Selenium was discovered in 1817 in Gripsholm, a Swedish city, by a Swedish chemist Jacob Berzelius. Selenium is a commonly occurring element in nature. It can be found in the atmosphere, lithosphere, biosphere, and hydrosphere of the Earth. The amount of this element present in nature and in the human organism is very diverse depending on the geographic region and diet.

The total amount of selenium in a human organism is ~3–20 mg.

Selenium is a trace element that is naturally present in many foods, added to others, and available as a dietary supplement. Selenium, which is nutritionally essential for humans, is a constituent of more than two dozen selenoproteins that play critical roles in reproduction, thyroid hormone metabolism, DNA synthesis, and protection from oxidative damage and infection.

Selenium is incorporated into selenoproteins that have a wide range of pleiotropic effects, ranging from anti oxidant and anti-inflammatory effects to the production of active thyroid hormone. In the past 10 years, the discovery of disease associated polymorphisms in seleno protein genes has drawn attention to the relevance of selenoproteins to health. The essential biological importance of selenium is associated with its occurrence in proteins and enzymes. Several selenium-dependent enzymes in which the active center contains selenium in the form of selenocysteine moiety have been identified. The best-characterized selenoenzymes commonly occurring in mammals are glutathione peroxidase, selenoprotein P, and thyroxine 5-deiodinase. Glutathione peroxidase and selenoprotein P catalyze redox reactions. Other enzymatic proteins that are involved in important functions of the organisms are formate dehydrogenase, nicotinic acid hydroxylase, glycine reductase, thiolase, and xanthine dehydrogenase.

Low selenium status has been associated with increased risk of mortality, poor immune function, and cognitive decline.

Higher selenium status or selenium supplementation has antiviral effects, is essential for successful male and female reproduction, and reduces the risk of autoimmune thyroid disease. Prospective studies have generally shown some benefit of higher selenium status on the risk of prostate, lung, colorectal, and bladder cancers, but findings from trials have been mixed, which probably emphasises the fact that supplementation will confer benefit only if intake of a nutrient is inadequate.

The eff ects of selenium on human health are multiple and complex, necessitating further research to optimize the benefits and reduce the risks of this potent trace mineral. 1, Reference: Marek Kieliszek; Selenium–Fascinating Microelement, Properties and Sources in Food; Molecules. 2019 Apr; 24(7): 1298. Published online 2019 Apr 3. doi: 10.3390/molecules24071298 2, Reference: Sunde RA. Selenium. In: Ross AC, Caballero B, Cousins RJ, Tucker KL, Ziegler TR, eds. Modern Nutrition in Health and Disease. 11th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2012:225-37 3 Reference: Rayman, M. P. (2012). Selenium and human health. The Lancet, 379(9822), 1256–1268. doi:10.1016/s0140-6736(11)61452-9

Prolonged selenium deficiency in human organism leads to serious diseases. Deficiency of this element adversely affects the functioning of the cardiovascular system and can be a direct cause of myocardial infarction. It is associated with endemic diseases: Keshan and Kashin-Beck.

As a result of epidemiological studies, it was concluded that moderate deficiency of selenium in daily diet affects the development of diseases resulting from reduced immunity. Selenium deficiency in daily diet can adversely affect the functioning of the nervous system. Among individuals with selenium deficiency, development of depression, or intensification of anxiety is observed; Alzheimer’s disease is also developed. This element is considered to be crucial in reducing the virulence of HIV and in decreasing the progression to full-blown AIDS. Selenium deficiency in pregnant women negatively affects the development of the embryo. Excess of selenium can be toxic to the organism. Acute selenium poisoning is rarely observed. The accurate determination of harmful doses of selenium is difficult because of the occurrence of various chemical forms of this element. A toxic effect on the organism can be exerted by both organic and inorganic forms of selenium. Toxicity of selenium (depends on the dose) is associated with competitive inhibition between selenium and sulfur, leading to the onset of sulfur metabolism (transformation). Selenium may substitute sulfur in amino acids (cysteine and methionine), whereas the inorganic compounds displace sulfur during the synthesis of mercapturic acids and during the reaction of selenites with thiol groups. 2 Reference: Marek Kieliszek; Selenium–Fascinating Microelement, Properties and Sources in Food; Molecules. 2019 Apr; 24(7): 1298. Published online 2019 Apr 3. doi: 10.3390/molecules24071298 

Groups at Risk of Selenium Inadequacy

Selenium deficiency is rare and selenium deficiency in isolation rarely causes overt illness. The following groups are among those most likely to have inadequate intakes of selenium.

1. People living in selenium-deficient regions

People in some countries whose diet consists primarily of vegetables grown in low-selenium areas are at risk of deficiency. The lowest selenium intakes in the world are in certain parts of China, where large proportions of the population have a primarily vegetarian diet and soil selenium levels are very low. Average selenium intakes are also low in some European countries, especially among populations consuming vegan diets. Although intakes in New Zealand were low in the past, they rose after the country increased its importation of high-selenium wheat.

2. People undergoing kidney dialysis

Selenium levels are significantly lower in patients undergoing long-term hemodialysis than in healthy individuals. Hemodialysis removes some selenium from the blood. In addition, hemodialysis patients are at risk of low dietary selenium intakes due to anorexia resulting from uremia and dietary restrictions. Although selenium supplementation increases blood levels in hemodialysis patients, more evidence is needed to determine whether supplements have beneficial clinical effects in these individuals.

