Selenium

An Essential Mineral that is heralded for its anti-oxidant capabilities, it forms a part of some anti-oxidant enzymes such as glutathione to confer protective effects. Taking more than needed, however, can cause oxidative damage and may be pro-diabetic.

This page features 67 unique references to scientific papers.

How to Take

Recommended dosage, active amounts, other details

An overall intake (foods and supplements) in the range of 200-300ug daily should be the goal for general health and well being with an emphasis on anti-carcinogenic properties.

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Human Effect Matrix

The Human Effect Matrix looks at human studies (it excludes animal and in vitro studies) to tell you what effects selenium has on your body, and how strong these effects are.

Grade Level of Evidence
Robust research conducted with repeated double-blind clinical trials
Multiple studies where at least two are double-blind and placebo controlled
Single double-blind study or multiple cohort studies
Uncontrolled or observational studies only
Level of Evidence
? The amount of high quality evidence. The more evidence, the more we can trust the results.
Outcome Magnitude of effect
? The direction and size of the supplement's impact on each outcome. Some supplements can have an increasing effect, others have a decreasing effect, and others have no effect.
Consistency of research results
? Scientific research does not always agree. HIGH or VERY HIGH means that most of the scientific research agrees.
Notes
Prostate Cancer Risk Minor Very High See study
A small decrease in prostate cancer risk is seen when comparing areas with high soil selenium (indicative of dietary intake of selenium) against areas with low soil selenium.

Scientific Research

Table of Contents:

  1. 1 Structure and recommendations
  2. 2 Functions in the body in normal dietary ranges
  3. 3 Different forms of selenium in the body
  4. 4 Effects of various intake levels
  5. 5 Different forms of selenium
  6. 6 Selenium and Glucose Metabolism
    1. 6.1 Gestational Diabetes
  7. 7 Selenium and Cancer
    1. 7.1 General
    2. 7.2 Prostate Cancer
    3. 7.3 Breast Cancer
  8. 8 Safety and Toxicity
    1. 8.1 General
    2. 8.2 Genotoxicity
    3. 8.3 Human Toxicity
    4. 8.4 Side-Effects with Safe Usage
    5. 8.5 Case Studies

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1Structure and recommendations


2Functions in the body in normal dietary ranges

It normally acts in concert with a class of enzymes and transporters called Selenoproteins (proteins with selenium in it), many of which are intrinsic anti-oxidant enzymes. In these selenoproteins, selenium acts as a prosthetic group or active site.[1]


3Different forms of selenium in the body

Selenium can take the form of various organic and non-organic compounds.

Non-organic forms typically revolve around Selenite, a triple-oxidized form of selenium. It can be converted via Glutathione into Selenade; this multiple step process produces some superoxide radicals.[2]

Organic forms include the selenoamino acids, which include selenocysteine, selenomethione, and Se-methylselenocysteine. The main active dietary form is selenomethionine.[3] Selenomethionine is a relatively stable compound, but has pro-oxidative metabolites such as Selenid and Methylselenol.[4]


4Effects of various intake levels

Deficiency of Selenium occurs when overall intake is less than 11ug, and 40ug is typically recommended as the minimum intake.[5] A slightly higher but still low dietary intake of selenium (55ug) is sufficient to support the needs of 25 selenoproteins[6][7] although there may be some interindividual differences.[8] Levels above this, but not yet into therapeutic dosages (200-300ug) are possibly in the range of what is needed to exert anti-carcinogenic effects[9][10] and doses up to the range of 750-800ug daily seem to be relatively free of harm.[11] Dosages of 1,500-1,600ug or above start to become associated with harm and doses nearing 3,000-5,000ug can cause direct DNA damage.[12][13][14]

Selenium metabolites can also regulate cell cycles and apoptosis, and aid in tumor regulation.[14]


5Different forms of selenium

The synthetic form called MethylSelenic Acid can be directly reduced into methylselenol and can avoid the B-lysase enzyme intermediate commonly seen with dietary selenium.[15]


6Selenium and Glucose Metabolism

Selenium has been noted in the past to aid glucose metabolism via acting as an insulin mimetic[16] and thus aiding the deposition of glucose into both fat and muscle cells.[17][18] These effects have also been seen in vivo.[19]

In populations that have sufficient selenium status, epidemiological research[20] and one intervention[21] have suggested that further supplementation may increase the risk for insulin resistance and Type II Diabetes. The intervention was dosed at 200mcg daily.

