Skip to main content Accessibility help
×
Home
Hostname: page-component-684899dbb8-ndjvl Total loading time: 0.912 Render date: 2022-05-28T01:02:10.333Z Has data issue: true Feature Flags: { "shouldUseShareProductTool": true, "shouldUseHypothesis": true, "isUnsiloEnabled": true, "useRatesEcommerce": false, "useNewApi": true }

A review of the epidemiological evidence for the ‘antioxidant hypothesis’

Published online by Cambridge University Press:  02 January 2007

SA Stanner*
Affiliation:
British Nutrition Foundation, 52–54 High Holborn, London WC1V 6RQ, UK
J Hughes
Affiliation:
7 Holmesdale Park, Coopers Hill Road, Nuffield, Surrey, RH1 4NW, UK
CNM Kelly
Affiliation:
British Nutrition Foundation, 52–54 High Holborn, London WC1V 6RQ, UK
J Buttriss
Affiliation:
British Nutrition Foundation, 52–54 High Holborn, London WC1V 6RQ, UK
*
*Corresponding author: Email s.stanner@nutrition.org.uk
Rights & Permissions[Opens in a new window]

Abstract

HTML view is not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.
Objective:

The British Nutrition Foundation was recently commissioned by the Food Standards Agency to conduct a review of the government's research programme on Antioxidants in Food. Part of this work involved an independent review of the scientific literature on the role of antioxidants in chronic disease prevention, which is presented in this paper.

Background:

There is consistent evidence that diets rich in fruit and vegetables and other plant foods are associated with moderately lower overall mortality rates and lower death rates from cardiovascular disease and some types of cancer. The ‘antioxidant hypothesis’ proposes that vitamin C, vitamin E, carotenoids and other antioxidant nutrients afford protection against chronic diseases by decreasing oxidative damage.

Results:

Although scientific rationale and observational studies have been convincing, randomised primary and secondary intervention trials have failed to show any consistent benefit from the use of antioxidant supplements on cardiovascular disease or cancer risk, with some trials even suggesting possible harm in certain subgroups. These trials have usually involved the administration of single antioxidant nutrients given at relatively high doses. The results of trials investigating the effect of a balanced combination of antioxidants at levels achievable by diet are awaited.

Conclusion:

The suggestion that antioxidant supplements can prevent chronic diseases has not been proved or consistently supported by the findings of published intervention trials. Further evidence regarding the efficacy, safety and appropriate dosage of antioxidants in relation to chronic disease is needed. The most prudent public health advice remains to increase the consumption of plant foods, as such dietary patterns are associated with reduced risk of chronic disease.

