Flavonoid-rich foods (FRF): A promising nutraceutical approach against lifespan-shortening diseases

Document Type: Review Article


1 State Key Laboratory of Natural Medicines, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, Jiangsu Province, PR China

2 Department of Veterinary Microbiology, Faculty of Animal Husbandry and Veterinary Sciences, Sindh Agriculture University Tandojam 70060, Pakistan

3 Faculty of Animal Production and Technology, Cholistan University of Veterinary and Animal Sciences, Bahawalpur 6300, Pakistan

4 Department of Physical Education, Shaanxi Normal University, Xian, Shaanxi Province, P.R China

5 School of Public Health, Nanjing Medical University, Jiangsu Province, 211166, P.R China

6 School of Pharmacy, Nanjing Medical University, Jiangsu Province, 211166, P.R China

7 Faculty of Health Sciences, University of Macau, Avenida de UniversidadeTaipa, Macau

8 Department of Veterinary Medicine, Faculty of Animal Husbandry and Veterinary Science, Sindh Agriculture University, Tandojam 70060, Pakistan

9 Liaquat University of Medical and Health Sciences, Jamshoro, Pakistan

10 Departmentof Poultry, Faculty of Agriculture, Zagazig University, Zagazig 44511, Egypt


It is well documented that life expectancy in developed countries at birth is going to increase from the 20th century. However, regrettably, a potential decline in life expectancy has been proposed for these nations in the 21st century due to a rapid upsurge in the prevalence of fatal degenerative diseases like cardiovascular diseases (CVD), cancer and diabetes. Collectively, these three diseases accounted for 65% of all deaths in urbanized societies and considered as a dynamic issue for shortening the genetically determined lifespan through increased mortalities, morbidities, disabilities, immense sufferings, and premature aging. These fatal degenerative diseases and premature aging are closely associated with oxidative stress produced by the free radicals in the body. In epidemiologic studies, flavonoid-rich foods (FRF) like fruits, vegetables, and beverages have been associated as protective agents against these diseases. These also have been observed for their geroprotective effects and help in preventing the premature aging and the deterioration of brain function, which is related to Alzheimer’s disease and dementia. In this review, we presented a comprehensive overview of the FRF for their potential role against lifespan-shortening complications, i.e., CVD, cancer, and diabetes. We also had drawn the future perspective and dietary guidelines to reduce the fatal diseases burden in urban populations.


1. De Leo F, Del Bosco F. Citrus flavonoids as bioactive compounds: Role, bioavailability, socio-economic impact and biotechnological approach for their modification, 9th ICABR International Conference on Agricultural Biotechnology: Ten Years Later, Ravello, Italy; 2005.
2. Shen JZ, Ng LJT, Ho SW. Therapeutic potential of phytochemicals in combination with drugs for cardiovascular disorders, Curr Pharm Des 2017;23: 961-966.
3. Kamboh AA,  Arain MA,  Mughal MJ,  Zaman A, Arain ZM,  Soomro AH. Flavonoids: health promoting phytochemicals for animal production -a review, J Anim Health Prod 2015; 3: 6-13.
4. Kris-Etherton PM, Harris WS, Appel LJ. Omega-3 fatty acids and cardiovascular disease. Arterioscler Thromb Vasc Biol 2003; 23:151-152.
5. Setchell KD,  Radd S. Soy and other legumes:‘Bean’around a long time but are they the ‘superfoods’ of the millennium and what are the safety issues for their constituent phytoestrogens? Asia Pac J Clini Nutr  2000;9:1-10.
6. Hancock RD,  McDougall GJ,  Stewart D. Berry fruit as ‘superfood’: hope or hype, Biologist 2007;54:73-79.
7. Bishop NA,  Guarente L. Genetic links between diet and lifespan: shared mechanisms from yeast to humans. Nat Rev Genet  2007;8:835-844.
