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Vol. 50, No. 2, 2006
Issue release date: February 2006
Ann Nutr Metab 2006;50:85–94

Immune-Enhancing Role of Vitamin C and Zinc and Effect on Clinical Conditions

Wintergerst E.S. · Maggini S. · Hornig D.H.
aBayer Consumer Care Ltd., Basel, and bReinach, Switzerland

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Vitamin C concentrations in the plasma and leukocytes rapidly decline during infections and stress. Supplementation of vitamin C was found to improve components of the human immune system such as antimicrobial and natural killer cell activities, lymphocyte proliferation, chemotaxis, and delayed-type hypersensitivity. Vitamin C contributes to maintaining the redox integrity of cells and thereby protects them against reactive oxygen species generated during the respiratory burst and in the inflammatory response. Likewise, zinc undernutrition or deficiency was shown to impair cellular mediators of innate immunity such as phagocytosis, natural killer cell activity, and the generation of oxidative burst. Therefore, both nutrients play important roles in immune function and the modulation of host resistance to infectious agents, reducing the risk, severity, and duration of infectious diseases. This is of special importance in populations in which insufficient intake of these nutrients is prevalent. In the developing world, this is the case in low- and middle-income countries, but also in subpopulations in industrialized countries, e.g. in the elderly. A large number of randomized controlled intervention trials with intakes of up to 1 g of vitamin C and up to 30 mg of zinc are available. These trials document that adequate intakes of vitamin C and zinc ameliorate symptoms and shorten the duration of respiratory tract infections including the common cold. Furthermore, vitamin C and zinc reduce the incidence and improve the outcome of pneumonia, malaria, and diarrhea infections, especially in children in developing countries.

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  1. Dietary Reference Intakes for vitamin C, vitamin E, selenium, and carotenoids. A report of the Panel on Antioxidants and Related compounds, Standing Committee on the Scientific Evaluation of Dietary Reference Intakes; Food and Nutrition Board, Institute of Medicine. Washington, National Academy Press, 2000, chapter 5: Vitamin C, pp 95–185.
  2. Carr AC, Frei B: Toward a new recommended dietary allowance for vitamin C based on antioxidant and health effects in humans. Am J Clin Nutr 1999;69:1086–1107.
  3. Dietary Reference Intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. A report of the Panel on Micronutrients, Standing Committee on the Scientific Evaluation of Dietary Reference Intakes; Food and Nutrition Board, Institute of Medicine. Washington, National Academy Press, 2000, chapter 12: Zinc, pp 442– 501.
  4. Hotz C, Brown KH; for the International Zinc Nutrition Consultative Group (IZiNCG): Assessment of the risk of zinc deficiency in populations and options for its control. Food Nutr Bull 2004;25:S91–S204.
  5. Brennan LA, Morris GM, Wasson GR, Hannigan BM, Barnett YA: The effect of vitamin C or vitamin E supplementation on basal and H2O2-induced DNA damage in human lymphocytes. Br J Nutr 2000;84:195–202.
  6. Fraga CG, Motchnik PA, Shigenaga MK, Helbock HJ, Jacob RA, Ames BN: Ascorbic acid protects against endogenous oxidative DNA damage in human sperm. Proc Natl Acad Sci USA 1991;88:11003–11006.
  7. Duthie SJ, Ma A, Ross MA, Collins AR: Antioxidant supplementation decreases oxidative DNA damage in human lymphocyte. Cancer Res 1996;56:1291–1295.
  8. Ames BN, Shigenaga MK, Hagen TM: Oxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad Sci USA 1993;90:7915–7922.
  9. Jacob RA: The integrated antioxidant system. Nutr Res 1995;15:755–766.
  10. Walmsley AR, Batten MR, Lad U, Bulleid NJ: Intracellular retention of procollagen within the endoplasmic reticulum is mediated by prolyl 4-hydroxylase. J Biol Chem 1999;274:14884–14892.
  11. Hallberg L, Hulthen L: Prediction of dietary iron absorption: an algorithm for calculating absorption and bioavailability of dietary iron. Am J Clin Nutr 2000;71:1147–1160.
  12. McCall KA, Huang C, Fierke CA: Function and mechanism of zinc metalloenzymes. J Nutr 2000;130:1437S–1446S.
  13. Powell SR: The antioxidant properties of zinc. J Nutr 2000;130:1447S–1454S.
  14. Oteiza PI, Olin KL, Fraga CG, Keen CL: Zinc deficiency causes oxidative damage to proteins, lipids and DNA in rat testes. J Nutr 1995;125:823–829.
  15. Vallee BL, Coleman JE, Auld DS: Zinc fingers, zinc clusters and zinc twists in DNA-binding protein domains. Proc Natl Acad Sci USA 1991;88:999–1003.
  16. Zago MP, Oteiza PI: The antioxidant properties of zinc: interaction with iron and antioxidants. Free Radic Biol Med 2001;31:266–274.
  17. Klug A, Schwabe JWR: Zinc fingers. FASEB J 1995;9:597–604.
  18. Zeng J, Heuchel R, Schaffner W, Kaegi JHR: Thionein (apometallothionein) can modulate DNA binding and transcription activation by zinc finger containing factor Sp1. FEBS Lett 1991;279:310–312.
  19. Huse M, Eck MJ, Harrison SC: A Zn2+ ion links the cytoplasmic tail of CD4 and the N-terminal region of Lck. J Biol Chem 1998;273:18729–18733.
  20. Lin RS, Rodriguez C, Veilette A, Lodish HF: Zinc is essential for binding of p56lck to CD4 and CD8α. J Biol Chem 1998;273:32878–32882.
  21. Parkin J, Cohen B: An overview of the immune system. Lancet 2001;357:1777–1789.
  22. Hughes DA: Antioxidant vitamins and immune function; in Calder PC, Field CJ, Gill HS (eds): Nutrition and Immune Function. Wallingford, CAB International, 2002, pp 171–191.
  23. Calder PC, Jackson AA: Under-nutrition, infection and immune function. Nutr Res Rev 2000;13:3–29.

