Unit 3 Module 2

Magnesium and The Thyroid Gland

Welcome to Module 2 of Magnesium and the Endocrine System in Human Health. In this module, we’ll explore the relationship between magnesium and the thyroid gland. While magnesium is often thought of in terms of energy production and muscle function, its role in thyroid hormone synthesis and metabolism is equally important.

Magnesium is essential for numerous biological processes that directly impact thyroid health, and plays a multifaceted role in thyroid physiology, acting as both a direct modulator of hormone synthesis and an indirect regulator of systemic processes that influence thyroid health. This module will review the biochemical, clinical, and epidemiological studies that outline magnesium’s involvement in thyroid hormone production, conversion, and regulation, while examining its interplay with essential cofactors and secondary hormonal pathways.

Mechanisms

One of the primary roles of magnesium within the human body is its role in ATP bioactivation. Adenosine triphosphate (ATP), the energy currency of the cell, must bind to a magnesium ion to become biologically active, forming a complex called Mg-ATP. This Mg-ATP complex is essential for powering nearly every cellular process that requires energy. [1]

Effects of Magnesium on the Thyroid Gland

Iodine Uptake

As with multiple hormones within the endocrine system, the Mg-ATP complex is indirectly required for the synthesis of thyroid hormones. This requirement begins with the uptake of iodide by thyroid follicular cells. The process is facilitated by sodium-iodide symporters (NIS). The NIS-mediated iodide uptake relies on the electrochemical sodium gradient, which is maintained by the sodium-potassium ATPase pump (Na+/K+ ATPase). [2,3] Magnesium plays a crucial role in the function of the sodium-potassium pump. It acts as an essential cofactor for ATP hydrolysis by the pump, with the Mg-ATP complex serving as the actual substrate for the enzyme. Consequently, magnesium indirectly facilitates the transport of iodine into thyroid follicular cells by enabling the sodium-potassium pump’s activity. [4]

Iodine Oxidation

Once iodine is taken up into thyroid follicular cells, it must be oxidized to its reactive form before thyroid hormones can be produced. This process utilizes an enzyme called thyroid peroxidase (TPO) which relies on hydrogen peroxide (H₂O₂) as its oxidizing agent. While magnesium doesn’t directly participate in this oxidation reaction, it plays a crucial role in supporting the enzymes responsible for H₂O₂ production. Notably, magnesium supports proper functioning of NADPH oxidase (NOX), an enzyme that generates the H₂O₂ necessary for TPO to carry out its iodide oxidation function. [11] Thus, magnesium’s indirect but vital contribution to this process underscores its importance in maintaining optimal thyroid function and hormone synthesis. [7,8]

Cofactor For Enzyme Reactions

Magnesium also indirectly plays an important role in thyroid function through its contribution as a cofactor for many enzyme reactions which include enzymes involved in the production of thyroid hormones and the thyroid hormone precursor thyroid stimulating hormone TSH. [6] Magnesium is crucial for the proper functioning of the deiodinase enzymes, which are responsible for converting T4 to T3. This conversion process is vital because T3 is the biologically active form of thyroid hormone, approximately five times more potent than T4. [6,14]

Influence on Thyroid Stimulating Hormone

In addition to aiding in hormone conversion, magnesium is necessary for the production of thyroid-stimulating hormone (TSH) in the pituitary gland. TSH regulates the release of thyroid hormones from the thyroid gland, and magnesium deficiency can disrupt this feedback loop [9]. More will be discussed on this in the next module on the pituitary gland.

Studies have shown that patients with low magnesium levels often have elevated TSH levels and reduced T4 and T3 levels, indicating impaired thyroid function [10]. This is particularly important when managing patients with thyroid disorders, as magnesium supplementation may help improve thyroid hormone levels and overall metabolic function.

