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Title: Vitamin C exhibits pro-oxidant activity

Source: Nature 392: pg 559 (9 April 1998)

Authors: I.D. Podmore, H. R. Griffiths, K. E. Herbert, N. Mistry, P. Mistry, J. Lunec

Division of Chemical Pathology, University of Leicester

Email: idp@le.ac.uk

Summary: A study of 30 healthy volunteers, ages 17 to 49. These volunteers took 500 mg of vitamin C daily for 6 weeks. DNA damage was measured in blood lymphocytes, to detect oxidative damage to DNA. DNA is made of 4 bases, Guanine, Cytosine, Adenine, and Thymine. Using Gas chromatography-Mass Spectrometry, the authors measured oxidized bases, 8- oxoguanine and 8-oxoadenine.

Normal values for oxidative damage are 30 lesions of 8-oxoguanine and 8 lesions of 8-oxoadenine per 100,000 guanine and adenine bases respectively. When vitamin C was administered, the pattern was reversed, with the guanine lesions decreasing and the adenine lesions increasing, changes which according to statistical tests were significant.

COMMENT:

This study is of interest because it provides a potentially useful method for examining optimum dosages of antioxidants. However, as a single study, it provides primarily a useful direction for further studies.

1. At the dosage studied, vitamin C did not increase the total number of DNA lesions. The pattern changed from predominantly Guanine lesions to predominantly Adenine lesions.

2. A dose-response relationship will be important to establish to lend credence to this line of inquiry. It would be exciting to see how different doses of vitamin C impact on the number of observed lesions. If doses of 200, 500, and 1,000 mg show a consistent pattern, then the evidence will be more credible.

3. Although this is an interesting study, it conflicts with large numbers of other studies which look specifically at the true endpoint, cancer, for which there is overwhelming evidence that high dosages of vitamin C, above 500 mg daily, reduce the risk of cancer, especially in combination with vitamin E.

CONTRASTING STUDIES

1. The following study of 11,000 people shows that vitamin C supplements, in conjunction with vitamin E, dramatically reduces the risk of cancer.

. Losonczy, K. G., Harris, T.B., and Havlik, R. J. "Vitamin E and vitamin C supplement use and risk of all-cause and coronary heart disease mortality in older persons: the Established Populations for Epidemiologic Studies of the Elderly", Am. J. Clin. Nutr. 64:190-6 (1996)

Study of 11,000 people over 66 for 3 years:

Relative risk

supplement use mortality heart disease cancer

none 1 1 1

multivitamin 1.04 1.14 1.08

both C and E 0.58 0.47 0.78

2. The following study of more than 11,000 people indicates that vitamin C intake reduces cancer risk.

Enstrom, JE, Kanim, L.E., and Klein, M.A., "Vitamin C intake and mortality among a sample of the United States population", Epidemiol. 3: 194-202 (1992)

11,348 noninstitutionalized U.S. adults age 25-74 years from NHANES I followed for 10 years. "The relation of the standardized mortality ratio (SMR) for all causes of death to increasing vitamin C intake is strongly inverse for males and weakly inverse for femalies. Among those with the highest vitamin C intake, males have an SMR of 0.65 for all causes, 0.78 for all cancers, and 0.58 for all cardiovascular diseases; females have an SMR of 0.90 for all causes, 0.86 for all cancers, and 0.75 for all cardiovascular diseases [vs. an SMR of 1.0 for all U.S. whites.]"

Reduced risk of developing condition over 10 year period

Condition All U.S. Men+vit C Women+vit C

Death 0% 35% 10%

Cancer 0% 22% 14%

Heart disease 0% 42% 25%