    External Resources

  24. Rossig L, Hoffmann J, Hugel B, Mallat Z, Haase A, Freyssinet JM: Vitamin C inhibits endothelial cell apoptosis in congestive heart failure. Circulation 2001;104:2182–2187.
  25. Price KD, Price CSC, Reynolds RD: Hyperglycemia-induced ascorbic acid deficiency promotes endothelial dysfunction and the development of atherosclerosis. Atherosclerosis 2001;158:1–12.
  26. Richartz BM, Werner GS, Ferrari M, Figulla HR: Reversibility of coronary endothelial vasomotor dysfunction in idiopathic dilated cardiomyopathy: acute effects of vitamin C. Am J Cardiol 2001;88:1001–1005.
  27. Heller R, Unbehaum A, Schellenberg B, Meyer B, Werner-Felmayer G, Werner ER: L-ascorbic acid potentiates endothelial nitric oxide synthesis via a chemical stabilization of tetrahydrobiopterin. J Biol Chem 2001;276:40–47.
  28. Smith AR, Visioli F, Hagen TM: Vitamin C matters: increased oxidative stress in cultured aortic endothelial cells without supplemental ascorbic acid. FASEB J 2002;16:125–144.
  29. Carr AC, Frei B: Human neutrophils oxidize low-density lipoprotein by a hypochlorous acid-dependent mechanism. The role of vitamin C. Biol Chem 2002;383:627–636.
  30. Levine M, Conry-Cantilena C, Wang Y, Welch RW, Washko PW, Dhariwal KR, Park JB, Lazarev A, Graumlich JF, King J, Cantilena LR: Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance. Proc Natl Acad Sci USA 1996;93:3704–3709.
  31. Muggli R: Vitamin C and phagocytes; in Cunningham-Rundles S (ed): Nutrient modulation of the immune response. New York, Basel, Hongkong, Marcel Dekker, 1992, pp 75–90.
  32. Anderson R, Oosthuizen R, Maritz R, Theron A, Van Rensburg AJ: The effects of increasing weekly doses of ascorbate on certain cellular and humoral immune functions in normal volunteers. Am J Clin Nutr 1980;33:71–76.
  33. Kay NE, Holloway DE, Hutton SW, Bona ND, Duane WC: Human T-cell function in experimental ascorbic acid deficiency and spontaneous scurvy. Am J Clin Nutr 1982;36:127–130.
  34. Panush RS, Delafuente JC, Katz P, Johnson J: Modulation of certain immunologic responses by vitamin C. III. Potentiation of in vitro and in vivo lymphocyte response. Int J Vitam Nutr Res Suppl 1982;23:35–47.
  35. Anderson R, Smit MJ, Joone GK, van Straden AM: Vitamin C and cellular immune functions: protection against hypochlorous acid-mediated inactivation of glyceraldehyde-3-phosphate dehydrogenase and ATP generation in human leucocytes as a possible mechanism of ascorbate-mediated immunostimulation. Ann NY Acad Sci 1990;587:34–48.
  36. Levy R, Shriker O, Porath A, Riesenberg K, Schlaeffer F: Vitamin C for the treatment of recurrent furunculosis in patients with impaired neutrophil functions. J Infect Dis 1996;173:1502–1505.
  37. Jacob RA, Kelley DS, Pianalto FS, Swendseid ME, Henning SM, Zhang JZ, Ames BN, Fraga CG, Peters JH: Immunocompetence and oxidant defense during ascorbate depletion of healthy men. Am J Clin Nutr 1991;54:1302S–1309S.
