Authors of a recent meta-analysis of 69 studies of selenium exposure and cancer risk have concluded that high selenium exposure can reduce cancer risk, especially high selenium exposure that is reflected in high plasma or serum selenium status and/or in high toenail concentrations [Cai 2016]. Admittedly, higher selenium intakes (as compared to lower selenium intakes) can affect different forms of cancer differently. We still need more research to sort out which forms and dosages of dietary and supplemental selenium are most effective at reducing cancer risk. In this article, I want to summarize the findings of Dr. Xianlei Cai and colleagues.
What is a meta-analysis of selenium exposure and cancer risk?
A meta-analysis is a research method of combining the data from several selected research studies to reach conclusions that have greater statistical power. In the present case, Cai et al selected 69 studies that met their inclusion criteria. Each one of the 69 selected studies had the following characteristics:
- was a randomized controlled trial or a cohort study or a case-control study
- considered selenium as a baseline exposure and cancer risk as an outcome
- was published in English between 1980 and 2014
- contained the necessary data for the meta-analysis
The 69 studies contained the data from 364,742 study participants with 26,138 cancer events. This was some serious number-crunching. For all of the results that follow, the researchers first checked to make sure that such variables as exposure mode, geographic region, and study design were not influencing the results independently. They also checked for a gender difference in the effect of selenium exposure and found no significant effect of gender.
What were the results of the meta-analysis?
All cancer risk.
The researchers concluded that high selenium exposure has a protective effect against cancer. That is to say, the study participants in the higher category of selenium exposure had significantly less risk of cancer than did study participants in the lower category of selenium exposure [Cai 2016].
Hurst et al, in a 2010 study that aimed at establishing optimal plasma selenium status, indicate that low plasma selenium status is generally thought to be plasma selenium concentrations below 100 nanograms per milliliter (also expressed as 100 micrograms per liter). Hurst et al suggest that a minimum plasma selenium status of 110 – 118 nanograms per milliliter is necessary for optimal expression of the selenoprotein P [Hurst 2010].
Breast cancer risk.
The researchers found that high selenium exposure decreased the risk of breast cancer.
Lung cancer risk.
The researchers found that high selenium exposure presented a protective effect on lung cancer.
Prostate cancer risk.
The researchers found that high selenium exposure decreased the risk of prostate cancer.
Note: In a separate article, I want to summarize the results of a 2012 meta-analysis focusing on selenium exposure and risk of prostate cancer. It was a meta-analysis that included 12 studies with a total of 13,254 participants and 5007 cases of prostate cancer [Hurst 2012]. That meta-analysis showed that the risk of prostate cancer decreased with increasing plasma/serum selenium up to 170 nanograms per milliliter.
What did the researchers conclude about selenium and cancer risk?
Dr. Cai and the team of researchers summarized the results of their meta-analysis as follows:
- an inverse relationship exists between selenium exposure and total cancer risk
- a downward trend exists between serum/plasma selenium status and cancer risk
- a downward trend exists between toenail selenium concentrations and cancer risk
- selenium exposure has different effects on specific types of cancer
- different forms of selenium supplements may present different effects on human health
- selenium intakes may need to be high enough to permit the full expression of selenoprotein P to optimize cancer-preventive effects
What are the mechanisms by which selenium exposure decreases cancer risk?
The exact nature of the positive effect of selenium intakes on the prevention of cancer is not known with certainty. There are various hypotheses to explain the positive effect:
- the antioxidant effect of the selenoproteins, the glutathione peroxidases and the selenoprotein P in particular
- selenium’s effect on the apoptosis of malignant cells
- selenium’s effect on DNA stability
A final note about selenium and cancer studies
Cai et al concentrated on studies of selenium exposure and cancer risk. Consequently, their meta-analysis did not include studies that involved testing the effect on cancer risk of a selenium supplement in combination with other antioxidants. Some important randomized controlled trials were thus not included in the Cai meta-analysis:
- The Linxian Nutritional Intervention study [Blot 1993]
- The Su.Vi.Max study [Hercberg 2010]
- The Antioxidant Supplement study [Bonelli 2013]
I will want to write more about the results of these randomized controlled trials of selenium and other antioxidants in forthcoming articles on this website. And, of course, I will be writing more about the big randomized controlled selenium trials:
- The Nutritional Prevention of Cancer Trial [Clark 1996]
- The Selenium and Vitamin E Cancer Prevention Trial (SELECT) [Lippman 2009]
- The PREvention of Cancer by Intervention with Selenium (PRECISE) [Larsen 2004]
Blot, W. J., Li, J. Y., Taylor, P. R., Guo, W., Dawsey, S., & Wang, G. Q. (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.
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.
Hercberg, S., Kesse-Guyot, E., Druesne-Pecollo, N., Touvier, M., Favier, A., Latino-Martel, P., & Galan, P. (2010). Incidence of cancers, ischemic cardiovascular diseases and mortality during 5-year follow-up after stopping antioxidant vitamins and minerals supplements: a postintervention follow-up in the SU.VI.MAX Study. International Journal of Cancer, 127(8), 1875-1881.
Hurst, R., Hooper, L., Norat, T., Lau, R., Aune, D., Greenwood, D. C., & Fairweather-Tait, S. J. (2012). Selenium and prostate cancer: systematic review and meta-analysis. The American Journal of Clinical Nutrition, 96(1), 111-122.
Hurst, R., Armah, C. N., Dainty, J. R., Hart, D. J., Teucher, B., Goldson, A. J., & Fairweather-Tait, S. J. (2010). Establishing optimal selenium status: results of a randomized, double-blind, placebo-controlled trial. The American Journal of Clinical Nutrition, 91(4), 923-931.
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.
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.