Nutraceuticals and Oral Supplements in Cancer Prevention: A Narrative Review

Page: [1021 - 1031] Pages: 11

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Abstract

Background: Epidemiological studies have shown that food is a compelling means of maintaining a state of well-being and preventing diseases. Many malignant diseases are related to nutrition, and the nutrient-organism interaction could define the balance between health and disease. Nutrients and dietary components influence epigenetic phenomena and modify drug response so that food-organism interactions may influence individual predisposition to disease and its potential therapeutic response.

Aims: In this review, we highlighted emerging opinions and data on a large cluster of nutraceuticals, as well as functional foods and specific dietary patterns, with respect to cancer, including breast, pancreas, prostate, and colorectal. Only those nutraceuticals and nutritional supplements yielding sufficient and convincing data have been reported in this review; molecules with inconclusive clinical evidence will not be discussed.

Conclusion: Growing and accumulating evidence is validating the use of nutraceuticals in cancer settings. However, a knowledge gap remains in terms of causal evidence for several compounds where a window for further clinical studies is left.

Keywords: Cancer, nutraceuticals, diet, supplementation, functional foods, dietary patterns.

Graphical Abstract

[1]
Díaz, G.D.; Paraskeva, C.; Thomas, M.G.; Binderup, L.; Hague, A. Apoptosis is induced by the active metabolite of vitamin D3 and its analogue EB1089 in colorectal adenoma and carcinoma cells: Possible implications for prevention and therapy. Cancer Res., 2000, 60(8), 2304-2312.
[PMID: 10786699]
[2]
Scaglione-Sewell, B.A.; Bissonnette, M.; Skarosi, S.; Abraham, C.; Brasitus, T.A. A vitamin D3 analog induces a G1-phase arrest in CaCo-2 cells by inhibiting cdk2 and cdk6: Roles of cyclin E, p21Waf1, and p27Kip1. Endocrinology, 2000, 141(11), 3931-3939.
[http://dx.doi.org/10.1210/endo.141.11.7782] [PMID: 11089522]
[3]
Yuan, C.; Sato, K.; Hollis, B.W.; Zhang, S.; Niedzwiecki, D.; Ou, F.S.; Chang, I.W.; O’Neil, B.H.; Innocenti, F.; Lenz, H.J.; Blanke, C.D.; Goldberg, R.M.; Venook, A.P.; Mayer, R.J.; Fuchs, C.S.; Meyerhardt, J.A.; Ng, K. Plasma 25-hydroxyvitamin D levels and survival in patients with advanced or metastatic colorectal cancer: Findings from CALGB/SWOG 80405 (Alliance). Clin. Cancer Res., 2019, 25(24), 7497-7505.
[http://dx.doi.org/10.1158/1078-0432.CCR-19-0877] [PMID: 31548349]
[4]
Kennel, K.A.; Drake, M.T. Vitamin D in the cancer patient. Curr. Opin. Support. Palliat. Care, 2013, 7(3), 272-277.
[http://dx.doi.org/10.1097/SPC.0b013e3283640f74] [PMID: 23912386]
[5]
Ng, K.; Nimeiri, H.S.; McCleary, N.J.; Abrams, T.A.; Yurgelun, M.B.; Cleary, J.M.; Rubinson, D.A.; Schrag, D.; Miksad, R.; Bullock, A.J.; Allen, J.; Zuckerman, D.; Chan, E.; Chan, J.A.; Wolpin, B.M.; Constantine, M.; Weckstein, D.J.; Faggen, M.A.; Thomas, C.A.; Kournioti, C.; Yuan, C.; Ganser, C.; Wilkinson, B.; Mackintosh, C.; Zheng, H.; Hollis, B.W.; Meyerhardt, J.A.; Fuchs, C.S. Effect of high-dose vs standard-dose vitamin D3 supplementation on progression-free survival among patients with advanced or metastatic colorectal cancer: The SUNSHINE randomized clinical trial. JAMA, 2019, 321(14), 1370-1379.
