What is Selenium and how does it act?
Selenium is a non-metallic element found is very small quantities in our body but it plays a fundamental role in balancing and maintaining our health by incorporating selenocysteine into selenium proteins.
What are Selenium Proteins?
These are the proteins responsible for the effects of Selenium.
The most important are:
Glutathione peroxidase (GPx1, GPx2, GPx3, GPx4) – Reduces oxidative stress and inflammation by getting rid of the peroxidase released in reactions that are toxic. For example, when the thyroid hormone is being formed, iodine is incorporated, and peroxidase is released. If there is no glutathione peroxidase, the peroxidase is not released and it will destroy the gland. This is why selenium is fundamental for thyroid health.
Glutathione peroxidase is also responsible for protecting the oxidative stress lipids triggered by free radicals, and which makes them “capable” of being deposited in arteries for example. They are only deposited if they are oxidized and if there is plaque.
Glutathione peroxidase also exists in the capsule and nucleus of sperm making it an essential component for both male and female fertility.
Iodothyronine deiodinases – Enzymes necessary for the formation of active thyroid hormones which need selenium.
Thioredoxin reductase – is the enzyme needed to regulate the intracellular oxidative state and to control cellular division. It protects proteins and DNA from damage caused by free radicals by suppressing oxidation.
Selenium Protein P – This is the protein that transports selenium and prevents the formation of Peroxynitrite (ONOO-).
Selenium Protein prostatic epithelia – Carries out a protective function similar to GPx in the thyroid’s secreting cells.
What are the Roles of Selenium?
. Anti-oxidant. Anti-inflammatory. Anti-thrombotic.
As we have already said, Glutathione peroxidase (GPx) removes peroxide thus decreasing the oxidized LDL on the arterial walls resulting in less inflammation, and reduced risk for thrombosis. Studies indicate a higher risk for cardiovascular disease in populations with selenium deficiencies.
There are also several studies, the largest of which is EURAMIC, which indicates an inverse relation between the quantity of selenium and the risk of a heart attack.
Epidemiological studies in fact never attributed great importance to the role of anti-oxidants in cardiovascular disease.
The EURAMIC study was carried out with the collaboration of 11 countries where they assessed the combined effects of selenium, vitamin E and beta carotene allied to the ingestion of fatty acids with acute myocardial infarction and breast cancer.
It protects against viral mutation although its deficiency is associated to more virulent and pathogenic strains.
There is for example Keshan Syndrome. This pathology is observed in China, in zones endemic with selenium deficiencies where infections with the Coxsackie virus are more common. Generally affected are children and women in childbearing years, who present a congested cardiomyopathy which leads to death. The seasonal and annual variation indicates that in addition to a deficiency in selenium, there may also be an infectious agent associated to the appearance of the disease. The Coxsackie virus has been isolated in patients carrying the Keshan disease, and studies on research animals with a deficiency of selenium show that Coxsackie virus causes myocarditis. The association to the virus leads researchers to believe in an important genetic mutation of viral RNA which changes from a non-virulent strain to a virulent strain because of the selenium deficiency.
Studies on animals show that the state of selenium is in fact important for maintaining the cell’s oxidative balance.
In research animals with selenium deficiencies, we can transform low-level virulent strains like the Flu virus (Influenza A, the Bangkok H3N2 strain) into virulent strains that cause disease. This is due to the production of inflammatory cytokines produced in the lungs of the animals with the deficiency, which is not observed in animals with adequate quantities of selenium. GPx is also proven to protect the organism from the mutations observed in the viral genome, which then becomes aggressive and virulent.
. Protects against cancer (prostate and breast)
We have known about the importance of selenium as a protector of cancer for some time now. Another day, we will talk about some studies that were badly conducted and consequently came to very different conclusions. But let’s focus on the basics: what type of selenium, and what dose. Not all selenium is identical and yes, the brand does matter.
For over 20 years, we have observed that zones, where the soil is deficient in selenium, have higher rates of cancer-related deaths.
Studies in animals indicate that supplementing with selenium lowers the incidence of tumors caused by chemicals, and in 2/3 of the animals with tumors caused by the virus.
Selenium’s anti-oxidizing effects protect the cell from oxidative damage, ultimately protecting the organism from cancer. There are innumerous publications that consider selenium as a chemical-preventing agent against tumors.
