Masters of Health Magazine November 2025 | Page 74

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]

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]

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]

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.

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]

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.

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]

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.