Vitamin C is found in high concentrations in white blood cells and is rapidly utilized during infection; reduced plasma concentrations are often associated with reduced immune function (see Siegel, 1993). Animal and human studies have suggested that the dietary requirements for vitamin C are increased in cancer, surgical trauma and infectious diseases (see Siegel, 1993). The belief that high intakes of vitamin C will prevent the onset of the common cold has not been substantiated scientifically, although the associated symptoms following infection appear to be reduced by a moderate intake (Coulehan et al., 1974). Rauling's claims regarding the effects of vitamin C on the common cold (Rauling, 1970) inspired a great deal of research into its effect on immune function in the 1970s and early 1980s (reviewed by Thomas and Holt, 1978; Siegel, 1993). Vitamin C deficiency in the guinea pig impairs lymphocyte proliferation, the delayed-type hypersensitivity (DTH) response to tuberculin, the ability of neutrophils to kill bacteria and the activity of cytotoxic T-cells and delays the rejection of skin allografts, but has little effect on antibody responses (for references, see Siegel, 1993). Providing vitamin C to mice increased spleen lymphocyte proliferation in response to mitogens but did not affect natural killer (NK)-cell activity or the antibody response to sheep red blood cells or lipopolysaccharide (LPS) (see Siegel, 1993). Vitamin C decreased or slowed tumour development in some animal models, but not others (see Siegel, 1993). Vitamin C deficiency in humans did not impair lymphocyte proliferation or alter the number of CD4+ or CD8+ cells in the circulation (Kay et al., 1982). However, Vitamin C (1-5 g daily for 3 days to several weeks) increased human T lymphocyte proliferation (Yonemoto et al., 1976; Anderson et al., 1980; Panush et al., 1982) and neutrophil motility towards LPS-activated autologous serum (Anderson et al., 1980). Some studies indicate that vitamin C increases circulating immunoglobulin (Ig) levels in humans (Prinz et al., 1977; Vallance, 1977; Ziemlanski et al., 1986), but other studies fail to show this (Anderson et al., 1980; Panush et al., 1982; Kennes et al., 1983). Jacob et al. (1991) studied the effect of vitamin C at different levels in the diet on immune function in a group of young, healthy non-smokers. The subjects first consumed a vitamin C-deficient diet and then gradually increased their vitamin C intake (from 5 to 250 mg day-1). The vitamin C-deficient diet decreased plasma and white-cell vitamin C concentrations by 50% and decreased the DTH response to seven recall antigens, but did not alter lymphocyte proliferation. Sixty or 250 mg vitamin C day-1 led to recovery of the DTH response, but did not affect lymphocyte proliferation. The authors suggest that the inconsistency regarding the influence of vitamin C on these two outcomes, both indicators of cell-mediated immunity, may result from the higher sensitivity of the DTH test, involvement of cells other than those isolated for in vitro cultures in the in vivo DTH response or other unknown factors. The lack of an effect on lymphocyte proliferation at an intake of 250 mg day-1 suggests that, at least in young individuals, only levels of vitamin C that approach pharmacological doses can produce a quantifiable effect on this parameter of immune function. It has been suggested that vitamin C intakes of 600 mg day-1 may be beneficial in reducing infections in individuals who undertake a large amount of physical activity: for instance, studies of marathon runners have found a significantly lower incidence of post-race upper respiratory infections in runners taking a daily supplement of 600 mg vitamin C (Peters, 1997).
One of the major problems in assessing the beneficial effects of dietary components on the immune system is the lack of a reliable marker of immune function that is known to be indicative of a long-term beneficial effect in terms of reducing the incidence of degenerative disorders in later life. Although not an immunological one, one recent study does provide an excellent example of the potential need to maintain adequate intakes of antioxidant nutrients in the middle years of life to prevent the accumulative damage caused by ROS being made manifest in later years. Jacques et al. (1997) examined the cross-sectional relationship between age-related lens opacities and vitamin C supplement use over a 10-12-year period in women without diagnosed cataract or diabetes. Use of vitamin C supplements for 10 years or more was associated with a 77% lower prevalence of early lens opacities and an 83% lower prevalence of moderate lens opacities, compared with women who did not use sup plements. Women who consumed vitamin C supplements for less than 10 years showed no evidence of a reduced prevalence of early opacities, suggesting that long-term consumption of vitamin C supplements may substantially reduce the development of age-related lens opacities. While the use of supplements might be required to obtain sufficient intakes of vitamin C to prevent this form of oxidative damage, it is hoped that the intake required to maintain optimal immune function can be obtained from a healthy diet containing fruit and vegetables rich in antioxidants. This should be the case, since epidemiological studies of populations having a lower incidence of cancer suggest that the benefits are associated with the intake of increased amounts of these foodstuffs rather than the taking of supplements (Block et al., 1992).
Vitamin C has been used to treat some clinical phagocytic cell dysfunctions. In Chediak-Higashi syndrome, which is characterized in part by defective neutrophil functions, vitamin C supplementation has been shown to increase neutrophil chemotaxis, improve bactericidal activity and reduce the length of clinical illness (Boxer et al., 1976). Vitamin C also appears to be beneficial in the treatment of chronic granulomatous disease (Anderson, 1982).
Vitamin C provides important antioxidant protection for plasma lipids and lipid membranes and can also neutralize phagocyte-derived oxidants released extracelluarly, thereby preventing oxidant-mediated tissue damage, particularly at sites of inflammatory activity. Other mechanisms that have been proposed for the immunostimulatory effects of vitamin C include modulation of intracellular cyclic-nucleotide levels, modulation of prostaglandin synthesis, enhancement of cytokine production, antagonism of the immunosuppressive interaction between histamines and white blood cells and the protection of 5-lipoxygenase (Anderson et al., 1990). There is a need for further research, not only into the mechanisms by which vitamin C can enhance immune-cell function, but also to define the level of intake required to maintain an optimal immune responsiveness throughout life and to reduce the incidence of degenerative disorders in later life.
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