8. Tuljapurkar S,  Li N,  Boe C. A universal pattern of mortality decline in the G7 countries. Nature 2000;405:789-792.
9. Murphy SL, Xu J, Kochanek KD. National vital statistics reports. National vital statistics reports. 2013;8:61.
10. Olshansky SJ,  Passaro DJ,  Hershow RC, Layden J,  Carnes BA,  Brody J,  et al. A potential decline in life expectancy in the United States in the 21st century, N Engl J Med 2005; 352:1138-1145.
11. Eyre H,  Kahn R,  Robertson RM,  Clark NG,  Doyle C,  Gansler T,  et al. Preventing cancer, cardiovascular disease, and diabetes: a common agenda for the American Cancer Society, the American Diabetes Association, and the American Heart Association, CA. Cancer J Clin 2004;54:190-207.
12. Kehrer JP  Klotz LO. Free radicals and related reactive species as mediators of tissue injury and disease: implications for Health. Critic Rev Toxicol 2015;45:765-798.
13. Mojsilove G,  Kuchta M. Dietary flavonoids and risk of coronary heart disease. Physiol Res 2001;50:529-535.
14. Yang X, Jiang Y, Yang J,  He J, Sun J,  Chen F,  et al. Prenylated flavonoids, promising nutraceuticals with impressive biological activities. Trends Food Sci Technol 2015; 44:93-104.
15. Croft KD. The chemistry and biological effects of flavonoids and phenolic acids. Ann N Y Acad Sci 1998; 854:435-442.
16. Catoni C,  Schaefer HM,  Peters A. Fruit for health: the effect of flavonoids on humoral immune response and food selection in a frugivorous bird. Funct Ecol 2008;22:649-654.
17. Shukitt-Hale B, Galli RL, Meterko V, Carey A, Bielinski DF, McGhie T, et al. Dietary supplementation with fruit polyphenolics ameliorates age-related deficits in behavior and neuronal markers of inflammation and oxidative stress. Age (Dordr) 2005;27:49-57.
18. Saravanan D,  Thirumalai D, Asharani IV. Anti-HIV flavonoids from natural products: A systematic review. Int J  Res  Pharm Sci 2016;6:248-255.
19. Liang Q, Chen H, Zhou X, Deng Q, Hu E, Zhao C, Gong X. Optimized microwave‐assistant extraction combined ultrasonic pretreatment of flavonoids from Periploca forrestii Schltr. and evaluation of its anti‐allergic activity. Electrophoresis 2017; 38:1113-1121.
20. Knekt P,  Kumpulainen J,  Jarvinen R,  Rissanen H,  Heliovaara M,  Reunanen A,  et al. Flavonoid intake and risk of chronic diseases, Am J Clin Nutr 2002; 76:560-568.
21. AlDrak N,  Abudawood M, Hamed SS, Ansar S. Effect of rutin on proinflammatory cytokines and oxidative stress in toxin-mediated hepatotoxicity. Toxin Rev 2017;37:1-8.
22. Middleton J, MD E. Biological properties of plant flavonoids: an overview, Int J Pharm 1996;34:344-348.
23. Scalbert A,  Johnson IT,  Saltmarsh M. Polyphenols: antioxidants and beyond. Am J Clin Nutr 2005; 81:215-217.
24. Kamboh AA. Flavonoid-rich Foods -Super Foods of the Millennium, LAP LAMBERT academic publishing Deutschland, Germany; 2012.
25. Behzad S, Sureda A, Barreca D, Nabavi SF, Rastrelli L, Nabavi SM. Health effects of phloretin: from chemistry to medicine. Phytochem Rev 2017;16:527-533.
26. Stanner S, Hughes J, Kelly C, Buttriss J. A review of the epidemiological evidence for the ‘antioxidant hypothesis’. Public Health Nutr 2004;7:407-422.
27. Malin AS, Qi D, Shu XO, Gao YT, Friedmann JM, Jin F, et al. Intake of fruits, vegetables and selected micronutrients in relation to the risk of breast cancer, Int J Cancer 2003; 105:413-418.
