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Can High Doses of Vitamin C Alter Gene Expression?

Many people believe that if a little bit of something is good, than a lot more must be better. That may not always be the case, especially when it comes to vitamins. Vitamin C, a well-known antioxidant at low doses, has been linked in epidemiological studies to the prevention of cardiovascular disorders or cancer by protecting DNA from oxidative damage. However, several in vitro studies have indicated that, at very high doses, antioxidants such as vitamin C or β-carotene may lose the ability to protect DNA, and may potentiate DNA damage in certain instances.

The Institute of Medicine (IOM) has defined the tolerable upper intake level (the highest level of daily intake that is likely to pose no risk of adverse health effects) for vitamin C at 2000 mg/day for adults. While this amount agrees with the United Kingdom’s supplement industry recommendations of 2000 mg/day, a report commissioned by the Food Standards Agency recommended that the upper level should be limited to 1000 mg/day, citing potential side effects, such as stomach cramps, diarrhea and flatulence. Although there is no evidence that high doses of vitamin C are toxic, additional safety studies at these high doses would help answer the question of safety of high doses of vitamin C.

The Food Standards Agency has funded a clinical study to assess the effects of ingestion of up to 2000 mg/day vitamin C, which will include the analysis of genetic markers to determine alterations in DNA made by the ingestion of large amounts of vitamin C. Through toxicogenomics, a field of genetic study utilizing microarrays that provide the opportunity to analyze thousands of genes at the same time, a clinical study will investigate whether high doses of vitamin C are affecting genes that are linked to either DNA protection or damage. DNA changes can be combinations of adaptation, protection or repair mechanisms.

The study, which should be completed at the end of the year, will take into account the potential expression of a wide array of genes, which should make a much more accurate assessment of the effects of vitamin C on the genome. The success of toxicogenomics depends on the ability to interpret the genetic data in relation to the classical toxicological information obtained in the clinical trial. Genetic arrays are increasingly being used to determine potential toxicity, and may open the door to understanding the levels at which nutrients may be consumed safely.

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