The theorized mechanism of action is that after a certain threshold of selenium intake (past the RDA, nearing the TUL) selenium builds up in pancreatic tissue[22] and exerts oxidative stress on beta-cells that secrete insulin.[23]

This may be an issue of selenium being anti-diabetic acutely (via acting as an insulin-mimetic and aiding in glucose deposition) but over time damaging beta-cells and exerting the opposite effect and being pro-diabetic.[24]

6.1. Gestational Diabetes

Several studies have found that Selenium levels decrease in women during pregnancy due to several phenomena such as increased lipid peroxidation, increased fetal requirement, hemodilutional phenomena and deposition in the placenta.[25][26][27][28][29][30]

A systematic review and meta-analysis, found that Selenium concentrations are lower in women with gestational hyperglycemia when compared to normoglycemic pregnant women. [30] The same study found that women with Gestational Diabetes Mellitus, had lower concentrations of Selenium than normal pregnant women in the second and third trimester, however, the difference was only significant in the third trimester. It is believed that this is due to the higher tendency of insulin resistance and higher activity of peroxidase enzymes, such as erythrocyte glutathione peroxidase, in the third trimester.[30] Thus, women with GDM or impaired glucose tolerance are more likely to be impacted by oxidative stress conditions. Selenium supplementation through food or dietary supplements may be beneficial for such populations.


7Selenium and Cancer

7.1. General

Selenium was first discovered to be related to cancer via correlational research showing higher cancer rates in areas with lower crop selenium content.[31]

Several metabolites of selenium may be involved with cancer regulation. Methylselenol is though to play a role[32][33][14]

Selenoproteins themselves, rather than individual selenoamino acids, are also implicated in cancer prevention. These selenoproteins are typically those that exert anti-oxidative effects[34] (Glutathione Peroxidases and Selenoprotein P) and alleviate cancer during the promotion stage.[35][36]

Specific selenoproteins that have been investigated for being linked to specific cancers include Glutathione Peroxidase 1 being associated with head and neck, lung and breast, and bladder and prostate cancers,[37][38][39][40] Glutathione Peroxidase 2 being associated with colorectal adenoma,[41][42] Selenoprotein P being associated with both colorectal adenoma and Prostate cancer,[43][44] Selenoprotein 15 being associated Head, Neck, breast and lung cancer,[45][46][47] and Thioredoxin reductase 1 being associated generally with most cancers.[48][49] Selenium also enhances the effects of tumor protein p53 which promotes DNA repair, apoptosis and inhibits proliferation.[50]

7.2. Prostate Cancer

Circulating selenium (independent of supplementation) is associated with a decrease in prostate cancer as assessed by a relatively small meta-analysis in a relatively dose-dependent manner up to a serum concentration of 170ng/mL, where it results in a relative risk ratio of 0.8 relative to 60ng/mL (set as baseline).[51] The same meta-analysis found a decreased risk of prostate cancer associated with toenail selenium levels at up to 1 μg/g, where the risk then rose again.

The Selenium and Vitamin E Cancer Prevention Trial (SELECT) found no association between selenium status (as measured in toenails) and prostate cancer in any of five selenum concentration quintiles in the population, whose selenium levels ranged from 0.48-8.97μg/g (mean 0.89μg/g, 95% CI 0.55-1.43μg/g).[52] Since there were only 13 cancer cases with toenail selenium levels less than 0.617μg/g included in this analysis,[52] this study represents a relatively selenium-replete United States population compared to patients who were in included in the previous meta-analysis.[51]

7.3. Breast Cancer

Higher selenium levels are correlated with a reduced risk of breast cancer. One meta-analysis, which examined 16 epidemiological studies, found that high selenium concentrations in serum were associated with a significant decrease in the risk of breast cancer (P=0.002), however, no such association was found between risk of breast cancer and selenium concentration in toe nails (P=0.17).[50]


