Abstract
There is substantial interest in the role of plant secondary metabolites as protective dietary agents. In particular, the involvement of flavonoids and related compounds has become a major topic in human nutrition research. Evidence from epidemiological and human intervention studies is emerging regarding the protective effects of various (poly)phenol-rich foods against several chronic diseases, including neurodegeneration, cancer and cardiovascular diseases. In recent years, the use of HPLC–MS for the analysis of flavonoids and related compounds in foods and biological samples has significantly enhanced our understanding of (poly)phenol bioavailability. These advancements have also led to improvements in the available food composition and metabolomic databases, and consequently in the development of biomarkers of (poly)phenol intake to use in epidemiological studies. Efforts to create adequate standardised materials and well-matched controls to use in randomised controlled trials have also improved the quality of the available data. In vitro investigations using physiologically achievable concentrations of (poly)phenol metabolites and catabolites with appropriate model test systems have provided new and interesting insights on potential mechanisms of actions. This article will summarise recent findings on the bioavailability and biological activity of (poly)phenols, focusing on the epidemiological and clinical evidence of beneficial effects of flavonoids and related compounds on urinary tract infections, cognitive function and age-related cognitive decline, cancer and cardiovascular disease.
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Notes
Flavonoids and related compounds are also referred to as polyphenols; however, a number of compounds, including hydroxycinnamates and phenolic acids, have only one phenolic ring. In this review, therefore, the term (poly)phenolic compounds will be used.
Mubarak et al. (2012) state they used 3-O-caffeoylquinic acid whereas in fact they used 5-O-caffeoyquinic acid. There is much confusion over caffeoylquinic acids with many suppliers, including Sigma, using non-IUPAC nomenclature. They refer to chlorogenic acid as 3-O-caffeoylquinic acid when it is 5-O-caffeoyquinic acid while their neochorogenic acid, marketed as 5-O-caffeoylquinic acid, is the 3-O-isomer. See Fig. 3.
References
Abarzua S, Serikawa T, Szewczyk M, Richter DU, Piechulla B, Briese V (2012) Antiproliferative activity of lignans against the breast carcinoma cell lines MCF 7 and BT 20. Arch Gynecol Obstet 285:1145–1151
Abbott NJ, Patabendige AA, Dolman DE, Yusof SR, Begley DJ (2010) Structure and function of the blood-brain barrier. Neurobiol Dis 37:13–25
Abd El Mohsen MM, Kuhnle G, Rechner AR, Schroeter H, Rose S, Jenner P, Rice-Evans CA (2002) Uptake and metabolism of epicatchin and its access to the brain after oral ingestion. Free Radic Biol Med 33:1693–1702
Actis-Goretta L, Lèvéques A, Giuffrida F, Romanov-Michailidis F, Viton F, Baron D, Duenas-Paton M, Gonzalez-Manana S, Santos-Buelga C, Williamson G, Dionisi F (2012) Elucidation of (−)-epicatechin metabolites after ingestion of chocolate by healthy humans. Free Radic Biol Med 53:787–795
Actis-Goretta L, Lèvéques A, Rein M, Teml A, Schäfer C, Hofmann U, Li H, Schwab M, Eichelbaum M, Williamson G (2013) Intestinal absorption, metabolism, and excretion of (−)-epicatechin in healthy humans assessed by using an intestinal perfusion technique. Am J Clin Nutr 98:924–933
Agostinho P, Cunha RA, Oliveira C (2010) Neuroinflammation, oxidative stress and the pathogenesis of Alzheimer’s disease. Curr Pharm Des 16:2766–2768
Ahn WS, Yoo J, Huh SW, Kim CK, Lee JM, Namkoong SE, Bae SM, Lee IP (2003) Protective effects of green tea extracts (Polyphenon E and EGCG) on human cervical lesions. Eur J Cancer Prev 12:383–390
Aires V, Limagne E, Cotte AK, Latruffe N, Ghiringhelli F, Delmas D (2013) Resveratrol metabolites inhibit human metastatic colon cancer cells progression and synergize with chemotherapeutic drugs to induce cell death. Mol Nutr Food Res 57:1170–1181
Akiyama H, Barger S, Barnum S, Bradt B, Bauer J, Cole GM, Cooper NR, Eikelenboom P, Emmerling M, Fiebich BL, Finch CE, Frautschy S, Griffin WS, Hampel H, Hull M, Landreth G, Lue L, Mrak R, Mackenzie IR, McGeer PL, O’Banion MK, Pachter J, Pasinetti G, Plata-Salaman C, Rogers J, Rydel R, Shen Y, Streit W, Strohmeyer R, Tooyoma I, Van Muiswinkel FL, Veerhuis R, Walker D, Webster S, Wegrzyniak B, Wenk G, Wyss-Coray T (2000) Inflammation and Alzheimer’s disease. Neurobiol Aging 21:383–421
Albini A, Tosetti F, Li VW, Noonan DM, Li WW (2012) Cancer prevention by targeting angiogenesis. Nat Rev Clin Oncol 9:498–509
Andres-Lacueva C, Shukitt-Hale B, Galli RL, Jaurequi O, Lamuela-Raventos RM, Joseph JA (2005) Anthocyanins in aged blueberry-fed rats are found centrally and may enhance memory. Nutr Neurosci 8:112–120
Arts IC, Hollman PC, Feskens EJ, Bueno de Mesquita HB, Kromhout D (2001) Catechin intake might explain the inverse relation between tea consumption and ischemic heart disease: the Zutphen Elderly Study. Am J Clin Nutr 74:227–232
Arts IC, Jacobs DR Jr, Gross M, Harnack LJ, Folsom AR (2002) Dietary catechins and cancer incidence among postmenopausal women: the Iowa Women’s Health Study (United States). Cancer Causes Control 13:373–382
Asher GN, Viera AJ, Weaver MA, Dominik R, Caughey M, Hinderliter AL (2012) Effect of hawthorn standardized extract on flow mediated dilation in prehypertensive and mildly hypertensive adults: a randomized, controlled cross-over trial. BMC Complement Altern Med 12:26. doi:10.1186/1472-6882-12-26
Azzini E, Vitaglione P, Intorre F, Napolitano A, Durazzo A, Fumagalli A, Catasta G, Rossi L, Venneria E, Raguzzini A, Palomba L, Fogiliano V, Maiani G (2010) Bioavailability of strawberry antioxidants in human subjects. Br J Nutr 104:1165–1173
Barberger-Gateau P, Raffaitin C, Letenneur L, Berr C, Tzourio C, Dartigues JF, Alperovitch A (2007) Dietary patterns and risk of dementia: the Three-City cohort study. Neurology 69:1921–1930
Barona J, Aristizabal JC, Blesso CN, Volek JS, Fernandez ML (2012) Grape polyphenols reduce blood pressure and increase flow-mediated vasodilation in men with metabolic syndrome. J Nutr 142:1626–1632
Barron D, Smarrito-Menozz C, Fumeaux R, Viton F (2012) Sythesis of dietary phenolic metabolites and isotopically labeled dietary phenolics. In: Spencer JPE, Crozier A (eds) Flavonoids and related compounds: bioavailability and function. CRC Press, Boca Raton, pp 233–280
Barzilai A, Melamed E (2003) Molecular mechanisms of selective dopaminergic neuronal death in Parkinson’s disease. Trends Mol Med 9:126–132
Baum L, Lam CW, Cheung SK, Kwok T, Lui V, Tsoh J, Lam L, Leung V, Hui E, Ng C, Woo J, Chiu HF, Goggins WB, Zee BC, Cheng KF, Fong CY, Wong A, Mok H, Chow MS, Ho PC, Ip SP, Ho CS, Yu XW, Lai CY, Chan MH, Szeto S, Chan IH, Mok V (2008) Six-month randomized, placebo-controlled, double-blind, pilot clinical trial of curcumin in patients with Alzheimer disease. J Clin Psychopharmacol 28:110–113
Benetou V, Orfanos P, Lagiou P, Trichopoulos D, Boffetta P, Trichopoulou A (2008) Vegetables and fruits in relation to cancer risk: evidence from the Greek EPIC cohort study. Cancer Epidemiol Biomarkers Prev 17:387–392
Bettuzzi S, Brausi M, Rizzi F, Castagnetti G, Peracchia G, Corti A (2006) Chemoprevention of human prostate cancer by oral administration of green tea catechins in volunteers with high-grade prostate intraepithelial neoplasia: a preliminary report from a one-year proof-of-principle study. Cancer Res 66:1234–1240
Bode LM, Bunzel D, Huch M, Cho GS, Ruhland D, Bunzi M, Bub A, Franz CM, Kulling SE (2013) In vivo and in vitro metabolism of trans-resveratrol by human gut microbiota. Am J Clin Nutr 97:295–309
Boffetta P, Couto E, Wichmann J, Ferrari P, Trichopoulos D, Bueno-de-Mesquita HB, van Duijnhoven FJ, Buchner FL, Key T, Boeing H, Nothlings U, Linseisen J, Gonzalez CA, Overvad K, Nielsen MR, Tjonneland A, Olsen A, Clavel-Chapelon F, Boutron-Ruault MC, Morois S, Lagiou P, Naska A, Benetou V, Kaaks R, Rohrmann S, Panico S, Sieri S, Vineis P, Palli D, van Gils CH, Peeters PH, Lund E, Brustad M, Engeset D, Huerta JM, Rodriguez L, Sanchez MJ, Dorronsoro M, Barricarte A, Hallmans G, Johansson I, Manjer J, Sonestedt E, Allen NE, Bingham S, Khaw KT, Slimani N, Jenab M, Mouw T, Norat T, Riboli E, Trichopoulou A (2010) Fruit and vegetable intake and overall cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). J Natl Cancer Inst 102:529–537
Bogdanski P, Suliburska J, Szulinska M, Stepien M, Pupek-Musialik D, Jablecka A (2012) Green tea extract reduces blood pressure, inflammatory biomarkers, and oxidative stress and improves parameters associated with insulin resistance in obese, hypertensive patients. Nutr Res 32:421–427
Boots AW, Wilms LC, Swennen EL, Kleinjans JC, Bast A, Haenen GR (2008) In vitro and ex vivo anti-inflammatory activity of quercetin in healthy volunteers. Nutrition 24:703–710
Borges G, Lean MEJ, Roberts SA, Crozier A (2013) Bioavailability of dietary (poly)phenols: a study with ileostomists to discriminate between absorption in the small and large intestine. Food Funct 4:754–762
Bosviel R, Durif J, Déchelotte P, Bignon YJ, Bernard-Gallon D (2012) Epigenetic modulation of BRCA1 and BRCA2 gene expression by equol in breast cancer cell lines. Br J Nutr 108:1187–1193
Botden IPG, Draijer R, Westerhof BE, Rutten JHW, Langendonk JG, Sijbrands EJG, Danser AHJ, Zock PL, van den Meiracker AH (2012) Red wine polyphenols do not lower peripheral or central blood pressure in high normal blood pressure and hypertension. Am J Hypertens 25:718–723
Botterweck AA, van den Brandt PA, Goldbohm RA (1998) A prospective cohort study on vegetable and fruit consumption and stomach cancer risk in The Netherlands. Am J Epidemiol 148:842–853
Bowman GL, Kaye JA, Moore M, Waichunas D, Carlson NE, Quinn JF (2007) Blood-brain barrier impairment in Alzheimer’s disease: stability and functional significance. Neurology 68:1809–1814
Bravo L, Saura-Calixto F, Goni I (1992) Effects of dietary fibre and tannins from apple pulp on the composition of faeces in rats. Br J Nutr 67:463–473
Bresciani L, Calani L, Bocchi L, Delucchi F, Savi M, Ray S, Brighenti F, Stilli D, Del Rio D (2014) Bioaccumulation of resveratrol metabolites in myocardial tissue is dose-time dependent and related to cardiac hemodynamics in diabetic rats. Nutr Metab Cardiovasc Dis 24:408–415
Breteler MM (2000) Vascular risk factors for Alzheimer’s disease: an epidemiologic perspective. Neurobiol Aging 21:153–160
Brown EM, Latimer C, McDougall GJ, Stewart D, Crozier A, Rowland I, Gill CIR (2014) In vitro and in vivo models of colorectal cancer: anti-genotoxic activity of berries. J Agric Food Chem 62:3852–3866
Burns J, Yokota T, Ashihara H, Lean MEJ, Crozier A (2002) Plant foods and herbal sources of resveratrol. J Agric Food Chem 50:3337–3340
Cai J, Pajak A, Li Y, Shestov D, Davis CE, Rywik S, Deev A, Tyroler HA (2004) Total cholesterol and mortality in China, Poland, Russia, and the US. Ann Epidemiol 14:399–408
Cai L, Ma D, Zhang Y, Liu Z, Wang P (2012) The effect of coffee consumption on serum lipids: a meta-analysis of randomized controlled trials. Eur J Clin Nutr 66:872–877
Calani L, Del Rio D, Luisa Callegari M, Morelli L, Brighenti F (2012) Updated bioavailability and 48 h excretion profile of flavan-3-ols from green tea in humans. Int J Food Sci Nutr 63:513–521
