Selenium and prostate cancer

Published: March, 2007

Selenium is a mineral with a long and interesting history. Discovered in 1817 and named after the moon goddess, it was considered a poison during much of the 19th century. In the 20th century, selenium found a use in many industries, from ceramics to rubber to agriculture; imagine life without selenium and you'll conjure up a world without photocopiers. No longer considered toxic, selenium is the active ingredient in many therapeutic shampoos. But the greatest potential for selenium is as a supplement to reduce the risk of prostate cancer.

Only time will tell if that potential will be fulfilled, but it makes selenium a timely topic for health-conscious men.

Meet the mineral

Selenium is found in the earth's crust, but its concentration is lower than gold's. Selenium finds its way into plants, then works its way up the food chain. But since the selenium content of soil varies widely from place to place, the selenium content of food varies and is hard to predict. In general, the best sources are whole grains, tomatoes and other vegetables, seafood, nuts (particularly Brazil nuts), garlic, and onions; meat and poultry also provide significant amounts.

Selenium is essential for human health, but since only tiny amounts are required, it is classified as a trace mineral. The Recommended Dietary Allowance for adult men is 55 micrograms. Daily amounts as high as 400 micrograms appear entirely safe; beyond that, supplements can cause hair loss, nausea, or diarrhea.

Selenium and the heart

Scientists don't fully understand how selenium functions in the body, but one important role is its antioxidant activity. As a result, doctors have wondered if it might help fight atherosclerosis. Indeed, in 1982, a Finnish study reported that people with low blood selenium levels had an increased risk for developing coronary artery disease, and a 1991 study of Finnish men linked low selenium levels to atherosclerosis of the carotid artery. But in 1995, the Harvard Physicians' Health Study cast considerable doubt on the hypothesis that selenium protects the heart. In fact, in American men, high selenium levels were associated with a very slight increase in heart attack risk. And a 2006 study reported that taking selenium supplements had no effect on cardiovascular disease.

Researchers are now concentrating on selenium and cancer. The first glimmers came from the observation that cancer is less common in parts of the world that have high levels of selenium in the soil. Experiments in test tubes and laboratory animals followed, and many found potential anticancer activities for selenium. But a 1996 publication really put selenium on the map.

The Nutritional Prevention of Cancer Trial

To learn if selenium supplements might reduce the risk of recurrent skin cancer, a team of scientists working at seven American health centers gave either 200 micrograms of selenium or a placebo to 1,312 volunteers with an average age of 63; the participants took their tablets daily for an average of four and a half years. When the results were analyzed in 1996, the researchers were disappointed to learn that there was no difference in the occurrence of skin cancer in the two groups, but they were startled to find that there were 50% fewer cancer deaths in the selenium group. Selenium was linked to a significant reduction in deaths from lung, colon, esophageal, and prostate cancer; protection appeared strongest for prostate cancer, with 63% fewer deaths in the men who took selenium. There were no cases of selenium toxicity. These results were greeted with great interest but also with caution; some doctors felt they were too good to be true, and most stressed the need for further research.

The Nutritional Prevention of Cancer Trial has issued two subsequent reports, which extend the observation period by 25 months, to the end of the trial. The initial hopes that selenium might reduce the incidence of lung and colorectal cancer did not hold up. But the men who received selenium continued to enjoy a 49% lower risk of prostate cancer through a follow-up period that averaged 7.6 years. The apparent protection was strongest in the men with the lowest blood selenium levels before starting the supplements and in men with PSA levels below 4.0 ng/ml.

The Harvard studies

The Nutritional Prevention of Cancer Trial is the only randomized clinical trial "" the gold standard of evaluation "" of selenium supplements that has been completed. Still, that trial did not settle the selenium question. For one thing, it designated skin cancer as its primary end point; prostate cancer was just a secondary end point. For another, every study, however well done, requires confirmation, particularly when the results are surprising. Indeed, a large trial of selenium for prostate cancer prevention is already under way. But until the results are available, scientists have tried to shed light on the issue by performing observational studies to compare the risk of prostate cancer in men with low and high selenium levels.

Just two years after the 1996 report, Harvard's Health Professionals Follow-up Study weighed in with a study of 33,737 men between the ages of 40 and 75. The researchers did not administer selenium supplements, nor did they measure blood levels of the mineral. Instead, they asked the volunteers to submit toenail clippings at the start of the study. The clippings were analyzed for selenium concentration, which reflects the selenium intake over the many months during which nails are formed.

When the scientists tracked the men for six years, they found that the men with the highest selenium levels at the start of the study had a 65% lower incidence of advanced prostate cancer than the men with the lowest levels, even after taking other prostate cancer risk factors into account. The Harvard team calculated that a daily consumption of 159 micrograms of selenium would prove protective.

A second Harvard study followed in 2004. The Physicians' Health Study collected blood samples in 1982 from 14,916 American doctors who were in good health. Over the next 13 years, the men with the highest initial blood selenium levels had a 48% lower incidence of advanced prostate cancer than those with the lowest levels. Men with high selenium levels who also had elevated PSA levels at the start of the study experienced the additional benefit of a lower risk of early prostate cancer.

Other opinions

The Harvard scientists are not the only ones who can measure selenium levels. Researchers worldwide have used nail clippings, blood samples, and dietary questionnaires to evaluate selenium consumption and the risk of prostate cancer. The populations have included men living in regions with low, moderate, and high soil selenium levels. Some studies were short-term; others followed their subjects for more than six years. One report evaluated more than 58,000 men, another just 150. Some studies took other prostate cancer risk factors into account, others did not. And while some studies included early prostate cancers, others focused on advanced cases or prostate cancer deaths.

With so many variables, it's not surprising that the results varied widely, with some studies reporting substantial protection from selenium while others found no benefit. But when researchers from Canada performed a meta-analysis of 16 individual trials, they found that a moderate intake of selenium was linked to a 26% reduction in the risk of developing prostate cancer. The protection appeared greater with higher selenium levels and was most pronounced for advanced cancers.

Tomorrow and today

It's a familiar refrain: The only way to sort out an unsettled area of research is to perform additional studies. In the case of selenium, a definitive randomized clinical trial is already in progress. Sponsored by the National Cancer Institute, the Selenium and Vitamin E Cancer Prevention Trial (SELECT) will evaluate the effects of selenium and vitamin E, singly or in combination, in 32,400 men.

SELECT will provide much-needed answers about selenium and another controversial supplement, vitamin E. But the results won't be announced for years. In the meantime, what's a man to do?

The choice is yours. It's far too early to recommend a supplement for all men, but it's certainly important to recommend a healthful diet that will provide good amounts of the mineral. And if you are attracted to supplements, selenium is a reasonable choice. The best dose and form of the mineral are not known, but since the 1996 trial used 200 micrograms a day, that dose seems appropriate. Similarly, it's wise to use an organic form of the mineral, such as the selenomethionine that the NPC administered in selenized yeast.

Historians tell us that selenium was named for a goddess, and geologists say that it's rarer than gold. Soon, doctors will tell us if it's worth its weight in health or if it's a false idol.

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