Introduction

Thyroid disorders affect about 200 million people in the world (0.8-5% of the population), and are four to seven times more common in women (Mircescu, 2010). These disorders are ubiquitous in the context that they are the root of many other diseases. Thyroid conditions include hyper/hypothyroidism, goiter, thyroid cancer, Graves’ disease (GD) and Hashimoto’s thyroiditis. Conventional treatment option for nodules and cancer is surgery. Medications are also used for many thyroid conditions. Pharmaceutical medications that are common for hypothyroid status include Synthroid and Cytomel. Hyperthyroidism is treated by radioactive iodine or anti-thyroid medications, such as Methimazole. There are several natural options available to treat thyroid conditions that can be used in conjunction with these medications or on their own, such as selenium (Se), kelp and zinc. However, more recent attention has been drawn to other options, such as magnesium, vitamin D and carnitine. The following is a summary of the current evidence on these natural treatment options.

Magnesium

Magnesium (Mg) is a vital part of cellular reactions; it is involved in metabolism, DNA replication, repair, transport mechanisms and cell proliferation. Food sources that are high in magnesium are whole and unrefined grains, seeds, cocoa, nuts, almonds, green leafy vegetables, avocados and fish (Blaszczyk, 2013). Magnesium has been used in a wide array of diseases, such as arrhythmia, hypertension, high cholesterol, premenstrual syndrome, asthma, diabetes and attention deficit hyperactivity disorder (ADHD), in doses of 100-400mg on average taken with meals (Micromedex, 2015). More recently, the relationship between Mg abnormalities and the development of thyroid disorders has been considered.

Evidence for magnesium

A growing body of evidence has shown the role and pattern of magnesium levels in thyroid disorders, including thyroid cancer and autoimmune thyroid disease. For example, after factoring out ethnicity, one meta-analysis showed a significant association between serum Mg and thyroid cancer. This retrospective analysis found that individuals with thyroid cancer had lower serum levels of Se and Mg, but higher levels of copper (Cu) than the healthy controls (Shen, 2015). Further benefit from these findings in a future study would be to understand the results in the context of ethnicity. Another study on metabolic disorders indicated that mineral deficiencies, including Mg, were found in patients with autoimmune thyroid disease, alongside protein and vitamin deficiencies (A, B’s and C). It suggests that an improved diet via maintenance of required daily intakes of vitamins and minerals could help decrease symptoms and prevent recurrence of malnutrition-induced thyroid disease (Kawicka, 2015). Although this study was done on a malnourished population, it offers unique results that warrant further exploratory studies to see if the effect to correct the thyroid diagnosis is maintained in a non-malnourished population. One prospective cohort study showed no evidence of association between thyroid cancer and micronutrient levels, including Mg, however this may have been partly attributed to the low statistical power of the study and lack of detail surrounding the population studied (O’Grady, 2014). Additionally, details were obtained via a food frequency questionnaire; it is possible that numerical, measurable outcomes could have different results if utilized in further study.

A well designed, cross sectional study divided patients into five groups: 1) subclinical-hypothyroid (SHY), 2) overt-hypothyroid (OHY), 3) subclinical-hyperthyroid (SHE), 4) overt-hyperthyroid (OHE), 5) patients under thyroxine therapy (EU), and normal controls. It showed that overtly hypothyroid patients had reduced serum Mg levels-OHY group, among other abnormal serum levels of nutrients (Abdel Gayoum, 2014), thus suggesting the need for diet modification and supplementation with this micronutrient. It would also be beneficial to do an extension of this type of study to examine whether this effect changes and/or is maintained past six months. A study examined the effects of Mg levels after treatment with thyroid medication; examining Mg as a pathology marker. The study demonstrated that using Methimazole in the treatment of hyperthyroidism due to Graves’ Disease led towards normalizing Mg levels (Klatka, 2013). These results are useful with further investigation on whether, in addition to Mg as a pathology marker, it could be used therapeutically, and a correction of Mg deficiency could be beneficial towards correcting thyroid abnormalities.

Vitamin D

Vitamin D is a fat soluble vitamin that is found in certain foods and can be produced internally when ultraviolet rays hit the skin. It is inactive and has to go through two transformations to be biologically active: primarily, the liver converts vitamin D to 25-hydroxyvitamin D (calcidiol), and secondly, the kidney converts calcidiol into 1,25 dihydroxyvitamin D (calcitriol) (NIH, 2015). The function of vitamin D in the body is for bone and cell growth, neurological function, normal inflammatory response and thyroid optimization. Food sources of vitamin D include cod liver oil, swordfish, salmon, milk and liver.

Evidence for Vitamin D

The role that vitamin D plays in the development and treatment of thyroid conditions, such as Graves’ disease and thyroid cancer, remains to be uncovered. One study showed that the prevalence of vitamin D deficiency was significantly higher in GD patients when compared to control subjects (56.25 vs. 10.00 %, p < 0.001). The same study also demonstrated that GD radioactive iodine therapy (RIT) failed in 27 (37.50 %) of patients whose serum 25(OH) D levels were < 20 ng/ml (Li, 2015). This suggests that vitamin D deficiency might be an independent risk factor for predicting failure of RIT in GD subjects. Another study found that low vitamin D was associated with three types of autoimmune thyroid disease (Ma, 2015).

