Prophylaxis of Non-communicable Diseases: Why Fruits and Vegetables may be  Better Chemopreventive Agents than Dietary Supplements Based on Isolated Phytochemicals?

Izabela       Koss-Mikołajczyk; Monika       Baranowska; Vanja       Todorovic; Adriana       Albini; Clementina       Sansone; Pierre       Andreoletti; Mustapha       Cherkaoui-Malki; Gérard       Lizard; Douglas       Noonan; Sladjana       Sobajic; Agnieszka       Bartoszek
Abstract

The World Health Organization (WHO) report from 2014 documented that non-communicable socalled civilization diseases such as cardiovascular disease, chronic respiratory diseases, cancer or type 2 diabetes are responsible for over 50% of all premature deaths in the world. Research carried out over the past 20 years has provided data suggesting that diet is an essential factor influencing the risk of development of these diseases. The increasing knowledge on chemopreventive properties of certain food ingredients, in particular, those of plant origin, opened the discussion on the possibility to use edible plants or their active components in the prevention of these chronic diseases. Health-promoting properties of plant foods are associated with the presence of secondary metabolites that can affect many biological mechanisms of critical importance to the proper functioning of the human organism. Particularly, there have been numerous investigations indicating strong physiological effects of bioactive plant phenols belonging to the flavonoid family. These observations initiated mass production of dietary supplements containing flavonoids commercialized under the name antioxidants, even if their chemical properties did not justify such a term. However, epidemiological studies revealed that isolated bioactive phytochemicals are not as effective as fruits and vegetables containing these substances whereas they are of interest of the functional food industry. In this paper, the critical assessment of reasons for this turn of events has been attempted and the concept of food synergy has been suggested as a future strategy of dietary chemoprevention.
Keywords: Chemoprevention, bioactive phytochemicals, antioxidants, flavonoids, civilization diseases, cancer, food synergy.
[1] 
WHO World Health Organization Global Status Report on noncommunicable diseases 2014 2014.
[2] 
Alemanno A, Garde A. The prevention of noncommunicable diseases in the European Union.Regulating tobacco, alcohol and unhealthy foods: The legal issues 2013.
[3] 
Fardet A, Boirie Y. Associations between food and beverage groups and major diet-related chronic diseases: An exhaustive review of pooled/meta-analyses and systematic reviews. Nutr Rev  2014; 72(12): 741-62.
[http://dx.doi.org/10.1111/nure.12153] [PMID:  25406801] 
[4] 
Nugent R. Chronic diseases in developing countries: health and economic burdens. Ann N Y Acad Sci  2008; 1136: 70-9.
[http://dx.doi.org/10.1196/annals.1425.027] [PMID:  18579877] 
[5] 
Popkin BM. Nutritional patterns and transitions. Popul Dev Rev  1993; 19: 138-57.
[http://dx.doi.org/10.2307/2938388] 
[6] 
Popkin BM, Nielsen SJ. The sweetening of the world’s diet. Obes Res  2003; 11(11): 1325-32.
[http://dx.doi.org/10.1038/oby.2003.179] [PMID:  14627752] 
[7] 
Health Statistics - Atlas on mortality in the European Union  2009.
[8] 
de Lorgeril M, Salen P, Martin JL, Monjaud I, Delaye J, Mamelle N. Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: Final report of the Lyon Diet Heart Study. Circulation  1999; 99(6): 779-85.
[http://dx.doi.org/10.1161/01.CIR.99.6.779] [PMID:  9989963] 
[9] 
Dinu M, Pagliai G, Casini A, Sofi F. Mediterranean diet and multiple health outcomes: An umbrella review of meta-analyses of observational studies and randomised trials. Eur J Clin Nutr  2017; 1: 1-14.
[PMID:  28488692] 
[10] 
 International Agency for Research on Cancer.  European prospective investigation into cancer and nutrition http://epic.iarc.fr/2018
[11] 
Garbisa S, Biggin S, Cavallarin N, Sartor L, Benelli R, Albini A. Tumor invasion: Molecular shears blunted by green tea. Nat Med  1999; 5(11): 1216.
[http://dx.doi.org/10.1038/15145] [PMID:  10545959] 
[12] 
Tosetti F, Ferrari N, De Flora S, Albini A. Angioprevention’: Angiogenesis is a common and key target for cancer chemopreventive agents. FASEB J  2002; 16(1): 2-14.
[http://dx.doi.org/10.1096/fj.01-0300rev] [PMID:  11772931] 
[13] 
Albini A, Tosetti F, Li VW, Noonan DM, Li WW. Cancer prevention by targeting angiogenesis. Nat Rev Clin Oncol  2012; 9(9): 498-509.
[http://dx.doi.org/10.1038/nrclinonc.2012.120] [PMID:  22850752] 
[14] 
Popolo A, Autore G, Pinto A, Marzocco S. Oxidative stress in patients with cardiovascular disease and chronic renal failure. Free Radic Res  2013; 47(5): 346-56.
[http://dx.doi.org/10.3109/10715762.2013.779373] [PMID:  23438723] 
[15] 
Kayama Y, Raaz U, Jagger A, et al. Diabetic cardiovascular disease induced by oxidative stress. Int J Mol Sci  2015; 16(10): 25234-63.
[http://dx.doi.org/10.3390/ijms161025234] [PMID:  26512646] 
[16] 
Siti HN, Kamisah Y, Kamsiah J. The role of oxidative stress, antioxidants and vascular inflammation in cardiovascular disease (a review). Vascul Pharmacol  2015; 71: 40-56.
[http://dx.doi.org/10.1016/j.vph.2015.03.005] [PMID:  25869516] 
[17] 
Russo GL. Ins and outs of dietary phytochemicals in cancer chemoprevention. Biochem Pharmacol  2007; 74(4): 533-44.
