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

  • SA Stanner (a1), J Hughes (a2), CNM Kelly (a1) and J Buttriss (a1)
Abstract
AbstractObjective:

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.

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*Corresponding author: Email s.stanner@nutrition.org.uk
References
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1Department of Health. Nutritional Aspects of Cardiovascular Disease. London: HMSO, 1994.
2Department of Health. Nutritional Aspects of the Development of Cancer. London: The Stationery Office, 1998.
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.
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.
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.
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.
7La Vecchia C, Decarli A, Pagano R. Vegetable consumption and risk of chronic disease. Epidemiology 1998; 9: 208–10.
8Poulsen H, Hensen B, Weimann A, Hensen SA, Sorensen M, Loft S. Antioxidants, DNA damage and gene expression. Free Radical Research 2000; 33: S339.
9Steinberg D. Low density lipoprotein oxidation and its pathobiological significance. Journal of Biological Chemistry 1997; 272(34): 20963–6.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
37British Nutrition Foundation. Briefing Paper: Selenium and Health. London: British Nutrition Foundation, 2001.
38Hollman P, Katan M. Health effects and bioavailability of dietary flavonols. Free Radical Research 1999; 31: S7580.
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.
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.
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.
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.
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.
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.
45Buring J, Hennekens C. The Women's Health Study: summary of study design. Journal of Myocardial Ischaemia 1992; 4: 27–9.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
63Marchioli R. Antioxidant vitamins and prevention of cardiovascular disease: laboratory, epidemiological and clinical trial data. Pharmacological Research 1999; 40: 227–38.
64Asplund K. Antioxidant vitamins in the prevention of cardiovascular disease: a systematic review. Journal of Internal Medicine 2002; 251: 372–92.
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.
66Poulsen H, Prieme H, Loft S. Role of oxidative DNA damage in cancer initiation and promotion. European Journal of Cancer Prevention 1998; 7: 916.
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.
68Lee I. Antioxidant vitamins in the prevention of cancer. Proceedings of the Association of American Physicians 1999; 111: 10–5.
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.
70Block G. Epidemiologic evidence regarding vitamin C and cancer. American Journal of Clinical Nutrition 1991; 54: 1310S–4S.
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.
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.
73Shamberger R, Frost D. Possible protective effect of selenium against human cancer. Canadian Medical Association Journal 1969; 100: 682.
74Clark L. The epidemiology of selenium and cancer. Federation Proceedings 1985; 44: 2584–9.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
96Rowe P. Beta-carotene takes a collective beating. Lancet 1996; 347(8996): 249.
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.
98Cerutti P. Oxy-radicals and cancer. Lancet 1994; 344: 862–3.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
114Hatch G. Asthma, inhaled oxidants, and dietary antioxidants. American Journal of Clinical Nutrition 1995; 61: 625S–30S.
115Schwartz J, Weiss S. Dietary factors and their relationship to respiratory symptoms: NHANES II. American Journal of Epidemiology 1990; 132: 6776.
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.
117Nomura A, Stemmermann G, Lee J, Craft N. Serum micronutrients and upper aerodigestive tract cancer. Cancer Epidemiology, Biomarkers & Prevention 1997; 6: 407–12.
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.
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.
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.
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.
122Hasselmark L, Malmgren R, Zetterstrom O, Unge G. Selenium supplementation in intrinsic asthma. Allergy 1993; 48: 30–6.
123Christen WG, Glynn RJ, Hennekens CH. Antioxidants and age-related eye disease. Current and future perspectives. Annals of Epidemiology 1996; 6: 60–6.
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.
125Hammond BJ, Wooten B, Snodderly D. Cigarette smoking and retinal carotenoids: implications for age-related macular degeneration. Vision Research 1996; 36: 3003–9.
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.
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.
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.
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.
130Evans J. Antioxidant vitamin and mineral supplements for age-related macular degeneration. Cochrane Database of Systematic Reviews 2002; 2: CD000254.
131Knekt P, Heliovaara M, Rissanen A, Aromaa A, Aaran RK. Serum antioxidant vitamins and risk of cataract. British Medical Journal 1992; 305: 1392–4.
132Taylor A, Jacques P, Epstein E. Relations among aging, antioxidant status, and cataract. American Journal of Clinical Nutrition 1995; 62: 1439S–47S.
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.
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.
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.
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.
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.
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.
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.
140Pryor W, Stahl W, Rock CL. Beta carotene: from biochemistry to clinical trials. Nutrition Reviews 2000; 58(2 Pt 1): 3953.
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.
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.
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.
144Steinberg D. Clinical trials of antioxidants in atherosclerosis: are we doing the right thing? Lancet 1995; 346(8966): 36–8.
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Public Health Nutrition
  • ISSN: 1368-9800
  • EISSN: 1475-2727
  • URL: /core/journals/public-health-nutrition
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