Vitamin C

From: http://www.ajcn.org/content/69/6/1086.full

SUMMARY AND CONCLUSIONS


Vitamin C is required for the optimal activity of several important biosynthetic enzymes and is therefore essential for various metabolic pathways in the body. A deficiency of this vitamin results in the symptoms of scurvy and death. Vitamin C acts as a cosubstrate for several mono- and dioxygenases and oxidases and maintains the active-site metal ions of these enzymes in the reduced state. Vitamin C also acts as an efficient scavenger of aqueous radicals and oxidants, thus protecting other biomolecules from oxidative damage. In addition, vitamin C can spare or recycle glutathione and vitamin E, 2 other important physiologic antioxidants.



Oxidative biomarker studies indicate that vitamin C protects against in vivo oxidation of lipids and DNA in humans, particularly in persons exposed to enhanced oxidative stress, such as smokers (Tables 1 and 2⇓⇓). Numerous epidemiologic studies strongly suggest that vitamin C lowers the incidence of and mortality from 2 of the most prevalent human diseases: cardiovascular disease (Tables 4 and 5⇓⇓) and cancer (Tables 6 and 7⇓⇓). This role of vitamin C in lowering disease incidence is most likely derived from its antioxidant activity, although other mechanisms may also contribute. In addition, vitamin C seems to have a substantial effect on cataract formation (Table 8⇓), again most likely through an antioxidant mechanism. As such, the potential of adequate vitamin C nutriture to benefit public health and reduce the economic and medical costs associated with these chronic diseases is enormous.



If the antioxidant function of vitamin C is accepted as relevant to and important for human health, then morbidity and mortality from cancer, cardiovascular disease, and cataract in addition to scurvy must be used as criteria for determining vitamin C requirements. Therefore, the current RDA of 60 mg/d must be reevaluated and adjusted if justified by the available data. The totality of evidence from the human studies presented in Tables 4–7⇓⇓⇓⇓ strongly suggests that a dietary intake of 90–100 mg vitamin C/d is associated with reduced risk of cardiovascular disease and cancer; there is no indication that 46 mg/d is adequate, ie, the amount on which the current RDA of 60 mg/d is based (7). Therefore, we suggest that the RDA for vitamin C be doubled to 120 mg/d. Even higher intakes of vitamin C, and possibly supplementation, may be required to reduce cataract risk (Table 8⇓), although the evidence is less secure because of the limited number of studies. Furthermore, chronic 500-mg/d doses or acute 1–3-g doses of vitamin C significantly improve vasoreactivity (Table 3⇓), an important consideration for the clinical expression of cardiovascular and cerebrovascular disease (eg, angina pectoris, myocardial infarction, and stroke).



One might argue that the suggested RDA of 120 mg vitamin C/d for optimal risk reduction of cardiovascular disease and cancer is derived solely from epidemiologic studies and not clinical trials, and epidemiologic studies cannot establish causality, but merely show associations. However, these data are the best available for estimating vitamin C adequacy in humans. Clinical trials will not provide this information for several reasons: 1) it is neither practical nor economically feasible to examine a range of vitamin C supplemental doses, ie, to perform detailed dose-response studies; 2) the beneficial effects of vitamin C with respect to cardiovascular disease and cancer appear to be derived from intakes well within the dietary range, ie, supplementation has little or no effect; and 3) without knowledge of exact baseline concentrations or intakes of vitamin C, total intakes cannot be determined. Thus, although clinical trials provide valuable information regarding the usefulness of supplements, they are unlikely to provide the data necessary to determine the RDA for vitamin C, because it appears to be well within the dietary range. Nevertheless, properly designed clinical trials, ie, double-blind, placebo-controlled, randomized trials of vitamin C supplementation in populations with low to very low vita- min C status, would be useful to provide the “proof of concept” that vitamin C can lower morbidity or mortality from cardiovascular disease, cancer, and cataract. Whether such trials are economically and logistically feasible and will be conducted in the foreseeable future is uncertain.