[http://dx.doi.org/10.1016/j.bcp.2007.02.014] [PMID:  17382300] 
[18] 
Li W, Guo Y, Zhang C, et al. Dietary phytochemicals and cancer chemoprevention: A perspective on oxidative stress, inflammation, and epigenetics. Chem Res Toxicol  2016; 29(12): 2071-95.
[http://dx.doi.org/10.1021/acs.chemrestox.6b00413] [PMID:  27989132] 
[19] 
Furukawa S, Fujita T, Shimabukuro M, et al. Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest  2004; 114(12): 1752-61.
[http://dx.doi.org/10.1172/JCI21625] [PMID:  15599400] 
[20] 
Sies H. Oxidative stress: A concept in redox biology and medicine. Redox Biol  2015; 4: 180-3.
[http://dx.doi.org/10.1016/j.redox.2015.01.002] [PMID:  25588755] 
[21] 
Lü JM, Lin PH, Yao Q, Chen C. Chemical and molecular mechanisms of antioxidants: Experimental approaches and model systems. J Cell Mol Med  2010; 14(4): 840-60.
[http://dx.doi.org/10.1111/j.1582-4934.2009.00897.x] [PMID:  19754673] 
[22] 
Hultqvist M, Olsson LM, Gelderman KA, Holmdahl R. The protective role of ROS in autoimmune disease. Trends Immunol  2009; 30(5): 201-8.
[http://dx.doi.org/10.1016/j.it.2009.03.004] [PMID:  19356981] 
[23] 
Pacher P, Beckman JS, Liaudet L. Nitric oxide and peroxynitrite in health and disease. Physiol Rev  2007; 87(1): 315-424.
[http://dx.doi.org/10.1152/physrev.00029.2006] [PMID:  17237348] 
[24] 
Fiedor J, Burda K. Potential role of carotenoids as antioxidants in human health and disease. Nutrients  2014; 6(2): 466-88.
[http://dx.doi.org/10.3390/nu6020466] [PMID:  24473231] 
[25] 
Galasso C, Corinaldesi C, Sansone C. Carotenoids from marine organisms: Biological functions and industrial applications. Antioxidants  2017; 6(4): 96-129.
[http://dx.doi.org/10.3390/antiox6040096] [PMID:  29168774] 
[26] 
Korge P, Calmettes G, Weiss JN. Increased reactive oxygen species production during reductive stress: The roles of mitochondrial glutathione and thioredoxin reductases. Biochim Biophys Acta  2015; 1847(6-7): 514-25.
[http://dx.doi.org/10.1016/j.bbabio.2015.02.012] [PMID:  25701705] 
[27] 
Bahorun T, Soobrattee MA, Luximon-Ramma V, Aruoma OI. Free radicals and antioxidants in cardiovascular health and disease. J Medic Update  2006; 1: 1-17.
[28] 
Ceriello A. Possible role of oxidative stress in the pathogenesis of hypertension. Diabetes Care  2008; 31(Suppl. 2): S181-4.
[http://dx.doi.org/10.2337/dc08-s245] [PMID:  18227482] 
[29] 
Chatterjee M, Saluja R, Kanneganti S, Chinta S, Dikshit M. Biochemical and molecular evaluation of neutrophil NOS in spontaneously hypertensive rats. Cell Mol Biol  2007; 53(1): 84-93.
[PMID:  17519116] 
[30] 
Dröge W. Free radicals in the physiological control of cell function. Physiol Rev  2002; 82(1): 47-95.
[http://dx.doi.org/10.1152/physrev.00018.2001] [PMID:  11773609] 
[31] 
Hanahan D, Weinberg RA. The hallmarks of cancer. Cell  2000; 100(1): 57-70.
[http://dx.doi.org/10.1016/S0092-8674(00)81683-9] [PMID:  10647931] 
[32] 
Hanahan D, Weinberg RA. Hallmarks of cancer: The next generation. Cell  2011; 144(5): 646-74.
[http://dx.doi.org/10.1016/j.cell.2011.02.013] [PMID:  21376230] 
[33] 
Surh YJ. Cancer chemoprevention with dietary phytochemicals. Nat Rev Cancer  2003; 3(10): 768-80.
[http://dx.doi.org/10.1038/nrc1189] [PMID:  14570043] 
[34] 
Valko M, Izakovic M, Mazur M, Rhodes CJ, Telser J. Role of oxygen radicals in DNA damage and cancer incidence. Mol Cell Biochem  2004; 266(1-2): 37-56.
[http://dx.doi.org/10.1023/B:MCBI.0000049134.69131.89] [PMID:  15646026] 
[35] 
Valko M, Rhodes CJ, Moncol J, Izakovic M, Mazur M. Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact  2006; 160(1): 1-40.
[http://dx.doi.org/10.1016/j.cbi.2005.12.009] [PMID:  16430879] 
[36] 
Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol  2007; 39(1): 44-84.
[http://dx.doi.org/10.1016/j.biocel.2006.07.001] [PMID:  16978905] 
[37] 
Halliwell B. Biochemistry of oxidative stress. Biochem Soc Trans  2007; 35(Pt 5): 1147-50.
[http://dx.doi.org/10.1042/BST0351147] [PMID:  17956298] 
[38] 
López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell  2013; 153(6): 1194-217.
[http://dx.doi.org/10.1016/j.cell.2013.05.039] [PMID:  23746838] 
[39] 
Aunan JR, Watson MM, Hagland HR, Søreide K. Molecular and biological hallmarks of ageing. Br J Surg  2016; 103(2): e29-46.
[http://dx.doi.org/10.1002/bjs.10053] [PMID:  26771470] 
[40] 
Pham-Huy LA, He H, Pham-Huy C. Free radicals, antioxidants in disease and health. Int J Biomed Sci  2008; 4(2): 89-96.
