Tag: SELECT study

Selenium still helps preventing cancer

Claus Hancke

January 26, 2009

A huge U.S. study showed that supplementation of selenium do not prevent cancer of the prostate. But this result is only valid if you get plenty of selenium in advance.

12 years ago it aroused hope and optimism when American Larry Clark could tell that the mineral selenium prevents cancer, particularly prostate cancer, the second most common cause of death from cancer in men. He had to stop his trial before expiry when he learned that far fewer selenium-treated than placebo-treated patients (placebo: Inert tablets) got cancer.

Now a second, much larger, selenium trial has been stopped prematurely. Also in this case the focus of interest was the effect against prostate cancer. This was also an American study. But SELECT, as the trial was named, unfortunately showed that selenium had no effect. One could even not exclude an, admittedly very little, harmful effect. So, it was stopped.

In the meantime, Clark’s trial has been studied more closely. Was it really as convincing as was first believed? With 1.312 participants it was not nearly as large as SELECT where 35.000 attended. Very important was that the final report which came in 2003 showed that the benefit was smaller than first believed. Some cases of prostate cancer among selenium treated had for various reasons been overlooked.

What was left was a statistically significant benefit among those who at the beginning of the experiment had the least selenium in the blood and with most certainty did not have incipient cancer of the prostate. The latter could be concluded from the very low values of PSA (Prostate-Specific Antigen) in the blood of these people. In this group, while the trial was in progress, the incidence of cancer of the prostate was three times less than in the placebo group.

More selenium in the U.S.
Now the question is whether the much larger SELECT trial cancels Clark’s trial. It seems to be the general opinion as for example reflected in the leading article of the same issue of the American medical journal, JAMA, where SELECT was published. So far physicians should not recommend selenium as a prevention against prostate cancer, it says.

And yet one can rightly come to the diametrically opposite conclusion: There is every reason to believe that selenium prevents cancer of the prostate, and presumably also other kinds of cancer.

The fact is that Americans, but not all Americans, get far more selenium in their diet than we Scandinavians. In Clark’s study, participants were selected on the basis of consistently having relatively little selenium in their diet for U.S. standards. Two-thirds had less than 122 micrograms of selenium per. liter of serum. In the SELECT study only one in five had that low values. In other words, it is conceivable that most of the SELECT participants already got plenty of selenium so that additional supplementation would not benefit them. In Denmark almost everybody get less selenium than the participants of both the first and the second study mentioned. Our values are typically 80 micrograms per liter.

This is in excellent compliance with the fact that incredible few participants died from prostate cancer during the SELECT study. Statistically one would have expected 75 to 100 deaths for this reason, during the 5.6 years duration of the study. But only one died (!).

A contributory cause may have been that the vast majority of participants in the SELECT study on their own underwent PSA measurement annually. Possible prostate cancer was therefore detected and treated early. On the other hand, other studies have shown that annual PSA measurement does not reduce mortality. Therefore it is not recommended in Denmark.

Despite the termination of the SELECT study, as a Dane you should still remember that the research that involves us – as opposed to Americans we get very little selenium in our diet – suggests that supplementation with selenium in the order of 1-2 tablets (100-200 micrograms) per day seems to reduce the risk of prostate cancer to a third.

By: Niels Hertz, M.D.

References:
1. Lippman SM et al. Effect of selenium and vitamin E on risk of prostate cancer and other cancers. JAMA online December 9, 2008: E1-E13
2. Gann PH. Randomized trials of antioxidant supplementation for cancer prevention. JAMA online December 9, 2008: E1-E2.
3. Selenium supplementation, baseline plasma selenium status and incidence of prostate cancer: An analysis of the complete treatment of the Nutritional Prevention of Cancer Trial. BJU Int. 2003;91:608-12.

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Selenium, A Potent Substance Against Cancer

Claus Hancke

January 18, 2006

Studies from all angles support the idea that selenium works against cancer. Even though there is need for more research, an optimal dose can be suggested.

Selenium prevents cancer. This is common knowledge which is only awaiting conclusive confirmation. It received recognition when, in 1996, an American researcher (Clark) showed in a randomised study that the frequency of cancer fell by 38%, and that the fatality rate of those with cancer fell by 50%, in participants who received daily supplement of 200 micrograms selenium.

The supposition that selenium is preventative for cancer is in fact much more extensively backed. This has been shown by a leading selenium expert, Margret Rayman from the University of Surrey in England, in a thorough, but also complicated, summary. She has also illuminated who selenium prevents cancer and, even more importantly, how much is needed.

Rayman reviews the many geographical studies that have, since the 1960’s, consistently shown that the populations who received the least amount of selenium also had the highest cancer rates. Animal studies are also discussed. If one gives selenium to a male dog, not only is there less damage to the DNA of prostate cells, but the damaged cells that remain also die normally instead of living on as cancer cells.

A certain pattern emerges when one looks at studies where the blood concentration of selenium is compared to the cancer rate in groups of people. In a French study of this type from 2005, the death rate from cancer after nine years was four times greater in the 25% of the study-group who received the least selenium than in those who received the most selenium. Typically the French receive as little selenium in their diets as the British. Many studies from many countries have shown similar results for lung cancer (a 26% lower risk of cancer was reported in those with diets rich in selenium), oesophagus cancer, stomach cancer, and not in the least, prostate cancer as well as possibly cancer of the large intestine.

How much is enough
The best evidence can always be found in randomised studies where neither the patients nor the doctors know who receives what. A Chinese study of this type has shown that selenium has an especially effective against liver cancer. As mentioned before, Clark’s study had similar results. It is intriguing that, even though Americans receive an average of 200 micrograms more selenium daily than us, an additional 200 micrograms was beneficial to most. The effects were nevertheless minimal in those who received the most selenium beforehand. These individuals already received close to the optimal dose. But third of the population who received the least beforehand, had their cancer risk halved, and their prostate cancer risk decreased by 86%, after taking supplementary selenium.

Typical Europeans receive too little selenium while Americans receive double as much and Japanese receive almost three times as much. It has become apparent that 70 micrograms of selenium is needed in the daily diet to maintain levels of the selenium based antioxidant GSHpx in the body. The Japanese and most Americans receive this amount in their diets while we do not. But why is their cancer risk reduced when they receive supplementary selenium? The reason cannot be GSHpx and may not even be the anti-oxidizing effects alone.

Rayman examines many possible explanations. One is that high doses of selenium lead to the formation of the simple selenium compound methylselenol; which can kill cancer cells, counteract the formation of blood vessels (which the cancer cells need to survive) and can inhibit cancer in other ways. But selenium is naturally an antioxidant, an immune system stimulant, an activator for cancer inhibiting genes, an inhibitor for growth factors, etc. There is not one, but many, mechanisms of action.

Unchecked amounts of selenium should not be taken. Studies indicate that sufficiently high doses of selenium can increase the risk of cancer as much as insufficient amounts. Clark’s study, as well as others, suggests that a daily supplement of 200 micrograms is optimal.

The reward can be large, but more research is needed. Currently a large clinical trail (called SELECT) is being undertaken in the U.S.A., but a study in the more selenium poor Europe would be better. Rayman believes that such a study should be undertaken. But who wants the placebo!?

By: Vitality Council

References:
1. Rayman M P. Selenium in cancer prevention: A review of the evidence and mechanism of action. Proceedings of the nutrition society. 2005;64:527-42.
2. Clark LC et al. Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer study group. JAMA 1996;276:1957-63.
3. Akbaraly NT et al. Selenium and mortality in the elderly: Results from the EVA study. Clin Chem. 2005;51:2117-23.

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