On the topic of cancer and selenium as a cancer chemo-preventive agent, we know some basic facts from published research:
- selenium prevents or delays tumor development in animals [Schrauzer]
- regions with low selenium intakes are regions with higher incidence of cancer [Schrauzer]
- greater exposure to selenium is associated with lower incidence of cancer [Cai]
- single interventions with high-selenium yeast preparations reduce the incidence of cancer [Clark; Yu; Li]
What do randomized controlled studies reveal about the efficacy of selenium and antioxidant combinations against the development of cancerous tumors, I wondered.
The first studies to come to mind were the Linxian Nutritional Intervention Studies, which are probably just as important in the history of selenium and cancer research as Professor Larry Clark’s Nutritional Prevention of Cancer study is.
Professor Blot’s Linxian Nutrition Intervention Studies in China
The Linxian studies were a very big research undertaking. The researchers enrolled 29,584 study participants aged 40 to 69 years from four Linxian County municipalities. The study participants lived in a region of China characterized by constantly low intakes of selenium and by high cancer mortality rates.
The researchers randomly placed the study participants into one of four research groups:
- Group A: the zinc and retinol (Vitamin A) group
- Group B: the riboflavin and niacin (B vitamins) group
- Group C: the Vitamin C and molybdenum group
- Group D: the high-selenium yeast, Vitamin E, and beta-carotene group
The study data showed that there were no interesting outcomes of the first three supplementation regimens. However, the data from Group D, the group taking a high-selenium yeast supplement daily, did show exciting results.
- 9% reduction in deaths from all causes
- 13% reduction in deaths from all forms of cancer
- 21% reduction in deaths from gastric cancer
- 20% reduction in deaths from various other cancers
The results from the Linxian Nutrition Intervention Studies confirmed what researchers had seen in animal studies: selenium prevented or delayed the development of cancer tumors [Blot].
Professor Hercberg’s Su.Vi.Max. Study in France
Next came reports from the big French study – the Supplémentation en Vitamines et Minéraux Antioxydants (Su.Vi.Max.) study – also a randomized, double-blind, placebo-controlled study. The Su.Vi.Max. study enrolled 13,017 adults aged 35 – 60 years of whom roughly 60% were women [Hercberg].
The treatment regimen consisted of the following micronutrients:
- 100 micrograms high-selenium yeast
- 6 milligrams beta-carotene
- 120 milligrams Vitamin C
- 30 milligrams Vitamin E
- 20 milligrams zinc
Study participants assigned to the control group took matching placebos daily.
The researchers followed the study participants were for a median period of 7.5 years. The study data revealed a surprising finding. The supplementation with micronutrients headed by 100 micrograms of high-selenium yeast produced significant health benefits in the French men but not in the French women:
- lower total cancer incidence
- lower all-cause mortality
- healthier aging [Assman 2015]
How to explain these unexpected sex differences in the effects of the Su.Vi.Max. study? The researchers suggested various hypotheses:
- The women in the study had higher baseline vitamin C and beta-carotene status than the men did — this could have made a difference.
- Hormonal differences could have resulted in a difference.
- There were differences in baseline antioxidant status between the men and the women. These baseline antioxidant status differences were associated with differences in cancer risk in men but not in women [Galan 2005].
Dr. Prasad’s Oral Cancer Study in India
Researchers in Hyderabad, India, reported the results of a smaller cancer chemoprevention study using high-selenium yeast in combination with antioxidants [Prasad]. The researchers enrolled 298 patients diagnosed with precancerous lesions in their mouths in either an active treatment group or a placebo group.
The patients in the active treatment group took the following selenium and antioxidant combination for a year:
- High-selenium yeast
- Vitamin A
The selenium and antioxidants combination supplement reduced the incidence of micronuclei and DNA adducts significantly. The placebo did not produce a reduction.
Note: The extent of micronucleated cells and carcinogen DNA adducts is an indicator of the extent of DNA damage. Reduction in the frequency of micronuclei and DNA adducts is an indication of reduced risk of cancer [Prasad].
Dr. Bonelli’s Recurrent Adenomas Study in Italy
Italian researchers tested the effects of selenium and antioxidant supplementation vis-à-vis the rate of the recurrence of adenomas in the large bowel.
The researchers enrolled 411 patients who had had polyps removed from their colons. Patients in the active treatment group took the following antioxidants in combination with 200 micrograms of selenium daily:
- 2 milligrams Vitamin A
- 4.4 milligrams of Vitamin B6
- 180 milligrams Vitamin C
- 30 milligrams Vitamin E
- 30 milligrams zinc gluconate
Patients assigned to the control group took matching placebos daily.
The researchers did colonoscopies on these patients at the 1-year, 3-year, and 5-year points of the study.
They found that the selenium and antioxidant treatment gave a 39% reduction in adenoma recurrence, both in the case of small tubular adenomas and of advanced adenomas. This is an exciting result because adenoma recurrence foretells increased risk of colorectal cancer [Bonelli 2013].