3. People living with HIV

Selenium levels are often low in people living with HIV, possibly because of inadequate intakes (especially in developing countries), excessive losses due to diarrhea, and malabsorption. Observational studies have found an association between lower selenium concentrations in people with HIV and an increased risk of cardiomyopathy, death, and, in pregnant women, HIV transmission to offspring and early death of offspring. 3 Reference:https://ods.od.nih.gov/factsheets/Selenium-HealthProfessional/

Selenium in the diet. Adults who are not found or established to be deficient in selenium are normally required 55 mcg (micrograms) for men and for women, but for pregnant women 60 mcg of selenium per day

Reference Atsauce: https://ods.od.nih.gov/factsheets/Selenium-HealthProfessional/ 

Selenium can interact with certain medications, and some medications can have an adverse effect on selenium levels. One example is provided below. Individuals taking this and other medications on a regular basis should discuss their selenium status with their healthcare providers.

Cisplatin

Cisplatin, an inorganic platinum chemotherapy agent, is used to treat ovarian, bladder, lung, and other cancers. Cisplatin can reduce selenium levels in hair and serum but whether these reductions have a clinically significant impact is not known. Some small studies have shown that selenium supplementation can reduce cisplatin’s toxicity but the authors of a Cochrane review concluded that the evidence that selenium supplementation alleviates the side effects of chemotherapy is insufficient.

Health Risks from Excessive Selenium

Chronically high intakes of the organic and inorganic forms of selenium have similar effects. Early indicators of excess intake are a garlic odor in the breath and a metallic taste in the mouth. The most common clinical signs of chronically high selenium intakes, or selenosis, are hair and nail loss or brittleness. Other symptoms include lesions of the skin and nervous system, nausea, diarrhea, skin rashes, mottled teeth, fatigue, irritability, and nervous system abnormalities. 1 Reference:https://ods.od.nih.gov/factsheets/Selenium-HealthProfessional/

There are a number of indications that selenium is important to the brain: during selenium depletion the brain receives a priority supply; the turnover rate of some neurotransmitters is altered in selenium deficiency; supplementation with selenium reduced intractable epileptic seizures in children; low plasma selenium concentrations in the elderly were significantly associated with senility and accelerated cognitive decline and brain selenium concentration in Alzheimer’s patients was only 60% of that in controls. Furthermore, the brain is deficient in catalase, thus peroxidation products such as hydrogen peroxide and primary peroxides must be removed by the antioxidant selenoenzymes.

A beneficial effect of selenium status on mood has been shown, at least when selenium status is “marginal”. In three studies, low selenium status was associated with a significantly greater incidence of depression and other negative mood states such as anxiety, confusion, and hostility.

Serum selenium concentrations decline with age. Marginal or deficient selenium concentrations might be associated with age-related declines in brain function, possibly due to decreases in selenium’s antioxidant activity.

Selenium, incorporated into specific seleno-enzymes, is essential to proper thyroid function and protect cells from oxidative damage induced by H2O2 during thyroid hormone synthesis while study has shown that oxidative stress markers are associated with cognitive decline in a highly cognitive functioning population. 

Selenium-dependent glutathione reductase and selenoproteins are important for their antioxidant activity, which is vital for the protection of the organism. Selenium affects the metabolic pathways by changing the activity of selenoproteins and plays a role in cellular defense against oxidative stress. Selenium concentration regulates the expression of selenoproteins. Different selenium concentrations may affect immunity and energy metabolism diversely. Increased levels of stress biomarkers have been reported in depression in recent studies, and this suggests that oxidative stress may be an important factor in the pathogenesis of depression. Selenium may have a protective role against anxiety and depression, possibly due to its protective effect on oxidative stress.

Lastly, selenium could potentially exert antidepressant effects through its modulatory role in various neurotransmitter systems. Selenium has been found to have significant modulatory effects on the dopaminergic, serotonergic, and noradrenergic systems, which are all involved in the physiopathology of depression and other psychiatric illnesses.

References: 1 Reference: Rayman, M. P. (2000). The importance of selenium to human health. The Lancet, 356(9225), 233–241. doi:10.1016/s0140-6736(00)02490-9 2 Reference: Berr, C., Balansard, B., Arnaud, J., Roussel, A.-M., & Alpérovitch, A. (2000). Cognitive Decline Is Associated with Systemic Oxidative Stress: The EVA Study. Journal of the American Geriatrics Society, 48(10), 1285–1291. doi:10.1111/j.1532-5415.2000.tb02603.x 3 Reference: Ruggeri, R. M., D’Ascola, A., Vicchio, T. M., Campo, S., Gianì, F., Giovinazzo, S., … Trimarchi, F. (2019). Selenium exerts protective effects against oxidative stress and cell damage in human thyrocytes and fibroblasts. Endocrine. doi:10.1007/s12020-019-02171-w 4 Reference: Elif Turan and Ozgul Karaaslan; The Relationship between Iodine and Selenium Levels with Anxiety and Depression in Patients with Euthyroid Nodular Goiter; Oman Med J. 2020 Jul; 35(4): e161. Published online 2020 Jul 31. doi: 10.5001/omj.2020.84 5 Reference: Wang, J., Um, P., Dickerman, B., & Liu, J. (2018). Zinc, Magnesium, Selenium and Depression: A Review of the Evidence, Potential Mechanisms and Implications. Nutrients, 10(5), 584. doi:10.3390/nu10050584

