By Sean Henahan, Access Excellence

TUCSON, AZ (12/25/96) Dietary supplementation with the micronutrient selenium may help protect against some types of cancers, according to an article in The Journal of the American Medical Association (JAMA).

Graphic: The Selenium Atom

Researchers at the Arizona Cancer Center set out to evaluate the effectiveness of selenium supplementation for preventing skin cancer in high-risk individuals. Some 1,312 patients received either placebo or 200 micrograms of selenium per day for a mean time of 4.5 years and a total follow-up of 6.4 years. The patient population was recruited from the Eastern Coastal plain of the U.S., an area with relatively low selenium levels in soil and crops and also high rates of skin cancer.

The researchers found that selenium supplementation did not reduce the incidence of skin cancers in study participants. However, they also evaluated the effect of selenium for preventing other types of cancers and for reducing cancer mortality. These secondary results indicate that when all cancers were studied, the selenium group had a 37 percent reduction in cancer incidence and a 50 percent reduction in cancer mortality, although there were no significant differences in deaths from all causes in the selenium group or the placebo group.

Of the nearly 200 new cases of cancer diagnosed, the selenium group had 63 percent fewer prostate cancers, 58 percent fewer colorectal cancers and 46 percent fewer lung cancers than the placebo group.

"Primarily because of the apparent reductions in total cancer mortality and total cancer incidence in the selenium group, the blinded phase of the trial was stopped early. No cases of selenium toxicity occurred. These apparent beneficial effects of selenium supplementation require confirmation in independent trials of appropriate design before public health recommendations regarding selenium supplementation can be made," reported study director Larry C. Clark, M.P.H., Ph.D.

The selenium dose of 200 micrograms per day used in the study is within the normal dietary intake of most Americans and provides approximately twice the projected typical dietary intake of the study patients, Dr. Clark notes.

Selenium was first associated with cancer risk in the late 1960s. Hypotheses explaining selenium's inhibition of tumor growth include antioxidant properties; the ability to alter carcinogen metabolism; effects on the endocrine and immune systems; and inhibition of protein synthesis.

In a related editorial in the same issue of JAMA, Graham A. Colditz, M.B.B.S., Dr.P.H., Brigham and Women's Hospital and Harvard Medical School, Boston, Mass., advised caution about the study and its findings. He pointed out several major concerns, including questions about the biological plausibility of the rapid and large effects observed, issues related to the interpretation of endpoints for cancer mortality and total cancer incidence (which were established well after the trial was underway), and limited applicability of the results for women.

Dr. Colditz writes: "This promising set of results ... require confirmation in further randomized trials designed to test the effect of selenium supplementation on cancer incidence and mortality ... For now it is premature to change individual behavior, to market specific selenium supplements, or to modify public health recommendations based on the results of this one randomized trial."

He continues: "As we await the results of further prevention research, known lifestyle changes that can reduce cancer risks (such as smoking cessation, consuming adequate amounts of fruits and vegetables each day, reducing intake of animal fat, and increasing physical activity) should be implemented."

Subsequent investigations early in the twentieth century established that blind staggers is only encountered in areas where the soil is very rich in the mineral selenium, and in which special plants grow ("indicator plants"; of the genus Astragalus) that accumulate selenium from the soil. Blind staggers develops in animals that graze on these selenium-rich indicator plants and is thus a manifestation of selenium toxicity. Selenium poisoning can lead to nausea, garlicky breath, flu-like symptoms, loss of hair, fingernails or hooves, neurological problems, liver damage, and in severe cases respiratory failure and death. In the recent past, selenium earned notoriety as a suspected cause of the poisoning of birds at California's Kesterton Reservoir.

The fact that selenium was also an essential nutrient did not come to light until the 1950s when Dr. Klaus Schwarz, a German physician-scientist made a breakthrough in understanding a perplexing form of liver failure in rats known as dietary hepatic necrosis. For reasons that were then unclear, rats developed fatal liver degeneration when fed a vitamin E-deficient diet in which the sole source of protein was torula yeast. Surprisingly, the vitamin E deficiency did not result in liver failure when brewer's yeast was the source of protein. The researchers then discovered that selenium was the hitherto unknown essential nutrient that was adequately supplied by brewer's yeast.

Schwarz recognized that either vitamin E or selenium could prevent liver damage, but that simultaneous deficiency of both resulted in fatal liver failure. Schwarz coined the term "ambogenous" to refer to two nutrients which can in effect "pinch hit" for each other in maintaining healthful physiological function.

Since vitamin E was known to protect cells from the damaging effects of highly reactive free radicals produced not only by certain toxins and high energy radiation but also by normal metabolism, it was logical to expect that selenium likewise was somehow contributing to protection from free radicals. This supposition was verified when, in 1973, scientist John T. Rotruck and colleagues published their demonstration that selenium is an obligatory component of the crucial antioxidant enzyme glutathione peroxidase.

The study appeared in JAMA: 12/24/96