[PMID:  23675073] 
[41] 
Hernández-García D, Wood CD, Castro-Obregón S, Covarrubias L. Reactive oxygen species: A radical role in development? Free Radic Biol Med  2010; 49(2): 130-43.
[http://dx.doi.org/10.1016/j.freeradbiomed.2010.03.020] [PMID:  20353819] 
[42] 
Schieber M, Chandel NS. ROS function in redox signaling and oxidative stress. Curr Biol  2014; 24(10): R453-62.
[http://dx.doi.org/10.1016/j.cub.2014.03.034] [PMID:  24845678] 
[43] 
European Food Safety Authority.  Draft guidance for scientific requirements for health claims related to antioxidants, oxidative damage and cardiovascular health 2017.
[44] 
AICR. American Institute for Cancer Research: Food, nutrition,physical activity, and the prevention of cancer: A global perspective 2007.
[45] 
AICR, Diet, Nutrition. Physical Activity and Cancer: A Global Perspective. Contionous UpDate Project Expert Report  2018.
[46] 
AICR. American Institute for Cancer Research: Food, nutrition, physical activity, and the prevention of cancer: A global perspective 1997.
[47] 
Loub WD, Wattenberg LW, Davis DW. Aryl hydrocarbon hydroxylase induction in rat tissues by naturally occurring indoles of cruciferous plants. J Natl Cancer Inst  1975; 54(4): 985-8.
[PMID:  1127728] 
[48] 
Mettlin C, Graham S. Dietary risk factors in human bladder cancer. Am J Epidemiol  1979; 110(3): 255-63.
[http://dx.doi.org/10.1093/oxfordjournals.aje.a112810] [PMID:  582494] 
[49] 
Wattenberg LW, Loub WD. Inhibition of polycyclic aromatic hydrocarbon-induced neoplasia by naturally occurring indoles. Cancer Res  1978; 38(5): 1410-3.
[PMID:  416908] 
[50] 
Olsen GW, Mandel JS, Gibson RW, Wattenberg LW, Schuman LM. A case-control study of pancreatic cancer and cigarettes, alcohol, coffee and diet. Am J Public Health  1989; 79(8): 1016-9.
[http://dx.doi.org/10.2105/AJPH.79.8.1016] [PMID:  2751016] 
[51] 
Le Marchand L, Yoshizawa CN, Kolonel LN, Hankin JH, Goodman MT. Vegetable consumption and lung cancer risk: A population-based case-control study in Hawaii. J Natl Cancer Inst  1989; 81(15): 1158-64.
[http://dx.doi.org/10.1093/jnci/81.15.1158] [PMID:  2545891] 
[52] 
Graham S, Marshall J, Mettlin C, Rzepka T, Nemoto T, Byers T. Diet in the epidemiology of breast cancer. Am J Epidemiol  1982; 116(1): 68-75.
[http://dx.doi.org/10.1093/oxfordjournals.aje.a113403] [PMID:  7102657] 
[53] 
Chyou PH, Nomura AM, Hankin JH, Stemmermann GN. A case-cohort study of diet and stomach cancer. Cancer Res  1990; 50(23): 7501-4.
[PMID:  2253198] 
[54] 
Shu XO, Gao YT, Yuan JM, Ziegler RG, Brinton LA. Dietary factors and epithelial ovarian cancer. Br J Cancer  1989; 59(1): 92-6.
[http://dx.doi.org/10.1038/bjc.1989.18] [PMID:  2757927] 
[55] 
Steinmetz KA, Potter JD, Folsom AR. Vegetables, fruit, and lung cancer in the Iowa Women’s Health Study. Cancer Res  1993; 53(3): 536-43.
[PMID:  8425185] 
[56] 
Steinmetz KA, Potter JD. Vegetables, fruit, and cancer prevention: A review. J Am Diet Assoc  1996; 96(10): 1027-39.
[http://dx.doi.org/10.1016/S0002-8223(96)00273-8] [PMID:  8841165] 
[57] 
Kirsh VA, Peters U, Mayne ST, et al. Prostate, lung, colorectal and ovarian cancer screening trial. Prospective study of fruit and vegetable intake and risk of prostate cancer. J Natl Cancer Inst  2007; 99(15): 1200-9.
[http://dx.doi.org/10.1093/jnci/djm065] [PMID:  17652276] 
[58] 
Cassidy A, Mukamal KJ, Liu L, Franz M, Eliassen AH, Rimm EB. High anthocyanin intake is associated with a reduced risk of myocardial infarction in young and middle-aged women. Circulation  2013; 127(2): 188-96.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.112.122408] [PMID:  23319811] 
[59] 
Cassidy A, O’Reilly EJ, Kay C, et al. Habitual intake of flavonoid subclasses and incident hypertension in adults. Am J Clin Nutr  2011; 93(2): 338-47.
[http://dx.doi.org/10.3945/ajcn.110.006783] [PMID:  21106916] 
[60] 
Jennings A, Welch AA, Fairweather-Tait SJ, et al. Higher anthocyanin intake is associated with lower arterial stiffness and central blood pressure in women. Am J Clin Nutr  2012; 96(4): 781-8.
[http://dx.doi.org/10.3945/ajcn.112.042036] [PMID:  22914551] 
[61] 
McCullough ML, Peterson JJ, Patel R, Jacques PF, Shah R, Dwyer JT. Flavonoid intake and cardiovascular disease mortality in a prospective cohort of US adults. Am J Clin Nutr  2012; 95(2): 454-64.
[http://dx.doi.org/10.3945/ajcn.111.016634] [PMID:  22218162] 
[62] 
García-Fernández E, Rico-Cabanas L, Rosgaard N, Estruch R, Bach-Faig A. Mediterranean diet and cardiodiabesity: A review. Nutrients  2014; 6(9): 3474-500.