  38. Heuser G, Vojdani A: Enhancement of natural killer cell activity and T and B cell function by buffered vitamin C in patients exposed to toxic chemicals; the role of protein kinase-C. Immunopharmacol Immunotoxicol 1997;19:291–312.
  39. Kennes B, Dumont I, Brohee D, Hubert C, Neve P: Effect of vitamin C supplements on cell-mediated immunity in older people. Gerontology 1983;29:305–310.
  40. Jayachandran M, Rani PJA, Arivazhagan P, Panneerselvam C: Neutrophil phagocytic function and humoral immune response with reference to ascorbate supplementation in aging humans. J Anti-Aging Med 2000;3:37–42.
  41. De la Fuente M, Fernandez MD, Burgos MS, Soler A, Prieto A, Miquel J: Immune function in aged women is improved by ingestion of vitamins C and E. Can J Physiol Pharmacol 1998;76:373–380.
  42. Siegel B, Morton JI: Vitamin C and the immune response. Experientia 1977;33:393–395.
  43. Mortola E, Okuda M, Ohno K, Watari T, Tsujimoto H, Hasegawa A: Inhibition of apoptosis and virus replication in feline immunodeficiency virus infected cells by N-acetyl cysteine and ascorbic acid. J Vet Med Sci 1998;60:1187–1193.
  44. Bucca C, Rolla G, Farina JC: Effect of vitamin C on transient increase of bronchial responsiveness in conditions affecting the airways. Ann NY Acad Sci 1992;669:175–187.
  45. Hamuy R, Berman B: Treatment of herpes simplex virus infections with topical antiviral agents. Eur J Dermatol 1998;8:310–319.
  46. Ibs K-H, Rink L: Zinc-altered immune function. J Nutr 2003;133:1452S–1456S.
  47. Keen CL, Gershwin ME: Zinc deficiency and immune function. Annu Rev Nutr 1990;10:415–431.
  48. Kay RG, Tasman-Jones C: Acute zinc deficiency in man during intravenous alimentation. Austr NZ J Surg 1975;45:325–330.
  49. Shankar AH, Prasad AS: Zinc-altered immune function: the biological basis of altered resistance to infection. Am J Clin Nutr 1998;68:447S–463S.
  50. Fraker PJ, King LE, Laakko T, Vollmer TL: The dynamic link between the integrity of the immune system and zinc status. J Nutr 2000;130:1399S–1406S.
  51. Prasad AS: Effects of zinc deficiency on immune functions. J Trace Elem Exp Med 2000;13:1–30.
  52. Amorin-Cruz JA, Moreiras O, Brzozowska A: Longitudinal changes in the intakes of vitamins and minerals of elderly Europeans. Eur J Clin Nutr 1996;50:S77–S85.
  53. Haller J, Weggemans RM, Lammi-Keefe CJ, Ferry M: Changes in the vitamin C status of elderly Europeans: plasma vitamins A, E, B6, B12, folic acid and carotenoids. Eur J Clin Nutr 1996;50:S32–S46.
  54. Wei W, Kim Y, Boudreau N: Association of smoking with serum and dietary levels of antioxidants in adults: NHANES III, 1988–1994. Am J Public Health 2001;91:258–264.
  55. Ibs K-H, Rink L: Zinc; in Hughes DA, Darlington LG, Bendich A (eds): Diet and Human Immune Function. Totowa, Humana Press, 2004, pp 241–259.
  56. Briefel RR, Bialostosky K, Kennedy-Stephensson J, McDowell MA, Ervin RB, Wright JD: Zinc intake of the US population: findings from the Third National Health and Nutrition Examination Survey, 1988–1994. J Nutr 2000;130:1367S–1373S.

