Brain cells are especially vulnerable to oxidative stress, which could be a factor in the pathology of neurodegenerative disorders. The danger of oxidative damage caused by free radicals (oxygen reactive species) is great because 1) the neurons use large quantities of oxygen, 2) the brain has high iron content, 3) neuronal mitochondria produce large quantities of hydrogen peroxide, and 4) neuronal membranes are full of polyunsaturated fatty acids, which are susceptible to oxidative stress [Shichiri, 2014]. Adequate supply of selenium and synthesis of antioxidant selenoproteins are necessary to counteract the harmful effects of oxidative stress.A review of the research literature on selenium and selenoprotein function in brain disorders reveals that selenium deficiency is associated with impaired cognitive function and impaired motor function [Pillai].
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?read more
Professor Urban Alehagen, Linköping University, Sweden, was one of the key researchers on the Q-Symbio clinical trial and has been the lead researcher on the KiSel-10 clinical trial. He has shown that joint selenium and Coenzyme Q10 supplementation of senior citizens with low selenium status reduces the risk of cardiovascular mortality and improves heart function.
The Swedish KiSel-10 Study provides randomized controlled trial evidence that a daily combination of an organic high-selenium yeast supplement and a pharmaceutical-grade Coenzyme Q10 supplement can reduce cardiovascular mortality, improve heart function, and increase health-related quality of life in senior citizens [Alehagen 2013].
Low blood selenium concentrations and higher risk of heart disease
Professor Urban Alehagen and a team of researchers from Linköping University investigated the blood selenium levels in 688 Swedish senior citizens. The mean blood selenium level was 67.1 micrograms per liter, which is quite low but not surprising, given that Sweden is a country with selenium-low soil and selenium-poor foodstuffs [Alehagen 2016].
When the researchers adjusted for gender, smoking, coronary artery disease, diabetes, chronic obstructive pulmonary disease, and impaired heart function, they found that the quartile of senior citizens with the lowest level of blood selenium had a 43% higher risk of all-cause mortality and a 56% higher risk of cardiovascular mortality[Alehagen 2016].read more
A 2012 meta-analysis and systematic review has shown an inverse association between plasma/serum selenium levels and prostate cancer advanced prostate cancer in particular. Denmark is in a low-selenium region of the world, and the Danish population as a whole has low selenium intakes and sub-optimal blood selenium levels. Danish researchers have, accordingly, investigated the association between pre-diagnostic selenium levels and the risk of total, advanced, and high-grade prostate cancer. Pictured here: the Dannebrog, Denmark’s national flag.
Higher blood selenium concentrations and higher blood selenoprotein P concentrations are significantly associated with reduced risk of high-grade prostate cancer [Outzen].
The researchers defined “advanced” prostate cancer as ≥T3 or with a Gleason-score ≥7. They defined “high-grade prostate cancer” as cancers having a Gleason score equal to or greater than 8.
Furthermore, in survival analyses, a higher pre-diagnostic level of plasma selenium is significantly associated with a lower risk of all-cause mortality in prostate cancer patients [Outzen].
Selenium and prostate cancer in the “Diet, Cancer, and Health” cohort
These are the conclusions from an analysis of the data from the Danish “Diet, Cancer, and Health” cohort. The cohort consists of 27,179 menliving in the greater metropolitan areas of Copenhagen and Aarhus who were recruited into the study. They were aged 50 – 64 years and had no previous record of cancer at the time of recruitment [Outzen].read more
Meta-analyses have shown an inverse association between plasma/serum selenium concentrations and the risk of prostate cancer. The same inverse association has also been seen in three high-quality studies of toenail selenium concentrations and the risk of prostate cancer. The data from the Netherlands Cohort Study clearly show that higher toenail selenium is associated with significantly reduced risk of prostate cancer.
Analysis of data from the Netherlands Cohort Study shows that higher toenail selenium concentrations are associated with a substantial reduction in the risk of advanced prostate cancer. Men in the highest quintile of toenail selenium had a statistically significant (p=0.001) 63% reduced risk of advanced (stage III-IV) prostate cancer compared to men in the lowest quintile of toenail selenium [Geybels].