. Brain function
Brain function is highly dependent on selenium. In cases of deficiency, the brain is the organ which is most protected by the organism. We need to combat oxidative stress in neurotransmitters, and protect GPx in gray matter as the brain does not have sufficient catalase, or other important anti-oxidizing enzymes other than GPx and Superoxide dismutase.
Without selenium, dopamine decreases.
There is a greater decrease in cognitive function in elderly people with selenium deficiencies.
In people with Alzheimer’s disease, we have observed a 60% reduction in selenium levels in the “control” population.
Some studies reveal an increase in depression, anxiety, mental confusion and hostility in people with selenium deficiencies.
A dose of 100 ug is used in some protocols to reduce anxiety, fatigue and in some cases, depression because the dose will act directly on the thyroid.
In doses over 500 ug per day (400 ug doses of some types of selenium may be toxic) there occurs a chelation effect on exterior toxic agents (cadmium, lead and mercury).
During all the biochemical processes in our body, oxidizing substances are released. For example, during infection, inflammation and when the body is fighting against aggressive exterior agents like tabacco.
We have an interior anti-oxidizing system which is mostly composed of GPx, Superoxide dismutase and catalase. These are the three principle anti-oxidizing enzymes. If our defense system becomes overwhelming with work (as a result of poor diet and an unhealthy lifestyle or even some medication) this internal anti-oxidizing system may fail and we could develop tissue damage.
We also have non-enzyme anti-oxidizing systems which include Vitamin E, Vitamin C beta carotene, uric acid and taurine.
. Strengthening the immune system
The efficiency of our body’s immune system decreases with age. Older people have far more infections than younger of even middle-aged people.
Actually, as many studies indicate, infections in older people are one of the major causes of death.
A selenium deficiency is accompanied by reduced immune-competence. Supplementing with selenium has immune-stimulating effects.
Some studies indicate that the quantity of selenium varies inversely to NK cells.
.Plays a fundamental role in the thyroid function helping to convert the inactive T4 thyroid hormone into T3, the active hormone. Without the thyroid nothing in our body works properly. We have already looked at these mechanisms in post 1.
. Also fundamental, as we have already seen, for above all male fertility.
Without adequate doses of selenium, and in its adequate form, there can be no health.
It is very much a balancing act which depends highly on GPx, one of the most important protection enzymes that we have in the anti-oxidizing process.
Which are the best sources of selenium? How do you combat its deficiency?
. Cereals (oats), eggs, liver, meat and poultry (turkey), codfish, seafood, onions, garlic, canned tuna fish (although there is a danger of the can’s lining containing bisphenol A which is a carcinogen) and mushrooms.
Wheat flour used in bread contains varied (0,06 ug/gr – 0,646 ug/gr), but some quantities of selenium.
People who do not eat bread (because they are for example gluten intolerant) generally have lower levels of selenium.
Bread, however, brings other problems such as bromine, which competes with the iodine in the thyroid, and I personally am not an advocate of bread. Because of the gluten but not only. If you are about to say that we have been eating bread since the time of Christ and that now we are obsessed about gluten, I will answer that yes, true but the gluten used today has nothing to do with the gluten used at the time of Christ. Today’s gluten is genetically modified and has adverse actions upon our organism. Experiment by removing gluten from your diet for two months and watch what happens. Rarely does it NOT bring benefits, and many at that.
For those who find it impossible to stop eating bread, the differences between white and dark bread are greatly varied depending on the manufacturing processes and the types of flour used. Although I am unable to extrapolate that dark bread is in fact richer than white, it is consistently the case.
Garlic and onions contain sulphurised compunds that are capable of storing great quantities of selenium if they are grown in rich soil, which generally does not happen. (formation of selenium methionine/ selenium cysteine, selenium organic compounds, are the preferred as we will discuss another day).
The difference between foods varies considerably depending on the type of soil they are grown in. In the example of the garlic and onions it may vary between 0.002 and 0.01 ug/gr, even reaching 68 ug/gr in soils that are rich in selenium!
Thus, we cannot affirm that all garlic and onions are rich in selenium: it depends on the soil in which they are grown, which we have seen may vary immensely.
