Facts, Articles, Research

What the science says (1990–2026): Selenium

These citations support correction of deficiency, specified forms, and elemental amounts — the same logic used in MD's Choice formulas. They are not claims that a supplement treats disease.

Clark NPC 1996; SELECT 2008 JAMA; 2023–2025 selenium reviews. Selenium is required for glutathione peroxidases. SELECT showed high-dose selenomethionine did not prevent prostate cancer in already-sufficient men. Correct deficiency; do not megadose.

These products are not intended to diagnose, treat, cure, or prevent disease. Historic monograph text below is kept for the original library.

Selenium

I. Physiological Role of Se

Se-dependent glutathione peroxidase - catalyzes breakdown of hydrogen peroxide and organic hyperoxides with glutathione serving as the hydrogen donor
ROOH + 2GSH® ROH + HOH + GSSG
1. Purified enzyme has a Se content of 0.34%, equivalent to 4 g atoms of Se per mole of enzyme. GSH-Px activity decreases with Se deficiency
2. GSH-P_x is highly specific for the donor substrate glutathione
3. Glutathione S-transferases also have GSH-P_x activity
  1. They are non Se-dependent
  2. They break down organic hydroperoxides but not H₂0₂
  3. Glutathione S-transferase activity increases with Se deficiency
Se-dependent glutathion peroxidase may help regulate mitochondrial substrate oxidation (Eur. J. Biochem. 84:337. 1978)
1. Oxidation of pyriuvate in Se adequate mitochondria decreased when hydroperoxide was being metabolized by Se-dependent GSH-P_x
2. No decrease in pyruvate oxidation was found when Se deficient mitochondria were used
Se may be necessary for proper function of the cytochrome P-450 system
1. Induction of the cytochrome P-450 system increases the Se requirement (Poultry Sci. 54:1152. 1975; J. Nutr. 102:857. 1972)
  1. Male rats are more susceptible than female rats to Se deficiency
  2. There is also a sex difference in the activity of MFO enzymes in rats
  3. Feminization of male rats by castration or injection of estrogen makes them more resistant to Se deficiency
  4. Masculinization of female rats by administration of testosterone makes them more susceptible to Se deficiency
  5. Phenobarbital also makes female rats more susceptible to Se deficiency
  6. Treatments that increase or decrease the susceptibility of rats to Se deficiency also increase or decrease activity of MFO enzyme system
  7. MFO system may play a role in the requirement of animals for Se
    1. In some lipophilic compounds containing S, the S is readily oxidized by the MFO enzyme system
    2. It is possible some biologically active form of Se is converted to an inactive oxidized form by MFO enzymes
2. Se deficiency impairs induction of cytochrome P-450 by phenobarbital (Arch. Biochem. Biophys. 170:124, 1975)
3. Severe Se deficiency causes a decrease in hepatic cytochrome P-450 (J. Environ. Pathol. Toxicol. 2:1127. 1979)
4. Se in the diet is necessary for maintenance of rat small intestinal mucosal cytochrome P-450 levels. (Pharmacologist 23:179, 1981)
5. Biochemical function underlying support of cytochrome P-450 levels by Se has not been identified
  1. Se deficiency increases hepatic microsomal heine oxygenase activity, indicating catabolism of heme (Heme is the prosthetic group of cytochrome P-450)
  2. A defect in heme synthesis was not found. (Biochem J. 168:105. 1977)
    1. Phenobarbital administration increases both synthesis and catabolism of heme in Se-deficient liver. (J. Biol. Chem. 253:6203, 1978)
    2. In control liver, phenobarbital stimulates heme synthesis but it diminishes heme catabolism
6. Effect of phenobarbital on cytochrome P-450 in Se deficiency
  1. Hepatic microsomal cytochrome P-450 consists of:
    1. NADPH-cytochrome P-450 reductase (also known as NADPH-cytochrome C reductase because it is usually assayed with cytochrome C as the substrate)
    2. A family of hemoproteins, the cytochrome P-450's
  2. It can be induced by certain xenobiotics such as phenobartibal
  3. A given xenobiotic characteristically affects certain forms of cytochrome P-450
  4. Cytochrome P-450 system is important for detoxifying xenobiotics or converting them to more easily excreted forms
  5. Phenobarbital induces synthesis of heme to be used primarilyy in the assembly of cytochrome P-450
    1. In control animals heme and apocytochrome P-450 are produced and assembled. Little heme is catabolized
    2. In Se deficient animals, the heme is produced but not efficiently assembled with the apoprotein
      – Consequently, less cytochrome P-450 is produced
      – Excess heme is thus present in the hepatocyte
      – Excess heme induces the catabolic enzyme microsomal heme oxygenase
      – The enzyme disposes of the excess heme
7. Se does not exert its effect on cytochrome P-450 through Se-dependent GSH-P_x
  1. Injection of Se into a deficient rat corrects the abnormality in heme metabolism within 12 hr (J. Biol. Chem. 253:6203, 1978)
  2. There is no detectable recovery of GSH-Px within 12 hr after injection of Se into a Se-deficient rat
  3. The abnormality in heme metabolism in Se deficiency suggests there is an undiscovered function of Se
8. A sheep muscle cytochrome contains Se (Biochem. Biophys. Res. Comm. 53:1031, 1973)
Se is a constituent of sperm
1. Se is essential for spermatogenesis (Biol. Reprod. 8'625, 1973)
2. Se is present in the protein of the capsule surrounding the sperm mitochondria and may have a structural function (Gamete Res. 4:139, 1981)
Selenoprotein P has been purified and quantitated in rat plasma but its function is unknown (J. Nutr. 119:1010, 1989)
1. The concentration of selenoprotein P in plasma is directly dependent on dietary Se up to 0.1 ppm
2. Selenoprotein P responds to slightly lower dietary Se intake than does glutathione peroxidase activity
  1. A Se supplement of 0.02 ppm
    1. Supported selenoprotein concentration 48% of control
    2. Plasma GSH-Px activity was only 12% of control
    3. Liver cytosolic GSH-Px activity was only 1% of control
3. Measurement of seloprotein P concentration provides a new assessment of Se status
4. Thyroxine 5¢ deiodinase (See J. Nutr. 125:864. 1995)

