Ingredient review

Selenium

Description

What is it?

Selenium is an essential trace mineral named after the Greek goddess of the moon, Selene, (33) as a result of the recent discovery of a similar element, tellurium, that was named after the Earth. (126) Selenium is directly incorporated into more than 25 proteins, which have a variety of functions including antioxidation (glutathione peroxidase, GPx; or thioredoxin reductases, TrxR), regulation of thyroid hormones (iodothyronine deiodinases), immunoregulation (methionine-R-sulfoxide reductase), as well as DNA synthesis, epigenetic modulation, cell signalling, and metabolism (various selenoproteins). (13)(33) Given these important functions, selenium has several therapeutic applications, such as to maintain and improve an individual’s immune and antioxidative profile, thyroid health, and endocrine function, to name a few. Selenium has had particular effectiveness in regions with low selenium intake (e.g., China) for reducing the risk of developing Keshan disease (86%), (139) as well as Kashin-Beck disease (81 to 82%) with 2.2 to 4.4 times better odds of improvement in existing cases. (110)(132

During the first year of life, adequate selenium intakes range between 15 to 20 μg for infants. For ages one to three, the recommended dietary allowance is 20 μg, and this amount increases incrementally by ~10 mg every four years, up to a maximum of 55 μg after the age of 14. (92) The RDAs are based on optimizing glutathione peroxidase (GPx) activity, (19) which occurs when plasma selenium is approximately 80 ng/ml, though Americans and Canadians often possess levels between 125 ng/ml and 145 ng/ml, respectively. (31

While selenium deficiencies are relatively rare in North America, lower selenium levels can lead to the development of many chronic conditions, including various forms of cancer, (5)(17)(18)(21)(27)(34)(39)(46)(50)(56)(94)(107)(124)(140) cardiovascular disease, (72)(100)(136) and gestational and type II diabetes. (12)(68)(125) Selenium deficiency may also lead to higher cardiovascular mortality and all-cause mortality. (60)(130) However, being aptly named after the moon, excessive selenium intake also has a dark side. (20)(96) Specifically, excessive selenium intake has been associated with increased risk of type II diabetes. (66)(67)(85)(122)(125

A number of foods contain relatively high concentrations of selenium, particularly Brazil nuts as well as fish and other seafood, meat, seeds, and grain products. (20)(118) In the majority of cases in North America, supplementation is typically indicated where there is significant suspected or demonstrated deficiency or suspected dysregulation of the physiological functions mentioned above. (49)

Main uses

Antioxidation
Chemoprevention and cancer therapy support
Insulin function (in cardiometabolic conditions)
Thyroid function

Formulations

In general, all forms of selenium are well absorbed, but differences exist between forms. Organic selenium compounds are considered to produce greater blood levels of selenium (e.g., selenomethionine or selenocysteine) compared with inorganic forms (e.g., selenite or selenate), but both appear to raise GPx activities to a similar extent. (20)(33) The following table is organized from highest to lowest bioavailability based on comparative studies.

Form
Characteristics
Selenomethionine (l-selenomethionine)
Organic
Equivalent bioavailability at equal doses of selenomethionine content to selenium-enriched yeast (103)(119)
~4.6x higher AUC than methylselenocysteine (40)
~2x more bioavailable than selenite, (129) with up to a 5.2x higher AUC (40)
~33% higher absorption than selenite, raising plasma selenium 72-89% more (26)(30)
~80% higher plasma selenium than selenate (30)
Selenium-enriched yeast
Selenium in brewer’s yeast (Saccharomyces cerevisiae) mainly provides organic forms of selenium (i.e., selenomethionine), but variability in the percentage of selenomethionine can occur between products. (41)
~1.5-2x more bioavailable than inorganic selenium (20)
~30% higher serum selenium than selenite, but produced equivalence in GPx activity (2)
~72% higher plasma selenium, but produced equivalence in Gpx activity (116)
Reduced oxidative stress biomarkers (8-iso-PGF2α & 8-OHdG), whereas a matched dose of selenomethionine did not, suggesting that additional properties of the yeast may provide added benefit to antioxidative stress over selenomethionine alone (103)
Methylselenocysteine
Organic
~4.6x lower AUC than selenomethionine, but 14% higher AUC than sodium selenite (40)
Sodium selenite (SeO3(2-))
Inorganic
~40% lower absorption than selenate, but was excreted 67% slower, supporting equivalence in their bioavailability (retention) (119)
Sodium selenate (SeO4(2-))
Inorganic
Sodium selenate increased GPx activity in Px with liver cirrhosis, but selenomethionine did not, suggesting that individuals with hepatic impairments, leading to a reduced ability to metabolize selenomethionine to selenide for incorporation into selenoproteins, may require inorganic selenium. (25)
Selenium chelates
Binding of an organic molecule (e.g., glycinate, citrate, apartate, etc.) to selenium to improve its absorption
No comparative evidence available for these formulations