Selenium in combination with antioxidants and cancer prevention
Blot and Linxian, Hercberg and Su.Vi.Max., Prasad and micronuclei and DNA adducts, Bonelli and recurrent adenomas – all good solid research results confirming the role of selenium and antioxidants in the prevention of cancer.
There remains to be described the 800-pound gorilla in the room: The Selenium and Vitamin E Cancer Prevention Trial (the SELECT study) in the United States.
The SELECT study of selenium and vitamin E and prostate cancer
The basic premise of the SELECT study – enrolling 35,533 men at hundreds of medical treatment sites in the U.S., Canada, and Puerto Rico – was that there was good reason to think that supplementation with selenium and vitamin E could prevent the development of prostate cancer [Lippman].
The SELECT study was stopped ahead of schedule because none of the supplementation regimens was showing the anticipated benefits [Klein].
Numerous selenium researchers have raised questions about the formulation of the selenium supplement (a synthetic l-selenomethionine supplement instead of a high-selenium yeast supplement) and about the high baseline selenium status of the study participants.
Why, given the good results of Professor Clark’s Nutritional Prevention of Cancer study, Professor Blot’s Linxian Nutrition Intervention study, Dr. Yu’s Qidong Selenium Treatment study, and Dr. Prasad’s Nutrition Intervention study, all with high-selenium yeast preparations, did the SELECT researchers choose to use a synthetic l-selenomethionine preparation?
I will want to address the issues raised by the misconceived SELECT study in a future article on this Web-site.
Selenium supplementation, alone and in combination with other antioxidants, has shown significant results in terms of the reduction of cancer incidence and cancer mortality. The exact mechanisms of selenium’s chemoprevention of cancer are not yet known.
Possible explanations for the efficacy of selenium in the prevention of cancer include but are not limited to the following effects of selenium:
- on the process of apoptosis
- on the activity of the selenium-dependent selenoenzymes
- on the functioning of the immune system
- on the metabolism of carcinogens
- on tumor cell growth [Lü 2016]
High-selenium yeast supplements are the most effective selenium supplements.
Assmann, K. E., Andreeva, V. A., Jeandel, C., Hercberg, S., Galan, P., & Kesse-Guyot, E. (2015). Healthy Aging 5 Years After a Period of Daily Supplementation With Antioxidant Nutrients: A Post Hoc Analysis of the French Randomized Trial SU.VI.MAX. American Journal of Epidemiology, 182(8), 694-704.
Blot, W. J., Li, J. Y., Taylor, P. R., Guo, W., Dawsey, S., Wang, G. Q., & Li, B. (1993). Nutrition intervention trials in Linxian, China: supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population. Journal of The National Cancer Institute, 85(18), 1483- 1492.
Bonelli, L., Puntoni, M., Gatteschi, B., Massa, P., Missale, G., Munizzi, F., & Bruzzi, P. (2013). Antioxidant supplement and long-term reduction of recurrent adenomas of the large bowel. A double-blind randomized trial. Journal of Gastroenterology, 48(6), 698-705.
Cai, X., Wang, C., Yu, W., Fan, W., Wang, S., Shen, N., & Wang, F. (2016). Selenium Exposure and Cancer Risk: an Updated Meta-analysis and Meta-regression. Scientific Reports, 619213.
Galan, P., Briançon, S., Favier, A., Bertrais, S., Preziosi, P., Faure, H., & Hercberg, S. (2005). Antioxidant status and risk of cancer in the SU.VI.MAX study: is the effect of supplementation dependent on baseline levels? The British Journal of Nutrition, 94(1), 125-132.
Hercberg, S., Galan, P., Preziosi, P., Bertrais, S., Mennen, L., Malvy, D., & Briançon, S. (2004). The SU.VI.MAX Study: a randomized, placebo-controlled trial of the health effects of antioxidant vitamins and minerals. Archives of Internal Medicine, 164(21), 2335-2342.
Klein, E. A., Thompson, I. J., Tangen, C. M., Crowley, J. J., Lucia, M. S., Goodman, P. J., & Baker, L. H. (2011). Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA, 306(14), 1549-1556.
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.
Lippman, S. M., Klein, E. A., Goodman, P. J., Lucia, M. S., Thompson, I. M., Ford, L. G., & … Coltman, C. J. (2009). Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). Jama, 301(1), 39-51.
Prasad, M. P., Mukundan, M. A., & Krishnaswamy, K. (1995). Micronuclei and carcinogen DNA adducts as intermediate end points in nutrient intervention trial of precancerous lesions in the oral cavity. European Journal of Cancer. Part B, Oral Oncology, 31B(3), 155159.
Schrauzer, G.N., White, D.A., & Schneider, C.J. (1977). Cancer mortality correlation studies–III: statistical associations with dietary selenium intakes. Bioinorganic Chemistry, 7(1):23-31.
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 contained in this review article is not intended as medical advice and should not be construed as such.