[http://dx.doi.org/10.1001/jama.2019.2402] [PMID: 30964527]
[6]
Alkan, A.; Köksoy, E.B. Vitamin D deficiency in cancer patients and predictors for screening (D-ONC study). Curr. Probl. Cancer, 2019, 43(5), 421-428.
[http://dx.doi.org/10.1016/j.currproblcancer.2018.12.008] [PMID: 30683325]
[7]
Chandler, P.D.; Chen, W.Y.; Ajala, O.N.; Hazra, A.; Cook, N.; Bubes, V.; Lee, I-M.; Giovannucci, E.L.; Willett, W.; Buring, J.E.; Manson, J.E. VITAL Research Group. Effect of Vitamin D3 supplements on development of advanced cancer. A secondary analysis of the VITAL randomized clinical trial. JAMA Network Open, 2020, 3(11), e2025850.
[8]
Han, J.; Guo, X.; Yu, X.; Liu, S.; Cui, X.; Zhang, B.; Liang, H. 25-hydroxyvitamin D and total cancer incidence and mortality: A meta-analysis of prospective cohort studies. Nutrients, 2019, 11(10), E2295.
[http://dx.doi.org/10.3390/nu11102295] [PMID: 31561503]
[9]
Manson, J.E.; Cook, N.R.; Lee, I.M. VITAL Research Group. Vitamin D supplements and prevention of cancer and cardiovascular disease. Engl J Med, 2019, 380(1), 33-44.
[http://dx.doi.org/10.1056/NEJMoa1809944]
[10]
Passarelli, M.N.; Karagas, M.R.; Mott, L.A.; Rees, J.R.; Barry, E.L.; Baron, J.A. Risk of keratinocyte carcinomas with vitamin D and calcium supplementation: A secondary analysis of a randomized clinical trial. Am. J. Clin. Nutr., 2020, 112(6), 1532-1539.
[http://dx.doi.org/10.1093/ajcn/nqaa267] [PMID: 33022713]
[11]
Pawlowska, E.; Szczepanska, J.; Blasiak, J. Pro- and antioxidant effects of vitamin C in cancer in correspondence to its dietary and pharmacological concentrations. Oxid. Med. Cell. Longev., 2019, 2019, 7286737.
[http://dx.doi.org/10.1155/2019/7286737]
[12]
Yang, C.S.; Luo, P.; Zeng, Z.; Wang, H.; Malafa, M.; Suh, N. Vitamin E and cancer prevention: Studies with different forms of tocopherols and tocotrienols. Mol. Carcinog., 2020, 59(4), 365-389.
[http://dx.doi.org/10.1002/mc.23160] [PMID: 32017273]
[13]
Zeng, Y.; Du, Q.; Zhang, Z.; Ma, J.; Han, L.; Wang, Y.; Yang, L.; Tao, N.; Qin, Z. Curcumin promotes cancer-associated fibroblasts apoptosis via ROS-mediated endoplasmic reticulum stress. Arch. Biochem. Biophys., 2020, 694, 108613.
[http://dx.doi.org/10.1016/j.abb.2020.108613] [PMID: 33010228]
[14]
Talib, W.H.; Alsayed, A.R.; Farhan, F.; Al Kury, L.T. Resveratrol and tumor microenvironment: Mechanistic basis and therapeutic targets. Molecules, 2020, 25(18), 4282.
[http://dx.doi.org/10.3390/molecules25184282] [PMID: 32961987]
[15]
Weinberg, S.E.; Sun, L.Y.; Yang, A.L.; Liao, J.; Yang, G.Y. Overview of inositol and inositol phosphates on chemoprevention of colitis-induced carcinogenesis. Molecules, 2020, 26(1), 31.
[http://dx.doi.org/10.3390/molecules26010031] [PMID: 33374769]
[16]
Puah, B.P.; Jalil, J.; Attiq, A.; Kamisah, Y. New insights into molecular mechanism behind anti-cancer activities of lycopene. Molecules, 2021, 26(13), 3888.
