Antioxidants for immune system support

Suboptimal antioxidant levels are linked to impaired immune responses and an increased susceptibility to infections.[1]

Evidence suggests that supplementation with antioxidants (including vitamin C, vitamin E, betacarotene, selenium, zinc, coenzyme Q10 and N-acetyl-cysteine) may improve a range of immune responses, supporting both innate (non-specific) and acquired (adaptive) immunity, while also protecting immune responses in individuals exposed to high levels of environmental free radicals or those with increased oxidative stress.[2,3]

During phagocytosis, a phenomenon known as the oxidative or respiratory burst occurs whereby increased cellular oxygen uptake results in the production of free radicals which contribute to the elimination of certain pathogenic microorganisms.[2,4] While an essential process, this release of free radicals can cause oxidative damage to the immune cells and surrounding tissues if adequate levels of antioxidants are not present. For optimal immune function and the maintenance of in vivo homeostasis, it appears an adequate balance of free radicals (oxidants) and antioxidants (the oxidant/antioxidant balance) must exist.[5]

Vitamin C

Vitamin C is one of the key water-soluble antioxidants in the body, where it scavenges free-radical oxygen and nitrogen species including superoxide, hydroxyl, peroxyl and nitroxide radicals, as well as non-radical reactive species including singlet oxygen, peroxynitrite and hypochlorite.[6] 

Accumulating high concentrations of vitamin C may protect immune cells including neutrophils, mononuclear phagocytes and lymphocytes from oxidative damage caused by free radicals released during the oxidative burst.[7]

Research shows that vitamin C supports numerous aspects of both innate and acquired immunity including the production and function of leukocytes, while also enhancing cellular motility, chemotaxis, phagocytosis and delayed-type hypersensitivity.[7,8] Vitamin C also indirectly supports immunity through the regeneration of vitamin E.[9] 

Infections and stress have been shown to reduce vitamin C concentrations in leukocytes and plasma.[8]

A number of randomised controlled intervention trials have shown that vitamin C supplementation reduces the severity and duration of respiratory tract infections including the common cold, although the exact dose and frequency of dosing has yet to be determined.[8,10]

Vitamin E

As a lipid-soluble antioxidant, vitamin E protects the cells including those of the immune system from lipid peroxidation. Immune cells are rich in polyunsaturated fatty acids, which puts them at an increased risk for oxidative damage.[11] 

To counteract this they also contain high concentrations of vitamin E, reducing the potential for cellular damage which may otherwise impair immune responses.[7]

In addition to its antioxidant benefits, vitamin E may increase resistance to viral and bacterial infections, increase humoral antibody production, improve cell-mediated immunity, and enhance lymphocyte, neutrophil and natural killer cell activity.[6,9]

Vitamin E deficiency may lead to impaired humoral and cell-mediated acquired immunity, including reduced B cell and T cell function. 

Immunosenescence, the phenomenon whereby immune function decreases with ageing, is largely characterised by decreased T cell function. Nutritional intervention utilising vitamin E has found that supplementation may restore T cell function, which may translate to enhanced resistance to infections which is of particular importance in the elderly population.[12] 

Betacarotene

Betacarotene is essential for immune function where it provides antioxidant activity in addition to being the precursor for the important immune modulator vitamin A. The antioxidant action of betacarotene has shown to provide protection to lymphocytes following exposure to free radicals released during the oxidative burst.[13]

In vivo and in vitro research shows that betacarotene may increase B and T cell proliferation and increase helper T cell lymphocytes.[9] Human studies reveal that betacarotene supplementation may enhance cell-mediated immune responses, protect against UV-induced photosuppression of immune function, increase lymphocyte counts, enhance natural killer cell activity and improve CD4:CD8 ratios, a marker of immune competence.[14-17] 

Vitamin A is integral to mucosal barrier maintenance and regeneration, providing the first line of defence against infection. Vitamin A deficiency may impact a number of immune processes, negatively impacting neutrophil, macrophage, T cell, B cell and natural killer cell function.[18] Vitamin A deficiency may also increase susceptibility to infections.[9]

Selenium

Selenium is found in high concentrations in immune tissues including the liver, spleen and lymph nodes.[19] It is necessary for the incorporation into selenoproteins, which are selenium-dependant enzymes that act as redox regulators, antioxidants and regulators of innate and acquired immunity.[7,20]

