Suboptimal antioxidant levels are linked to impaired immune responses and an increased susceptibility to infections.
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.
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.
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.
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.
Infections and stress have been shown to reduce vitamin C concentrations in leukocytes and plasma.
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]
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.
To counteract this they also contain high concentrations of vitamin E, reducing the potential for cellular damage which may otherwise impair immune responses.
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.
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.
In vivo and in vitro research shows that betacarotene may increase B and T cell proliferation and increase helper T cell lymphocytes. 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. Vitamin A deficiency may also increase susceptibility to infections.
Selenium is found in high concentrations in immune tissues including the liver, spleen and lymph nodes. 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. Selenium deficiency has also been shown to reduce the oxidative burst, while higher levels of selenium produced a stronger, more effective oxidative burst.
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.
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.
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]
Ubiquinol, the reduced form of coenzyme Q10, is potent lipid-soluble antioxidant, being the only endogenously synthesised lipophilic antioxidant. Coenzyme Q10 has been described as the key lipid-soluble antioxidant, with the ability to regenerate other antioxidants including vitamins C and E.
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. 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.
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. These results echo those found in animal studies.
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