8Safety and Toxicity

8.1. General

Much danger of excessive selenium comes through the pro-oxidant compound sodium selenite (thrice oxygenated selenium bound to sodium); this compound is able to induce tumor death via its pro-oxidant abilities, but is also toxic to other cells.[5]

8.2. Genotoxicity

In vitro studies noted that high Se intake can be toxic and have adversely effect on the integrity of genomic DNA in various tissues and organs.[53] When human peripheral blood lymphocytes was exposed to high concentrations of two inorganic salts of selenium-sodium selenite (2.9 x 10-5 M) and sodium selenate (2.65 x 10-5 M), it was found to be lethal.[54] One study that examined DNA oxidation in rats suggests that high dietary intake of inorganic selenium may induce DNA damage in the liver.[55] Although the mechanisms responsible for the adverse effects of high doses of Se are not completely understood, the effects can be severe with DNA damage, oxidative stress, and cell death induction.[53]

8.3. Human Toxicity

Toenails and fingernails damage[56] can occur after high ingestion of selenium. Nail samples are in fact frequently used to estimate selenium status.[57][58][59][60]

One clinical trial examined the plasma response and toxicity reports from 24 men with prostate cancer who received either 1600 or 3200 mcg/day of selenized yeast for up to 24 months. The 3200 mcg/day doses produced more symptoms of selenium toxicity (garlic breath, brittle hair and nails, stomach upset, dizziness) than the 1600 mcg/day doses, but these symptoms were not severe and did not correlate with peaks in plasma selenium levels. The study suggests that doses of selenized yeast greater than 400 mcg/day can be given in controlled situations, for extended periods of time, without serious toxicity.[12]

8.4. Side-Effects with Safe Usage

An observational study shows that dietary exposure to selenium compounds of around 300 mcg per day can have early toxic effect on endocrine function, particularly on the synthesis of thyroid hormones, and NK-cell suppression.[61] One clinical trial randomized subjects to 100 mcg, 200 mcg, or 300 mcg selenium-enriched yeast or placebo tablets for 5 years and found that in euthyroid subjects, selenium supplementation decreased serum TSH and FT4 concentrations by 0.066mIU/I and 0.11 pmol/I, respectively, per 100 mcg/day increase.[62]

Human experimental trials have associated selenium intake with an increased risk for type 2 diabetes.[21] One observational study found that after a median follow-up of 16 years, subjects developed diabetes with an average dietary selenium intake of 55.7 mcg/day, with an odds ratio of 1.29 (95% CI: 1.10, 1.52) for diabetes associated with a 10 mcg/day increase in selenium intake.[63] A clinical trial that assigned subjects with type 2 diabetes to 200 μg/day or placebo for 3 months revealed deterioration in blood glucose control and noted a significant increase in fasting plasma glucose by almost 20 mg/dL in the selenium group and a decrease of about 20 mg/dL in the placebo group.[64] Another clinical trial assigned nondiabetic patients to selenium 200 mcg/day or placebo and found that after a follow up of about 7.7 years, selenium supplementation significantly increased the risk for the disease, with a hazard ratio of 1.55 (95% CI, 1.03 to 2.33).[21]

8.5. Case Studies

A case report of 201 subjects who ingested a liquid dietary supplement that contained 200 times the labeled concentration of selenium (~41,749 mcg/day) noted symptoms including diarrhea, fatigue, hair loss, joint pain, nail discoloration or brittleness, and nausea. Patients often continued to experience hair and nail changes, memory loss, mood swings, fatigue, muscle pains, and garlic breath 90 days after the exposure to selenium had ended.[65]

Another case of a misformulated dietary supplement which contained over 40,000 mcg of Se examined selenium exposure in 97 subjects through nail sample tests. Subjects self-reported high occurrences of dermatological lesions, muscle and joint pain, and neuropsychological signs and symptoms including fatigue, confusion, memory loss, anxiety, fingertip tingling, depression, anger, irritability, insomnia, dizziness and imbalance, eye and vision problems and headache.[66]

A case of xanthotrichia, or yellow hair discoloration, has been reported with selenium sulfide 2.5% shampoo and dihydroxyacetone.[67]

Scientific Support & Reference Citations

References

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(Common misspellings for Selenium include selenum, selenim, selinium, selinim, selenyum)

(Editors who contributed to this page include GregoryLopez, , )