Type
Research Article
Copyright
Copyright © CAB International 2004

References

1Department of Health. Nutritional Aspects of Cardiovascular Disease. London: HMSO, 1994.Google Scholar
2Department of Health. Nutritional Aspects of the Development of Cancer. London: The Stationery Office, 1998.Google Scholar
3Goldberg, J, Flowerdew, G, Smith, E, Brody, J, Tso, M. Factors associated with age-related macular degeneration: an analysis of data from the first National Health and Nutrition Examination Survey. American Journal of Epidemiology 1998; 128: 700–10.CrossRefGoogle Scholar
4Mares-Perlman, J, Brady, WE, Klein, BE, Klein, R, Haus, GJ, Palta, M, et al. Diet and nuclear lens opacities. American Journal of Epidemiology 1995; 141: 322–34.CrossRefGoogle ScholarPubMed
5Brown, L, Rimm, EB, Seddon, JM, Giovannucci, EL, Chasan-Taber, L, Spiegelman, D, et al. A prospective study of carotenoid intake and risk of cataract extraction among US men. American Journal of Clinical Nutrition 1999; 70: 517–24.CrossRefGoogle ScholarPubMed
6Miedema, I, Feskens, EJ, Heederik, D, Kromhout, D. Dietary determinants of long-term incidence of chronic nonspecific lung diseases. The Zutphen Study. American Journal of Epidemiology 1993; 138: 3745.CrossRefGoogle ScholarPubMed
7La Vecchia, C, Decarli, A, Pagano, R. Vegetable consumption and risk of chronic disease. Epidemiology 1998; 9: 208–10.CrossRefGoogle ScholarPubMed
8Poulsen, H, Hensen, B, Weimann, A, Hensen, SA, Sorensen, M, Loft, S. Antioxidants, DNA damage and gene expression. Free Radical Research 2000; 33: S339.Google ScholarPubMed
9Steinberg, D. Low density lipoprotein oxidation and its pathobiological significance. Journal of Biological Chemistry 1997; 272(34): 20963–6.CrossRefGoogle ScholarPubMed
10Gey, K, Puska, P, Jordan, P, Moser, U. Inverse correlation between plasma vitamin E and mortality from ischemic heart disease in cross-cultural epidemiology. American Journal of Clinical Nutrition 1991; 53(Suppl. 1): 326S–34S.CrossRefGoogle ScholarPubMed
11Su, L, Bui, M, Kardinaal, A, Gomez-Aracena, J, Martin-Moreno, J, Martin, B, et al. Differences between plasma and adipose tissue biomarkers of carotenoids and tocopherols. Cancer Epidemiology, Biomarkers & Prevention 1991; 7(11): 1043–8.Google Scholar
12Riemersma, RA, Oliver, M, Elton, RA, Alfthan, G, Vartiainen, E, Salo, M, et al. Plasma antioxidants and coronary heart disease: vitamins C and E, and selenium. European Journal of Clinical Nutrition 1990; 44: 143–50.Google Scholar
13Hertog, MG, Kromhout, D, Aravanis, C, Blackburn, H, Buzina, R, Fidanza, F, et al. Flavonoid intake and long-term risk of coronary heart disease and cancer in the Seven Countries Study. Archives of Internal Medicine 1995; 155: 381–6.CrossRefGoogle ScholarPubMed
14Shamberger, R. Selenium and heart disease 2: selenium and other trace element intakes and heart disease in 25 countries. In: Hemphill, d, ed. Trace Substances in Environmental Health. Columbia, MO: University of Missouri Press, 1978.Google Scholar
15Beaglehole, R, Jackson, R, Watkinson, J, Scragg, R, Yee, R. Decreased blood selenium and risk of myocardial infarction. International Journal of Epidemiology 1990; 19: 918–22.CrossRefGoogle ScholarPubMed
16Ramirez, J, Flowers, N. Leukocyte ascorbic acid and its relationship to coronary artery disease in man. American Journal of Clinical Nutrition 1980; 33: 2079–87.CrossRefGoogle ScholarPubMed
17Stampfer, M, Hennekens, C, Manson, J, Colditz, G, Rosner, B, Willett, W. Vitamin E consumption and the risk of coronary disease in women. New England Journal of Medicine 1993; 328(20): 1444–9.CrossRefGoogle ScholarPubMed
18Rimm, E, Stampfer, M, Ascherio, A, Giovannucci, E, Colditz, G, Willett, W. Vitamin E consumption and the risk of coronary heart disease in men. New England Journal of Medicine 1993; 328: 1450–6.CrossRefGoogle ScholarPubMed
19Knekt, P, Reunanen, A, Jarvinen, R, Seppanen, R, Heliovaara, M, Aromaa, A. Antioxidant vitamin intake and coronary mortality in a longitudinal population study. American Journal of Epidemiology 1994; 139: 1180–9.CrossRefGoogle Scholar
20Kushi, L, Folsom, A, Prineas, R, Mink, P, Wu, Y, Bostick, R. Dietary antioxidant vitamins and death from coronary heart disease in postmenopausal women. New England Journal of Medicine 1996; 334: 1156–62.CrossRefGoogle ScholarPubMed
21Yochum, L, Folsom, A, Kushi, L. Intake of antioxidant vitamins and risk of death from stroke in postmenopausal women. American Journal of Clinical Nutrition 2000; 72: 476–83.CrossRefGoogle ScholarPubMed
22Gaziano, J, Hennekens, C. The role of beta-carotene in the prevention of cardiovascular disease. Annals of the New York Academy of Sciences 1993; 691: 148–55.CrossRefGoogle ScholarPubMed
23Christen, W, Gaziano, J, Hennekens, C. Design of Physicians' Health Study II – a randomized trial of beta-carotene, vitamins E and C, and multivitamins, in prevention of cancer, cardiovascular disease, and eye disease, and review of results of completed trials. Annals of Epidemiology 2000; 10(2): 125–34.CrossRefGoogle Scholar
