Saturday, April 4, 2009

Jon's Health Tips - Selenium/Vitamin E

Selenium is among the many supplements I have used and then stopped using. It was hyped as a prostate cancer preventive – I saw an ad only last week still hyping it that way – but the most recent research – published within the last month and first on the reports below debunks this. (The report adds to the concern about Vitamin E, another supplement I have quit on.)

Effect of Selenium and Vitamin E on Risk of Prostate Cancer and Other Cancers

In the January 7, 2009 issue of the Journal of the American Medical Association, Dr. Scott Lippman and associates presented the results of the Selenium and Vitamin E Cancer Prevention Trial (SELECT). This is a phase 3 randomized, prospective, placebo controlled trial evaluating 4 arms; placebo, selenium (200_g/day), vitamin E (400IU/day), or both for prostate cancer (prostate cancer) prevention. The trial rationale was based on the observation that these compounds tested for chemoprevention in other trials suggested benefit. Surprisingly, SELECT was stopped early as no benefit was demonstrated on interim analysis.

The plan was for a minimum of 7 years of treatment and it included men age 50 years or older for African Americans and age 55 years or older for all other races. Men were without a diagnosis of prostate cancer, had a PSA <4ng/ml and a digital rectal examination not suspicious for prostate cancer. SELECT was activated in 2001 and participants had office visits every 6 months. The primary end point was prostate cancer incidence as determined by routine clinical management. Guidelines for PSA screening were not enforced, as PSA screening was controversial at the time of study design. The trial design was intent-to-treat.

A total of 35,533 men were accrued and randomly assigned at 427 centers in the US. Important risk factors were well-balanced among the groups and median overall follow-up was 5.46 years. Adherence to both study agents averaged 65% at 5 years. In September, 2008 the independent data and safety monitoring committee met and reviewed data for interim analysis. They recommended study discontinuation as there was no evidence of benefit from either study agent and no possibility of a benefit to the planned degree with additional follow-up. The 5-year incidence of prostate cancer in the 4 groups was; placebo 4.43%, selenium 4.56%, vitamin E 4.93%, and both agents 4.56%. There was a concern over the statistically non-significant increase in prostate cancer in the vitamin E alone group and a non-significant increase in diabetes mellitus associated with selenium. The study agents had no significant effects on the overall incidence of cardiovascular events.

Earlier reports:

Dietary Supplement Selenium May Play a Role in the Prevention of Prostate Cancer

Clinical trials have shown that selenium supplementation could reduce the risk of prostate cancer by approximately 50 percent. Yan Dong, assistant professor in the Department of Structural and Cellular Biology at Tulane University School of Medicine, is working to identify the mechanisms by which selenium might act to protect against prostate cancer. She found that selenium could dampen the signaling intensity of androgen, which plays a critical role in promoting the development of prostate cancer. The data her team collects will lay the groundwork for using selenium in combination with an anti-androgen as a new modality for the prevention and/or treatment of prostate cancer.

Selenium To Prevent Prostate Cancer? More Answers Needed

A mineral diet supplement that lowers the risk of prostate cancer by 50 percent?

While there’s no definitive proof, scientists are intrigued about the connection between prostate cancer risk and selenium, according to the December issue of Mayo Clinic Health Letter.

Selenium is a trace mineral that’s essential to good health. While it’s not an antioxidant, selenium is an element in the synthesis of proteins to make antioxidant enzymes. It is found in foods including nuts, meats, fish, poultry, eggs, dairy and whole grains. Typically, diet alone provides more than the Recommended Dietary Allowance of 55 micrograms (mcg).

Interest in the selenium and prostate cancer connection spiked in 1996 because of a surprise finding in a skin cancer study. Male participants took 200 mcg of selenium every day. Compared to men taking the placebo, the men taking selenium were found to have 63 percent fewer cases of prostate cancer. Two years later, the rates of prostate cancer remained 49 percent lower than the control group.