[http://dx.doi.org/10.3390/molecules26133888] [PMID: 34202203]
[17]
Kim, Y.; Kim, J. N-6 polyunsaturated fatty acids and risk of cancer: Accumulating evidence from prospective studies. Nutrients, 2020, 12(9), 2523.
[http://dx.doi.org/10.3390/nu12092523] [PMID: 32825393]
[18]
Lee, K.H.; Seong, H.J.; Kim, G.; Jeong, G.H.; Kim, J.Y.; Park, H.; Jung, E.; Kronbichler, A.; Eisenhut, M.; Stubbs, B.; Solmi, M.; Koyanagi, A.; Hong, S.H.; Dragioti, E.; de Rezende, L.F.M.; Jacob, L.; Keum, N.; van der Vliet, H.J.; Cho, E.; Veronese, N.; Grosso, G.; Ogino, S.; Song, M.; Radua, J.; Jung, S.J.; Thompson, T.; Jackson, S.E.; Smith, L.; Yang, L.; Oh, H.; Choi, E.K.; Shin, J.I.; Giovannucci, E.L.; Gamerith, G. Consumption of fish and omega-3 fatty acids and cancer risk: An umbrella review of meta-analyses of observational studies. Adv. Nutr., 2020, 11(5), 1134-1149.
[http://dx.doi.org/10.1093/advances/nmaa055] [PMID: 32488249]
[19]
Thilakarathna, W.P.D.W.; Rupasinghe, H.P.V.; Ridgway, N.D.; Thilakarathna, W.P.D.W. Mechanisms by which probiotic bacteria attenuate the risk of hepatocellular carcinoma. Int. J. Mol. Sci., 2021, 22(5), 2606.
[http://dx.doi.org/10.3390/ijms22052606] [PMID: 33807605]
[20]
Molska, M.; Reguła, J. Potential mechanisms of probiotics action in the prevention and treatment of colorectal cancer. Nutrients, 2019, 11(10), 2453.
[http://dx.doi.org/10.3390/nu11102453] [PMID: 31615096]
[21]
Cruz, B.C.S.; Sarandy, M.M.; Messias, A.C.; Gonçalves, R.V.; Ferreira, C.L.L.F.; Peluzio, M.C.G. Preclinical and clinical relevance of probiotics and synbiotics in colorectal carcinogenesis: A systematic review. Nutr. Rev., 2020, 78(8), 667-687.
[http://dx.doi.org/10.1093/nutrit/nuz087] [PMID: 31917829]
[22]
Fong, W.; Li, Q.; Yu, J. Gut microbiota modulation: A novel strategy for prevention and treatment of colorectal cancer. Oncogene, 2020, 39(26), 4925-4943.
[http://dx.doi.org/10.1038/s41388-020-1341-1] [PMID: 32514151]
[23]
Rodriguez-Arrastia, M.; Martinez-Ortigosa, A.; Rueda-Ruzafa, L.; Folch Ayora, A.; Ropero-Padilla, C.; Rodriguez-Arrastia, M. Probiotic supplements on oncology patients’ treatment-related side effects: A systematic review of randomized controlled trials. Int. J. Environ. Res. Public Health, 2021, 18(8), 4265.
[http://dx.doi.org/10.3390/ijerph18084265] [PMID: 33920572]
[24]
Devarajan, N.; Jayaraman, S.; Mahendra, J.; Venkatratnam, P.; Rajagopal, P.; Palaniappan, H.; Ganesan, S.K.; Devarajan, N. Berberine-A potent chemosensitizer and chemoprotector to conventional cancer therapies. Phytother. Res., 2021, 35(6), 3059-3077.
[http://dx.doi.org/10.1002/ptr.7032] [PMID: 33559280]
[25]
Mali, A.V.; Padhye, S.B.; Anant, S.; Hegde, M.V.; Kadam, S.S. Anticancer and antimetastatic potential of enterolactone: Clinical, preclinical and mechanistic perspectives. Eur. J. Pharmacol., 2019, 852, 107-124.