II. Tissue Distribution of Se

(See J. Anim. Sci. 65:1712, 1987; J. Nutr. 119:1146, 1989)

Concentration of Se in blood is variable, depending on dietary intake
1. 75% of ovine red cell Se is in glutathione peroxidase (Biochemistry 13>1825. 1974)
2. Most of the Se in human plasma is in the a- and b- globulins (Clin. Chem. Acta 16:311. 1967.)
3. Human blood Se levels are usually near 20 mg/dl
  1. Low blood Se levels seem to be associated with Iow plasma levels with no fall in cell Se
  2. Blood Se is reduced with some kinds of cancer
Organs levels of Se
1. Kidney and liver have highest concentrations
2. Cardiac muscle contains appreciably more Se than skeletal muscle
3. Intestinal and lung tissues can be relatively high
4. Nerve and adipose tissue are low

III. Absorption and Metabolism of Se

Percent of Se intake absorbed

Rat: > 90% (Trace Elements in Human Health and Disease II. 1976)
Human: 44-70% (Trace Elements in Human Health and Disease I1. 1976)

Swine: 72-75% (J. Anim. Sci. 61:173. 1985)

	Supplemental Se (ppm)
31 to 35 d on diet	0	0.3	0.5	1.0
Se intake (mg) Fecal Se (mg) Urinary Se (mg) Se retention (mg) Se retention (%) Apparent Se absorption (%)	66 46 6 14 21.2 30.3	346 95 97 154 44.5 72.5	529 131 174 224 42.3 75.2	1088 271 409 408 37.5 75.1

Dairy Cows: 28-48% (J. Dairy Sci. 67:219. 1984)
Sheep: 40%(J. Nutr. 119:1146, 1989)

Excretion of Se
1. Urine is primary route in monogastric animals
2. Feces is primary route in ruminants
  1. 59.4% (From J. Nutr. 119:1146, 1989)
  2. Before rumen function develops, young ruminants excrete more Se in urine and less in feces than older animals
  3. Se administered IV or sub Q is generally excreted to a greater extent in urine and less in feces
3. Amount of Se excreted in bile is small (~ 2%).
4. When large quantities of Se are ingested, some is lost in breath as dimethyl selenide
Se metabolism by rumen microbes
1. Se content of' rumen microbes in sheep exceeds daily dietary Se by 46-fold (DM basis), 11-fold (N basis), or 26-fold (S basis)
2. Incorporation of ⁷⁵Se by rumen microbes is inversely proportional to previous dietary intake by host animal
3. Once Se has been incorporated into microbial cells, its availability to the host animal appears to be low
4. Most of the Se excreted in feces is inorganic and insoluble in water or organic solvents
  1. Ruminant animals could contribute to a loss of Se from the Se cycle
  2. Se deficiency is becoming more of a problem in heavily grazed areas
Maternal-fetal interrelationships of Se and vitamin E
1. Selenium (J. Nutri. 119:1128-1137, 1989)
2. Placental transfer of vitamin E in the bovine is inefficient so prepartal maternal supplementation provides minimal protection of the neonate from vitamin E deficiency (J. Nutr. 119:1156-1164, 1989)