28. Zhang X, Shu XO, Gao YT, Yang G, Li Q, Li H, et al.  Soy food consumption is associated with lower risk of coronary heart disease in Chinese women. J Nutr 2003;133:2874-2878.
29. Huang SL, Lin KC,  Pan WH.  Dietary factors associated with physician‐diagnosed asthma and allergic rhinitis in teenagers: analyses of the first Nutrition and Health Survey in Taiwan. Clin Exp Aller 2001;31:259-264.
30. Liu RH.  Health benefits of fruit and vegetables are from additive and synergistic combinations of phytochemicals. Am J Clin Nutr 2003;78:517-520.
31. WHO. The world health report: reducing risks, promoting healthy life, World Health Organization; 2002.
32. Pallauf K, Duckstein N,  Rimbach G. A literature review of flavonoids and lifespan in model organisms. Proc Nutr Soc 2017;76:145-162.
33. Harborne JB,  Williams CA. Advances in flavonoid research since 1992. Phytochemistry 2000; 55:481-504.
34. Liu RH. Health-promoting components of fruits and vegetables in the diet. Adv Nutr 2013; 4:384S-392S.
35. Butt MS, Imran A, Sharif MK, Ahmad RS, Xiao H, Imran M, et al. Black tea polyphenols: a mechanistic treatise. Crit Rev Food Sci Nutr 2014; 54:1002-1011.
36. Mink PJ, Scrafford CG, Barraj LM, Harnack L, Hong CP, Nettleton JA, et al. Flavonoid intake and cardiovascular disease mortality: a prospective study in postmenopausal women. Am J Clin Nutr 2007; 85:895-909.
37. Bhagwat S, Haytowits DB, Holden JM. USDA Database for the flavonoid content of selected foods. Nutrient Data Laboratory, Beltsville Human Nutrition Research Center Agricultural Research Service U.S. Departament of Agriculture 2011; 1:159.
38. Giampieri F, Forbes-Hernandez TY, Gasparrini M, Alvarez-Suarez JM, Afrin S, Bompadre S, et al. Strawberry as a health promoter: an evidence based review, Food Funct 2015; 6:1386-1398.
39. de Pascual-Teresa S, Sanchez-Ballesta MT. Anthocyanins: from plant to health. Phytochem Rev 2008; 7:281-299.
40. Nijveldt RJ, van Nood E, van Hoorn DE, Boelens PG, van Norren K, van Leeuwen PA. Flavonoids: a review of probable mechanisms of action and potential applications. Am J Clin Nutr 2001; 74:418-425.
41. Abarikwu SO, Olufemi PD, Lawrence CJ, Wekere FC, Ochulor AC, Barikuma AM. Rutin an antioxidant flavonoid, induces glutathione and glutathione peroxidase activities to protect against ethanol effects in cadmium‐induced oxidative stress in the testis of adult rats. Andrologia 2017; 49:7.
42. Atef Y, El-Fayoumi HM, Abdel-Mottaleb Y, Mahmoud MF. Quercetin and tin protoporphyrin attenuate hepatic ischemia reperfusion injury: role of HO-1. Naunyn-Schmiedeberg’s Arch Pharmacol2017; 390:871-881.
43. Ren W, Qiao Z, Wang H, Zhu L, Zhang L. Flavonoids: promising anticancer agents. Med Res Rev 2003; 23:519-534.
44. Kawaii S, Lansky EP. Differentiation-promoting activity of pomegranate (Punica granatum) fruit extracts in HL-60 human promyelocytic leukemia cells. J Med Food 2004; 7:13-18.
45.Gonzales GB, Smagghe G, Grootaert C, Zotti M, Raes K, Camp JV. Flavonoid interactions during digestion, absorption, distribution and metabolism: a sequential structure–activity/property relationship-based approach in the study of bioavailability and bioactivity. Drug Metab Rev 2015; 47:175-190.
46. Day AJ,  Canada FJ, Diaz JC,  Kroon PA, McLauchlan R, Faulds CB, et al. Dietary flavonoid and isoflavone glycosides are hydrolysed by the lactase site of lactase phlorizin hydrolase. FEBS Lett 2000; 468:166-170.