Camfield DA, Scholey A, Pipingas A, Silberstein R, Kras M, Nolidin K, Wesnes K, Pase M, Stough C (2012) Steady state visually evoked potential (SSVEP) topography changes associated with cocoa flavanol consumption. Physiol Behav 105:948–957
Canevelli M, Adali N, Kelaiditi E, Cantet C, Ousset PJ, Cesari M (2014) Effects of Gingko biloba supplementation in Alzheimer’s disease patients receiving cholinesterase inhibitors: data from the ICTUS study. Phytomedicine 21:888–892
Carroll RE, Benya RV, Turgeon DK, Vareed S, Neuman M, Rodriguez L, Kakarala M, Carpenter PM, McLaren C, Meyskens FL Jr, Brenner DE (2011) Phase IIa clinical trial of curcumin for the prevention of colorectal neoplasia. Cancer Prev Res 4:354–364
Casini ML, Marelli G, Papaleo E, Ferrari A, D’Ambrosio F, Unfer V (2006) Psychological assessment of the effects of treatment with phytoestrogens on postmenopausal women: a randomized, double-blind, crossover, placebo-controlled study. Fertil Steril 85:972–978
Cassidy A, Rimm EB, O’Reilly EJ, Logroscino G, Kay C, Chiuve SE, Rexrode KM (2012) Dietary flavonoids and risk of stroke in women. Stroke 43:946–951
Cassidy A, Mukamal KJ, Liu L, Franz M, Eliassen AH, Rimm EB (2013) High anthocyanin intake is associated with a reduced risk of myocardial infarction in young and middle-aged women. Circulation 127:188–196
Caugant DA, Levin BR, Lidin-Janson G, Whittam TS, Svanborg Eden C, Selander RK (1983) Genetic diversity and relationships among strains of Escherichia coli in the intestine and those causing urinary tract infections. Prog Allergy 33:203–227
Chanet A, Milenkovic D, Claude S, Maier JA, Kamran Khan M, Rakotomanomana N, Shinkurak S, Bérard AM, Bennetau-Pelissero C, Mazur A, Morand C (2013) Flavanone metabolites decrease monocyte adhesion to TNF-α-activated endothelial cells by modulating expression of atherosclerosis-related genes. Br J Nutr 110:587–598
Checkoway H, Powers K, Smith-Weller T, Franklin GM, Longstreth WT Jr, Swanson PD (2002) Parkinson’s disease risks associated with cigarette smoking, alcohol consumption, and caffeine intake. Am J Epidemiol 155:732–738
Cheng AL, Hsu CH, Lin JK, Hsu MM, Ho YF, Shen TS, Ko JY, Lin JT, Lin BR, Ming-Shiang W, Yu HS, Jee SH, Chen GS, Chen TM, Chen CA, Lai MK, Pu YS, Pan MH, Wang YJ, Tsai CC, Hsieh CY (2001) Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res 21:2895–2900
Chiva-Blanch G, Urpi-Sarda M, Ros E, Arranz S, Valderas-Martinez P, Casas R, Sacanella E, Llorach R, Lamuela-Raventos RM, Andres-Lacueva C, Estruch R (2012) Dealcoholized red wine decreases systolic and diastolic blood pressure and increases plasma nitric oxide: short communication. Circ Res 111:1065–1068
Chiva-Blanch G, Urpi-Sarda M, Ros E, Valderas-Martinez P, Casas R, Arranz S, Guillen M, Lamuela-Raventos RM, Llorach R, Andres-Lacueva C, Estruch R (2013) Effects of red wine polyphenols and alcohol on glucose metabolism and the lipid profile: a randomized clinical trial. Clin Nutr 32:200–206
Cho JM, Chang SY, Kim DB, Needs PW, Jo YH, Kim MJ (2012) Effects of physiological quercetin metabolites on interleukin-1β-induced inducible NOS expression. J Nutr Biochem 23:1394–1402
Choan E, Segal R, Jonker D, Malone S, Reaume N, Eapen L, Gallant V (2005) A prospective clinical trial of green tea for hormone refractory prostate cancer: an evaluation of the complementary/alternative therapy approach. Urol Oncol 23:108–113
Chow H, Hakim IA, Vining DR, Crowell JA, Ranger-Moore J, Chew WM, Celaya CA, Rodney SR, Hara Y, Alberts DS (2005) Effects of dosing condition on the oral bioavailability of green tea catechins after single-dose administration of Polyphenon E in healthy individuals. Clin Cancer Res 11:4627–4633
Chun OK, Chung SJ, Claycombe KJ, Song WO (2008) Serum C-reactive protein concentrations are inversely associated with dietary flavonoid intake in U.S. adults. J Nutr 138:753–760
Claude S, Boby C, Rodriguez-Mateos A, Spencer JP, Gerard N, Morand C, Milenkovic D (2014) Flavanol metabolites reduce monocyte adhesion to endothelial cells through modulation of expression of genes via p38-MAPK and p65-Nf-kB pathways. Mol Nutr Food Res 58:1016–1027
Clifford MN (2000) Anthocyanins—nature, occurrence and dietary burden. J Sci Food Agric 80:1063–1072
Commenges D, Scotet V, Renaud S, Jacqmin-Gadda H, Barberger-Gateau P, Dartigues JF (2000) Intake of flavonoids and risk of dementia. Eur J Epidemiol 16:357–363
Cook A, Pryer J, Shetty P (2000) The problem of accuracy in dietary surveys. Analysis of the over 65 UK National Diet and Nutrition Survey. J Epidemiol Community Health 54:611–616
Cooke EM (1974) Escherichia coli and man. Churchill Livingstone, Edinburgh, pp 31–46
Corder R, Crozier A, Kroon PA (2003) Drinking your health? It’s too early to say. Nature 426:119
Cottart CH, Nivet-Antoine V, Beaudeux JL (2014) Review of recent data on the metabolism, biological effects, and toxicity of resveratrol in humans. Mol Nutr Food Res 58:7–21
Crews WD Jr, Harrison DW, Griffin ML, Addison K, Yount AM, Giovenco MA, Hazell J (2005) A double-blinded, placebo-controlled, randomized trial of the neuropsychologic efficacy of cranberry juice in a sample of cognitively intact older adults: pilot study findings. J Altern Complement Med 11:305–309
Croteaux R, Kutchan TM, Lewis NG (2000) Natural products (secondary metabolites). In: Buchanan BB, Gruissem W, Jones RL (eds) Biochemistry and molecular biology of plants. American Society of Plant Physiologists, Rockville, pp 1250–1318
Crozier A (2013) Absorption, metabolism, and excretion of (−)-epicatechin in humans: an evaluation of recent findings. Am J Clin Nutr 98:861–862
Crozier A, Jaganath IB, Clifford MN (2006a) Phenols, polyphenols and tannins: an overview. In: Crozier A, Clifford MN, Ashihara H (eds) Plant secondary metabolites: occurrence, structure and role in the human diet. Blackwell Publishing, Oxford, pp 1–24
Crozier A, Yokota T, Jaganath IB, Marks S, Saltmarsh M, Clifford MN (2006b) Secondary metabolites as dietary components in plant-based foods and beverages. In: Crozier A, Clifford MN, Ashihara H (eds) Plant secondary metabolites: occurrence, structure and role in the human diet. Blackwell Publishing, Oxford, pp 208–302
Crozier A, Del Rio D, Clifford MN (2010) Bioavailability of dietary flavonoids and phenolic compounds. Mol Asp Med 31:446–467
Crozier TWM, Stalmach A, Lean MEJ, Crozier A (2012) Espresso coffees, caffeine and chlorogenic acid intake: potential health implications. Food Funct 3:30–33
Curtis PJ, Sampson M, Potter J, Dhatariya K, Kroon PA, Cassidy A (2012) Chronic ingestion of flavan-3-ols and isoflavones improves insulin sensitivity and lipoprotein status and attenuates estimated 10-year CVD risk in medicated postmenopausal women with type 2 diabetes: a 1-year, double-blind, randomized, controlled trial. Diabetes Care 35:226–232
Curtis PJ, Potter J, Kroon PA, Wilson P, Dhatariya K, Sampson M, Cassidy A (2013) Vascular function and atherosclerosis progression after one year of flavonoid intake in statin-treated postmenopausal women with type 2 diabetes: a double-blind randomized controlled trial. Am J Clin Nutr 97:93–942
Czank C, Cassidy A, Zhang Q, Morrison DJ, Preston T, Kroon PA, Botting NP, Kay CD (2013) Human metabolism and elimination of the anthocyanin, cyanidin-3-glucoside: a 13C-tracer study. Am J Clin Nutr 97:995–1003
Dai Q, Borenstein AR, Wu Y, Jackson JC, Larson EB (2006) Fruit and vegetable juices and Alzheimer’s disease: the Kame Project. Am J Med 119:751–759
Dall’Asta M, Calani L, Tedeschi M, Jechiu L, Brighenti F, Del Rio D (2012) Identification of microbial metabolites derived from in vitro fecal fermentation of different polyphenolic food sources. Nutrition 28:197–203
Dall’Asta M, Derlindati E, Curella V, Mena P, Calani L, Ray S, Zavaroni I, Brighenti F, Del Rio D (2013) Effects of naringenin and its phase II metabolites on in vitro human macrophage gene expression. Int J Food Sci Nutr 64:843–849
D’Archivio M, Santangelo C, Scazzocchio B, Vari R, Filesi C, Masella R, Giovannini C (2008) Modulatory effects of polyphenols on apoptosis induction: relevance for cancer prevention. Int J Mol Sci 9:213–228
Davidson MH, Maki KC, Dicklin MR, Feinstein SB, Witchger M, Bell M, McGuire DK, Provost JC, Liker H, Aviram M (2009) Effects of consumption of pomegranate juice on carotid intima-media thickness in men and women at moderate risk for coronary heart disease. Am J Cardiol 104:936–942
Davinelli S, Sapere N, Visentin M, Zella D, Scapagnini G (2013) Enhancement of mitochondrial biogenesis with polyphenols: combined effects of resveratrol and equol in human endothelial cells. Immun Ageing 10:28. doi:10.1186/1742-4933-10-28
Day AJ, Canada FJ, Diaz JC, Kroon PA, McLauchlan R, Faulds CB, Plumb GW, Morgan MR, Williamson G (2000) Dietary flavonoids and isoflavones glycosides are hydroylysed by the lactase site of lactase phloridzin hydrolase. FEBS Lett 468:166–170
de Bock M, Derraik JGB, Brennan CM, Biggs JB, Morgan PE, Hodgkinson SC, Hofman PL, Cutfield WS (2013) Olive (Olea europaea L.) leaf polyphenols improve insulin sensitivity in middle-aged overweight men: a randomized, placebo-controlled, crossover trial. PLoS ONE 8:e57622
de Ferrars RM, Czank C, Zhang Q et al (2014) The pharmacokinetics of anthocyanins and their metabolites in humans. Br J Pharmacol 171:3268–3282
de Visser KE, Eichten A, Coussens LM (2006) Paradoxical roles of the immune system during cancer development. Nat Rev Cancer 6:24–37
Del Bo C, Riso P, Campolo J, Moller P, Loft S, Klimis-Zacas D, Brambilla A, Rizzolo A, Porrini M (2013) A single portion of blueberry (Vaccinium corymbosum L) improves protection against DNA damage but not vascular function in healthy male volunteers. Nutr Res 33:220–227
Del Rio D, Calani L, Brighenti F (2013a) Green tea flavan-3-ol bioavailability. In: Preedy V (ed) Tea in health and disease prevention. Academic Press, London, pp 413–424
Del Rio D, Rodriguez-Mateos A, Spencer JPE, Tognolini M, Borges G, Crozier A (2013b) Dietary (poly)phenolics in human health: structures, bioavailability, and evidence of protective effects against chronic diseases. Antioxid Redox Signal 18:1818–1892
Dellafiora L, Mena P, Cozzini P, Brighenti F, Del Rio D (2013) Modelling the possible bioactivity of ellagitannin-derived metabolites. In silico tools to evaluate their potential xenoestrogenic behavior. Food Funct 4:1442–1451
Delucchi F, Berni R, Frati C, Cavalli S, Graiani G, Sala R, Chaponnier C, Gabbiana G, Del Rio D, Bocchi L, Lagrasta C, Quiani F, Stilli D (2012) Resveratrol treatment reduces cardiac progenitor cell dysfunction and prevents morpho-functional ventricular remodeling in type-1 diabetic rats. PLoS ONE 7:e39836
Deprez S, Brezillon C, Rabot S, Philippe C, Mila I, Lapierre C, Scalbert A (2000) Polymeric proanthocyanidins are catabolized by human colonic microflora into low-molecular-weight phenolic acids. J Nutr 130:2733–2738
Derlindati E, Dall’Asta M, Ardigò D, Brighenti F, Zararoni I, Crozier A, Del Rio D (2012) Quercetin-3-O-glucuronide affects the gene expression profile of M1 and M2a human macrophages exhibiting anti-inflammatory effects. Food Funct 3:1144–1152
Desideri G, Kwik-Uribe C, Grassi D, Necozione S, Ghiadoni L, Mastroiacovo D, Raffaele A, Ferri L, Bocale R, Lechiara MC, Marini C, Ferri C (2012) Benefits in cognitive function, blood pressure, and insulin resistance through cocoa flavanol consumption in elderly subjects with mild cognitive impairment: the Cocoa, Cognition, and Aging (CoCoA) Study. Hypertension 60:794–801