24Manson, JE, Gaziano, JM, Jonas, MA, Hennekens, CH. Antioxidants and cardiovascular disease: a review. Journal of the American College of Nutrition 1993; 12: 426–32.CrossRefGoogle ScholarPubMed
25Salonen, JT, Nyyssonen, K, Salonen, R, Lakka, HM, Kaikkonen, J, Porkkala-Sarataho, E, et al. Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) study: a randomized trial of the effect of vitamins E and C on 3-year progression of carotid atherosclerosis. Journal of Internal Medicine 2000; 248(5): 377–86.CrossRefGoogle Scholar
26Gey, K, Brubacher, G, Stahelin, H. Plasma levels of antioxidant vitamins in relation to ischemic heart disease and cancer. American Journal of Clinical Nutrition 1987; 45: 1368–77.CrossRefGoogle ScholarPubMed
27Street, D, Comstock, G, Salkeld, R, Schuep, W, Klag, M. Serum antioxidants and myocardial infarction. Are low levels of carotenoids and alpha-tocopherol risk factors for myocardial infarction? Circulation 1994; 90(3): 1154–61.CrossRefGoogle ScholarPubMed
28Kok, F, de Bruijn, A, Hofman, A, Vermeeren, R, Valkenburg, H. Is serum selenium a risk factor for cancer in men only? American Journal of Epidemiology 1987; 125: 12–6.CrossRefGoogle ScholarPubMed
29Gey, K, Moser, U, Jordan, P, Stahelin, H, Eichholzer, M, Ludin, E. Increased risk of cardiovascular disease at suboptimal plasma concentrations of essential antioxidants: an epidemiological update with special attention to carotene and vitamin C. American Journal of Clinical Nutrition 1993; 57(Suppl. 5): 787S–97S.CrossRefGoogle ScholarPubMed
30Khaw, KT, Bingham, S, Welch, A, Luben, R, Wareham, N, Oakes, S, et al. Relation between plasma ascorbic acid and mortality in men and women in EPIC–Norfolk prospective study: a prospective population study. European Prospective Investigation into Cancer and Nutrition. Lancet 2001; 357(9257): 657–63.CrossRefGoogle ScholarPubMed
31Muntwyler, J, Hennekens, CH, Manson, JE, Buring, JE, Gaziano, JM. Vitamin supplement use in a low-risk population of US male physicians and subsequent cardiovascular mortality. Archives of Internal Medicine 2002; 162(13): 1472–6.CrossRefGoogle Scholar
32Salonen, J, Alfthan, G, Huttunen, J, Pikkarainen, J, Puska, P. Association between cardiovascular death and myocardial infarction and serum selenium in a matched-pair longitudinal study. Lancet 1982; 2(8291): 175–9.CrossRefGoogle Scholar
33Virtamo, J, Valkeila, E, Alfthan, G, Punsar, S, Huttunen, J, Karvonen, M. Serum selenium and the risk of coronary heart disease and stroke. American Journal of Epidemiology 1985; 122: 276–82.CrossRefGoogle ScholarPubMed
34Miettinen, TA, Alfthan, G, Huttunen, JK, Pikkarainen, J, Naukkarinen, V, Mattila, S, et al. Serum selenium concentration related to myocardial infarction and fatty acid content of serum lipids. British Medical Journal 1983; 287: 517–9.CrossRefGoogle ScholarPubMed
35Ringstad, J, Fonnebo, V. The Tromso Heart Study: serum selenium in a low-risk population for cardiovascular disease and cancer and matched controls. Annals of Clinical Research 1987; 19(5): 351–4.Google Scholar
36Salvini, S, Hennekens, C, Morris, J, Willett, W, Stampfer, M. Plasma levels of the antioxidant selenium and risk of myocardial infarction among US physicians. American Journal of Cardiology 1995; 76: 1218–21.CrossRefGoogle Scholar
37British Nutrition Foundation. Briefing Paper: Selenium and Health. London: British Nutrition Foundation, 2001.Google Scholar
38Hollman, P, Katan, M. Health effects and bioavailability of dietary flavonols. Free Radical Research 1999; 31: S7580.CrossRefGoogle ScholarPubMed
39Blot, W, Li, JY, Taylor, PR, Guo, W, Dawsey, S, Wang, GQ, et al. Nutrition intervention trials in Linxian, China: supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population. Journal of the National Cancer Institute 1993; 85: 1483–92.CrossRefGoogle ScholarPubMed
40The 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. New England Journal of Medicine 1994; 330: 1029–35.CrossRefGoogle Scholar
41Leppala, JM, Virtamo, J, Fogelholm, R, Huttonen, JK, Albanes, D, Taylor, PR, et al. Controlled trial of alpha-tocopherol and beta-carotene supplements on stroke incidence and mortality in male smokers. Arteriosclerosis, Thrombosis, and Vascular Biology 2000; 20(1): 230–5.CrossRefGoogle ScholarPubMed
42Omenn, GS, Goodman, GE, Thornquist, MD, Balmes, J, Cullen, MR, Glass, A, et al. Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. New England Journal of Medicine 1996; 334: 1150–5.CrossRefGoogle ScholarPubMed
43Hennekens, CH, Buring, JE, Manson, JE, Stampfer, M, Rosner, B, Cook, NR, et al. Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease. New England Journal of Medicine 1996; 334(18): 1145–9.CrossRefGoogle ScholarPubMed