[http://dx.doi.org/10.3390/nu6093474] [PMID:  25192027] 
[63] 
Di Pietro N, Di Tonno P, Pandolfi A. Carotenoids in cardiovascular disease prevention. JSM Atheroscler  2016; 1: 1002-15.
[64] 
Sporn MB. Approaches to prevention of epithelial cancer during the preneoplastic period. Cancer Res  1976; 36(7 PT 2): 2699-702.
[PMID:  1277177] 
[65] 
Sporn MB, Suh N. Chemoprevention: An essential approach to controlling cancer. Nat Rev Cancer  2002; 2(7): 537-43.
[http://dx.doi.org/10.1038/nrc844] [PMID:  12094240] 
[66] 
Chen C, Kong AN. Dietary cancer-chemopreventive compounds: From signaling and gene expression to pharmacological effects. Trends Pharmacol Sci  2005; 26(6): 318-26.
[http://dx.doi.org/10.1016/j.tips.2005.04.004] [PMID:  15925707] 
[67] 
De Flora S, Izzotti A, D’Agostini F, Balansky RM, Noonan D, Albini A. Multiple points of intervention in the prevention of cancer and other mutation-related diseases. Mutat Res  2001; 480-481: 9-22.
[http://dx.doi.org/10.1016/S0027-5107(01)00165-8] [PMID:  11506795] 
[68] 
Conklin KA. Dietary antioxidants during cancer chemotherapy: Impact on chemotherapeutic effectiveness and development of side effects. Nutr Cancer  2000; 37(1): 1-18.
[http://dx.doi.org/10.1207/S15327914NC3701_1] [PMID:  10965514] 
[69] 
Piasek A, Bartoszek A, Namieśnik J. [Phytochemicals that counteract the cardiotoxic side effects of cancer chemotherapy] Postepy Hig Med Dosw  2009; 63: 142-58.
[PMID:  19502676] 
[70] 
Boffetta P, Couto E, Wichmann J, et al. Fruit and vegetable intake and overall cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). J Natl Cancer Inst  2010; 102(8): 529-37.
[http://dx.doi.org/10.1093/jnci/djq072] [PMID:  20371762] 
[71] 
George SM, Park Y, Leitzmann MF, et al. Fruit and vegetable intake and risk of cancer: A prospective cohort study. Am J Clin Nutr  2009; 89(1): 347-53.
[http://dx.doi.org/10.3945/ajcn.2008.26722] [PMID:  19056579] 
[72] 
Hung HC, Joshipura KJ, Jiang R, et al. Fruit and vegetable intake and risk of major chronic disease. J Natl Cancer Inst  2004; 96(21): 1577-84.
[http://dx.doi.org/10.1093/jnci/djh296] [PMID:  15523086] 
[73] 
Seeram NP, Adams LS, Henning SM, et al. In vitro antiproliferative, apoptotic and antioxidant activities of punicalagin, ellagic acid and a total pomegranate tannin extract are enhanced in combination with other polyphenols as found in pomegranate juice. J Nutr Biochem  2005; 16(6): 360-7.
[http://dx.doi.org/10.1016/j.jnutbio.2005.01.006] [PMID:  15936648] 
[74] 
Shibata A, Paganini-Hill A, Ross RK, Henderson BE. Intake of vegetables, fruits, beta-carotene, vitamin C and vitamin supplements and cancer incidence among the elderly: A prospective study. Br J Cancer  1992; 66(4): 673-9.
[http://dx.doi.org/10.1038/bjc.1992.336] [PMID:  1419605] 
[75] 
Ali HM, Abo-Shady A, Sharaf Eldeen HA, et al. Structural features, kinetics and SAR study of radical scavenging and antioxidant activities of phenolic and anilinic compounds. Chem Cent J  2013; 7(1): 53-62.
[http://dx.doi.org/10.1186/1752-153X-7-53] [PMID:  23497653] 
[76] 
Khairia MY, Azza M, Ezzo MI, El-Sayed AA, Hazzaa AH. EL-Medany MA. Chemopreventive effects of curcumin analogs in DMH-Induced colon cancer in albino rats model. Future J Pharmaceut Sci  2015; 1(2): 57-72.
[http://dx.doi.org/10.1016/j.fjps.2015.11.001] 
[77] 
Barra L, Chandrasekaran R, Corato F, Brunet C. The challenge of ecophysiological biodiversity for biotechnological applications of marine microalgae. Mar Drugs  2014; 12(3): 1641-75.
[http://dx.doi.org/10.3390/md12031641] [PMID:  24663117] 
[78] 
Lordan S, Ross RP, Stanton C. Marine bioactives as functional food ingredients: Potential to reduce the incidence of chronic diseases. Mar Drugs  2011; 9(6): 1056-100.
[http://dx.doi.org/10.3390/md9061056] [PMID:  21747748] 
[79] 
Potter JD. The failure of cancer chemoprevention. Carcinogenesis  2014; 35(5): 974-82.
[http://dx.doi.org/10.1093/carcin/bgu063] [PMID:  24618374] 
[80] 
Dinkova-Kostova AT, Massiah MA, Bozak RE, Hicks RJ, Talalay P. Potency of Michael reaction acceptors as inducers of enzymes that protect against carcinogenesis depends on their reactivity with sulfhydryl groups. Proc Natl Acad Sci USA  2001; 98(6): 3404-9.
[http://dx.doi.org/10.1073/pnas.051632198] [PMID:  11248091] 
[81] 
Lee JS, Surh YJ. Nrf2 as a novel molecular target for chemoprevention. Cancer Lett  2005; 224(2): 171-84.
[http://dx.doi.org/10.1016/j.canlet.2004.09.042] [PMID:  15914268] 
[82] 
Giudice A, Montella M. Activation of the Nrf2-ARE signaling pathway: A promising strategy in cancer prevention. BioEssays  2006; 28(2): 169-81.