Men in the highest quintile of toenail selenium concentrations had a toenail selenium level higher than 0.617 micrograms of selenium per gram of toenail. Men in the lowest quintile of toenail selenium concentrations has a toenail selenium level lower than 0.469 micrograms of selenium per gram of toenail [Geybels].read more
The latest clinical evidence shows that selenium supplementation of older adults with 200 micrograms of a high-selenium yeast preparation for up to three years does not adversely affect pancreatic beta-cell function or insulin sensitivity.
Results from a clinical trial comparing 200 micrograms of selenium supplementation with placebo supplementation show no effect of the selenium supplementation on measures of insulin secretion and insulin action [Jacobs].
These results can be regarded as important evidence that selenium supplementation for up to three years in older individuals has no diabetes causing effects in humans [Jacobs].
The researchers who conducted the selenium and insulin resistance study concluded that the results of the study do not show a causal role for selenium in the development of insulin resistance or in the development of type-2 diabetes [Jacobs].
Research design of the selenium and insulin resistance study
Background: In 2016, researchers at the Arizona Cancer Center in Tucson reported on the results of the Selenium Trial [Thompson].read more
There are many risk factors associated with the development of prostate cancer: age, family history, geographic region, insulin growth factor, nationality, and race. One risk factor that merits investigation is the relationship between blood selenium concentrations and prostate cancer risk.
Quote: “Selenium most probably has a protective role against the development of prostate cancer and its progression to advanced stages. Therefore, selenium supplementation can be proposed for prevention of prostate cancer.”
These words are taken from the conclusion of a 2018 systematic review and meta-analysis of studies of the association between selenium and prostate cancer [Sayehmiri].
The meta-analysis is based on the data from 38 journal medical articles that included 36,419 prostate cancer cases and 105,293 healthy controls. There were 22 case-control studies, 6 cohort studies, and 10 randomized controlled trials included in the meta-analysis [Sayehmiri].
Selenium levels associated with risk of prostate cancer
The pooled relative risk from the 38 studies of the association of selenium concentration and prostate cancer risk showed a statistically significant 14% risk reduction with higher levels of blood selenium or toe nail selenium.read more
Brain tissue produces many free radicals (reactive oxygen species). The oxidative stress caused by an imbalance between potentially harmful free radicals and antioxidants to neutralize them is associated with ageing and with the onset of Alzheimer’s disease. Reduced levels of the selenium-dependent antioxidant enzyme glutathione peroxidase correlate strongly with cognitive decline and the risk of Alzheimer’s disease.
Blood selenium concentrations are significantly lower in patients with Alzheimer’s disease compared to healthy controls. This reduction in selenium concentration is directly associated with the observed reduced levels of the important antioxidant selenoprotein, glutathione peroxidase, in Alzheimer’s disease patients.
These are the conclusions of the authors of a 2017 meta-analysis of 12 case-control studies of selenium concentrations in Alzheimer’s disease patients and healthy controls. The 12 case-control studies comprised 594 Alzheimer’s disease patients and 472 healthy controls [Reddy].
Significantly decreased selenium levels were seen in the blood circulation of Alzheimer’s disease patients as compared to healthy controls.
Decreased selenium levels were also seen in the red blood cells and cerebrospinal fluid of Alzheimer’s patients as compared to healthy controls. However, the difference in selenium concentrations did not reach the level of statistical significance.
Age matching between the Alzheimer’s disease patients and healthy controls showed decreased selenium levels regardless of the age of the patients. This is interesting because advanced age is considered a risk factor for Alzheimer’s disease.
Controlling for socio-economic, geographical, and environmental differences also showed the decreased selenium levels in Alzheimer’s disease patients compared to the healthy controls.
A direct association was seen between decreased selenium levels and glutathione peroxidase levels in Alzheimer’s disease patients.
What is glutathione peroxidase, and why is it important?