    External Resources

  57. Boxer LA, Albertini DF, Baehner RL, Oliver JM: Impaired microtubule assembly and polymorphonuclear function in the Chediak-Higashi syndrome correctable by ascorbic acid. Br J Haematol 1979;43:207–213.
  58. Anderson R: Effects of ascorbate on normal and abnormal leucocyte functions. Int J Vitam Nutr Res 1982;23(suppl):23–24.
  59. Perafan RC, Franca LFS, Alves ACF, Sanchez JA Jr: Acrodermatitis enteropathica: case report and review of the literature. Pediatr Dermatol 2002;19:426–431.
  60. Fischer Walker C, Black RE: Zinc and the risk of infectious disease. Annu Rev Nutr 2004;24:255–275.
  61. Hemila H, Chalker E, D’Souza RRD, Douglas RM, Treacy B: Vitamin C for preventing and treating the common cold. Cochrane Database Syst Rev 2004, issue 4, Art No CD000980.pub2. DOI: 10.1002/14651858.CD000980.pub2.
  62. Hunt C, Chakravorty NK, Annan G, Habibzadeh N, Schorah CJ: The clinical effects of vitamin C supplementation in elderly hospitalized patients with acute respiratory infections. Int J Vitam Nutr Res 1994;64:212–219.
  63. Peters EM, Goetzsche JM, Grobbelaar B, Noakes TD: Vitamin C supplementation reduces the incidence of postrace symptoms of upper-respiratory-tract infection in ultramarathon runners. Am J Clin Nutr 1993;57:170–174.
  64. Mastaloudis A, Morrow JD, Hopkins DW, Devarau S, Traber MG: Antioxidant supplementation prevents exercise-induced lipid peroxidation, but not inflammation, in ultramarathon runners. Free Radic Biol Med 2004;36:1329–1341.
  65. Korant BD, Kauer JE, Butterworth BE: Inhibition by zinc of rhinovirus protein cleavage: interaction with capside polypeptides. J Virol 1976;18:293–306.
  66. Merluzzi VJ, CiprianoD, McNeil D, Fuchs V, Supeau C, Rosenthal AS, Skiles JW: Evaluation of zinc complexes on the replication of rhinovirus 2 in-vitro. Res Commun Chem Pathol Pharmacol 1989;66:425–440.
  67. Kelly RW, Abel MH: Copper and zinc inhibit the metabolism of prostaglandin by the human uterus. Biol Reprod 1983;28:883–889.
  68. Jackson JL, Peterson C, Lesho E: A meta-analysis of zinc salt lozenges and the common cold. Arch Intern Med 1997;157:2373S–2376S.
  69. Marshall I: Zinc for the common cold. Cochrane Database Syst Rev 1999, issue 2, Art No CD001364. DOI: 10.1001/14651858. CD001364.
  70. Al-Nakib W, Higgins PG, Barrow I, Batsone G, Tyrell DA: Prophylaxis and treatment of rhinovirus colds with zinc gluconate lozenges. J Antimicrob Chemother 1987;20:893–901.
  71. Farr BM, Conner EM, Betts RF, Oleske J, Minnefor A, Gwaltney JM: Two randomized controlled trials of zinc gluconate lozenges therapy of experimentally induced rhinovirus colds. Antimicrob Agents Chemother 1987;31:1183–1187.
  72. Turner RB: Ineffectiveness of intranasal zinc gluconate for prevention of experimental rhinovirus colds. Clin Infect Dis 2001;33:1865–1870.
  73. Turner RB, Cetnarowski WE: Effect of treatment with zinc gluconate or zinc acetate on experimental and natural colds. Clin Infect Dis 2000;31:1202–1208.
  74. Prasad AS, Fitzgerald JT, Bao B, Beck FW, Chandrasekar PH: Duration of symptoms and plasma cytokine levels in patients with the common cold treated with zinc acetate. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 2000;133:245–252.
  75. Eby GA: Zinc ion availability – the determinant of efficacy in zinc lozenge treatment of common colds. J Antimicrob Chemother 1997;40:483–493.
  76. Zinc Investigators’ Collaborative Group: Bhutta ZA, Black RE, Brown KH, Meeks Gardner J, Gore S, Hidajat J, Khatun F, Martorell R, Ninh NX, Penny ME, Rosado JL, Roy SK, Ruel M, Sazawal S, Shankar A: Prevention of diarrhea and pneumonia by zinc supplementation in children in developing countries: pooled analysis of randomized controlled trials. J Pediatr 1999;135:689–697.
