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Table of Contents
Vol. 51, No. 4, 2007
Issue release date: September 2007
Section title: Review
Ann Nutr Metab 2007;51:301–323
(DOI:10.1159/000107673)

Contribution of Selected Vitamins and Trace Elements to Immune Function

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

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Article / Publication Details

First-Page Preview
Abstract of Review

Accepted: 2/21/2007
Published online: 8/28/2007

Number of Print Pages: 23
Number of Figures: 1
Number of Tables: 3

ISSN: 0250-6807 (Print)
eISSN: 1421-9697 (Online)

For additional information: http://www.karger.com/ANM

Abstract

Adequate intakes of vitamins and trace elements are required for the immune system to function efficiently. Micronutrient deficiency suppresses immune functions by affecting the innate T-cell-mediated immune response and adaptive antibody response, and leads to dysregulation of the balanced host response. This increases the susceptibility to infections, with increased morbidity and mortality. In turn, infections aggravate micronutrient deficiencies by reducing nutrient intake, increasing losses, and interfering with utilization by altering metabolic pathways. Insufficient intake of micronutrients occurs in people with eating disorders, in smokers (both active and passive), in individuals with chronic alcohol abuse, in patients with certain diseases, during pregnancy and lactation, and in the elderly. With aging a variety of changes are observed in the immune system, which translate into less effective innate and adaptive immune responses and increased susceptibility to infections. Antioxidant vitamins and trace elements (vitamins C, E, selenium, copper, and zinc) counteract potential damage caused by reactive oxygen species to cellular tissues and modulate immune cell function through regulation of redox-sensitive transcription factors and affect production of cytokines and prostaglandins. Adequate intake of vitamins B6, folate, B12, C, E, and of selenium, zinc, copper, and iron supports a Th1 cytokine-mediated immune response with sufficient production of proinflammatory cytokines, which maintains an effective immune response and avoids a shift to an anti-inflammatory Th2 cell-mediated immune response and an increased risk of extracellular infections. Supplementation with these micronutrients reverses the Th2 cell-mediated immune response to a proinflammatory Th1 cytokine-regulated response with enhanced innate immunity. Vitamins A and D play important roles in both cell-mediated and humoral antibody response and support a Th2-mediated anti-inflammatory cytokine profile. Vitamin A deficiency impairs both innate immunity (mucosal epithelial regeneration) and adaptive immune response to infection resulting in an impaired ability to counteract extracellular pathogens. Vitamin D deficiency is correlated with a higher susceptibility to infections due to impaired localized innate immunity and defects in antigen-specific cellular immune response. Overall, inadequate intake and status of these vitamins and minerals may lead to suppressed immunity, which predisposes to infections and aggravates malnutrition.


Article / Publication Details

First-Page Preview
Abstract of Review

Accepted: 2/21/2007
Published online: 8/28/2007

Number of Print Pages: 23
Number of Figures: 1
Number of Tables: 3

ISSN: 0250-6807 (Print)
eISSN: 1421-9697 (Online)

For additional information: http://www.karger.com/ANM


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Scrimshaw NS, Taylor CE, Gordon JE: Effects of infections on nutritional status. Interactions of nutrition and infection. Monogr Ser World Health Organ 1968;57:44–46.
  2. Calder PC, Jackson AA: Under-nutrition, infection and immune function. Nutr Res Rev 2000;13:3–29.

    External Resources

  3. Field CJ, Johnson IR, Schley PD: Nutrients and their role to host resistance to infection. J Leukoc Biol 2002;71:16–32.
  4. Scrimshaw NS, San Giovanni JP: Synergism of nutrition, infection, and immunity: an overview. Am J Clin Nutr 1997;66:464S–477S.
  5. Bhaskaram P: Micronutrient malnutrition, infection, and immunity: an overview. Nutr Res 2002;60:S440–S445.
  6. Manore MM: Chronic dieting in active women: what are the health consequences? Womens Health Issues 1996;6:332–341.
  7. Margetts BM, Jackson AA: Interactions between people’s diet and their smoking habits: the dietary and nutritional survey of British adults. BMJ 1993;307:1381–1384.
  8. Romieu T: Nutrition and lung health. Int J Tuberc Lung Dis 2005;9:362–374.
  9. van den Berg H, van der Gaag M, Hendriks H: Influence of lifestyle on vitamin bioavailability. Int J Vitam Nutr Res 2001;72:53–59.
  10. Barringer TA, Kirk JK, Santaniello AC, Long Foley K, Michielutta R: Effect of a multivitamin and mineral supplement on infection and quality of life. Ann Intern Med 2003;138:365–371.
  11. Ladipo OA: Nutrition in pregnancy: mineral and vitamin supplements. Am J Clin Nutr 2000;72(suppl):280S–290S.
  12. Tucker K: Micronutrient status and aging. Nutr Rev 1995;53:S9–S15.
  13. 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(suppl 2):S32–S46.

