Alternative Medicine Review 1998 (Jun); 3 (3): 170–173 ~ FULL TEXT
Jeffrey S. Bland, Ph.D.
The paper entitled, "Vitamin C Exhibits Pro-oxidant
Properties," which appeared recently in the journal Nature has attracted
considerable attention. Authors Podmore, Griffiths, Herbert, et al describe
the potential pro-oxidant effects of daily supplementation with 500 mg
of vitamin C on DNA base oxidation in vivo. 
Their conclusion raises concern because a vast number of individuals regularly
supplement their diets with vitamin C in the belief that it has antioxidant
The results of the study are paradoxical. The authors
found that the oxidation of guanine (a purine) in DNA was significantly
reduced after vitamin C supplementation, but the oxidation of adenine (also
a purine) was significantly elevated. The oxidation of nucleic acids is
indicative of oxidative stress being placed on DNA with the concomitant
exposure to reactive oxygen species, such as hydroxyl radical. The oxidation
of adenine suggests that vitamin C (supplemented at 500 mg) participated
as a pro-oxidant, whereas the reduced level in the oxidation of guanine
suggests it acted as an antioxidant.
Is vitamin C a pro-oxidant or an antioxidant? The answer
to this question is not available from the data or its interpretation in
the paper. The results are contradictory. The failure of the authors to
point out this paradox in the conclusions drawn from their work is a significant
oversight. They focus solely on the oxidation of adenine, and conclude
that a supplement of 500 mg vitamin C acts as a pro-oxidant, while ignoring
the observed antioxidant effects with regard to guanine. It is certainly
well established that vitamin C can serve as a pro-oxidant through formation
of ascorbyl radical. It is also known this radical is quenched by vitamin
E to yield tocopheryl radical, which, in turn is reduced by the conversion
of glutathione to oxidized glutathione. High doses of vitamin C could increase
the concentration of ascorbyl radical that, if not quenched by vitamin
E, could result in an increased oxidant burden. The observation in the
Podmore et al study that guanine oxidation was reduced with supplementation
of 500 mg vitamin C strongly suggests this was not the case. The presence
of oxidized adenine remains a contradiction.
It has recently been pointed out that adenine is easily
oxidized in the extraction procedure of lymphocytes for DNA. 
Therefore, it is possible that the observed adenine oxidation was not a
result of vitamin C intake, but rather a result of experimental techniques
used in the extraction of the DNA. Although the study opens the door for
more investigation, it should not lead to the conclusion that a supplement
of 500 mg vitamin C is dangerous. Until the apparent contradiction in the
data relative to the oxidation of adenine versus the antioxidation of guanine
is resolved, this paper simply represents an interesting observation in
the absence of replication or mechanistic understanding.
1. Podmore ID, Griffiths HR, Herbert KE, et al. Vitamin
C exhibits pro-oxidant properties. Nature 1998;392:559.
2. Jenner A, England TG, Aruoma OI, Halliwell B. Measurement
of oxidative DNA damage by gas chromatographymass spectrometry: ethanethiol
prevents artifactual generation of oxidized DNA bases. Biochem J 1998;331:365-369.