Immune Regulation

One of its key roles of magnesium is in immune regulation. When magnesium levels are low, the body tends to produce more pro-inflammatory cytokines, such as TNF-α and IL-6, which can exacerbate inflammation in the thyroid gland. Animal and in vitro studies have shown that magnesium deficiency induces an inflammatory response, activating immune cells and increasing the production of reactive oxygen species, which can contribute to chronic inflammation. [21] Additionally, magnesium deficiency impairs the function of regulatory T-cells, which are crucial for keeping autoimmune responses in check. This disruption can lead to a heightened autoimmune attack on the thyroid. [18]

Magnesium Deficiency and Hypothyroidism

Hypothyroidism, or an underactive thyroid, is one of the most common endocrine disorders, affecting millions of people worldwide. Symptoms can include fatigue, weight gain, depression, and sensitivity to cold. While iodine deficiency is often cited as a cause, magnesium deficiency can also play a significant role in the development and progression of hypothyroidism due to its indirect effects upon the thyroid gland as mentioned previously. [4]

When magnesium is deficient or insufficient, studies have indicated that this can lead to decreased uptake of iodine by thyroid follicular cells, thereby causing thyroid hormone disorders. [6,9,10] Animal experiments have also shown that magnesium deficiency significantly decreases radioactive iodine uptake by thyroid cells, while supplementation does the opposite. [13] Hypothyroidism may also be indirectly worsened by the reduced production of hydrogen peroxide that is utilized for the oxidation of iodine which is essential for the synthesis of the thyroid hormones. [11,12]

Magnesium plays a key role in supporting deiodinase enzymes, which convert the thyroid hormone T4 into its active form, T3. When magnesium levels are low, deiodinase activity decreases, resulting in reduced amounts of active thyroid hormone (T3) in the blood. [6,14] This issue is especially relevant for individuals who experience symptoms of hypothyroidism even though their TSH levels are normal, as magnesium deficiency may be the reason for their low T3 levels.

Magnesium Deficiency and Autoimmune Thyroiditis

Research increasingly suggests that low magnesium levels are correlated with autoimmune thyroiditis, especially Hashimoto’s thyroiditis. Clinical studies have found that individuals with severely low magnesium (defined as ≤0.55 mmol/L) are significantly more likely to develop Hashimoto’s thyroiditis and hypothyroidism compared to those with normal magnesium levels. Furthermore, low serum magnesium is often associated with increased positivity for thyroglobulin antibodies (TGAb), which are markers of thyroid autoimmunity. These findings indicate that magnesium deficiency is not only common among those with autoimmune thyroid disorders but may also play a role in the progression and severity of the disease. [10,15,17,18,19,20]

In addition, low magnesium intake correlates with elevated inflammatory markers (e.g., hs-CRP, IL-6), creating an environment that may impair immune function increasing the risk for auto-immune disease. [22] Magnesium supplementation in experimental diabetes partially restored thyroid function and reduced renal impairment, suggesting indirect immune stabilization. [23] Moreover, magnesium plays a protective role as an antioxidant. It supports the production of glutathione, a powerful antioxidant that helps defend thyroid cells against oxidative damage. When magnesium is deficient, glutathione levels drop, leaving the thyroid more vulnerable to inflammation and injury. [24]

Practical Implications for Clinical Practice

So how does this translate into clinical practice and personal application? First, it’s important to assess magnesium status in patients with thyroid disorders, particularly those with hypothyroidism. Symptoms like fatigue, muscle cramps, anxiety and irritability may be indicators of magnesium insufficiency or deficiency, and testing serum magnesium levels can help confirm this but may not always indicate an underlying deficiency since the body tightly regulates the amount of magnesium that is present in the blood.

In terms of treatment, magnesium supplementation is relatively straightforward and can be easily incorporated into a patient’s thyroid management plan and general nutrition plan. For most adults, a daily magnesium supplement of 400 mg is considered safe and effective.

Magnesium citrate and magnesium glycinate are commonly used forms due to their high absorption rates and minimal side effects.

(Editors note: I personally get my elemental magnesium by adding 1/4 teaspoon of food grade Epsom salt (magnesium sulfate) to every liter of water I drink. It is very cheap and very bioavailable. 1/4 tsp in 1 liter of water will give you around 125 mg of elemental magnesium per liter of water. 1 pound of Epsom salt is enough to last around six months and at $10 per pound that provides a significant savings compared to standard supplements.

It’s also important to educate individuals on dietary sources of magnesium. Foods like nuts, seeds, leafy greens, and whole grains are rich in magnesium and can help maintain adequate levels. However, if sufficiency or deficiency is suspected, supplementation is a simple and effective way to restore magnesium levels and ensure optimal thyroid function.