Curiously, most cattle breeders give the animals selenium supplements, therefore, meat is a source of selenium, as are eventually eggs, depending on the quality of selenium the chickens have been given.
Cattle breeders supplement with selenium because it contributes to the following characteristics:
– Improves the animal’s immune system (less mastitis of the udder)
– Improves the animal’s anti-oxidizing capabilities conferring better organoleptic properties (the taste is better)
– Improves the animal’s fertility
– Improves immunity transfer to the calves
– Better retained placenta, a problem the breeders are often faced with, and often leads to an increase in mortality (of the cows)
Our diet, in the majority of cases, is in fact deficient in selenium. Thus the importance of supplementing, and personally, it is one of the few supplements that I use at my clinic. A proper diet should be able to provide us with what we need but unfortunately, soils are not what they once were because they are worn out.
Improved energy and vitality are commonly and quickly reported by the conversion of the inactive thyroid hormone into an active hormone, which will in turn act upon the hormone receptor.
Which is the best “form” of Selenium?
Supplements may contain different forms of selenium: Selenomethionine, Selenite, and
Selenate. Some brands simply mix the yeast with the selenite or the selenate, according to the Linus Pauling Institute. If the brand you are taking contains selenium yeast and it is listed in the makeup, then this is the preferred form to take as we shall see ahead.
Selenium exists in two forms: organic (Selenomethionine and Selenocysteine) and inorganic (selenite and selenate).
Both forms are used in supplements.
The organic form is almost totally absorbed by the body (about 90%), while only about 50% of the inorganic form of selenite is absorbed. Selenate is better adsorbed than selenite, but a large quantity is excreted in the urine, thereby not used by the body.
The skeletal muscle is responsible for storing 28 to 46% of the selenium pool in our bodies.
All forms of selenium are converted into hydrogen selenide, selenium’s cellular form of storage, which are then “again” transformed into selenocysteine and incorporated into selenoproteins, responsible for carrying out the extremely important functions we discussed in part 1.The excess is methylated and eliminated through the urine and respiration. The excessive selenite may be oxidized resulting in the production of species that are reactive to oxygen (ROS) and produce toxic effects in our body. These selenoproteins are important because they protect our DNA, they are important for reproduction, for protecting us from infection, for the proper functioning of the thyroid, protection against cancer, cardiac disease and oxidative stress, amongst others.
The organic form
The organic form is formed by selenomethionine, selenocysteine, and selenium yeast.
Plants absorb inorganic selenium from the soil and “transform” it into an organic form and accumulate it. The majority, like selenomethionine, given that selenium substitutes sulphur during the synthesis of methionine amino-acids, is incorporated into proteins in place of methionine. This is the predominant form found in Brazil chestnuts, cereal, vegetables and fish.
These are the plants that transform inorganic selenium into organic.
Animals that feed off of these plants acquire the selenium that is stored in the plant. The majority is selenomethionine, which is stored in plants and animals in the greatest amount.
The other organic form, aside from selenomethionine, is selenocysteine, the form selenium must be in, in order to be considered part of the 25 selenoproteins extremely important to our health.
Selenium yeast is another organic form produced for enriching food and producing supplements, and it is the most recommended form of supplementation.
Selenium yeast remains stable in the presence of vitamin C and low toxicity, and it is natural and non-synthetic. Furthermore, it is well-absorbed and collected by the organism, affording great benefits to our health.
60 to 80% of selenium yeast is composed of selenomethionine, but many other species, with important biological functions not mentioned in the other forms of selenium, can be found in this formulation. Examples include Methylselenocysteine and its derivative gamma-glutamyl-selenium-methylselenocysteine, which are organic forms that can be found in onions, garlic, raw vegetables like cauliflower and broccoli. This is also the form more closely related to cancer prevention and it is better than the simple form of selenomethionine.
Obtained by growing Sacharomyces cerevisae (baker’s yeast) in an environment rich in inorganic selenium, generally known as selenite. Yeast is capable of incorporating selenium into its own protein ultimately becoming an integral part of this. Yeast is sterilized by heat and becomes “inactive”, meaning it does not comprise living matter, therefore there is no risk of infection.
There may be crossed reactions if there are allergies to Candida spp.
