Some of the most common ones include:. Of course, it's worth noting that some of these overlap with symptoms of thyroid disease. Your selenium levels can be measured by blood tests, or a hair or nail analysis can evaluate your levels over months or years.
Though this isn't a routine test if you have thyroid disease it's usually performed only if a selenium deficiency or toxicity is suspected , you or your healthcare provider may want to check your levels at some point to make sure they're within normal limits.
It's helpful to know what your goal should be, particularly if you have any of the symptoms mentioned above. The Food and Nutrition Board FNB at the Institute of Medicine of the National Academies recommends that healthy people age 14 years and older get 55 mcg of selenium daily from all sources. The recommendation goes up to 60 mcg per day if you're pregnant and 70 mcg per day if you're breastfeeding. You can safely take in up to mcg per day between food and supplements. There are two forms of selenium: organic selenomethionine and selenocysteine and inorganic selenate and selenite.
Foods that are good sources of selenium include:. Selenium can be found in supplements either alone or in combination formulas in multivitamins. Due to its overall effects in the body, research is being conducted on whether or not selenium supplementation may affect glucose metabolism, as well as help prevent cancer, thyroid disease, heart disease, and the cognitive decline that occurs as we age.
While low levels of selenium are a concern, high levels can result in selenium toxicity over time. In particular, be careful with Brazil nuts; because they contain so much selenium—as much as 90 mcg per nut—you can actually trigger selenium toxicity by eating them too often.
Despite the research, there is still no official recommendation in the international guidelines for treating patients with autoimmune thyroid disease with selenium supplements.
For those with thyroid disease and low selenium levels, supplementation can be beneficial, but for those whose selenium levels are normal to high, supplementation could potentially result in toxicity.
Before you consider adding handfuls of Brazil nuts to your diet or taking selenium supplements, you should have your selenium levels evaluated by your healthcare provider. They can then offer guidance on whether you might benefit from increasing your dietary selenium or adding supplements. Keep in mind that if you choose to supplement with selenium, you should calculate your dietary intake, and be sure to count any selenium in multivitamins and supplements so that your daily intake doesn't exceed the mcg daily recommended upper intake level.
Losing weight with thyroid disease can be a struggle. These patients were assigned at random to methimazole, 10 or 20 mg depending on thyroid hormone level, with either selenium mg daily or placebo. Patients were examined by one investigator who was not aware of the assignments. Selenium was continued until week 24, when it was discontinued. Methimazole doses were evaluated and adjusted at weeks 4,12 and Labs were drawn at weeks 4, 12 and There were 35 patients in each group.
Selenium levels in the body depend on the characteristics of the population and its diet, geographic area, and soil composition. In the thyroid, selenium is required for the antioxidant function and for the metabolism of thyroid hormones.
Regarding thyroid pathology, selenium intake has been particularly associated with autoimmune disorders. The literature suggests that selenium supplementation of patients with autoimmune thyroiditis is associated with a reduction in antithyroperoxidase antibody levels, improved thyroid ultrasound features, and improved quality of life. Selenium supplementation in Graves' orbitopathy is associated with an improvement of quality of life and eye involvement, as well as delayed progression of ocular disorders.
The organic form of selenium seems to be the preferable formulation for supplementation or treatment. Maintaining a physiological concentration of selenium is a prerequisite to prevent thyroid disease and preserve overall health. Supplementation with the organic form is more effective, and patients with autoimmune thyroiditis seem to have benefits in immunological mechanisms. Selenium supplementation proved to be clinically beneficial in patients with mild to moderate Graves' orbitopathy.
Selenium levels in the body are dependent on the population's characteristics and its diet and geographical area mainly on the soil composition [ 1 , 2 ]. This micronutrient has been studied over the last years, and scientific reports have revealed its crucial role in the maintenance of immune-endocrine function, metabolism, and cellular homeostasis. The thyroid gland is characterized by a high concentration of selenium, which is incorporated into selenoproteins.
Some of these selenoproteins have an important antioxidant activity, contributing to the antioxidant defense in the thyroid by removing oxygen free radicals generated during the production of thyroid hormones. Being incorporated into iodothyronine deiodinases, selenium plays also an essential role in the metabolism of thyroid hormones.