Though interesting, the results aren’t conclusive and don’t address possible risks from selenium supplements. A small study published this year indicated that taking 200 mcg of selenium daily may increase the risk of diabetes by 50 percent.

Selenium not helpful

Selenium supplementation, for example in mineral tablets, might not be that beneficial for the majority of people according to researchers writing in the open access journal Genome Biology. Although this trace element is essential in the diet of humans, it seems that we have lost some of the need for selenium, which occurs in proteins and is transported in blood plasma, when our evolutionary ancestors left the oceans and evolved into mammals.

The research team including Alexey Lobanov and Vadim Gladyshev of the University of Nebraska-Lincoln and Dolph Hatfield of the National Institutes of Health conducted the genetic analysis. “Several trace elements are essential micronutrients for humans and animals but why some organisms use certain ones to a greater extent than others is not understood” comments Gladyshev. “We’ve found that the evolutionary change from fish to mammals was accompanied by a reduced use of proteins containing selenium.”

Selenium-containing proteins evolved in prehistoric times. Several human disorders have been associated with a deficiency in the trace element, among them are Keshan disease, a heart disorder affecting primarily children in certain provinces of China where the soil is deficient in selenium, and Myxedermatous Endemic Cretinism, a rare form of mongolism attributed to deficiencies in selenium and iodine found in certain areas of Africa. Selenium supplementation was thought to be necessary to prevent these and other diseases even in the areas with adequate selenium supply.

The evolved reduced reliance on selenium invites questions regarding the widely accepted use of supplements incorporating this trace element to maximize amounts of proteins that rely on it. Supplements are taken without knowing which groups of the population can benefit.

Interestingly, only 20% of lower organisms use selenium-based proteins, and, for example, fungi and vascular plants do not. Some insects have also lost the need for selenium during the course of evolution. Aquatic environments seem to favor an increased reliance on selenium because of environmental factors. Selenoprotein-rich Sea urchins, for instance, feed on algae, which themselves contain a lot of selenium.

Gladyshev concludes: “The evolved reduced utilization of selenium-containing proteins in mammals raises important questions in human and animal nutrition. Selenoprotein expression is regulated such that people don’t need to rely so heavily on dietary selenium which is often present in excess amounts in the diet. Individuals should consider their age, sex and medical needs before taking such supplements on a regular basis.”

Selenium may prevent high risk-bladder cancer

A study published in the December issue of Cancer Prevention Research, a journal of the American Association for Cancer Research, suggests that selenium, a trace mineral found in grains, nuts and meats, may aid in the prevention of high-risk bladder cancer.

Researchers from Dartmouth Medical School compared selenium levels in 767 individuals newly diagnosed with bladder cancer to the levels of 1,108 individuals from the general population. Findings showed an inverse association between selenium and bladder cancer among women, some smokers and those with p53 positive bladder cancer.

In the entire study population, there was no inverse association between selenium and bladder cancer, but women (34 percent), moderate smokers (39 percent) and those with p53 positive cancer (43 percent) had significant reductions in bladder cancer with higher rates of selenium.

"There are different pathways by which bladder cancer evolves and it is thought that one of the major pathways involves alterations in the p53 gene," said corresponding author Margaret Karagas, Ph.D., professor of community and family medicine of the Norris Cotton Cancer Center at Dartmouth. "Bladder cancers stemming from these alternations are associated with more advanced disease."

While other studies have shown a similar association between selenium and bladder cancer among women, this study is one of the first to show an association between selenium and p53 positive bladder cancer.

"Ultimately, if it is true that selenium can prevent a certain subset of individuals, like women, from developing bladder cancer, or prevent certain types of tumors, such as those evolving through the p53 pathway, from developing, it gives us clues about how the tumors could be prevented in the future and potentially lead to chemopreventive efforts," Karagas said.

Karagas hopes to replicate these findings on a larger scale in order to examine the connection between selenium and bladder cancer in women and those with p53 tumors, as well as with patient prognosis.

No comments: