relevant hypothesis is that the oxidative modification of low-density lipoprotein (LDL) and other lipoproteins promote atherogenesis (Berliner and Heinecke, 1996; Devaraj and Jialal, 1996; Witztum and Steinberg, 1991). Several lines of evidence suggest that oxidized LDL (oxLDL) is pro-atherogenic. Furthermore, data support the in vivo existence of oxLDL (Berliner and Heinecke, 1996; Witztum and Steinberg, 1991). In vitro studies have clearly shown that vitamin C at concentrations greater than 40 µmol/L (0.8 mg/dL) inhibits the oxidation of isolated LDL induced by transition metals, free-radical initiators, and activated human neutrophils and macrophages (Jialal and Grundy, 1991; Jialal et al., 1990; Scaccini and Jialal, 1994). This is because vitamin C effectively scavenges aqueous reactive oxygen species (ROS) and reactive nitrogen species (RNS), which prevents them from attacking LDL. Thus, in vitro vitamin C clearly functions as an antioxidant.
Studies shown in Table 5-1 examined the effect of vitamin C supplementation alone on biomarkers of lipid peroxidation. Of the 13 studies, 7 showed that vitamin C supplementation resulted in a significant decrease in lipid oxidation products in plasma, LDL, or urine. The vitamin C supplements that resulted in positive effects ranged from 500 to 2,000 mg/day. The most convincing evidence that vitamin C functions as an antioxidant in vivo is the study by Reilly et al. (1996) showing that supplementation of smokers with 2.0 g vitamin C for 5 days was associated with a significant reduction in urinary isoprostanes, an indicator of oxidative stress. In the remaining six studies in which vitamin C was supplemented in amounts ranging from 500 to 6,000 mg/day, there was no significant effect of vitamin C supplementation on lipid oxidation products in plasma, urine, or plasma LDL.
Carr and Frei (1999) examined the effect on LDL oxidation of supplementation with vitamin C in combination with vitamin E and β-carotene. Although these investigators have clearly shown that the supplements decrease LDL oxidation, it is difficult to assess the contribution of vitamin C alone.
Vitamin C supplementation (2,000 mg/day for 4 to 12 months) in 41 patients with non-atrophic gastritis decreased gastric mucosal nitrotyrosine, a measure of RNS activity (Table 5-2) (Mannick et al., 1996). Thus, from this study and the study by Reilly et al. (1996), it can be concluded that supplementation with vitamin C results in an antioxidant effect in vivo because it significantly reduces nitrotyrosine and urinary isoprostanes.
However, with respect to the effect of vitamin C on LDL oxidation, the data are inconclusive. This could be explained by the fact