    External Resources

  14. Martins I, Dantas A, Guoimar S, Amorim Cruz A: Vitamin and mineral intakes in elderly. J Nutr Health Aging 2002;6:63–65.
  15. Castle S: Clinical relevance of age-related immune dysfunction. Clin Infect Dis 2000;31:578–585.
  16. Burns EA, Goodwin JS: Effect of aging on immune function. J Nutr Health Aging 2004;8:9–18.
  17. Lesourd BM: Nutrition: a major factor influencing immunity in the elderly. J Nutr Health Aging 2004;8:28–37.
  18. Parkin J, Cohen B: An overview on the immune system. Lancet 2001;357:1777–1789.
  19. Delves PJ, Roitt IM: The immune system. First of two parts. N Engl J Med 2000a;343:37–49.
  20. Delves PJ, Roitt IM: The immune system. Second of two parts. N Engl J Med 2000;343:108–117.
  21. Paajanen L: Effects of cow’s milk and its processing on gastrointestinal symptoms and delayed-type immune responses; PhD thesis, University of Helsinki, 2005, ISBN 952-10-2800-9.
  22. Berger A: Th1 and Th2 responses: what are they? BMJ 2000;321:424.
  23. Albers R, Antoine JM, Bourdet-Sicard R, Calder PC, Gleeson M, Lesourd B, Samartin IR, Sanderson IA, van Loo J, Vas Dias FW, Watzl B: Markers to measure immunomodulation in human nutrition intervention studies. Br J Nutr 2005;94:452–481.
  24. Chandra RK, Sudhakaran L: Regulation of immune responses by vitamin B6. Ann NY Acad Sci 1990;585:404–423.
  25. Rall LC, Meydani SN: Vitamin B6 and immune competence. Nutr Rev 1993;51:217–225.
  26. Trakatellis A, Dimitriadou A, Trakatelli M: Pyridoxine deficiency: new approaches in immunosuppression and chemotherapy. Postgrad Med J 1997;73:617–622.
  27. Ockhuizen T, Spanhaak S, Mares N, Veenstra J, Wedel M, Mulder J, van den Berg H: Short-term effects of marginal vitamin B deficiencies on immune parameters in healthy young volunteers. Nutr Res 1990;10:483–492.
  28. Miller LT, Kerkvliet NT: Effect of vitamin B6 on immune competence in the elderly. Ann NY Acad Sci 1990;587:49–54.
  29. Long KZ, Santos JL: Vitamins and the regulation of the immune response. Pediatr Infect Dis J 1999;18:283–290.
  30. Kwak HK, Hansen CM, Leklem JE, Hardin K, Shultz TD: Improved vitamin B-6 status is positively related to lymphocyte proliferation in young women consuming a controlled diet. J Nutr 2002;132:3308–3313.
  31. Dhur A, Galan P, Hercberg S: Folate status and the immune system. Prog Food Nutr Sci 1991;15:43–60.
  32. Courtemanche C, Elson-Schwab I, Mashiyuama ST, Kerry N, Ames BN: Folate deficiency inhibits the proliferation of primary human CD8+ T lymphocytes in vitro. J Immunol 2004;173:3186–3189.
  33. Troen AM, Mitchell B, Sorensen B, Wener MH, Johnston A, Wood B, Selhub J, McTiernan A, Yasui Y, Oral E, Potter JD, Ulrich CM: Unmetabolized folic acid in plasma is associated with reduced natural killer cell cytotoxicity among postmenopausal women. J Nutr 2006;136:189–194.
  34. Ravaglia G, Forti P, Maioli F, Bastagli L, Facchini A, Mariani E, Savarino L, Sassi S, Cucinotta D, Lenaz G: Effect of micronutrient status on natural killer cell immune function in healthy free-living subjects aged ≥90 years. Am J Clin Nutr 2000;71:590–598.
  35. Bunout D, Barrera G, Hirsch S, Gattas V, de la Maza MP, Haschke F, Steenhout P, Klassen P, Hager C, Avendano M, Petermann M, Munoz C: Effects of a nutritional supplement on the immune response and cytokine production in free-living Chilean elderly. JPEN J Parenter Enteral Nutr 2004;28:348–354.
  36. Bailey LB, Gregory JF III: Folate; in Bowman BA, Russel RM (eds): Present Knowledge in Nutrition, ed 9. Washington, ILSI Press, 2006, pp 278–301.
  37. Tamura J, Kubota K, Murakami H, Sawamura M, Matsushima T, Tamura T, Saitoh T, Kurabayashi H, Naruse T: Immunomodulation by vitamin B12: augmentation of CD8+ T lymphocytes and natural killer (NK) cell activity in vitamin B12-deficient patients by methyl-B12 treatment. Clin Exp Immunol 1999;116:28–32.
  38. Fata FT, Herzlich B, Schiffman G, Ast AL: Impaired antibody responses to pneumococcal polysaccharide in elderly patients with low serum vitamin B12 levels. Ann Intern Med 1996;124:299–304.