Devore EE, Kang JH, Breteler MM, Grodstein F (2012) Dietary intakes of berries and flavonoids in relation to cognitive decline. Ann Neurol 72:135–143
Dewick PM (2009) Medicinal natural products: a biosynthetic approach, 3rd edn. Wiley, Chichester
Dohadwala MM, Holbrook M, Hamburg NM, Shenouda SM, Chung WB, Titas M, Kluge MA, Wang N, Palmisano J, Milbury PE, Blumberg JB, Vita JA (2011) Effects of cranberry juice consumption on vascular function in patients with coronary artery disease. Am J Clin Nutr 93:934–940
Donnenberg MS, Welch RA (1996) Virulence determinants of uropathogenic Escherichia coli. In: Mobley HLT, Warren JW (eds) Urinary tract infections: molecular pathogenesis and clinical management. ASM Press, Washington, pp 135–174
Donovan JL, Manach C, Rios L, Morand C, Scalbert A, Remesy C (2002) Procyanidins are not bioavailable in rats fed a single meal containing a grapeseed extract or the procyanidin dimer B-3. Br J Nutr 87:299–306
Donovan JL, Manach C, Faulks RM, Kroon P (2006) Absorption and metabolism of dietary plant secondary metabolites. In: Crozier A, Clifford MN, Ashihara H (eds) plant secondary metabolites. Occurrence, structure and role in the human diet. Blackwell Publishing, Oxford, pp 303–351
Duffy R, Wiseman H, File SE (2003) Improved cognitive function in postmenopausal women after 12 weeks of consumption of a soya extract containing isoflavones. Pharmacol Biochem Behav 75:721–729
Edwards RL, Lyon T, Litwin SE, Rabovsky A, Symons JD, Jalili T (2007) Quercetin reduces blood pressure in hypertensive subjects. J Nutr 137:2405–2411
Egert S, Bosy-Westphal A, Seiberl J, Kürbitz C, Settler U, Plachta-Danielzik S, Wagner AE, Frank J, Schrezenmeir J, Rimbach G, Wolffram S, Müller MJ (2009) Quercetin reduces systolic blood pressure and plasma oxidised low-density lipoprotein concentrations in overweight subjects with a high-cardiovascular disease risk phenotype: a double-blinded, placebo-controlled cross-over study. Br J Nutr 102:1065–1074
Engelhart MJ, Geerlings MI, Meijer J, Kiliaan A, Ruitenberg A, van Swieten JC, Stijnen T, Hofman A, Witteman JC, Breteler MM (2004) Inflammatory proteins in plasma and the risk of dementia: the Rotterdam study. Arch Neurol 61:668–672
Enseleit F, Sudano I, Periat D, Winnik S, Wolfrum M, Flammer AJ, Frohlich GM, Kaiser P, Hirt A, Haile SR, Krasniqi N, Matter CM, Uhlenhut K, Hogger P, Neidhart M, Luscher TF, Ruschitzka F, Noll G (2012) Effects of pycnogenol on endothelial function in patients with stable coronary artery disease: a double-blind, randomized, placebo-controlled, cross-over study. Eur Heart J 33:1589–1597
Erk T, Renouf M, Williamson G, Melcher R, Steiling H, Richling E (2014) Absorption and isomerization of caffeoylquinic acids from different foods using ileostomist volunteers. Eur J Nutr 53:159–166
Eseberri I, Lasa A, Churruca I, Portillo MP (2013) Resveratrol metabolites modify adipokine expression and secretion in 3T3-L1 pre-adipocytes and mature adipocytes. PLoS ONE 8:e63918
Fang J (2014) Some anthocyanins could be efficiently absorbed across the gastrointestinal mucosa: extensive presystemic metabolism reduces apparent bioavailability. J Agric Food Chem. doi:10.1021/jf405356b
Favero A, Parpinel M, Franceschi S (1998) Diet and risk of breast cancer: major findings from an Italian case-control study. Biomed Pharmacother 52:109–115
Feliciano RP, Meudt JJ, Shanmuganayagam D, Krueger CG, Reed JD (2013) Ratio of “A-type” to “B-type” proanthocyanidin interflavan bonds affects extra-intestinal pathogenic Escherichia coli invasion of gut epithelial cells. J Agric Food Chem 62:7730–7737
Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin D, Forman D, Bray F (2012) GLOBOCAN 2012 v1.0, cancer incidence and mortality worldwide: IARC cancer base no. 11 [Internet]. International Agency for Research on Cancer, Lyon, France, 2013. http://globocan.iarc.fr
Fernandes I, Marques F, De Freitas V, Mateus N (2013) Antioxidant and antiproliferative properties of methylated metabolites of anthocyanins. Food Chem 141:2923–2933
Ferreira D, Marais JPJ, Coleman CM, Slade D (2010) Procyanidins: chemistry and biology. In Mander L, Liu H-W (eds) Comprehensive natural products II. Chemistry and biology, vol 6 carbohydrates, nucleosides and nucleic acids. Elsevier, Amsterdam, pp 605–661
Feskanich D, Ziegler RG, Michaud DS, Giovannucci EL, Speizer FE, Willett WC, Colditz GA (2000) Prospective study of fruit and vegetable consumption and risk of lung cancer among men and women. J Natl Cancer Inst 92:1812–1823
Field DT, Williams CM, Butler LT (2011) Consumption of cocoa flavanols results in an acute improvement in visual and cognitive functions. Physiol Behav 103:255–260
Flammer AJ, Sudano I, Wolfrum M, Thomas R, Enseleit F, Periat D, Kaiser P, Hirt A, Hermann M, Serafini M, Leveques A, Luscher TF, Ruschitzka F, Noll G, Corti R (2012) Cardiovascular effects of flavanol-rich chocolate in patients with heart failure. Eur Heart J 33:2172–2180
Flammer AJ, Martin EA, Gossl M, Widmer RJ, Lennon RJ, Sexton JA, Loeffler D, Khosla S, Lerman LO, Lerman A (2013) Polyphenol-rich cranberry juice has a neutral effect on endothelial function but decreases the fraction of osteocalcin-expressing endothelial progenitor cells. Eur J Nutr 52:289–296
Fleschhut J, Kratzer F, Rechkemmer G, Kulling SE (2006) Stability and biotransformation of various dietary anthocyanins in vitro. Eur J Nutr 45:7–18
Foo LY, Lu Y, Howell AB, Vorsa N (2000) The structure of cranberry proanthocyanidins which inhibit adherence of uropathogenic p-fimbriated Escherichia coli in vitro. Phytochemistry 54:173–181
Forester SC, Waterhouse AL (2008) Identification of cabernet sauvignon anthocyanin gut microflora metabolites. J Agric Food Chem 56:9299–9304
Foxman B (2003) Epidemiology of urinary tract infections: incidence, morbidity, and economic costs. Dis Mon 49:53–70
Foxman B (2010) The epidemiology of urinary tract infection. Nat Rev Urol 7:653–660
Franceschi S, Parpinel M, La Vecchia C, Favero A, Talamini R, Negri E (1998) Role of different types of vegetables and fruit in the prevention of cancer of the colon, rectum, and breast. Epidemiology 9:338–341
Francis ST, Head K, Morris PG, Macdonald IA (2006) The effect of flavanol-rich cocoa on the fMRI response to a cognitive task in healthy young people. J Cardiovasc Pharmacol 47(Suppl 2):S215–S220
Freese R, Vaarala O, Turpeinen AM, Mutanen M (2004) No difference in platelet activation or inflammation markers after diets rich or poor in vegetables, berries and apple in healthy subjects. Eur J Nutr 43:175–182
Gage FH (2000) Mammalian neural stem cells. Science 287:1433–1438
Galindo P, Rodriguez-Gómez I, González-Manzano S, Dueñas M, Jiménez R, Mendéndez C, Vargas F, Tamargo J, Santos-Buelga C, Pérez-Vizcaíno F, Duarte J (2012) Glucuronidated quercetin lowers blood pressure in spontaneously hypertensive rats via deconjugation. PLoS ONE 7:e32673
Gee JM, DuPont SM, Day AJ, Plumb GW, Williamson G, Johnson IT (2000) Intestinal transport of quercetin glycosides in rats involves both deglycosylation and interaction with the hexose transport pathway. J Nutr 130:2765–2771
Giménez-Bastida JA, González-Sarrías A, Larrosa M, Tomás-Barberán F, Espín JC, García-Conesa MT (2012a) Ellagitannin metabolites, urolithin A glucuronide and its aglycone urolithin A, ameliorate TNF-α-induced inflammation and associated molecular markers in human aortic endothelial cells. Mol Nutr Food Res 56:784–796
Giménez-Bastida JA, Larrosa M, González-Sarrías A, Tomás-Barberán F, Espín JC, García-Conesa MT (2012b) Intestinal ellagitannin metabolites ameliorate cytokine-induced inflammation and associated molecular markers in human colon fibroblasts. J Agric Food Chem 60:8866–8876
González CA, Pera G, Agudo A, Bueno-de-Mesquita HB, Ceroti M, Boeing H, Schulz M, Del Giudice G, Plebani M, Carneiro F, Berrino F, Sacerdote C, Tumino R, Panico S, Berglund G, Siman H, Hallmans G, Stenling R, Martinez C, Dorronsoro M, Barricarte A, Navarro C, Quiros JR, Allen N, Key TJ, Bingham S, Day NE, Linseisen J, Nagel G, Overvad K, Jensen MK, Olsen A, Tjonneland A, Buchner FL, Peeters PH, Numans ME, Clavel-Chapelon F, Boutron-Ruault MC, Roukos D, Trichopoulou A, Psaltopoulou T, Lund E, Casagrande C, Slimani N, Jenab M, Riboli E (2006) Fruit and vegetable intake and the risk of stomach and oesophagus adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST). Int J Cancer 118:2559–2566
González CA, Lujan-Barroso L, Bueno-de-Mesquita HB, Jenab M, Duell EJ, Agudo A, Tjonneland A, Boutron-Ruault MC, Clavel-Chapelon F, Touillaud M, Teucher B, Kaaks R, Boeing H, Steffen A, Trichopoulou A, Roukos D, Karapetyan T, Palli D, Tagliabue G, Mattiello A, Tumino R, Ricceri F, Siersema PD, Numans ME, Peeters PP, Parr CL, Skeie G, Lund E, Quiros JR, Sanchez-Cantalejo E, Navarro C, Barricarte A, Dorronsoro M, Ehrnstrom R, Regner S, Khaw KT, Wareham N, Key TJ, Crowe FL, Blaker H, Romieu I, Riboli E (2012) Fruit and vegetable intake and the risk of gastric adenocarcinoma: a reanalysis of the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST) study after a longer follow-up. Int J Cancer 131:2910–2919
González-Barrio R, Borges G, Mullen W, Crozier A (2010) Bioavailability of anthocyanins and ellagitannins following consumption of raspberries by healthy humans and subjects with an ileostomy. J Agric Food Chem 58:3933–3939
González-Barrio R, Edwards CA, Crozier A (2011a) Colonic catabolism of ellagitannins, ellagic acid, and raspberry anthocyanins: in vivo and in vitro studies. Drug Metab Dispos 39:1680–1688
González-Barrio R, Truchado P, Ito H, Espín JC, Tomás-Barberán FA (2011b) UV and MS identification of urolithins and nasutins, the bioavailable metabolites of ellagitannins and ellagic acid in different mammals. J Agric Food Chem 59:1152–1162
González-Gallego J, García-Mediavilla MV, Sánchez-Campos S, Tuñón MJ (2010) Fruit polyphenols, immunity and inflammation. Br J Nutr 104(Suppl 3):S15–S27
González-Sarrías A, Miguel V, Merino G, Lucas R, Morales JC, Tomás-Barberán F, Alvarez AI, Espin JC (2013) The gut microbiota ellagic acid-derived metabolite urolithin A and its sulfate conjugate are substrates for the drug efflux transporter breast cancer resistance protein (ABCG2/BCRP). J Agric Food Chem 61:4352–4359
Gualdoni GA, Kovarik JJ, Hofer J, Dose F, Pignitter M, Doberer D, Steinberger P, Somoza V, Wolzt M, Zlabinger GT (2014) Resveratrol enhances TNF-α production in human monocytes upon bacterial stimulation. Biochim Biophys Acta 1840:95–105
Guay DR (2009) Cranberry and urinary tract infections. Drugs 69:775–807
Guerrero L, Margalef M, Pons Z, Quiñones M, Arola L, Arola-Arnal A, Muguerza B (2013) Serum metabolites of proanthocyanidin-administered rats decrease lipid synthesis in HepG2 cells. J Nutr Biochem 24:2092–2099
Guo W, Kong E, Meydani M (2009) Dietary polyphenols, inflammation, and cancer. Nutr Cancer 61:807–810
Guo XD, Zhang DY, Gao XJ, Parry J, Lui K, Lui BL, Wang M (2013) Quercetin and quercetin-3-O-glucuronide are equally effective in ameliorating endothelial insulin resistance through inhibition of reactive oxygen species-associated inflammation. Mol Nutr Food Res 57:1037–1045
Hamburg NM, Palmisano J, Larson MG, Sullivan LM, Lehman BT, Vasan RS, Levy D, Mitchell GF, Vita JA, Benjamin EJ (2011) Relation of brachial and digital measures of vascular function in the community: the Framingham heart study. Hypertension 57:390–396
Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70
Harborne JB (1993) Introdction to ecological biochemistry. Elsevier Academic Press, London
Hartley L, Flowers N, Holmes J, Clarke A, Stranges S, Hooper L, Rees K (2013) Green and black tea for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev 6:CD009934
Haslam E, Cai Y (1994) Plant polyphenols (vegetable tannins)—gallic acid metabolism. Nat Prod Rep 11:41–66
Hassellund SS, Flaa A, Sandvik L, Kjeldsen SE, Rostrup M (2012) Effects of anthocyanins on blood pressure and stress reactivity: a double-blind randomized placebo-controlled crossover study. J Hum Hypertens 26:396–404
Hassellund SS, Flaa A, Kjeldsen SE, Seljeflot I, Karlsen A, Erlund I, Rostrup M (2013) Effects of anthocyanins on cardiovascular risk factors and inflammation in pre-hypertensive men: a double-blind randomized placebo-controlled crossover study. J Hum Hypertens 27:100–106
Heber D (2008) Multitargeted therapy of cancer by ellagitannins. Cancer Lett 269:262–278
Heiss C, Dejam A, Kleinbongard P, Schewe T, Sies H, Kelm M (2003) Vascular effects of cocoa rich in flavan-3-ols. JAMA 290:1030–1031
Heiss C, Finis D, Kleinbongard P, Hoffmann A, Rassaf T, Kelm M, Sies H (2007) Sustained increase in flow-mediated dilation after daily intake of high-flavanol cocoa drink over 1 week. J Cardiovasc Pharmacol 49:74–80
Henderson VW, St John JA, Hodis HN, Kono N, McCleary CA, Franke AA, Mack WJ (2012) Long-term soy isoflavone supplementation and cognition in women: a randomized, controlled trial. Neurology 78:1841–1848
Henning SM, Niu Y, Liu Y, Lee NH, Hara Y, Thames GD, Minutti RR, Carpenter CL, Wang H, Heber D (2005) Bioavailability and antioxidant effect of epigallocatechin gallate administered in purified form versus as green tea extract in healthy individuals. J Nutr Biochem 16:610–616
Hidalgo M, Martin-Santamaria S, Recio I, Sanchez-Moreno C, de Pascual-Teresa B, Rimbach G, de Pascual-Teresa S (2012) Potential anti-inflammatory, anti-adhesive, anti/estrogenic, and angiotensin-converting enzyme inhibitory activities of anthocyanins and their gut metabolites. Genes Nutr 7:295–306
Ho L, Ferruzzi MG, Janle EM, Wang J, Ging B, Chen TY, Lobo J, Cooper B, Wu QL, Talcott ST, Perciavl SS, Simon JE, Pasinetti GM (2013) Identification of brain-targeted bioactive dietary quercetin-3-O-glucuronide as a novel intervention for Alzheimer’s disease. FASEB J 27:769–781
Hodgson JM, Puddey IB, Woodman RJ, Mulder TPJ, Fuchs D, Scott K, Croft KD (2012) Effects of black tea on blood pressure: a randomized controlled trial. Arch Intern Med 172:186–188
Hodis HN, Mack WJ, LaBree L, Selzer RH, Liu CR, Liu CH, Azen SP (1998) The role of carotid arterial intima-media thickness in predicting clinical coronary events. Ann Intern Med 128:262–269
Hodis HN, Mack WJ, Kono N, Azen SP, Shoupe D, Hwang-Levine J, Petitti D, Whitfield-Maxwell L, Yan M, Franke AA, Selzer RH, Group WsISHR (2011) Isoflavone soy protein supplementation and atherosclerosis progression in healthy postmenopausal women: a randomized controlled trial. Stroke 42:3168–3175
Hoensch H, Groh B, Edler L, Kirch W (2008) Prospective cohort comparison of flavonoid treatment in patients with resected colorectal cancer to prevent recurrence. World J Gastroenterol 14:2187–2193
Hooper L, Kay C, Abdelhamid A, Kroon PA, Cohn JS, Rimm EB, Cassidy A (2012) Effects of chocolate, cocoa, and flavan-3-ols on cardiovascular health: a systematic review and meta-analysis of randomized trials. Am J Clin Nutr 95:740–751
Howell AB (2007) Bioactive compounds in cranberries and their role in prevention of urinary tract infections. Mol Nutr Food Res 51:732–737
Howell AB, Reed JD, Krueger CG, Winterbottom R, Cunningham DG, Leahy M (2005) A-type cranberry proanthocyanidins and uropathogenic bacterial anti-adhesion activity. Phytochemistry 66:2281–2291
Hy LX, Keller DM (2000) Prevalence of AD among whites: a summary by levels of severity. Neurology 55:198–204
Irace C, Marini H, Bitto A, Altavilla D, Polito F, Adamo EB, Arcoraci V, Minutoli L, Di Benedetto A, Di Vieste G, de Gregorio C, Gnasso A, Corrao S, Licata G, Squadrito F (2013) Genistein and endothelial function in postmenopausal women with metabolic syndrome. Eur J Clin Invest 43:1025–1031
Ishisaka A, Kawabata K, Miki S, Shiba Y, Minekawa S, Nishikawa T, Mukai R, Terao J, Kawai Y (2013) Mitochondrial dysfunction leads to deconjugation of quercetin glucuronides in inflammatory macrophages. PLoS ONE 8:e80843
Ishisaka A, Mukai R, Terao J, Shibata N, Kawai Y (2014) Specific localization of quercetin-3-O-glucuronide in human brain. Arch Biochem Biophys. doi:10.1016/j.abb.2014.05.025
Jaganath IB, Mullen W, Edwards CA, Crozier A (2006) The relative contribution of the small and large intestine to the absorption and metabolism of rutin in man. Free Radic Res 40:1035–1046
Jellinger KA (2001) Cell death mechanisms in neurodegeneration. J Cell Mol Med 5:1–17
Jepson RG, Craig JC (2007) A systematic review of the evidence for cranberries and blueberries in UTI prevention. Mol Nutr Food Res 51:738–745
Jepson RG, Craig JC (2008) Cranberries for preventing urinary tract infections. Cochrane Database Syst Rev CD001321. doi:10.1002/14651858.CD001321.pub4
Jimenez-Ramsey LM, Rogler JC, Housley TL, Butler LG, Elkin RG (1994) Absorption and distribution of 14C-labelled condensed tannins and related Sorghum phenolics in chickens. J Agric Food Chem 42:963–967
Jin J-S, Hattori M (2009) Further studies on a human intestinal bacterium Ruminococcus sp. END-1 for transformation of plant lignans to mammalian lignans. J Agric Food Chem 57:7537–7542
Jin J-S, Kakiuchi N, Hattori M (2007) Enantioselective oxidation of enterodiol to enterolactone by human intestinal bacteria. Biol Pharm Bull 30:2204–2206
Johnson JR (1991) Virulence factors in Escherichia coli urinary tract infection. Clin Microbiol Rev 4:80–128
Johnson JR, Russo TA (2002) Extraintestinal pathogenic Escherichia coli: “The other bad E. coli”. J Lab Clin Med 139:155–162
Johnson JR, Brown JJ, Carlino UB, Russo TA (1998) Colonization with and acquisition of uropathogenic Escherichia coli as revealed by polymerase chain reaction-based detection. J Infect Dis 177:1120–1124
Kahle K, Kraus M, Scheppach W, Ackermann M, Ridder F, Richling E (2006) Studies on apple and blueberry fruit constituents: Do the polyphenols reach the colon after ingestion? Mol Nutr Food Res 50:418–423
Kam A, Li KM, Razmovski-Naumovski V, Nammi S, Chan K, Li GQ (2014) Gallic acid protects against endothelial injury by restoring the depletion of DNA methyltransferase 1 and inhibiting proteasome activities. Int J Cardiol 171:231–242
Kampa M, Nifli AP, Notas G, Castanas E (2007) Polyphenols and cancer cell growth. Rev Physiol Biochem Pharmacol 159:79–113
Kang Z, Zhu H, Jiang W, Zhang S (2013) Protocatechuic acid induces angiogenesis through PI3K-Akt-eNOS-VEGF signalling pathway. Basic Clin Pharmacol Toxicol 113:221–227
Karatzi KN, Papamichael CM, Karatzis EN, Papaioannou TG, Aznaouridis KA, Katsichti PP, Stamatelopoulos KS, Zampelas A, Lekakis JP, Mavrikakis ME (2005) Red wine acutely induces favorable effects on wave reflections and central pressures in coronary artery disease patients. Am J Hypertens 18:1161–1167
Karlsen A, Retterstol L, Laake P, Paur I, Bohn SK, Sandvik L, Blomhoff R (2007) Anthocyanins inhibit nuclear factor-κB activation in monocytes and reduce plasma concentrations of pro-inflammatory mediators in healthy adults. J Nutr 137:1951–1954
Kay CD, Mazza G, Holub BJ (2005) Anthocyanins exist in the circulation primarily as metabolites in adult men. J Nutr 135:2582–2588
Keli SO, Hertog MG, Feskens EJ, Kromhout D (1996) Dietary flavonoids, antioxidant vitamins, and incidence of stroke: the Zutphen study. Arch Intern Med 156:637–642
Kelly LA, Seidlova-Wuttke D, Wuttke W, O’Leary JJ, Norris LA (2014) Estrogen receptor alpha augments changes in hemostatic gene expression in HepG2 cells treated with estradiol and phytoestrogens. Phytomedicine 21:155–158
Kennedy DO, Wightman EL, Reay JL, Lietz G, Okello EJ, Wilde A, Haskell CF (2010) Effects of resveratrol on cerebral blood flow variables and cognitive performance in humans: a double-blind, placebo-controlled, crossover investigation. Am J Clin Nutr 91:1590–1597
Kesse-Guyot E, Fezeu L, Andreeva VA, Touvier M, Scalbert A, Hercberg S, Galan P (2012) Total and specific polyphenol intakes in midlife are associated with cognitive function measured 13 years later. J Nutr 142:76–83
Kim K, Bae ON, Lim KM, Noh JY, Kang S, Chung KY, Chung JH (2012) Novel antiplatelet activity of protocatechuic acid through the inhibition of high shear stress-induced platelet aggregation. J Pharmacol Exp Ther 34:704–711
Kim J, Lee H, Lee O, Lee K-H, Lee Y-B, Young KD, Jeong YH, Choue R (2013) Isoflavone supplementation influenced levels of triglyceride and luteunizing hormone in Korean postmenopausal women. Arch Pharm Res 36:306–313
Kiss AK, Granica S, Stolarczyk M, Melzig MF (2012) Epigenetic modulation of mechanisms involved in inflammation: influence of selected polyphenolic substances on histone acetylation state. Food Chem 131:1015–1020
Kitagawa K, Hougaku H, Yamagami H, Hashimoto H, Itoh T, Shimizu Y, Takahashi D, Murata S, Seike Y, Kondo K, Hoshi T, Furukado S, Abe Y, Yagita Y, Sakaguchi M, Tagaya M, Etani H, Fukunaga R, Nagai Y, Matsumoto M, Hori M, Group OS (2007) Carotid intima-media thickness and risk of cardiovascular events in high-risk patients. Results of the Osaka Follow-Up Study for Carotid Atherosclerosis 2 (OSACA2 Study). Cerebrovasc Dis 24:35–42
Knekt P, Kumpulainen J, Jarvinen R, Rissanen H, Heliovaara M, Reunanen A, Hakulinen T, Aromaa A (2002) Flavonoid intake and risk of chronic diseases. Am J Clin Nutr 76:560–568
Knust U, Hull WE, Spielhalder B, Bartsch H, Strowitzki T, Owen RW (2006) Analysis of enterolignon glucuronides in serum and urine by HPLC–ESI–MS. Food Chem Toxicol 44:1038–1049
Kravitz BA, Corrada MM, Kawas CH (2009) Elevated C-reactive protein levels are associated with prevalent dementia in the oldest-old. Alzheimers Dement 5:318–323
Krikorian R, Nash TA, Shidler MD, Shukitt-Hale B, Joseph JA (2010a) Concord grape juice supplementation improves memory function in older adults with mild cognitive impairment. Br J Nutr 103:730–734
Krikorian R, Shidler MD, Nash TA, Kalt W, Vinqvist-Tymchuk MR, Shukitt-Hale B, Joseph JA (2010b) Blueberry supplementation improves memory in older adults. J Agric Food Chem 58:3996–4000
Krikorian R, Boespflug EL, Fleck DE, Stein AL, Wightman JD, Shidler MD, Sadat-Hossieny S (2012) Concord grape juice supplementation and neurocognitive function in human aging. J Agric Food Chem 60:5736–5742
Krueger CG, Vestling MM, Reed JD (2004) Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry of anthocyanin-polyflavan-3-ol polymers in cranberry fruit (Vaccinium macrocarpon, ait.) and spray dried cranberry juice. In: Waterhouse AL, Kenedy JA (eds) Red wine color: revealing the mysteries. ACS symp ser 886. Washington, DC, pp 232–246
Krueger CG, Reed JD, Feliciano RP, Howell AB (2013) Quantifying and characterizing proanthocyanidins in cranberries in relation to urinary tract health. Anal Bioanal Chem 405:4385–4395
Kuhnert N, Clifford MN, Muller A (2010a) Oxidative cascade reactions yielding polyhydroxy-theaflavins and thea citrins in the formation of black tea thearubigins: evdince by tandem LC-MS. Food Funct 1:180–199