There are studies which show that ischemic cardiac disease and cardiac insufficiency may be the result of a deficient state of anti-oxidation in an individual. A decrease in mortality in older people supplemented with CoQ10 and selenium yeast was observed when compared to the placebo group.
Many compositions associate vitamin E, which strengthens selenium’s anti-oxidizing effect.
The ignorance form
Selenium selenite and selenate. Selenite and selenate, as we have seen, are less easily observed than their organic form.
Selenite cannot be taken with vitamin C, zinc, copper and other minerals or else it becomes inactive. It is the most used form in animal feed.
When excessive, it takes on pro-oxidizing properties which may cause toxic effects.
We can take advantage of this effect for the apoptosis measured by ROS in cancerous cells. These cells are more susceptible to oxidizing stress than normal cells.
Selenate does not react with minerals and it can be absorbed in the presence of vitamin C.
Selenite has the added problem that if in low doses it can be a protection against cancer, in high doses it works as a mutagen and may favor the development of tumors.
Selenate presents 1/10 of the mutagen power of selenium and is about 40% less toxic.
If the person is not prone to allergies, the best form of supplementation is selenium yeast.
What is the recommended dose of selenium? Can it be toxic? Risks of excess selenium?
All the selenium we ingest either comes from plants or water. Animals feed on plants and if we are not vegetarians, they are a good source of selenium, especially because cattle is supplemented in order to benefit breeders in regard to production.
So what doses should we take, and is it really necessary to supplement our diets?
In Portugal, most soils are very poor in selenium, according to studies carried out. All studies can be consulted online so I will not detail the data here.
In the meantime, and according to a European study (in which Portugal randomly contributed with only 27 individuals) the country actually showed the highest levels compared to other members. Could it be because of the population’s high consumption of liver? Seafood? Meat? Cereals? The truth however is that 27 individuals alone do not statistically represent a relevant sample size.
When the form of supplement is selenium yeast, if we take the maximum recommended dose of 200 ug per day, even patients who are not selenium deficient would not reach levels of toxicity. This is indicated by several studies so, it is yet another motive for this to be the preferred form.
The recommended dose for adults is 50 to 200 ug/day. Between diet and supplementation, we should not exceed 400 ug/day.
It is worth mentioning that each Brazil chestnut has an average of 55 ug of selenium in the form of selenomethionine, and if we eat more than 8 per day we could easily reach toxic levels. A maximum of 2-3 per day are recommended.
Signs of toxicity:
. Hair loss, garlic breath, stained nails and teeth
. Gastro-intestinal disturbances, nausea and vomitting
. Skin lesions, weakness and a decrease in cognitive function
Factors which affect toxicity:
. The chemical form (organic or inorganic which we discussed in part 4)
. The quantity ingested
. Susceptibility of the animal species
. Other nutrients. For example, the consumption of elevated levels of sulphur and protein can reduce the toxic effects of the excessive consumption of selenium due to the formation of Se sulphites which favor the excretion of selenium through bile.
The greater danger that no one talks about is the industrial exposure to toxins and pigments, electrical equipment, fungicides, glass factories or semi-conductors for example.
There are however populations that are selenium-deprived and where supplementation is fundamental:
– Immune deficiencies
– Chronic diseases
– Premature children (minimum doses of 15 ug/day)
– People with HIV or AIDS
– People who take statins
Taking a blood test does not validate our selenium reserves.
Determination in hair and nails furnishes information about chronic exposure, in other words, in the last 6 to 12 months before the evaluation is preferred.
Statins and Selenium
The controversy on whether to prescribe, or not, statins because they cause horrible problems does not make any sense. We have to consider the facts and not the opinions.
To me, as a medical clinical pathologist who has worked in hormonal modulation for over 10 years, what I am concerned with are the chemical reactions, and the chemical form in the genesis of pathology.
I never prescribe anything without knowing how and where it acts on the body to render the intended effect. In addition, due to my professional training as a medical clinical pathologist, I always think about how the body works chemically and may react to a determined substance I have prescribed.
If on the one hand, statins lower cholesterol levels and reduce the number of heart attacks, the fact is that more and more we are verifying an increase in congestive heart failure.
The “epidemic” increase of chronic heart failure is well-known. I will not discuss the direct relationship with statins, especially because even though all diseases are multi-factorial, there are studies that point in all the directions that are convenient to us.