Selenium, an essential trace element for humans, has a direct effect on thyroid hormone metabolism and oxidation-reduction processes. The functioning of the thyroid gland is critically dependent on iodine and selenium, in order to ensure that it functions properly. An insufficient amount of selenium in the body is associated with an increased risk of thyroid disease.1

Selenium can be considered the key to the health of the thyroid gland. It is a necessary trace element for the synthesis and functioning of thyroid hormones. The concentration of selenium in the thyroid gland is higher than in any other organ in the body. Selenium works with iodine to activate three different selenium-dependent iodothyronine deiodinases, which can then activate or deactivate thyroid hormones. All three isoforms of deiodinases are selenium-containing enzymes, so dietary or supplemental selenium is essential for triiodothyronine (T3) production. This process (and selenium) is essential for normal growth, development and metabolism.2

Selenium deficiency is associated with hypothyroidism, Hashimoto's disease, an enlarged thyroid gland, thyroid cancer, and Graves' disease.

One study of 1,900 participants found a relationship between serum selenium concentrations and the size of the thyroid gland. A protective effect of selenium against enlarged thyroid gland and thyroid tissue damage was observed. In this particular study, these results were only significant for female participants.3

Another study looked at the effect of selenium on Graves' orbitopathy (when the thyroid gland produces too much thyroid hormone). The researchers compared treatment with selenium to treatment with pentoxifylline (Pentilin), an anti-inflammatory drug. The selenium treatment group reported improved quality of life and slowed the progression of Graves' orbitopathy compared to the pentoxifylline (Pentilin) treatment group.4 1 Atsauce: 1) Wichman, J., Winther, K. H., Bonnema, S. J., & Hegedüs, L. (2016). Selenium Supplementation Significantly Reduces Thyroid Autoantibody Levels in Patients with Chronic Autoimmune Thyroiditis: A Systematic Review and Meta-Analysis. Thyroid, 26(12), 1681–1692. doi:10.1089/thy.2016.0256 2) Triggiani, V., Tafaro, E., Giagulli, V., Sabba, C., Resta, F., Licchelli, B., & Guastamacchia, E. (2009). Role of Iodine, Selenium and Other Micronutrients in Thyroid Function and Disorders. Endocrine, Metabolic & Immune Disorders - Drug Targets, 9(3), 277–294. doi:10.2174/187153009789044392 3) Derumeaux, H., Valeix, P., Castetbon, K., Bensimon, M., Boutron-Ruault, M., Arnaud, J., & Hercberg, S. (2003). Association of selenium with thyroid volume and echostructure in 35- to 60-year-old French adults. European Journal of Endocrinology, 148(3), 309–315. doi:10.1530/eje.0.1480309 4) Marcocci, C., Kahaly, G. J., Krassas, G. E., Bartalena, L., Prummel, M., Stahl, M., … Wiersinga, W. (2011). Selenium and the Course of Mild Graves’ Orbitopathy. New England Journal of Medicine, 364(20), 1920–1931. doi:10.1056/nejmoa1012985

1. For a long time, selenium was considered a toxic element. Poisoning with this element led to the development of severe anemia, bone stiffness, hair loss, and blindness. These symptoms have been observed in humans and animals in areas where the content of this element in the soil was ~1000 times greater in comparison with soils with an average amount of selenium in the other regions of the world.
2. Selenium gets its name from the Greek word "selene," which means "moon." Selene was the Greek goddess of the moon.
3. Selenium is a nonmetal. Like many nonmetals, it exhibits different colors and structures (allotropes) depending on the conditions.
4. Brazil nuts are high in selenium, even if they are grown in soil that is not rich in the element. A single nut provides enough selenium to meet the daily requirement for a human adult.
5. The primary use of selenium is to decolorize glass, to color glass red, and to make the pigment China Red. Other uses are in photocells, in laser printers and photocopiers, in steels, in semiconductors, and in assorted medicinal preparations.
6. Selenium is protective against mercury poisoning.

Zinc is an essential bio-element, which plays a fundamental role in a wide range of biochemical processes. This metal is a major component of various proteins and is an important modulator of the immune and nervous systems. It is the second most abundant trace metal in humans after iron and it is the only metal which appears in all enzyme classes.

Zinc is involved in numerous aspects of cellular metabolism. It is required for the catalytic activity of over 300 enzymes and 1000 transcription factors and it plays a role in immune function, protein synthesis, wound healing, DNA synthesis and cell division. Zinc also supports normal growth and development during pregnancy, childhood, and adolescence and is required for proper sense of taste and smell.

In the brain, zinc is stored in specific synaptic vesicles by glutamatergic neurons and can modulate neuronal excitability. It plays a key role in synaptic plasticity and so in learning. Zinc homeostasis also plays a critical role in the functional regulation of the central nervous system. Dysregulation of zinc homeostasis in the central nervous system that results in excessive synaptic zinc concentrations is believed to induce neurotoxicity through mitochondrial oxidative stress (e.g., by disrupting certain enzymes involved in the electron transport chain), the dysregulation of calcium homeostasis, glutamatergic neuronal excitotoxicity, and interference with intraneuronal signal transduction. 1 Reference: Nowak G., Szewczyk B.: Mechanism contributing to antidepressant zinc actions. Pol. J. Pharmacol., 2002, 54, 587–592. PMID: 12866713 2 Reference: Prakash A, Bharti K, Majeed AB (April 2015). "Zinc: indications in brain disorders". Fundam Clin Pharmacol. 29 (2): 131–149. doi:10.1111/fcp.12110. PMID 25659970. S2CID 21141511 3 Reference: https://ods.od.nih.gov/factsheets/Zinc-HealthProfessional/

