On this blog site, seleniumfacts.com, we focus on the health and nutritional benefits of selenium supplementation. We look at the following types of studies:
- human studies more so than lab studies or animal studies
- intervention studies more so than observational studies
- randomized controlled studies whenever possible
Cancer and Selenium as a single intervention agent
The best studies of selenium as a single intervention to prevent or treat cancer show significant results in regions with low selenium intakes and/or high cancer risk.
Professor Clark’s NPC study
The big breakthrough came when Professor Larry Clark published the results of the Nutritional Prevention of Cancer (NPC) study in the prestigious journal JAMA: The Journal of the American Medical Association.
The NPC study was a multi-center randomized, double-blind, placebo-controlled study carried out in a selenium-poor region of the southeastern United States. The study participants who took 200 micrograms of a high selenium yeast preparation over an average 4.5-year period showed significant health benefits (as compared to placebo):
- 50% lower cancer mortality
- 37% lower total cancer incidence
- 46% lower lung cancer incidence
- 58% lower colorectal cancer incidence
- 63% lower prostate cancer incidence [Clark]
The study participants were 75% American men; consequently, there were no meaningful data with respect to breast cancer.
In 2006, Dr. Reid and colleagues reported the results of a secondary analysis of the NPC data regarding selenium supplementation and the risk of colorectal cancers. The analysis revealed a significant reduction of risk in two sub-sets of study participants:
- Study participants whose baseline selenium status was in the lowest tertile of the group
- Study participants known to be current smokers [Reid 2006]
Dr. Yu’s primary liver cancer studies
In Qidong County, a selenium-poor region in China, Dr. Yu and colleagues studied the efficacy of selenium supplements against hepatitis B virus and primary liver cancer.
- Selenized table salt as the selenium intervention agent produced a 35% reduction in primary liver cancer as compared to the effect of non-selenized table salt.
- Daily high-selenium yeast tablets as the selenium intervention agent resulted in zero development of primary liver cancer in hepatitis B patients over a four-year period. In the same period, six percent of the hepatitis B study participants taking the placebo preparation developed primary liver cancer [Yu].
Especially interesting: in both Yu studies, the rate of primary liver cancer started rising when the study participants stopped taking the selenized selenium supplements. Continuous intervention with selenium had a cancer chemo-preventive effect [Yu].
Professor Li’s primary liver cancer study
In a later and bigger study in Qidong County, a region with a known high risk for liver cancer, Dr. Li and colleagues tested 2,065 study participants for three years. They randomly assigned the study participants to a treatment group taking a selenium supplement or to a placebo group.
In the selenium treatment group, the level of micronucleus cells in lymphocytes was significantly lower than in the placebo group.
Note: A test for micronucleus cells is a reliable test for compounds that are carcinogens that cause cancer by doing damage to genes.
Furthermore, in the selenium treatment group, the occurrence of new cases of liver cancer was significantly lower than in the control group.
Dr. Karamali’s study of selenium and women with cervical intraepithelial neoplasia
Dr. Karamali and colleagues reported long-term beneficial effects of adjunct selenium treatment of women with grade 1 cervical intraepithelial neoplasia grade 1 (CIN1).
Note: Cervical intraepithelial neoplasia is the medical term for the precancerous abnormal growth of epithelial cells on the surface of the cervix.
The women in Dr. Karamali’s study were randomly assigned to a treatment group receiving 200 micrograms per day of a high-selenium yeast preparation or to a placebo group.
- Supplementation with selenium led to the regression of cervical intraepithelial neoplasia.
- Supplementation with selenium had beneficial effects on the women’s metabolic profiles, e.g. decreased fasting glucose levels and increased insulin sensitivity.
- Supplementation with selenium was associated with decreased oxidative stress [Karamali].
PRECISE pilot studies with high-selenium yeast preparations
The PRECISE study was designed as a high-power study of the effect of high-selenium yeast supplements on 32,000 cancer patients in the United States, the United Kingdom, Denmark, and Sweden. The full-blown PRECISE study did not get off the ground because of a lack of funding.
Instead, the necessary funding went to the Selenium and Vitamin E Cancer Prevention Trial conducted by the Southwest Oncology Group in the United States. The PRECISE researchers did, however, conduct pilot studies in Denmark and the United Kingdom.
The study participants in the two PRECISE pilot study samples received high-selenium yeast preparations, SelenoPrecise® supplements, variously at rates of 100, 200, or 300 micrograms per day. Six months of supplementation with each dosage increased the study participants’ plasma and whole blood levels significantly.
