Selenium

Last Updated: September 28, 2022

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.

Selenium is most often used for.



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1.

Sources and Composition

1.1

Origin and Composition

Selenium is an essential trace mineral that can be found in organic and inorganic forms. The primary organic forms are the selenoamino acids, selenocysteine, selenomethione, and Se-methylselenocysteine. The main active dietary form is selenomethionine.[1] Other notable organic forms are selenoneine, which is the major form in tuna [2], and γ-glutamyl-Se-selenomethyl-selenocysteine, which is found in a variety of plant foods.[3]

Selenite and selenate, the inorganic forms found in soil and water, are used by plants and animals to synthesize the organic forms. Plants mainly synthesize selenomethionine, whereas animal synthesis of selenomethionine from selenite is negligible, with synthesis of selenocysteine being more viable.[1]

1.2

Sources and Structure

The selenium content of food correlates with the total protein content due to the ability of Se-amino acids to replace sulfur in proteins, although there are many notable exceptions depending on the physiology of the organism. Intake varies considerably by region depending on the levels in soil, the growing conditions of crops, the diets of livestock, and the local diet.[3][4]

Brazil nuts contain the most selenium per gram of any measured food; two Brazil nuts daily for 12 weeks has been observed to increase serum selenium levels by 64.2% in adults from New Zealand.[4][5] Other nuts and seeds provide more modest amounts of selenium, with Greek sesame seeds being a known region-specific exception, showcasing the extreme variability by region.[6]

Selenium is consistently high in seafood and generally high in meats and eggs, although subject to variation depending on feed and animal supplementation.[4] Dairy, particularly cheese, is also a significant source, with selenium content being inversely correlated with the fat content[7]

Legumes such as lentils can be notable sources but vary depending on the species of legume. Wheat flour used in bread and pasta also provides nutritionally important amounts of selenium. Vegetables and fruits are not usually significant sources of selenium, however there are reports of Indian onions and portobello mushrooms being potent sources.[4]

A wide variety of foods can supply significant amounts of selenium, with fish and Brazil nuts being the most consistent sources.

1.3

Biological Significance

It normally acts in concert with a class of enzymes and transporters called Selenoproteins (proteins with selenium in them), many of which are intrinsic anti-oxidant enzymes. In these selenoproteins, selenium acts as a prosthetic group or active site.[8] Distinctly, Selenoprotein S is involved in protection against endoplasmic reticulum stress and regulation of proinflammatory cytokine release.[9]

Selenium is essential for the functioning of the iodothyronine deiodinases which catalyze the deiodination of thyroid hormones, converting T4 to T3 and rT3, with implications for growth and thermogenesis.[9]

In thioredoxin reductases it plays a role in redox reactions that control transcription factors, cell proliferation and apoptosis.[9][10] Thioredoxin reductases can also reduce dehydroascorbic acid, an oxidized form of ascorbic acid.[11]

1.5

Deficiency

Deficiency of Selenium occurs when overall intake is less than 11ug, and 40ug is typically recommended as the minimum intake.[13] Selenium deficiency in children can result in Keshan disease, named for the county in China where where patients exhibited a severe and often fatal form of cardiomyopathy.[14] Keshan disease is correlated with selenium intake, status, and GPx activity; supplementation of selenium reduces its incidence. There is a likely role of various viral infections, which are likely exacerbated by selenium deficiency.[15]

1.6

Sufficiency and Excess

Intake of 55ug is sufficient to support the needs of 25 selenoproteins[16][17] although there may be some interindividual differences.[18] 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[19][20] and doses up to the range of 750-800ug daily seem to be relatively free of harm.[21] 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.[22][23][24]

1.7

Formulations and Variants

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.[25]

Organic forms include the selenoamino acids, which include selenocysteine, selenomethione, and Se-methylselenocysteine. The main active dietary form is selenomethionine.[1] Selenomethionine is a relatively stable compound, but has pro-oxidative metabolites such as Selenid and Methylselenol.[26]

Selenium metabolites can also regulate cell cycles and apoptosis, and aid in tumor regulation.[24]

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.[27]

2.

