRP)/Bcrp1 and multidrug resistance protein 3 (MRP3)/Mrp3 are involved in the pharmacokinetics of resveratrol. Mol. Pharmacol. 2009, 75, 876–885.

     Not in our library10.1124/mol.108.052019

149. 149.

     Hussain, M. M., Fatma, S., Pan, X., Iqbal, J., Intestinal lipoprotein assembly. Curr. Opin. Lipidol. 2005, 16, 281–285.

     Not in our library10.1097/01.mol.0000169347.53568.5a

150. 150.

     Escudero‐Lopez, B., Calani, L., Fernandez‐Pachon, M. S., Ortega, A. et al., Absorption, metabolism, and excretion of fermented orange juice (poly)phenols in rats. Biofactors 2014, 40, 327–335.

     Not in our library10.1002/biof.1152

151. 151.

     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.

     Not in our library10.1039/c3fo60024f

152. 152.

     Nardini, M., Cirillo, E., Natella, F., Scaccini, C., Absorption of phenolic acids in humans after coffee consumption. J. Agric. Food Chem. 2002, 50, 5735–5741.

     Not in our library10.1021/jf0257547

153. 153.

     Natsume, M., Osakabe, N., Oyama, M., Sasaki, M. et al., Structures of (‐)‐epicatechin glucuronide identified from plasma and urine after oral ingestion of (‐)‐epicatechin: differences between human and rat. Free Radic. Biol. Med. 2003, 34, 840–849.

     Not in our library10.1016/s0891-5849(02)01434-x

154. 154.

     Pimpao, R. C., Dew, T., Figueira, M. E., McDougall, G. J. et al., Urinary metabolite profiling identifies novel colonic metabolites and conjugates of phenolics in healthy volunteers. Mol. Nutr. Food Res. 2014, 58, 1414–1425.

     Not in our library10.1002/mnfr.201300822

155. 155.

     Felgines, C., Talavera, S., Gonthier, M. P., Texier, O. et al., Strawberry anthocyanins are recovered in urine as glucuro‐ and sulfoconjugates in humans. J. Nutr. 2003, 133, 1296–1301.

     Not in our library10.1093/jn/133.5.1296

156. 156.

     Lampe, J. W., Isoflavonoid and lignan phytoestrogens as dietary biomarkers. J. Nutr. 2003, 133, 956S–964S.

     Not in our library10.1093/jn/133.3.956s

157. 157.

     Sawai, Y., Kohsaka, K., Nishiyama, Y., Ando, K., Serum concentrations of rutoside metabolites after oral administration of a rutoside formulation to humans. Arzneimittelforschung 1987, 37, 729–732.

     Not in our library

158. 158.

     Adlercreutz, H., van der, W. J., Kinzel, J., Attalla, H. et al., Lignan and isoflavonoid conjugates in human urine. J. Steroid Biochem. Mol. Biol. 1995, 52, 97–103.

     Not in our library10.1016/0960-0760(94)00146-d

159. 159.

     Axelson, M., Setchell, K. D., The excretion of lignans in rats – evidence for an intestinal bacterial source for this new group of compounds. FEBS Lett. 1981, 123, 337–342.

     Not in our library10.1016/0014-5793(81)80322-5

160. 160.

     Duenas, M., Surco‐Laos, F., Gonzalez‐Manzano, S., Gonzalez‐Paramas, A. M. et al., Deglycosylation is a key step in biotransformation and lifespan effects of quercetin‐3‐O‐glucoside in Caenorhabditis elegans. Pharmacol. Res. 2013, 76, 41–48.

     Not in our library10.1016/j.phrs.2013.07.001

161. 161.

     Aura, A. M., O'Leary, K. A., Williamson, G., Ojala, M. et al., Quercetin derivatives are deconjugated and converted to hydroxyphenylacetic acids but not methylated by human fecal flora in vitro. J. Agric. Food Chem. 2002, 50, 1725–1730.

     Not in our library10.1021/jf0108056

162. 162.

