Our bodies cannot make selenium for us

Daily selenium intakes?  We need to get this essential trace element – selenium — in our diets and in our supplements because our bodies cannot make it for us. The work of Dr. Gerhard N. Schrauzer, Dr. Raymond J. Shamberger, and Dr. Douglas V. Frost has shown that there is an inverse relationship between our selenium status and the risk of cancer mortality.  Animal studies show an inverse correlation between selenium status and incidence of cancer.  Observational studies show lower risk of various types of cancer with higher selenium status.

Intervention studies of selenium supplementation and cancer
Clinical studies in China
Large interventional studies in China, a region of the world with selenium-poor soils and foodstuffs, have shown that selenium supplements protect against hepatitis B virus and primary liver cancer [Yu] and that supplementation with a combination of selenium and other antioxidants reduces cancer incidence and mortality in a region characterized by high cancer mortality rates [Blot].

The Nutritional Prevention of Cancer (NPC) trial
The work of Dr. Larry Clark (Nutritional Prevention of Cancer trial) and his fellow researchers has shown that long-term daily supplementation with 200 micrograms of an organic high-selenium yeast preparation resulted in significant reductions in prostate, colorectal, and lung cancer as well as in total cancer [Clark].

The Selenium and Vitamin E Cancer Prevention Trial (SELECT) trial
Instead of attempting to replicate the NPC trial by using the same organic high-selenium yeast preparation, the SELECT trial researchers used an entirely different selenium preparation, a synthetic selenomethionine preparation, and they added a vitamin E preparation to the treatment. Supplementation with the new preparation failed to produce the same health benefits as the NPC trial preparation had, and the SELECT study was halted early.

The problem in the SELECT study seems to have been caused by the formulation and the study design and not by the selenium per se (I want to include more discussion of selenomethionine and other selenium species in future articles on this website).

The Bonelli selenium and recurrent adenomas trial
The long-term Bonelli study showed that supplementation for five years with the following nutritional supplements significantly reduced the number of patients having a recurrence of an adenoma in the large colon:

• 200 micrograms of selenium
• 30 milligrams of zinc
• 2 milligrams of vitamin A
• 180 milligrams of vitamin C
• 30 milligrams of vitamin E

The protective effect of the supplements, provided by Pharma Nord (Denmark), persisted well past the initial five-year supplementation period.

Note: I want to write in more detail about the NPC trial, the SELECT trial, and the Bonelli trial in future articles on this website.

Intervention study of selenium and Coenzyme Q10 and heart disease
For four years, Professor Urban Alehagen and researchers at Linköping University in Sweden gave healthy elderly citizens aged 70 – 88 years a daily combination of 200 micrograms of selenium and 200 milligrams of Coenzyme Q10 or matching placebos.  The study participants who received the active treatment of selenium and Coenzyme Q10 showed significantly reduced risk of cardiovascular mortality both at the initial check-up at 5.2 years (on average) and again at further follow-up at 10 years after the initiation of the treatment [Alehagen].

Antioxidant properties of selenium-dependent enzymes
One plausible explanation of the protective effect of selenium and Coenzyme Q10 supplementation against cancer and against heart disease is based on the important antioxidant properties of the two substances. Selenium is an essential component of the antioxidant glutathione peroxidase enzymes and other selenium-dependent antioxidant enzymes that serve to minimize the damage caused by such harmful free radicals as the hydrogen peroxides and organic peroxides to proteins and DNA in the cells.

The biochemistry of selenium
The biochemistry of selenium is complicated with respect to daily selenium intakes and selenium status.  For example, in the NPC trial, 200 micrograms of selenium daily showed significant health benefits; supplementation with 400 micrograms of selenium, however, did not [Reid]. Clearly, the form and the dosage of the selenium supplement are important.

Different formulations and dosages of selenium
Different forms of selenium supplements seem to have different effects with respect to the uptake and storage of selenium. Consequently, it is difficult to specify exact formulations and exact dosages that will achieve and maintain desired blood selenium concentrations [Thomson].

