Ascorbic acid (vitamin C) in health and disease

Ascorbic acid and common cold

The most widely known health beneficial effect of ascorbic acid (vitamin C) is for the prevention or relief of common cold. Pauling [33] suggested that ingestion of 1–2 g of ascorbic acid effectively prevents/ ameliorate common cold. The role of oral vitamin C in the prevention and treatment of colds remains controversial despite many controlled trials. Several clinical trails with varying doses of ascorbic acid showed that ascorbic acid does not have significant prophylactic effect, but reduced the severity and duration of symptoms of cold during the period of infection. Randomized and non-randomized trials on vitamin C to prevent or treat the common cold showed that consumption of ascorbic acid as high as 1.0 g/day for several winter months, had no consistent beneficial effect on the incidence of common cold. For both preventive and therapeutic trials, there was a consistent beneficial but generally modest therapeutic effect on duration of cold symptoms. There was no clear indication of the relative benefits of different regimes of vitamin C doses. However, in trials that tested vitamin C after cold symptoms occurred, there was some evidence of greater benefits with large dose than with lower doses [34].

There has been a long-standing debate concerning the role of ascorbic acid in boosting immunity during cold infections. Ascorbic acid has been shown to stimulate immune system by enhancing T-cell proliferation in response to infection. These cells are capable of lysing infected targets by producing large quantities of cytokines and by helping B cells to synthesize immunoglobulins to control inflammatory reactions. Further, it has been shown that ascorbic acid blocks pathways that lead to apoptosis of T-cells and thus stimulate or maintain T cell proliferation to attack the infection. This mechanism has been proposed for the enhanced immune response observed after administration of vitamin C during cold infections [35].

Ascorbic acid (vitaminC) and wound healing

Ascorbic acid plays a critical role in wound repair and healing/regeneration process as it stimulates collagen synthesis. Adequate supplies of ascorbic acid are necessary for normal healing process especially for post-operative patients. It has been suggested that there will be rapid utilization of ascorbic acid for the synthesis of collagen at the site of wound/ burns during post-operative period [36]. Hence, administration of 500 mg to 1.0 g/day of ascorbic acid are recommended to accelerate the healing process [8].

Ascorbic acid (vitamin C) and atherosclerosis

Lipid peroxidation and oxidative modification of low density lipoproteins (LDL) are implicated in development of atherosclerosis [37]. Vitamin C protects against oxidation of isolated LDL by different types of oxidative stress, including metal ion dependent and independent processes [38]. Addition of iron to plasma devoid of ascorbic acid resulted in lipid peroxidation, whereas endogenous and exogenous ascorbic acid was found to inhibit the lipid oxidation in iron-over loaded human plasma [39]. Similarly, when ascorbic acid was added to human serum supplemented with Cu2+, antioxidant activity rather than pro-oxidant effects were observed [40].

Ascorbic acid is known to prevent the oxidation of LDL primarily by scavenging the free radicals and other reactive oxygen species in the aqueous milieu [41]. In addition, in vitro studies have shown that physiological concentrations of ascorbic acid strongly inhibit LDL oxidation by vascular endothelial cells [42]. Adhesion of leukocytes to the endothelium is an important step in initiating atherosclerosis. In vivo studies have demonstrated that ascorbic acid inhibits leukocyte-endothelial cell interactions induced by cigarette smoke [43,44] or oxidized LDL [45]. Further, lipophilic derivatives of ascorbic acid showed protective effect on lipid-peroxide induced endothelial injury [46].

A number of studies have been carried out in humans to determine the protective effect of ascorbic acid supplementation (500–100 mg/day) on in vivo and ex vivo lipid peroxidation in healthy individuals and smoker. The findings are inconclusive as ascorbic acid supplementation showed a reduction or no change in lipid peroxidation products [10,47-50]. In this context, it is important to note that during ex vivo LDL oxidation studies, water soluble ascorbic acid is removed during initial LDL isolation step itself. Therefore, no change in ex vivo would be expected [15]. Overall, both in vitro and in vivo experiments showed that ascorbic acid protects isolated LDL and plasma lipid peroxidation induced by various radical or oxidant generating systems. However, a recent report demonstrated that large doses of exogenous iron (200 mg) and ascorbic acid (75 mg) promoted the release of iron from iron binding proteins and also enhanced in vitro lipid peroxidation in serum of guinea pigs. This finding supports the hypothesis that high intake of iron along with ascorbic acid could increase in vivo lipid peroxidation of LDL and therefore could increase risk of atherosclerosis [51]. However, Chen et al., [52] demonstrated that ascorbic acts as an antioxidant towards lipids even in presence of iron over load in in vivo systems.

Numerous studies have looked at the association between ascorbic acid intake and the risk of developing cardiovascular disease (CHD). A large prospective epidemiological study in Finnish men and women suggested that high intake of ascorbic acid was associated with a reduced risk of death from CHD in women and not in men [53]. Similarly, another study showed that high intake of ascorbic acid in American men and women appeared to benefit only women [54,55]. A third American cohort study suggested that cardiovascular mortality was reduced in both sexes by vitamin C [56]. In the UK, a study showed that the risk of stroke in those with highest intake of vitamin C was only half that of subjects with the lowest intake and no evidence suggestive of lower rate of CHD in those with high vitamin C intake [57]. However, a recent meta analysis on the role of ascorbic acid and antioxidant vitamins showed no evidence of significant benefit in prevention of CHD [58]. Thus, no conclusive evidence is available on the possible protective effect of ascorbic acid supplementation on cardiovascular disease.