IV. Interaction of Se with Other Elements

Se and vitamin E have a sparing effect on each other
1. Both vitamin E and Se-dependent GSH-Px guard against accumulation of organic hydroperoxides but by different mechanisms:
  1. Vitamin E prevents formation of these highly toxic products
  2. Glutathione peroxidase converts them to the less harmful alcohols
2. Vitamin E is metabolized more rapidly in Se-deficient rats than in controls (J. Nutr. Sci. Vitaminol 23:273, 1977)
3. A combination of both is more effective in prevention of white muscle disease than either alone
Se and sulfur: Increased S can reduce Se status
1. Increased sulfur intake may increase incidence of white muscle disease
2. Sheep fed a Iow-S diet (0.07%) maintain higher levels of Se in plasma and wool than when the diet contains 0.2% S
Arsenic protects against Se toxicity by increasing bile excretion of Se
Se-Zn interaction (see J. Nutr. 119:916, 1989)
1. Se had an antagonistic effect on Zn absorption by Zn-depleted rats
2. Zn had an antagonistic effect on Se absorption by Zn adequate rats
Cadmium and mercury
1. When Se is excessive, Cd and Hg reduce its toxicity
2. Se reduces toxicity of Hg and Cd
3. Inorganic mercury and methylmercury more severly affect Se-deficient animals than controls
  1. Liver cysteine concentration is lower in the Se deficient rat than in the control
    1. Presumably because cysteine is used in the synthesis of the markedly accelerated GSH synthesis
  2. The decrease in cysteine concentration could impair metallothionein synthesis
    1. This could reduce mercury sequestration and lead to increased toxicity
  3. Mercury metabolism may lead to oxidative stress either by inactivating protective enzymes or by producing free radicals (Ann. NY Acad. Sci. 355:212, 1980)
Se and vitamin B6 (J. Nutr. 119:1962-1972, 1989)
1. Se-methionine is a major form of Se in plant tissues
2. In animal tissues, Se is incorporated into specific selenoproteins (including GSH-P_x) as Se cysteine
  1. Conversion of methionine to cysteine by the transulfuration pathway requires pyridoxal-5'-phosphate
  2. If Se methionine is converted to Se cysteine by the same pathway, a deficiency of vitamin B₆ would inhibit utilization of Se methionine for synthesis of GSH-P_x and other specific Se cysteine-containing proteins
3. Erythrocyte levels of Se and GSH-P_x were lower in vitamin B₆-deficient rats than in control rats
4. Tissue retention of ⁷⁵Se provided as Se methionine was increased in vitamin B₆ deficient rats
5. The proportion of ⁷⁵Se retained in muscle and liver as Se cysteine was reduced
6. These findings suggest the conversion of Se methionine to a form available
  for GSH-P_x synthesis is reduced by vitamin B₆ deficiency

V. Se Requirements

(See Ulrey, D.E. 1987. Biochemical and physiological indicators of selenium status in animals. J. Anim. Sci. 65:1712-1726)

Safe and adequate intakes for humans
1. Infants 0-0.5 yrs........10-40 mg/day
2. Infants 0.5-1 yrs........20-60 mg/day
3. Children I-3 yrs.........20-80 mg/day
4. Children 4-6 yrs........30-120 mg/day
5. Others......................40-200 mg/day
Domestic ruminants.........0.1 - 0.2 ppm diet DM
Swine and poultry.............0.1 ppm