I am only concerned with the patient’s well-being, which I am sure is the case with all doctors, but rationally speaking, without prejudice and static ideas, as if “change” is going to destroy my structure as a very careful and concerned doctor, who has always given her patients her best, now questions the following.
This conversation was only about discussing the difference between selenium and statins. We have already covered cholesterol and statins and we need to learn more about the “thyroid”, the hormone that all doctors should know how to “manipulate” given its impact on all our systems. See the following course at www.gemae.pt.
The fact is that without selenoproteins (there are 22,000 known proteins and only 25 selenoproteins that contain selenocysteine) all chemical mechanisms that protect from oxidation and inflammation in our bodies are in danger.
The fact is that statins inhibit a substance known as IPP (Isopentenyl pyrophosphate) which is necessary for synthesizing selenoproteins.
The selenium we ingest does not “roam about freely” in our body. It is incorporated into Selenomethionine or Selenocysteine. And Selenocysteine also does not exist “freely” in our cells. It is also incorporated into selenoproteins.
Selenoproteins are importante because they help with:
– Anti-oxidizing function
– Muscle cardiac function
– Musculoskeletal function
– Immune system
– Thyroid function
– Reproductive function
– Tumor prevention
How do statins act to lower cholesterol?
They lower the production of Mevalonic and mevalonate acid, which is needed to produce cholesterol. Thus, less mevalonate equals less cholesterol.
But mevalonato is also needed to synthesize IPP, and without IPP we will not be able to form Selenocysteine and consequently, selenoproteins (review part 1).
Without selenoproteins, everything we have discussed about the protection selenium offers will make no sense.
Amongst statin’s accessory effects we have myopathy and polyneuropathy.
Myopathy derived from a lack of selenium is very similar to myopathy as a consequence of using statins (which was long associated to the patient’s enzymatic congenital defects): muscular pain, especially after physical activity, weakness, sensitivity and fatigue. Microscopically, the pattern of microfibrils is identical in its disorganization and in the dysfunction of the mitochondria.
Today we know of another mechanism derived from the use of statins as the genesis of myopathies: the decrease in mevalonate and IPP, and also the decrease in selenoproteins and all its important actions on our organism.
My opinion in regard to taking statins has already been expressed by me here.
Less than 10% of patients need them as in the great majority of cases, correcting the thyroid function corrects our cholesterol levels, as well as innumerous other situations.
In addition, it is well-known that statins inhibit the formation of CoQ10, an important factor for producing tissual energy, and an anti-oxidant for important soluble lipids.
But if you take CoQ10 you eliminate the detrimental effects of statins, given selenium does not eliminate the inability to produce selenoproteins as this selenium cannot be “incorporated” into Selenocysteine since it inhibits the formation of IPP, an essential substance.
And without Selenocysteine, there are no selenoproteins.
Let’s not forget that heart failure has a death rate at five years of over 75%, which is superior to any death rate caused by tumors.
Also remember that heart failure is chemically characterized by:
Low production levels for ATP, an increase in mitochondrial dysfunction, an increase in oxidative stress and damage by free radicals, an increase in endothelium dysfunction and compromised metabolism of calcium.
Some studies show a decrease in death from cardiac disease, better cardiac function and a reduction in biomarkers for cardiac disease, in patients that take statins and are despite everything, supplemented with CoQ10 and selenium yeast.
Some studies consider selenium and anti-oxidants as “forbidden” to patients who take statins because they inhibit its action.
Science implies a multiplicity of impossible factors that must be kept in mind, yet no one has the absolute truth.
To finish this annex of my work, I propose that my colleagues review Keshan Syndrome to understand that the relation between the decrease in selenium and selenoproteins plays an important role in the genesis of congestive cardiomyopathy. My rationality leads me to also think that there is a genetic factor given that Keshan Syndrome is endemic. But the fact is that selenium does improve the situation.
I prescribe the lowest dose possible of statins to all my patients who need to take them, and I always prescribe selenium yeast with vitamin E and CoQ10 with it.
I try in this way to protect patient’s selenoproteins, namely glutathione peroxidase, as well as the liver from hepatic lesions that statins may also cause. No more than the commonly used paracetamol (acetaminophen).
Speak to your doctor. Most of them are well-informed and will know how to help you.