Selenium can be available both in organic compounds selenomethionine and selenocysteine and in inorganic compounds selenite and selenate [ 1 ]. Considering that the organic form has better absorption, it seems to be the preferable formulation for supplementation or treatment [ 3 ]. Selenomethionine is found in vegetable sources especially cereals , selenium yeast, and other selenium supplements [ 1 ]. Selenium is incorporated into body proteins in place of methionine; therefore, supplements containing selenomethionine are those which have more bioavailable selenium.
In turn, selenocysteine, a selenium analogue of the amino acid cysteine, is found mainly in animal foods. The inorganic forms selenate and selenite are the components of dietary supplements. By mechanisms not yet completely clarified, reduced selenium levels are found in smokers and with advanced age; selenium depletion has also been associated with the consumption of eggs, white rice, alcohol, and coffee [ 5 ].
In general, no difference exists in the recommended dietary allowance of selenium between men and women [ 8 ]. Even though the daily intake of selenium in Europe does not reach the recommended levels, the opposite spectrum—excess of selenium in the body with toxic effects—can also occur in rare occasions.
This rare situation was mainly reported by epidemiological studies in populations living in areas with high selenium concentration in the soil and can result from acute poisoning or prolonged exposure to high levels of selenium [ 9 ].
Selenium toxicity symptoms include nausea, vomiting, abdominal pain, diarrhea, hair loss, brittle nails, peripheral neuropathy, and the characteristic smell of garlic in sweat and breath.
MacFarquhar et al. After the supplement was suspended, serum and urine selenium concentrations decreased gradually with time and returned to normal by weeks 1 to 2 for urine and started to normalize at week 6 for serum. The level of selenium in the plasma depends directly on the selenium intake and correlates well with the organic availability of this nutrient. In order to include original studies, 5 publications were added by cross-reference.
At the end, we selected 69 publications for final assessment. The vital role of selenium in thyroid function began to be questioned because of a condition described in Zaire Democratic Republic of the Congo , known as myxedematous endemic cretinism, which was characterized by a deficit of iodine and selenium, hypothyroidism, myxedema, developmental problems, and intellectual disability [ 11 ].
From that moment, more studies were conducted to investigate the role of this nutrient in the thyroid. In fact, it was found that selenium deficiency decreases the synthesis of thyroid hormones, as it decreases the function of selenoproteins, in particular iodothyronine deiodinases DIOs , which are responsible for the conversion of T4 to T3.
This decreased production of thyroid hormones leads to the stimulation of the hypothalamic-pituitary axis due to the lack of negative feedback control, increasing TSH production. TSH stimulates the DIOs to convert T4 to T3 [ 12 ], with consequent production of hydrogen peroxide, which is not adequately removed by less active glutathione peroxidases GPx and accumulates itself in the thyroid tissue causing thyrocyte damage with subsequent fibrosis.
The thyroid gland is characterized by a high tissue concentration of selenium 0. Since it is incorporated into selenoproteins, which have an important antioxidant activity, selenium contributes to the antioxidant defense in the thyroid, by removing oxygen free radicals generated during the production of thyroid hormones [ 14 , 15 ].
Being incorporated into iodothyronine deiodinases, selenium plays also an essential role in the metabolism of thyroid hormones [ 1 , 16 ]. So far, about 25 selenoproteins were described [ 17 ]. The iodothyronine deiodinases control the thyroid hormone turnover and catalyze the conversion of T4 to its biologically active form, T3, through the removal of an iodine atom from the external ring [ 18 ]. They can also inactivate thyroid hormones by the removal of an iodine atom of the inner ring, with the conversion of T4 to reverse T3 rT3 , the inactive metabolite.
Glutathione peroxidases are responsible for glandular protection, since they remove the excess of oxygen free radicals produced during normal synthesis of the thyroid hormones [ 19 , 20 ]. Main groups of selenoproteins found in the thyroid gland and their function [ 1 , 2 ]. Selenoprotein P is the main source of selenium in plasma; therefore, it constitutes the main transporter and distributor of this micronutrient [ 21 ]. It is produced by hepatocytes and has a crucial role in selenium homeostasis, since it ensures selenium retention in the body and promotes its distribution to the liver and extrahepatic tissues, including its transportation to the brain in conditions associated with nutrient deficit [ 22 ].
However, it seems that in the case of selenium deprivation and in the absence of this transporter, endocrine organs and the brain are preferentially supplied.