Kuhnert N, Dryman JW, Obuchowicz J, Clifford MN, Witt M (2010b) Mass spectrometric characterization of balck tea thearubigins leading to an oxidative cascade hypothesis for thea rubigin formation. Rapid Commun Mass Spectrom 24:3387–3404
Kumar NB, Cantor A, Allen K, Riccardi D, Besterman-Dahan K, Seigne J, Helal M, Salup R, Pow-Sang J (2004) The specific role of isoflavones in reducing prostate cancer risk. Prostate 59:141–147
Kumar NB, Krischer JP, Allen K, Riccardi D, Besterman-Dahan K, Salup R, Kang L, Xu P, Pow-Sang J (2007) A Phase II randomized, placebo-controlled clinical trial of purified isoflavones in modulating steroid hormones in men diagnosed with localized prostate cancer. Nutr Cancer 59:163–168
Kyle JA, Sharp L, Little J, Duthie GG, McNeill G (2010) Dietary flavonoid intake and colorectal cancer: a case-control study. Br J Nutr 103:429–436
La Vecchia C, Chatenoud L, Franceschi S, Soler M, Parazzini F, Negri E (1999) Vegetables and fruit and human cancer: update of an Italian study. Int J Cancer 82:151–152
Landete JM (2012) Plant and mammalian lignans: a review of source, intake, metabolism, intestinal bacteria and health. Food Res Int 46:410–424
Lang R, Dieminger N, Beusch A, Lee YM, Dunkel A, Suess B, Skurk T, Wahl A, Hauner H, Hofmann T (2013) Bioappearance and pharmacokinetics of bioactives upon coffee consumption. Anal Bioanal Chem 405:8487–8503
Larrosa M, García-Conesa MT, Espín JC, Tomás-Barberán FA (2010) Ellagitannins, ellagic acid and vascular health. Mol Aspects Med 31:513–539
Larson A, Witman MAH, Guo Y, Ives S, Richardson RS, Bruno RS, Jalili T, Symons JD (2012a) Acute, quercetin-induced reductions in blood pressure in hypertensive individuals are not secondary to lower plasma angiotensin-converting enzyme activity or endothelin-1: nitric oxide. Nutr Res 32:557–564
Larson AJ, Symons JD, Jalili T (2012b) Therapeutic potential of quercetin to decrease blood pressure: review of efficacy and mechanisms. Adv Nutr 3:39–46
Larsson SC, Hakansson N, Naslund I, Bergkvist L, Wolk A (2006) Fruit and vegetable consumption in relation to pancreatic cancer risk: a prospective study. Cancer Epidemiol Biomarkers Prev 15:301–305
Larsson SC, Andersson SO, Johansson JE, Wolk A (2008) Fruit and vegetable consumption and risk of bladder cancer: a prospective cohort study. Cancer Epidemiol Biomarkers Prev 17:2519–2522
Lasa A, Churruca I, Eseberri I, Andrés-Lacueva C, Portillo MP (2012) Delipidating effect of resveratrol metabolites in 3T3-L1 adipocytes. Mol Nutr Food Res 56:1559–1568
Laurent S, Cockcroft J, Van Bortel L, Boutouyrie P, Giannattasio C, Hayoz D, Pannier B, Vlachopoulos C, Wilkinson I, Struijker-Boudier H (2006) Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J 27:2588–2605
Le Bars PL, Velasco FM, Ferguson JM, Dessain EC, Kieser M, Hoerr R (2002) Influence of the severity of cognitive impairment on the effect of the Ginkgo biloba extract EGb 761 in Alzheimer’s disease. Neuropsychobiology 45:19–26
Lee MJ, Maliakal P, Chen L, Meng X, Bondoc FY, Prabhu S, Lambert G, Mohr S, Yang CS (2002) Pharmacokinetics of tea catechins after ingestion of green tea and (−)-epigallocatechin-3-gallate by humans: formation of different metabolites and individual variability. Cancer Epidemiol Biomarkers Prev 11:1025–1032
Lee KW, Bode AM, Dong Z (2011) Molecular targets of phytochemicals for cancer prevention. Nat Rev Cancer 11:211–218
Legos JJ, Tuma RF, Barone FC (2002) Pharmacological interventions for stroke: failures and future. Expert Opin Investig Drugs 11:603–614
Letenneur L, Proust-Lima C, Le Gouge A, Dartigues JF, Barberger-Gateau P (2007) Flavonoid intake and cognitive decline over a 10-year period. Am J Epidemiol 165:1364–1371
Li CM, Leverence R, Trombley JD, Xu SF, Yang J, Tian Y, Reed JD, Hagerman AE (2010) High molecular weight persimmon (Diospyros kaki L.) proanthocyanidin: a highly galloylated, A-linked tannin with an unusual flavonol terminal unit, myricetin. J Agric Food Chem 258:9033–9042
Lindsay J, Laurin D, Verreault R, Hebert R, Helliwell B, Hill GB, McDowell I (2002) Risk factors for Alzheimer’s disease: a prospective analysis from the Canadian Study of Health and Aging. Am J Epidemiol 156:445–453
Liu Z-M, Ho SC, Chen Y-M, Ho YP (2012a) The effects of isoflavones combined with soy protein on lipid profiles, C-reactive protein and cardiovascular risk among postmenopausal Chinese women. Nutr Metab Cardiovasc Dis 22:712–719
Liu XX, Li SH, Chen JZ, Sun K, Wang XJ, Wang XG, Hui RT (2012b) Effect of soy isoflavones on blood pressure: a meta-analysis of randomized controlled trials. Nutr Metab Cardiovasc Dis 22:463–470
Liu Z-M, Ho SC, Chen YM, Woo J (2013) Effect of soy protein and isoflavones on blood pressure and endothelial cytokines: a 6-month randomized controlled trial among postmenopausal women. J Hypertens 31:384–392
Liu Z-M, Ho SC, Chen Y-M, Ho S, To K, Tomlinson B, Woo J (2014) Whole soy, but not purified daidzein, had a favorable effect on improvement of cardiovascular risks: a 6-month randomized, double-blind, and placebo-controlled trial in equol-producing postmenopausal women. Mol Nutr Food Res 58:709–717
Lodi F, Winterbone M, Tribolo S, Needs PW, Hughes DA, Kroon PA (2012) Human quercetin conjugated metabolites attenuate TNF-α-induced changes in vasomodulatory molecules in an HUASMCs/HUVECs Co-culture model. Planta Med 78:1571–1573
Ludwig IA, de Peña M, Cid C, Crozier A (2013) Catabolism of coffee chlorogenic acids by human colonic microbiota. BioFactors 39:623–632
Ludwig IA, Clifford MN, Lean MEJ, Crozier A (2014a) Coffee: biochemistry and potential impact on health. Food Funct 5:1695–1717
Ludwig IA, Mena P, Calani L,Cid C, Del Rio D, Lean MEJ, Crozier A (2014b) Variations in the caffeine and chlorogenic acid content of coffees: what are we drinking? Food Funct 5:1718–1726
Lynn A, Hamadeh H, Leung WC, Russell JM, Barker ME (2012) Effects of pomegranate juice supplementation on pulse wave velocity and blood pressure in healthy young and middle-aged men and women. Plant Foods Hum Nutr 67:309–314
Magee PJ, Allsopp P, Samaletdin A, Rowland IR (2014) Daidzein, R-(+)equol and S-(−)equol inhibit the invasion of MDA-MB-231 breast cancer cells potentially via the down-regulation of matrix metalloproteinase-2. Eur J Nutr 53:345–350
Magyar K, Halmosi R, Palfi A, Feher G, Czopf L, Fulop A, Battyany I, Sumegi B, Toth K, Szabados E (2012) Cardioprotection by resveratrol: a human clinical trial in patients with stable coronary artery disease. Clin Hemorheol Microcirc 50:179–187
Mainini G, Torella M, Di Donna MC, Esposito E, Ercolano S, Correa R, Cucinella G, Stradella L, Luisi A, Basso A, Cerreto FV, Cicatiello R, Matteo M, De Franciscis P (2013) Nonhormonal management of postmenopausal women: effects of a red clover-based isoflavones supplementation on climacteric syndrome and cardiovascular risk serum profile. Clin Exp Obstet Gynecol 40:337–341
Manach C, Williamson G, Morand C, Scalbert A, Rémésy C (2005) Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. Am J Clin Nutr 81(Suppl 1):230S–242S
Manzano S, Williamson G (2010) Polyphenols and phenolic acids from strawberry and apple decrease glucose and transport by human intestinal Caco-2 cells. Mol Nutr Food Res 54:1773–1780
Marmet C, Actis-Goretta L, Renouf M, Giuffrida F (2014) Quantification of phenolic acids and their methylates, glucuronides, sulfates and lactones metabolites in human plasma by LC-MS/MS after oral ingestion of soluble coffee. J Pharm Biomed Anal 88:617–625
Marniemi J, Alanen E, Impivaara O, Seppanen R, Hakala P, Rajala T, Ronnemaa T (2005) Dietary and serum vitamins and minerals as predictors of myocardial infarction and stroke in elderly subjects. Nutr Metab Cardiovasc Dis 15:188–197
Martín MÁ, Fernández-Millán E, Ramos S, Bravo L, Goya L (2014) Cocoa flavonoid epicatechin protects pancreatic beta cell viability and function against oxidative stress. Mol Nutr Food Res 58:447–456
Martinez ME (2005) Primary prevention of colorectal cancer: lifestyle, nutrition, exercise. Recent Results Cancer Res 166:177–211
McCann MJ, Rowland IR, Roy NC (2013) Anti-proliferative effects of physiological concentrations of enterolactone in models of prostate tumourigenesis. Mol Nutr Food Res 57:212–224
McGhie TK, Walton MC (2007) The bioavailability and absorption of anthocyanins: towards a better understanding. Mol Nutr Food Res 51:702–713
Milbury PE, Kalt W (2010) Xenobiotic metabolism and berry flavonoid transport across the blood brain barrier. J Agric Chem 58:3950–3956
Mink PJ, Scrafford CG, Barraj LM, Harnack L, Hong CP, Nettleton JA, Jacobs DR Jr (2007) Flavonoid intake and cardiovascular disease mortality: a prospective study in postmenopausal women. Am J Clin Nutr 85:895–909
Mix JA, Crews WD Jr (2000) An examination of the efficacy of Ginkgo biloba extract EGb761 on the neuropsychologic functioning of cognitively intact older adults. J Altern Complement Med 6:219–229
Mix JA, Crews WD Jr (2002) A double-blind, placebo-controlled, randomized trial of Ginkgo biloba extract EGb 761 in a sample of cognitively intact older adults: neuropsychological findings. Hum Psychopharmacol 17:267–277
Miyanaga N, Akaza H, Hinotsu S, Fujioka T, Naito S, Namiki M, Takahashi S, Hirao Y, Horie S, Tsukamoto T, Mori M, Tsuji H (2012) Prostate cancer chemoprevention study: an investigative randomized control study using purified isoflavones in men with rising prostate-specific antigen. Cancer Sci 103:125–130
Mogollon JA, Bujold E, Lemieux S, Bourdages M, Blanchet C, Bazinet L, Couillard C, Noel M, Dodin S (2013) Blood pressure and endothelial function in healthy, pregnant women after acute and daily consumption of flavanol-rich chocolate: a pilot, randomized controlled trial. Nutr J 12:41. doi:10.1186/1475-2891-12-41
Moreno E, Andreu A, Pigrau C, Kuskowski MA, Johnson JR, Prats G (2008) Relationship between Escherichia coli strains causing acute cystitis in women and the fecal E. coli population of the host. J Clin Microbiol 46:2529–2534
Moreno-Luna R, Muñoz-Hernandez R, Miranda ML, Costa AF, Jimenez-Jimenez L, Vallejo-Vaz AJ, Muriana FJG, Villar J, Stiefel P (2012) Olive oil polyphenols decrease blood pressure and improve endothelial function in young women with mild hypertension. Am J Hypertens 25:1299–1304
Morris MC, Evans DA, Tangney CC, Bienias JL, Wilson RS (2006) Associations of vegetable and fruit consumption with age-related cognitive change. Neurology 67:1370–1376
Mubarak A, Bondonno CP, Liu AH, Considine MJ, Rich L, Mas E, Croft KD, Hodgson JM (2012) Acute effects of chlorogenic acid on nitric oxide status, endothelial function, and blood pressure in healthy volunteers: a randomized trial. J Agric Food Chem 60:9130–9136
Mullen W, Rouanet J-M, Auger C, Teissedre P-L, Caldwell ST, Hartley RC, Lean MEJ, Edwards CA, Crozier A (2008) The bioavailability of [2-14C]quercetin-4′-glucoside in rats. J Agric Food Chem 56:12127–12137
Mursu J, Nurmi T, Tuomainen TP, Salonen JT, Pukkala E, Voutilainen S (2008) Intake of flavonoids and risk of cancer in Finnish men: the Kuopio Ischaemic Heart Disease Risk Factor Study. Int J Cancer 123:660–663
Nagahama Y, Nabatame H, Okina T, Yamauchi H, Narita M, Fujimoto N, Murakami M, Fukuyama H, Matsuda M (2003) Cerebral correlates of the progression rate of the cognitive decline in probable Alzheimer’s disease. Eur Neurol 50:1–9
Nagy K, Actis-Goretta L, Redeuil K, Barron D, Fumeaux R, Giuffrida F, Cruz-Hernandez C, Destaillats F (2013) Identification of cholesteryl ester of ferulic acid in human plasma by mass spectrometry. J Chromatogr A 1301:162–168
