Does Vitamin C Cause DNA Damage?

Two articles on the topic.  The first is from the Linus Pauling Institute, the second a letter from another researcher.

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From the Linus Pauling Institute at Oregon State University

Does Vitamin C Cause Cancer - or Here We Go Again!

A study in the June 15, 2001, issue of the journal Science shows that lipid hydroperoxides (rancid fat molecules) can react with vitamin C to form products that could potentially harm DNA, although the reaction of these products with DNA was not demonstrated in the study. Hence, it was suggested that vitamin C can form genotoxins (DNA-damaging agents) from lipid hydroperoxides, the implication being that vitamin C may enhance mutagenesis and the risk of cancer.

However, such a conclusion would be unwarranted. The study is a test tube experiment, showing some intriguing chemistry of vitamin C. The study does not, however, describe biochemistry or biology, and its relevance to reactions occurring in cells and tissues of the human body is unknown. Many reactions of vitamin C occur in vitro (in the test tube) that will not and cannot occur in vivo (in the living organism). Why? Because the physiological environment of the cell and the body contains thousands of substances that also react with vitamin C and lipid hydroperoxides, derailing the chemistry observed in a test tube system.

For example, lipid hydroperoxides don't just wait around in vivo to bump into a vitamin C molecule, but instead are very rapidly reduced to harmless alcohols by a number of enzymes. Thus, the reaction rate of lipid hydroperoxides with these enzymes compared to the reaction rate of the lipid hydroperoxides with vitamin C is of crucial importance. Curiously, the reaction rate of lipid hydroperoxides with vitamin C was not measured in the Science study. From what we know from the study, incubations were done for two hours, an eternity in biochemical terms. Enzymatic reactions as those indicated above to reduce lipid hydroperoxides to harmless alcohols that do not react with vitamin C usually take a fraction of a second, not two hours!

In our own studies, we have shown that vitamin C effectively inhibits the formation of lipid hydroperoxides in the first place. Thus, when human plasma is exposed to oxidizing conditions, vitamin C forms the first line of antioxidant defense, and no lipid hydroperoxides are formed. Lipid hydroperoxides begin to form only after vitamin C has been exhausted. Thus, in these experiments lipid hydroperoxides and vitamin C did not co-exist in human plasma, and thus never had the opportunity to react with each other!

What's more, the Science study used a concentration of lipid hydroperoxides of 400 ”ĶiM, which in biochemical terms is a ton. Studies have shown that in human blood, lipid hydroperoxides may exist in concentrations of about 10 ? 40 nM, which is 10,000-fold lower than what was used in the Science experiment. Again, this casts serious doubt on the relevance of these results for living organisms.

What have we learned from the Science study? Some intriguing in vitro chemistry of vitamin C. The physiological relevance of these results has yet to be demonstrated. To conclude from this study that vitamin C causes cancer would be as preposterous as to say that we have found a cure for cancer based on a simple test tube experiment.  In fact, many animal studies and cell culture experiments have demonstrated anticancer effects of vitamin C, and the vitamin has been used therapeutically in human cancer patients with some apparent benefit.

What's more, although vitamin C supplements are often singled out as potential troublemakers, the body does not distinguish between dietary vitamin C and supplemental vitamin C ? it's all the same substance. Thus, if vitamin C indeed causes cancer, the advice would be not only to stop taking supplements, but also to stop eating vitamin C-rich fruits and vegetables ? an absurd recommendation! We know that vitamin C-rich foods lower the risk of cancer, heart disease, stroke and other diseases, so the more fruits and vegetables you eat, the better. And if you choose to take vitamin C supplements, stick to it, as the evidence indicates that you will do yourself a lot of good, and certainly no harm!

Honoring a Scientific Giant with Nutritional Research Toward Longer, Better Lives

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Most people who refer to vitamin C causing DNA damage are referring to a report in SCIENCE MAGAZINE by Ian Blair. I challenged Blair's assertions, and a shortened version of the following letter was published in SCIENCE....

June 15, 2001

TO: Ian A. Blair
Center for Cancer Pharmacology
University of Pennsylvania
ian@spirit.gcrc.upenn.edu


Unfortunately your paper in SCIENCE regarding ascorbic acid and DNA damage was published while you were out of the country and unavailable for quick comment. Of course, it is disappointing that the news media made such headlines out of research that does not appear to be new. The issue of whether vitamin C is a pro-oxidant or anti-oxidant has been debated for some time now. The fact that your paper concluded from a test-tube study that vitamin C concentrations equivalent to a 200 mg. dosage in humans could be genotoxic is not confirmed by epidemiological or human studies which your paper did not cite.

The submission date on your paper was February 2001, and your paper cited other references as late year 2000. The following reports, which includes reports up to the year 2000, encompassing a review of human studies with vitamin C and DNA damage, do not confirm your findings, and should have been included in your paper, am I correct?

I was wondering why your paper did not cite these references and why you did not inform the news media that your findings were not confirmed by human nor epidemiological studies? Your comments to the news media left the door open that it is possible for vitamin C to promote cancer. The references below are for your review, with the total abstracts following. Don't you think you should clear this matter up by clarifying the conclusion from your paper in light of other contrary research studies conducted outside of test tubes?

For example, researchers at Johns Hopkins University could not find evidence of a "significant main effect or interaction effect on oxidative DNA damage as measured by urinary 8-OHdG in non-smoking adults" with 500 milligrams/day of vitamin C supplementation. [Cancer Epidemiol Biomarkers Prev 2000 Jul;9(7):647-52]

Another study, conducted by researchers in Germany found that 1000 mg. of vitamin C consumed by smokers and non-smokers for 7 days did not produce DNA damage as measured by the number of micronuclei in blood lymphocytes. [Free Radic Res 2001 Mar;34(3):209-19]

In yet another study conducted by Immunosciences Laboratory, twenty healthy volunteers were divided into four groups and given either placebo or daily doses of 500, 1,000 or 5,000 mg of ascorbic acid for a period of 2 weeks. This study concluded that "ascorbic acid is an antioxidant and that doses up to 5,000 mg neither induce mutagenic lesions nor have negative effects on NK cell activity, apoptosis, or cell cycle." [Cancer Detect Prev 2000;24(6):508-23]

In London researchers measured the effects of 260 milligrams/day of vitamin C and vitamin C + iron in humans and concluded that there was "no compelling evidence for a pro-oxidant effect of ascorbate supplementation, in the presence or absence of iron, on DNA base damage measured by GC-MS." [Biochem Biophys Res Commun 2000 Nov 2;277(3):535-40]

In Ireland, researchers gave 1000 mg. of vitamin C to volunteers for 42 days and concluded that "supplementation with vitamin C decreased significantly H2O2-induced DNA damage in peripheral blood lymphocytes." [Br J Nutr 2000 Aug;84(2):195-202]