The thyroid gland may be able to accumulate, retain, and recycle selenium efficiently, even in the absence of selenoprotein P [ 23 ]. Several studies have focused on the importance of selenium in thyroid function and autoimmune processes, aiming at understanding if supplementation of this micronutrient may have an impact on the evolution of thyroid disease. In fact, the effect of selenium supplementation on the evolution of Hashimoto's thyroiditis, a condition characterized by the presence of antithyroperoxidase and antithyroglobulin antibodies TPOAb and TgAb, resp.
Gartner et al. Patients were divided into two groups: one group that was supplemented with sodium selenite and the other group that just kept therapy with levothyroxine. In this trial, patients receiving selenium supplementation reported better well-being compared with the placebo group. On the other hand, Duntas et al. The aim of this study was to assess the effect of the treatment with selenium in patients with autoimmune thyroiditis through the impact on the level of TPOAb and TgAb after 3 and 6 months.
Turker et al. Furthermore, they also found that the suppression rate decreases with time. Adapted from [ 26 ]. A prospective study by Nacamulli et al. Esposito D. The authors also measure CXCL10 levels to evaluate the possibility of a modulation of the autoimmune mechanism by selenomethionine.
The authors conclude that TSH, the levels of thyroid hormones and TPOAb, thyroid echogenicity, and CXCL10 concentration did not show a statistical difference at baseline and after 3 and 6 months between the control and the supplemented group. In fact, they observed an increase in FT3 levels after 3 and 6 months and a decrease in FT4 levels after 3 months in the group supplemented with selenium versus baseline levels; in the control group, the authors observed a decrease in FT3 after 3 and 6 months when compared to baseline.
In pregnancy, supplementation of selenium appears to influence thyroid function and may be beneficial. Mao et al. They found that the group supplemented with selenium did not show a significant decrease in thyroid peroxidase antibodies, though a minor change of thyroid function without clear clinical meaning occurred.
Negro et al. It is important to note that, in most of the studies that focus on the relevance of selenium to thyroid disease, the authors did not measure selenium concentration prior to, during, and after supplementation.
Furthermore, the most frequent primary outcome measurement was thyroid Ab levels, so at the present time, there is no recommendation for selenium supplementation in patients with autoimmune thyroiditis. Recently, some clinical trials were designed to answer some of these still open questions. Unlike some other studies about this issue, in this trial, plasma selenium concentrations will be measured periodically to assess selenium intake.
This is also the first study that will evaluate selenium's mechanisms of action in autoimmune thyroiditis and the effect of selenium supplementation on LT4 dosage. Selenium is inserted as selenocysteine Secys , the 21st amino acid in the genetic code, into selenoproteins by a complex cotranslational mechanism encoded by the opal stop codon UGA in mRNAs; the Secys insertion sequence, which recruits the Secys-binding protein 2 SBP2 , appears to be a key factor in this process 5 — 7.
The translation process requires an exclusive tRNA, known as tRNA [Ser]sec , whose selenium-induced methylated isoform constitutes a regulating mechanism in the synthesis of selenoproteins 8 , 9.
Some selenoproteins of the human selenoproteome display multiple genes performing similar functions. The main selenoprotein families are the glutathione peroxidases GPxs; seven genes , the thioredoxin reductases TRxs; three genes and the iodothyronine deiodinases DIs; three genes 10 — The GPxs, which possess oxidoreductase functions, protect the cell from oxidative stress.
The TRxs form a cellular redox system, existing in many organisms, which is essential for cell development and proliferation. The selenoproteins expressed in the thyroid and their functions are displayed in Table 1. It may thus be hypothesized that the essential micronutrient selenium, in the form of Secys, modulates redox-sensitive signaling pathways and thereby potentially modifies selenoprotein gene expression.
These findings have aroused growing interest of the scientific community in this multifaceted element. In this context, whereas selenium administration for cancer chemoprevention produced questionable results, those of selenium supplementation in patients with autoimmune thyroid disease have been more encouraging. This review comprises an in-depth discussion of the link between selenium and thyroid function; it provides a critical analysis of the data contained in recent studies, an update and evaluation of current knowledge with regard to the mechanisms of action of selenium, and reflections on the prospects for selenium supplementation in thyroid pathology.
Selenium, the distribution of which in nature varies widely depending on soils and geographic areas, reaches the human food chain through ingestion of edible plants, with the result that selenium levels in food and in humans normally reflect selenium soil content, and vice versa This natural variability is reflected, for example, in the fact that the soil of central and southern European countries is generally poor in selenium content, resulting in mild regional selenopenia, whereas in most North American regions it is abundant.