At the same time, studies have shown a correlation between zinc deficiency and thyroid gland hormone levels. Zinc is necessary for the proper functioning of the enzyme deiodinase, which activates the inactive thyroxine (T4) hormone into a more active form - triiodothyronine (T3), ensuring all thyroid gland functions in the human body. 4 Reference: Maxwell, C., & Volpe, S. L. (2007). Effect of Zinc Supplementation on Thyroid Hormone Function. Annals of Nutrition and Metabolism, 51(2), 188–194. doi:10.1159/000103324

Zinc affects several aspects of the immune system. It is crucial for the normal development and function of innate immune cells, neutrophils and natural killer or NK cells. Zinc deficiency also affects macrophages – large cells that draw in and digest foreign particles. Zinc deficiency affects phagocytosis, intracellular killing and cytokine production. Zinc deficiency negatively affects the growth and function of T and B cells. Zinc’s ability to act as an antioxidant and stabilise membranes suggests that it plays a role in preventing free radical-induced injury during inflammatory processes. 5 Reference: Prasad AS. Zinc in human health: effect of zinc on immune cells. Mol Med. 2008 May-Jun;14(5-6):353-7. doi: 10.2119/2008-00033.Prasad. PMID: 18385818; PMCID: PMC2277319.

Zinc deficiency is characterized by growth retardation, loss of appetite, and impaired immune function. In more severe cases, zinc deficiency causes hair loss, diarrhea, delayed sexual maturation, impotence, hypogonadism in males, and eye and skin lesions. Weight loss, delayed healing of wounds, taste abnormalities, and mental lethargy can also occur. Many of these symptoms are non-specific and often associated with other health conditions; therefore, a medical examination is necessary to ascertain whether a zinc deficiency is present. People at risk of zinc deficiency or inadequacy need to include good sources of zinc in their daily diets.

Groups at Risk of Zinc Inadequacy

1. People with gastrointestinal and other diseases

Gastrointestinal surgery and digestive disorders (such as ulcerative colitis, Crohn’s disease, and short bowel syndrome) can decrease zinc absorption and increase endogenous zinc losses primarily from the gastrointestinal tract and, to a lesser extent, from the kidney. Other diseases associated with zinc deficiency include malabsorption syndrome, chronic liver disease, chronic renal disease, sickle cell disease, diabetes, malignancy, and other chronic illnesses. Chronic diarrhea also leads to excessive loss of zinc.

2. Vegetarians

The bioavailability of zinc from vegetarian diets is lower than from non-vegetarian diets because vegetarians do not eat meat, which is high in bioavailable zinc and may enhance zinc absorption. In addition, vegetarians typically eat high levels of legumes and whole grains, which contain phytates that bind zinc and inhibit its absorption.

3. Pregnant and lactating women

Pregnant women, particularly those starting their pregnancy with marginal zinc status, are at increased risk of becoming zinc insufficient due, in part, to high fetal requirements for zinc. Lactation can also deplete maternal zinc stores.

4. Older infants who are exclusively breastfed

Breast milk provides sufficient zinc (2 mg/day) for the first 4–6 months of life but does not provide recommended amounts of zinc for infants aged 7–12 months, who need 3 mg/day. In addition to breast milk, infants aged 7–12 months should consume age-appropriate foods or formula containing zinc. Zinc supplementation has improved the growth rate in some children who demonstrate mild-to-moderate growth failure and who have a zinc deficiency.

5. People with sickle cell disease

Results from a large cross-sectional survey suggest that 44% of children with sickle cell disease have a low plasma zinc concentration, possibly due to increased nutrient requirements and/or poor nutritional status. Zinc deficiency also affects approximately 60%–70% of adults with sickle cell disease. 

6. Alcoholics

Approximately 30%–50% of alcoholics have low zinc status because ethanol consumption decreases intestinal absorption of zinc and increases urinary zinc excretion. In addition, the variety and amount of food consumed by many alcoholics is limited, leading to inadequate zinc intake. 6 Reference: https://ods.od.nih.gov/factsheets/Zinc-HealthProfessional/  

Zinc in the diet. Adults who are not found or established to be deficient in Zinc are normally required 11 mg for men, 8 mg for women and 11 mg for pregnant women of Zinc per day

Reference Atsauce: https://ods.od.nih.gov/factsheets/Zinc-HealthProfessional/

Zinc supplements have the potential to interact with several types of medications. A few examples are provided below. Individuals taking these medications on a regular basis should discuss their zinc intakes with their healthcare providers.

1. Antibiotics

Both quinolone antibiotics (such as Cipro®) and tetracycline antibiotics (such as Achromycin® and Sumycin®) interact with zinc in the gastrointestinal tract, inhibiting the absorption of both zinc and the antibiotic. Taking the antibiotic at least 2 hours before or 4–6 hours after taking a zinc supplement minimizes this interaction.

2. Penicillamine

Zinc can reduce the absorption and action of penicillamine, a drug used to treat rheumatoid arthritis. To minimize this interaction, individuals should take zinc supplements at least 2 hours before or after taking penicillamine.

