1. Selenium is an essential trace element that functions in the body as part of selenoproteins but can be toxic at high levels. 2. A misformulated liquid dietary supplement resulted in 201 cases of selenium poisoning due to the selenium concentration being approximately 200 times the labeled amount. 3. Symptoms of selenium toxicity included hair loss, nail discoloration, and worsening of gastrointestinal symptoms.

1. Selenium- functions and clinical
significance
Namrata Chhabra
MHPE, MD, CMCL FAIMER FELLOW
REGIONAL INSTITUTION,
Principal-in charge, Professor& Head, Department of Biochemistry,
SSR Medical College, Mauritius

2. A case series report
 A chiropractor noted common symptoms of gastrointestinal illness and hair loss
among several of his patients.
 In response to their symptoms, the patients had doubled the dose of a dietary
supplement that they acquired from the chiropractor office.
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3. A case series report
 The patients subsequently noted worsening symptoms, including nail
discoloration.
 Two couples contacted the local health department, where investigators
identified the common exposure and initiated an investigation.
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4. A case series report
 The dietary supplement was identified as the common exposure among all
affected persons.
 The FDA subsequently tested the product and determined the selenium
concentration to be approximately 200 times the labeled concentration.
 The misformulated liquid dietary supplement resulted in 201 cases of selenium
poisoning.
 What might have been the mechanism of Selenium toxicity?
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5. Selenium
 Selenium is required for maintenance of health.
 It is a trace element that is essential in small amounts; however, it can be toxic at
high levels.
 Unlike plants, most animals including humans require selenium for the
appropriate functioning of several selenium-dependent enzymes known as
selenoproteins.
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6. Occurrence of selenium
 Selenium is found in the environment in soil.
 Selenium content of food is largely dependent on location and soil conditions,
which vary widely.
 Soils of certain areas in the Great Plains and Western United States as well as
other parts of the world have high concentrations of selenium, which are taken
up by plants.
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7. Sources of Selenium
 The richest food sources of selenium are organ meats and seafood, followed by
muscle meats.
 Garlic, onion, and broccoli), wheat, other grains (including Brazil nuts), and soy
are rich in selenomethionine and contain smaller amounts of selenocysteine and
selenate
 Selenium supplements are available in several forms.
 Sodium selenite and sodium selenate are inorganic forms of selenium
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8. Recommended dietary allowance(RDA)
 RDA is 55 μg/d for persons 19 years or older, with a tolerable upper intake limit
of 400 μg/d.
 The amount of selenium available in a diverse diet with meat, grains, vegetables,
and nuts is typically sufficient to negate the necessity for supplementation.
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9. Functions of Selenium
1) Selenoproteins
Selenium exerts various biological functions mainly as part of the amino acid,
selenocysteine.
Selenocysteine is found in at least 25 selenocysteine-containing proteins
(selenoproteins).
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10. Examples of selenoproteins
1) Glutathione peroxidase
Five selenium-containing glutathione peroxidases (GPx1-4 and GPx6) have been
identified.
GPx isoenzymes are all antioxidant enzymes that reduce potentially damaging
reactive oxygen species (ROS), such as hydrogen peroxide and lipid hydroperoxides,
to harmless products like water and alcohols by coupling their reduction with the
oxidation of glutathione.
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11. Reaction catalyzed by Glutathione peroxidase
Reduced glutathione is required for the activity of glutathione peroxidase, an antioxidant Selenium
containing metalloenzyme that decomposes hydrogen peroxide to water.
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12. Examples of selenoproteins
2) Thioredoxin reductases
The protein thioredoxin, together with thioredoxin reductase( TrxR), NADPH, and
FAD, constitute the thioredoxin antioxidant system involved in the reduction of
antioxidant enzymes (e.g. methionine sulfoxide reductases, and ribonucleotide
reductase-and of many oxidation/reduction (redox)-sensitive signaling proteins .
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13. Reaction catalyzed by thioredoxin reductase
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14. Examples of selenoproteins
3) Iodothyronine deiodinases (thyroid hormone deiodinases)
The thyroid gland releases very small amounts of biologically active thyroid
hormone (triiodothyronine or T3) and larger amounts of an inactive form of thyroid
hormone (T3 precursor: thyroxine or T4) into the circulation.