Severe selenopenia, as observed in large areas of central Asia, contributes to the manifestation of Kashin-Beck osteochondropathy and of Keshan disease, a severe cardiomyopathy characterized by fulminant heart failure Foods that are particularly rich in selenium are shellfish, crabs, kidney, liver, and Brazil nuts.
Although diet is the main source of selenium intake, improvement of dietary intake depends on characterization of selenium bioavailability from various food sources The chief forms of selenium in plants are selenate, which is directly translocated from the soil, and selenium-containing proteins in which selenomethionine SeMet and Secys replace methionine and cysteine, respectively.
Both SeMet and Secys are synthesized via complex biosynthetic pathways The incorporation of SeMet into the body proteins by substitution of methionine is a unique property of SeMet providing a means of selenium storage in tissues; this feature makes it particularly beneficial as a form of nutritional supplementation Selenium supplements are recommended in severely selenopenic areas, and various forms of selenium have been applied in interventional trials.
In contrast to the inorganic form, SeMet and yeast are capable, due to their binding to proteins, of raising serum selenium levels in a dose-dependent manner irrespective of individual nutritional selenium status Two soluble selenoproteins, GPx-3 and particularly selenoprotein P SePP , the latter registering a better response to SeMet administration, account for blood selenium In experimental studies, deletion of the SePP gene results in a dramatic fall of selenium in many tissues SePP produced in the liver transports selenium to the peripheral organs, whereas suppression of SePP synthesis leads to increased selenium urinary excretion and decreased whole-body selenium SePP determination is thus considered the most reliable biomarker of selenium status and may be used to ensure both efficacy of treatment and patient compliance When used as nutritional supplements, both SeMet and selenite are metabolized in volatile selenium excretion products in the caecum and the colon It should, however, be emphasized that the diagnoses of diabetes were self-reported and that, in contrast to the European trials, the study took place in an area with a high basal selenium content.
In , it was found not only that selenium is abundantly present in the thyroid but also that this organ contains more selenium per gram of tissue than any other organ Interestingly, under conditions of selenium restriction and genetic inactivation of SePP, the selenium transporter, the thyroid retains its selenium content quantitatively to an even higher degree than does the brain 19 , This points to a hierarchical system with the thyroid protected to ensure maintenance of selenium content, presumably via locally produced SePP, in situations of limited supply 5 , 19 , This is the pathway via which selenium conveys the biochemical properties of DIs that, by removing specific iodine moieties from thyroid hormones, regulate the conversion of T 4 to T 3 and rT 3 5 , The fact that within this deiodination process Secys has a dominant role underlines the dependency of DI activity on selenium levels.
Three of seven siblings were identified with symptoms of abnormal thyroid hormone metabolism due to deficiency of selenoprotein biosynthesis. Consecutive studies aiming to improve selenoprotein biosynthesis by supplementing the diet of these siblings with various doses of organic and inorganic selenium failed to ameliorate the thyroid function, despite an increase in selenium and SePP levels by SeMet and selenite administration, respectively It was concluded that the rise of selenium concentration via SeMet supplementation in SBP2-deficient patients is insufficient to restitute the selenoprotein synthesis, suggesting that selenium was not a limiting factor in these patients Because it was observed that the molecule contains its functional domains, it may possibly be further synthesized downstream, which would explain the relatively mild clinical profile characterized by growth retardation, high T 4 , low T 3 , normal TSH, and normal selenium levels.
Severe endemic iodine deficiency leads to a type of mental retardation called endemic cretinism, of which there are two distinct forms: neurological and myxedematous cretinism. Severe selenium deficiency, when combined with severe endemic iodine deficiency, has been found to be determinant in the pathogenesis of endemic myxedematous cretinism, as has been reported in northern Zaire; this finding suggests yet another link between selenium and thyroid pathology 39 — Selenium deficiency results in reduction of selenoprotein GPx activity, which detoxifies hydrogen peroxide H 2 O 2 and lipid peroxidation.
In iodine deficiency states, the high TSH stimulates the production in thyroid cells of H 2 O 2 , which can induce thyroid gland destruction and fibrosis, in turn impeding cell proliferation and repair 42 — The deficient removal of the toxic H 2 O 2 by insufficient GPx activity has thus been attributed to selenium deficit.