Nakayama H, Tsuge N, Sawada H, Higashi Y (2013) Chronic intake of onion extract containing quercetin improved postprandial endothelial dysfunction in healthy men. J Am Coll Nutr 32:160–164
Nambi V, Chambless L, Folsom AR, He M, Hu Y, Mosley T, Volcik K, Boerwinkle E, Ballantyne CM (2010) Carotid intima-media thickness and presence or absence of plaque improves prediction of coronary heart disease risk: the ARIC (Atherosclerosis Risk In Communities) study. J Am Coll Cardiol 55:1600–1607
Nanri A, Yoshida D, Yamaji T, Mizoue T, Takayanagi R, Kono S (2008) Dietary patterns and C-reactive protein in Japanese men and women. Am J Clin Nutr 87:1488–1496
Narayan RK, Michel ME, Ansell B, Baethmann A, Biegon A, Bracken MB, Bullock MR, Choi SC, Clifton GL, Contant CF, Coplin WM, Dietrich WD, Ghajar J, Grady SM, Grossman RG, Hall ED, Heetderks W, Hovda DA, Jallo J, Katz RL, Knoller N, Kochanek PM, Maas AI, Majde J, Marion DW, Marmarou A, Marshall LF, McIntosh TK, Miller E, Mohberg N, Muizelaar JP, Pitts LH, Quinn P, Riesenfeld G, Robertson CS, Strauss KI, Teasdale G, Temkin N, Tuma R, Wade C, Walker MD, Weinrich M, Whyte J, Wilberger J, Young AB, Yurkewicz L (2002) Clinical trials in head injury. J Neurotrauma 19:503–557
Naruszewicz M, Laniewska I, Millo B, Dłuzniewski MÇ (2007) Combination therapy of statin with flavonoids rich extract from chokeberry fruits enhanced reduction in cardiovascular risk markers in patients after myocardial infraction (MI). Atherosclerosis 194:179–184
Nestel PJ, Yamashita T, Sasahara T, Pomeroy S, Dart A, Komesaroff P, Owen A, Abbey M (1997) Soy isoflavones improve systemic arterial compliance but not plasma lipids in menopausal and perimenopausal women. Arterioscler Thromb Vasc Biol 17:3392–3398
Nestel P, Fujii A, Zhang L (2007) An isoflavone metabolite reduces arterial stiffness and blood pressure in overweight men and postmenopausal women. Atherosclerosis 192:184–189
Neufingerl N, Zebregs YEMP, Schuring EAH, Trautwein EA (2013) Effect of cocoa and theobromine consumption on serum HDL-cholesterol concentrations: a randomized controlled trial. Am J Clin Nutr 97(6):1201–1209
Neveu V, Perez-Jimenez J, Vos F, Crespy V, du Chaffaut L, Mennen L, Knox C, Eisner R, Cruz J, Wishart D, Scalbert A (2010) Phenol-Explorer: an online comprehensive database on polyphenol contents in foods. Database (Oxford). doi:10.1093/database/bap024
Nguyen MM, Ahmann FR, Nagle RB, Hsu CH, Tangrea JA, Pames HL, Sokoloff MH, Gretzer MB, Chow HHS (2012) Randomized, double-blind, placebo-controlled trial of Polyphenon E in prostate cancer patients before prostatectomy: evaluation of potential chemopreventive activities. Cancer Prev Res 5:290–298
Nuñez-Sánchez MA, García-Villalba R, Monedero-Saiz T, García-Talavera NV, Gómez-Sánchez MB, Sánchez-Álvarez C, García-Albert AM, Rodríguez-Gil FJ, Ruiz-Marín M, Pastor-Quirante FA, Martínez-Díaz F, Yáñez-Gascón MJ, González-Sarrías A, Tomás-Barberán FA, Espín JC (2014) Targeted metabolic profiling of pomegranate polyphenols and urolithins in plasma, urine and colon tissues from colorectal cancer patients. Mol Nutr Food Res 58:1199–1211
Nurk E, Refsum H, Drevon CA, Tell GS, Nygaard HA, Engedal K, Smith AD (2009) Intake of flavonoid-rich wine, tea, and chocolate by elderly men and women is associated with better cognitive test performance. J Nutr 139:120–127
Nurnberger J, Keflioglu-Scheiber A, Opazo Saez AM, Wenzel RR, Philipp T, Schafers RF (2002) Augmentation index is associated with cardiovascular risk. J Hypertens 20:2407–2414
Nussbaum RL, Ellis CE (2003) Alzheimer’s disease and Parkinson’s disease. N Engl J Med 348:1356–1364
Ohara K, Wakabayashi H, Taniguchi Y, Shindo K, Yajima H, Yoshida A (2013) Quercetin-3-O-glucuronide induces ABCA1 expression by LXRα activation in murine macrophages. Biochem Biophys Res Commun 441:929–934
Okushio K, Suzuki M, Matsumoto N, Nanjo F, Hara Y (1999) Identification of (−)-epicatechin metabolites and their emtabolic fate in rats. Drug Metab Disp 27:309–316
Omar MH, Mullen W, Stalmach A, Auger C, Rouanet J-M, Teisdre P-L, Caldwell ST, Hartley RC, Crozier A (2012) Absorption, disposition, metabolism and excretion of [3-14C]caffeic acid in rats. J Agric Food Chem 60:5205–5214
Orgogozo JM, Dartigues JF, Lafont S, Letenneur L, Commenges D, Salamon R, Renaud S, Breteler MB (1997) Wine consumption and dementia in the elderly: a prospective community study in the Bordeaux area. Rev Neurol 153:185–192
Ottaviani JI, Momma TY, Heiss C, Kuhnle GK, Kwik-Uribe C, Schroeter H, Keen CL (2011) The stereochemical configuration of flavonols influences the level and metabolism of flavonols in humans and their biological activity in vivo. Free Radic Biol Med 50:237–244
Ottaviani JI, Kwik-Uribe C, Keen CL, Schroeter H (2012a) Intake of dietary procyanidins does not contribute to the pool of circulating flavonols in humans. Am J Clin Nutr 95:851–858
Ottaviani JI, Momma TY, Kuhnle GK, Keen CL, Schroeter H (2012b) Structurally related (−)-epicatechin metabolites in humans: assessment using de novo chemically synthesized authentic metabolites. Free Radic Biol Med 52:1403–1412
Palmer TD, Willhoite AR, Gage FH (2000) Vascular niche for adult hippocampal neurogenesis. J Comp Neurol 425:479–494
Pappas E, Schaich KM (2009) Phytochemicals of cranberries and cranberry products: characterization, potential health effects, and processing stability. Crit Rev Food Sci Nutr 49:741–781
Pase MP, Scholey AB, Pipingas A, Kras M, Nolidin K, Gibbs A, Wesnes K, Stough C (2013) Cocoa polyphenols enhance positive mood states but not cognitive performance: a randomized, placebo-controlled trial. J Psychopharmacol 27:451–458
Peng HW, Cheng FC, Huang YT, Chen CF, Tsai TH (1998) Determination of naringenin and its glucuronide conjugate in rat plasma and brain tissue by high-performance liquid chromatography. J Chromatogr B Biomed Sci Appl 714:369–374
Peterson JJ, Dwyer JT, Jacques PF, McCullough ML (2012) Associations between flavonoids and cardiovascular disease incidence or mortality in European and US populations. Nutr Rev 70:491–508
Pfeuffer M, Auinger A, Bley U, Kraus-Stojanowic I, Laue C, Winkler P, Rüfer CE, Frank J, Bosch-Saadatmandi C, Rimbach G, Schrezenmeir J (2013) Effect of quercetin on traits of the metabolic syndrome, endothelial function and inflammation in men with different APOE isoforms. Nutr Metab Cardiovasc Dis 23:403–409
Piazzon A, Vrhovsek U, Masuero D, Mattivi F, Mandoj F, Nardini M (2012) Antioxidant activity of phenolic acids and their metabolites: synthesis and antioxidant properties of the sulfate derivatives of ferulic and caffeic acids and of the acyl glucuronide of ferulic acid. J Agric Food Chem 60:12312–12323
Pipingas A, Silberstein RB, Vitetta L, Rooy CV, Harris EV, Young JM, Frampton CM, Sali A, Nastasi J (2008) Improved cognitive performance after dietary supplementation with a Pinus radiata bark extract formulation. Phytother Res 22:1168–1174
Pitout JD (2012) Extraintestinal pathogenic Escherichia coli: a combination of virulence with antibiotic resistance. Front Microbiol 3:9. doi:10.3389/fmicb.2012.00009
Polak JF, Pencina MJ, O’Leary DH, D’Agostino RB (2011) Common carotid artery intima-media thickness progression as a predictor of stroke in multi-ethnic study of atherosclerosis. Stroke 42:3017–3021
Polycarpou E, Meira LB, Carrington S, Tyrrell E, Modjtahedi H, Carew MA (2013) Resveratrol-3-O-d-glucuronide and resveratrol-4′-O-D-glucuronide inhibit colon cancer cell growth: evidence for a role of A3 adenosine receptors, cyclin D1 depletion, and G1 cell cycle arrest. Mol Nutr Food Res 57:1708–1717
Potischman N, Freudenheim JL (2003) Biomarkers of nutritional exposure and nutritional status: an overview. J Nutr 133(Suppl 3):873S–874S
Pratico D, Trojanowski JQ (2000) Inflammatory hypotheses: novel mechanisms of Alzheimer’s neurodegeneration and new therapeutic targets? Neurobiol Aging 21:441–445; discussion 451–453
Qin Y, Xia M, Ma J, Hao Y, Liu J, Mou H, Cao L, Ling W (2009) Anthocyanin supplementation improves serum LDL- and HDL-cholesterol concentrations associated with the inhibition of cholesteryl ester transfer protein in dyslipidemic subjects. Am J Clin Nutr 90:485–492
Qin Y, Niu K, Zeng Y, Liu P, Yi L, Zhang T, Zhang QY, Zhu JD, Mi MT (2013) Isoflavones for hypercholesterolaemia in adults. Cochrane Database Syst Rev 6:CD009518
Qiu Z, Zhou B, Jin L, Yu H, Liu L, Liu Y, Qin C, Xie S, Zhu F (2013) In vitro antioxidant and antiproliferative effects of ellagic acid and its colonic metabolite, urolithins, on human bladder cancer T24 cells. Food Chem Toxicol 59:428–437
Ras RT, Zock PL, Draijer R (2011) Tea consumption enhances endothelial-dependent vasodilation; a meta-analysis. PLoS ONE 6:e16974
Ray S, Miglio C, Eden T, Del Rio D (2014) Assessment of vascular and endothelial dysfunction in nutritional studies. Nutr Metab Cardiovasc Dis 24:940–946
Redeuil K, Smarrito-Menozzi C, Guy P, Rezzi S, Dionisi F, Williamson G, Nagy K, Renouf M (2011) Identification of novel circulating coffee metabolites in human plasma by liquid chromatography-mass spectrometry. J Chromatogr A 1218:4678–4688
Reed JD (1995) Nutritional toxicology of tannins and related polyphenols in forage legumes. J Animal Sci 73:1516–1528
Reed JD, Krueger CG, Vestling MM (2005) MALDI-TOF mass spectrometry of oligomeric food polyphenols. Phytochemistry 66:2248–2263
Rendeiro C, Spencer JP, Vauzour D, Butler LT, Ellis JA, Williams CM (2009) The impact of flavonoids on spatial memory in rodents: from behaviour to underlying hippocampal mechanisms. Genes Nutr 4:251–270
Ried K, Sullivan TR, Fakler P, Frank OR, Stocks NP (2012) Effect of cocoa on blood pressure. Cochrane Database Syst Rev 8:CD008893
Ringman JM, Frautschy SA, Teng E, Begum AN, Bardens J, Beigi M, Gylys KH, Badmaev V, Heath DD, Apostolova LG, Porter V, Vanek Z, Marshall GA, Hellemann G, Sugar C, Masterman DL, Montine TJ, Cummings JL, Cole GM (2012) Oral curcumin for Alzheimer’s disease: tolerability and efficacy in a 24-week randomized, double blind, placebo-controlled study. Alzheimers Res Ther 4:43
Riso P, Klimis-Zacas D, Del Bo C, Martini D, Campolo J, Vendrame S, Moller P, Loft S, De Maria R, Porrini M (2013) Effect of a wild blueberry (Vaccinium angustifolium) drink intervention on markers of oxidative stress, inflammation and endothelial function in humans with cardiovascular risk factors. Eur J Nutr 52:949–961
Roberts RO, Geda YE, Knopman DS, Boeve BF, Christianson TJ, Pankratz VS, Kullo IJ, Tangalos EG, Ivnik RJ, Petersen RC (2009) Association of C-reactive protein with mild cognitive impairment. Alzheimers Dement 5:398–405
Rodriguez-Mateos A, Rendeiro C, Bergillos-Meca T, Tabatabaee S, George T, Heiss C, Spencer JP (2013) Intake and time dependence of blueberry flavonoid-induced improvements in vascular function: a randomized, controlled, double-blind, crossover intervention study with mechanistic insights into biological activity. Am J Clin Nutr 98:1179–1191
Rodriguez-Mateos A, Heiss C, Borges G, Crozier A (2014a) Berry (poly)phenols and cardiovascular health. J Agric Food Chem 62:3842–3851
Rodriguez-Mateos A, Pino-Garcia RD, George TW, Vidal-Diez A, Heiss C, Spencer JP (2014b) Impact of processing on the bioavailability and vascular effects of blueberry (poly)phenols. Mol Nutr Food Res. doi:10.1002/mnfr.201400231
Ronald A (2003) The etiology of urinary tract infection: traditional and emerging pathogens. Dis Mon 49:71–82