[http://dx.doi.org/10.1002/bies.20359] [PMID:  16435293] 
[83] 
Bryan HK, Olayanju A, Goldring CE, Park BK. The Nrf2 cell defence pathway: Keap1-dependent and -independent mechanisms of regulation. Biochem Pharmacol  2013; 85(6): 705-17.
[http://dx.doi.org/10.1016/j.bcp.2012.11.016] [PMID:  23219527] 
[84] 
Magesh S, Chen Y, Hu L. Small molecule modulators of Keap1-Nrf2-ARE pathway as potential preventive and therapeutic agents. Med Res Rev  2012; 32(4): 687-726.
[http://dx.doi.org/10.1002/med.21257] [PMID:  22549716] 
[85] 
Kwak MK, Itoh K, Yamamoto M, Kensler TW. Enhanced expression of the transcription factor Nrf2 by cancer chemopreventive agents: Role of antioxidant response element-like sequences in the nrf2 promoter. Mol Cell Biol  2002; 22(9): 2883-92.
[http://dx.doi.org/10.1128/MCB.22.9.2883-2892.2002] [PMID:  11940647] 
[86] 
Nioi P, McMahon M, Itoh K, Yamamoto M, Hayes JD. Identification of a novel Nrf2-regulated antioxidant response element (ARE) in the mouse NAD(P)H:quinone oxidoreductase 1 gene: Reassessment of the ARE consensus sequence. Biochem J  2003; 374(Pt 2): 337-48.
[http://dx.doi.org/10.1042/bj20030754] [PMID:  12816537] 
[87] 
Kensler TW, Wakabayashi N, Biswal S. Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway. Annu Rev Pharmacol Toxicol  2007; 47: 89-116.
[http://dx.doi.org/10.1146/annurev.pharmtox.46.120604.141046] [PMID:  16968214] 
[88] 
Kaspar JW, Niture SK, Jaiswal AK. Nrf2:INrf2 (Keap1) signaling in oxidative stress. Free Radic Biol Med  2009; 47(9): 1304-9.
[http://dx.doi.org/10.1016/j.freeradbiomed.2009.07.035] [PMID:  19666107] 
[89] 
Niture SK, Kaspar JW, Shen J, Jaiswal AK. Nrf2 signaling and cell survival. Toxicol Appl Pharmacol  2010; 244(1): 37-42.
[http://dx.doi.org/10.1016/j.taap.2009.06.009] [PMID:  19538984] 
[90] 
Cooke D, Steward WP, Gescher AJ, Marczyło T. Anthocyans from fruits and vegetables--does bright colour signal cancer chemopreventive activity? Eur J Cancer  2005; 41(13): 1931-40.
[http://dx.doi.org/10.1016/j.ejca.2005.06.009] [PMID:  16084717] 
[91] 
Dudley JI, Lekli I, Mukherjee S, Das M, Bertelli AA, Das DK. Does white wine qualify for French paradox? Comparison of the cardioprotective effects of red and white wines and their constituents: Resveratrol, tyrosol, and hydroxytyrosol. J Agric Food Chem  2008; 56(20): 9362-73.
[http://dx.doi.org/10.1021/jf801791d] [PMID:  18821770] 
[92] 
Wald N, Idle M, Boreham J, Bailey A. Low serum-vitamin-A and subsequent risk of cancer. Preliminary results of a prospective study. Lancet  1980; 2(8199): 813-5.
[http://dx.doi.org/10.1016/S0140-6736(80)90169-5] [PMID:  6107496] 
[93] 
Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group.The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med  1994; 330(15): 1029-35.
[http://dx.doi.org/10.1056/NEJM199404143301501] [PMID:  8127329] 
[94] 
Omenn GS, Goodman GE, Thornquist MD, et al. Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med  1996; 334(18): 1150-5.
[http://dx.doi.org/10.1056/NEJM199605023341802] [PMID:  8602180] 
[95] 
Ulrich CM, Potter JD. Folate and cancer-timing is everything. JAMA  2007; 297(21): 2408-9.
[http://dx.doi.org/10.1001/jama.297.21.2408] [PMID:  17551134] 
[96] 
Gaziano JM, Glynn RJ, Christen WG, et al. Vitamins E and C in the prevention of prostate and total cancer in men: The Physicians’ Health Study II randomized controlled trial. JAMA  2009; 301(1): 52-62.
[http://dx.doi.org/10.1001/jama.2008.862] [PMID:  19066368] 
[97] 
Clark LC, Combs GF Jr, Turnbull BW, et al. Nutritional Prevention of Cancer Study Group.Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. JAMA  1996; 276(24): 1957-63.
[http://dx.doi.org/10.1001/jama.1996.03540240035027] [PMID:  8971064] 
[98] 
Peters U. Vitamin E and selenium supplementation and risk of prostate cancer in the VITamins And Lifestyle (VITAL) study cohort. Cancer Causes Control 2008; 19: 101-7.Vinceti M, Filippini T, Del Giovane C, Dennert G, Zwahlen M, Brinkman M, Zeegers MP, Horneber M, D’Amico R, Crespi CM. Selenium for preventing cancer. Cochrane Database Syst Rev 2018.
[99] 
Jacobs DR Jr, Steffen LM. Nutrients, foods, and dietary patterns as exposures in research: A framework for food synergy. Am J Clin Nutr  2003; 78(3)(Suppl.): 508S-13S.
[http://dx.doi.org/10.1093/ajcn/78.3.508S] [PMID:  12936941] 
[100] 
Boileau TW, Liao Z, Kim S, Lemeshow S, Erdman JW Jr, Clinton SK. Prostate carcinogenesis in N-methyl-N-nitrosourea (NMU)-testosterone-treated rats fed tomato powder, lycopene, or energy-restricted diets. J Natl Cancer Inst  2003; 95(21): 1578-86.
