This proposed definition is based on several criteria: (1) the substance is found in human diets; (2) the content of the substance has been measured in foods commonly consumed; and (3) in humans, the substance decreases the formation of adverse effects of reactive oxygen and nitrogen species in vivo.
Additionally, based on its review of the scientific literature on dietary antioxidants and related compounds, and on the availability of data relating the intake of these substances to potential benefits to human health, in its second report the panel will evaluate the extent to which beta-carotene and other selected carotenoids, vitamin C, vitamin E, and selenium play a role in health. DRIs will be set for these food components if adequate data are available and if their role in health can be established and quantified. Therefore, for some of these nutrients and food components, their DRIs may not be determined by or related to their possible action as an antioxidant.
Selected References
General
Diaz MN, Frei B, Vita JA, Keaney JF. 1997. Antioxidants and atherosclerotic heart disease. N Engl J Med 337:408–416.
Halliwell B. 1990. How to characterize a biological antioxidant. Free Rad Res Commun 9:1–32.
Halliwell B. 1996. Antioxidants. In: Ziegler EE, Filer LJ Jr., eds. Present Knowledge in Nutrition. Washington, DC: ILSI Press. Pp. 596–603.
Halliwell B. 1997. Antioxidants and human disease: A general introduction. Nutr Rev 55:S44–S49.
Halliwell B. 1997. Antioxidants: The basics—What are they and how to evaluate them. Adv Pharmacol 38:3–20.
Krinsky NI. 1992. Mechanism of action of biological antioxidants. Proc Soc Exp Biol Med 200:248–254.
Sies H. 1985. Oxidative stress: Introductory remarks. In: Sies H, ed. Oxidative Stress. London: Academic Press. Pp. 1–8.
Sies H. 1993. Strategies of antioxidant defense. Eur J Biochem 215:213–219.
Steinmetz KA, Potter JD. 1996. Vegetables, fruit, and cancer prevention: A review. J Am Diet Assoc 96:1027–1039.
Voelker R. 1994. Recommendations for antioxidants: How much evidence is enough? J Am Med Assoc 271:1148–1149.
Beta-Carotene and Other Carotenoids
The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. 1994. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med 330:1029–1035.
Clinton SK. 1998. Lycopene: Chemistry, biology, and implications for human health and disease. Nutr Rev 56:35–51.
Hennekens CH, Buring JE, Manson JE, Stampfer M, Rosner B, Cook NR, Belanger C, LaMotte F, Gaziano JM, Ridker PM, Willett W, Peto R. 1996. Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease. N Engl J Med 334:1145–1149.
International Agency for Research on Cancer, World Health Organization. 1998. Carotenoids. IARC Handbooks of Cancer Prevention. Vol. 2. Oxford University Press. Pp. 1–326.
Krinsky NI. 1993. Actions of carotenoids in biological systems. Annu Rev Nutr 13:561–587.
Mangels AR, Holden JM, Beecher GR, Forman MR, Lanza E. 1993. Carotenoid content of fruits and vegetables: An evaluation of analytic data. J Am Diet Assoc 93:284–296.
Mayne ST. 1996. Beta-carotene, carotenoids, and disease prevention in humans. FASEB J 10:690–701.
Mayne ST. 1998. Beta-carotene, carotenoids and cancer prevention. In: DeVita VT Jr., Hellman S, Rosenberg SA, eds. Principles and Practice of Oncology Updates, 5th edition. Philadelphia: Lippincott-Raven Publishers. In press.
Omenn GS, Goodman GE, Thornquist MD, Balmes J, Cullen MR, Glass A, Keogh JP, Meyskens FL, Valanis B, Williams JH, Barnhart S, Hammar S. 1996. Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med 334:1150–1155.
Vitamin C
Englard S, Seifter S. 1986. The biochemical functions of ascorbic acid. Annu Rev Nutr 6:365–406.
Harris JR, ed. 1996. Ascorbic Acid: Biochemistry and Biomedical Cell Biology. Vol. 25. New York: Plenum Press.
Jacob RA. 1994. Vitamin C. In: Shils ME, Olson JA, Shike M, eds. Modern Nutrition in Health and Disease, 8th edition. Philadelphia: Lea & Febiger.
Packer L, Fuchs J, eds. 1997. Vitamin C in Health and Disease. New York: Marcel Dekker.
Sies H, Stahl W. 1995. Vitamins E and C, beta-carotene, and other carotenoids as antioxidants. Am J Clin Nutr 62:1315S–1321S.
Vitamin E
Burton GW, Traber MG, Acuff RV, Walters DN, Kayden H, Hughes L, Ingold K. 1998. Human plasma and tissue alpha-tocopherol concentrations in response to supplementation with deuterated natural and synthetic vitamin E. Am J Clin Nutr 67:669–684.
Heinonen OP, Albanes D, Virtamo J, Taylor PR, Huttunen JK, Hartman AM, Haapakoski J, Malila N, Rautalahti M, Ripatti S, Mäenpää H, Teerenhovi L, Koss L, Virolainen M, Edwards BK. 1998. Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: Incidence and mortality in a controlled trial. J Natl Cancer Inst 90:440–446.
Packer L, Fuchs J, eds. 1993. Vitamin E in Health and Disease. New York: Marcel Dekker.
Stephens NG, Parsons A, Schofield PM, Kelly F, Cheeseman K, Mitchinson MJ. 1996. Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS). Lancet 347:781–786.
Stampfer MJ, Hennekens C, Manson JE, Colditz GA, Rosner B, Willett WC. 1993. Vitamin E consumption and the risk of coronary disease in women. N Engl J Med 328: 1444–1449.
Traber MG, Sies H. 1996. Vitamin E in humans: Demand and delivery. Annu Rev Nutr 16:321–347.
Selenium
Hill KE, Xia Y, Akesson B, Boeglin ME, Burk RF. 1996. Selenoprotein P concentration in plasma is an index of selenium status in selenium-deficient and selenium-supplemented Chinese subjects. J Nutr 126:138–145.
Stadtman TC. 1991. Biosynthesis and function of selenocysteine-containing enzymes. J Biol Chem 266:16257–16260.
Thomson C, Ong LK, Robinson MF. 1985. Effects of supplementation with high-selenium wheat bread on selenium, glutathione peroxidase and related enzymes in blood components of New Zealand residents . Am J Clin Nutr 41:1015–1022.
Varo P, Alfthan F, Huttunen JK, Aro A. 1994. Nationwide selenium supplementation in Finland—Effects on diet, blood and tissue levels, and health. In: Burk RF, ed. Selenium in Biology and Human Health. New York: Springer-Verlag. Pp. 197–218.
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