3. Diuretics

Thiazide diuretics such as chlorthalidone (Hygroton®) and hydrochlorothiazide (Esidrix® and HydroDIURIL®) increase urinary zinc excretion by as much as 60%. Prolonged use of thiazide diuretics could deplete zinc tissue levels, so clinicians should monitor zinc status in patients taking these medications. 1 Reference: Lomaestro BM, Bailie GR. Absorption interactions with fluoroquinolones. 1995 update. Drug Saf 1995;12:314-33. [PubMed abstract] 2 Reference: Penttilä O, Hurme H, Neuvonen PJ. Effect of zinc sulphate on the absorption of tetracycline and doxycycline in man. Eur J Clin Pharmacol 1975;9:131-4. [PubMed abstract] 3 Reference: Natural Medicines Comprehensive Database. Zinc. 4 Reference: Brewer GJ, Yuzbasiyan-Gurkan V, Johnson V, Dick RD, Wang Y. Treatment of Wilson’s disease with zinc: XI. Interaction with other anticopper agents. J Am Coll Nutr 1993;12:26-30. [PubMed abstract] 5 Reference: Wester PO. Urinary zinc excretion during treatment with different diuretics. Acta Med Scand 1980;208:209-12. [PubMed abstract]

Zinc is found in abundance in the human brain. Patients with depression may have decreased consumption of food sources rich in zinc and consistently low dietary zinc intakes may contribute to depressive symptoms by further lowering available zinc, therefore zinc supplementation may have a potential influence on depressive symptoms. In preclinical studies, single- or long- term treatment with zinc has been shown to have antidepressant-like effects.

According to recently introduced hypotheses of antidepressant action, one of major goals to be modified by an antidepressant is the NMDA glutamate receptor. The mechanism of antidepressant activity of zinc might be related to its direct antagonism at NMDA receptor. Besides the central nervous system, zinc is also involved in the immune/inflammatory regulation in depressive disorders.

In the hippocampus and cortex, zinc ions regulate synaptic transmission or act as neurotransmitters, modulating many ligand- and voltage-gated ion channels. Disruption of zinc homeostasis in these regions has been implicated in many disturbances in cognition, behavioral and emotional regulation through mechanisms of decreased neurogenesis and neuronal plasticity.

Zinc deficiency has also been implicated in the endocrine pathway of depression. Persistently high levels of cortisol have been implicated in the development of depression via hyperactivity of the hypothalamic–pituitary–adrenal (HPA) axis. Increased plasma cortisol levels could, therefore, potentially mediate the relationship between zinc deficiency and depression.

The relationship between serum zinc levels and depression could be partially explained by reverse causation, whereby depression influences the intake, bioavailability or biological regulation of zinc. Oxidative stress and its accompanying immune-inflammatory response have been linked to the pathophysiology of depression. In response to oxidative stress, levels of pro-inflammatory cytokines (e.g., interleukin 1 (IL-1) and IL-6) increase and, in turn, decrease of the level of albumin and increase the synthesis of metallothioneins. Albumin is the main zinc transporter, and a decrease in albumin coupled with an increase in metallothioneins may compound to decrease serum levels of zinc.

References 1 Reference: Elham Ranjbar, Jamal Shams, Masoumeh Sabetkasaei, Minoo M-Shirazi, Bahram Rashidkhani, Ali Mostafavi, Eiliyaz Bornak, Javad Nasrollahzadeh; Effects of zinc supplementation on efficacy of antidepressant therapy, inflammatory cytokines, and brain-derived neurotrophic factor in patients with major depression; 2 Reference: Pilc A., Kodziñska A., Nowak G.: A role for glutamate in the treatment of anxiety and depression: focus on group I metabotropic glutamate (mGlu) receptors. Drugs Fut., 2002, 27, 753–763. 3 Reference: Jessica Wang, Phoebe Um, Barbra A. Dickerman and Jianghong Liu1; Zinc, Magnesium, Selenium and Depression: A Review of the Evidence, Potential Mechanisms and Implications; Nutrients. 2018 May; 10(5): 584. Published online 2018 May 9. doi: 10.3390/nu10050584

Zinc is an essential element involved in many basic biochemical reactions of the thyroid gland. Zinc is necessary for the production of the hormones triiodothyronine (T3), thyroxine (T4) and thyroid-stimulating hormone (TSH).

T4 is the main thyroid gland hormone, which is a kind of bodyreserve, while T3 is a much more active hormone. If necessary, one molecule of iodine is separated from T4, and it turns into an active hormone - T3.

This trace element participates in the synthesis of thyrotropin-releasing hormone (TRH) in the hypothalamus and in the synthesis of thyrotropin or thyroid-stimulating hormone (TSH) in the pituitary gland.1

Some studies have shown that zinc deficiency and low zinc concentration in the serum can cause changes in thyroid gland structure and thyroid gland hormone metabolism. Also, studies have shown that taking zinc can increase the concentration of thyroid gland hormones.1

In a study where subjects took zinc supplements, they had improvements in all thyroid gland hormone levels (especially T3) as well as in the rate of metabolism in the state of rest. Another study showed that taking zinc alone or in combination with selenium can improve thyroid gland function in women with hypothyroidism.2

Zinc deficiency can cause hypothyroidism. On the other hand, hypothyroidism can cause zinc deficiency because thyroid gland hormones are needed for zinc absorption. 1 Atsauce: 1) Beserra, J. B., Morais, J. B. S., Severo, J. S., Cruz, K. J. C., de Oliveira, A. R. S., Henriques, G. S., & do Nascimento Marreiro, D. (2021). Relation Between Zinc and Thyroid Hormones in Humans: a Systematic Review. Biological Trace Element Research. doi:10.1007/s12011-020-02562-5 2) Mahmoodianfard, S., Vafa, M., Golgiri, F., Khoshniat, M., Gohari, M., Solati, Z., & Djalali, M. (2015). Effects of Zinc and Selenium Supplementation on Thyroid Function in Overweight and Obese Hypothyroid Female Patients: A Randomized Double-Blind Controlled Trial. Journal of the American College of Nutrition, 34(5), 391–399. doi:10.1080/07315724.2014.926161

