Reactive oxygen species (ROS) are by-products of metabolism that increase in the body during inflammation, smoking, and exposure to agents such as radiation and certain drugs. ROS cause damage to DNA and other molecules, and they are implicated in the development and progression of cancer. Antioxidants from endogenous and dietary sources can neutralize and destroy ROS and may play a role in cancer prevention. Experimental and animal studies have shown that treatment with single or combined antioxidants prevents neoplastic transformation of normal cells and inhibits tumor growth. Human observational studies suggest that high intake of antioxidant-rich foods, notably fruits, vegetables, and grains, is inversely related to cancer risk. However, prospective human studies that began to accrue data in the 1990s did not always confirm this relationship. Randomized, controlled clinical trials using specific antioxidant supplementation have also produced mixed results, but study limitations and confounding factors often make it difficult to derive definitive conclusions. Antioxidant supplementation during cancer treatment remains controversial. Radiotherapy and certain chemotherapeutic agents rely on ROS to destroy cancer cells. Although antioxidant supplementation may help protect normal cells from ROS damage and may have palliative effects during cancer treatment, studies suggest that cancer cells may also be protected from ROS damage, thereby reducing treatment efficacy and patient survival. This article reviews evidence for the impact of antioxidant supplementation and antioxidant-rich diets on cancer risk and mortality. It also outlines some of the factors that may have contributed to the conflicting outcomes reported.
American Cancer Society. Cancer Statistics Center: 2017 estimates. Atlanta, GA: American Cancer Society. Available from: https://cancerstatisticscenter.cancer.org/#/
Hassan W, Noreen H, Rheman S, et al. Oxidative stress and antioxidants potential of one hundred medicinal plants. Curr Top Med Chem. 2017; 17:1336–70.
Valko M, Izakovic M, Mazur M, et al. Role of oxygen radicals in DNA damage and cancer incidence. Mol Cell Biochem. 2004; 266:37–56.
Borek C. Free radical processes in multistage carcinogenesis. Free Radic Res Commun. 1991; 12–13:745–50.
Halliwell B. Free radicals and antioxidants: updating a personal view. Nutr Rev. 2012; 70:257–65.
Borek C, Ong A, Mason H, et al. Selenium and vitamin E inhibit radiogenic and chemical induced transformation in vitro via different mechanisms. Proc Natl Acad Sci USA. 1986; 83:1490–4.
Khanzode SS, Muddeshwar MG, Khanzode SD, et al. Antioxidant enzymes and lipid peroxidation in different stages of breast cancer. Free Radic Res. 2004; 38:81–5.
Steinmetz KA, Potter JD. Vegetables, fruit, and cancer prevention: a review. J Am Diet Assoc. 1996; 96:1027–39.
Borek C. Antioxidants and radiation therapy. J Nutr. 2004; 134:3207S–9S.
Lewenda BD, Kelly KM, Ladas EJ, et al. Should supplemental antioxidant administration be avoided during chemotherapy and radiation therapy? J Natl Cancer Inst. 2008; 100:773–83.
Borek C, Pardo F. Vitamin E and apoptosis: a dual role. In: Pasquier C, ed. Biennial Meeting of the Society for Free Radicals Research International: Paris, France July 16–20, 2002. Bologna, Italy: Medimond Inc. Monduzzi (Editore); 2002. pp. 327–31.
Sigounas G, Anagnostu A, Steiner M. dl-Alpha tocopherol induces apoptosis in erythroleukemia, prostate, and breast cancer cells. Nutr Cancer. 1997; 28:30–5.
Bairati I, Meyer F, Jobin E, et al. Antioxidant vitamins supplementation and mortality: a randomized trial in head and neck cancer patients. Int J Cancer. 2006; 119:2221–4.
Ma Y, Chapman J, Levine M, et al. High-dose parenteral ascorbate enhanced chemosensitivity of ovarian cancer and reduced toxicity of chemotherapy. Sci Transl Med. 2014; 6:222ra18.
Parrow NL, Leshin JA, Levin M. Parenteral ascorbate as a cancer therapeutic: a reassessment based on pharmacokinetics. Antioxid Redox Signal. 2013; 19:2141–56.
Kennedy M, Bruninga K, Mutlu EA, et al. Successful and sustained treatment of chronic radiation proctitis with antioxidant vitamins E and C. Am J Gastroenterol. 2001; 96:1080–4.
Willett WC. Fruits, vegetables, and cancer prevention: turmoil in the produce section. J Natl Cancer Inst. 2010; 102:510–1.
Turati F, Pelucchi C, Guercio V, et al. Allium vegetable intake and gastric cancer: a case-control study and meta-analysis. Mol Nutr Food Res. 2015; 59:171–9.
Boffeta P, Wichmann J, Ferrari P, 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; 102:529–37.
Griffiths K, Aggarwal BB, Singh RB, et al. Food antioxidants and their anti-inflammatory properties: a potential role in cardiovascular diseases and cancer prevention. Diseases. 2016; 4:E28.
George SM, Park KY, Leizmann MF, et al. Fruit and vegetables intake and risk of cancer: a prospective cohort study. Am J Clin Nutr. 2009; 89:347–53.