Interactions with Glucose Metabolism

2.1

Insulin

Selenium has been noted in the past to aid glucose metabolism by acting as an insulin mimetic[28] and thus, aiding the deposition of glucose into both fat and muscle cells.[29][30] These effects have also been seen in vivo.[31]

2.2

Diabetes

In populations that have sufficient selenium status, epidemiological research[32] and one intervention[33] have suggested that further supplementation may increase the risk for insulin resistance and type 2 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[34] and exerts oxidative stress on beta-cells that secrete insulin.[35]

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.[36]

However, one intervention found that supplementation of selenium by pregnant women who were not deficient in selenium, did not result in increases of adiponectin, a marker of insulin resistance. [37]

Supplementation of selenium for insulin resistance or type 2 diabetes is not recommended due to its possible pro-diabetic effects.

2.3

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.[38][39][40][41][42][43]

A systematic review and meta-analysis, found that selenium concentrations are lower in women with gestational hyperglycemia, when compared to normoglycemic pregnant women. [43] 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 differences were 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.[43]

Women with GDM or impaired glucose tolerance are more likely to be impacted by oxidative stress and more likely to have lower concentrations of selenium. Increasing selenium intake through food or dietary supplements may be beneficial for such populations.

3.

Interactions with Cancer Metabolism

3.1

General

Selenium was first discovered to be related to cancer via correlational research showing higher cancer rates in areas with lower crop selenium content.[44]

Several metabolites of selenium may be involved with cancer regulation. Methylselenol is thought to play a role[45][46][24]

Selenoproteins themselves, rather than individual selenoamino acids, are also implicated in cancer prevention. These selenoproteins are typically those that exert anti-oxidative effects[47] (Glutathione Peroxidases and Selenoprotein P) and alleviate cancer during the promotion stage.[48][49]

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,[50][51][52][53] Glutathione Peroxidase 2 being associated with colorectal adenoma,[54][55] Selenoprotein P being associated with both colorectal adenoma and prostate cancer,[56][57] Selenoprotein 15 being associated Head, Neck, breast and lung cancer,[58][59][60] and Thioredoxin reductase 1 being associated generally with most cancers.[61][62] Selenium also enhances the effects of tumor protein p53 which promotes DNA repair, apoptosis and inhibits proliferation.[63]

3.2

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).[64] 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).[65] Since there were only 13 cancer cases with toenail selenium levels less than 0.617μg/g included in this analysis,[65] this study represents a relatively selenium-replete United States population compared to patients who were in included in the previous meta-analysis.[64]

3.3

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)[63]

4.

Interactions with Aesthetics

4.1

Skin

Acne vulgaris is a chronic skin disease characterized by follicular hyperkeratinization, hormonally-mediated sebum overproduction, and chronic inflammation of the pilosebaceous unit.[66] It is believed that the damaging of lipids in the skin via free radicals is responsible for the inflammatory component of acne. Recent research has found that those who suffer from acne are unable to mitigate this damage efficiently because their antioxidant defense system is overwhelmed. [66]

Thus, based on this research, new studies have aimed to look at the effect of antioxidant supplementation on lesion counts.

A single-blind, placebo-controlled study that aimed to compare silymarin, n-acetylcysteine, and selenium to placebo in reducing lesion counts, found that after eight weeks of supplementation, there was a notable reduction in lesion count in all of the experimental groups, however, the reduction in lesion count was only statistically significant in the n-acetylcysteine and silymarin groups.[67]

Selenium supplementation is not very effective in reducing lesion counts in those who suffer from acne.

5.