  39. Stabler SP, Lindenbaum J, Allen RH: Vitamin B12 deficiency in the elderly: current dilemmas. Am J Clin Nutr 1997;66:741–749.
  40. Hughes DA: Antioxidant vitamins and immune function; in Calder PC, Field CJ, Gill HS (eds): Nutrition and Immune Function. Wallingford, CAB International, 2000, pp 171–191.
  41. Ames BN, Shigenaga MK, Hagen TM: Oxidants, antioxidants, and the degenerative disease of aging. Proc Natl Acad Sci USA 1993;90:7915–7922.
  42. Wintergerst ES, Maggini S, Hornig DH: The immune-enhancing role of vitamin C and zinc and effect on clinical conditions. Ann Nutr Metab 2006;50:85–94.
  43. 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.
  44. Jeng KC, Yang CS, Siu WY, Tsai YS, Liao WJ, Kuo JS: Supplementation with vitamin C and E enhances cytokine production by peripheral blood mononuclear cells in healthy adults. Am J Clin Nutr 1996;64:960–965.
  45. Haertel C, Strunk T, Bucsky P, Schultz C: Effects of vitamin C on intracytoplasmic cytokine production in human whole blood monocytes and lymphocytes. Cytokine 2004;27:101–106.
  46. Johnston CS: Complement component C1q unaltered by ascorbate supplementation in healthy men and women. J Nutr Biochem 1991;2:499–501.
  47. 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.
  48. 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.
  49. 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.
  50. Wannamethee SG, Lowe GDO, Rumley A, Bruckdorfer KR, Whincup PH: Association of vitamin C status, fruit and vegetable intakes, and markers of inflammation and hemostasis. Am J Clin Nutr 2006;83:567–574.
  51. Jialal I, Singh U: Is vitamin C an anti-inflammatory agent? Am J Clin Nutr 2006;83:525–526.
  52. 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.
  53. Hamuy R, Berman B: Treatment of herpes simplex virus infections with topical antiviral agents. Eur J Dermatol 1998;8:310–319.
  54. Hume R, Weyers E: Changes in leukocyte ascorbic acid during the common cold. Scot Med J 1973;18:3–7.
  55. Douglas RM, Hemilä H, Chalker E, Treacy B: Vitamin C for preventing and treating the common cold. Cochrane Database of Systematic Reviews 2007, Issue 3. Art. No.: CD 000980. DOI:10.1002/14651858. CD000980.pub.3.
  56. 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.
  57. Palazetti S, Rousseau AS, Richard MJ, Favier A, Margaritis I: Antioxidant supplementation preserves antioxidant response in physical training and low antioxidant intake. Br J Nutr 2004;91:91–100.
  58. Fischer CP, Hiscock NJ, Penkowa M, Basu S, Vessby B, Kallner A, Sjoeberg LB, Pedersen BK: Supplementation with vitamins C and E inhibits the release of interleukin-6 from contracting human skeletal muscle. J Physiol 2004;558:633–645.
  59. Nieman DC, Peters EM, Henson DA, Nevines EI, Thompson MM: Influence of vitamin C supplementation on cytokine changes following an ultramarathon. J Interferon Cytokine Res 2000;20:1029–1035.
  60. Petersen EW, Ostrowski K, Ibfelt T, Richelle M, Offord E, Halkjaer-Kristensen J, Pedersen BK: Effect of vitamin C supplementation on cytokine response and on muscle damage after strenuous exercise. Am J Physiol Cell Physiol 2001;280:C1570–C1575.
  61. Thompson D, Williams C, McGregor SJ, Nicholas CW, McArdle F, Jackson MJ, Powell JR: Prolonged vitamin C supplementation and recovery from demanding exercise. Int J Sport Nutr Exerc Metab 2001;11:466–481.
  62. Stephensen CB: Vitamin A, infection, and immunity. Annu Rev Nutr 2001;21:167–192.
  63. Villamor E, Fawzi WW: Effects of vitamin A supplementation on immune responses and correlation with nutritional outcome. Clin Microbiol Rev 2005;18:446–464.
  64. Sommer A, Katz J, Tarwotjo I: Increased risk of respiratory disease and diarrhea in children with preexisting mild vitamin A deficiency. Am J Clin Nutr 1984;40:1090–1095.
  65. Barreto ML, Santos LMP, Assis AMO, Araujo MP, Farenzena GG, Santos PA, Fiaccone RL: Effect of vitamin A supplementation on diarrhoea and acute lower-respiratory tract infections in young children in Brazil. Lancet 1994;344:228–231.