[http://dx.doi.org/10.1016/j.ejphar.2019.02.022] [PMID: 30771348]
[26]
Cutone, A.; Rosa, L.; Ianiro, G.; Lepanto, M.S.; Bonaccorsi di Patti, M.C.; Valenti, P.; Musci, G. Lactoferrin’s anti-cancer properties: Safety, selectivity, and wide range of action. Biomolecules, 2020, 10(3), 456.
[http://dx.doi.org/10.3390/biom10030456]
[27]
O’Neill, E.J.; Termini, D.; Albano, A.; Tsiani, E. Anti-cancer properties of theaflavins. Molecules, 2021, 26(4), 987.
[http://dx.doi.org/10.3390/molecules26040987] [PMID: 33668434]
[28]
Imran, M.; Rauf, A.; Shah, Z.A.; Saeed, F.; Imran, A.; Arshad, M.U.; Ahmad, B.; Bawazeer, S.; Atif, M.; Peters, D.G.; Mubarak, M.S. Chemo-preventive and therapeutic effect of the dietary flavonoid kaempferol: A comprehensive review. Phytother. Res., 2019, 33(2), 263-275.
[http://dx.doi.org/10.1002/ptr.6227] [PMID: 30402931]
[29]
Li, Y.; Li, S.; Meng, X.; Gan, R.Y.; Zhang, J.J.; Li, H.B. Dietary natural products for prevention and treatment of breast cancer. Nutrients, 2017, 9(7), 728.
[http://dx.doi.org/10.3390/nu9070728] [PMID: 28698459]
[30]
Mokbel, K.; Mokbel, K. Chemoprevention of breast cancer with vitamins and micronutrients: A concise review. In Vivo, 2019, 33(4), 983-997.
[http://dx.doi.org/10.21873/invivo.11568] [PMID: 31280187]
[31]
Hossain, S.; Beydoun, M.A.; Beydoun, H.A.; Chen, X.; Zonderman, A.B.; Wood, R.J. Vitamin D and breast cancer: A systematic review and meta-analysis of observational studies. Clin. Nutr. ESPEN, 2019, 30, 170-184.
[http://dx.doi.org/10.1016/j.clnesp.2018.12.085] [PMID: 30904218]
[32]
Ren, X.; Xu, P.; Zhang, D.; Liu, K.; Song, D.; Zheng, Y.; Yang, S.; Li, N.; Hao, Q.; Wu, Y.; Zhai, Z.; Kang, H.; Dai, Z. Association of folate intake and plasma folate level with the risk of breast cancer: A dose-response meta-analysis of observational studies. Aging (Albany NY), 2020, 12(21), 21355-21375.
[http://dx.doi.org/10.18632/aging.103881] [PMID: 33146633]
[33]
Dell’Acqua, G; Richards, A; Thornton, MJ The potential role of nutraceuticals as an adjuvant in breast cancer patients to prevent hair loss induced by endocrine therapy. Nutrients, 2020, 12(11), 3537.
[http://dx.doi.org/10.3390/nu12113537]
[34]
Xie, M.; Liu, J.; Tsao, R.; Wang, Z.; Sun, B.; Wang, J. Whole grain consumption for the prevention and treatment of breast cancer. Nutrients, 2019, 11(8), 1769.
[http://dx.doi.org/10.3390/nu11081769] [PMID: 31374888]
[35]
Chapelle, N.; Martel, M.; Toes-Zoutendijk, E.; Barkun, A.N.; Bardou, M. Recent advances in clinical practice: Colorectal cancer chemoprevention in the average-risk population. Gut, 2020, 69(12), 2244-2255.
[http://dx.doi.org/10.1136/gutjnl-2020-320990] [PMID: 32989022]
[36]
Wang, X.; Yang, D.Y.; Yang, L.Q.; Zhao, W.Z.; Cai, L.Y.; Shi, H.P. Anthocyanin consumption and risk of colorectal cancer: A meta-analysis of observational studies. J. Am. Coll. Nutr., 2019, 38(5), 470-477.