Other Medical Conditions

5.1

Kashin-Beck disease

Kashin-Beck disease (KBD) is a endemic, degenerative osteoarthropathy, which is mainly distributed from northeastern to southwestern China. It is a disease characterized by enlarged and shortened fingers, arthritic pain, morning stiffness, deformed joints with limited motion in the extremities, excessive apoptosis, and dedifferentiation of chondrocytes.[68]

Several studies have found that KBD is prominent in areas that have soils, plants, animals, and humans that are deficient in selenium. One particular study found that in the Heilongjiang Province in China, the mean serum selenium concentration is roughly 20 ng/L, nearly one-tenth of the mean found in the United States.[69] Such studies have found that KBD is almost exclusive to selenium-poor belts like this. Other studies have found that the severity of KBD in a particular area is closely tied to the selenium content there.[69]

A meta-analysis conducted in 2015, examined twenty-six studies and found that there were significant differences in whole blood selenium levels, serum selenium levels, selenium levels in the hair, and urinary selenium levels between subjects with KBD and healthy controls, with the former having significantly lower levels of selenium on all indicated measures.[68]

Ever since selenium deficiency has been recognized as a possible factor in the onset of KBD, several interventional studies have aimed to look at the effects of selenium supplementation on the incidence of developing KBD, with the majority finding that supplementation reduced the risk of developing KBD.[69]

It is theorized that selenium’s role in preventing the incidence of KBD may be attributed to its ability to protect cartilage tissue from the effects of the T-2 toxin, a mycotoxin found in grains that has been hypothesized to contribute to the onset of KBD.[69]

This possible mechanism likely explains why one epidemiological interventional study found that the experimental groups that were given either selenium-iodine salt or rice from areas where there was no prevalence of KBD, were less likely to develop more X-ray lesions, and more likely to have higher metaphyseal repair rates than the control groups.[70]

KBD is exclusive to areas where foods are contaminated by the T-2 toxin and where there exists a deficiency of selenium. Supplementation of selenium can prevent the onset of KBD and help treat it.

5.2

Pre-eclampsia

Pre-eclampsia is a disease that affects pregnant women. It is known to be a leading cause of maternal mortality and morbidity worldwide. The disorder is diagnosed by high blood pressure and large amounts of protein in the urine on or after the 20th week of gestation. [71] In more severe cases of the disorder, there is the presence of systemic endothelial dysfunction, microangiopathy, elevated liver enzymes and red blood cell breakdown. [72]

An animal study found that pregnant rats that were fed selenium free-diets, prior to and following conception, were found to have significant increases in systolic blood pressure and proteinuria, when compared to pregnant rats fed normal selenium diets (239 μg/kg selenium) or high selenium diets (1000 μg/kg selenium). The rats that were deprived of selenium were also found to have significant decreases in liver glutathione peroxidase and thioredoxin peroxidase. [73]

Several observational studies have established that women who suffer from pre-eclampsia, have significantly lower levels of selenium plasma and lower toenail selenium concentrations. [74] [75] [76] [77] [78] Lower levels were also found to be significantly associated with more severe expression of the disorder. [78]

Serum soluble vascular endothelial growth factor receptor-1 (sFlt-1) is a tyrosine kinase protein and anti-angiogenic factor that is associated with the risk of pre-eclampsia.

A randomized controlled trial, with 230 primiparous pregnant women, found that supplementation of selenium (60 μg/d, as Se-enriched yeast) by the experimental group (n=115), from 12 to 14 weeks of gestation until delivery, resulted in significantly lower concentrations of sFlt-1 when compared to the control group (n=115). [79]

A double-blind, randomized, placebo-controlled trial found that pregnant women who were given 100 μg of selenium per day, from the first trimester until the day of delivery, were less likely to develop pre-eclampsia, however, this was not found to be significant (p > 0.05). [42]

A systematic review and meta-analysis, concluded from thirteen observational studies and three randomized control trials, that there exists an inverse association of blood selenium levels and the risk of pre-eclampsia. This review found that supplementation of selenium significantly reduces the incidence of pre-eclampsia (p=0.02). [80] However, the authors of one of the studies which this meta-analysis uses, have critiqued this interpretation because the authors of the meta-analysis failed to distinguish that there was a significant reduction in selenium concentrations in umbilical venous samples in the pre-eclampsia group. The authors also critiqued several other aspects of the review, stating that the errors would affect the results of the meta-analysis. [81]

Several observational studies have found that women with lower levels of selenium in their blood are more likely to develop pre-eclampsia than women with adequate levels of Selenium in their blood. Supplementation of selenium has been demonstrated in randomized controlled trials to lower the incidence of pre-eclampsia.