These observations have been corroborated by the results of other studies demonstrating that selenium supplementation reduced serum T 4 , free T 4 , and rT 3 levels after 2 months of treatment As a result, the lack of selenium enhances the availability of H 2 O 2 , which is essential for thyroid hormone production, whereas reduced type I iodothyronine deiodinase activity results in higher T 4 and lower T 3 levels. The past two decades have seen the ever increasing awareness of the essential role of selenium in the regulation of thyroid function as well as its importance in thyroid pathogenesis, as evidenced by the finding that severe selenium deficiency contributes to the manifestation of myxedematous cretinism.
These observations support a conclusive link between the thyroid and selenium. Autoimmune thyroiditis AIT , the prototype of autoimmune diseases, is characterized by T-cell-mediated autoimmune attacks often resulting in thyroid cell destruction. On the basis of the link described above between selenium and the thyroid, several studies applying organic and inorganic selenium compounds were undertaken in patients with AIT in areas with low to borderline low selenium content.
The first prospective placebo-controlled clinical study with selenium in AIT was conducted in the selenium-deficient area of Bavaria in southern Germany This was the first study showing that protracted administration of a stable physiological dose of inorganic selenium exerts a positive impact on the course of AIT. Patients who received Na 2 SeO 3 exhibited better thyroid echogenicity after 6 months of treatment.
This is consistent with a recent large French study in which, in a population aged 35—60 yr, selenium was found to be inversely related to thyroid volume, another tentative finding being that selenium might have a protective effect against goiter in women In none of these studies was selenium found to affect thyroid hormone synthesis.
This is in agreement with previous results showing that selenium treatment, even in individuals with a minimal thyroid hormone synthesis defect—as indicated by a positive iodine-perchlorate discharge test—does not modify thyroid hormone levels These interventional studies were carried out in a group of euthyroid patients with AIT under treatment with l -T 4 ; they composed a fairly homogeneous study group, marked by considerable variation with regard to local availability of selenium and iodine.
Their risk is also higher for progressive development of hypothyroidism during gestation Moreover, women who had had an abortion had significantly lower selenium hair content than controls Selenium concentration varies during pregnancy but tends to be lower in the third trimester, indicating that women with low selenium intake may be exposed to high risk during pregnancy 58 , It can be inferred that determination of selenium status and selenium supplementation could be of importance in the management of thyroid disease in pregnancy.
Within this framework, a study performed in Italy supplementing SeMet in pregnant women with AIT resulted in lower incidence of PPT and of permanent hypothyroidism by comparison with two other study groups, one placebo and one control The women treated with selenium showed lower anti-TPO levels, whereas they displayed improved ultrasound morphology when compared with controls.
It should be emphasized that the reduction in anti-TPO was greater in the SeMet group than the decreased titer induced by the gestational immunosuppression in the control group. As has rightly been stated in a recent commentary 61 , this study not only provides further evidence in favor of screening thyroid function during pregnancy but, in the event that the results are conclusively confirmed, additionally offers a potentially preventive approach for PPT.
A summary of prospective studies on selenium supplementation in AIT and their level of evidence, based on the strength of each study, is presented in Table 2. The grading scheme recommended by the Grading of Recommendations, Assessments, Development and Evaluation Working Groups was employed to rate evidence of efficiency 65 , classifying studies into four categories: A strong ; B moderate—further research recommended to enhance the weight of evidence ; C low ; and D very low—any estimate is tentative.
Description and level of evidence of the studies showing an effect via selenium supplementation in patients with AIT. Despite a lack of evidence at the highest level A, the findings of the aforementioned studies demonstrate that both SeMet and sodium selenite are effective in slowing the activity of AIT, as reflected by the progressive reduction of anti-TPO and improvement of ultrasound results.
The proposed mechanisms in the reported studies are based on the reduced ROS damage via enhanced expression of the GPxs and improvement of redox status in the thyrocyte through increasing activity of TRxs; the latter may play a more crucial role than previously assumed in the regulation of intrathyroid selenium.
Furthermore, thyroid gland functioning is sustained via enhanced DI expression by means of selenium administration. The observation that positive effects of selenium supplementation have been registered in regions of both selenium deficiency and sufficiency lends support to the hypothesis that the result comes about via pharmacological actions, rather than a correction of selenium deficiency.
Nonetheless, considerable uncertainty remains as to whether the observed differences in anti-TPO reduction are due to the different methodologies applied, the duration of treatment, individual response to selenium supplementation, geographical iodine content, or some combination of the above.
Because many patients did not respond, a more individualized approach would be advisable, which could be accomplished via analysis of SePP levels and stratification of the patients according to the degree of their autoimmune disease.
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