47. Walle T, Otake Y, Walle UK, Wilson FA. Quercetin glucosides are completely hydrolyzed in ileostomy patients before absorption. J Nut 2000; 130:2658-2661.
48. Martin KR,  Appel CL. Polyphenols as dietary supplements: a double-edged sword. Nutr Diet Suppl 2010; 2:1-12.
49. Cassidy A, Brown JE, Hawdon A, Faughnan MS, King LJ, Millward J, et al. Factors affecting the bioavailability of soy isoflavones in humans after ingestion of physiologically relevant levels from different soy foods. J Nutr 2006; 136:45-51.
50. Jalal F, Nesheim MC, Agus Z, Sanjur D, Habicht JP. Serum retinol concentrations in children are affected by food sources of beta-carotene, fat intake, and anthelmintic drug treatment. Am J Clin Nutr 1998; 68:623-629.
51. Porrini M,  Riso P,  Testolin G. Absorption of lycopene from single or daily portions of raw and processed tomato.  Br JNutr 1998; 80:353-361.
52. Bugianesi R, Salucci M, Leonardi C, Ferracane R, Catasta G, Azzini E, et al. Effect of domestic cooking on human bioavailability of naringenin, chlorogenic acid, lycopene and beta-carotene in cherry tomatoes. Eur J Nutr 2004; 43:360-366.
53. Kun S, Milner J. Heating blocks garlic’s ability to suppress 7, 12-dimethylbenz (a) anthracene bioactivation, J Nutr 1999; 129:657-661.
54. Trichopoulou A, Vasilopoulou E. Mediterranean diet and longevity. Br JNutr 2000; 84: S205-S209.
55. Barringer TA. Mediterranean diets and cardiovascular disease. Curr Atheroscler Rep 2001; 3:437-445.
56. Salas-Salvado J, Bullo M,  Babio N, Martinez-Gonzalez MA,  Ibarrola-Jurado N, Basora J, et al. Reduction in the incidence of type 2 diabetes with the Mediterranean diet: results of the PREDIMED-Reus nutrition intervention randomized trial. Diabetes Care 2011; 34:14-19.
57. Centers for Disease Control and Prevention CDC. National diabetes fact sheet: general information and national estimates on diabetes in the united states, 2007. Atlanta, GA: U.S. Department of health and human services, centre for disease control and prevention; 2008.
58. Yang W,  Lu J,  Weng J,  Jia W,  Ji L,  Xiao J,  et al. Prevalence of diabetes among men and women in China. New Eng J Med 2010; 362:1090-1101.
59. Gillies CL, Abrams KR, Lambert PC, Cooper NJ, Sutton AJ, Hsu RT, et al. Pharmacological and lifestyle interventions to prevent or delay type 2 diabetes in people with impaired glucose tolerance: systematic review and meta-analysis. BMJ 2007; 334:299.
60. Oberley LW. Free radicals and diabetes. Free Radic Biol Med 1988; 5:113-124.
61. Asmat U, Abad K,  Ismail K. Diabetes mellitus and oxidative stress-a concise review. Saudi Pharma J 2016; 24:547-553.
62. Wang PY, Fang JC, Gao ZH, Zhang C, Xie SY. Higher intake of fruits, vegetables or their fiber reduces the risk of type 2 diabetes: A meta‐analysis. J Diabet Invest 2016; 7:56-69.
63. Meinilä J, Valkama A,  Koivusalo SB, Stach-Lempinen B, Lindström J, Kautiainen H, et al. Healthy Food Intake Index (HFII)-Validity and reproducibility in a gestational-diabetes-risk population. BMC Public Health 2016; 16:680-690.
64. Tuomilehto J, Hu G, Bidel S, Lindström J, Jousilahti P. Coffee consumption and risk of type 2 diabetes mellitus among middle-aged Finnish men and women. JAMA 2004; 291:1213-1219.