Other Important Nutrients for Thyroid Health

Appropriate amounts of other trace elements are also necessary for optimal thyroid gland health. These include iodine [25], selenium [26], zinc [27], iron [18], and vitamins, especially vitamins D [28], and vitamin A. [27]

Conclusion

In this module, we’ve covered how magnesium influences thyroid hormone production and how its deficiency can contribute to thyroid disorders. Understanding this relationship can help optimize thyroid function and better manage patients with thyroid disorders. In an upcoming module, we’ll explore how magnesium impacts the adrenal glands and its role in regulating the body’s stress response.

References

1. Dunn J, Grider MH. Physiology, Adenosine Triphosphate. [Updated 2023 Feb 13]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK553175/

2. Ravera S, et al. The Sodium/Iodide Symporter (NIS): Molecular Physiology and Preclinical and Clinical Applications. Annu Rev Physiol. 2017 Feb 10;79:261-289. https://pmc.ncbi.nlm.nih.gov/articles/PMC5739519/

3. Hingorani M, et al. The biology of the sodium iodide symporter and its potential for targeted gene delivery. Curr Cancer Drug Targets. 2010 Mar;10(2):242-67. doi: 10.2174/156800910791054194. PMID: 20201784; PMCID: PMC3916908. https://pmc.ncbi.nlm.nih.gov/articles/PMC3916908/

4. Ryan M. F. (1991). The role of magnesium in clinical biochemistry: an overview. Annals of clinical biochemistry, 28 ( Pt 1), 19–26. https://journals.sagepub.com/doi/pdf/10.1177/000456329102800103?download=true

5. Shulhai AM, et al. The Role of Nutrition on Thyroid Function. Nutrients. 2024 Jul 31;16(15):2496. doi: 10.3390/nu16152496. PMID: 39125376; PMCID: PMC11314468. https://pmc.ncbi.nlm.nih.gov/articles/PMC11314468/

6. Kolanu BR, et al. Activities of Serum Magnesium and Thyroid Hormones in Pre-, Peri-, and Post-menopausal Women. Cureus. 2020 Jan 3;12(1):e6554. https://pmc.ncbi.nlm.nih.gov/articles/PMC6996468/

7. Aoyagi K, et al. Role of Mg2+ in activation of NADPH oxidase of human neutrophils: evidence that Mg2+ acts through G-protein. Biochem Biophys Res Commun. 1992 Jul 15;186(1):391-7. https://www.sciencedirect.com/science/article/abs/pii/S0006291X05808204

8. Yamaguchi T, et al. Essential requirement of magnesium ion for optimal activity of the NADPH oxidase of guinea pig polymorphonuclear leukocytes. Biochem Biophys Res Commun. 1983 Aug 30;115(1):261-7. https://www.sciencedirect.com/science/article/abs/pii/0006291X83909981

9. Moncayo R, Moncayo H. The WOMED model of benign thyroid disease: Acquired magnesium deficiency due to physical and psychological stressors relates to dysfunction of oxidative phosphorylation. BBA Clin. 2014 Nov 12;3:44-64. https://pmc.ncbi.nlm.nih.gov/articles/PMC4661500/

10. Wang K, er al. Severely low serum magnesium is associated with increased risks of positive anti-thyroglobulin antibody and hypothyroidism: A cross-sectional study. Sci Rep. 2018 Jul 2;8(1):9904. https://pmc.ncbi.nlm.nih.gov/articles/PMC6028657/

11. Cross AR, et al. Spontaneous activation of NADPH oxidase in a cell-free system: unexpected multiple effects of magnesium ion concentrations. Biochem J. 1999 Feb 15;338 ( Pt 1)(Pt 1):229-33. https://pmc.ncbi.nlm.nih.gov/articles/PMC1220046/

12. Szanto I, et al. H2O2 Metabolism in Normal Thyroid Cells and in Thyroid Tumorigenesis: Focus on NADPH Oxidases. Antioxidants (Basel). 2019 May 10;8(5):126. https://pmc.ncbi.nlm.nih.gov/articles/PMC6563055/

13. Humphray HP, Heaton FW. Relationship between the thyroid hormone and mineral metabolism in the rat. J Endocrinol. 1972 Apr;53(1):113-23. https://joe.bioscientifica.com/view/journals/joe/53/1/joe_53_1_011.xml

14 . Demers LM, Spencer C. Tietz Textbook of Clinical Chemistry and Molecular Diagnosis. St. Louis, Missouri: Elsevier Saunders; 2006. The Thyroid: Pathophysiology and Thyroid Function Testing; pp. 2053–2084.

