Vitamin C has a clearly established role in collagen biosynthesis, the lack of which leads to the symptoms of scurvy. Vitamin C is required for the synthesis of "repair" collagen and is specifically required for the incorporation and crosslinking of proline and lysine residues in collagen biosynthesis (Moser and Bendich, 1991). Impairment of collagen synthesis in basement membranes and subsequent reduction in the integrity of the mucosal epithelium may explain the capillary fragility and increased incidence of periodontal disease observed in vitamin C deficiency (Chatterjee, 1978). Failure of wound healing, gum lesions and abnormal bone development are other symptoms of vitamin C deficiency that are linked to impaired collagen synthesis.
Biochemical functions of vitamin C have been reviewed (Sauberlich, 1994; Moser and Bendich, 1991). Aside from its role in collagen synthesis and wound healing, some important known functions of vitamin C are:
- Water soluble antioxidant in cells, tissues and the gastrointestinal tract;
- Synthesis of adrenal steroids and catecholamines;
- Synthesis of carnitine (hydroxylation of trimethyllysine);
- Synthesis of bioactive amines in the brain and nervous system;
- Metabolism of tyrosine, histidine, tryptophan and cholesterol;
- Detoxification of toxins, natural compounds and other xenobiotics by liver microsomes;
- Drug metabolism;
- Folic acid metabolism;
- Iron absorption;
- Maintenance of trace minerals (zinc, copper, manganese, iron) in the reduced state;
- Normal functioning and stability of leukocytes and erythrocytes;
- Antihistamine and anti-inflammatory;
- Anti-endotoxin ;
- Hydroxylation and activation of vitamin D.
Of these functions, the antioxidant ones are of great interest to researchers. The antioxidant role of vitamin C appears to be a common link in its role in the function and integrity of various cell types in the body, in detoxification functions and in the normal functioning of the adrenal glands, lungs, brain, eye and immune system. A. Vitamin C and Immunity
Ascorbic acid and glutathione are the most plentiful soluble antioxidants in leukocytes and erythrocytes. Extensive recycling of vitamin C occurs in neutrophils, monocytes and macrophages (May et al., 1999; Washko et al., 1993), and this process is stimulated by the presence of bacteria (Wang et al., 1997). Vitamin C deficiency impairs the bactericidal activity of neutrophils (Goldschmidt, 1991). Chronic, low-grade skin infections in humans have been shown to respond to vitamin C supplementation (Levy et al., 1996). Ascorbic acid enhances macrophage production of nitric oxide, which is involved in bactericidal reactions (Mizutani et al., 1998). Supplementation with both vitamin C and E potentiates white blood cell function in healthy adults (Jeng et al., 1996).
Vitamin C has an antihistamine effect (Johnston and Huang, 1991; Johnston et al., 1992), resulting in reduced plasma histamine levels and possible enhancement of neutrophil chemotaxis and improved bronchial dilation during infection (Gershoff, 1993). In related findings, vitamin C has been shown to attenuate the damaging effects of bacterial Escherichia coli endotoxin on the lungs of sheep (Dwenger et al., 1994) and guinea pigs (Benito and Bosch, 1997). Vitamin C has also been shown to impart protection against E. coli endotoxin (lipopolysaccharide) damage to the liver (Cadenas et al., 1998) and heart (Rojas et al., 1996), possibly by induction of the mixed-function oxidase system (Takahashi et al., 1997). High concentrations of endotoxin inhibit uptake of vitamin C by the adrenal cortical cells (Garcia and Municio, 1990).
In ruminants, limited evidence exists of the effect of vitamin C on immune function. Researchers at Auburn University reported both positive effects (Blair and Cummins, 1984) (Figure 1) and no effect (Cummins and Brunner, 1989) on plasma immunoglobulin concentration of colostrum-deprived dairy calves. Hidiroglou et al. (1995) reported no effect of vitamin C alone (0,1 or 2 g per day) on immunoglobulin concentrations or lymphocyte response to mitogen in dairy calves. However, the same authors reported a trend for increased immunoglobulin M (IgM) in plasma when calves received both vitamin C and vitamin E. Roth and Kaeberle (1985) reported that parenteral ascorbic acid (20 mg per kg body weight) reversed the suppressive effects of dexamethasone on neutrophil function and tended to enhance neutrophil phagocytosis of Staph. aureus bacteria. Ascorbic acid supplementation reduced respiratory rate, rectal temperature and serum cortisol level and increased serum thyroid hormone (T4) in heat-stressed lambs (Kobeisy et al., 1997). High environmental temperature has been reported to reduce plasma vitamin C concentrations in Holstein cattle, especially above 80†F (26.6†C) (Singh, 1957). Given these limited data, it would appear that the role of supplemental vitamin C in ruminants deserves further study.