  66. Beaton GH, Martorell R, Aronson KJ, Edmonston B, McCabe G, Ross AC, Harvey B: Effectiveness of Vitamin A Supplementation in the Control of Young Child Morbidity and Mortality in Developing Countries. ACC/SCN State-of-the-Art Series. Nutrition Policy Discussion Paper No. 13. Geneva, 1993.
  67. The Vitamin A and Pneumonia Working Group: Potential interventions for the prevention of childhood pneumonia in developing countries: a meta-analysis of data from field trials to assess the impact of vitamin A supplementation on pneumonia morbidity and mortality. Bull World Health Organ 1995;73:609–619.
  68. Long KZ, Montoya Y, Hertzmark E, Santos JI, Rosado JL: A double-blind, randomized, clinical trial on the effect of vitamin A and zinc supplementation on diarrheal disease and respiratory tract infections in children in Mexico City, Mexico. Am J Clin Nutr 2006;83:693–700.
  69. Shankar AH: Nutritional modulation of malaria morbidity and mortality. J Infect Dis 2000;182:S37–S53.
  70. Karyadi E, West CE, Schultink W, Newlan RHN, Gross R, Amin Z, Dolmans WMV, Schlebush H, van der Meer JWM: A double-blind placebo-controlled study of vitamin A and zinc supplementation in persons with tuberculosis in Indonesia: effects on clinical response and nutritional status. Am J Clin Nutr 2002;75:720–727.
  71. Reifen R: Vitamin A as an anti-inflammatory agent. Proc Nutr Soc 2002;61:397–400.
  72. Thurnham D, Northrop-Clewes C, McCullough F, Das B, Lunn P: Innate immunity, gut integrity, and vitamin A in Gambian and Indian infants. J Infect Dis 2000;182:S23–S28.
  73. Ramakrishnan U, Web AL, Ologoudou K: Infection, immunity, and vitamins; in Gershwin NE, Nestel P, Keen CL (eds): Handbook of Nutrition and Immunity. Totowa, Humana Press, 2004, pp 93–115.
  74. Dawson HD, Li NQ, Deciccio KL, Nibert JA, Ross AC: Chronic marginal vitamin A status reduces natural killer cell number and activity and function in aging Lewis rats. J Nutr 1999;129:1510–1517.
  75. Aukrust P, Mueller F, Ueland T, Svardal A, Berge R, Froland SS: Decreased vitamin A levels in common variable immunodeficiency: vitamin A supplementation in vivo enhances immunoglobulin production and downregulates inflammatory responses. Eur J Clin Invest 2000;30:252–259.
  76. Halevy O, Arazi Y, Melamed D, Friedman A, Sklan D: Retinoic acid receptor-alpha gene expression is modulated by dietary vitamin A and by retinoic acid in chicken T lymphocytes. J Nutr 1994;124:2139–2146.
  77. Cantorna MT, Nashold FE, Hayes C: In vitamin A deficiency multiple mechanism establish a regulatory T helper cell imbalance with excess Th1 and insufficient Th2 function. J Immunol 1994;152:1515–1522.
  78. Rahman MM, Mahalanabis D, Alvarez JO, Wahed MA, Islam MA, Habte D: Effect of early vitamin A supplementation on cell-mediated immunity in infants younger than 6 months. Am J Clin Nutr 1997;65:144–148.
  79. Semba RD: Vitamin A as ‘anti-infective’ therapy. J Nutr 1999;129:783–791.
  80. Semba RD, Calder PC, Field CJ, Gill HS: Vitamin A, infection and immune function. Front Nutr Sci 2002;151–169.
  81. Semba RD: Vitamin A; in Hughes DA, Darlington LG, Bendich A (eds): Diet and Human Immune Function. Totowa, Humana Press, 2004, pp 105–131.
  82. Hayes CE, Nashold FE, Spach KM, Pedersen LB: The immunological functions of the vitamin D endocrine system. Cell Molec Biol 2003;49:277–300.
  83. Griffin MD, Xing N, Kumar R: Vitamin D and its analogs as regulators of immune activities and antigen presentation. Annu Rev Nutr 2003;23:117–145.
  84. Cantorna MT, Zhu Y, Froicu M, Wittke A: Vitamin D status, 1,25-dihydroxy- vitamin D3, and the immune system. Am J Clin Nutr 2004;80:1717S–1720S.
  85. Veldman CM, Cantorna MT, DeLuca HF: Expression of 1,25-dihydroxyvitamin D3 receptor in the immune system. Arch Biochem Biophys 2000;374:334–338.
  86. Reichel H, Koeffler HP, Norman AW: Regulation of immune system 1α,25-dihydroxyvitamin D3 by hematopoietic cells. Prog Clin Biol Res 1990;332:81–97.