6.

Safety and Toxicity

6.1

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.[13]

6.2

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.[82] 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.[83] One study that examined DNA oxidation in rats suggests that high dietary intake of inorganic selenium may induce DNA damage in the liver.[84] 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.[82]

6.3

Human Toxicity

Toenails and fingernails damage[85] can occur after high ingestion of selenium. Nail samples are in fact frequently used to estimate selenium status.[86][87][88][89]

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.[90]

6.4

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.[91] 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.[92]

Human experimental trials have associated selenium intake with an increased risk for type 2 diabetes.[93] 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.[94] 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.[95] 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).[93]

6.5

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.[96]

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.[97]

A case of xanthotrichia, or yellow hair discoloration, has been reported with selenium sulfide 2.5% shampoo and dihydroxyacetone.[98]

References
2.^Yamashita Y, Yabu T, Yamashita MDiscovery of the strong antioxidant selenoneine in tuna and selenium redox metabolismWorld J Biol Chem.(2010 May)
4.^Navarro-Alarcon M, Cabrera-Vique CSelenium in food and the human body: a reviewSci Total Environ.(2008 Aug)
5.^Thomson CD, Chisholm A, McLachlan SK, Campbell JMBrazil nuts: an effective way to improve selenium statusAm J Clin Nutr.(2008 Feb)
6.^Pappa EC, Pappas AC, Surai PFSelenium content in selected foods from the Greek market and estimation of the daily intakeSci Total Environ.(2006 Dec 15)
7.^Barclay MNI, MacPherson A, Dixon JSelenium Content of a Range of UK FoodsJ Food Compost Anal.(1995 Dec)
8.^Papp LV, Lu J, Holmgren A, Khanna KKFrom selenium to selenoproteins: synthesis, identity, and their role in human healthAntioxid Redox Signal.(2007 Jul)
9.^Rayman MPSelenium and human healthLancet.(2012 Mar 31)
10.^Mustacich D, Powis GThioredoxin reductaseBiochem J.(2000 Feb 15)
11.^May JM, Cobb CE, Mendiratta S, Hill KE, Burk RFReduction of the ascorbyl free radical to ascorbate by thioredoxin reductaseJ Biol Chem.(1998 Sep 4)
13.^Letavayová L, Vlcková V, Brozmanová JSelenium: from cancer prevention to DNA damageToxicology.(2006 Oct 3)
15.^Roman M, Jitaru P, Barbante CSelenium biochemistry and its role for human healthMetallomics.(2014 Jan)
16.^Stadtman TCDiscoveries of vitamin B12 and selenium enzymesAnnu Rev Biochem.(2002)
17.^Moghadaszadeh B, Beggs AHSelenoproteins and their impact on human health through diverse physiological pathwaysPhysiology (Bethesda).(2006 Oct)
20.^Combs GF Jr, Clark LC, Turnbull BWAn analysis of cancer prevention by seleniumBiofactors.(2001)
22.^Reid ME, Stratton MS, Lillico AJ, Fakih M, Natarajan R, Clark LC, Marshall JRA report of high-dose selenium supplementation: response and toxicitiesJ Trace Elem Med Biol.(2004)