44Lee, IM, Cook, NR, Manson, JE, Buring, JE, Hennekens, CH. Beta-carotene supplementation and incidence of cancer and cardiovascular disease: the Women's Health Study. Journal of the National Cancer Institute 1999; 91(24): 2102–6.CrossRefGoogle ScholarPubMed
45Buring, J, Hennekens, C. The Women's Health Study: summary of study design. Journal of Myocardial Ischaemia 1992; 4: 27–9.Google Scholar
46De Klerk, N, Musk, AW, Ambrosini, GL, Eccles, JL, Hansen, J, Olsen, N, et al. Vitamin A and cancer prevention II: comparison of the effects of retinol and beta-carotene. International Journal of Cancer 1998;75(3): 362–7.3.0.CO;2-0>CrossRefGoogle ScholarPubMed
47Greenberg, E, Baron, JA, Karagas, MR, Stukel, TA, Nierenberg, DW, Stevens, MM, et al. Mortality associated with low plasma concentration of beta carotene and effect of oral supplementation. Journal of the American Medical Association 1996; 275(9): 699703.CrossRefGoogle ScholarPubMed
48Hercberg, S, Galan, P, Preziosi, P, Roussel, AM, Arnaud, J, Richard, MJ, et al. Background and rationale behind the SU.VI.MAX Study, a prevention trial using nutritional doses of a combination of antioxidant vitamins and minerals to reduce cardiovascular diseases and cancers. SUpplementation en VItamines et Mineraux AntioXydants Study. International Journal for Vitamin and Nutrition Research 1998; 68(1): 320.Google ScholarPubMed
49Rapola, J, Virtamo, J, Ripatti, S, Huttunen, JK, Albanes, D, Taylor, PR, et al. Randomised trial of alpha-tocopherol and beta-carotene supplements on incidence of major coronary events in men with previous myocardial infarction. Lancet 1997; 349(9067): 1715–20.CrossRefGoogle ScholarPubMed
50Rapola, JM, Virtamo, J, Ripatti, S, Haukka, JK, Huttunen, JK, Albanes, D, et al. Effects of alpha tocopherol and beta carotene supplements on symptoms, progression, and prognosis of angina pectoris. Heart 1998; 79(5): 454–8.CrossRefGoogle ScholarPubMed
51Stephens, N, Parsons, A, Schofield, P, Kelly, F, Cheeseman, K, Mitchinson, M. Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS). Lancet 1996; 347: 781–6.CrossRefGoogle Scholar
52GISSI-Prevenzione Investigators. Dietary supplementation with n –3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results from the GISSI-Prevenzione trial. Lancet 1999; 354: 447–55.CrossRefGoogle Scholar
53Yusuf, S, Dagenais, G, Pogue, J, Bosch, J, Sleight, P. Vitamin E supplementation and cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. New England Journal of Medicine 2000; 342(3): 154–60.Google Scholar
54de Gaetano, G. Low-dose aspirin and vitamin E in people at cardiovascular risk: a randomised trial in general practice. Collaborative Group of the Primary Prevention Project. Lancet 2001; 357: 8995.Google Scholar
55Manson, JE, Gaziano, JM, Spelsberg, A, Ridker, PM, Cook, NR, Buring, JE, et al. A secondary prevention trial of antioxidant vitamins and cardiovascular disease in women. Rationale, design, and methods. The WACS Research Group. Annals of Epidemiology 1995; 5(4): 261–9.CrossRefGoogle ScholarPubMed
56Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002; 360: 2333.CrossRefGoogle Scholar
57Boaz, M, Smetana, S, Weinstein, T, Matas, Z, Gafter, V, Iaina, A, et al. Secondary prevention with antioxidants of cardiovascular disease in endstage renal disease (SPACE): randomised placebo-controlled trial. Lancet 2000; 356: 1213–8.CrossRefGoogle ScholarPubMed
58Hodis, HN, Mack, WJ, LaBree, L, Cahin-Hemphill, L, Sevanian, A, Johnson, R, et al. Serial coronary angiographic evidence that antioxidant vitamin intake reduces progression of coronary artery atherosclerosis. Journal of the American Medical Association 1995; 273(23): 1849–54.CrossRefGoogle ScholarPubMed
59Fang, JC, Kinlay, S, Beltrame, J, Hikiti, H, Wainstein, M, Behrendt, D, et al. Effect of vitamins C and E on progression of transplant-associated arteriosclerosis: a randomised trial. Lancet 2002; 359: 1108–13.CrossRefGoogle Scholar
60Tornwall, M, Virtamo, J, Haukka, J, Albanes, D, Huttunen, J. Alpha-tocopherol (vitamin E) and beta-carotene supplementation does not affect the risk for large abdominal aortic aneurysm in a controlled trial. Atherosclerosis 2001; 157(1): 167–73.CrossRefGoogle ScholarPubMed
61Tornwall, M, Virtamo, J, Haukka, J, Aro, A, Albanes, D, Huttunen, J. The effect of alpha-tocopherol and beta-carotene supplementation on symptoms and progression of intermittent claudication in a controlled trial. Atherosclerosis 1999; 147(1): 193–7.CrossRefGoogle Scholar
62Vivekananthan, D, Penn, MS, Sapp, SK, Hsu, A, Topol, EJ. Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomised trials. Lancet 2003; 361(9374): 2017–23.CrossRefGoogle ScholarPubMed
63Marchioli, R. Antioxidant vitamins and prevention of cardiovascular disease: laboratory, epidemiological and clinical trial data. Pharmacological Research 1999; 40: 227–38.CrossRefGoogle ScholarPubMed