    External Resources

  87. Boonstra A, Barrat FJ, Crain C, Heath VL, Savelkoul HF, O’Garra A: 1α,25-Dihydroxyvitamin D3 has a direct effect on naïve CD4(+) T cells to enhance the development of Th2 cells. J Immunol 2001;167:4974–4980.
  88. Penna G, Adorini L: 1α,25-Dihydroxyvitamin D3 inhibits differentiation, maturation, activation and survival of dendritic cells leading to impaired alloreactive T cell activation. J Immunol 2000;164:2405–2411.
  89. Banchereau J, Steinman RM: Dendritic cells and the control of immunity. Nature 1998;392:245–252.
  90. Yang S, Smith C, Prahl JM, Luo X, DeLuca HF: Vitamin D deficiency suppresses cell-mediated immunity in vivo. Arch Biochem Biophys 1993;303:98–106.
  91. DeLuca HF, Cantorna MT: Vitamin D: its role and uses in immunology. FASEB J 2001;15:2579–2585.
  92. Lemire JM, Archer DC, Beck L, Spiegelberg HL: Immunosuppressive actions of 1,25(OH)2D3: preferential inhibition of Th1 functions. J Nutr 1995;125:1704S–1708S.
  93. Hypponen E, Laara E, Reunanen A, Jarvelin MR, Virtanen SM: Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. Lancet 2001;358:1500–1503.
  94. The EURODIAB Substudy 2 Study Group: Vitamin D supplement in early childhood and risk for type I (insulin-dependent) diabetes mellitus. Diabetologia 1999;42:51–54.
  95. Witte KK, Clark AL: Chronic heart failure and multiple micronutrient supplementation: realistic hope or idealistic conjecture? Heart Fail Monit 2005;4:123–129.

