Physiological Role of Antioxidants in the Immune System

      This paper is only available as a PDF. To read, Please Download here.


      Diets contain naturally occurring antioxidant compounds that can stabilize highly reactive, potentially harmful molecules called free radicals. Free radicals are generated during normal cellular metabolism and result from the metabolism of certain drugs or xenobiotics. Exposure to UV light, cigarette smoke, and other environmental pollutants also increases the body's free radical burden. The harmful activities of free radicals are associated with damage to membranes, enzymes, and DNA. The ability of antioxidants to destroy free radicals protects the structural integrity of cells and tissues. This review focuses on data indicating that the functions of the human immune system depend on the intake of micronutrients, which can act as antioxidants. Recent clinical trials have found that antioxidant supplementation can significantly improve certain immune responses. Specifically, supplementation with vitamins C, E, and A or β-carotene increased the activation of cells involved in tumor immunity in the elderly. Supplementation with the antioxidant vitamins also protected immune responses in individuals exposed to certain environmental sources of free radicals. Supplementation with vitamin A, a relatively weak antioxidant, decreases morbidity and mortality associated with measles infections in children.

      Key words

      Abbreviation key:

      DTH (delayed-type hypersensitivity)


        • Atkinson W.L.
        • Orenstein W.A.
        • Krugman S.
        The resurgence of measles in the United States, 1989–1990.
        Annu. Rev. Med. 1992; 43: 451
        • Barclay A.J.G.
        • Foster A.
        • Sommer A.
        Vitamin A supplements and mortality related to measles: a randomized clinical trial.
        Br. Med. J. 1987; 294: 294
        • Bendich A.
        Antioxidant vitamins and their-functions in immune responses.
        in: Bendich A. Phillips M. Tengerdy R.P. Antioxidant Nutrients and Immune Functions. Plenum Press, New York, NY1990: 33
        • Bendich A.
        Carotenoids and immunity.
        Clin. Appl. Nutr. 1991; 1: 45
        • Bendich A.
        • Olson J.A.
        Biological actions of carotenoids.
        Fed. Am. Soc. Exp. Biol. J. 1989; 3: 1927
        • Bendich A.
        • Shapiro S.S.
        Effect of β-carotene and canthaxanthin on the immune responses of the rat.
        J. Nutr. 1986; 116: 2254
        • Bogden J.D.
        • Oleske J.M.
        • Lavenhar M.A.
        • Munves E.M.
        • Kemp F.W.
        • Bruening K.S.
        • Holding K.J.
        • Denny T.N.
        • Guarino M.A.
        • Holland B.K.
        Effects of one year of supplementation with zinc and other micronutrients on cellular immunity in the elderly.
        J. Am. Coll. Nutr. 1990; 9: 214
        • Byers T.E.
        • Graham S.
        • Haughey B.P.
        • Marshall J.R.
        • Swanson M.K.
        Diet and lung cancer risk: findings from the western New York diet study.
        Am. J. Epidemiol. 1987; 125: 351
        • Coutsoudis A.
        • Coovadia H.M.
        • Broughton M.
        • Salisbury R.T.
        • Elson I.
        Micronutrient utilization during measles treated with vitamin A or placebo.
        Int. J. Vitam. Nutr. Res. 1991; 61: 199
        • Coutsoudis A.
        • Kiepiela P.
        • Coovadia H.M.
        • Broughton M.
        Vitamin A supplementation enhances specific IgG antibody levels and total lymphocyte numbers while improving morbidity in measles.
        Pediatr. Infect. Dis. J. 1992; 11: 203
        • Coutsoudis A.
        • Zwane M.
        • Coovadia H.M.
        • Gouws E.
        Dietary intake of vitamin A in African pre-school children in Umlazi.
        South Africa Int. J. Vitam. Nutr. Res. 1992; 62: 3
        • Donawho C.K.
        • Kripke M.L.
        Evidence that the local effect of ultra-violet radiation on the growth of murine melanomas is immunologically mediated.
        Cancer Res. 1991; 51: 4176
        • Ellison J.B.
        Intensive vitamin therapy in measles.
        Br. Med. J. 1932; 2: 708
        • Fuller C.J.
        • Faulkner H.
        • Bendich A.
        • Parker R.S.
        • Roe D.A.
        Effect of β-carotene supplementation on photosuppression of delayed-type hypersensitivity in normal young men.
        Am. J. Clin. Nutr. 1992; 56: 684
        • Gensler H.L.
        Reduction of immunosuppression in UV-irradiated mice by dietary retinyl palmitate plus canthaxanthin.
