Selenium is certainly not the only nutritional factor that plays a role in Hashimoto’s Thyroiditis (HT) (see previous blog post,). Other known dietary factors that affect the disease are iodine, vitamin D, iron, and debatably gluten (see next blog post).
Iodine is a complicated factor in the disease, as too little as well as too much can exacerbate the progression and symptoms of thyroid disease. It has been known that iodine deficiency causes hypothyroidism, and it often did, worldwide, before the implementation of iodized salt (in developed countries) because iodine is necessary to produce thyroid hormones (T3 and T4), and cannot be produced by the body. Excess iodine, though, exacerbates HT and even hypothyroidism in some individuals.
In a normal thyroid gland, tyrosine molecules are iodinated by thyroid peroxidase (TPO) in the presence of hydrogen peroxide (H2O2). These mono- or di- iodotyrosines combine in different combinations to create T3 (with three iodine molecules attached) or T4 (with 4 iodine molecules attached) thyroid hormones which are released into the bloodstream after processing in the thyrocyte to release the thyroglobulin attached in their production.
High iodine intake inhibits the synthesis of thyroid hormone synthesis and antioxidant capacities of the thyroid gland by inducing apoptosis of thyrocytes and generating reactive oxygen species (which may be part of the reason that Se is decreased in HT patients). Reactive oxygen species are generated by the organification of iodine, which occurs in the thyroid. Apoptosis is more complicated. Iodine excess causes thyrocytes to upregulate ICAM-1, an adhesion molecule, which changes the immunogenicity of the cells. This upregulation is synergistically stimulated by H2O2, generated by iodine organification, which activates ICAM transcription. When a subset of CD4+ T-cells, Th1 cells, encounter ICAM-1 they bind to it and are stimulated to release the cytokine IL-6, as well as interferon gamma (IFN- γ) and tumor necrosis factor (TNF-α), which signify that there is a foreign pathogen that must be eliminated (ICAM binding allows the leukocytes to migrate into the thyroid, where they recognize foreign antigens present due to high iodine, such as highly iodinated thyroglobulin). IL-6, IFN- γ, and TNF-α lead to the downregulation or inactivation of T-reg cells, which dampen the immune response and help to anergize (de-activate) leukocytes which recognize foreign antigen in the absence of inflammation. Therefore, this combination of reactive oxygen species, production of cytokines via ICAM-1 upregulation, and dampening of T-regulatory t cells eventually leads to activation of the adaptive immune system without it being checked. This eventually leads to the production of antibodies against the thyroid and therefore its destruction.
The previously described processes will occur in any individual with excessive and chronic iodine intake. In particularly susceptible individuals, however, the iodine excess does all of the above as well as inducing Th17 (a type of CD4+, cytokine producing T-cell) production, which enters the thyroid and secretes pro-inflammatory cytokines and induces CD8+ cytotoxic T-cell activation. These individuals also produce TRAIL in response to high iodine, which is a TNF-related apoptosis-inducing ligand. Both of these phenomenon lead to the attack and destruction of the parenchyma cells of the thyroid.
It is now firm knowledge that iodine intake levels slightly below or above normal levels (about 150 mcg/L) are associated with disease risk. Iodine levels should be tested in all individuals, not just those suffering from thyroid disease, since iodine not only affects the disease progression and symptoms, but can also induce hypothyroidism or autoimmune thyroid disease (HT). Duntas, L. H. states that, “excessive iodine intake ([median urinary iodine excretion]>300 μg/l) could well become a serious public health concern because of its ability to substantially increase subclinical hypothyroidism and [Autoimmune Thyroiditis] rates.” Therefore, the threat is not necessarily an increase in overt cases of thyroid disease, but rather the rise of subclinical thyroid issues, lowering the quality of life for numerous patients nd persisting by not being easily identifiable.
Vitamin D had been considered merely a fat-soluble vitamin, but recently has been acknowledged as a steroid hormone. It is responsible for regulating many immune processes. It is known without doubt that vitamin D is found lowered in HT patients, as a result of auto-immune processes. Some studies have also shown that vitamin D supplementation lowered TPO and Tg antibodies, though more trials must be done before this relationship is confirmed. Calcitriol (1a ,25(OH)2 D, the active form of vitamin D used by the body), mainly strengthens the innate immune response via antimicrobial peptide (defensin, etc) regulation. In addition, it dampens the adaptive immune response (the B and T cell response that triggers HT) by “inhibiting the pro-inflammatory effects of Th1 and Th17 cells and enhancing the anti-inflammatory activities of Th2 and Treg cells.” This alone would protect against HT progression, but vitamin D also helps protect against autoimmunity by inhibiting certain dendritic cell subsets from maturing or presenting antigen.
In addition, it has been postulated that chronic infection may actually cause autoimmunity. For example, Epstein-barr virus (a whole-body herpes virus that causes mononucleosis, EBV), may be a causal agent of auto-immune disease and vitamin-d regulated immune responses increase CD8+ T-cells, which clear cells infected with EBV to eliminate the virus.
Thyroid peroxidase (TPO) is a heme (iron) containing enzyme. Iron deficiency causes TPO to be inactive, leading to less T3 and T4 hormone being produced, causing the symptoms of thyroid disease, “In rodent studies, iron deficiency, with or without anemia, decreased serum T4 and T3 concentrations, lowered 5¢ -deiodinase activity, and reduced the ability to thermoregulate in response to a cold environment.” Furthermore, it has been proposed that iron deficiency also decreases the ability of T3 to bind to its receptors at extra-thyroid locations.
Meloni et al found that out of 14 hashimotos patients 6 had iron deficiency. The cause of iron deficiency in HT patients is often not the actual pathogenesis of HT, but the often comorbidity of auto-immune gastritis, which inhibits the absorption of nutrients. This gastritis is often related to celiac disease, found in many HT patients. This will be explored in the next post.