Vingeliene S, Chan DS, Aune D, et al. An update of WCRF/AICR systematic literature review on esophageal and gastric cancers and citrus fruits intake. Cancer Causes Control. 2016; 27:837–51.
Wu AH, Yu MC, Tseng CC, et al. Green tea and risk of breast cancer in Asian Americans. Int J Cancer. 2003; 106:574–9.
Graff RE, Patterson A, Lis RT. Dietary lycopene intake and risk of prostate cancer defined by ERG protein expression. Am J Clin Nutr. 2016; 103:851–60.
Davis CD, Tsuji PA, Milner JA. Selenoproteins and cancer prevention. Annu Rev Nutr. 2012; 32:73–95.
Weiss JF, Landauer MR. Protection against ionizing radiation by antioxidant nutrients and phytochemicals. Toxicology. 2003; 189:1–20.
Aslam R, Gibbons D, Ghezzi P. Online information on antioxidants: information quality indicators, commercial interests, and ranking by Google. Front Public Health. 2017; 5:90.
Patterson RE, White E, Kristal AR, et al. Vitamin supplements and cancer risk: the epidemiologic evidence. Cancer Causes Control. 1997; 8:786–802.
Blot WJ, Li JY, Taylor PR, et al. Nutrition intervention trials in Linxian, China: supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population. J Natl Cancer Inst. 1993; 85:1483–92.
Qiao YL, Dawsey SM, Kamangar F, et al. Total and cancer mortality after supplementation with vitamins and minerals: follow-up of the Linxian General Population Nutrition Intervention Trial [published erratum appears in J Natl Cancer Inst. 2010;102:140]. J Natl Cancer Inst. 2009; 101:507–18.
Virtamo J, Pientinen P, Huttunen JK, et al. Incidence of cancer and mortality following alpha-tocopherol and beta-carotene supplementation: a postintervention follow-up. J Am Med Assoc. 2003; 290:476–85.
Omenn GS, Goodman GE, Thorquist MD, et al. Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med. 1996; 334:1150–5.
Goodman GE, Thornquist MD, Balmes J, et al. The Beta-Carotene and Retinol Efficacy Trial: incidence of lung cancer and cardiovascular disease mortality during 6-year follow-up after stopping beta-carotene and retinol supplements. J Natl Cancer Inst. 2004; 96:1743–50.
Hennekens CH, Buring JE, Manson JE, et al. Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease. N Engl J Med. 1996; 334:1145–9.
Alpha Tocopherol, Beta Carotene Cancer Prevention Study Group. The effect of vitamin E and beta carotene on incidence of lung cancer and other cancers in male smokers. N Engl J Med. 1994; 330:1029–35.
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. J Am Med Assoc. 2009; 301:52–62.
Lee IM, Cook NR, Manson JE, et al. Beta-carotene supplementation and incidence of cancer and cardiovascular disease: the Women’s Health Study. J Natl Cancer Inst. 1999; 91:2102–6.
Lee IM, Cook NR, Graziano JM, et al. Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women’s Health Study: a randomized controlled trial. J Am Med Assoc. 2005; 294:56–65.
Clark LC, Combs GF Jr, Turnbull BW, et al. Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin: a randomized controlled trial. J Am Med Assoc. 1996; 276:1957–63.
Algotar AM, Stratton MS, Ahmann FR, et al. Phase 3 clinical trial investigating the effect of selenium supplementation in men at high risk for prostate cancer. Prostate. 2013; 73:328–35.
Helzlsouer KJ, Huang HY, Alberg AJ, et al. Association between alpha-tocopherol, gamma-tocopherol, selenium, and subsequent prostate cancer. J Natl Cancer Inst. 2000; 92:2018–23.
Li H, Stampfer MJ, Giovannucci EL, et al. A prospective study of plasma selenium levels and prostate cancer risk. J Natl Cancer Inst. 2004; 96:696–703.
Lippman SM, Klein EA, Goodman PJ, et al. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). J Am Med Assoc. 2009; 301:39–51.
Klein EA, Thompson IM Jr, Tangen CM, et al. Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). J Am Med Assoc. 2011; 306:1549–56.
Hercberg S, Galan P, Preziosi P, et al. The SU.VI.MAX study: a randomized, placebo-controlled trial of the health effects of antioxidant vitamins and minerals. Arch Intern Med. 2004; 164:2335–42.
Bouayed J, Bohn T. Exogenous antioxidants – double-edged sword in cellular redox state: health beneficial effects at physiologic doses versus deleterious effects at high doses. Oxid Med Cell Longev. 2010; 3:228–37.
Schwingshakl L, Hoffmann G. Does a Mediterranean-type diet reduce cancer risk? Curr Nutr Rep. 2016; 5:9–17.
Fortmann SP, Burda BU, Senger CA, et al. Vitamin and mineral supplements in the primary prevention of cardiovascular disease and cancer: an updated systematic evidence review for the U.S. Preventive Services Task Force. Ann Intern Med. 2013; 159:824–34.
Borek C. Antioxidants and cancer. Sci Med (Phila). 1997; 4:51–62.
Niki E, Noguchi N, Tsuchihashi H, Gotoh N. Interaction among vitamin C, vitamin E, and beta-carotene. Am J Clin Nutr. 1995; 62(6 Suppl):1322S–6S.
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