[http://dx.doi.org/10.1093/jnci/djg081] [PMID:  14600090] 
[101] 
Stacewicz-Sapuntzakis M, Bowen PE. Role of lycopene and tomato products in prostate health. Biochim Biophys Acta  2005; 1740(2): 202-5.
[http://dx.doi.org/10.1016/j.bbadis.2005.02.004] [PMID:  15949687] 
[102] 
Venè R, Benelli R, Minghelli S, Astigiano S, Tosetti F, Ferrari N. Xanthohumol impairs human prostate cancer cell growth and invasion and diminishes the incidence and progression of advanced tumors in TRAMP mice. Mol Med  2012; 18: 1292-302.
[http://dx.doi.org/10.2119/molmed.2012.00174] [PMID:  22952060] 
[103] 
Venè R, Cardinali B, Arena G, et al. Glycogen synthase kinase 3 regulates cell death and survival signaling in tumor cells under redox stress. Neoplasia  2014; 16(9): 710-22.
[http://dx.doi.org/10.1016/j.neo.2014.07.012] [PMID:  25246272] 
[104] 
Liu RH, Liu J, Chen B. Apples prevent mammary tumors in rats. J Agric Food Chem  2005; 53(6): 2341-3.
[http://dx.doi.org/10.1021/jf058010c] [PMID:  15769178] 
[105] 
Liu RH. Potential synergy of phytochemicals in cancer prevention: Mechanism of action. J Nutr  2004; 134(12)(Suppl.): 3479S-85S.
[http://dx.doi.org/10.1093/jn/134.12.3479S] [PMID:  15570057] 
[106] 
Horváth G, Kemény Á, Barthó L, et al. Effects of some natural carotenoids on TRPA1- and TRPV1-induced neurogenic inflammatory processes in vivo in the mouse skin. J Mol Neurosci  2015; 56(1): 113-21.
[http://dx.doi.org/10.1007/s12031-014-0472-7] [PMID:  25645682] 
[107] 
Jacobs DR, Tapsell LC, Temple NJ. Food synergy: The key to balancing the nutrition research effort. Public Health Rev  2012; 33: 507-29.
[http://dx.doi.org/10.1007/BF03391648] 
[108] 
Sansone C, Galasso C, Orefice I, et al. The green microalga Tetraselmis suecica reduces oxidative stress and induces repairing mechanisms in human cells. Sci Rep  2017; 7: 41215-27.
[http://dx.doi.org/10.1038/srep41215] [PMID:  28117410] 
[109] 
Dutta-Roy AK. Dietary components and human platelet activity. Platelets  2002; 13(2): 67-75.
[http://dx.doi.org/10.1080/09537100120111540] [PMID:  11897042] 
[110] 
Admasu TD, Chaithanya Batchu K, Barardo D, et al. Drug synergy slows aging and improves healthspan through IGF and SREBP lipid signaling. Dev Cell  2018; 47(1): 67-79.e5.
[http://dx.doi.org/10.1016/j.devcel.2018.09.001] [PMID:  30269951] 
[111] 
Ellsworth JL, Kushi LH, Folsom AR. Frequent nut intake and risk of death from coronary heart disease and all causes in postmenopausal women: The Iowa Women’s Health Study. Nutr Metab Cardiovasc Dis  2001; 11(6): 372-7.
[PMID:  12055701] 
[112] 
Fraser GE, Sabaté J, Beeson WL, Strahan TM. A possible protective effect of nut consumption on risk of coronary heart disease. The Adventist Health Study. Arch Intern Med  1992; 152(7): 1416-24.
[http://dx.doi.org/10.1001/archinte.1992.00400190054010] [PMID:  1627021] 
[113] 
Kushi LH, Meyer KA, Jacobs DR Jr. Cereals, legumes, and chronic disease risk reduction: Evidence from epidemiologic studies. Am J Clin Nutr  1999; 70(3)(Suppl.): 451S-8S.
[http://dx.doi.org/10.1093/ajcn/70.3.451s] [PMID:  10479217] 
[114] 
Baranowska M, Suliborska K, Chrzanowski W, Kusznierewicz B, Namieśnik J, Bartoszek A. The relationship between standard reduction potentials of catechins and biological activities involved in redox control. Redox Biol  2018; 17: 355-66.
[http://dx.doi.org/10.1016/j.redox.2018.05.005] [PMID:  29803149] 
[115] 
Ramiro E, Franch A, Castellote C, et al. Flavonoids from Theobroma cacao down-regulate inflammatory mediators. J Agric Food Chem  2005; 53(22): 8506-11.
[http://dx.doi.org/10.1021/jf0511042] [PMID:  16248545] 
[116] 
Ramiro-Puig E, Casadesús G, Lee HG, et al. Neuroprotective effect of cocoa flavonoids on in vitro oxidative stress. Eur J Nutr  2009; 48(1): 54-61.
[http://dx.doi.org/10.1007/s00394-008-0761-4] [PMID:  19043659] 
[117] 
Martín MA, Ramos S, Mateos R, et al. Protection of human HepG2 cells against oxidative stress by cocoa phenolic extract. J Agric Food Chem  2008; 56(17): 7765-72.
[http://dx.doi.org/10.1021/jf801744r] [PMID:  18680371] 
[118] 
Martín MA, Ramos S, Mateos R, Izquierdo-Pulido M, Bravo L, Goya L. Protection of human HepG2 cells against oxidative stress by the flavonoid epicatechin. Phytother Res  2010; 24(4): 503-9.
[PMID:  20041424] 
[119] 
Mattoli L, Mercati V, Burico M, et al. Experimental evidence of the presence of bimolecular caffeine/catechin complexes in green tea extracts. J Nat Prod  2018; 81(11): 2338-47.