The glutathione peroxidases (abbreviated GPx) are a family of antioxidant enzymes (selenoproteins) that reduce and thus neutralize potentially harmful radicals like hydrogen peroxide and lipid hydroperoxides. In so doing, the GPx enzymes lessen the extent of oxidative stress damage.read more
A recent study has found a relatively high mortality risk in elderly Swedish subjects with low selenium status. Supplementation with a high-selenium yeast supplement and a Coenzyme Q10 supplement for four years resulted in significantly reduced risk of death from heart disease, better maintained heart function, and better quality of life for senior citizens. The beneficial effect of the supplementation has persisted through the 12th year of follow-up.
Low plasma/serum selenium concentrations are associated with increased risk of death from heart disease and increased risk of death from all causes. Professor Urban Alehagen and a team of researchers at Linköping University in Sweden have investigated the relationship between low selenium levels and the risk of heart disease.
Selenium supplements suggested for adults with very low Se levels
The Swedish study shows that adults with a serum selenium concentration below 57 micrograms per liter are at significantly higher risk of death from all causes (43% increased risk) and death from heart disease (56% increased risk) [Alehagen 2016]. 57 micrograms of selenium per liter of serum. Wow! That’s low.
These significant associations remained solid even after the researchers had adjusted for the effects of possibly modifying factors:read more
The KiSel-10 study was done in Sweden, which is known to have selenium-poor soil and selenium-low foodstuffs. Consequently, daily supplementation with 200 micrograms of a high-selenium yeast preparations was appropriate. In geographical regions with higher levels of selenium in the soil and in the food, lesser selenium dosages may be needed. Selenium is an essential micro-nutrient, it has known antioxidant functions in the body, and it is associated with good thyroid health and good immune system defense.
Combining high-selenium yeast and Coenzyme Q10 supplements gives elderly people in low selenium regions good protection against heart disease. That seems to be the take-home lesson from a 12-year follow-up analysis of the Swedish KiSel-10 study [Alehagen 2018].
Protective effects of selenium and CoQ10 persist 12 years
Originally, Professor Urban Alehagen and researchers at the University in Linköping enrolled 443 elderly Swedish citizens who were living in a community in which selenium intakes in the food were known to be low. They randomly assigned the study participants to take a combination of 200 micrograms of selenium in a high-selenium yeast tablet and 200 milligrams of Coenzyme Q10 daily or to take matching placebos. The supplementation study lasted for four years [Alehagen 2013].read more
Selenocysteine is the 21st amino acid. The trace element selenium plays its important biological roles in the body as a component of selenocysteine. Selenocysteine is found in at least 25 selenoproteins including selenoprotein P and the various glutathione peroxidases, thioredoxin reductases, and iodothyronine deiodinases.
The results of clinical studies give us an estimate of what an individual’s optimal serum or plasma selenium status is.
Plasma selenium status below 100 micrograms per liter – also expressed as 100 nanograms per milliliter – is generally regarded as sub-optimal plasma selenium status [Hurst 2010].
Plasma selenium status of at least 110 – 118 micrograms per liter is considered necessary for the optimal expression of selenoprotein P [Hurst 2010].
Letsiou et al [2014] set the lower limit for optimal selenoprotein P activity at 120 micrograms per liter or higher.
Plasma selenium status of 120 up to 170 micrograms per liter is considered necessary for reducing the risk of prostate cancer [Hurst 2012].
Studies show that there are sex and age differences in the absorption and distribution of selenium taken in from the diet and from supplements [Letsiou 2014; Galan 2005].
Note: The Mayo Medical Laboratories report serum concentrations of 70 to 150 micrograms per liter as the adult reference range for residents of the United States. The mean population serum concentration is 98 micrograms per liter [Mayo], but, remember, depending on the range and standard deviation of the data, the mean can be very little useful. The important thing about the United States is that there is regional variation in selenium intakes and status. See below.
Selenium intake and selenium status
The primary sources of selenium are the diet and supplements. The human body does not synthesize selenium. It is difficult to calculate accurately how much selenium an individual gets from food. It can also be difficult to know precisely how much selenium an individual absorbs from a supplement because of the variation in the form and formulation of the selenium supplements on the market.read more
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