Antioxidant Supplements May Raise Women's Skin Cancer Risk
Mechanism isn't clear and new findings don't apply to men.

See John Cartmell's comments following article.

 French scientists have reported that antioxidant supplements, which include vitamins C, E and beta carotene, may increase women's risk of skin cancer.
By Kathleen Doheny, HealthDay Reporter


Taking antioxidant supplements won't protect against skin cancer and may actually boost the risk, at least in women, according to a new French study.

"Taking into consideration our results, we are particularly concerned by the use of long-term supplementation, notably in sun-seekers and people wanting to look tanned [using beta-carotene]," said researcher Dr. Serge Hercberg, professor of nutrition at the Medical University of Paris.

The new findings come on the heels of a study, published in mid-August in the Archives of Internal Medicine, that found that antioxidants don't prevent heart disease risk in high-risk women.

In the new French study, published in the September issue of The Journal of Nutrition, Hercberg's team looked at the effects of antioxidant doses on skin cancer. The research was conducted as part of a larger study that looked at the effects of antioxidants on cancer and ischemic heart disease.

Antioxidant nutrients are thought to reduce disease risk by cutting down on the unhealthy effects of "free radical" molecules that damage cells.

The researchers assigned almost 7,900 women and more than 5,100 men to take either an oral daily capsule of antioxidant or a placebo that looked the same. The antioxidants included 120 milligrams of vitamin C, 30 milligrams of vitamin E, 6 milligrams of beta-carotene, 100 milligrams of selenium and 20 milligrams of zinc.

"They are not high doses," Hercberg said. "They are at a level below a lot of pills you can find to buy over the counter."

The men and women were followed for about 7.5 years. In that time, 157 cases of any form of skin cancers were reported, including 25 melanomas, the most deadly form.

The team found that, in women, the incidence of all types of skin cancer combined was actually higher in the antioxidant group, and so was their incidence of melanoma.

But the incidence of non-melanoma skin cancers, when evaluated separately, did not differ between the antioxidant and placebo groups in men or women. In men, there was no difference in any form of skin cancer (including melanoma) between the two groups.

In the antioxidant group, 51 women developed skin cancer, while 30 in the placebo group did. Among the men, 43 in the placebo group and 33 in the antioxidant group got skin cancers.

As for melanoma, the incidence did not differ significantly between the men's treatment group -- 6 in the placebo group and 3 in the antioxidant group got it. But 3 women on placebo and 13 on antioxidants got melanoma -- a significant difference, the researchers said.

Antioxidant studies have yielded mixed results, Hercberg stressed. For example, in previous studies, researchers saw a higher risk of lung cancer in heavy smokers who regularly took high doses of beta-carotene.

Studies have suggested that antioxidant supplements might protect against prostate cancer incidence in men with low blood levels of prostate specific antigen (PSA), Hercberg said. But research has also suggested that the nutrients might increase prostate cancer risk in men with a high PSA. PSA levels are a marker for pre-existing prostate cancer risk.

That could also be happening in the women who got more skin cancers after taking antioxidants, he theorized. If their skin cancer had already been developing, taking an antioxidant might not help, Hercberg speculated.

While the study is interesting, further research is needed to confirm it, said Dr. Ariel Ostad, a spokesman for the Skin Cancer Foundation and a New York City dermatologist not involved in the study.

He said the study did have one serious limitation. "It does not take into account sunscreen use," he said. If the participants tended not to use sunscreen, that could have affected the results.

Meanwhile, Ostad added, taking care in the sun is important, and "sunscreens are by far the most powerful" weapon to prevent skin cancers.

(SOURCES: Serge Hercberg, M.D., Ph.D., professor, nutrition, Medical University of Paris, France, and director, department of nutritional epidemiology, French Institute for Health and Medical Research; Ariel Ostad, M.D., dermatologist and spokesman, Skin Cancer Foundation, New York City; September 2007, Journal of Nutrition)

John Cartmell comments:

The reader should not be too quick to embrace any one study as truth. As one scientist below comments, "While the study is interesting, further research is needed to confirm it."

There are many variables that can affect the end results in any research study. For me, this study raises more questions than it answers.

  • How many of those who developed melanoma in the study had a history of digestive disorders like Irritable Bowel Syndrome where absorption of antioxidants and other nutrients might be impaired?
  • How many of them had an undiagnosed melanoma, or history of having other cancers?
  • How many had a history of severe sunburn, which, by damaging DNA, can increase the risk of developing skin cancer?
  • How many smoked, used alcohols, ate a diet high in refined foods (low in antioxidants), or a diet low in raw fruits and vegetables (high in antioxidants), or had diabetes (high blood sugar suppresses the immune system)?
  • Did any subjects have a history of supplementing with antioxidants prior to the study, and if so, in what amounts?
  • Was the health and health history of those who participated in the study generally similar?
  • Who paid for the study?