Selenium deficiency is linked to impaired innate and acquired immunity and appears to increase susceptibility and progression of viral infections.[7] Selenium deficiency has also been shown to reduce the oxidative burst, while higher levels of selenium produced a stronger, more effective oxidative burst.[21]

Selenium supplementation provides an immunostimulant effect, enhancing cell-mediated and humoral immunity.[7,19] Research has also emerged suggesting that selenium supplementation may divert immune responses away from the Th2-type that drives allergic asthma, instead promoting the Th1-type which may offer protection against viral infections and cancer.[21]

Zinc

Zinc is critical for maintaining both innate and acquired immunity, with even a small deficiency impairing numerous aspects of immune function.[22] 

Zinc deficiency has been shown to impair epithelial barrier function, reduce cell-mediated immune responses, decrease T cells, impair macrophage function (including phagocytosis), reduce killer cell activity and decrease antibody-dependent cytotoxicity.[8,22] With these facts in mind it is easy to see why zinc deficiency may increase an individual’s susceptibility to various infections.[7]

Zinc supplementation may improve immune function by increasing T cell activity, complement C3 levels and phagocytic activity, and has been shown to reduce the severity and duration of the common cold.[22-24]

Coenzyme Q10

Ubiquinol, the reduced form of coenzyme Q10, is potent lipid-soluble antioxidant, being the only endogenously synthesised lipophilic antioxidant.[25] Coenzyme Q10 has been described as the key lipid-soluble antioxidant, with the ability to regenerate other antioxidants including vitamins C and E.[26]

Several research models of immune function investigating phagocytic rate, circulating antibody levels, neoplasia, and viral and parasitic infections found that coenzyme Q10 possesses important immunomodulating activity.[27] Human studies have reported increases in IgG, T4-lymphocytes, and T4:T8 lymphocyte ratios with coenzyme Q10 supplementation.[28,29]

N-acetyl-cysteine (NAC) and glutathione

NAC is a precursor of glutathione, an important endogenously synthesised antioxidant pivotal in maintaining the cellular redox state. Changes in intracellular glutathione levels can have profound effects on immune function, with deficiencies of both cysteine and glutathione found in conditions of compromised immune function, including HIV.[30,31]

Both NAC and glutathione have demonstrated beneficial effects on immune function in animal and human studies. Individuals with optimum intracellular glutathione levels were found to have significantly higher numbers of CD4+ T cells than those with low glutathione levels, while supplementation with NAC increased CD4+ T cell numbers in individuals with suboptimal glutathione levels.[32]

Supplementation with NAC in postmenopausal women was found to have a modulatory and strengthening effect on immune function, improving lymphocyte, neutrophil and cytokine levels, and bringing these levels closer to those found in the younger control group.[1] These results echo those found in animal studies.

References

1. Arranz L, Fernández C, Rodríguez A, et al. The glutathione precursor N-acetylcysteine improves immune function in postmenopausal women. Free Radic Biol Med 2008 Nov 1;45(9):1252-1262. [PDF]
    
2. Knight JA. Review: Free radicals, antioxidants, and the immune system. Ann Clin Lab Sci 2000;30(2):145-158. [Abstract]
    
3. Bendich A. Physiological role of antioxidants in the immune system. J Dairy Sci 1993 Sep;76(9):2789-9274. [Abstract]
    
4. Paiva CN, Bozza MT. Are reactive oxygen species always detrimental to pathogens? Antioxid Redox Signal 2014;20(6):1000-1037. [Full text]
    
5. de la Fuente M, Victor VM. Anti-oxidants as modulators of immune function. Immunol Cell Biol 2000;78(1):49-54. [Full text]
    
6. Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide, 3rd ed. Sydney: Churchill Livingstone Elsevier, 2010.
    
7. Drake VJ. Nutrition and Immunity. Linus Pauling Institute Micronutrient Information Centre, 2010 Aug. Viewed 14 October 2015, http://lpi.oregonstate.edu/infocenter/immunity.html
    
8. Wintergerst ES, Maggini S, Hornig DH. Immune-enhancing role of vitamin C and zinc and effect on clinical conditions. Ann Nutr Metab 2006;50(2):85-94. [Abstract]
    
9. Hechtman L, Harris K, Bridgeman K. The Immune System In: Hechtman L. Clinical Naturopathic Medicine (pp.280-417). Sydney: Churchill Livingstone Elsevier, 2014.
    