15. Mikulska AA, Karaźniewicz-Łada M, et al. Metabolic Characteristics of Hashimoto's Thyroiditis Patients and the Role of Microelements and Diet in the Disease Management-An Overview. Int J Mol Sci. 2022 Jun 13;23(12):6580. https://pmc.ncbi.nlm.nih.gov/articles/PMC9223845/

16 . Moncayo R, Moncayo H. Practical Guidelines for Diagnosing and Treating Thyroid Disease Based on the WOMED Metabolic Model of Disease Focusing on Glycolysis and Coenzyme Q10 Deficiency-A Clinical Alternative to the 2021 Retired Clinical Practice Guidelines of the Endocrine Society. Diagnostics (Basel). 2022 Jan 4;12(1):107. https://pmc.ncbi.nlm.nih.gov/articles/PMC8774471/

17. Mikulska AA, et al. Characteristics of Hashimoto's Thyroiditis Patients and the Role of Microelements and Diet in the Disease Management-An Overview. Int J Mol Sci. 2022 Jun 13;23(12):6580. https://pmc.ncbi.nlm.nih.gov/articles/PMC9223845/

18. Kravchenko V, Zakharchenko T. Thyroid hormones and minerals in immunocorrection of disorders in autoimmune thyroid diseases. Front Endocrinol (Lausanne). 2023 Aug 30;14:1225494. https://pmc.ncbi.nlm.nih.gov/articles/PMC10499380/

19 . Khan SZA, et al. Minerals: An Untapped Remedy for Autoimmune Hypothyroidism? Cureus. 2020 Oct 17;12(10):e11008. https://pmc.ncbi.nlm.nih.gov/articles/PMC7574993/

20. Bryliński Ł, et al. Effects of Trace Elements on Endocrine Function and Pathogenesis of Thyroid Diseases-A Literature Review. Nutrients. 2025 Jan 22;17(3):398. https://pmc.ncbi.nlm.nih.gov/articles/PMC11819802/

21. Nielsen FH. Magnesium deficiency and increased inflammation: current perspectives. J Inflamm Res. 2018 Jan 18;11:25-34. doi: 10.2147/JIR.S136742. https://pmc.ncbi.nlm.nih.gov/articles/PMC5783146/

22. Chacko SA, et al. Relations of dietary magnesium intake to biomarkers of inflammation and endothelial dysfunction in an ethnically diverse cohort of postmenopausal women. Diabetes Care. 2010 Feb;33(2):304-10. https://pmc.ncbi.nlm.nih.gov/articles/PMC2809271/

23. Ige AO, et al. Amelioration of thyroid dysfunction by magnesium in experimental diabetes may also prevent diabetes-induced renal impairment. Heliyon. 2019 May 8;5(5):e01660. https://pmc.ncbi.nlm.nih.gov/articles/PMC6513790/

24. Zheltova AA, et al. Magnesium deficiency and oxidative stress: an update. Biomedicine (Taipei). 2016 Dec;6(4):20. https://pmc.ncbi.nlm.nih.gov/articles/PMC5112180/

25. Sang Z, et al. Exploration of the safe upper level of iodine intake in euthyroid Chinese adults: a randomized double-blind trial. Am J Clin Nutr. 2012;95(2):367- 373.

26. Hu Y, Feng W, et al. Effect of selenium on thyroid autoimmunity and regulatory T cells in patients with Hashimoto’s thyroiditis: A prospective randomized- controlled trial. Clin Transl Sci. 2021;14(4):1390-1402.

27. Rabbani E, et al. Randomized Study of the Effects of Zinc, Vitamin A, and Magnesium Co-supplementation on Thyroid Function, Oxidative Stress, and hs-CRP in Patients with Hypothyroidism. Biol Trace Elem Res. 2021;199(11):4074-4083.

28. Bhakat B, et al. A Prospective Study to Evaluate the Possible Role of Cholecalciferol Supplementation on Autoimmunity in Hashimoto’s Thyroiditis. J Assoc Physicians India. 2023;71(1):1. Accessed July 23, 2024. https://journal-api.s3.ap-south- 1.amazonaws.com/issues/January2023.pdf