The recommended dietary allowance (RDA) of
vitamin C has traditionally been based on the prevention of the
vitamin C deficiency disease,
scurvy. While higher intakes of
vitamin C may exert additional health benefits, the limited Phase III randomized placebo-controlled trials (RCTs) of
vitamin C supplementation have not found consistent benefit with respect to
chronic disease prevention. To date, this has precluded upward adjustments of the current RDA. Here we argue that Phase III RCTs-designed principally to test the safety and efficacy of pharmaceutical drugs-are ill suited to assess the health benefits of essential nutrients; and the currently available scientific evidence is sufficient to determine the optimum intake of
vitamin C in humans. This evidence establishes biological plausibility and mechanisms of action for
vitamin C in the primary prevention of
coronary heart disease,
stroke, and
cancer; and is buttressed by consistent data from prospective cohort studies based on blood analysis or dietary intake and well-designed Phase II RCTs. These RCTs show that
vitamin C supplementation lowers
hypertension, endothelial dysfunction, chronic
inflammation, and Helicobacter pylori
infection, which are independent risk factors of
cardiovascular diseases and certain
cancers. Furthermore,
vitamin C acts as a biological
antioxidant that can lower elevated levels of oxidative stress, which also may contribute to
chronic disease prevention. Based on the combined evidence from human metabolic, pharmacokinetic, and observational studies and Phase II RCTs, we conclude that 200 mg per day is the optimum dietary intake of
vitamin C for the majority of the adult population to maximize the
vitamin's potential health benefits with the least risk of inadequacy or adverse health effects.