[http://dx.doi.org/10.1080/07315724.2018.1531084] [PMID: 30589398]
[37]
Ben, S.; Du, M.; Ma, G.; Qu, J.; Zhu, L.; Chu, H.; Zhang, Z.; Wu, Y.; Gu, D.; Wang, M. Vitamin B2 intake reduces the risk for colorectal cancer: A dose-response analysis. Eur. J. Nutr., 2019, 58(4), 1591-1602.
[http://dx.doi.org/10.1007/s00394-018-1702-5] [PMID: 29744609]
[38]
Zhang, L.; Zou, H.; Zhao, Y.; Hu, C.; Atanda, A.; Qin, X.; Jia, P.; Jiang, Y.; Qi, Z. Association between blood circulating vitamin D and colorectal cancer risk in Asian countries: A systematic review and dose-response meta-analysis. BMJ Open, 2019, 9(12), e030513.
[http://dx.doi.org/10.1136/bmjopen-2019-030513] [PMID: 31874870]
[39]
Fontana, F.; Raimondi, M.; Marzagalli, M.; Di Domizio, A.; Limonta, P. Natural compounds in prostate cancer prevention and treatment: Mechanisms of action and molecular targets. Cells, 2020, 9(2), 460.
[http://dx.doi.org/10.3390/cells9020460] [PMID: 32085497]
[40]
Liu, Y.; Wang, X.; Sun, X.; Lu, S.; Liu, S. Vitamin intake and pancreatic cancer risk reduction: A meta-analysis of observational studies. Medicine (Baltimore), 2018, 97(13), e0114.
[http://dx.doi.org/10.1097/MD.0000000000010114] [PMID: 29595633]
[41]
Li, L.; Gai, X. The association between dietary zinc intake and risk of pancreatic cancer: A meta-analysis. Biosci. Rep., 2017, 37(3), BSR20170155.
[http://dx.doi.org/10.1042/BSR20170155]
[42]
Divella, R.; Daniele, A.; Savino, E.; Paradiso, A. Anticancer effects of nutraceuticals in the Mediterranean diet: An epigenetic diet model. Cancer Genom. Proteom., 2020, 17(4), 335-350.
[http://dx.doi.org/10.21873/cgp.20193] [PMID: 32576579]
[43]
Reboredo-Rodríguez, P.; Varela-López, A.; Forbes-Hernández, T.Y.; Gasparrini, M.; Afrin, S.; Cianciosi, D.; Zhang, J.; Manna, P.P.; Bompadre, S.; Quiles, J.L.; Battino, M.; Giampieri, F. Phenolic compounds isolated from olive oil as nutraceutical tools for the prevention and management of cancer and cardiovascular diseases. Int. J. Mol. Sci., 2018, 19(8), 2305.
[http://dx.doi.org/10.3390/ijms19082305] [PMID: 30082650]
[44]
Emma, M.R.; Augello, G.; Di Stefano, V.; Azzolina, A.; Giannitrapani, L.; Montalto, G.; Cervello, M.; Cusimano, A. Potential uses of olive oil secoiridoids for the prevention and treatment of cancer: A narrative review of preclinical studies. Int. J. Mol. Sci., 2021, 22(3), 1234.
[http://dx.doi.org/10.3390/ijms22031234] [PMID: 33513799]
[45]
Merra, G.; Noce, A.; Marrone, G.; Cintoni, M.; Tarsitano, M.G.; Capacci, A.; De Lorenzo, A. De Lorenzo. A. Influence of Mediterranean diet on human gut microbiota. Nutrients, 2020, 13(1), 7.
[http://dx.doi.org/10.3390/nu13010007] [PMID: 33375042]
[46]
Zhang, K.; Dai, H.; Liang, W.; Zhang, L.; Deng, Z. Fermented dairy foods intake and risk of cancer. Int. J. Cancer, 2019, 144(9), 2099-2108.