  77. Bhandari N, Bahl R, Taneja S, Strand T, Molbak K, Ulvik RJ, Sommerfelt H, Bhan MK: Effect of routine zinc supplementation on pneumonia in children aged 6 months to 3 years: randomised controlled trial in an urban slum. BMJ 2002;324:1358–1360.
  78. Zinc Investigators’ Collaborative Group: Bhutta ZA, Bird SM, Black RE, Brown KH, Gardner JM, Hidayat A, Khatun F, Martorell R, Ninh NX, Penny ME, Rosado JL, Roy SK, Ruel M, Sazawal S, Shankar A: Therapeutic effects of oral zinc in acute and persistent diarrhea in children in developing countries: pooled analysis of randomized controlled trials. Am J Clin Nutr 2000;72:1516–1522.
  79. Brooks WA, Yunus M, Santosham M, Wahed MA, Nahar K, Yeasmin S, Black RE: Zinc for severe pneumonia in very young children: double-blind placebo-controlled trial. Lancet 2004;363:1683–1688.
  80. Baqui AH, Black RE, El Arifeen S, Yunus M, Chakraborty J, Ahmed S, Vaughan JP: Effect of zinc supplementation started during diarrhoea on morbidity and mortality in Bangladeshi children: community randomised trial. BMJ 2002;325:1059.
  81. Mahalanabis D, Lahiri M, Paul D, Gupta S, Gupta A, Wahed MA, Khaled MA: Randomized, double-blind, placebo-controlled clinical trial of the efficacy of treatment with zinc and vitamin A in infants and young children with severe acute lower respiratory infection. Am J Clin Nutr 2004;79:430–436.
  82. Black RE: Zinc deficiency, infectious disease, and mortality in the developing world. J Nutr 2003;133:1485S–1489S.
  83. Fraker PJ, King LE, Laako T, Vollmer TL: The dynamic link between the integrity of the immune system and zinc status. J Nutr 2000;130:399S–406S.
  84. Castillo-Duran C, Vial P, Uauy R: Trace mineral balance during acute diarrhea in infants. J Pediatr 1988;113:452–457.
  85. Baqui AH, Zaman K, Persson LA, El-Arifeen S, Yunus-Mohammad BN, Black RE: Simultaneous weekly supplementation of iron and zinc is associated with lower morbidity due to diarrhea and acute lower respiratory infection in Bangladeshi infants. J Nutr 2003;133:4150–4157.
  86. Rahman MM, Vermund SH, Wahed MA, Fuchs GJ, Baqui AH, Alvarez JO: Simultaneous zinc and vitamin A supplementation in Bangladeshi children: randomized double blind controlled trial. BMJ 2001;323:314–318.
  87. Bhatnagar S, Natchu UCM: Zinc in child health and disease. Indian J Pediatr 2004;71:991–995.
  88. Gupta DN, Mondal SK, Ghosh S, Rajendran K, Sur D, Manna B: Impact of zinc supplementation on diarrhoeal morbidity in rural children of West Bengal. Acta Paediatr 2003;92:531–536.
  89. Al-Sonboli N, Gurgel RQ, Shenkin A, Hart CA, Cuevas LE: Zinc supplementation in Brazilian children with acute diarrhea. Ann Trop Paediatr 2003;23:3–8.
  90. MacLeod WB, Krebs NF, Westcott JL, Fawzi WW, Premji ZG, Mwanakasale V, Simon JL, and the Zinc against Plasmodium Study Group: Plasma zinc concentrations are depressed during acute phase response in children with falciparum malaria. J Nutr 2005;135:802–807.
  91. Gibson RS, Huddle JM: Suboptimal zinc status in pregnant Malawian women: its association with low intakes of poorly available zinc, frequent reproductive cycling, and malaria. Am J Clin Nutr 1998;67:702–709.
  92. Zinc against Plasmodium Study Group: Effect of zinc on the treatment of Plasmodium falciparum malaria in children: a randomized controlled trial. Am J Clin Nutr 2002;76:805–812.
  93. Bates C, Evans PH, Dardenne M, Prentice A, Lunn PG, Northropclewes CA, Hoare S, Cole TJ, Horan SJ, Longman SC, Stirling D, Aggett PJ: A trial of zinc supplementation in young rural Gambian children. Br J Nutr 1993;69:243–255.

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