Rosa NN, Aura AM, Saulnier L, Holopainen-Mantila U, Poutanen K, Micard V (2013) Effects of disintegration on in vitro fermentation and conversion patterns of wheat aleurone in a metabolical colon model. J Agric Food Chem 61:5805–5816
Rossi M, Negri E, Talamini R, Bosetti C, Parpinel M, Gnagnarella P, Franceschi S, Dal Maso L, Montella M, Giacosa A, La Vecchia C (2006) Flavonoids and colorectal cancer in Italy. Cancer Epidemiol Biomarkers Prev 15:1555–1558
Rotches-Ribalta M, Andres-Lacueva C, Estruch R, Escribano E, Urpi-Sarda M (2012a) Pharmacokinetics of resveratrol metabolic profile in healthy humans after moderate consumption of red wine and grape extract tablets. Pharmacol Res 66:375–382
Rotches-Ribalta M, Urpi-Sarda M, Llorach R et al (2012b) Gut and microbial resveratrol metabolite profiling after moderate long-term consumption of red wine versus dealcoholized red wine in humans by an optimized ultra-high-pressure liquid chromatography tandem mass spectrometry method. J Chromatogr A 1265:105–113
Rothwell JA, Fillâtre Y, Martin J-F, Lyan B, Pujos-Guillot E, Fezeu L, Hercberg S, Comte B, Galan P, Touvier, Manach C (2014) Biomarkers of coffee consumption identified by non-targeted metabolomics profiling of cohort study subjects. PLoS ONE 9:e93474
Ruel G, Lapointe A, Pomerleau S, Couture P, Lemieux S, Lamarche B, Couillard C (2013) Evidence that cranberry juice may improve augmentation index in overweight men. Nutr Res 33:41–49
Ruitenberg A, den Heijer T, Bakker SL, van Swieten JC, Koudstaal PJ, Hofman A, Breteler MM (2005) Cerebral hypoperfusion and clinical onset of dementia: the Rotterdam Study. Ann Neurol 57:789–794
Ruotolo R, Calani L, Fietta E, Brighenti F, Crozier A, Meda C, Maggi A, Ottonello S, Del Rio D (2013) Anti-estrogenic activity of a human resveratrol metabolite. Nutr Metab Cardiovasc Dis 23:1086–1092
Russo TA, Johnson JR (2003) Medical and economic impact of extraintestinal infections due to Escherichia coli: focus on an increasingly important endemic problem. Microbes Infect 5:449–456
Ryan J, Croft K, Mori T, Wesnes K, Spong J, Downey L, Kure C, Lloyd J, Stough C (2008) An examination of the effects of the antioxidant Pycnogenol on cognitive performance, serum lipid profile, endocrinological and oxidative stress biomarkers in an elderly population. J Psychopharmacol 22:553–562
Saha S, Hollands W, Needs PW, Ostertag LM, de Roos B, Duthie GG, Kroon PA (2012) 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 65:592–602
Sahebkar A (2013) Effects of resveratrol supplementation on plasma lipids: a systematic review and meta-analysis of randomized controlled trials. Nutr Rev 71:822–835
Salas-Salvado J, Garcia-Arellano A, Estruch R, Marquez-Sandoval F, Corella D, Fiol M, Gomez-Gracia E, Vinoles E, Aros F, Herrera C, Lahoz C, Lapetra J, Perona JS, Munoz-Aguado D, Martinez-Gonzalez MA, Ros E (2008) Components of the Mediterranean-type food pattern and serum inflammatory markers among patients at high risk for cardiovascular disease. Eur J Clin Nutr 62:651–659
Scalbert A, Brennan L, Manach C, Andres-Lacueva C, Dragsted LO, Draper J, Rappaport SM, van der Hooft JJ, Wishart DS (2014) The food metabolome: a window over dietary exposure. Am J Clin Nutr 99:1286–1308
Scheline RR (1991) Handbook of mammalian metabolism of plant compounds. CRC Press, Boca Raton
Scholey AB, French SJ, Morris PJ, Kennedy DO, Milne AL, Haskell CF (2010) Consumption of cocoa flavanols results in acute improvements in mood and cognitive performance during sustained mental effort. J Psychopharmacol 24:1505–1514
Schrader C, Ernst IMA, Sinnecker H, Soukup ST, Kulling SE, Rimbach G (2012) Genistein as a potential inducer of the anti-atherogenic enzyme paraoxonase-1: studies in cultured hepatocytes in vitro and in rat liver in vivo. J Cell Mol Med 16:2331–2341
Schroeter H, Heiss C, Balzer J, Kleinbongard P, Keen CL, Hollenberg NK, Sies H, Kwik-Uribe C, Schmitz HH, Kelm M (2006) (−)-Epicatechin mediates beneficial effects of flavanol-rich cocoa on vascular function in humans. Proc Natl Acad Sci USA 103:1024–1029
Schwartz JL, Baker V, Larios E, Chung FL (2005) Molecular and cellular effects of green tea on oral cells of smokers: a pilot study. Mol Nutr Food Res 49:43–51
Selma MV, Espín JC, Tomás-Barberán FA (2009) Interaction between phenolics and gut microbiota: role in human health. J Agric Food Chem 57:6485–6501
Sharma RA, Euden SA, Platton SL, Cooke DN, Shafayat A, Hewitt HR, Marczylo TH, Morgan B, Hemingway D, Plummer SM, Pirmohamed M, Gescher AJ, Steward WP (2004) Phase I clinical trial of oral curcumin: biomarkers of systemic activity and compliance. Clin Cancer Res 10:6847–6854
Sharrett AR, Ballantyne CM, Coady SA, Heiss G, Sorlie PD, Catellier D, Patsch W (2001) Coronary heart disease prediction from lipoprotein cholesterol levels, triglycerides, lipoprotein(a), apolipoproteins A-I and B, and HDL density subfractions: the Atherosclerosis Risk in Communities (ARIC) Study. Circulation 104:1108–1113
Shen Y, Croft KD, Hodgson JM, Kyle R, Lee IL, Wang Y, Stocker R, Ward NC (2012) Quercetin and its metabolites improve vessel function by inducing eNOS activity via phosphorylation of AMPK. Biochem Pharmacol 84:1036–1044
Shrime MG, Bauer SR, McDonald AC, Chowdhury NH, Coltart CE, Ding EL (2011) Flavonoid-rich cocoa consumption affects multiple cardiovascular risk factors in a meta-analysis of short-term studies. J Nutr 141:1982–1988
Siasos G, Tousoulis D, Kokkou E, Oikonomou E, Kollia M-E, Verveniotis A, Gouliopoulos N, Zisimos K, Plastiras A, Maniatis K, Stefanadis C (2014) Favorable effects of Concord grape juice on endothelial function and arterial stiffness in healthy smokers. Am J Hypertens 27:38–45
Singh BN, Shankar S, Srivastava RK (2011) Green tea catechin, epigallocatechin-3-gallate (EGCG): mechanisms, perspectives and clinical applications. Biochem Pharmacol 82:1807–1821
Siow RC, Mann GE (2010) Dietary isoflavones and vascular protection: activation of cellular antioxidant defenses by SERMs or hormesis? Mol Aspects Med 31:468–477
Sorond FA, Lipsitz LA, Hollenberg NK, Fisher ND (2008) Cerebral blood flow response to flavanol-rich cocoa in healthy elderly humans. Neuropsychiatr Dis Treat 4:433–440
Spencer JP (2008a) Flavonoids: modulators of brain function? Br J Nutr 99E(Suppl 1):ES60–ES77
Spencer JP (2008b) Food for thought: the role of dietary flavonoids in enhancing human memory, learning and neuro-cognitive performance. Proc Nutr Soc 67:238–252
Spencer JPE, Crozier A (eds) (2012) Flavonoids and related compounds: bioavailability and function. CRC Press, Boca Raton
Spencer JP, Vafeiadou K, Williams RJ, Vauzour D (2012) Neuroinflammation: modulation by flavonoids and mechanisms of action. Mol Aspects Med 33:83–97
Spires TL, Hannan AJ (2005) Nature, nurture and neurology: gene-environment interactions in neurodegenerative disease. FEBS Anniversary Prize Lecture delivered on 27 June 2004 at the 29th FEBS Congress in Warsaw. FEBS J 272:2347–2361
Squadrito F, Marini H, Bitto A, Altavilla D, Polito F, Adamo EB, D’Anna R, Arcoraci V, Burnett BP, Minutoli L, Di Benedetto A, Di Vieste G, Cucinotta D, de Gregorio C, Russo S, Corrado F, Saitta A, Irace C, Corrao S, Licata G (2013) Genistein in the metabolic syndrome: results of a randomized clinical trial. J Clin Endocrinol Metab 98:3366–3374
Stalmach A, Mullen W, Barron D, Uchida K, Yokota T, Steiling H, Williamson G, Crozier A (2009) Metabolite profiling of hydroxycinnamate derivatives in plasma and urine following the ingestion of coffee by humans: identification of biomarkers of coffee consumption. Drug Metab Dispos 37:1759–1768
Stalmach A, Steiling H, Williamson G, Crozier A (2010) Bioavailability of chlorogenic acids following acute ingestion of coffee by humans with an ileostomy. Arch Biochem Biophys 501:98–105
Stalmach A, Edwards CA, Wightman JD, Crozier A (2012) Gastrointestinal stability and bioavailability of (poly)phenolic compounds following ingestion of Concord grape juice by humans. Mol Nutr Food Res 56:497–509
Stalmach A, Williamson G, Crozier A (2014) Impact of dose on the bioavailability of coffee chlorogenic acids in humans. Food Funct 5:1727–1737
Stamey TA, Timothy M, Millar M, Mihara G (1971) Recurrent urinary infections in adult women. The role of introital enterobacteria. Calif Med 115:1–19
Steffen M, Kuhle C, Hensrud D, Erwin PJ, Murad MH (2012) The effect of coffee consumption on blood pressure and the development of hypertension: a systematic review and meta-analysis. J Hypertens 30:2245–2254
Stolarczyk M, Piwowarski JP, Granica S, Stefańska J, Naruszewicz M, Kiss AK (2013) Extracts from Epilobium sp. Herbs, their components and gut microbiota metabolites of epilobium ellagitannins, urolithins, inhibit hormone-dependent prostate cancer cells-(LNCaP) proliferation and PSA secretion. Phytother Res 27:1842–1848
Stoner GD, Mukhtar H (1995) Polyphenols as cancer chemopreventive agents. J Cell Biochem Suppl 22:169–180
Storniolo CE, Moreno JJ (2012) Resveratrol metabolites have an antiproliferative effect on intestinal epithelial cancer cells. Food Chem 134:1385–1391
Su TR, Lin JJ, Tsai CC, Huang TK, Yang ZK, Wu MO, Zheng YQ, Su CC, Wu YJ (2013) Inhibition of melanogenesis by gallic acid: possible involvement of the PI3K/Akt, MEK/ERK and Wnt/β-catenin signaling pathways in B16F10 cells. Int J Mol Sci 14:20443–20458
Suganuma M, Okabe S, Oniyama M, Tada Y, Ito H, Fujiki H (1998) Wide distribution of [3H](−)-epigallocatechin gallate, a cancer preventive tea polyphenol, in mouse tissue. Carcinogenesis 19:1771–1776
Suliburska J, Bogdanski P, Szulinska M, Stepien M, Pupek-Musialik D, Jablecka A (2012) Effects of green tea supplementation on elements, total antioxidants, lipids, and glucose values in the serum of obese patients. Biol Trace Elem Res 149:315–322
Taku K, Umegaki K, Sato Y, Taki Y, Endoh K, Watanabe S (2007) Soy isoflavones lower serum total and LDL cholesterol in humans: a meta-analysis of 11 randomized controlled trials. Am J Clin Nutr 85:1148–1156
Takumi H, Nakamura H, Simizu T, Harada R, Kometani T, Nadamoto T, Mukai R, Murota K, Kawai Y, Terao J (2012) Bioavailability of orally administered water-dispersible hesperetin and its effect on peripheral vasodilatation in human subjects: implication of endothelial functions of plasma conjugated metabolites. Food Funct 3:389–398
Teede HJ, Dalais FS, Kotsopoulos D, Liang YL, Davis S, McGrath BP (2001) Dietary soy has both beneficial and potentially adverse cardiovascular effects: a placebo-controlled study in men and postmenopausal women. J Clin Endocrinol Metab 86:3053–3060
Teede HJ, McGrath BP, DeSilva L, Cehun M, Fassoulakis A, Nestel PJ (2003) Isoflavones reduce arterial stiffness: a placebo-controlled study in men and postmenopausal women. Arterioscler Thromb Vasc Biol 23:1066–1071
Terrill TH, Waghorn GC, Woolley DJ, McNabb WC, Barry TN (1994) Assay and digestion of 14C-labelled condensed tannins in the gastrointestinal tract of sheep. Br J Nutr 72:467–477
Theodoratou E, Kyle J, Cetnarskyj R, Farrington SM, Tenesa A, Barnetson R, Porteous M, Dunlop M, Campbell H (2007) Dietary flavonoids and the risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev 16:684–693
Tome-Carneiro J, Larrosa M, Yanez-Gascon MJ, Davalos A, Gil-Zamorano J, Gonzalvez M, Garcia-Almagro FJ, Ruiz Ros J, Tomas-Barberan FA, Espin JC, Garcia-Conesa M-T (2013) One-year supplementation with a grape extract containing resveratrol modulates inflammatory-related microRNAs and cytokines expression in peripheral blood mononuclear cells of type 2 diabetes and hypertensive patients with coronary artery disease. Pharmacol Res 72:69–82