In the UK PRECISE pilot study, 200 micrograms of SelenoPrecise® high-selenium yeast supplements per day resulted in significantly higher plasma selenium levels and higher increases from baseline selenium status than had been the case for Professor Clark’s NPC study participants [Larsen].
Regrettably, we did not get to find out whether a large randomized controlled trial with 200 micrograms of SelenoPrecise® high-selenium yeast supplements per day would have replicated the significant results in the NPC study and the Qidong studies.
SELECT study: The Selenium and Vitamin E Cancer Prevention Trial
It remains for me to report on the SELECT study.
The SELECT study was halted before its scheduled completion date because preliminary data showed that neither selenium nor vitamin E reduced the risk of prostate cancer in the period 2001 – 2004. I will want to write extensively about the SELECT study in a future article.
For now, suffice it to say that the SELECT study was the wrong study. The SELECT study was conducted:
- in the wrong group of study participants (high baseline selenium status)
- with the wrong selenium preparation (a synthetic l-selenomethionine preparation instead of an organic high-selenium yeast preparation)
With hindsight, we can regret that the SELECT study funding (reportedly $114 million) did not go to the PRECISE study instead.
What have we learned from the cancer and selenium studies?
Dr. Lee and colleagues did a meta-analysis of randomized controlled trials of the effects of selenium supplements on cancer prevention.
They concluded: Single interventions with selenium supplements are effective at reducing the risk of cancer in low baseline serum selenium level populations and in populations with high risk for cancer.
Conclusion: randomized controlled studies of selenium and cancer
Randomized controlled studies are expensive to set up and run. It is difficult for researchers to get funding for big expensive studies of selenium because selenium is an element.
Even so, there have been noteworthy studies done on the efficacy of selenium supplementation to prevent and/or treat various forms of cancer. In a future article, I will present the cancer chemopreventive evidence from studies of selenium supplementation in combination with other antioxidants.
The following studies of selenium plus other antioxidants in the prevention of cancer are important:
- Professor Blot’s Linxian study
- Professor Hercberg’s Su.Vi.Max. study
- Dr. Bonelli’s Recurrent Adenomas study
- Dr. Prasad’s Micronuclei and DNA Adducts study
- The Southwest Oncology Group’s SELECT study
Clark, L. C., Combs, G. J., Turnbull, B. W., Slate, E. H., Chalker, D. K., Chow, J., & Taylor, J. R. (1996). 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, 276(24), 1957-1963.
Karamali, M., Nourgostar, S., Zamani, A., Vahedpoor, Z., & Asemi, Z. (2015). The favourable effects of long-term selenium supplementation on regression of cervical tissues and metabolic profiles of patients with cervical intraepithelial neoplasia: a randomised, double-blind, placebo-controlled trial. The British Journal of Nutrition, 114(12), 2039-2045.
Larsen, E. H., Hansen, M., Paulin, H., Moesgaard, S., Reid, M., & Rayman, M. (2004). Speciation and bioavailability of selenium in yeast-based intervention agents used in cancer chemoprevention studies. Journal of AOAC International, 87(1), 225-232.
Lee, E.H., Myung, S.K., Jeon, Y.J., Kim, Y., Chang, Y.J., Ju, W., Seo, H.G., & Huh B.Y. (2011). Effects of selenium supplements on cancer prevention: meta-analysis of randomized controlled trials. Nutr Cancer, 63(8):1185-95.
Li, W., Zhu, Y., Yan, X., Zhang, Q., Li, X., Ni, Z., & … Zhu, J. (2000). [The prevention of primary liver cancer by selenium in high risk populations]. Zhonghua Yu Fang Yi Xue Za Zhi [Chinese Journal of Preventive Medicine], 34(6), 336-338.
Reid, M. E., Duffield-Lillico, A. J., Sunga, A., Fakih, M., Alberts, D. S., & Marshall, J. R. (2006). Selenium supplementation and colorectal adenomas: an analysis of the nutritional prevention of cancer trial. International Journal of Cancer, 118(7), 1777-1781.
Yu, S. Y., Zhu, Y. J., & Li, W. G. (1997). Protective role of selenium against hepatitis B virus and primary liver cancer in Qidong. Biological Trace Element Research, 56(1), 117-124.
The information presented in this review article is not intended as medical advice and should not be construed as such.