Dosing & administration

Adverse effects

Similar rates of adverse events have been reported between selenium and control groups across various systematic reviews; (43)(75)(91)(120)(121) however, one analysis indicated that there was a five times higher relative risk of an adverse event (i.e., gastric discomfort, headache, or skin rash) compared to control groups in Hashimoto’s thyroiditis. (127

One large trial showed that the daily use of 200 μg over seven to 12 years increased the likelihood of alopecia (28%) and dermatitis (17%), (79) while the use of 800 μg for 16 weeks did not lead to brittle hair or nails. This may suggest that selenium toxicity might only be observed as a result of extremely long and high intakes. (119) For example, the use of 300 μg per day as selenium-enriched yeast over five years increased the likelihood of all-cause mortality after ten years as compared to placebo by 59%, while doses between 100-200 μg did not increase the risk. (98

It should be noted that various analyses have also shown that long-term selenium use may increase the risk of developing type II diabetes. Analyses of randomized controlled trials using >200 μg over three to 13 years showed that selenium increased the relative risk of type II diabetes by 9 to 11%, (85)(123) though findings may be inconsistent. (67) Analyses of observational studies show even greater associations with up to two times greater odds of developing type II diabetes. (66)(125) There the may only be a small window of optimized benefit for selenium blood levels (100 to 130 µg/L) to avoid an increased risk of type II diabetes, as this association is observed at both relatively lower (<100 µg/L) and higher blood levels (>130 µg/L). (125) It should also be noted that despite selenium’s benefits on insulin metabolism (as noted in the “cardiometabolic profile” section above), selenium can potentially increase blood glucose or HbA1c in type II diabetes. (42)

Pharmacokinetics

Absorption

  • Selenium is well absorbed with more than 95% of the organic form selenomethionine, up to 90% of inorganic selenate, and up to 50% of inorganic selenite being absorbed. (81)(119)
  • Selenomethionine is absorbed by intestinal methionine transporters. (24)

Distribution

  • With adequate intake, selenium is primarily used for the synthesis of selenoproteins.
  • The majority of selenium is stored in the liver, but it can be redistributed to other tissues and organs, including the kidneys, brain, reproductive organs, and muscles, when selenium levels are reduced.
  • An individual weighing 70 kg likely stores between 10 to 15 mg of selenium. (24)

Metabolism

  • In the liver, selenomethionine is metabolized to selenocysteine via the transsulfuration pathway, and subsequently to selenide via selenocysteine lyase.
  • Alternatively, it can be metabolized to methylselenol via cystathionine γ-lyase and subsequently demethylated to selenide.
  • Selenite and selenate are also metabolized to selenide by thioredoxin reductases (selenoproteins) or in a reaction with glutathione.
  • Selenide may either produce smaller metabolites for excretion or can help re-synthesize selenoproteins as needed. (24)

Excretion

  • Regulation of selenium stores is mainly determined by its rate of excretion and not its absorption. After intake is sufficient to optimize selenoprotein content, further intake is almost completely counteracted by increased excretion. (24)
  • Selenium is primarily excreted in the urine, though it can also be excreted via stool, lost skin cells, or respiration. (24)(26)(119)
  • Approximately 55 μg is lost each day when consuming placebo, but this increases dose-dependently when selenium is introduced. (119)
  • Approximately 90% of selenium was excreted in 40 hours for selenate and in 121 hours for selenite. (119)

References

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