Zinc has been found to be an essential trace element for the immune system. However, at the cellular and molecular level, the mechanisms of zinc actions on the immune system are relatively recent and its effects are diverse. 1 Reference: Rink, L. (2000). Zinc and the immune system. Proceedings of the Nutrition Society, 59(04), 541–552. doi:10.1017/s0029665100000781

Adequate levels of zinc in the body are essential for the formation and function of different populations of lymphocytes (the main immune cells), such as the division, maturation and differentiation (development into different forms) of T-cells (or T-lymphocytes); lymphocyte response to mitogens (small bioactive proteins or peptides that induce cells to start dividing or increase the rate of division). At the same time, zinc is important for programming lymphoid and myeloid cell death; gene transcription and biomembrane function. Lymphocytes are one of the types of cells activated by zinc. Zinc is a structural component of various proteins, neuropeptides, hormone receptors and polynucleotides. Zinc deficiency results in rapid and marked atrophy of the thymus, impaired cell-mediated cutaneous sensitivity and lymphopenia. Primary and secondary antibody responses are reduced in zinc deficiency, particularly for those antigens that require T-cell help, such as those in heterologous red blood cells. In addition, antibody response and the generation of splenic cytotoxic T-cells after immunisation are reduced. Zinc also inhibits the production of tumour necrosis factor, which is implicated in the pathophysiology of cachexia and wasting in acquired immune deficiency syndrome. 2 :Reference: Baum MK, Shor-Posner G, Campa A. Zinc status in human immunodeficiency virus infection. J Nutr. 2000 May;130(5S Suppl):1421S-3S. doi: 10.1093/jn/130.5.1421S. PMID: 10801954.

In short, zinc is absolutely essential for the functioning of the thymus and the normal functioning of the immune system. Zinc prevents immunodeficiency by stimulating antibody synthesis and providing antiviral effects.

1. The element was probably named by the alchemist Paracelsus after the German word Zinke and supposedly meant "tooth-like, pointed or jagged" (metallic zinc crystals have a needle-like appearance). Zink could also imply "tin-like" because of its relation to German zinn meaning tin.
2. The oldest known pills were made of the zinc carbonates hydrozincite and smithsonite. The pills were used for sore eyes and were found aboard the Roman ship Relitto del Pozzino, wrecked in 140 BC.
3. Alchemists burned zinc metal in air and collected the resulting zinc oxide on a condenser. Some alchemists called this zinc oxide lana philosophica, Latin for "philosopher's wool", because it collected in wooly tufts, whereas others thought it looked like white snow and named it nix album.
4. Zinc is a natural insect repellent and sun screen, protecting lips and skin.
5. Zinc is 100% recyclable. Over 80% of the zinc available for recycling is currently recycled.

L-tyrosine is a replaceable (non-essential) aromatic amino acid that serves as a raw material in the body for the synthesis of various other substances, for example, it is a precursor for the synthesis of the thyroid gland hormone thyroxine (T4) (produced by iodination of tyrosine), the pigment melanin and other biologically active substances such as catecholamines - epinephrine (adrenaline), norepinephrine (noradrenaline) and dopamine. These are very important biologically active substances that are synthesised in the neuron and released in the synapse; binding to the receptors of another cell, they transmit a nerve impulse from the synapse to the cell (neurotransmitters), which are closely related to the corresponding concentration of L-tyrosine in the body.

L-tyrosine is part of many natural proteins, including enzymes. In the body, L-tyrosine is synthesised from phenylalanine with the help of the enzyme phenylalanine-4-hydroxylase.

How does tyrosine work in our body? First, the thyroid gland absorbs iodine from food. Once these iodine molecules are oxidised, they are ready to attach to the tyrosine found in thyroglobulin (a protein produced by the thyroid gland). When iodine and tyrosine combine, they create thyroid gland hormone precursors, monoiodotyrosine (T1) and diiodotyrosine (T2). T1 and T2 then combine to form the thyroid gland hormones triiodothyronine (T3; thyroglobulin with three iodine molecules) and thyroxine (T4, thyroglobulin with four iodine molecules). T4 and T3 are the primary thyroid gland hormones that are essential for regulating metabolic processes throughout the body.

So, to summarise the roles of tyrosine in the body, the following should be mentioned:

A lack of tyrosine can cause thyroid gland dysfunction, such as hypothyroidism, as well as cause depression or increased nervousness due to impaired catecholamine synthesis.

L-Tyrosine is considered safe in most doses, but you should still consult your doctor before using it if you are taking any medications. It can interact with medications, including some medications used to treat thyroid gland disorders or depression.

Monoamine oxidase inhibitors (MAOIs) - Tyrosine can cause serious increases in blood pressure in people taking antidepressants known as MAOIs. This rapid rise in blood pressure, also called a “hypertensive crisis,” can lead to a heart attack or stroke. People taking MAOIs should avoid foods and supplements that contain tyrosine. For instance:

Levodopa - Tyrosine should not be used at the same time as levodopa, a medicine used to treat Parkinson's disease. Levodopa may interfere with the absorption of tyrosine.

In some cases, extra use of tyrosine can cause insomnia, restlessness, palpitations, headaches, stomach disorders and heartburn.