64Asplund, K. Antioxidant vitamins in the prevention of cardiovascular disease: a systematic review. Journal of Internal Medicine 2002; 251: 372–92.CrossRefGoogle ScholarPubMed
65Morris, C, Carson, S. Routine vitamin supplementation to prevent cardiovascular disease: a summary of the evidence for the US Preventive Services Task Force. Annals of Internal Medicine 2003; 139(1): 5670.CrossRefGoogle Scholar
66Poulsen, H, Prieme, H, Loft, S. Role of oxidative DNA damage in cancer initiation and promotion. European Journal of Cancer Prevention 1998; 7: 916.Google ScholarPubMed
67Ziegler, R, Colavito, E, Hartge, P, McAdams, MJ, Schoenberg, JB, Mason, TJ, et al. Importance of alpha-carotene, beta-carotene, and other phytochemicals in the etiology of lung cancer. Journal of the National Cancer Institute 1996; 88(9): 612–5.CrossRefGoogle ScholarPubMed
68Lee, I. Antioxidant vitamins in the prevention of cancer. Proceedings of the Association of American Physicians 1999; 111: 10–5.CrossRefGoogle ScholarPubMed
69National Academy of Sciences, Food and Nutrition Board. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium and Carotenoids. Washington, DC: National Academy Press, 2000.Google Scholar
70Block, G. Epidemiologic evidence regarding vitamin C and cancer. American Journal of Clinical Nutrition 1991; 54: 1310S–4S.CrossRefGoogle ScholarPubMed
71Howe, GR, Hirohata, T, Hislop, TG, Iscovich, JM, Yuan, JM, Katsouyanni, K, et al. Dietary factors and risk of breast cancer: combined analysis of 12 case – control studies. Journal of the National Cancer Institute 1990; 82: 561–9.CrossRefGoogle ScholarPubMed
72Loria, C, Klag, M, Caulfield, L, Whelton, P. Vitamin C status and mortality in US adults. American Journal of Clinical Nutrition 2000; 72: 139–45.CrossRefGoogle ScholarPubMed
73Shamberger, R, Frost, D. Possible protective effect of selenium against human cancer. Canadian Medical Association Journal 1969; 100: 682.Google ScholarPubMed
74Clark, L. The epidemiology of selenium and cancer. Federation Proceedings 1985; 44: 2584–9.Google ScholarPubMed
75Knekt, P, Marniemi, J, Teppo, L, Heliovaara, M, Aromaa, A. Is low selenium status a risk factor for lung cancer? American Journal of Epidemiology 1998; 148: 975–82.CrossRefGoogle ScholarPubMed
76Shamberger, R, Rukovena, E, Longfield, A, Tytko, S, Deodhar, S, Willis, C. Antioxidants and cancer. I. Selenium in blood of normal and cancer patients. Journal of the National Cancer Institute 1973; 50: 863–70.CrossRefGoogle Scholar
77Knekt, P, Aromaa, A, Maatela, J, Alfthan, G, Aaran, RK, Hakama, M, et al. Serum selenium and subsequent risk of cancer among Finnish men and women. Journal of the National Cancer Institute 1990; 82: 864–8.CrossRefGoogle ScholarPubMed
78Yoshizawa, K, Willett, WC, Morris, SJ, Stampfer, MJ, Spiegelman, D, Rimm, EB, et al. Study of prediagnostic selenium level in toenails and the risk of advanced prostate cancer. Journal of the National Cancer Institute 1998; 90: 1219–24.CrossRefGoogle ScholarPubMed
79Fernandez-Banares, F, Cabre, E, Esteve, M, Mingorance, MD, Abad-Lacruz, A, Lachica, M, et al. Serum selenium and risk of large size colorectal adenomas in a geographical area with a low selenium status. American Journal of Gastroenterology 2002; 97(8): 2103–8.CrossRefGoogle Scholar
80Knekt, P, Jarvinen, R, Seppanen, R, Hellovaara, M, Teppo, L, Pukkala, E, et al. Dietary flavonoids and the risk of lung cancer and other malignant neoplasms. American Journal of Epidemiology 1997; 146(3): 223–30.CrossRefGoogle ScholarPubMed
81Hirvonen, T, Virtamo, J, Korhonen, P, Albanes, D, Pietinen, P. Flavonol and flavone intake and the risk of cancer in male smokers (Finland). Cancer Causes & Control 2001; 12: 789–96.CrossRefGoogle Scholar
82Hertog, M, Feskens, E, Hollman, P, Katan, M, Kromhout, D. Dietary antioxidant flavonoids and cancer risk in the Zutphen Elderly Study. Nutrition and Cancer 1994; 22: 175–84.CrossRefGoogle ScholarPubMed
83Arts, I, Jacobs, DJ, Harnack, L, Gross, M, Folsom, A. Dietary catechins in relation to coronary heart disease death amongst postmenopausal women. Epidemiology 2001; 12: 668–75.CrossRefGoogle Scholar
84Albanes, D, Malila, N, Taylor, PR, Huttunen, JK, Virtamo, J, Edwards, BK, et al. Effects of supplemental alpha-tocopherol and beta-carotene on colorectal cancer: results from a controlled trial (Finland). Cancer Causes & Control 2000; 11: 197205.CrossRefGoogle Scholar
85Virtamo, J, Edwards, BK, Virtanen, M, Taylor, PR, Malila, N, Albanes, D, et al. Effects of supplemental alpha-tocopherol and beta-carotene on urinary tract cancer: incidence and mortality in a controlled trial (Finland). Cancer Causes & Control 2000; 11(10): 933–9.CrossRefGoogle Scholar
86Rautalahti, MT, Virtamo, JR, Taylor, PR, Heinonen, OP, Albanes, D, Haukka, JK, et al. The effects of supplementation with alpha-tocopherol and beta-carotene on the incidence and mortality of carcinoma of the pancreas in a randomized, controlled trial. Cancer 1999; 86: 3742.3.0.CO;2-F>CrossRefGoogle Scholar