[http://dx.doi.org/10.1021/acs.jnatprod.8b00168] [PMID:  30372064] 
[120] 
Colon M, Nerin C. Molecular interactions between caffeine and catechins in green tea. J Agric Food Chem  2014; 62(28): 6777-83.
[http://dx.doi.org/10.1021/jf5011287] [PMID:  24980214] 
[121] 
Meng Q, Li S, Huang J, et al. Importance of the nucleophilic property of tea polyphenols. J Agric Food Chem  2019; 67(19): 5379-83.
[http://dx.doi.org/10.1021/acs.jafc.8b05917] [PMID:  30406649] 
[122] 
Hamed I, Özogul F, Özogul Y, Regenstein JM. Marine bioactive compounds and their health benefits: A review. Compr Rev Food Sci Food Saf  2015; 14: 446-65.
[http://dx.doi.org/10.1111/1541-4337.12136] 
[123] 
Baci D, Gallazzi M, Cascini C, et al. Downregulation of pro-inflammatory and pro-angiogenic pathways in prostate cancer cells by a polyphenol-rich extract from olive mill wastewater. Int J Mol Sci  2019; 20(2): 307-24.
[http://dx.doi.org/10.3390/ijms20020307] [PMID:  30646518] 
[124] 
Bassani B, Rossi T, De Stefano D, et al. Potential chemopreventive activities of a polyphenol rich purified extract from olive mill wastewater on colon cancer cells. J Funct Foods  2016; 27: 236-48.
[http://dx.doi.org/10.1016/j.jff.2016.09.009] 
[125] 
Rossi T, Bassani B, Gallo C, et al. Effect of a Purified extract of olive mill waste water on endothelial cell proliferation, apoptosis, migration and capillary-like structure in vitro and in vivo. J Bioanal Biomed  2015; 12: 12-20.
[126] 
Vílchez C, Forján E, Cuaresma M, Bédmar F, Garbayo I, Vega JM. Marine carotenoids: Biological functions and commercial applications. Mar Drugs  2011; 9(3): 319-33.
[http://dx.doi.org/10.3390/md9030319] [PMID:  21556162] 
[127] 
Jacobs DR. Challenges in research in nutritional epidemiology
	Nutritional health: Strategies for disease prevention 2nd ed 2006; 25-35.
[128] 
Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PS. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med  1998; 64(4): 353-6.
[http://dx.doi.org/10.1055/s-2006-957450] [PMID:  9619120] 
[129] 
Suresh D, Srinivasan K. Tissue distribution & elimination of capsaicin, piperine & curcumin following oral intake in rats. Indian J Med Res  2010; 131: 682-91.
[PMID:  20516541] 
[130] 
Zeng X, Cai D, Zeng Q, et al. Selective reduction in the expression of UGTs and SULTs, a novel mechanism by which piperine enhances the bioavailability of curcumin in rat. Biopharm Drug Dispos  2017; 38(1): 3-19.
[http://dx.doi.org/10.1002/bdd.2049] [PMID:  27882569] 
[131] 
Khafif A, Schantz SP, Chou TC, Edelstein D, Sacks PG. Quantitation of chemopreventive synergism between (-)-epigallocatechin-3-gallate and curcumin in normal, premalignant and malignant human oral epithelial cells. Carcinogenesis  1998; 19(3): 419-24.
[http://dx.doi.org/10.1093/carcin/19.3.419] [PMID:  9525275] 
[132] 
Balasubramanian S, Eckert RL. Green tea polyphenol and curcumin inversely regulate human involucrin promoter activity via opposing effects on CCAAT/enhancer-binding protein function. J Biol Chem  2004; 279(23): 24007-14.
[http://dx.doi.org/10.1074/jbc.M314331200] [PMID:  15044435] 
[133] 
Eckert RL, Crish JF, Efimova T, Balasubramanian S. Opposing action of curcumin and green tea polyphenol in human keratinocytes. Mol Nutr Food Res  2006; 50(2): 123-9.
[http://dx.doi.org/10.1002/mnfr.200500125] [PMID:  16404707] 
[134] 
Johnson JJ, Nihal M, Siddiqui IA, et al. Enhancing the bioavailability of resveratrol by combining it with piperine. Mol Nutr Food Res  2011; 55(8): 1169-76.
[http://dx.doi.org/10.1002/mnfr.201100117] [PMID:  21714124] 
[135] 
Lewandowska A, Przychodzeń W, Kusznierewicz B, Kołodziejski D, Namieśnik J, Bartoszek A. Isothiocyanates may chemically detoxify mutagenic amines formed in heat processed meat. Food Chem  2014; 157: 105-10.
[http://dx.doi.org/10.1016/j.foodchem.2014.01.082] [PMID:  24679758] 
[136] 
Al-Hijazeen M, Lee EJ, Mendonca A, Ahn DU. Effect of oregano essential oil (Origanum vulgare subsp. hirtum) on the storage stability and quality parameters of ground chicken breast meat. Antioxidants  2016; 5(2): 2076-3921.
[http://dx.doi.org/10.3390/antiox5020018] [PMID:  27338486] 
[137] 
Podsędek A, Redzynia M, Klewicka E, Koziołkiewicz M. Matrix effects on the stability and antioxidant activity of red cabbage anthocyanins under simulated gastrointestinal digestion. BioMed Res Int  2014; 2014365738
[http://dx.doi.org/10.1155/2014/365738] [PMID:  24575407] 
[138] 
Tynek M, Szukalska E, Bartoszek A. Influence of cabbage juices on oxidative changes of rapeseed oil and lard. Eur J Lipid Sci Technol  2009; 111: 1142-9.