Tribolo S, Lodi F, Winterbone MS, Saha S, Needs PW, Hughes DA, Kroon PA (2013) Human metabolic transformation of quercetin blocks its capacity to decrease endothelial nitric oxide synthase (eNOS) expression and endothelin-1 secretion by human endothelial cells. J Agric Food Chem 61:8589–8596
Trollor JN, Smith E, Baune BT, Kochan NA, Campbell L, Samaras K, Crawford J, Brodaty H, Sachdev P (2010) Systemic inflammation is associated with MCI and its subtypes: the Sydney Memory and Aging Study. Dement Geriatr Cogn Disord 30:569–578
Truelsen T, Thudium D, Gronbaek M (2002) Amount and type of alcohol and risk of dementia: the Copenhagen City Heart Study. Neurology 59:1313–1319
Tufenkji N, Rifai OJ, Harmidy K, Eydelnant IA (2010) Cranberry derived proanthocyanidins can prevent pathogen invasion of kidney epithelial cells. Food Res Intern 43:922–924
Uhlenhut K, Högger P (2012) Facilitated cellular uptake and suppression of inducible nitric oxide synthase by a metabolite of maritime pine bark extract (Pycnogenol). Free Radic Biol Med 53:305–313
Umadevi S, Gopi V, Simna SP, Parthasarathy A, Yousuf SMJ, Elangovan V (2012) Studies on the cardio protective role of gallic acid against age-induced cell proliferation and oxidative stress in H9C2 (2-1) cells. Cardiovasc Toxicol 12:304–311
Ungvari Z, Bagi Z, Feher A, Recchia FA, Sonntag WE, Pearson K, de Cabao R, Csiszar A (2010) Resveratrol confers endothelial protection via activation of the antioxidant transcription factor Nrf2. Am J Physiol Heart Circ Physiol 299:H18–H24
Urpi-Sarda M, Monagas M, Khan N, Llorach R, Lamuela-Raventós RM, Jáurequi O, Estruch R, Izquierdo-Pulido A, Andrés-Laxueva C (2009) Targeted metabolic profiling of phenolics in urine and plasma after regular consumption of cocoa by liquid chromatography-tandem mass spectrometry. J Chromatogr A 1216:7258–7267
USDA (2007) USDA database for the flavonoid content of selected foods release, 21st edn. USDA, Belstville
Usui T, Tochiya M, Sasaki Y, Muranaka K, Yamakage H, Himeno A, Shimatsu A, Inaguma A, Ueno T, Uchiyama S, Satoh-Asahara N (2013) Effects of natural S-equol supplements on overweight or obesity and metabolic syndrome in the Japanese, based on sex and equol status. Clin Endocrinol 78:365–372
van de Wetering K, Burkon A, Feddema W, Bot A, de Jong H, Somoza V, Borst P (2009) Intestinal breast cancer resistant protein (BCPP)/Berp1 and multidrug resistant protein 3 (MRP3)/Mrp3 are involved in pharmacokinetics resveratrol. Mol Pharmacol 7:876–885
van der Hooft JJ, de Vos RC, Mihaleva V, Bino RJ, Ridder L, de Roo N, Jacobs DM, van Duynhoven JP, Vervoot J (2012) Structural elucidation and quantification of phenolic conjugates present in human urine after tea intake. Anal Chem 84:7263–7271
Vauzour D (2012) Dietary polyphenols as modulators of brain functions: biological actions and molecular mechanisms underpinning their beneficial effects. Oxid Med Cell Longev 2012 914273. doi:10.1155/2012/914273
Vauzour D (2014) Effect of flavonoids on learning, memory and neurocognitive performance: relevance and potential implications for Alzheimer’s disease pathophysiology. J Sci Food Agric 94:1042–1056
Vetterli L, Brun T, Giovannoni L, Bosco D, Maechler P (2011) Resveratrol potentiates glucose-stimulated insulin secretion in INS-1E β-cells and human islets through a SIRT1-dependent mechanism. J Biol Chem 28:6049–6060
Vicinanza R, Zhang Y, Henning SM, Heber D (2013) Pomegranate juice metabolites, ellagic acid and urolithin a, synergistically inhibit androgen-independent prostate cancer cell growth via distinct effects on cell cycle control and apoptosis. Evid Based Complement Alternat Med 2013:247504. doi:10.1155/2013/247504
Vitaglione P, Donnarumma G, Napolitano A, Galvano F, Gallo A, Scalfi L, Fogliano V (2007) Protocatechuic acid is the major human metabolite of cyanidin-glucosides. J Nutr 137:2043–2048
Vlachopoulos C, Aznaouridis K, Stefanadis C (2010) Prediction of cardiovascular events and all-cause mortality with arterial stiffness: a systematic review and meta-analysis. J Am Coll Cardiol 55:1318–1327
Walker J, Schueller K, Schaefer LM, Pignitter M, Esefelder L, Somoza V (2014) Resveratrol and its metabolites inhibit pro-inflammatory effects of lipopolysaccharides in U-937 macrophages in plasma-representative concentrations. Food Funct 5:74–84
Wang J, Ferruzzi MG, Ho L, Blount J, Janie EM, Gong B, Pan Y, Gowda GA, Raferty D, Arrieta-Cruz I, Sharma V, Cooper B, Lobo J, Simon JE, Zhang C, Cheng A, Qian X, Ono K, Teplow DB, Pavlides C, Dixon RA, Pasinetti GM (2012a) Brain-targeted proanthocyanidin metabolites for Alzheimer’s disease treatment. J Neurosci 32:5144–5150
Wang D, Xia M, Yan X, Li D, Wang L, Xu Y, Jin T, Ling W (2012b) Gut microbiota metabolism of anthocyanin promotes reverse cholesterol transport in mice via repressing miRNA-10b. Circ Res 111:967–981
Wang X, Ouyang YY, Liu J, Zhao G (2014) Flavonoid intake and risk of CVD: a systematic review and meta-analysis of prospective cohort studies. Br J Nutr 111:1–11
West SG, McIntyre MD, Piotrowski MJ, Poupin N, Miller DL, Preston AG, Wagner P, Groves LF, Skulas-Ray AC (2014) Effects of dark chocolate and cocoa consumption on endothelial function and arterial stiffness in overweight adults. Br J Nutr 111:653–661
Widlansky ME, Duffy SJ, Hamburg NM, Gokce N, Warden BA, Wiseman S, Keaney JF Jr, Frei B, Vita JA (2005) Effects of black tea consumption on plasma catechins and markers of oxidative stress and inflammation in patients with coronary artery disease. Free Radic Biol Med 38:499–506
Wishart DS, Jewison T, Guo AC, Wilson M, Knox C, Liu Y, Djoumbou Y, Mandal R, Aziat F, Dong E, Bouatra S, Sinelnikov I, Arndt D, Xia J, Liu P, Yallou F, Bjorndahl T, Perez-Pineiro R, Eisner R, Allen F, Neveu V, Greiner R, Scalbert A (2013) HMDB 3.0—the human metabolome database in 2013. Nucleic Acids Res 41(Database issue):D801–d807. doi:10.1093/nar/gks1065
Woodward G, Kroon P, Cassidy A, Kay C (2009) Anthocyanin stability and recovery: implications for the analysis of clinical and experimental samples. J Agric Food Chem 57:5271–5278
World Cancer Research Fund and the American Institue for Cancer Research (2009) Policy and action for cancer prevention. Food, nutrition, and physical activity: a global perspective. American Institute for Cancer Research, Washington
World Cancer Research Fund and the American Institute for Cancer Research (1997) Food, nutrition and the prevention of cancer: a global perspective. American Institute for Cancer Research, Washington
Wright ORL, Netzel GA, Sakzewski AR (2013) A randomized, double-blind, placebo-controlled trial of the effect of dried purple carrot on body mass, lipids, blood pressure, body composition, and inflammatory markers in overweight and obese adults: the QUENCH trial. Can J Physiol Pharmacol 91:480–488
Yamamoto S, Tsukamoto T, Terai A, Kurazono H, Takeda Y, Yoshida O (1997) Genetic evidence supporting the fecal-perineal-urethral hypothesis in cystitis caused by Escherichia coli. J Urol 157:1127–1129
Yochum L, Kushi LH, Meyer K, Folsom AR (1999) Dietary flavonoid intake and risk of cardiovascular disease in postmenopausal women. Am J Epidemiol 149:943–949
Yubero N, Sanz-Buenhombre M, Guadarrama A, Villanueva S, Carrion JM, Larrarte E, Moro C (2013) LDL cholesterol-lowering effects of grape extract used as a dietary supplement on healthy volunteers. Int J Food Sci Nutr 64:400–406
Zaciragic A, Lepara O, Valjevac A, Arslanagic S, Fajkic A, Hadzovic-Dzuvo A, Avdagic N, Alajbegovic A, Mehmedika-Suljic E, Coric G (2007) Elevated serum C-reactive protein concentration in Bosnian patients with probable Alzheimer’s disease. J Alzheimers Dis 12:151–156
Zahedi M, Ghiasvand R, Feizi A, Asgari G, Darvish L (2013) Does quercetin improve cardiovascular risk factors and inflammatory biomarkers in women with type 2 siabetes: a double-blind randomized controlled clinical trial. Int J Prev Med 4:777–785
Zamora-Ros R, Jimenez C, Cleries R, Agudo A, Sanchez MJ, Sanchez-Cantalejo E, Molina-Montes E, Navarro C, Chirlaque MD, Maria Huerta J, Amiano P, Redondo ML, Barricarte A, Gonzalez CA (2013) Dietary flavonoid and lignan intake and mortality in a Spanish cohort. Epidemiology 24:726–733
Zamora-Ros R, Touillaud M, Rothwell JA, Romieu I, Scalbert A (2014) Measuring exposure to the polyphenol metabolome in observational epidemiologic studies: current tools and applications and their limits. Am J Clin Nutr 100:11–26
Zhang SM, Hunter DJ, Rosner BA, Giovannucci EL, Colditz GA, Speizer FE, Willett WC (2000) Intakes of fruits, vegetables, and related nutrients and the risk of non-Hodgkin’s lymphoma among women. Cancer Epidemiol Biomarkers Prev 9:477–485
Zhang M, Jagdmann GE Jr, Van Zandt M, Sheeler R, Beckett P, Schroeter H (2013a) Chemical synthesis and characterization of epicatechin gluronides and sulfates:bioanalytical standards for epicatechin metabolite identification. J Nat Prod 76:157–169
Zhang T, Liang X, Shi L et al (2013b) Estrogen receptor and PI3K/Akt signaling pathway Involvement in S-(−)equol-induced activation of Nrf2/ARE in endothelial cells. PLoS ONE 8:e79075
Zhao C, Deng W, Gage FH (2008) Mechanisms and functional implications of adult neurogenesis. Cell 132:645–660
Zheng W, Zhang Y, Ma D, Shi Y, Liu C, Wang P (2012) (±)Equol inhibits invasion in prostate cancer DU145 cells possibly via down-regulation of matrix metalloproteinase-9, matrix metalloproteinase-2 and urokinase-type plasminogen activator by antioxidant activity. J Clin Biochem Nutr 51:61–67
Zhu Y, Xia M, Yang Y, Liu F, Li Z, Hao Y, Mi M, Jin T, Ling W (2011) Purified anthocyanin supplementation improves endothelial function via NO-cGMP activation in hypercholesterolemic individuals. Clin Chem 57:1524–1533
Zhu Y, Ling W, Guo H, Song F, Ye Q, Zou T, Li D, Zhang Y, Li G, Xiao Y, Liu F, Li Z, Shi Z, Yang Y (2013) Anti-inflammatory effect of purified dietary anthocyanin in adults with hypercholesterolemia: a randomized controlled trial. Nutr Metab Cardiovasc Dis 23:843–849
Zielinski T, Dzielinska Z, Januszewicz A, Rynkun D, Makowiecka Ciesla M, Tyczynski P, Prejbisz A, Demkow M, Kadziela J, Naruszewicz M, Januszewicz M, Juraszynski Z, Korewicki J, Ruzyllo W (2007) Carotid intima-media thickness as a marker of cardiovascular risk in hypertensive patients with coronary artery disease. Am J Hypertens 20:1058–1064
Zini A, Del Rio D, Stewart AJ, Mandioli J, Merelli E, Sola P, Nichelli P, Serafini M, Brighenti F, Edwards CA, Crozier A (2006) Do flavan-3-ols from green tea reach the human brain? Nutr Biosci 9:57–61
Zunino SJ, Parelman MA, Freytag TL, Stephensen CB, Kelley DS, Mackey BE, Woodhouse LR, Bonnel EL (2012) Effects of dietary strawberry powder on blood lipids and inflammatory markers in obese human subjects. Br J Nutr 108:900–909
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Rodriguez-Mateos, A., Vauzour, D., Krueger, C.G. et al. Bioavailability, bioactivity and impact on health of dietary flavonoids and related compounds: an update. Arch Toxicol 88, 1803–1853 (2014). https://doi.org/10.1007/s00204-014-1330-7
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DOI: https://doi.org/10.1007/s00204-014-1330-7
Keywords
- Dietary flavonoids
- Related compounds
- Absorption
- Metabolism
- Colonic catabolism
- Bioactivity
- Urinary tract infections
- Neurogenerative disorders
- Cancer
- Cardiovascular disease