87Frieling, UM, Schaumberg, DA, Kupper, TS, Muntwyler, J, Hennekens, CH. A randomized, 12-year primary-prevention trial of beta carotene supplementation for nonmelanoma skin cancer in the Physician's Health Study. Archives of Dermatology 2000; 136(2): 179–84.CrossRefGoogle ScholarPubMed
88Green, A, Williams, G, Neale, R, Hart, V, Leslie, D, Parsons, P, et al. Daily sunscreen application and betacarotene supplementation in prevention of basal-cell and squamous-cell carcinomas of the skin: a randomised controlled trial. Lancet 1999 354: 723–9.CrossRefGoogle ScholarPubMed
89Klein, E, Lippman, SM, Thompson, IM, Goodman, PJ, Albanes, D, Taylor, PR, et al. The selenium and vitamin E cancer prevention trial. World Journal of Urology 2003; 21: 21–7.Google ScholarPubMed
90Rayman, M, Clark, L. Selenium in cancer prevention. In: Roussel, AM, ed. Trace Elements in Man and Animals 10. New York: Kluwer Academic/Plenum Publishers, 1999.Google Scholar
91Greenberg, ER, Baron, JA, Stukel, TA, Stevens, MM, Mandel, JS, Spencer, SK, et al. A clinical trial of beta carotene to prevent basal-cell and squamous-cell cancers of the skin. The Skin Cancer Prevention Study Group. New England Journal of Medicine 1990; 323: 789–95.CrossRefGoogle ScholarPubMed
92Clark, LC, Combs, GF Jr, Turnbull, BW, Slate, EH, Chalker, DK, Chow, J, et al. Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group. Journal of the American Medical Association 1996; 276: 1957–63.CrossRefGoogle ScholarPubMed
93Clark, LC, Dalkin, B, Krongrad, A, Combs, GF Jr, Turnbull, RW, Slate, EH, et al. Decreased incidence of prostate cancer with selenium supplementation: results of a double-blind cancer prevention trial. British Journal of Urology 1998; 81: 730–4.CrossRefGoogle ScholarPubMed
94Albanes, D, Heinonen, OP, Taylor, PR, Virtamo, J, Edwards, BK, Rautalahti, M, et al. Alpha-tocopherol and beta-carotene supplements and lung cancer incidence in the alpha-tocopherol, beta-carotene cancer prevention study: effects of base-line characteristics and study compliance. Journal of the National Cancer Institute 1996; 88: 1560–70.CrossRefGoogle ScholarPubMed
95Virtamo, J, Pietinen, P, Huttunen, JK, Korhonen, P, Malila, N, Virtanen, MJ, et al. ATBC Study Group Incidence of cancer and mortality following alpha-tocopherol and beta-carotene supplementation: a postintervention follow-up. Journal of the American Medical Association 2003; 290: 476–85.Google ScholarPubMed
96Rowe, P. Beta-carotene takes a collective beating. Lancet 1996; 347(8996): 249.CrossRefGoogle ScholarPubMed
97Darlington, S, Williams, G, Neale, R, Frost, C, Green, A. A randomized controlled trial to assess sunscreen application and beta carotene supplementation in the prevention of solar keratoses. Archives of Dermatology 2003; 139(4): 451–5.CrossRefGoogle ScholarPubMed
98Cerutti, P. Oxy-radicals and cancer. Lancet 1994; 344: 862–3.CrossRefGoogle ScholarPubMed
99Handelman, G, Packer, L, Cross, C. Destruction of tocopherols, carotenoids, and retinol in human plasma by cigarette smoke. American Journal of Clinical Nutrition 1996; 63: 559–65.CrossRefGoogle ScholarPubMed
100Blot, W, Li, J, Taylor, P, Guo, W, Dawsey, S, Li, B. The Linxian trials: mortality rates by vitamin–mineral intervention group. American Journal of Clinical Nutrition 1995; 62: 1424S–6S.CrossRefGoogle ScholarPubMed
101Greenberg, ER, Baron, JA, Tosteson, TD, Freeman, DH Jr, Beck, GS, Bond, JH, et al. A clinical trial of antioxidant vitamins to prevent colorectal adenoma. Polyp Prevention Study Group. New England Journal of Medicine 1994; 331: 141–7.CrossRefGoogle ScholarPubMed
102Carr, AC, Frei, B. Toward a new recommended dietary allowance for vitamin C based on antioxidant and health effects in humans. American Journal of Clinical Nutrition 1999; 69: 1086–107.CrossRefGoogle Scholar
103Albanes, D, Heinonen, OP, Huttunen, JK, Taylor, PR, Virtamo, J, Edwards, BK, et al. Effects of alpha-tocopherol and beta-carotene supplements on cancer incidence in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study. American Journal of Clinical Nutrition 1995; 62: 1427S–30S.CrossRefGoogle ScholarPubMed
104Heinonen, OP, Albanes, D, Virtamo, J, Taylor, PR, Huttunen, JK, Hartman, AM, et al. Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: incidence and mortality in a controlled trial. Journal of the National Cancer Institute 1998; 90(6): 440–6.CrossRefGoogle Scholar
105London, R, Sundaram, G, Murphy, L, Manimekalai, S, Reynolds, M, Goldstein, P. The effect of vitamin E on mammary dysplasia: a double blind study. Obstetrics and Gynecology 1985; 65: 104–6.Google ScholarPubMed
106Ernster, V, Goodson, WR, Hunt, T, Petrakis, N, Sickles, E, Miike, R. Vitamin E and benign breast ‘disease’: a double-blind, randomized clinical trial. Surgery 1985; 97: 490–4.Google ScholarPubMed