10. Hemilä H, Chalker E. Vitamin C for preventing and treating the common cold. Cochrane Database Syst Rev 2013;1:CD000980. [Abstracts]
     
11. Pekmezci D. Vitamin E and immunity. Vitam Horm 2011;86:179-215. [Abstracts]
     
12. Wu D, Meydani SN. Age-associated changes in immune function: impact of vitamin E intervention and the underlying mechanisms. Endocr Metab Immune Disord Drug Targets 2014;14(4):283-289. [Abstract]
     
13. Bendich A. Carotenoids and the immune response. J Nutr 1989;119(1):112-115. [Full text]
     
14. Hughes DA, Wright AJ, Finglas PM, et al. The effect of beta-carotene supplementation on the immune function of blood monocytes from healthy male nonsmokers. J Lab Clin Med 1997;129(3):309-317. [Abstract]
     
15. Fuller CJ, Faulkner H, Bendich A, et al. Effect of beta-carotene supplementation on photosuppression of delayed-type hypersensitivity in normal young men. Am J Clin Nutr 1992 Oct;56(4):684-90. [Full text]
     
16. Murata T, Tamai H, Morinobu T, et al. Effect of long-term administration of beta-carotene on lymphocyte subsets in humans. Am J Clin Nutr 1994;60(4):597-602. [Full text]
     
17. Watson RR, Prabhala RH, Plezia PM, Alberts DS. Effect of beta-carotene on lymphocyte subpopulations in elderly humans: evidence for a dose-response relationship. Am J Clin Nutr 1991;53(1):90-94. [Full text]
     
18. Stephensen CB. Vitamin A, infection, and immune function. Annu Rev Nutr 2001;21:167-192. [Abstract]
     
19. Rayman MP. The importance of selenium to human health. Lancet 2000;356(9225):233-141. [Abstract]
     
20. Hoffmann PR, Berry MJ. The influence of selenium on immune responses. Mol Nutr Food Res 2008;52(11):1273-1280. [Full text]
     
21. Huang Z, Rose AH, Hoffmann PR. The role of selenium in inflammation and immunity: from molecular mechanisms to therapeutic opportunities. Antioxid Redox Signal 2012;16(7):705-743. [Full text]
     
22. Larson CP, Roy SK, Khan AI, et al. Zinc treatment to under-five children: applications to improve child survival and reduce burden of disease. J Health Popul Nutr 2008;26(3):356-365. [Full text]
     
23. Sheikh A, Shamsuzzaman S, Ahmad SM, et al. Zinc influences innate immune responses in children with enterotoxigenic Escherichia coli-induced diarrhoea. J Nutr 2010;140(5):1049-1056. [Full text]
     
24. Kurugöl Z, Akilli M, Bayram N, Koturoglu G. The prophylactic and therapeutic effectiveness of zinc sulphate on common cold in children. Acta Paediatr 2006;95(10):1175-1181. [Abstract]
     
25. Molyneux SL, Young JM, Florkowski CM, et al. Coenzyme Q10: Is there a clinical role and a case for measurement? Clin Biochem Rev 2008;29(2):71-82. [Full text]
     
26. Bhagavan HN, Chopra RK. Plasma coenzyme Q10 response to oral ingestion of coenzyme Q10 formulations. Mitochondrion 2007;S7:S78-88. [Abstract]
     
27. Folkers K, Wolaniuk A. Research on coenzyme Q10 in clinical medicine and in immunomodulation. Drugs Exp Clin Res 1985;11(8):539-545. [Abstract]
     
28. Folkers K, Morita M, McRee J Jr. The activities of coenzyme Q10 and vitamin B6 for immune responses. Biochem Biophys Res Commun 1993;193(1):88-92. [Abstract]
     
29. Folkers K, Hanioka T, Xia LJ, et al. Coenzyme Q10 increases T4/T8 ratios of lymphocytes in ordinary subjects and relevance to patients having the AIDS related complex. Biochem Biophys Res Commun 1991;176(2):786-791. [Abstract]
     
30. Dröge W, Breitkreutz R. Glutathione and immune function. Proc Nutr Soc 2000;59(4):595-600. [Abstract]
     
31. Dröge W. Cysteine and glutathione deficiency in AIDS patients: a rationale for the treatment with N-acetyl-cysteine. Pharmacology 1993;46(2):61-65. [Abstract]
     
32. Kinscherf R, Fischbach T, Mihm S, et al. Effect of glutathione depletion and oral N-acetyl-cysteine treatment on CD4+ and CD8+ cells. FASEB J 1994;8(6):448-451. [Full text]

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