    External Resources

  96. Mahon BD, Gordon SA, Cruz J, Cosman F, Cantorna MT: Cytokine profile in patients with multiple sclerosis following vitamin D supplementation. J Neuroimmunol 2003;134:128–132.
  97. Schleithoff SS, Zittermann A, Tenderich G, Berthold HK, Stehle P, Koerfer R: Vitamin D supplementation improves cytokine profiles in patients with congestive heart failure: a double-blind, randomized, placebo-controlled trial. Am J Clin Nutr 2006;83:754–759.
  98. Zittermann A, Schleithoff SS, Tenderich G, Berthold HK, Koerfer R, Stehle P: Low vitamin D status: A contributing factor in the pathogenesis of congestive heart failure? J Am Coll Cardiol 2003;41:105–112.
  99. Meydani SN, Han SN, Wu D: Vitamin E and immune response in the aged: molecular mechanism and clinical implications. Immunol Rev 2005;205:269–284.
  100. Miller RA: The aging immune system: primer and prospectus. Science 1996;273:70–74.
  101. Meydani SN, Meydani M, Blumberg JB, Leka LS, Siber G, Loszewski R, Thompson C, Pedrosa MC, Diamond RD, Stollar BD: Vitamin E supplementation and in vivo immune response in healthy elderly subjects. A randomized controlled trial. JAMA 1997;277:1380–1386.
  102. Meydani SN, Barklund MP, Liu S, Miller RA, Cannon JG, Morow FD, Rocklin R, Blumberg JB: Vitamin E supplementation enhances cell-mediated immunity in healthy elderly subjects. Am J Clin Nutr 1990;53:557–563.
  103. Pallast E, Schouten E, de Waart F, Fonk H, Doekes G, von Blomberg B, Kok FJ: Effect of 50- and 100-mg vitamin E supplements on cellular immune function in non-institutionalized elderly persons. Am J Clin Nutr 1999;69:1273–1281.
  104. Meydani SN, Leka LS, Fine BC, Dallal GE, Keusch GT, Singh MF, Hamer DH: Vitamin E and respiratory tract infections in elderly nursing home residents: a randomized controlled trial. JAMA 2004;292:828–836.
  105. Graat JM, Schouten EG, Kok FJ: Effect of daily vitamin E and multivitamin/multimineral supplementation on acute respiratory tract infections in elderly persons. JAMA 2002;288:715–721.
  106. De la Fuente M, Ferrandez 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.
  107. Park OJ, Kim HYP, Kim WK, Kim YJ, Kim SH: Effect of vitamin E supplementation on antioxidant defense systems and humoral immune response in young, middle-aged and elderly Korean women. J Nutr Sci Vitaminol 2003;49:94–99.
  108. DeWaart FG, Portengen L, Doekes G, Verwaal CJ, Kok FJ: Effect of 3 months vitamin E supplementation on indices of the cellular and humoral immune response in elderly subjects. Br J Nutr 1997;78:761–774.
  109. Hara M, Tanaka K, Hirota Y: Immune response to influenza vaccine in healthy adults and the elderly: association with nutritional status. Vaccine 2005;23:1457–1463.
  110. Lee CYJ, Wan JMF: Vitamin E supplementation improves cell-mediated immunity and oxidative stress of Asian men and women. J Nutr 2000;130; 2932–2937.
  111. Han SN, Adolfsson O, Lee CK, Prolla TA, Ordovas J, Meydani SN: Vitamin E and gene expression in immune cells. Ann NY Acad Sci 2004;1031:96–101.
  112. Han SN, Meydani SN: Vitamin E; in Hughes DA, Darlington LG, Bendich A (eds): Diet and Human Immune Function. Totowa, Humana Press, 2004, pp 149–164.
  113. Vassilakopoulos T, Karatsa MH, Katsaounou P, Kollintza A, Zakynthinos S, Roussos C: Antioxidants attenuate the plasma cytokine response to exercise in humans. J Appl Physiol 2003;94:1025–1032.
  114. Kowdley KV, Mason JB, Meydani SN, Cornwall S, Grand RJ: Vitamin E deficiency and impaired cellular immunity related to intestinal fat malabsorption. Gastroenterology 1992;102:2139–2142.
  115. Ghalaut VS, Ghalaut PS, Kharb S, Singh GP: Vitamin E in intestinal fat malabsorption. Ann Nutr Metab 1995;39:296–301.
  116. Arthur JR, McKenzie R, Beckett GJ: Selenium in the immune system. J Nutr 2003;1457S–1459S.
  117. Ferencik M, Ebringer L: Modulatory effects of selenium and zinc on the immune system. Folia Microbiol 2003;48:417–426.
  118. Ryan-Harshman M, Aldoori W: The relevance of selenium to immunity, cancer, and infectious/inflammatory diseases. Can J Diet Prac Res 2005;66:98–102.
  119. Klotz LO, Kroencke KD, Buchczyk DP, Sies H: Role of copper, zinc, selenium, and tellurium in the cellular defense against oxidative and nitrosative stress. J Nutr 2003;133:1448S–1451S.
  120. Beckett GJ, Arthur JR, Miller SM, McKenzie RC: Selenium; in Hughes DA, Darlington LG, Bendich A (eds): Diet and Human Immune Function. Totowa, Humana Press, 2004, pp 217–240.
  121. Broome CS, McArdle F, Kyle JAM, Andrews F, Lowe NM, Hart CA, Arthur JR, Jackson MJ: An increase in selenium intake improves immune function and poliovirus handling in adults with marginal selenium status. Am J Clin Nutr 2004;80:154–162.
  122. Kiremidjian-Schumacher L, Roy M, Wishe H, Cohen MW, Stotzky G: Supplementation with selenium and human immune cell functions. Biol Trace Element Res 1994;41:115–127.
  123. Roy M, Kiremidjian-Schumacher L, Wishe H, Cohen MW, Stotzky G: Supplementation with selenium restores age-related decline in immune cell function. Proc Soc Exp Biol Med 1995;209:369–375.
  124. Hawkes WC, Kelley DS, Taylor PC: The effects of dietary selenium on the immune system in healthy men. Biol Trace Element Res 2001;81:189–213.
  125. Peretz A, Neve J, Desmedt J, Duchateau J, Dramaix M, Famaey JP: Lymphocyte response is enhanced by supplementation of elderly subjects with selenium-enriched yeast. Am J Clin Nutr 1991;53:1323–1328.
  126. Girodon F, Galan P, Monget AL, Boutron-Ruault MC, Brunet-Lecomte P, Preziosi P, Arnaud J, Manuguerra JC, Hercberg S: Impact of trace elements and vitamin supplementation on immunity and infections in institutionalized elderly patients. A randomized controlled trial. Arch Intern Med 1999;159:748–754.
  127. Faure P, Ramon O, Favier A, Halimi S: Selenium supplementation decreased nuclear factor-kappa B activity in peripheral blood mononuclear cells from type 2 diabetic patients. Eur J Clin Invest 2004;34:475–481.
  128. Prasad AS: Effects of zinc deficiency on immune functions. J Trace Elem Exp Med 2000;13:1–30.
  129. Ibs KH, Rink L: Zinc-altered immune function. J Nutr 2003;133:1452S–1456S.
  130. Fraker PJ, King LE: Reprogramming of the immune system during zinc deficiency. Ann Rev Nutr 2004;24:277–298.
  131. Powell SR: The antioxidant properties of zinc. J Nutr 2000;130:1447S–1454S.
  132. Kuppusamy UR, Dharmani M, Kanthimathi MS, Indran M: Antioxidant enzyme activities of human peripheral blood mononuclear cells exposed to trace elements. Biol Trace Element Res 2005;106:29–39.
  133. Ho E, Courtemanche C, Ames BN: Zinc deficiency induces oxidative DNA damage and increased p53 expression in human lung fibroblasts. J Nutr 2003;133:2543–2548.
  134. Prasad AS: Effects of zinc deficiency on Th1 and Th2 cytokine shifts. J Infect Dis 2000;182(suppl):S62–S68.

