Hashimoto’s thyroiditis (chronic lymphocytic thyroiditis) is one of the most common autoimmune disorders of the thyroid and has complex factors which result in an autoimmune reaction resulting in the destruction of thyroid gland and constant inflammation via antibodies mainly against thyroperoxidase (TPO-AB). Accompanying clinical symptoms are elevated thyroid stimulating hormone (TSH) accompanied by paradoxically low free thyroid (T3 and T4) levels. It initially may lack symptoms other than elevated TPO-AB, then progress to hypothyroidism as the synthesis of thyroid hormone becomes increasingly impaired, which can essentially only be treated with synthetic thyroid hormone as a replacement measure. It is thus quintessential to investigate avenues of preventing progressive thyroid gland destruction via preventing autoimmunity to thyroid antigens by simple balance of vitamin co-factors involved in thyroid synthesis and autoimmunity.

Recent studies have investigated the effects of glutathione on Hashimoto’s thyroiditis. These speculations were fueled with anecdotal and case-study type evidence that glutathione (GSH) supplementation via intravenous supplementation of synthetic glutathione or oral supplementation with precursors to glutathione, such as cysteine, improved the conditions of cancer. There has also been preliminary evidence that glutathione plays an important role in the improvement of diabetes, neurodegenerative disorders, and other inflammatory and autoimmune diseases (via providing the redox potential of glutathione peroxidase). These speculations originated from the antioxidant function of glutathione, as the most abundant antioxidant in mammalian cells, as well as its involvement in immune system function (where it helps reduce reactive oxygen species after respiratory burst in phagocytes and also acts as a thiol regulator of the immune system, aiding in the shift from innate to adaptive immunity, therefore dampening inflammatory responses). Oxidation via free radicals generated by metabolic processes can damage organelles as well as DNA, resulting in serious disease. Damage caused by the presence of many reactive oxygen species or reduced cellular reduction potential also triggers inflammation. Hydrogen peroxide, H2O2, is produced and necessary for thyroperoxidase to fix iodine to tyrosyl residues of thyrocytes, thus glutathione peroxidase is necessary in the thyroid gland to neutralize excess H2O2. Studies investigating the role of glutathione in Hashimoto’s thyroiditis, though, have been less than conclusive.

It is important to understand that active, reduced, glutathione peroxidase requires a co-factor of selenium to function. It has been known for a long time, with substantial evidence, that selenium deficiency can exacerbate Hashimoto’s symptoms. Selenium supplementation has been shown to reduce TPO-AB and improve mood in some studies, though definitive knowledge has yet to have been obtained about its efficacy. It is being speculated that the positive effects are due to selenium’s role in glutathione peroxidase’s function. It is known that selenoproteins (using a selenocysteine form of selenium) include glutathione peroxidase and thioredoxin reductase, yet they also function as the iodothyronine deiodinase enzymes which convert T4 to the active, T3 form (and vice versa, depending on the isoform). In addition, selenium is involved in the upregulation of T-reg cells and CD4+ T cells, dampening inflammation (reducing cytokine production) via a SELENOS selenoprotein (which decreases cytokine production of TNF-a and IL-1b, known factors in Hashimoto’s thyroiditis), and the suppression of a certain MHCII expression on thyrocytes, reducing chances for antibody formation. Selenium aids these processes, including reduction (anti-oxidation) in adequate quantities, but is actually cytotoxic, producing opposite effects, at high levels (within about a 200 mcg range!).

The investigation of glutathione peroxidase as a main factor in the pathogenesis of Hashimoto’s thyroiditis is due to the known importance of selenium (which I necessary for glutathione peroxidase’s function) as well as the postulation that in the absence of adequate antioxidant activity, the damage thyroid gland and associated enzyme materials are what provide the antigens to which an autoimmune response is mounted, in the presence of “foreign” antigen and stresses cells due to reactive hydrogen peroxide. In addition, the thyroid gland contains more grams of selenium per tissue than any other organ in the body. Some studies have confirmed this hypothesis, reporting that, “mean [glutathione] levels in [Hashimoto’s thyroiditis] patients is markedly lower compared to healthy controls. The fall in [glutathione] levels coincided with a marked elevation of [glutathione peroxidase] activities in [H Hashimoto’s thyroiditis] patients; [glutathione] levels were inversely and significantly correlated with TPO-AB titers,” which presents clear and logical support for glutathione being a major to main factor in the etiology of Hashimoto’s thyroiditis. This, sadly, has not been replicated as it should be if it were strictly true. One study found that glutathione peroxidase levels and selenium levels were not correlated, nor were the levels altered in patients who were currently under treatment with levothyroxine for hypothyroidism (late Hashimoto’s). In addition, a meta-analytical study found that there was a high bias risk in many studies supporting selenium and glutathione’s role in Hashimoto’s thyroiditis, claiming that. “evidence to support or refute the efficacy of selenium supplementation in people with Hashimoto’s thyroiditis is incomplete and not reliable to help inform clinical decision making.”

It is imperative that larger scale studies investigating selenium and glutathione peroxidases’ role in the etiology of Hashimoto’s thyroiditis as well as certain aspects of their mechanisms in the pathogenesis are performed. Prior to such information, it would be unscientific and biased to make any claims about the involvement of such things in the disease. With the current information, it is sound to claim that selenium levels ought to be checked and supplemented if low, due solely to their implications in the immune response and the regulation of conversion between T3 and T4. As for the glutathione aspect, prior to knowing whether it is implicated in the disease, it would be completely risk free and perhaps beneficial to consume foods rich in glutamate, cysteine, and glycine, glutathione’s precursors (as supplementation done in excess may be detrimental).









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