Because tyrosine is involved in the production of thyroid gland hormones, you should not take it if you have been diagnosed with a thyroid disorder such as hyperthyroidism or Graves' disease.

The recommended daily dietary allowance (RDA) for tyrosine is 25 mg per kilogram of body weight.1 Assuming that a person receives half of the required amino acid, this amounts to 12.5 mg per kg. Thus, a person weighing 70 kg should consume about 875 mg of tyrosine per day, which is the amount used to calculate the RDA. Tyrosine is found in a variety of foods, such as peanuts, fish, chicken, turkey, soy, eggs, and cottage cheese. It is also in pumpkin seeds, oats, wheat, beans, sesame seeds, avocados, and bananas. 1 Atsauce: George M. Kapalka, in Nutritional and Herbal Therapies for Children and Adolescents, 2010

Hypothyroidism, or reduced thyroid function, means that the thyroid gland produces insufficient amounts of important hormones that have an impact on all metabolic processes.  The most common causes of hypothyroidism are chronic autoimmune thyroiditis, the use of various medications, radiation therapy, and thyroid surgery. It should also be taken into account that people are reluctant to use sea vegetables, such as kelp, in their diet, as well as because of the taste, people prefer salt without iodine addition, which is also the reason why iodine deficiency is becoming more and more common.

The most common symptoms of hypothyroidism are fatigue, increased sensitivity to cold, dry skin, brittle hair, a person looking much older than they actually are. Women often have irregular menstruation, cognitive disorders, depression.

It has also been shown that people with thyroid disease, whether hyperthyroid or hypothyroid, have very fluctuating tyrosine levels in the blood serum, and those with hypothyroidism (low thyroid hormone levels) usually have lower than normal blood tyrosine levels.

Combined with the proven fact that the use of medications (for example, levothyroxine, a synthetic thyroid gland hormone used to treat thyroid diseases and disorders) improves the metabolism of tyrosine in the liver, it may be worth consulting a doctor and considering the possibility to supplement everyday life with both thyroid medication and tyrosine (either by following a special diet or using nutritional supplements).

If you choose to supplement your everyday life with L-tyrosine, remember that it is more effective to use it together with other minerals that can improve thyroid function, such as zinc and selenium. Zinc helps to improve the conversion of thyroxine (T4) to triiodothyronine (T3) in hypothyroid patients with insufficient thyroid function. Selenium, on the other hand, helps reduce thyroid antibodies and is also involved in the conversion of T4 to T3.

Among the 66 species of kelp, Fucus vesiculosus is one of the most prominent in the shallow waters of the Arctic region - the Atlantic Ocean, the North Pacific Ocean, the Barents, White, Norwegian, Baltic and Irminger seas. These algae dominate shallow water macroalgal populations at depths of 0.5-4 m in marine waters. They are used not only in food, but also in cosmetics, biological fertilisers, animal feed and the pharmaceutical industry.1

Fucus vesiculosus contains a range of health-promoting compounds such as fucoidans, polyphenols, fucoxanthin and a source of essential minerals, including iodine, which is highly bioavailable, and selenium, which plays a key role in regulating thyroid gland function. Bladderwrack is particularly rich in iodine and is used as a natural source of iodine, which is organically incorporated into cellular metabolism.

Alginic acid found in kelp (up to 35% of dry mass) is known in the food industry. It serves as an ingredient in soups and soup mixes as an emulsifier, thickener and stabiliser. On the other hand, preparations based on alginates (salts of alginic acid) are used to treat heartburn and gastric acid reflux.2 Alginic acid stimulates phagocytosis, thereby increasing the antimicrobial, antiviral and antifungal activity of cells; binds the excess amount of immunoglobulin E, due to which allergy develops; promotes the synthesis of immunoglobulin A (antibodies), which increases the body's resistance to microbes. Likewise, thanks to alginic acid, Fucus vesiculosus lowers blood pressure, removes harmful radionuclides and heavy metals and weakens body intoxication.

Another important component of Fucus vesiculosus is fucoidans. Fucoidans are polysaccharides from the Fucus family, compounds unique to brown algae (kelp). Various pharmacological effects of fucoidans have been reported, including antioxidant, anti-obesity, antidiabetic, antiageing, antimicrobial, anticancer (by modulating the host immune system and inhibiting tumour angiogenesis), anticoagulant, and anti-inflammatory effects.1

Fucus vesiculosus reduces the activity of trans-sialidase in the blood, an enzyme associated with cholesterol accumulation, by as much as 36%.3 This may be useful in patients with hypothyroidism, as slow metabolism is associated with the excessive accumulation of lipids and glucose.

Summing up the valuable qualities of Fucus vesiculosus, it should be mentioned that it effectively cleanses the body of slags and toxins, as well as maintains the health of the endocrine system. Recommended for hypothyroidism, blood circulation disorders, poisoning with heavy metal salts. Fucus vesiculosus slows down the development of atherosclerosis, and reduces the level of cholesterol in the blood. Bladderwrack polysaccharides swell, increase their volume and irritate the intestinal mucosa, thereby stimulating peristalsis, promoting intestinal cleansing, which is used to reduce weight in obese people. Polysaccharides bind toxins, remove them from the body. Bladderwrack alginates remove heavy metals and radionuclides from the body. Bladderwrack contains more trace elements than land plants. 1 Atsauces: 1) Ekaterina D. Obluchinskaya, Olga N. Pozharitskaya, Denis V. Zakharov, Elena V. Flisyuk, Inna I. Terninko, Yulia E. Generalova, Irina E. Smekhova, and Alexander N. Shikov; The Biochemical Composition and Antioxidant Properties of Fucus vesiculosus from the Arctic Region; Mar Drugs. 2022 Mar; 20(3): 193.; doi: 10.3390/md20030193 2) Mandel, Daggy, Brodie, & Jacoby. (2000). Review article: alginate-raft formulations in the treatment of heartburn and acid reflux. Alimentary Pharmacology and Therapeutics, 14(6), 669–690. doi:10.1046/j.1365-2036.2000.00759.x 3) Aksenov, D. V., Kaplun, V. V., Tertov, V. V., Sobenin, I. A., & Orekhov, A. N. (2007). Effect of plant extracts on trans-sialidase activity in human blood plasma. Bulletin of Experimental Biology and Medicine, 143(1), 46–50. doi:10.1007/s10517-007-0013-2