        Carcinogenesis. 1989; 10: 203
        • Goodwin J.S.
        • Bums E.L.
        Aging, nutrition, and immune function.
        Clin. Appl. Nutr. 1991; 1: 85
        • Heimburger D.C.
        • Krundieck C.L.
        • Butterworth C.E.
        Role of folate in prevention of cancers of the lung and cervix.
        J. Am. Coll. Nutr. 1987; 6: 425
        • Hussey G.D.
        • Klein M.
        A randomized, controlled trial of vitamin A in children with severe measles.
        New England J. Med. 1990; 323: 160
        • Johnson J.D.
        • Houches D.P.
        • Kluwe W.M.
        • Craig D.K.
        • Fisher G.L.
        Effects of mainstream and environmental tobacco smoke on the immune system in animals and humans: a review.
        Crit. Rev. Toxicol. 1990; 20: 369
        • Machlin L.J.
        • Bendich A.
        Free radical tissue damage: protective role of antioxidant nutrients.
        Fed. Am. Soc. Exp. Biol. J. 1987; 1: 441
        • Malter M.
        • Schriever G.
        • Eiber U.
        Natural killer cells, vitamins, and other blood components of vegetarian and omnivorous men.
        Nutr. Cancer. 1989; 12: 271
        • Meydani S.N.
        • Barklund M.P.
        • Liu S.
        Vitamin E supplementation enhances cell-mediated immunity in healthy elderly subjects.
        Am. J. Clin. Nutr. 1990; 52: 557
        • Nauss K.M.
        Influence of vitamin A status on the immune system.
        in: Bauemfeind C.J. Vitamin A Deficiency and Its Control. Academic Press, Inc., Orlando, FL1986: 207
        • Pacht E.R.
        • Kasek H.
        • Mohammed J.R.
        • Cromwell D.G.
        • Davis W.B.
        Deficiency of vitamin E in the alveolar fluid of cigarette smokers: influence on alveolar macrophage cytotoxicity.
        J. Clin. Invest. 1986; 77: 789
        • Penn N.D.
        • Purkins L.
        • Kelleher J.
        • Heatley R.V.
        • Mascie-Taylor B.H.
        • Belfield P.W.
        The effect of dietary vitamin-supplementation with vitamin A, C, and E on cell-mediated immune function in elderly long-stay patients: a randomized controlled trial.
        Age Ageing. 1991; 20: 169
        • Punnonen K.
        • Autio P.
        • Kiistala U.
        In-vivo effects of solar-simulated ultraviolet irradiation on antioxidant enzymes and lipid peroxidation in human epidermis.
        Br. J. Dermatol. 1991; 125: 18
        • Roitt I.M.
        • Brostoff J.
        • Male D.K.
        Gower Medical Publ., New York, NY1985
        • Schectman G.J.
        • Byrd C.
        • Hoffmann R.
        Ascorbic acid requirements for smokers: analysis of a population survey.
        Am. J. Clin. Nutr. 1991; 53: 1466
        • Schwartz J.L.
        • Shklar G.
        • Flynn E.
        The administration of beta carotene to prevent and regress oral carcinoma in the hamster cheek pouch and the associated enhancement of the immune response.
        in: Bendich A. Phillips M. Tengerdy R.P. Antioxidant Nutrients and Immune Functions: Advances in Experimental Biology and Medicine. Plenum Press, New York, NY1990: 77
        • Semba R.D.
        • Scott A.L.
        • Natadisastra G.
        • Wirasasmita S.
        • Mele L.
        • Ridwan E.
        • West K.P.
        • Sommer A.
        Depressed immune response to tetanus in children with vitamin A deficiency.
        J. Nutr. 1992; 122: 101
        • Stryker W.S.
        • Kaplan L.A.
        • Stein E.A.
        • Stampfer M.
        • Sober A.
        • Willett W.C.
        The relation of diet, cigarette smoking, and alcohol consumption to plasma β-carotene and α-tocopherol levels.
        Am. J. Epidemiol. 1988; 127: 283
        • Tomita Y.
        • Himeno K.
        • Nomoto K.
        • Endo H.
        • Hirohata T.
        Augmentation of tumor immunity against syngeneic tumors in mice by β-carotene.
        J. Nutr. Cancer Inst. 1987; 78: 679
        • Visek W.J.
        Diet and cancer.
        in: Prinsley D.M. Sandstead H.H. Nutrition and Aging. Alan R. Liss, Inc., New York, NY1990: 301
        • Watson R.R.
        • Prabhala R.H.
        • Plezia P.M.
        • Alberts D.S.
        Effect of β-carotene on lymphocyte subpopulations in elderly humans: evidence for a dose-response relationship.
        Am. J. Clin. Nutr. 1991; 53: 90
        • Wayne S.J.
        • Rhyne R.L.
        • Garry P.J.
        • Goodwin J.S.
        Cell-mediated immunity as a predictor of morbidity and mortality in subjects over 60.
        J. Gerontol. 1990; 45: 45