Most of the biologically active T3 in the circulation and inside cells is generated by
the removal of one iodine atom from T4 in a reaction catalyzed by selenium-
dependent iodothyronine deiodinase enzymes
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15. Reaction catalyzed by selenium dependent
iodothyronine deiodinase
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16. Examples of selenoproteins
 Selenoprotein P is predominantly produced by the liver and is secreted in the
plasma.
 It functions as an antioxidant that protects cells from oxidative damage by
enabling full activity of thioredoxin reductases and glutathione peroxidases.
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17. Examples of selenoproteins
 Selenoprotein W- It is expressed in numerous tissues, with highest levels found
in skeletal muscle and heart.
 Its expression in the brain has been found to confer protection against oxidative
stress-induced neuronal cell death.
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18. Examples of selenoproteins
 Methionine-R-sulfoxide reductase B1 (formerly selenoprotein R)
 The methionine sulfoxide reduction system is involved in the protection against
oxidative stress and is especially critical for the regeneration of proteins
damaged by reactive oxygen species (ROS).
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19. Selenium deficiency
 Insufficient selenium intake may negatively affect the activity of several
selenium-responsive enzymes, including glutathione peroxidases, iodothyronine
deiodinases, selenoprotein W, and methionine-R-sulfoxide reductase.
 Prolonged selenium deficiency may likely contribute to Keshan and Kashin-Beck
diseases.
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20. Risk factors of Selenium deficiency
 Chronically ill patients who were receiving total parenteral nutrition (TPN)
without added selenium for prolonged periods of time.
 Following bariatric surgery
 Severe gastrointestinal conditions, such as Crohn's disease.
 Metabolic disorders, including phenylketonuria, homocystinuria, and maple
syrup urine disease (if the treatment does not include supplementation with
Selenium)
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21. Keshan disease
 Keshan disease is a fatal form of dilated cardiomyopathy that was first described
in young women and children in a selenium-deficient region in China.
 The acute form of the disease is characterized by the sudden onset of cardiac
insufficiency, while the chronic form results in moderate-to-severe heart
enlargement with varying degrees of cardiac insufficiency.
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22. Clinical manifestations
 Typical manifestations are :
 fatigue after even mild exercise,
 cardiac arrhythmia and palpitations,
 loss of appetite,
 cardiac insufficiency,
 cardiomegaly, and
 congestive heart failure.
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23. Prophylaxis
 Once the disease is established, selenium is of little or no therapeutic value.
 Prophylaxis consisting of oral administration of selenium 3 months before the
periods of highest anticipated risk is highly effective.
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24. Kashin-beck disease
 A selenium-responsive bone and joint disease (osteoarthropathy) has been
detected in children aged 5–13 years in China and less extensively in south-east
Siberia.
 The disease is characterized by joint necrosis resulting in structural shortening of
the fingers and long bones with consequent growth retardation and stunting.
 Kashin-Beck disease also occurs in areas where the availability of soil selenium
for crop growth is low.
 The selenium contents of hair and of whole blood are abnormally low and the
blood content of Glutathione peroxidase is reduced.
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25. Selenium Toxicity
 Acute and fatal toxicities have occurred with accidental or suicidal ingestion of
gram quantities of selenium.
 Chronic selenium toxicity (selenosis) may occur with smaller doses of selenium
over long periods of time.
 The most frequently reported symptoms of selenosis are hair and nail brittleness
and loss.
 Other symptoms may include gastrointestinal disturbances, skin rashes, a garlic
breath odor, fatigue, irritability, and neurologic disorders.
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26. Summary
1. Selenium is a trace element that is essential in small amounts, but like all
essential elements, selenium can be toxic at high levels.
2. Selenium exerts various biological functions mainly as part of the amino acid,
selenocysteine, which is found in at least 25 selenocysteine-containing proteins
(selenoproteins).
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27. Summary
3. Insufficient selenium intake may negatively affect the activity of several
selenium-responsive enzymes, including glutathione peroxidases, iodothyronine
deiodinases, selenoprotein W, and methionine-R-sulfoxide reductase.
4. Keshan disease is a fatal form of dilated cardiomyopathy that was first described
in young women and children in a selenium-deficient region in China.
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28. Summary
5. Kashin-Beck disease is characterized by joint necrosis – epiphyseal degeneration
of the arm and leg joints resulting in structural shortening of the fingers and long
bones with consequent growth retardation and stunting.
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29. Thank you
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