There are no clinical studies supporting the safety of Fucus vesiculosus, but based on the use of Fucus as a traditional food, moderate consumption of the seaweed is generally considered safe. Seaweed can be exposed to chemical contamination present in the water in which it is harvested, so its origin and manufacturer's quality requirements are of particular importance. Cases of Fucusnephrotoxicity, possibly due to arsenic contamination, have been reported. Therefore, pay attention if products containing algae are unusually cheap or are not registered with food safety authorities.

Due to the limited number of studies, there are no well-defined recommendations for daily doses of bladderwrack; however, mostly, it is recommended not to exceed 500 mg daily.

Pregnancy and breastfeeding period: Fucus vesiculosus is probably not safe to use during pregnancy or breastfeeding unless prescribed by a doctor.

Allergy to iodine: Fucus vesiculosus can contain large amounts of iodine, which can cause an allergic reaction in sensitive people. Do not use them as a food product in excessive amounts, but it can be used as a dietary supplement in controlled amounts.

Surgery: Fucus vesiculosus can slow down blood clotting. This can cause additional bleeding during and after surgery. Tell your doctor how much algae you are taking and, if necessary, stop taking Fucus vesiculosus at least 2 weeks before surgery if your doctor tells you to.

Drug interactions:

Be careful if you use:

Taking Fucus vesiculosus together with lithium may increase the risk of changes in thyroid gland function.

Taking Fucus vesiculosus with medicines for a hyperactive thyroid gland can change the effects of these medicines.

Fucus vesiculosus can slow down blood clotting. Taking them with medicines that also slow down blood clotting can increase the risk of bruising and bleeding.1 1 Atsauce: 1) https://medlineplus.gov/druginfo/natural/726.html

In our latitudes, a common phenomenon is a reduced thyroid function, or hypothyroidism. Almost every third or fourth woman has it. Women are more affected by this problem, because the function of the thyroid gland and its activity is influenced by the psycho-emotional state. The thyroid gland is very sensitive to adrenaline and the stress hormone cortisol. Typical signs of hypothyroidism are freezing (intolerance to cold), fluid retention, and it is especially evident in premenopausal age.1

The body of a healthy adult contains 15 to 20 mg of iodine, of which 70 to 80% is located in the thyroid gland. In the case of a chronic iodine deficiency, the iodine content in the thyroid gland may fall below 20 µg. If a sufficient amount of iodine is available to the body, then the thyroid gland “uses” about 60 µg of iodine per day to balance its loss and maintain the synthesis of thyroid hormones; accordingly, iodine is an essential component of the hormones produced by the thyroid gland.2

The body does not produce iodine, so it is essential to consume foods that contain iodine or to take iodine with food additives or nutritional supplements. Iodine is found in a variety of foods, however seafood has a higher iodine content because marine plants and animals are able to concentrate iodine from seawater. Iodine is found in large quantities in organic form in algae, incl. Fucus vesiculosus . If the body does not have enough iodine, it cannot produce enough thyroid gland hormones. Thus, iodine deficiency can cause thyroid gland enlargement, hypothyroidism, and intellectual disability in infants and children whose mothers were iodine deficient during pregnancy.3 Strict vegans are especially at risk because their daily food intake is limited.4

Fucus vesiculosus contains the flavonoid fucoxanthin and is reported to have the highest antioxidant activity among edible seaweeds. Fucus vesiculosus, rich in minerals and halides including iodine, has shown beneficial effects in the treatment of thyroid gland dysfunction such as Hashimoto's disease and sub-clinically

hypothyroidism. Fucus also has the ability to reduce the activity of trans-sialidase in the blood, which is associated with the accumulation of cholesterol. This may be important in hypothyroid patients whose metabolism is associated with hyperlipidemia.5 1 Atsauce: 1) https://nra.lv/veseliba/181158-veseliba-vairogdziedzera-disfunkcija-21-gadsimta-pandemija.htm 2) Zimmermann, M. B. (2009). Iodine Deficiency. Endocrine Reviews, 30(4), 376–408. doi:10.1210/er.2009-0011 10.1210/er.2009-0011 3) https://www.thyroid.org/iodine-deficiency/ 4) Lightowler HJ, Davies GJ. Iodine intake and iodine deficiency in vegans as assessed by the duplicate-portion technique and urinary iodine excretion. Br J Nutr 1998;80(6):529-535. 5) Jill Stansbury,Paul Saunders, David Winston; Promoting Healthy Thyroid Function with Iodine, Bladderwrack, Guggul and Iris; ©2012, Jill Stansbury, ND Journal Compilation ©2012, AARM; DOI 10.14200/jrm.2012.1.1008