     Crozier, A., Absorption, metabolism, and excretion of (‐)‐epicatechin in humans: an evaluation of recent findings. Am. J. Clin. Nutr. 2013, 98, 861–862.

     Not in our library10.3945/ajcn.113.072009

163. 163.

     Actis‐Goretta, L., Leveques, A., Rein, M., Teml, A. et al., Intestinal absorption, metabolism, and excretion of (‐)‐epicatechin in healthy humans assessed by using an intestinal perfusion technique. Am. J. Clin. Nutr. 2013, 98, 924–933.

     Not in our library10.3945/ajcn.113.065789

164. 164.

     Clifford, M. N., van der Hooft, J. J., Crozier, A., Human studies on the absorption, distribution, metabolism, and excretion of tea polyphenols. Am. J. Clin. Nutr. 2013, 98, 1619S–1630S.

     Not in our library10.3945/ajcn.113.058958

165. 165.

     Monagas, M., Urpi‐Sarda, M., Sanchez‐Patan, F., Llorach, R. et al., Insights into the metabolism and microbial biotransformation of dietary flavan‐3‐ols and the bioactivity of their metabolites. Food Funct. 2010, 1, 233–253

     Not in our library10.1039/c0fo00132e

166. 166.

     Kuijsten, A., Arts, I. C., Vree, T. B., Hollman, P. C., Pharmacokinetics of enterolignans in healthy men and women consuming a single dose of secoisolariciresinol diglucoside. J. Nutr. 2005, 135, 795–801.

     Not in our library10.1093/jn/135.4.795

167. 167.

     Seeram, N. P., Henning, S. M., Zhang, Y., Suchard, M. et al., Pomegranate juice ellagitannin metabolites are present in human plasma and some persist in urine for up to 48 hours. J. Nutr. 2006, 136, 2481–2485.

     Not in our library10.1093/jn/136.10.2481

168. 168.

     Gross, M., Pfeiffer, M., Martini, M., Campbell, D. et al., The quantitation of metabolites of quercetin flavonols in human urine. Cancer Epidemiol. Biomarkers Prev. 1996, 5, 711–720.

     Not in our library

169. 169.

     Vetrani, C., Rivellese, A. A., Annuzzi, G., Mattila, I. et al., Phenolic metabolites as compliance biomarker for polyphenol intake in a randomized controlled human intervention. Food Res. Int. 2014, 63, 233–238.

     Not in our library

170. 170.

     Griffith, L. G., Wells, A., Stolz, D. B., Engineering liver. Hepatology 2014, 60, 1426–1434.

     Not in our library10.1002/hep.27150

171. 171.

     Mandenius, C. F., Andersson, T. B., Alves, P. M., Batzl‐Hartmann, C. et al., Toward preclinical predictive drug testing for metabolism and hepatotoxicity by using in vitro models derived from human embryonic stem cells and human cell lines – a report on the Vitrocellomics EU‐project. Altern. Lab. Anim. 2011, 39, 147–171.

     Not in our library10.1177/026119291103900210

172. 172.

     Barron, D., Smarrito‐Menozzi, C., Viton, F., (Bio)chemical labelling tools for studying absorption & metabolism of dietary phenols – an overview. Curr. Org. Chem. 2012, 16, 663–690.

     Not in our library

173. 173.

     Saha, S., Hollands, W., Needs, P. W., Ostertag, L. M. et al., Human O‐sulfated metabolites of (‐)‐epicatechin and methyl‐(‐)‐epicatechin are poor substrates for commercial aryl‐sulfatases: implications for studies concerned with quantifying epicatechin bioavailability. Pharmacol. Res. 2012, 65, 592–602.

     Not in our library10.1016/j.phrs.2012.02.005

174. 174.

     Actis‐Goretta, L., Leveques, A., Giuffrida, F., Romanov‐Michailidis, F. et al., Elucidation of (‐)‐epicatechin metabolites after ingestion of chocolate by healthy humans. Free Radic. Biol. Med. 2012, 53, 787–795.