24.^Brozmanová J, Mániková D, Vlčková V, Chovanec MSelenium: a double-edged sword for defense and offence in cancerArch Toxicol.(2010 Dec)
28.^Stapleton SRSelenium: an insulin-mimeticCell Mol Life Sci.(2000 Dec)
31.^Ghosh R, Mukherjee B, Chatterjee MA novel effect of selenium on streptozotocin-induced diabetic miceDiabetes Res.(1994)
32.^Laclaustra M, Navas-Acien A, Stranges S, Ordovas JM, Guallar ESerum selenium concentrations and diabetes in U.S. adults: National Health and Nutrition Examination Survey (NHANES) 2003-2004Environ Health Perspect.(2009 Sep)
33.^Stranges S, Marshall JR, Natarajan R, Donahue RP, Trevisan M, Combs GF, Cappuccio FP, Ceriello A, Reid MEEffects of long-term selenium supplementation on the incidence of type 2 diabetes: a randomized trialAnn Intern Med.(2007 Aug 21)
38.^Kosanovic M, Jokanovic M, Jevremovic M, Dobric S, Bokonjic DMaternal and fetal cadmium and selenium status in normotensive and hypertensive pregnancyBiol Trace Elem Res.(2002 Nov)
41.^Tan M, Sheng L, Qian Y, Ge Y, Wang Y, Zhang H, Jiang M, Zhang GChanges of serum selenium in pregnant women with gestational diabetes mellitusBiol Trace Elem Res.(2001 Dec)
42.^Tara F, Maamouri G, Rayman MP, Ghayour-Mobarhan M, Sahebkar A, Yazarlu O, Ouladan S, Tavallaie S, Azimi-Nezhad M, Shakeri MT, Boskabadi H, Oladi M, Sangani MT, Razavi BS, Ferns GSelenium supplementation and the incidence of preeclampsia in pregnant Iranian women: a randomized, double-blind, placebo-controlled pilot trialTaiwan J Obstet Gynecol.(2010 Jun)
43.^Askari G, Iraj B, Salehi-Abargouei A, Fallah AA, Jafari TThe association between serum selenium and gestational diabetes mellitus: a systematic review and meta-analysisJ Trace Elem Med Biol.(2015 Jan)
44.^Shamberger RJ, Frost DVPossible protective effect of selenium against human cancerCan Med Assoc J.(1969 Apr 12)
47.^Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser JFree radicals and antioxidants in normal physiological functions and human diseaseInt J Biochem Cell Biol.(2007)
48.^Valko M, Rhodes CJ, Moncol J, Izakovic M, Mazur MFree radicals, metals and antioxidants in oxidative stress-induced cancerChem Biol Interact.(2006 Mar 10)
49.^Valko M, Izakovic M, Mazur M, Rhodes CJ, Telser JRole of oxygen radicals in DNA damage and cancer incidenceMol Cell Biochem.(2004 Nov)
50.^Hu YJ, Dolan ME, Bae R, Yee H, Roy M, Glickman R, Kiremidjian-Schumacher L, Diamond AMAllelic loss at the GPx-1 locus in cancer of the head and neckBiol Trace Elem Res.(2004 Nov)
51.^Ichimura Y, Habuchi T, Tsuchiya N, Wang L, Oyama C, Sato K, Nishiyama H, Ogawa O, Kato TIncreased risk of bladder cancer associated with a glutathione peroxidase 1 codon 198 variantJ Urol.(2004 Aug)
53.^Moscow JA, Schmidt L, Ingram DT, Gnarra J, Johnson B, Cowan KHLoss of heterozygosity of the human cytosolic glutathione peroxidase I gene in lung cancerCarcinogenesis.(1994 Dec)
54.^Al-Taie OH, Uceyler N, Eubner U, Jakob F, Mörk H, Scheurlen M, Brigelius-Flohe R, Schöttker K, Abel J, Thalheimer A, Katzenberger T, Illert B, Melcher R, Köhrle JExpression profiling and genetic alterations of the selenoproteins GI-GPx and SePP in colorectal carcinogenesisNutr Cancer.(2004)
