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Does the Source of Selenium Matter in Cancer Prevention?

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What if some of the largest clinical studies assessing the benefits (or risks) of selenium supplementation in cancer prevention have used the wrong form? That looks to be the case as a new study from the University of Miami sheds light on the different effects of selenium-rich yeast versus another popular form, selenomethionine. What the researchers have discovered is that there are proteins produced when making selenium-rich yeast that have anti-cancer properties beyond simply providing a source of selenium.

The Role and Importance of Selenium

The trace mineral selenium functions primarily as a component of the antioxidant enzyme glutathione peroxidase. This valuable enzyme works with vitamin E and plays a pivotal role in preventing free radical damage to cell membranes. Not surprisingly, low levels of selenium in the body have been linked to a higher risk for cancer, cardiovascular disease, inflammatory diseases, and other conditions associated with increased free radical damage including premature aging and cataract formation. Low selenium levels are also associated with low immune function. Even in people with normal blood selenium levels selenium supplementation (200 mcg/day) boosts immune function. In one double-blind study it resulted in a 118 percent increase in the ability of white blood cells to kill tumor cells and 82.3 percent increase in the activity of a type of white blood cell known as a “natural killer cell.” These white blood cells are given this name because of their powerful ability to kill cancer cells and microorganisms.1

The Health Benefits of High Selenium Yeast Go Beyond the Mineral

Maintaining proper selenium levels appear to be important in protecting against many health conditions, but some of the studies show some advantages to selenium-rich yeast that indicate there may be other compounds responsible for the observed effects in addition to selenium. For example, in one double-blind, placebo-controlled trial, 69 healthy men were given selenium from a selenium-rich yeast known as SelenoExcell (200 or 285 μg/day) or selenomethionine (200 μg/day) for nine months. While blood selenium levels increased by 93 percent, 54 percent, and 86 percent in the selenomethionine and low- and high-dose SelenoExcell groups, respectively, only the men receiving the SelenoExcell demonstrated a decrease in oxidative stress. Levels of standard markers of oxidative damage, 8-OHdG and 8-iso-PGF2α, were decreased 34 percent and 28 percent, respectively, versus no change in the selenomethionine group.2 These results indicate there are additional factors in the high-selenium yeast contributing to the antioxidant effects. These additional factors could explain the difference in the results seen in prostate cancer prevention.

A Closer Look at Selenium and Prostate Cancer

The results from studies looking at selenium in prostate cancer prevention have brought conflicting results. These may be related to the form of selenium being used and the ability of selenium to be incorporated into prostate cells. In the Nutritional Prevention of Cancer (NPC) study, supplementation with SelenoExcell, a selenium-enriched yeast, was associated with a 52 percent decrease in prostate cancer incidence.3 In contrast, in the SELECT study, selenomethionine failed to show any protective effects alone or when combined with synthetic vitamin E.4 The difference in results may be entirely related to the form of selenium being used (see above in regards to antioxidant activity).

One factor used to explain differing results is the effect of selenium supplementation on the concentration of selenium within prostate tissue. Selenomethionine has been shown to have only a modest effect in increasing prostate tissue selenium levels.5 In contrast, results from a double-blind study in men with prostate cancer show high-selenium yeast is significantly more effective in increasing selenium levels in prostate tissue.6 In the study, 53 men were randomized to receive placebo, 200 mcg of SelenoExcell, or 400 mcg of SelenoExcell for four to six weeks prior to surgery to remove their prostate gland. Results showed a clear dose effect in increasing the selenium content in prostatic tissue and provided a greater degree of selenium incorporation in prostate tissue compared to published results with selenomethionine. Specifically, while selenomethionine (200 mcg per day) was shown to increase the prostate selenium levels by 22 percent, SelenoExcell produced a 34 percent increase at the 200 mcg/day dosage and a 92 percent increase at the 400 mcg per day dosage. It is thought that increased selenium uptake in the prostate after supplementation with SelenoExcell as compared to selenomethionine may a key factor in the different results seen in the NPC and SELECT studies, but there are other considerations as well.