     Not in our library10.1016/j.freeradbiomed.2012.05.023

175. 175.

     Jacobs, D. M., Deltimple, N., van, V. E., van Dorsten, F. A. et al., (1)H NMR metabolite profiling of feces as a tool to assess the impact of nutrition on the human microbiome. NMR Biomed. 2008, 21, 615–626.

     Not in our library10.1002/nbm.1233

176. 176.

     Hanhineva, K., Aura, A. M., Rogachev, I., Matero, S. et al., In vitro microbiotic fermentation causes an extensive metabolite turnover of rye bran phytochemicals. PLoS One 2012, 7, e39322.

     Not in our library10.1371/journal.pone.0039322

177. 177.

     Grun, C. H., van Dorsten, F. A., Jacobs, D. M., Le, B. M. et al., GC‐MS methods for metabolic profiling of microbial fermentation products of dietary polyphenols in human and in vitro intervention studies. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 2008, 871, 212–219.

     Not in our library10.1016/j.jchromb.2008.04.039

178. 178.

     Oleaga, C., Ciudad, C. J., Izquierdo‐Pulido, M., Noe, V., Cocoa flavanol metabolites activate HNF‐3beta, Sp1, and NFY‐mediated transcription of apolipoprotein AI in human cells. Mol. Nutr. Food Res. 2013, 57, 986–995.

     Not in our library10.1002/mnfr.201200507

179. 179.

     Awad, A. B., Fink, C. S., Phytosterols as anticancer dietary components: evidence and mechanism of action. J. Nutr. 2000, 130, 2127–2130.

     Not in our library10.1093/jn/130.9.2127

180. 180.

     Wong, A., Chemical and microbiological considerations of phytosterols and their relative efficacies in functional foods for the lowering of serum cholesterol levels in humans: a review. J. Funct. Foods 2014, 6, 60–72.

     Not in our library

181. 181.

     Moussa, M., Landrier, J. F., Reboul, E., Ghiringhelli, O. et al., Lycopene absorption in human intestinal cells and in mice involves scavenger receptor class B type I but not Niemann‐Pick C1‐like 1. J. Nutr. 2008, 138, 1432–1436.

     Not in our library10.1093/jn/138.8.1432

182. 182.

     Sen, A., Ren, J., Ruffin, M. T., Turgeon, D. K. et al., Relationships between serum and colon concentrations of carotenoids and fatty acids in randomized dietary intervention trial. Cancer Prev. Res. (Phila) 2013, 6, 558–565.

     Not in our library10.1158/1940-6207.capr-13-0019

183. 183.

     Khachik, F., Carvalho, L., Bernstein, P. S., Muir, G. J. et al., Chemistry, distribution, and metabolism of tomato carotenoids and their impact on human health. Exp. Biol. Med. (Maywood) 2002, 227, 845–851.

     Not in our library10.1177/153537020222701002

184. 184.

     Faria, A., Meireles, M., Fernandes, I., Santos‐Buelga, C. et al., Flavonoid metabolites transport across a human BBB model. Food Chem. 2014, 149, 190–196.

     Not in our library10.1016/j.foodchem.2013.10.095

185. 185.

     Sergent, T., Garsou, S., Schaut, A., De, S. S. et al., Differential modulation of ochratoxin A absorption across Caco‐2 cells by dietary polyphenols, used at realistic intestinal concentrations. Toxicol. Lett. 2005, 159, 60–70.

     Not in our library10.1016/j.toxlet.2005.04.013

186. 186.

     Bailey, D. G., Malcolm, J., Arnold, O., Spence, J. D., Grapefruit juice–drug interactions. Br. J. Clin. Pharmacol. 1998, 46, 101–110.

     Not in our library10.1046/j.1365-2125.1998.00764.x

187. 187.

     Lampe, J. W., Interindividual differences in response to plant‐based diets: implications for cancer risk. Am. J. Clin. Nutr. 2009, 89, 1553S–1557S.