55.^Mörk H, al-Taie OH, Bähr K, Zierer A, Beck C, Scheurlen M, Jakob F, Köhrle JInverse mRNA expression of the selenocysteine-containing proteins GI-GPx and SeP in colorectal adenomas compared with adjacent normal mucosaNutr Cancer.(2000)
57.^Méplan C, Nicol F, Burtle BT, Crosley LK, Arthur JR, Mathers JC, Hesketh JERelative abundance of selenoprotein P isoforms in human plasma depends on genotype, se intake, and cancer statusAntioxid Redox Signal.(2009 Nov)
58.^Hu YJ, Korotkov KV, Mehta R, Hatfield DL, Rotimi CN, Luke A, Prewitt TE, Cooper RS, Stock W, Vokes EE, Dolan ME, Gladyshev VN, Diamond AMDistribution and functional consequences of nucleotide polymorphisms in the 3'-untranslated region of the human Sep15 geneCancer Res.(2001 Mar 1)
59.^Kumaraswamy E, Malykh A, Korotkov KV, Kozyavkin S, Hu Y, Kwon SY, Moustafa ME, Carlson BA, Berry MJ, Lee BJ, Hatfield DL, Diamond AM, Gladyshev VNStructure-expression relationships of the 15-kDa selenoprotein gene. Possible role of the protein in cancer etiologyJ Biol Chem.(2000 Nov 10)
60.^Jablonska E, Gromadzinska J, Sobala W, Reszka E, Wasowicz WLung cancer risk associated with selenium status is modified in smoking individuals by Sep15 polymorphismEur J Nutr.(2008 Feb)
61.^Lincoln DT, Ali Emadi EM, Tonissen KF, Clarke FMThe thioredoxin-thioredoxin reductase system: over-expression in human cancerAnticancer Res.(2003 May-Jun)
63.^Babaknejad N, Sayehmiri F, Sayehmiri K, Rahimifar P, Bahrami S, Delpesheh A, Hemati F, Alizadeh SThe relationship between selenium levels and breast cancer: a systematic review and meta-analysisBiol Trace Elem Res.(2014 Jun)
64.^Hurst R, Hooper L, Norat T, Lau R, Aune D, Greenwood DC, Vieira R, Collings R, Harvey LJ, Sterne JA, Beynon R, Savovic J, Fairweather-Tait SJSelenium and prostate cancer: systematic review and meta-analysisAm J Clin Nutr.(2012 Jul)
65.^Kristal AR1, Darke AK, Morris JS, Tangen CM, Goodman PJ, Thompson IM, Meyskens FL Jr, Goodman GE, Minasian LM, Parnes HL, Lippman SM, Klein EABaseline Selenium Status and Effects of Selenium and Vitamin E Supplementation on Prostate Cancer RiskJ Natl Cancer Inst.(2014 Feb 22)
68.^Yang L, Zhao GH, Yu FF, Zhang RQ, Guo XSelenium and Iodine Levels in Subjects with Kashin-Beck Disease: a Meta-analysisBiol Trace Elem Res.(2016 Mar)
69.^Yao Y, Pei F, Kang PSelenium, iodine, and the relation with Kashin-Beck diseaseNutrition.(2011 Nov-Dec)
71.^Eiland E, Nzure C, Faulkner MPreeclampsia 2012J Pregnancy.(2012 Jun))
72.^Al-Jameil N, Aziz Khan F, Fareed Khan M, Tabassum HA brief overview of preeclampsiaJ Clin Med Res.(2014 Feb)
73.^Vanderlelie J, Venardos K, Perkins AVSelenium deficiency as a model of experimental pre-eclampsia in ratsReproduction.(2004 Nov)
74.^Vanderlelie J, Perkins AVSelenium and preeclampsia: A global perspectivePregnancy Hypertens.(2011 Jul-Oct)
75.^Mistry HD, Wilson V, Ramsay MM, Symonds ME, Broughton Pipkin FReduced selenium concentrations and glutathione peroxidase activity in preeclamptic pregnanciesHypertension.(2008 Nov)
77.^Maleki A, Fard MK, Zadeh DH, Mamegani MA, Abasaizadeh S, Mazloomzadeh SThe relationship between plasma level of Se and preeclampsiaHypertens Pregnancy.(2011)
79.^Rayman MP, Searle E, Kelly L, Johnsen S, Bodman-Smith K, Bath SC, Mao J, Redman CWEffect of selenium on markers of risk of pre-eclampsia in UK pregnant women: a randomised, controlled pilot trialBr J Nutr.(2014 Jul 14)
80.^Xu M, Guo D, Gu H, Zhang L, Lv SSelenium and Preeclampsia: a Systematic Review and Meta-analysisBiol Trace Elem Res.(2016 Jun)
81.^Mistry HD, Broughton Pipkin F, Kurlak LOLetter Regarding: Selenium and Preeclampsia: A Systemic Review and Meta-AnalysisBiol Trace Elem Res.(2016 May)
82.^Valdiglesias V, Pásaro E, Méndez J, Laffon BIn vitro evaluation of selenium genotoxic, cytotoxic, and protective effects: a reviewArch Toxicol.(2010 May)
83.^Biswas S, Talukder G, Sharma AChromosome damage induced by selenium salts in human peripheral lymphocytesToxicol In Vitro.(2000 Oct)
84.^Wycherly BJ, Moak MA, Christensen MJHigh dietary intake of sodium selenite induces oxidative DNA damage in rat liverNutr Cancer.(2004)
86.^Steven Morris J, Stampfer MJ, Willett WDietary selenium in humans toenails as an indicatorBiol Trace Elem Res.(1983 Dec)
87.^Hunter DJ, Morris JS, Chute CG, Kushner E, Colditz GA, Stampfer MJ, Speizer FE, Willett WCPredictors of selenium concentration in human toenailsAm J Epidemiol.(1990 Jul)
88.^van den Brandt PA, Goldbohm RA, van't Veer P, Bode P, Hermus RJ, Sturmans FPredictors of toenail selenium levels in men and womenCancer Epidemiol Biomarkers Prev.(1993 Mar-Apr)
89.^Longnecker MP, Stampfer MJ, Morris JS, Spate V, Baskett C, Mason M, Willett WCA 1-y trial of the effect of high-selenium bread on selenium concentrations in blood and toenailsAm J Clin Nutr.(1993 Mar)
90.^Reid ME, Stratton MS, Lillico AJ, Fakih M, Natarajan R, Clark LC, Marshall JRA report of high-dose selenium supplementation: response and toxicitiesJ Trace Elem Med Biol.(2004)
91.^Vinceti M, Wei ET, Malagoli C, Bergomi M, Vivoli GAdverse health effects of selenium in humansRev Environ Health.(2001 Jul-Sep)
92.^Winther KH, Bonnema SJ, Cold F, Debrabant B, Nybo M, Cold S, Hegedüs LDoes selenium supplementation affect thyroid function? Results from a randomized, controlled, double-blinded trial in a Danish populationEur J Endocrinol.(2015 Jun)
93.^Stranges S, Marshall JR, Natarajan R, Donahue RP, Trevisan M, Combs GF, Cappuccio FP, Ceriello A, Reid MEEffects of long-term selenium supplementation on the incidence of type 2 diabetes: a randomized trialAnn Intern Med.(2007 Aug 21)
94.^Stranges S, Sieri S, Vinceti M, Grioni S, Guallar E, Laclaustra M, Muti P, Berrino F, Krogh VA prospective study of dietary selenium intake and risk of type 2 diabetesBMC Public Health.(2010 Sep 21)
96.^MacFarquhar JK, Broussard DL, Melstrom P, Hutchinson R, Wolkin A, Martin C, Burk RF, Dunn JR, Green AL, Hammond R, Schaffner W, Jones TFAcute selenium toxicity associated with a dietary supplementArch Intern Med.(2010 Feb 8)
98.^Prevost N, English JC 3rdXanthotrichia (yellow hair) due to selenium sulfide and dihydroxyacetoneJ Drugs Dermatol.(2008 Jul)