Chemically, oxidation happens when a hydrogen atom (proton) is lost from a molecule. The resulting "free radical" molecule is unstable, and prone to "steal" back a proton from another nearby molecule, causing in turn, more oxidation in a chain reaction sequence. If molecules of body tissues are caught in these oxidation reactions, cell damage, mutation of DNA or cell death can occur. The oxygen-based metabolism of higher animals creates many free radical side products that must be controlled.

Antioxidant nutrients and enzymes counteract oxidation by easily becoming oxidized while remaining relatively stable despite losing a hydrogen atom. In this way, antioxidant nutrients protect our tissues from oxidation reactions by "taking the hit". Some antioxidants can restore other antioxidants by donating a hydrogen atom (becoming oxidized). This is why taking a variety of antioxidants, not just one or two, is so important; antioxidants work as a group. Antioxidants nutrients include vitamins A, C, E, beta-carotene, Zinc, Selenium, polyphenols (in coffee, tea and chocolate) pycnogenols (in the pulp of berries), and enzymes Super Oxide Dismutase (SOD) and glutathione peroxidase.

There have been thousands of studies on antioxidants and cancer. One interesting study in 2004 compared the different effects of low doses of antioxidants vs. high doses, on cancer. The following excerpt is from the abstract of this study, "Rationale for Using High-Dose Multiple Dietary Antioxidants as an Adjunct to Radiation Therapy and Chemotherapy":

Most oncologists do not recommend antioxidants to their patients during standard therapy, but some may recommend them at low doses after completion of therapy. The use of antioxidants and their derivatives in combination with standard therapy may be harmful, because endogenously made antioxidants (glutathione-and antioxidant enzyme–elevating agents) at any dose—or dietary antioxidants and their derivatives, such as vitamin A, including retinoic acid; vitamin C; vitamin E as d-{alpha}-tocopheryl succinate and natural ß-carotene at low doses—may protect cancer cells during therapy, and because low doses of individual dietary antioxidants may stimulate the proliferation of residual cancer cells.

Dietary antioxidants at high doses induce differentiation, proliferation inhibition, and apoptosis, depending on the dose and type of antioxidants, treatment schedule, and type of tumor cells, without producing similar effects on most normal cells in vitro and in vivo. The growth-inhibiting effect of these agents on cancer cells may not involve antioxidant action but may involve changes in expression of genes and levels of proteins and translocation of certain proteins from one cellular compartment to another. A mixture of retinoic acid, vitamin E, vitamin C, and carotenoids produces ~50% proliferation inhibition in human melanoma cells in culture at doses that do not reduce proliferation when used individually. Doubling only the dose of vitamin C in the mixture causes about 90% proliferation inhibition. In addition to dietary antioxidants and their derivatives, endogenously made antioxidants such as over expression of mitochondrial manganese-superoxide dismutase and the glutathione-elevating agent N-acetylcysteine (NAC) reduce the proliferation of cancer cells in culture.

Laboratory data show that antioxidants protect cancer cells when dietary or endogenously made antioxidants are administered only one time, at low doses that do not affect the proliferation of cancer cells, shortly before therapeutic agents.

Laboratory experiments also show that growth-inhibiting (high) doses of vitamin E, vitamin C, and retinoic acid administered before and after irradiation enhance the effect of x-irradiation on cancer cells in culture and protect normal fibroblasts against some radiation damage. Vitamin A and ß-carotene at high doses, administered daily before x-irradiation and during the entire observation period, produces a >90% cure rate in mice with transplanted breast adenocarcinoma; whereas treatment with radiation alone or antioxidant alone is ineffective.

Some proposed mechanisms for the enhanced effect of x-irradiation and chemotherapeutic agents by dietary antioxidants and their derivatives include the following: a) high doses of dietary antioxidants before irradiation or chemotherapeutic agents initiate damage in cancer cells but not in normal cells, and cancer cells suffer additional damage during treatment with these agents through mechanisms other than free radicals.

Interestingly, the level of antioxidants used in the study, "Antioxidant Supplements May Raise Women's Skin Cancer Risk" are, except for zinc, generally considered to be low doses: "120 milligrams of vitamin C, 30 milligrams of vitamin E, 6 milligrams of beta-carotene, 100 milligrams of selenium and 20 milligrams of zinc." The reader should note the misprint of 100 milligrams of selenium. It should read 100 micrograms. Selenium toxicity occurs in healthy people at levels somewhat higher than 400 micrograms/day. One hundred milligrams of selenium is equal to 100,000 micrograms, clearly a very toxic and potentially lethal dose of selenium.

John W. Cartmell, MS

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