Potential problems of ascorbate and iron supplementation: pro-oxidant effect in vivo?

The comparison was undertaken between the effects of ascorbate versus ascorbate plus iron supplementation on DNA damage. Twenty healthy subjects with initial levels of plasma ascorbate of 67.2 +/- 23.3 micromol/l were randomly assigned to and cycled through one of three supplementation regimes: placebo, 260 mg/d ascorbate, 260 mg/d ascorbate plus 14 mg/d iron for 6 weeks separated by 8-week washout periods. Supplementation did not cause a rise in total oxidative DNA damage measured by GC-MS. However, a significant decrease occurred in levels of 8-oxo-7,8-dihydroguanine by ascorbate supplementation and 5-hydroxymethyl uracil by both ascorbate and ascorbate plus iron supplementation, relative to the pre-supplemental levels but not to the placebo group. In addition, levels of 5-hydroxymethyl hydantoin and 5-hydroxy cytosine increased significantly, only relative to pre-supplementation, by ascorbate plus iron treatment. No compelling evidence for a pro-oxidant effect of ascorbate supplementation, in the presence or absence of iron, on DNA base damage was observed.