Although the study of molecular mechanisms of vitamin D are beyond the scope of this article, the following should be noted as it illustrates the potential for future vitamin D therapy. The mortality due to anaplastic thyroid cancer (ATC) is high because of fast progression of the disease and its high metastatic potential with no effective treatment existing. The active form of vitamin D3, 1α,25(OH)2D3, has been shown to thwart metastases in pre-clinical studies, but has not been used clinically because of its potential to create a state of hypercalcemia. A recent study unveiled that a category of less-calcemic vitamin D analogs, 19-nor-2α-(3-hydroxypropyl)-1α,25-dihydroxyvitamin D3 (MART-10), is more potent than 1α,25(OH)2D3 in repressing cancer growth and metastasis in a variety of cancers. The study showed that both 1α,25(OH)2D3 and MART-10 could effectively inhibit the migration and invasion of ATC cells, suggesting hopeful future clinical application (Chiang, 2015). Another emerging supplement for thyroid disorders is carnitine.

Carnitine

Carnitine is found in different forms. L-Carnitine (LC) is made up of methionine and lysine. It is part of an effective shuttling mechanism that transports long chain acyl groups into the mitochondrial matrix to produce energy from fat (Olpin, 2005). LC metabolism within the body occurs via dietary intake, synthesis, and reabsorption in the kidney. It is absorbed by the jejunum, through a sodium dependent transporter (Gross, 1986). This transporter takes up LC, while Acetyl LC (ALC) requires the removal of the acetyl group before absorption. The levels of absorption are dose and source dependent. Usual therapeutic dosage ranges are between 500 to 2000 milligrams per day depending on the use (Malaguarnera M, 2011). It has been used for diabetes, osteoporosis, kidney and liver disease, and more recently, for thyroid diseases.

Evidence for Carnitine

Research suggests that diminished fatty acid oxidation can be corrected by carnitine supplementation. One randomized, double blind, placebo controlled study consisted of women who were given thyroid hormones to treat benign thyroid nodules. They were divided into three groups; a) those who received placebo for six months, b) those who had placebo for two months followed by carnitine 2 or 4 g/day for two months, then back to placebo, and c) those who got carnitine 2 or 4 g/day for four months and then, placebo. The placebo group displayed symptoms of hyperthyroidism, such as muscle weakness, shortness of breath, heart palpitations, nervousness, and insomnia, amongst others. The second group had hyperthyroid symptoms during the two months of placebo, but those symptoms disappeared after two months of carnitine supplementation, and returned again during the last two months of placebo. The last group had no hyperthyroid symptoms until they stopped receiving carnitine at the end of the first four months (Benvenga, 2001). The results, although not reaching statistical significance, were still meaningful from a clinical standpoint, and showed a time-sensitive benefit of carnitine supplementation in hyperthyroidism.

The basis of why carnitine supplementation is useful for many clinical thyroid settings derived from the understanding that hyperthyroidism lowers tissue carnitine levels. It was shown that urinary excretion of carnitine is increased in hyperthyroid individuals (Maebashi, 1977). One study showed that there were no differences found in the serum ALC profiles between hypo-, hyper- and euthyroid states before and after treatment with thyroxine or Thionamide therapy (Wong, 2013). Despite this, most evidence has shown a significant reduction in carnitine (mostly esterified portion) in hyperthyroid individuals, with a return to normal levels as euthyroid status was achieved (Sinclair, 2005). This indicates that further investigation is needed to better understand the mechanisms by which thyroid conditions could result or cause a deficiency in carnitine. So far, LC is thought to inhibit both triiodothyronine (T3) and thyroxine (T4) entry into the cell nuclei, and thus supplementation could be beneficial to increase tissue levels (Benvenga S. A., 2004).

Other thyroid diagnoses, such as thyroid storm, were successfully treated with a combination of conventional treatment, such as Methimazole and LC (Benvenga S. L., 2003). Another study showed an awakening from a coma caused by thyroid storm after intravenous administration of LC (Kimmoun, 2011). The methods by which carnitine elicits these effects on the thyroid is not fully understood. Some studies have shown that LC can also modulate thyroid hormone action in peripheral tissues, most often through inhibition (Benvenga S. , 2005)

Conclusion

Overall, given that thyroid conditions can be detrimental if they are not treated and overlap with other diagnoses, it is imperative that several effective treatment options be considered, including conventional and natural ones. Evidence has suggested a relationship pattern between lower Mg levels and their potential correlation that could help in treating thyroid autoimmune and other thyroid-related diseases. Vitamin D has shown efficacy in preventing migration of certain thyroid cancer cells, helping predict the success of certain conventional thyroid treatments. Carnitine effectively modulates thyroid metabolites in peripheral tissues and can correct inherent carnitine deficiencies caused by hyperthyroidism. These three powerful supplements have recently shown promise as potential effective therapeutic targets in thyroid disease, enabling a greater spectrum of choice of natural treatments for practitioners and patients.