[http://dx.doi.org/10.1002/ejlt.200800021] 
[139] 
Kato T, Michikoshi K, Minowa Y, Maeda Y, Kikugawa K. Mutagenicity of cooked hamburger is reduced by addition of onion to ground beef. Mutat Res  1998; 420(1-3): 109-14.
[http://dx.doi.org/10.1016/S1383-5718(98)00151-X] [PMID:  9838070] 
[140] 
Peters CM, Green RJ, Janle EM, Ferruzzi MG. Formulation with ascorbic acid and sucrose modulates catechin bioavailability from green tea. Food Res Int  2010; 43(1): 95-102.
[http://dx.doi.org/10.1016/j.foodres.2009.08.016] [PMID:  20161530] 
[141] 
Brahmbhatt M, Gundala SR, Asif G, Shamsi SA, Aneja R. Ginger phytochemicals exhibit synergy to inhibit prostate cancer cell proliferation. Nutr Cancer  2013; 65(2): 263-72.
[http://dx.doi.org/10.1080/01635581.2013.749925] [PMID:  23441614] 
[142] 
Gautam S, Platel K, Srinivasan K. Influence of β-carotene-rich vegetables on the bioaccessibility of zinc and iron from food grains. Food Chem  2010; 122: 668-72.
[http://dx.doi.org/10.1016/j.foodchem.2010.03.028] 
[143] 
Veda S, Platel K, Srinivasan K. Varietal differences in the bioaccessibility of β-carotene from mango (Mangifera indica) and papaya (Carica papaya) fruits. J Agric Food Chem  2007; 55(19): 7931-5.
[http://dx.doi.org/10.1021/jf0712604] [PMID:  17715885] 
[144] 
Giovannucci E. A review of epidemiologic studies of tomatoes, lycopene, and prostate cancer. Exp Biol Med (Maywood)  2002; 227(10): 852-9.
[http://dx.doi.org/10.1177/153537020222701003] [PMID:  12424325] 
[145] 
Canene-Adams K, Lindshield BL, Wang S, Jeffery EH, Clinton SK, Erdman JW Jr. Combinations of tomato and broccoli enhance antitumor activity in dunning r3327-h prostate adenocarcinomas. Cancer Res  2007; 67(2): 836-43.
[http://dx.doi.org/10.1158/0008-5472.CAN-06-3462] [PMID:  17213256] 
[146] 
Keck AS, Qiao Q, Jeffery EH. Food matrix effects on bioactivity of broccoli-derived sulforaphane in liver and colon of F344 rats. J Agric Food Chem  2003; 51(11): 3320-7.
[http://dx.doi.org/10.1021/jf026189a] [PMID:  12744661] 
[147] 
Liu Y, Liu M, Chen Q, et al. Blueberry polyphenols ameliorate visible light and lipid-induced injury of retinal pigment epithelial cells. J Agric Food Chem  2018; 66(48): 12730-40.
[http://dx.doi.org/10.1021/acs.jafc.8b05272] [PMID:  30411897] 
[148] 
Moon H, Rhee MS. Synergism between carvacrol or thymol increases the antimicrobial efficacy of soy sauce with no sensory impact. Int J Food Microbiol 2016; 217: 35-41.induced hepatotoxicity: A comprehensive update. J Clin Transl Hepatol  2016; 4: 131-42.
[149] 
Hardman WE. Walnuts have potential for cancer prevention and treatment in mice. J Nutr  2014; 144(4)(Suppl.): 555S-60S.
[http://dx.doi.org/10.3945/jn.113.188466] [PMID:  24500939] 
[150] 
Jensen GS, Attridge VL, Benson KF, Beaman JL, Carter SG, Ager D. Consumption of dried apple peel powder increases joint function and range of motion. J Med Food  2014; 17(11): 1204-13.
[http://dx.doi.org/10.1089/jmf.2014.0037] [PMID:  25271471] 
[151] 
Jaganathan SK, Vellayappan MV, Narasimhan G, et al. Chemopreventive effect of apple and berry fruits against colon cancer. World J Gastroenterol  2014; 20(45): 17029-36.
[http://dx.doi.org/10.3748/wjg.v20.i45.17029] [PMID:  25493015] 
[152] 
Seeram NP, Adams LS, Henning SM, et al. In vitro antiproliferative, apoptotic and antioxidant activities of punicalagin, ellagic acid and a total pomegranate tannin extract are enhanced in combination with other polyphenols as found in pomegranate juice. J Nutr Biochem  2005; 16(6): 360-7.
[http://dx.doi.org/10.1016/j.jnutbio.2005.01.006] [PMID:  15936648] 
[153] 
Sansone C, Galasso C, Orefice I, et al. The green microalga Tetraselmis suecica reduces oxidative stress and induces repairing mechanisms in human cells. Sci Rep  2017; 7: 41215.
[http://dx.doi.org/10.1038/srep41215] [PMID:  28117410] 
[154] 
Jacobs DR Jr, Gross MD, Tapsell LC. Food synergy: An operational concept for understanding nutrition. Am J Clin Nutr  2009; 89(5): 1543S-8S.
[http://dx.doi.org/10.3945/ajcn.2009.26736B] [PMID:  19279083] 
[155] 
Koss-Mikołajczyk I, Kusznierewicz B, Wiczkowski W, Sawicki T, Bartoszek A. The comparison of betalain composition and chosen biological activities for differently pigmented prickly pear (Opuntia ficus-indica) and beetroot (Beta vulgaris) varieties. Int J Food Sci Nutr  2019; 70(4): 442-52.
[http://dx.doi.org/10.1080/09637486.2018.1529148] [PMID:  30632828] 
Cite As
Current Pharmaceutical Design

Prophylaxis of Non-communicable Diseases: Why Fruits and Vegetables may be Better Chemopreventive Agents than Dietary Supplements Based on Isolated Phytochemicals?

Abstract