    External Resources

  135. 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. Zinc Investigators’ Collaborative Group. J Pediatr 1999;135:689–697.
  136. 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.
  137. Fischer Walker C, Black RE: Zinc and the risk for infectious disease. Annu Rev Nutr 2004;24:255–275.
  138. Brooks WA, Santosham M, Naheed A, Goswami D, Waheed MA, Diener-West M, Faruque ASG, Black RE: Effect of weekly zinc supplements on incidence of pneumonia and diarrhea in children younger than 2 years in an urban, low-income population in Bangladesh: randomized controlled trial. Lancet 2005;366:999–1004.
  139. Bose A, Coles CL, Gunavathi, John H, Moses P, Raghupathy P, Kirubakaran C, Black RE, Brooks WA, Santosham M: Efficacy of zinc in the treatment of severe pneumonia in hospitalized children <2 y old. Am J Clin Nutr 2006;83:1089–1096.
  140. Sazawal S, Black RE, Jalla S, Mazumdar S, Sinha A, Bhan MK: Zinc supplementation reduces the incidence of acute lower respiratory infections in infants and pre-school children: a double-blind, controlled trial. Pediatrics 1998;102:1–5.
  141. 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.
  142. Chang AB, Torzillo PJ, Boyce NC, White AV, Stewart PM, Wheaton GR, Purdie DM, Wakerman J, Valery PC: Zinc and vitamin A supplementation in indigenous Australian children hospitalized with lower respiratory tract infection: a randomized controlled trial. Med J Austr 2006;184:107–112.
  143. Korant BD, Kauer JE, Butterworth BE: Inhibition by zinc of rhinovirus protein cleavage: interaction with capside polypeptides. J Virol 1976;18:293–306.
  144. Marshall I: Zinc for the common cold. Cochrane Database Syst Rev 1999;(2):CD001364. DOI: 10.1001/14651858.
  145. Turner RB: Ineffectiveness of intranasal zinc gluconate for prevention of experimental rhinovirus colds. Clin Infect Dis 2001;33:1865–1870.
  146. 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.
  147. 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.
  148. Eby GA: Zinc ion availability – the determinant of efficacy in zinc lozenge treatment of common colds. J Antimicrob Chemother 1997;40:483–493.
  149. Andriollo-Sanchez M, Hininger-Favier I, Meunier N, Toti E, Zaccaria M, Brandolini-Bunlon M, Polito A, O’Connor JM, Ferry M, Coudray C, Roussel AM: Zinc intake and status in middle-aged and older European subjects: the ZENITH study. Eur J Clin Nutr 2005;59(suppl 2):S37–S41.
  150. Briefel RR, Bialostosky K, Kennedy-Stephenson J, McDowell MA, Erwin RBR, Wright JD: Zinc intake of the US population: findings from the third National Health and Nutrition Examination Survey, 1998–1994. J Nutr 2000;130:1367S–1373S.
  151. Cakman I, Rohwer J, Schütz RM, Kirchner H, Rink L: Dysregulation between TH1 and TH2 T cell subpopulation in the elderly. Mech Ageing Dev 1996;87:197–209.
  152. Bogden JD: Influence of zinc on immunity in the elderly. J Nutr Health Aging 2004;8:248–254.
  153. Prasad AS, Fitzgerald JT, Hess JW, Kaplan J, Pelen F, Dardenne M: Zinc deficiency in elderly patients. Nutrition 1993;9:218–224.
  154. Cossack ZT: T-lymphocyte dysfunction in the elderly associated with zinc deficiency and subnormal nucleoside phosphorylase activity: effect of zinc supplementation. Eur J Cancer Clin Oncol 1989;25:973–976.
  155. Fortes C, Forastiere F, Agabiti N, Fano V, Pacifici R, Virgili F, Piras G, Guigi L, Bartyoloni C, Tricerri A, Zuccaro P, Ebrahim S, Perucci CA: The effect of zinc and vitamin A supplementation on immune response in an older population. J Am Geriatr Soc 1993;46:19–26.
  156. Provinciali M, Montenovo A, DiStefano G, Colombo M, Daghetta L, Carati M, Veroni C, Cassino R, Della Torre F, Fabris N: Effect of zinc or zinc plus arginine supplementation on antibody titre and lymphocyte subsets after influenza vaccination in elderly subjects: a randomized controlled trial. Age Ageing 1998;27:715–722.
  157. Chang KL, Hung TC, Hsieh BS, Chen YH, Chen TF, Cheng HL: Zinc at pharmacological concentrations affects cytokine expression and induces apoptosis of human peripheral blood mononuclear cells. Nutrition 2006;22:465–474.
  158. Percival SS: Copper and immunity. Am J Clin Nutr 1998;67:1064S–1085S.
  159. Bonham M, O’Connor JM, Hannigan BM, Strain JJ: The immune system as a physiological indicator of marginal copper status? Br J Nutr 2002;87:393–403.
  160. Minatel L, Carfagnini JC: Copper deficiency and immune response in ruminants. Nutr Res 2000;2010:1519–1529.