In addition to acting as an antioxidant, selenium-rich yeast may also offer protection against cancer by immune system effects, detoxification of antagonistic metals, inactivation of nuclear transcription factors that stimulate cancer growth, and a host of effects on DNA and cellular replication. Recently, researchers at the University of Miami evaluated the effects of a group selenium-containing compounds from selenium-rich yeast known as selenoglycoproteins (SGPs).7 The SGPs were evaluated for their impact on the interactions of lung and breast tumor cells with cells that line blood vessels (endothelial cells). Currently there are no therapies aimed at preventing the spread of cancer by specifically targeting the adhesion and migration of tumor cells into other areas of the body. Results from the detailed study showed that SGPs extracted from Selenium-enriched yeast possess the ability to reduce the adhesion of tumor cells to endothelial cells. In addition, the researchers also showed that SGPs also blocked the migration of tumor cells into underlying tissue. Furthermore, SGPs were shown to block the tumor promoting effects of nuclear factor kappa-B (NF-κB). This action has profound effects as NF-κB is a master regulator of pro-inflammatory reactions and gene expression. NF-κB activation is a key factor in cancer cell growth and metastasis. By blocking NF-κB, the SGPs have an effect far beyond the action of simply providing a form of selenium.

Comments

If the science above is confusing, let me try to restate what it is telling us. Basically, it has long been assumed that selenium-rich yeast was beneficial because it provided a superior form of selenium. Once absorbed the selenium would be utilized as a valuable antioxidant as part of an antioxidant enzyme known as glutathione peroxidase. What the emerging science indicates is that the selenium-containing proteins that are produced in the process of making high-selenium yeast may turn out to be more important than the selenium itself. In other words, these proteins may be the real protective factor. VR

References:

1 Kiremidjian-Schumacher L, Roy M, Wishe HI, et al. Supplementation with selenium and human immune cell functions. II. Effect on cytotoxic lymphocytes and natural killer cells. Biol Trace Elem Res 1994;41:115-127.

2 Richie JP Jr, Das A, Calcagnotto AM, et al. Comparative effects of two different forms of selenium on oxidative stress biomarkers in healthy men: a randomized clinical trial. Cancer Prev Res (Phila). 2014 Aug;7(8):796-804.

3 Duffield-Lillico AJ, Dalkin BL, Reid ME, et al. Selenium supplementation, baseline plasma selenium status and incidence of prostate cancer: an analysis of the complete treatment period of the Nutritional Prevention of Cancer Trial. BJU Int. 2003 May;91(7):608-12.

4 Lippman SM, Klein EA, Goodman PJ, et al. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA. 2009 Jan 7;301(1):39-51.

5 Sabichi AL, Lee JJ, Taylor RJ, et al. Selenium accumulation in prostate tissue during a randomized, controlled short-term trial of l-selenomethionine: a Southwest Oncology Group Study. Clin Cancer Res. 2006 Apr 1;12(7 Pt 1):2178-84.

6 Algotar AM, Stratton MS, Xu MJ, et al. Dose-dependent effects of selenized yeast on total selenium levels in prostatic tissue of men with prostate cancer. Nutr Cancer. 2011;63(1):1-5.

7 Wrobel JK, Choi JJ, Xiao R, et al. Selenoglycoproteins attenuate adhesion of tumor cells to the brain microvascular endothelium via a process involving NF-κB activation. J Nutr Biochem. 2015 Feb;26(2):120-9.

Michael T. Murray, ND, is widely regarded as one of the world’s leading authorities on natural medicine. He is a graduate, former faculty member and serves on the Board of Regents of Bastyr University in Seattle, WA. The author of more than 30 books on health nutrition, Murray is also director of product development and education for Natural Factors Nutritional Products. For more information, visit www.doctormurray.com.