65. Huxley R, Lee CM, Barzi F, Timmermeister L, Czernichow S, Perkovic V, et al. Coffee, decaffeinated coffee, and tea consumption in relation to incident type 2 diabetes mellitus: a systematic review with meta-analysis. Arch Intern Med 2009; 169:2053-2063.
66. Rosengren A, Dotevall A, Wilhelmsen L, Thelle D, Johansson S. Coffee and incidence of diabetes in Swedish women: a prospective 18-year follow-up study. J Intern Med 2004; 255:89-95.
67. Iso H, Date C, Wakai K, Fukui M, Tamakoshi A. The relationship between green tea and total caffeine intake and risk for self-reported type 2 diabetes among Japanese adults. Ann Intern Med 2006; 144:554-562.
68. Saeed M, Naveed M, Arif M, Kakar MU, Manzoor R, Abd EHM, et al. Green tea (Camellia sinensis) and l-theanine: Medicinal values and beneficial applications in humans-A comprehensive review. Biomed Pharmacol 2017; 95:1260-1275.
69. Satoh T, Igarashi M, Yamada S, Takahashi N, Watanabe K. Inhibitory effect of black tea and its combination with acarbose on small intestinal α-glucosidase activity. J Ethnopharmacol 2015; 161:147-155.
70. El-Demerdash FM, Yousef MI, El-Naga NI. Biochemical study on the hypoglycemic effects of onion and garlic in alloxan-induced diabetic rats. Food Chem Toxicol 2005; 43:57-63.
71. Vinayagam R, Xu B. Antidiabetic properties of dietary flavonoids: a cellular mechanism review. Nutr Metab 2015; 12:60-79.
72. Bahmani M, Nejad ASM, Shah NA, Shah SA, Rafieian-Kopaei M, Mahmoodnia L. Survey on ethnobotanical uses of anti-cancer herbs in Southern region of Ilam, West Iran. J Biol Res-BollettinodellaSocietàItaliana di Biologia Sperimentale 2017; 90:19-25.
73. Higdon JV, Delage B, Williams DE, Dashwood RH. Cruciferous vegetables and human cancer risk: epidemiologic evidence and mechanistic basis. Pharmacol Res 2007; 55:224-236.
74. Lam TK  Gallicchio L, Lindsley K, Shiels M, Hammond E, Tao XG, et al. Cruciferous vegetable consumption and lung cancer risk: a systematic review. Cancer Epidemiol Biomarkers Prev 2009; 18:184-195.
75. Verhoeven DT, Goldbohm RA, van Poppel G, Verhagen H, van den Brandt PA. Epidemiological studies on brassica vegetables and cancer risk. Cancer Epidemiol Biomarkers Prev 1996; 5:733-748.
76. Keck AS, Finley JW. Cruciferous vegetables: cancer protective mechanisms of glucosinolate hydrolysis products and selenium. Integr Cancer Ther 2004; 3:5-12.
77. Tian T,  Li J,  Li B,  Wang Y, Li M,  Ma D,  et al. Genistein exhibits anti-cancer effects via down-regulating FoxM1 in H446 small-cell lung cancer cells. Tumor Biol 2014; 35:4137-4145.
78. Giovannucci E, Rimm EB, Liu Y, Stampfer MJ, Willett WC. A prospective study of tomato products, lycopene, and prostate cancer risk. J Natl Cancer Inst 2002; 94:391-398.
79. Hayakawa S, Saito K, Miyoshi N, Ohishi T,  Oishi Y, Miyoshi M, et al. Anti-cancer effects of green tea by either anti-or pro-oxidative mechanisms. Asian Pacific J Cancer Preve 2016; 17:1649-1654.
80. Mandal S. Curcumin, a promising anti-cancer therapeutic: it’s bioactivity and development of drug delivery vehicles. Inter J Drug ResTechnol 2017; 6:14.
81. Volate SR, Davenport DM, Muga SJ, Wargovich MJ. Modulation of aberrant crypt foci and apoptosis by dietary herbal supplements (quercetin, curcumin, silymarin, ginseng and rutin). Carcinogenesis 2005; 26:1450-1456.
82. Caragay AB. Cancer‐preventive foods and ingredients. Arthritis Rheum 1992; 25:1510.
83. Setchell KD. Soy isoflavones-benefits and risks from nature’s selective estrogen receptor modulators (SERMs). J Am Coll Nutr 2001; 20:354S-362S.
84. Harris J. The anti-inflammatory and anti-carcinogenic effects mediated by Genistein in breast cancer, Doctoral dissertation, Cardiff Metropolitan University; 2017.
85. Tse G, Eslick GD. Soy and isoflavone consumption and risk of gastrointestinal cancer: a systematic review and meta-analysis. Eur J Nutr 2016; 55:63-73.
86. Jung H, Ahn S, Kim BS, Shin SY, Lee YH,  Lim Y. Isoflavones as modulators of adenosine monophosphate-activated protein kinase. Appl Biol Chem 2016; 59:217-225.
87. Salti GI, Grewal S, Mehta RR, Gupta TD, Boddie Jr AW, Constantinou AI. Genistein induces apoptosis and topoisomerase II-mediated DNA breakage in colon cancer cells. Eur J Cancer 2000 1;36:796-802.
88. Kwok CS, Boekholdt SM, Lentjes MA, Loke YK, Luben RN, Yeong JK, et al. Habitual chocolate consumption and risk of cardiovascular disease among healthy men and women. Heart2015; 101:1279-1287.
89. Di Lorenzo A, Curti V, Tenore GC, Nabavi SM, Daglia M. Effects of tea and coffee consumption on cardiovascular diseases and relative risk factors: an update. Curr Pharm Des 2017; 23:2474-2487.
90. Rechner AR, Kroner C. Anthocyanins and colonic metabolites of dietary polyphenols inhibit platelet function. Thromb Res 2005; 116:327-334.
91. Xia M, Ling W, Zhu H, Wang Q, Ma J, Hou M,  et al. Anthocyanin prevents CD40-activated proinflammatory signaling in endothelial cells by regulating cholesterol distribution. Arterioscler Thromb Vasc Biol 2007; 27:519-524.
92. Haseeb S, Alexander B, Baranchuk A. Wine and cardiovascular health: A comprehensive review. Circulation 2017; 136:1434-1448.
93. Dauchet L, Kesse-Guyot E,  Czernichow S,  Bertrais S, Estaquio C, Peneau S, et al. Dietary patterns and blood pressure change over 5-y follow-up in the SU.VI.MAX cohort. Am J Clin Nutr 2007; 85:1650-1656.
94. Ramdath DD, Padhi EM, Sarfaraz S, Renwick S, Duncan AM. Beyond the cholesterol-lowering effect of soy protein: a review of the effects of dietary soy and its constituents on risk factors for cardiovascular disease. Nutrients 2017; 9:324.
95. Hughes LA, Arts IC, Ambergen T, Brants HA, Dagnelie PC, Goldbohm RA, et al. Higher dietary flavone, flavonol, and catechin intakes are associated with less of an increase in BMI over time in women: a longitudinal analysis from the Netherlands Cohort Study. Am J Clin Nutr 2008; 88:1341-1352.
96. Shenoy SF, Kazaks AG, Holt RR, Chen HJ, Winters BL, San Khoo C, et al. The use of a commercial vegetable juice as a practical means to increase vegetable intake: a randomized controlled trial. Nutr J 2010; 9:38-48.
97. Hung HC, Joshipura KJ, Jiang R, Hu FB, Hunter D, Smith-Warner SA, et al. Fruit and vegetable intake and risk of major chronic disease. J Natl Cancer Inst 2004; 96:1577-1584.
98. Krauss RM, Eckel RH,  Howard B, Appel LJ, Daniels SR, Deckelbaum RJ, et al. AHA scientific statement: AHA dietary guidelines Revision 2000: A statement for healthcare professionals from the nutrition committee of the american heart Association.  J Nutr 2001; 131:132-146.
99. Anisimov VN. Life span extension and cancer risk: myths and reality. Exp Gerontol 2001; 36:1101-1136.
100.  Ferrari CK. Functional foods, herbs and nutraceuticals: towards biochemical mechanisms of healthy aging. Biogerontology 2004; 5:275-289.
101. Koltover V. Antioxidant biomedicine: from free radical chemistry to systems biology mechanisms. Russ Chem Bull 2010; 59:37-42.
102. Williamson G,  Holst B. Dietary reference intake (DRI) value for dietary polyphenols: are we heading in the right direction? Br J Nutr 2008; 99:55-58.
103. Grosso G,  Estruch R. Nut consumption and age-related disease. Maturitas 2016; 84:11-16.
104. Jang S, Johnson RW. Can consuming flavonoids restore old microglia to their youthful state? Nutr Rev 2010; 68:719-728.
105. Shukitt-Hale B, Lau FC, Joseph JA. Berry fruit supplementation and the aging brain. J Agric Food Chem 2008; 56:636-641.
106. Shukitt-Hale B, Carey A, Simon L, Mark DA, Joseph JA. Effects of Concord grape juice on cognitive and motor deficits in aging. Nutrition 2006; 22:295-302.
107. Joseph JA, Shukitt-Hale B, Denisova NA, Bielinski D, Martin A, McEwen JJ, et al. Reversals of age-related declines in neuronal signal transduction, cognitive, and motor behavioral deficits with blueberry, spinach, or strawberry dietary supplementation, J Neurosci 1999; 19:8114-8121.
108. Joseph JA, Denisova NA, Arendash G, Gordon M, Diamond D, Shukitt-Hale B, et al. Blueberry supplementation enhances signaling and prevents behavioral deficits in an Alzheimer disease model. Nutr Neurosci 2003; 6:153-162.
109. Sutherland BA, Rahman RM, Appleton I. Mechanisms of action of green tea catechins, with a focus on ischemia-induced neurodegeneration, J Nutr Biochem 2006; 17:291-306.
110. Milerova J, Cerovska J, Zamrazil V, Bilek R, Lapcik O, Hampl R. Actual levels of soy phytoestrogens in children correlate with thyroid laboratory parameters. Clin Chem Lab Med 2006; 44:171-174.
111. Chandra AK,  De N. Goitrogenic/antithyroidal potential of green tea extract in relation to catechin in rasts. Food Chem Toxicol 2010; 48:2304-2311.
112. Egert S, Rimbach G. Which sources of flavonoids: complex diets or dietary supplements? Adv Nutr 2011; 2:8-14.
113. Mateos R, Lecumberri E, Ramos S, Goya L, Bravo L. Determination of malondialdehyde (MDA) by high-performance liquid chromatography in serum and liver as a biomarker for oxidative stress: Application to a rat model for hypercholesterolemia and evaluation of the effect of diets rich in phenolic antioxidants from fruits. J Chromatogr B Analyt Technol Biomed Life Sci 2005; 827:76-82.
114. Medina-Remón A, Barrionuevo-González A, Zamora-Ros R, Andres-Lacueva C, Estruch R, Martínez-González MA, et al. Rapid Folin–Ciocalteu method using microtiter 96-well plate cartridges for solid phase extraction to assess urinary total phenolic compounds, as a biomarker of total polyphenols intake. Anal Chim Acta 2009; 634:54-60.
115. Schatzkin A. Dietary change as a strategy for preventing cancer. Cancer Metastasis Rev 1997; 16:377-392.
116. Ferguson LR. Nutrigenomics approaches to functional foods. J Am Diet Assoc 2009; 109:452-458.
117. Bigliardi B,  Galati F. Innovation trends in the food industry: the case of functional foods. Trend Food Sci Technol 2013; 31:118-129.
118. Feeney MJ. Fruits and the prevention of lifestyle-related diseases. Clin Exp Pharmacol Physiol 2004; 31:11-13.
119. Weisburger JH. Chemopreventive effects of cocoa polyphenols on chronic diseases. Exp Biol Med (Maywood) 2001; 226:891-897.