Different dietary factors affecting selenium uptake
Individuals vary in their biochemistry.  Diets vary in their chemistry.  Various characteristics of healthy people and patients affect the absorption and retention of selenium.  For example, there seems to be considerable difference in the way that smokers and non-smokers process dietary and supplemental selenium. Some diets may contain more (or fewer) vitamins and minerals that are helpful to or antagonistic to selenium. Some diets may contain other substances that affect the absorption and activity of selenium in the body, e.g. heavy metals such as mercury.

Low selenium status and cancer risk
An important question has long been: does cancer cause low selenium status, or does low selenium status contribute to the development of cancer?

Willett and colleagues designed a study to minimize the possibility that it is the cancer that causes the low selenium status.  They then found that the patients in the lowest quintile of blood selenium concentration have a risk of death from cancer twice as high as the patients in the highest quintile of blood selenium concentration.  Low selenium status is a contributing cause to the developing of cancer.

Necessary and sufficient blood selenium concentrations
At this point (2016), our knowledge base does not give precise information about the necessary blood selenium concentrations to achieve the following outcomes:

• optimal glutathione peroxidase activity
• optimal selenoprotein P activity
• optimal immune function
• optimal protection against the development of cancer and heart disease

Bio-markers of adequate selenium status
Selenium researchers are still investigating which bio-markers are the most suitable markers of adequate selenium status.  Toenail selenium concentration and hair concentrations have been suggested as better long-term markers than plasma selenium concentrations.  Plasma glutathione peroxidase and platelet glutathione peroxidase concentrations have been studied. More recently, a consensus has begun to develop around the suitability of selenoprotein P (SEPP) concentrations as a suitable marker of selenium status.

In a future article, I will want to present the findings of the Hurst randomized controlled study in the United Kingdom.  Hurst et al attempted to establish optimal selenium status and to relate optimal selenium status to optimal selenium intakes, a difficult task.

Why is optimal selenium status essential?
The biological functions of selenium come primarily from its incorporation into the amino acid selenocysteine, which is itself an important component of 25 different selenoproteins. Among these selenoproteins, the following biological functions deserve our attention:

• the glutathione peroxidases are important antioxidant enzymes
• the thioredoxin reductases regulate cell growth and regenerate other antioxidants, notably Coenzyme Q10
• the iodothyronine deiodinases regulate thyroid gland function
• the selenoprotein P is the most abundant selenoprotein in plasma and acts as an antioxidant in addition to performing other important biological functions

Randomized controlled studies have shown that selenium supplementation is associated with protective effects against the development of cancer and heart disease.

Sources

Alehagen, U., Aaseth, J., & Johansson, P. (2015). Reduced Cardiovascular Mortality 10 Years after Supplementation with Selenium and Coenzyme Q10 for Four Years: Follow-Up Results of a Prospective Randomized Double-Blind Placebo-Controlled Trial in Elderly Citizens. Plos One, 10(12), e0141641.

Blot, W.J., Li, J.Y., Taylor, P.R., Guo, W., Dawsey, S., Wang, G.Q., Yang, C.S., Zheng, S.F., Gail, M., Li, G.Y. (1993).  Nutrition intervention trials in Linxian, China: supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population. J Natl Cancer Inst, 85(18):1483-92.

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 LC, Combs GF, Jr., Turnbull BW, et al. 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. 1996;276(24):1957-1963.

Hurst, R., Armah, C.N., Dainty J.R., Hart, D.J., Teucher, B., Goldson, A.J., Broadley, M.R., Motley, A.K., Fairweather-Tait, S.J.  (2010).  Establishing optimal selenium status: results of a randomized, double-blind, placebo-controlled trial. Am J Clin Nutr, 91(4):923-31.

Reid ME, Duffield-Lillico AJ, Slate E, et al. The nutritional prevention of cancer: 400 μg per day selenium treatment. Nutr Cancer. 2008;60(2):155-163.

Thomson, C.D. (2004). Assessment of requirements for selenium and adequacy of selenium status: a review. Eur J Clin Nutr 58, 391-402.

Willett, W.C., Polk, B.F., & Morris,J.S. (1983). Prediagnostic serum selenium and risk of cancer. Lancet, ii: 130-4.

Yu SY, Zhu YJ, Li WG. Protective role of selenium against hepatitis B virus and primary liver cancer in Qidong. Biol Trace Elem Res. 1997;56(1):117-124.