Vitamin C Not Genotixic
By Bill Sardi, Knowledge of Health, Inc.
Last June a report in the journal Science indicated high-dose vitamin C may, under certain circumstances, be toxic to genetic material, inducing DNA mutations. Worldwide headlines called for a halt to consumption of more than 200 milligrams of vitamin C in food supplements.
This recommendation was based on a study conducted in a laboratory dish and it did not prove these adverse reactions could actually occur inside living cells. Subsequent limited human studies do not support the notion that high-dose vitamin C can harm DNA.
The following report conclusively shows that high-dose vitamin C is not genotoxic. The report (below), printed in the Journal of Biological Chemistry ahead of publication schedule because of itsimportance, concludes that high intracellular concentrations of vitamin C can PREVENT oxidation-induced mutations in human cells. The newspress has not chosen to give any attention to this report.
Special note: the report does indicate vitamin C does induce oxidation when combined with free (unbound) metals such as iron and copper. This is why vitamin C is essentially an incomplete vitamin without accompanying iron-binding bioflavonoid pigments which are found along side natural sources of vitamin C. Grapes contain vitamin C and iron, but also have iron-binding pigments.
Therefore, you never see a rusty grape. Similarly, iron and oxygen, two of the agents needed to induce oxygen free radicals, are found in red blood cells but the red hemoglobin pigment binds the iron preventing it from inducing free radicals and destroying the red cell.
J Biol Chem 2002 Mar 7
Vitamin C prevents DNA mutation induced by oxidative stress.
Lutsenko EA, Carcamo JM, Golde DW.
Mol. Hematology, Memorial Sloan-Kettering Cancer Center, New York, NY10021.
The precise role of vitamin C in the prevention of DNA mutations is controversial. While ascorbic acid has strong antioxidant properties, it also has pro-oxidant effects in the presence of free transition metals. Vitamin C was recently reported to induce the decomposition of lipid hydroperoxides independent of metal interactions, suggesting that it could cause DNA damage.
In order to directly address the role of vitamin C in maintaining genomic integrity, we developed a genetic system for quantifying guanine base mutations induced in human cells under oxidative stress. The assay utilized a plasmid construct encoding the cDNA for chloramphenicol acetyl transferase modified to contain an amber stop codon, which was restored to wild type by G to T transversion induced by oxidative stress.
The mutation frequency was determined from the number of plasmids containing the wild type chloramphenicol acetyl transferase gene rescued from oxidatively stressed cells. Cells were loaded with vitamin C by exposingthem to dehydroascorbic acid (DHA), therebyavoiding transition metal related pro-oxidant effects of ascorbicacid. We found that vitamin C loading resulted in substantially decreased mutations induced by H2O2. Depletion of glutathione led to cytotoxicity and an increase in H2O2-induced mutation frequency, however mutation frequency was prominently decreased in depleted cells preloaded with vitamin C.
The mutation results correlated with a decrease in total 8-oxo-guanine (8-oxo-dG) measured in genomic DNA of cells loaded with vitamin C and oxidatively stressed. These findings directly support the concept that high intracellular concentrations of vitamin C can prevent oxidation-induced mutations in human cells.
The report in Science that alleged high-dosevitamin C induces DNA mutations is shown below.
Science 2001 Jun 15;292(5524):2083-6
Vitamin C-induced decomposition of lipidhydroperoxides to endogenous genotoxins.
Lee SH, Oe T, Blair IA.
Center for Cancer Pharmacology, University of Pennsylvania, 1254 BRB II/III, 421 Curie Boulevard, Philadelphia, PA 19104-6160, USA.
Epidemiological data suggest that dietary antioxidants play a protectiverole against cancer. This has led to the proposal that dietary supplementation with antioxidants such as vitamin C (vit C) may be useful in disease prevention. However, vit C has proved to be ineffective in
cancer chemoprevention studies.
In addition, concerns have been raised over potentially deleterious transition metal ion-mediated pro-oxidant effects. We have now determined that vit C induces lipid hydroperoxide decomposition to the DNA-reactive bifunctional electrophiles 4-oxo-2-nonenal, 4,5-epoxy-2(E)-decenal, and 4-hydroxy-2-nonenal. The compound 4,5-Epoxy-2(E)-decenal is a precursor of
etheno-2'-deoxyadenosine, a highly mutagenic lesion found in human DNA.
Vitamin C-mediated formation of genotoxins from lipid hydroperoxides in the absence of transition metal ions could help explain its lack of efficacy as a cancer chemoprevention agent.