Selenium and cancer prevention: The Linxian Study

The Nutrition Intervention Trials conducted in the Linxian province in China yielded some of the first promising results linking selenium supplementation to the reduction of cancer incidence and mortality.  The Linxian province at the time was characterized by a selenium-poor diet.

The treatment group that received selenium supplements was the group that showed significant health benefits of the supplementation:

• Significantly lower total mortality
• Significantly lower cancer mortality
• Significantly lower stomach cancer mortality

The reduced mortality rates began to become apparent already after 1 – 2 years of supplementation.  The patterns for reductions in cancer incidence generally approximated the patterns for cancer mortality [Blot].

The Linxian study results were exciting because they were published in the Journal of the National Cancer Institute and because they appeared before the results of the Nutritional Prevention of Cancer study in the United States [Clark].

The Linxian study of selenium and cancer
How was the study designed?  The researchers recruited 29,584 adults aged 40-69 from four Linxian communities.  They randomly assigned the study participants to one of four treatment groups:

• Group A: retinol and zinc supplementation
• Group B: riboflavin and niacin supplementation
• Group C: vitamin C and molybdenum supplementation
• Group D: selenium, beta carotene, and vitamin E supplementation

The dosages used were approximately one to two times greater than the U.S. Recommended Daily Allowances.

Data linking selenium to reduced risk of cancer
Then, the researchers followed the incoming data for mortality and cancer incidence from 1986 to 1991.  Analysis of the data from the five-year period of supplementation showed that only the treatment group receiving daily dosages of selenium, beta-carotene, and vitamin E had significantly less cancer incidence and mortality [Blot].

Additional health benefits of selenium supplementation
Of the four treatment groups in the Linxian Nutrition Intervention Trials, treatment group D – the selenium, beta-carotene, and vitamin E group – also had the greatest reduction in stroke mortality.  Somewhat surprisingly, the reduction in death from stroke was not accompanied by a prevalent end-of-trial reduction in high blood pressure rates, as might have been expected [Mark 1998].

Researchers conducted a parallel clinical study in Linxian province in which 3318 men and women were randomly assigned to receive daily supplements consisting of 26 vitamins and minerals, including selenium, in doses that were typically double or triple the United States Recommended Daily Allowances, or placebos, for 6 years.  The outcome of that parallel study showed an association between the active supplementation and reductions in cerebrovascular disease and in blood pressure levels [Mark 1996].

The really big selenium and cancer studies
The results of the Linxian study were encouraging for selenium scientists and researchers.  Since Linxian, there have been other big selenium supplementation and cancer risk studies that have yielded promising.

In future articles, I will want to delve into the design and results of these studies:

The Selenium and Oral Cancer Study, 1995 [Prasad]
Supplementation for one year with a high-selenium yeast preparation in combination with vitamin A, riboflavin, and zinc significantly reduced the frequency of micronuclei and DNA adducts as compared to a placebo treatment.  The formation of micronuclei and DNA adducts are usually signs of DNA damage and the beginning of cancerous activity.

The Nutritional Prevention of Cancer Study, 1996 [Clark]
Supplementation for 4.5 years with a high-selenium yeast preparation was associated with significant reductions in total cancer mortality, total cancer incidence, and lung, colorectal, and prostate cancer incidence.

The Qidong (China) Primary Liver Cancer Study, 1997 [Yu]
Supplementation for two years with a high-selenium yeast preparation significantly reduced the risk of primary liver cancer.

The Qidong (China) Primary Liver Cancer Study, 2000 [Li]
Supplementation for three years with a high-selenium yeast preparation significantly reduced the risk of primary liver cancer.

The Su.Vi.Max Study, 2004 [Hercberg]
Supplementation for 7.5 years with selenium and zinc and antioxidant vitamins reduced total cancer incidence and all-cause mortality in men but not in women.

The Prevention of Cancer by Intervention by Selenium (PRECISE) Study, 2004 [Larsen]
Supplementation with equal dosages (300 micrograms daily) of the SelenoPrecise® high-selenium yeast preparation and a synthetic l-selenomethionine preparation showed significantly higher whole blood selenium concentrations in the high-selenium yeast treatment group.

The SELECT Study, 2009 [Lippman]
Supplementation for five years with selenium alone or in combination with Vitamin E did not significantly reduce the incidence of prostate cancer.  Two possible explanations for the lack of a significant result have been proposed:

• the form of the selenium supplement used in the study (it was a synthetic l-selenomethionine supplement that lacked the species diversity of high-selenium yeast preparations.)
• the unusually high baseline plasma selenium concentrations of the study participants

The Recurrent Adenomas Study, 2013 [Bonelli]
Supplementation for four years with selenium, zinc, and antioxidant vitamins significantly reduced the recurrence of adenomas in the large intestine.

The all-important formulation of the selenium supplement
There are two things especially interesting about the design of these selenium and cancer studies:

• The differences in the use of selenium as a stand-alone supplement or in combination with other micronutrients
• The difference in the formulation of the selenium supplement itself

High-selenium yeast preparations best
At present, the available studies show that the high-selenium yeast preparation containing organic selenomethionine, Se-methylselenocysteine, and small amounts of as many as 30 other selenium species gives the best intake, bio-availability, and cancer protection.

Sources

Blot, W. J., Li, J. Y., Taylor, P. R., Guo, W., Dawsey, S., Wang, G. Q., et al.  (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.

Clark, L. C., Combs, G. F., Turnbull, B. W., Slate, E., & Alberts, D.  (1996).  The nutritional prevention of cancer with selenium 1983-1993; a randomized clinical trial. JAMA, 276: 1957-1963.

Clark, L. C., Dalkin, B., Krongrad, A., Combs, G. F., & Turnbull, B. W.  (1998). Decreased incidence of prostate cancer with selenium supplementation: results of a double-blind cancer prevention trial. Brit. J. Urol, 81: 730-734.

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.

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.

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.

Mark, S. D., Wang, W., Fraumeni, J. J., Li, J. Y., Taylor, P. R., Wang, G. Q., & Blot, W. J. (1998). Do nutritional supplements lower the risk of stroke or hypertension? Epidemiology (Cambridge, Mass.), 9(1), 9-15.

Mark, S. D., Wang, W., Fraumeni, J. J., Li, J. Y., Taylor, P. R., Wang, G. Q., & Blot, W. J. (1996). Lowered risks of hypertension and cerebrovascular disease after vitamin/mineral supplementation: the Linxian Nutrition Intervention Trial. American Journal of Epidemiology, 143(7), 658-664.

Prasad, M. P., Mukunda, 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. Eur. J. Cancer B Oral Oncol, 31B: 155-159.

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 used as such.