It is interesting to note that selenium concentrations are preferentially maintained in the brain even when the selenium concentrations in the blood circulation, in the liver, and in the skeletal tissues are depleted [Pillai].
Selenium supplementation may help to reduce the progression of the pathology of neurodegenerative diseases: Alzheimer’s, Huntington’s, and Parkinson’s [Pillai].
Selenium and Selenoproteins
What do we know about the trace element selenium and its incorporation into selenoproteins?
- Selenium content in food varies considerably from region to region. Selenium content in food depends upon regional soil selenium content [Pillai].
- Selenium intakes from food tend to be much lower in Europe and the Middle East than in much of the United States [Stoffaneller & Morse]
- Selenium intakes in the US tend to vary according to the selenium content of the soil.
- Abnormally low levels of selenium in the body can lead to neurological problems, cardiovascular problems, cancer, and reduced immune system function [Pillai].
- Dietary intake of selenium is converted to selenocysteine, the 21st amino acid [Pillai].
- Selenocysteine is an essential component of some 25 known selenoproteins. There are three well-studied sub-families of selenoproteins: the glutathione peroxidases, the thioredoxin reductases, and the iodothyronine deiodinases [Pillai].
In North America, the following regions are characterized by low-selenium soils and thus low selenium content in plant and animal foodstuffs [National Research Council]:
- the Pacific Northwest region of the USA
- the South Atlantic seaboard region of the USA
- the northeastern United States
- Arizona and New Mexico
- the Atlantic provinces of Canada
- the interior of British Columbia
- west-central Alberta
- northern Ontario
- the eastern townships and lower St. Lawrence regions of Quebec
Selenoproteins and Brain Function
The Glutathione Peroxidases (abbreviated GPx)
GPx1 and GPx4 are the most common forms of glutathione peroxidase in the brain. GPx1 acts an antioxidant scavenger of harmful free radicals in both neurons and astrocytes. GPx4 functions as an antioxidant protector in the cytosol, the mitochondria, and the nucleus of neurons [Pillai].
Studies show that the GPx selenoproteins have potential roles in the prevention and/or treatment of Alzheimer’s, Huntington’s, and Parkinson’s diseases as well as in cases of epilepsy.
The Thioredoxin Reductases (abbreviated TrxR)
It is the TrxR1 and TrxR2 selenoproteins that are most involved in brain function. These selenoproteins act as antioxidants and reduce the extent of oxidative stress in the brain. They are thought to have a protective role in Alzheimer’s disease and in epilepsy [Pillai].
The Iodothyronine Deiodinases (abbreviated DIO)
The role of the selenoprotein sub-family called the iodothyronine deiodinases in neurodegenerative diseases is not yet clearly understood. What is known is that DIOs are important to the activation and deactivation of the thyroid hormones [Pillai].
The Selenoprotein P (abbreviated Sepp1 or SelP)
Sepp1 is the selenoprotein that contains the most selenium in the blood plasma. When selenium levels fall, the levels of Sepp1 fall correspondingly. Consequently, Sepp1 is often used as a marker for the level of selenium in the body.
Sepp1 acts as a transporter of selenium in the body. It transports selenium from the liver to the brain and to other tissues. As such, it is important for the distribution and homeostasis of selenium [Pillai].
Remember: even in times of selenium deficiency, selenium is maintained preferentially in the brain [Pillai].
The Selenoprotein W (abbreviated SelW)
Animal studies have shown that SelW protects the glial cells (the non-neuronal cells in the central nervous system) against oxidative stress caused by heavy metals [Pillai].
Selenium and Selenoproteins and Neurodegenerative Diseases
Alzheimer’s Disease
Studies have shown decreased levels of selenium in patients with Alzheimer’s disease. Studies have indicated that adequate levels of selenium may prevent or reduce the pathology of Alzheimer’s disease [Pillai].
Huntington’s Disease
Studies have shown that an increase in oxidative stress is countered by an increase in GPx activity in the brain in Huntington’s disease. An animal study shows that selenium supplementation reduces oxidative stress and lipid peroxidation in the brain [Pillai].
Parkinson’s Disease
Plasma selenium levels decrease in patients with Parkinson’s disease. This decrease may be caused by greater selenium utilization for the production of selenoproteins in the brain for the purpose of preventing further oxidative damage [Pillai].
Selenium-Enriched Yeast Formulation Best
Animal studies of the effect of different selenium compounds such as synthetic L-selenomethionine, inorganic sodium selenite, and organic high-selenium yeast (also called selenium-enriched yeast) on the development of metastatic brain lesions have shown that the selenium-enriched yeast formulation resulted in a higher survival rate and in decreased tumor growth as compared to controls [Wrobel].
A study of the comparative effects of two forms of selenium supplement – selenomethionine supplements and high-selenium yeast supplements – has shown reductions in biomarkers of oxidative stress following supplementation with the organic high-selenium yeast but not with the selenomethionine supplementation in healthy men. The study findings suggest that selenium species other than selenomethionine in the high-selenium yeast account for the decrease in oxidative stress [Richie].
Conclusion: Selenium and Selenoproteins Can Reduce the Progression of Neurodegenerative Diseases
Selenium and selenoproteins may reduce the progression of the pathology of some neurodegenerative diseases: Alzheimer’s, Huntington’s, and Parkinson’s. One mechanism of action is the selenoproteins’ antioxidant protection against oxidative stress in the brain. Other possible mechanisms of action need further investigation [Pillai].
In addition, more research into the effect of specific species of selenium and into the effect of specific dosages is needed. For example, the selenium species selenomethylselenocysteine that is found in high-selenium yeast formulations may be especially suitable for the promotion of selenoprotein synthesis [Pillai].
Sources
National Research Council. (1983). Selenium in Nutrition. Revised Edition. Washington, DC: The National Academies Press.
Pillai, R., Uyehara-Lock, J. H. Bellinger, F. P. (2014). Selenium and selenoprotein function in brain disorders. International Union of Biochemistry and Molecular Biology. 66(4): 229-239.
Richie, J. P., Arun, D., Calcagnotto, A. M., Sinha, R., Neidig, W. & El-Bayoumy, K. (2014). Comparative effects of two different forms of selenium on oxidative stress biomarkers in healthy men: a randomized clinical trial. Cancer Prev Res (Phila), 7(8): 796–804.
Shichiri, M. (2014). The role of lipid peroxidation in neurological disorders. J Clin Biochem Nutr, 54(3): 151–160.
Stoffaneller, R., & Morse, N. L. (2015). A review of dietary selenium intake and selenium status in Europe and the Middle East. Nutrients, 7(3), 1494–1537.
Wrobel, J.K., Seelbach, M.J., Chen, L., Power, R.F. & Toborek, M. (2013). Supplementation with selenium-enriched yeast attenuates brain metastatic growth. Nutr Cancer. 65(4):563–570.
The information contained in this review article is not intended as medical advice and should not be construed as such.