VI. Se Deficiency

Se deficiency in humans: Keshan disease in parts of China
1. Myocardial necrosis with varying degrees of cell infiltration and fibrosis
2. Myocardial necrosis in similar to mulberry heart disease in swine
3. Leg muscles also degenerate in some patients
4. Mostly school age children only in certain areas are affected
5. Morbidity is about 1% in affected areas and approximately half of the victims die
6. Disease is not responsive to conventional medical treatments but can be prevented with adequate Se
Muscular dystrophy
1. Occurs in chicks, pigs, foals, calves and lambs
2. Occurs primarilyy between 3-4 wk of age in lambs and 4-6 wk of age in calves, but up to several months of age may be affected
3. Characterized by degeneration of Striated muscle and cardiac muscle
4. Affected muscles may have elevated levels of several minerals
5. Superoxide dismutase activity is low in very young lambs. This may contribute to the higher incidence of white muscle disease. (see J. Nutr. 114:1909, 1984)
Exudative diathesis in chicks
1. Edema on the breast, wing and neck
2. Abnormal permeability of capillary walls allows fluid to accumulate
3. Prevented by either vitamin E or Se
4. High correlation between plasma GSH-P_x and ability of Se to prevent exudative diathesis
Pancreatic fibrosis in chicks
1. Atrophy of the pancrease
2. Associated with impaired absorption of lipid and vitamin E
3. Reduced GSH-P_x in pancreas
4. Can be prevented only by Se
Liver necrosis in pigs and rats
Mulberry heart disease in pigs (similar to Keshan disease in humans)
Reproductive disorders
1. Reduced egg production and hatchability in hens
2. Reduced litter size and increased pig mortality in swine.
3. Reduced ova fertilization rate and increased embryonic death in sheep
4. Increased incidence of retained placentas and cystic ovaries in dairy cows
  1. High instances of retained placenta have been observed in dairy herds in areas with a history of white muscle disease
  2. Unexplained placental retention is not always due to inadequate Se (high instances have been reported in Nebraska and South Dakota)
  3. Effectiveness of Se, vitamin E or both has not been consistent in different investigations
  4. Se-dependent GSH-P_x may be effective only if other components of the system for protecting against lipid peroxidation are intact

VII. Se Toxicity

Accumulator plants
1. Most plants accumulate < 30 ppm of Se but 5 ppm or more of Se is potentially toxic
2. Accumulator plants may accumulate up to 1% (10,000 ppm) Se
  1. Indicator plants require Se for growth
    1. Called indicator plants because their presence identifies Se-bearing soils
    2. These plants synthesize organic Se compounds from forms of Se in the soil which are unavailable to other plants
    3. When these plants die, they release Se in forms available to other plants
  2. Secondary Se accumulators
    1. Do not require Se for growth but are able to accumulate Se
Se accumulator plants are less palatable when Se content is high, so sheep or cattle usually discriminate against them unless forced to consume them
Acute Se toxicity - ingestion of a sufficient quantity of seleniferous we will produce severe symptoms (8-16 g/kg BW of plant material containing 400-800 ppm of Se may be fatal to sheep)
1. Staggering gait, stands with lowered head and drooped ears
2. Elevated body temperature
3. Diarrhea
4. Weak, rapid pulse, labored respiration
5. Prostration and death
Chronic Se toxicity - consumption of feeds containing 5-40 ppm Se over a period of weeks or months
1. Lameness
2. Sloughing of hooves
3. Loss of hair
4. Emaciation
5. Dullness
6. Damage to liver and brain
7. Treated in India by feeding excess sulfur
The difference between a 0.1 to 0.3 ppm Se requirement and a potentially harmful level of 2 to 5 ppm may seem narrow, but:
1. Toxic levels are 10-50 times greater than Se requirements
2. This range is much wider than the difference between requirements and toxic amounts of Cu for sheep

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Selenium — Se (atomic number 34)

A trace element in glutathione peroxidase, an enzyme that mops up peroxides. The gap between enough and too much is narrower than for many vitamins.

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Vitamin A	Vitamin B1 (Thiamin)	Vitamin B2 (Riboflavin)	Vitamin B3 (Niacin)
Vitamin B5 (Pantothenic Acid)	Vitamin B6	Vitamin B12	Vitamin C
Vitamin D	Vitamin E	Vitamin K	Biotin
Folic Acid

Calcium	Magnesium	Phosphorus	Sodium, Potassium, Chloride
Sulfur (Sulfer)

Boron	Chromium	Cobalt	Copper
Fluorine	Iodine	Iron	Manganese
Molybdenum	Nickel (Nickle)	Selenium	Silicon
Tin	Vanadium	Zinc	Ultra Trace

What the science says (1990–2026): Selenium

Selenium

Vitamins, Major Elements, Trace Elements, Toxic Elements

Vitamins

Major Elements

Trace Elements

Toxic Elements

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