     Not in our library10.3945/ajcn.2009.26736d

188. 188.

     Yum, K., Hong, S. G., Healy, K. E., Lee, L. P., Physiologically relevant organs on chips. Biotechnol. J. 2014, 9, 16–27.

     Not in our library10.1002/biot.201300187

189. 189.

     Surco‐Laos, F., Cabello, J., Gomez‐Orte, E., Gonzalez‐Manzano, S. et al., Effects of O‐methylated metabolites of quercetin on oxidative stress, thermotolerance, lifespan and bioavailability on Caenorhabditis elegans. Food Funct. 2011, 2, 445–456.

     Not in our library10.1039/c1fo10049a

190. 190.

     Cilla, A., Alegria, A., Barbera, R., in: Morales‐Gonzales J. A. (Ed.), Oxidative Stress and Chronic Degenerative Diseases‐a Role for Antioxidants Rijeka, InTech, Croatia 2013, 131–151.

     Not in our library

191. 191.

     Tavares, L., Figueira, I., Macedo, D., McDougall, G. J. et al., Neuroprotective effect of blackberry (Rubus sp.) polyphenols is potentiated after simulated gastrointestinal digestion. Food Chem. 2012, 131, 1443–1452.

     Not in our library

192. 192.

     Tavares, L., Figueira, I., McDougall, G. J., Vieira, H. L. et al., Neuroprotective effects of digested polyphenols from wild blackberry species. Eur. J. Nutr. 2013, 52, 225–236.

     Not in our library10.1007/s00394-012-0307-7

193. 193.

     Ferruzzi, M. G., The influence of beverage composition on delivery of phenolic compounds from coffee and tea. Physiol. Behav. 2010, 100, 33–41.

     Not in our library10.1016/j.physbeh.2010.01.035

194. 194.

     Konishi, Y., Shimizu, M., Transepithelial transport of ferulic acid by monocarboxylic acid transporter in Caco‐2 cell monolayers. Biosci. Biotechnol. Biochem. 2003, 67, 856–862.

     Not in our library10.1271/bbb.67.856

195. 195.

     Watanabe, H., Yashiro, T., Tohjo, Y., Konishi, Y., Non‐involvement of the human monocarboxylic acid transporter 1 (MCT1) in the transport of phenolic acid. Biosci. Biotechnol. Biochem. 2006, 70, 1928–1933.

     Not in our library10.1271/bbb.60093

196. 196.

     Gill, R. K., Saksena, S., Alrefai, W. A., Sarwar, Z. et al., Expression and membrane localization of MCT isoforms along the length of the human intestine. Am. J. Physiol. Cell Physiol. 2005, 289, C846–C852.

     Not in our library10.1152/ajpcell.00112.2005

197. 197.

     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, 630–635.

     Not in our library10.1093/jn/132.4.630

198. 198.

     Reboul, E., Borel, P., Proteins involved in uptake, intracellular transport and basolateral secretion of fat‐soluble vitamins and carotenoids by mammalian enterocytes. Prog. Lipid Res. 2011, 50, 388–402.

     Not in our library10.1016/j.plipres.2011.07.001

Cited by papers we hold 7

• Sodium-dependent glucose transporter 1 and glucose transporter 2 mediate intestinal transport of quercetrin in Caco-2 cells · 2020
  Not checked
• Carotenoids and Chlorophylls as Antioxidants · 2020
  No notice
• Nutritional Importance of Carotenoids and Their Effect on Liver Health: A Review · 2019
  No notice
• Host‐related factors explaining interindividual variability of carotenoid bioavailability and tissue concentrations in humans · 2017
  No notice
• Catechins and Their Therapeutic Benefits to Inflammatory Bowel Disease · 2017
  No notice
• Review: In vivo and postmortem effects of feed antioxidants in livestock: a review of the implications on authorization of antioxidant feed additives · 2016
  Not checked
• Algae as nutritional and functional food sources: revisiting our understanding · 2016
  No notice

Reads

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