    External Resources

  161. Linder MC, Hazegh-Azam M: Copper biochemistry and molecular biology. Am J Clin Nutr 1996;63:797S–811S.
  162. Pan YJ, Loo G: Effect of copper deficiency on oxidative DNA damage in Jurkat T-lymphocytes. Free Rad Biol Med 2000;28:824–830.
  163. Harvey LJ, Majsak-Newman G, Dainty JR, Lewis DJ, Langford NJ, Crews HM, Fairweather-Tait SJ: Adaptive responses in men fed low- and high-copper diets. Br J Nutr 2003;90:161–168.
  164. Pena MM, Lee J, Thiele DJ: A delicate balance: homeostatic control of copper uptake and distribution. J Nutr 1999;129:1251–1260.
  165. Kelly DS, Daudu PA, Taylor PC, Mackey BE, Turnlund JR: Effects of low-copper diets on human immune response. Am J Clin Nutr 1995;62:412–416.
  166. Sherman AR: Immune dysfunction in iron, copper, and zinc deficiencies; in Bogden JD, Klevay LM (eds): Clinical Nutrition of the Essential Trace Elements and Minerals: The Guide for Health Professionals. Totowa, Humana Press, 2000, pp 309–331.
  167. Hopkins RG, Failla ML: Transcriptional regulation of the interleukin-2 gene expression is impaired by copper deficiency in Jurkat human T lymphocytes. J Nutr 1999;129:596–601.
  168. Turnlund JR, Jacob RA, Keen CL, Strain JJ, Kelly DA, Domek JM, Keyes WR, Ensunsa JL, Lykkesfeldt J, Coulter J: Long-term high copper intake: effects on indexes of copper status, antioxidant status, and immune function in young men. Am J Clin Nutr 2004;79:1037–1044.
  169. Failla ML, Hopkins RG: Is low copper status immunosuppressive? Nutr Rev 1998;56:59–64.

    External Resources

  170. Rock E, Mazur A, O’Connor JM, Bonham MP, Rayssiguier Y, Strain JJ: The effect of copper supplementation on red blood cell oxidizability and plasma antioxidants in middle-aged healthy volunteers. Free Rad Biol Med 2000;28:324–329.
  171. Weiss G: Iron; in Hughes DA, Darlington LG, Bendich A (eds): Diet and Human Immune Function. Totowa, Humana Press, 2004, pp 203–215.
  172. Schaible UE, Kaufmann SHE: Iron and microbial infection. Nat Rev Microbiol 2004;2:946–953.
  173. Weiss G: Iron and immunity: a double-edged sword. Eur J Clin Invest 2002;32(suppl 1):70–78.
  174. Oppenheimer SJ: Iron and its relation to immunity and infectious disease. J Nutr 2001;131:616S–635S.
  175. Brock JH, Mulero V: Cellular and molecular aspects of iron and immune function. Proc Nutr Soc 2000;59:537–540.
  176. Walker EM, Walker SM: Effects of iron overload on the immune system. Ann Clin Lab Sci 2000;30:354–365.
  177. Thorson JA, Smith KM, Gomez F, Naumann PW, Kemp JD: Role of iron in T cell activation: Th-1 clones differ from Th-2 clones in their sensitivity to inhibition for DNA synthesis caused by IGG Mabs against transferrin receptor and iron chelators desferrioxamine. Cell Immunol 1991;134:126–127.
  178. Beard JL: Iron biology in immune function, muscle metabolism and neuronal functioning. J Nutr 2001;131:568S–580S.
  179. Jason J, Archibald K, Nwanyanwu OC, Bell M, Jensen RJ, Gunter E, Buchanan I, Larned J, Kazembe PN, Dobbie H, Jarvis WR: The effect of iron deficiency on lymphocyte cytokine production and activation: preservation of hepatic iron but not at all cost. Clin Exp Immunol 2001;126:466–473.
  180. Ahluwalia N, Sun J, Krause D, Mastro A, Handte G: Immune function is impaired in iron-deficient home-bound, older women. Am J Clin Nutr 2004;79:516–521.
  181. Stolzfus RJ, Dreyfuss M: Guideline for the Use of Iron Supplements to Prevent and Treat Iron Deficient Anemia. Washington, ILSI Press, 1989, pp 1–39.
  182. Nyakeriga AM, Troye-Blomberg M, Dorfman JR, Alexander ND,Bäck R,Kortok M,Chemtai AK, Marsh K,Williams TN: Iron deficiency and malaria among children living in the coast of Kenya. J Infect Dis 2004;190:439–447.
  183. Gera T, Sachdev HPS: Effect of iron supplementation on incidence on infectious illness in children: systematic review: BMJ 2002;325:1142–1151.
  184. Sazawal S, Black RE, Ramsan M, Chwaya HM, Stoltzfus RJ, Dutta A, Dhingra U, Kabole I, Deb S, Othman MK, Kabole FM: Effect of routine prophylactic supplementation with iron and folic acid on admission to hospital and mortality in preschool children in a high malaria transmission setting: community-based, randomized placebo-controlled trial. Lancet 2006;367:133–143.
  185. Tielsch JM, Kathry SK, Stolzfus RJ, Katz J, LeClerq SC, Adhikari R, Mullany LC, Shresta S, Black RE: Effect of routine prophylactic supplementation with iron and folic acid on preschool child mortality in Southern Nepal: community-based cluster-randomized, placebo-controlled trial. Lancet 2006;367:144–152.
  186. Iannotti LL, Tielsch JM, Black MM, Black RE: Iron supplementation in early childhood: health benefits and risks. Am J Clin Nutr 2006;84:1261–1276.
  187. English M, Snow RW: Iron and folic acid supplementation and malaria risk. Lancet 2006;367:90–91.