[http://dx.doi.org/10.1002/ijc.31959] [PMID: 30374967]
[47]
Sharifi, M.; Moridnia, A.; Mortazavi, D.; Salehi, M.; Bagheri, M.; Sheikhi, A. Kefir: A powerful probiotics with anticancer properties. Med. Oncol., 2017, 34(11), 183.
[http://dx.doi.org/10.1007/s12032-017-1044-9] [PMID: 28956261]
[48]
Law, B.M.H.; Waye, M.M.Y.; So, W.K.W.; Chair, S.Y. Hypotheses on the potential of rice bran intake to prevent gastrointestinal cancer through the modulation of oxidative stress. Int. J. Mol. Sci., 2017, 18(7), 1352.
[http://dx.doi.org/10.3390/ijms18071352] [PMID: 28672811]
[49]
Villa-Rivera, M.G.; Ochoa-Alejo, N. Chili pepper carotenoids: Nutraceutical properties and mechanisms of action. Molecules, 2020, 25(23), 5573.
[http://dx.doi.org/10.3390/molecules25235573] [PMID: 33260997]
[50]
Shin, J.; Song, M.H.; Oh, J.W.; Keum, Y.S.; Saini, R.K. Pro-oxidant actions of carotenoids in triggering apoptosis of cancer cells: A review of emerging evidence. Antioxidants, 2020, 9(6), 532.
[http://dx.doi.org/10.3390/antiox9060532] [PMID: 32560478]
[51]
Rowles, J.L., III; Erdman, J.W., Jr Carotenoids and their role in cancer prevention. Biochim. Biophys. Acta Mol. Cell Biol. Lipids, 2020, 1865(11), 158613.
[http://dx.doi.org/10.1016/j.bbalip.2020.158613] [PMID: 31935448]
[52]
Saini, R.K.; Keum, Y.S.; Daglia, M.; Rengasamy, K.R. Dietary carotenoids in cancer chemoprevention and chemotherapy: A review of emerging evidence. Pharmacol. Res., 2020, 157, 104830.
[http://dx.doi.org/10.1016/j.phrs.2020.104830] [PMID: 32344050]
[53]
Koklesova, L.; Liskova, A.; Samec, M.; Buhrmann, C.; Samuel, S.M.; Varghese, E.; Ashrafizadeh, M.; Najafi, M.; Shakibaei, M.; Büsselberg, D.; Giordano, F.A.; Golubnitschaja, O.; Kubatka, P. Carotenoids in cancer apoptosis-The road from bench to bedside and back. Cancers (Basel), 2020, 12(9), 2425.
[http://dx.doi.org/10.3390/cancers12092425] [PMID: 32859058]
[54]
Paśko, P.; Galanty, A.; Zagrodzki, P.; Luksirikul, P.; Barasch, D.; Nemirovski, A.; Gorinstein, S. Dragon fruits as a reservoir of natural polyphenolics with chemopreventive properties. Molecules, 2021, 26(8), 2158.
[http://dx.doi.org/10.3390/molecules26082158] [PMID: 33918584]
[55]
Fonseca, L.R.S.; Silva, G.R.; Luís, Â.; Cardoso, H.J.; Correia, S.; Vaz, C.V.; Duarte, A.P.; Socorro, S. Sweet cherries as anti-cancer agents: From bioactive compounds to function. Molecules, 2021, 26(10), 2941.
[http://dx.doi.org/10.3390/molecules26102941] [PMID: 34063349]
[56]
Mantzorou, M.; Zarros, A.; Vasios, G.; Theocharis, S.; Pavlidou, E.; Giaginis, C. Cranberry: A promising natural source of potential nutraceuticals with anticancer activity. Anticancer. Agents Med. Chem., 2019, 19(14), 1672-1686.
[http://dx.doi.org/10.2174/1871520619666190704163301] [PMID: 31272361]