120. Duthie GG,  Gardner PT,  Kyle JA. Plant polyphenols: are they the new magic bullet?. Proc Nutr Soc 2003; 62:599-603.
121. Gardner E, Ruxton C, Leeds A. Black tea–helpful or harmful? A review of the evidence. Euro J Clini Nutr 2007; 61:3-18.
122. Nurtjahja-Tjendraputra E, Ammit AJ, Roufogalis BD, Tran VH, Duke CC. Effective anti-platelet and COX-1 enzyme inhibitors from pungent constituents of ginger. Thromb Res 2003; 111:259-265.
123. Bellavia A, Larsson SC, Bottai M, Wolk A,  Orsini N. Fruit and vegetable consumption and all-cause mortality: a dose-response analysis. Am J Clin Nutr 2013; 98:454-459.
124. Zhang X, Shu XO, Xiang YB, Yang G, Li H, Gao J. Cruciferous vegetable consumption is associated with a reduced risk of total and cardiovascular disease mortality. Am J Clin Nutr 2011;94: 240-246.
125. Leenders M, Sluijs I, Ros MM, Boshuizen HC, Siersema PD, Ferrari P. Fruit and vegetable consumption and mortality european prospective investigation into cancer and nutrition. Am J Epidemiol2013;178:590-602.
126. Andersen LF, Jacobs DR, Carlsen MH, Blomhoff R.  Consumption of coffee is associated with reduced risk of death attributed to inflammatory and cardiovascular diseases in the Iowa Women’s Health Study.  Am J Clin Nutr 2006; 83:1039-1046.
127. Kuriyama S, Shimazu T, Ohmori K, Kikuchi N, Nakaya N, Nishino Y, et al.  Green tea consumption and mortality due to cardiovascular disease, cancer, and all causes in Japan: the Ohsaki study. JAMA 2006; 296:1255-1265.
128. Nagura J, Iso H, Watanabe Y, Maruyama K, Date C, Toyoshima H, et al.  Fruit, vegetable and bean intake and mortality from cardiovascular disease among Japanese men and women: the JACC Study. Br J Nutr 2009; 102:285-292.
129. Sahyoun NR, Jacques PF, Zhang XL, Juan W, McKeown NM. Whole-grain intake is inversely associated with the metabolic syndrome and mortality in older adults. Am J Clin Nutr 2006; 83:124-131.
130. Sauvaget C, Nagano J, Hayashi M, Spencer E, Shimizu Y, Allen N. Vegetables and fruit intake and cancer mortality in the Hiroshima/Nagasaki Life Span Study. Br J Cancer 2003; 88:689-694.
131. Genkinger JM, Platz EA, Hoffman SC, Comstock GW, Helzlsouer KJ. Fruit, vegetable, and antioxidant intake and all-cause, cancer, and cardiovascular disease mortality in a community-dwelling population in Washington County, Maryland. Am J Epidemiol 2004; 160:1223-1233.
132. Tucker KL, Hallfrisch J, Qiao N, Muller D, Andres R, Fleg JL. The combination of high fruit and vegetable and low saturated fat intakes is more protective against mortality in aging men than is either alone: the Baltimore Longitudinal Study of Aging. J Nutr 2005; 135:556-561.
133. Bazzano LA, He J, Ogden LG, Loria CM, Vupputuri S, Myers L, et al. Fruit and vegetable intake and risk of cardiovascular disease in US adults: the first National Health and Nutrition Examination Survey Epidemiologic Follow-up Study. Am J Clin Nutr 2002; 76:93-99.
134. Strandhagen E, Hansson PO, Bosaeus I, Isaksson B, Eriksson H. High fruit intake may reduce mortality among middle-aged and elderly men. The Study of Men Born in 1913. Eur J Clin Nutr 2000; 54:337-341.
135. Rissanen TH, Voutilainen S, Virtanen JK, Venho B, Vanharanta M, Mursu J, et al. Low intake of fruits, berries, and vegetables is associated with excess mortality in men: the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study.  J Nutr 2003; 133:199-204.