Handbook of Vitamin C Research

Vitamin C: Daily Requirements, Dietary Sources and Adverse Effects 243supplements in prevention of cancer in middle-aged and older men. In the Women'sAntioxidant Cardiovascular Study with a double-blind, placebo-controlled 2 2 2 factorialtrial of vitamin C, 8,171 women were randomly enrolled into treatment and placebo groups.The treatment groups consumed 500 mg of ascorbic acid daily, natural-source vitamin E (600IU of -tocopherol every other day), and -carotene (50 mg every other day). Duration andcombined use of the three antioxidants also had no effect on cancer incidence and cancerdeath. There were no statistically significant effects of use of any antioxidant on total cancerincidence. They concluded that supplementation with vitamin C, vitamin E, or -caroteneoffers no overall benefit in the primary prevention of total cancer mortality (site). Lee et al(2001) and Blair (2008) have reported that vitamin C induces lipid hydroperoxidedecomposition to the DNA-reactive bifunctional electrophiles 4-oxo-2-nonenal,4,5-epoxy-2(E)-decenal, and 4-hydroxy-2-nonenal. 4,5-Epoxy-2(E)-decenal is a precursor of etheno-2'-deoxyadenosine, a highly mutagenic compound found in human DNA. They concluded thatvitamin C-mediated formation of genotoxins from lipid hydroperoxides in the absence oftransition metal ions might be ascribed to its lack of efficacy as a cancer chemopreventionagent.In epidemiologic studies, vitamin C levels in plasma were positively associated withcoronary heart disease (CHD) and stroke (Levine et al., 1996). The relative risk of CHD andstroke was reduced by 26% with serum vitamin C levels of 63-153 µmol/L compared withconcentrations of 6-23 µmol/L (Panel on Dietary Antioxidants and Related Compounds).Vitamin C inhibited LDL oxidation, a process which is involved in the formation ofatherosclerotic plaques (Harris 1996). Some studies have shown beneficial effects of highdoses of vitamin C on endothelial-dependent vasodilation (May 2000; Carr and Frei, 1999).In a study pooled from the analysis of 9 cohort studies, the results indicated that dietaryintake of antioxidant vitamins was only weakly linked to a reduced CHD risk. However, highvitamin C intake was associated with a lowered incidence of major CHD events (Knekt et al.,2004). The cardioprotective function of vitamin C may be ascribed to lowering bloodpressure (Ness et al., 1997), protecting membrane lipids from free radical damage (Andersonet al., 1995), protecting lipids indirectly by sparing or reconstituting the active forms ofvitamin E (Tappel 1962), reversing endothelial dysfunction (Hamabe et al., 2001), loweringischemic heart disease (Gey et al., 1987), improving the endothelium-dependent vasomotorcapacity of coronary arteries (Solzbach et al., 1997), and modulating congestive heart failure(CHF) by increasing the availability of nitric oxide (Hornig et al., 1998).Daily RequirementsVitamin C is generally regarded as safe (GRAS) in amounts obtained from foods. It iscommonly used as an antioxidant food additive. Its sodium, potassium, and calcium salts arewater-soluble thus cannot protect lipids from oxidation. To enhance lipid solubility, ascorbicacid is esterified to long-chain fatty acids (ascorbyl palmitate or ascorbyl stearate) that can beutilized as food antioxidants in lipid-soluble systems. Vitamin C supplements are also GRASin recommended amounts, although there are rarely reported side effects including nausea,vomiting, heartburn, abdominal cramps, diarrhea, and headache. For some populations,