107Malila, N, Virtamo, J, Virtanen, M, Albanes, D, Tangrea, J, Huttunen, J. The effect of alpha-tocopherol and beta-carotene supplementation on colorectal adenomas in middle-aged male smokers. Cancer Epidemiology, Biomarkers & Prevention 1999; 8(6): 489–93.Google ScholarPubMed
108Hofstad, B, Vatn, M, Andersen, S, Owen, R, Larsen, S, Osnes, M. The relationship between faecal bile acid profile with or without supplementation with calcium and antioxidants on recurrence and growth of colorectal polyps. European Journal of Cancer Prevention 1998; 7(4): 287–94.CrossRefGoogle ScholarPubMed
109Yu, S, Zhu, YJ, Li, WG, Huang, QS, Huang, CZ, Zhang, QN, et al. A preliminary report on the intervention trials of primary liver cancer in high-risk populations with nutritional supplementation of selenium in China. Biological Trace Element Research 1991; 29: 289–94.CrossRefGoogle Scholar
110Yu, S, Zhu, J, Li, W. Protective role of selenium against hepatitis B virus and primary liver cancer in Qidong. Biological Trace Element Research 1997; 56: 117–24.CrossRefGoogle ScholarPubMed
111Li, W. Preliminary observations on effect of selenium yeast on high risk populations with primary liver cancer. Chung Hua Yu Fang I Hsueh Tsa Chih 1992; 26: 269–71.Google ScholarPubMed
112Duffield-Lillico, AJ, Dalkin, BL, Reid, ME, Turnbull, BW, Slate, EH, Jacobs, ET, et al. Nutritional Prevention of Cancer Study Group. Selenium supplementation, baseline plasma selenium status and incidence of prostate cancer: an analysis of the complete treatment period of the Nutritional Prevention of Cancer Trial. BJU International 2003; 91(7): 608–12.CrossRefGoogle Scholar
113Forastiere, F, Pistelli, R, Sestini, P, Fortes, C, Renzoni, E, Rusconi, F, et al. Consumption of fresh fruit rich in vitamin C and wheezing symptoms in children. SIDRIA Collaborative Group, Italy (Italian Studies on Respiratory Disorders in Children and the Environment). Thorax 2000; 55: 283–8.CrossRefGoogle Scholar
114Hatch, G. Asthma, inhaled oxidants, and dietary antioxidants. American Journal of Clinical Nutrition 1995; 61: 625S–30S.CrossRefGoogle ScholarPubMed
115Schwartz, J, Weiss, S. Dietary factors and their relationship to respiratory symptoms: NHANES II. American Journal of Epidemiology 1990; 132: 6776.CrossRefGoogle Scholar
116Schwartz, J, Weiss, S. Relationship between dietary vitamin C intake and pulmonary function in the First National Health and Nutrition Examination Survey (NHANES I). American Journal of Clinical Nutrition 1994; 59: 110–4.CrossRefGoogle Scholar
117Nomura, A, Stemmermann, G, Lee, J, Craft, N. Serum micronutrients and upper aerodigestive tract cancer. Cancer Epidemiology, Biomarkers & Prevention 1997; 6: 407–12.Google ScholarPubMed
118Kalayci, O, Besler, T, Kilinc, K, Sekerel, B, Saraclar, Y. Serum levels of antioxidant vitamins (alpha tocopherol, beta carotene, and ascorbic acid) in children with bronchial asthma. Turkish Journal of Pediatrics 2000; 42(1): 1721.Google ScholarPubMed
119Hu, G, Cassano, P. Antioxidant nutrients and pulmonary function: the Third National Health and Nutrition Examination Survey (NHANES III). American Journal of Epidemiology 2000; 151(10): 975–81.CrossRefGoogle Scholar
120Romieu, I, Sienra-Monge, JJ, Ramirez-Aguilar, M, Tellez-Rojo, MM, Moreno-Macias, H, Reyes-Ruiz, NI, et al. Antioxidant supplementation and lung functions among children with asthma exposed to high levels of air pollutants. American Journal of Respiratory and Critical Care Medicine 2002; 166(5): 703–9.CrossRefGoogle ScholarPubMed
121Rautalahti, M, Virtamo, J, Haukka, J, Heinonen, OP, Sundvall, J, Albanes, D, et al. The effect of alpha-tocopherol and beta-carotene supplementation on COPD symptoms. American Journal of Respiratory and Critical Care Medicine 1997; 156(5): 1447–52.CrossRefGoogle ScholarPubMed
122Hasselmark, L, Malmgren, R, Zetterstrom, O, Unge, G. Selenium supplementation in intrinsic asthma. Allergy 1993; 48: 30–6.Google ScholarPubMed
123Christen, WG, Glynn, RJ, Hennekens, CH. Antioxidants and age-related eye disease. Current and future perspectives. Annals of Epidemiology 1996; 6: 60–6.CrossRefGoogle ScholarPubMed
124Johnson, EL, Hammond, BR, Yeum, KJ, Qin, J, Wang, XD, Castaneda, C, et al. Relation among serum and tissue concentrations of lutein and zeaxanthin and macular pigment density. American Journal of Clinical Nutrition 2000; 71: 1555–62.CrossRefGoogle ScholarPubMed
125Hammond, BJ, Wooten, B, Snodderly, D. Cigarette smoking and retinal carotenoids: implications for age-related macular degeneration. Vision Research 1996; 36: 3003–9.CrossRefGoogle ScholarPubMed
126West, S, Vitale, S, Hallfrisch, J, Munoz, B, Muller, D, Bressler, S, et al. Are antioxidants or supplements protective for age-related macular degeneration? Archives of Ophthalmology 1994; 112(2): 222–7.CrossRefGoogle ScholarPubMed
