Beta-carotene supplements activate cancer-causing enzymes, study suggests

provided by University of Texas Medical Branch at Galveston


study by scientists at the Univer- sity of Texas Medical Branch at Galveston (UTMB) and the University of Bologna in Italy casts further doubt on the value of taking beta-carotene supplements as a means to prevent cancer.

According to research being published in the April 29 issue of the journal Nature, beta-carotene supplements increase the activity of certain proteins which, during the normal processing of certain toxic compounds, turn those compounds into potentially harmful, cancer-causing ones.

If those proteins are hyper-activated, "you're getting more cancer-causing bang for your buck every time you're exposed to a carcinogen such as when you smoke a cigarette," says Marvin Legator, a UTMB professor of environmental toxicology and of preventive medicine and community health, corresponding author of the new study.

The new results which were obtained by studying rats point to at least one potential mechanism behind the seemingly paradoxical health effects of supplementing one's diet with beta-carotene. Previous epidemiological and animal studies suggested that taking beta-carotene supplements might prevent cancer in humans. That inference was supported by the fact that beta-carotene is an antioxidant a chemical that can mop up harmful oxygen molecules called free radicals which, if allowed to run rampant in cells, can damage genetic material in ways that may lead to cancer.

But studies of humans who consented to take vitamin supplements unexpectedly showed that taking beta-carotene either alone or in combination with vitamin A or vitamin E actually increased lung-cancer incidence and mortality. Those studies, which were published in 1994 and 1996, looked at heavy smokers and asbestos workers.

The new rat study is among the first to suggest a mechanism by which beta-carotene might lead to these adverse effects. Researchers measured levels of several enzymes belonging to a family of proteins known as cytochrome P450s. These enzymes metabolize a number of carcinogenic compounds (such as polycyclic aromatic hydrocarbons, dioxins and nitrosamines) contained in cigarette smoke and in the environment. The activity of those enzymes was boosted in the lungs of rats that were fed beta-carotene supplements but not in rats that weren't.

Researchers don't know whether beta-carotene has a similar effect in humans. But if it does, these results are decidedly relevant to public health, they say. That's because most carcinogens acquire their cancer-causing capabilities after being acted on by enzymes such as the cytochrome P450s, which act similarly in humans and in rats. Only after this interaction are carcinogens able to induce the genetic damage that leads to cancer.

"Most compounds that are considered carcinogenic are not carcinogenic by themselves," Legator explains.

Sherif Abdel-Rahman, UTMB assistant professor of environmental toxicology and preventive medicine and community health, a coauthor of the study, notes: "In humans and particularly in smokers high levels of these enzymes would predispose an individual to greater cancer risk." Abdel-Rahman adds that the cancer-boosting effect of beta-carotene might be more pronounced in people who inherit forms of cytochrome P450 that are naturally highly active.

Professor Moreno Paolini of the University of Bologna, senior author of the study, says, "We think that our findings are relevant to public health policy and that they should be considered before widespread supplementation with these micronutrients is recommended."

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