Antioxidant supplements suggested to increase skin cancer risk in women

Intake of supplements containing vitamin C, vitamin E, beta-carotene, selenium and zinc may increase the risk of developing melanomas in women, a French follow-up study claims.

In 2007, the results of the randomized controlled SU.VI.MAX trial suggested an up to 4-fold higher risk of total skin cancers and melanomas in a group of women receiving a daily combination of antioxidants (120 mg vitamin C, 30 mg vitamin E, 6 mg beta-carotene, 100 mcg selenium and 20 mg zinc) compared to a placebo after a median of 7.5 years (1). Conversely, in men, no significant differences were found between the treatment groups. In order to investigate possible residual or delayed effects of antioxidant supplementation on skin cancer incidence, the SU.VI.MAX participants were followed up for additional 5 years after the end of the supplementation period (2). The results of this follow-up study indicate that the elevated skin cancer risk receded when antioxidant supplementation was stopped.

The researchers speculate that supplementation may play a causative role in the enhanced development of pre-existing skin tumors in women. They concede that it is unlikely that new tumors of the skin may develop over a time period as short as the supplementation periods of their trials. The findings that only women (and not men) showed an increased disease risk should be interpreted with caution because of the relatively small number of events within subgroups of skin cancer, which is a principal limitation of the study, they commented.

In other large studies, no evidence of an association between daily use of supplemental antioxidants (at doses similar to those used in the SU.VI.MAX trial) and melanoma risk was found, and the results did not vary by sex (3, 4). Experts criticize that the findings of the SUVIMAX trial and the follow-up study could be explained by methodological shortcomings: the analyses were limited to a subsample of participants who agreed to answer a single question on their lifetime sun exposure, which could introduce selection bias and limit generalizability. In addition, the statistical analysis was based on only 16 skin cancer cases, limiting its significance (5).

Among the multiple melanoma risk factors, sunlight exposure at early ages, number of nevi and family history are believed to be the most important ones.

1. Hercberg S. et al. Antioxidant supplementation increases the risk of skin cancers in women but not in men. J Nutr. 2007; 137:2098–105.
2. Ezzedine K. et al. Incidence of skin cancers during 5-year follow-up after stopping antioxidant vitamins and mineral supplementation. European Journal of Cancer. 2010.
3. Asgari M. M. et al. Antioxidant supplementation and risk of incident melanomas - Results of a large prospective cohort study. Arch Dermatol. 2009; 145(8):879–882.
4. Feskanich D et al. Dietary intakes of vitamins A, C, and E and risk of melanoma in two cohorts of women. Br J Cancer. 2003; 88(9):1381–1387.
5. Green A. C. et al. Antioxidant supplementation and risk of skin cancers. J. Nutr. 2008; 138:978.