127Delcourt, C, Cristol, JP, Tessier, F, Leger, CL, Descomps, B, Papoz, L. Age-related macular degeneration and antioxidant status in the POLA study. POLA Study Group. Pathologies Oculaires Liees a l'Age. Archives of Ophthalmology 1999; 117: 1384–90.CrossRefGoogle Scholar
128Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E and beta carotene for age-related cataract and vision loss: AREDS report no. 9. Archives of Ophthalmology 2001; 119(10): 1439–52.CrossRefGoogle Scholar
129Taylor, H, Tikellis, G, Robman, LD, McCarty, CA, McNeil, JJ. Vitamin E supplementation and macular degeneration: randomised controlled trial. British Medical Journal 2002; 325: 11.CrossRefGoogle ScholarPubMed
130Evans, J. Antioxidant vitamin and mineral supplements for age-related macular degeneration. Cochrane Database of Systematic Reviews 2002; 2: CD000254.Google Scholar
131Knekt, P, Heliovaara, M, Rissanen, A, Aromaa, A, Aaran, RK. Serum antioxidant vitamins and risk of cataract. British Medical Journal 1992; 305: 1392–4.CrossRefGoogle ScholarPubMed
132Taylor, A, Jacques, P, Epstein, E. Relations among aging, antioxidant status, and cataract. American Journal of Clinical Nutrition 1995; 62: 1439S–47S.CrossRefGoogle ScholarPubMed
133Jacques, PF, Chylack, LT Jr, Hankinson, SE, Khu, PM, Rogers, G, Friend, J, et al. Long-term nutrient intake and early age-related nuclear lens opacities. Archives of Ophthalmology 2001; 119: 1009–19.CrossRefGoogle ScholarPubMed
134Lyle, B, Mares-Perlman, J, Klein, B, Klein, R, Greger, J. Antioxidant intake and risk of incident age-related nuclear cataracts in the Beaver Dam Eye Study. American Journal of Epidemiology 1999; 149(9): 801–9.CrossRefGoogle ScholarPubMed
135Hankinson, SE, Stampfer, MJ, Seddon, JM, Colditz, GA, Rosner, B, Speizer, FE, et al. Nutrient intake and cataract extraction in women: a prospective study. British Medical Journal 1992; 305(6849): 335–9.CrossRefGoogle ScholarPubMed
136Chylack, LT Jr, Brown, NP, Bron, A, Hurst, M, Kopcke, W, Thien, U, et al. The Roche European American Cataract Trial (REACT): a randomized clinical trial to investigate the efficacy of an oral antioxidant micronutrient mixture to slow progression of age-related cataract. Ophthalmic Epidemiology 2002; 9(1): 4980.Google ScholarPubMed
137Teikari, J, Virtamo, J, Rautalahti, M, Palmgren, J, Liesto, K, Heinonen, O. Long-term supplementation with alpha-tocopherol and beta-carotene and age-related cataract. Acta Ophthalmologica Scandinavica 1997; 75(6): 634–40.CrossRefGoogle ScholarPubMed
138Christen, W, Manson, JE, Glynn, RJ, Gaziano, JM, Sperduto, RD, Buring, JE, et al. A randomized trial of beta carotene and age-related cataract in US physicians. Archives of Ophthalmology 2003; 121: 372–8.CrossRefGoogle ScholarPubMed
139Brown, B, Zhao, XQ, Chait, A, Fisher, LD, Cheung, MC, Morse, JS, et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. New England Journal of Medicine 2001; 345: 1583–92.CrossRefGoogle ScholarPubMed
140Pryor, W, Stahl, W, Rock, CL. Beta carotene: from biochemistry to clinical trials. Nutrition Reviews 2000; 58(2 Pt 1): 3953.CrossRefGoogle ScholarPubMed
141Handelman, G, Machlin, LJ, Fitch, K, Weiter, JJ, Dratz, EA. Oral alpha-tocopherol supplements decrease plasma gamma-tocopherol levels in humans. Journal of Nutrition 1985; 115(6): 807–13.CrossRefGoogle ScholarPubMed
142Jiang, Q, Christen, S, Shigenaga, MK, Ames, BN. Gamma-tocopherol, the major form of vitamin E in the US diet, deserves more attention. American Journal of Clinical Nutrition 2001; 74(6): 714–22.CrossRefGoogle ScholarPubMed
143Czernichow, S, Hercberg, S. Interventional studies concerning the role of antioxidant vitamins in cardiovascular diseases: a review. Journal of Nutrition, Health & Aging 2001; 5: 188–95.Google ScholarPubMed
144Steinberg, D. Clinical trials of antioxidants in atherosclerosis: are we doing the right thing? Lancet 1995; 346(8966): 36–8.CrossRefGoogle ScholarPubMed
You have Access
293
Cited by

Save article to Kindle

To save this article to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

A review of the epidemiological evidence for the ‘antioxidant hypothesis’
Available formats
×

Save article to Dropbox

To save this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you used this feature, you will be asked to authorise Cambridge Core to connect with your Dropbox account. Find out more about saving content to Dropbox.

A review of the epidemiological evidence for the ‘antioxidant hypothesis’
Available formats
×

Save article to Google Drive

To save this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you used this feature, you will be asked to authorise Cambridge Core to connect with your Google Drive account. Find out more about saving content to Google Drive.

A review of the epidemiological evidence for the ‘antioxidant hypothesis’
Available formats
×
×

Reply to: Submit a response

Please enter your response.

Your details

Please enter a valid email address.

Conflicting interests

Do you have any conflicting interests? *