The Extrathyroidal Role of Iodine

[Jam]

The Extrathyroidal Role of Iodine - Hormones Matter

Iodine deficiency can affect processes outside of thyroid hormones via the extrathyroidal action of inorganic iodine.

www.hormonesmatter.com

Conclusion and Future Developments​

We can appreciate from recent studies that the human genome is set to respond to iodine and at the same time utilize it for fighting infections. When one is sufficiently replete of iodine, they are able to destroy microorganisms directly but also ramp up multiple indirect and direct mechanisms by the intricate network of the human immune system. Overall, from the above discussion we can conclude the following:

• Iodine can directly kill microorganisms such as bacteria, viruses, and yeast by interfering with their electron transport chain, protein synthesis or cell membrane.
• The immune system can utilize iodine in powerful compounds such as hypoiodite to kill microorganisms.
• Iodine and iodide can enter immune cells and affect genetic transcription and the function of immune cells. These effects have been shown to enhance the immune system in human cells as well as within large animals.
• Iodine has been used successfully to treat cancers. Part of its anti-tumor effects are both direct (on tumor cells) but by also activating the immune system.
• Some women with infertility or recurrent pregnancy loss seem to have low iodine levels in their reproductive tissue.
• Immune cells are able to produce thyroid hormones given the proper environment.
• “Normal” thyroid blood tests do not necessarily correlate with complete iodine body sufficiency.

Certainly more studies are underway to define the role of extrathyroidal iodine in all body compartments. For example, the author speculates that iodine is important for liver detoxification. This is because cell culture studies showed that iodine can increase levels of Cytochrome P450 enzymes which is likely to also occur in the liver in response to iodine replenishment. While it would be difficult to attain complete review and consensus regarding the recommended daily doses of iodine, the research presented above suggests that we certainly need more than what is currently recommended.

 

[Jam]

More from the same researcher:

Frontiers | A Role for Iodide and Thyroglobulin in Modulating the Function of Human Immune Cells

Iodine is an essential element required for the function of all organ systems. Although the importance of iodine in thyroid hormone synthesis and reproductio...

www.frontiersin.org

Introduction​

Iodine is an essential mineral required for the biosynthesis of thyroid hormones and subsequent proper function of metabolic pathways of all body organs (1). Disorders stemming from iodine deficiency or insufficiency are a worldwide issue affecting approximately two billion people including school-aged children (2, 3). The requirement for sufficient iodine levels encompasses all stages of life (2, 4). First, increased iodine levels are required during pregnancy, and reduced amounts lead to miscarriages and reproductive failures (5–8). This is in-part due to the role of iodine-derived thyroid hormones, thyroxine (T4), and triiodothyronine (T3), for optimal fetal brain development (9, 10). Second, congenital hypothyroidism, defined by reduced thyroid hormones leading to stunted mental and physical development during early childhood, is caused by insufficient iodine intakes (2–4, 11). In adults, non-optimal iodine intake causes hypothyroidism and goiter formation that could be reversed with increased iodine intakes or supplementation (2, 4, 12, 13). Therefore, iodine is required at all stages of life, and its decreased uptake will lead to potentially life threatening conditions and/or severe reduction of quality of life.

Production of thyroid hormones begins with iodide transportation into thyroid follicular cells in the thyroid gland via the sodium iodide symporter (NIS) (14, 15). Iodide molecules are then shuttled through another receptor, PENDRIN, into the thyroid colloid/lumen. Membrane bound thyroid peroxidase (TPO) enzymes oxidize iodide into iodine, a reaction needed for the eventual conjugation or organification of iodine into tyrosyl compounds present on the large dimeric protein thyroglobulin (TG). These biochemical pathways are the source of iodinated tyrosines that eventually form thyroid hormones T4 and T3. T4 forms 80–90% of total biologically active hormones made by the thyroid and are stored in TG (15–17). TG is endocytosed by follicular cells and undergoes proteolytic degradation thereby releasing mostly T4 and relatively low amounts of T3 into peripheral blood. The activity of tissue bound deiodinase enzymes converts T4 into the more biologically active hormone T3 (15, 18). Ultimately, thyroid hormones affect the metabolic processes of cells, which include gluconeogenesis, glycogenolysis, thermogenesis, and protein metabolism (15).

Interestingly, thyroid hormones can directly affect multiple branches of the immune system by enhancing dendritic cell antitumor immunity, B cell differentiation, phagocytosis, natural killer cytotoxicity, inducing higher expression of cytokines, and increasing the frequency of T cell memory cells (19–23). The effects of thyroid hormones on immune cells are due in-part through activation of protein kinase C signaling (20). Furthermore, immune cells are able to produce TSH and utilize TSH to increase T3 levels (24, 25). Thus, far no significant sources of de novo T4 that could affect tissue or blood hormone levels have been identified other than the thyroid gland. However, intriguing findings by Nagao et al. and others demonstrated the likelihood of extrathyroidal T4 synthesis in thyroidectomized rats (26, 27). Others have shown the presence of low intracellular levels of thyroxine in cardiomyocytes utilizing radioactive iodide 125I, and the presence of “thyroxine-like” compounds in 131I-pulsed leukocytes (28, 29). The prospect of extrathyroidal T4 production is strengthened by experiments demonstrating the presence of iodinated tyrosines and thyroid biosynthesis machinery (NIS, TG, and TPO) in multiple tissues including the endometrium, placenta, mammary glands, thymus, testis, liver, and kidneys (30–34). These studies reflect the potential for iodide influx into these tissues. Overall, sources of extrathyroidal thyroxine remain elusive.

The direct effects of inorganic iodine or iodide on cellular activity of immune cells, outside of thyroid hormones, remain relatively unexplored. Evidence for possible direct role for iodine on immune cells was demonstrated by Marani et al. wherein school children deficient in iodine had reduced immune responses despite normal thyroid hormone levels (35–37). Further studies on human breast cancer cells demonstrated the effects of Lugol’s solution, composed of molecular iodine (I2) and potassium iodide (KI), on the transcriptional activity of these cells (38). Other iodine concentrating tissues have been identified including ovaries, salivary glands, and the thymus (39, 40). Similarly, a 1971 study by Stolc showed that 131I-pulsed leukocytes could concentrate iodide intracellularly (28). Xiaoyi et al. studied the cytotoxic effects of molecular iodine in murine immune cells and found, increased lymphocyte survival, slightly reduced CD4/CD8 ratios, and increased IFNγ/IL4 ratio upon activation. Nonetheless, the effects and mechanisms of iodide, as well as molecular iodine, on the function immune cells remains ill explored. The immune system not only protects against foreign pathogens, tumors, and autoimmune responses but it can also modulate and provide a growth milieu during tissue repair and pregnancy through the production of growth factors and angiogenesis (41–43). During the stages of pregnancy, the balance between pro- and anti-inflammatory factors needs to be actively balanced through production of multiple cytokines and immune agents (41, 44).

Due to the importance of iodine and thyroid hormones in pregnancy and the modulatory roles of the immune system on this process, we sought to explore the interplay between thyroid-related molecules and the immune system. In this study, we have examined the effects of inorganic iodine/iodide on cellular function and assessed if immune cells could secrete thyroid hormones. To this end, we have analyzed the expression of iodide transporters in normal donor peripheral immune cells and determined if iodide induces functional changes in the activity these cells. Our studies show a pronounced iodide-induced transcriptional and cytokine response by human peripheral blood leukocytes that were not attributed to new thyroid hormone synthesis. Interestingly, substantial amounts of thyroid hormones were released upon incubation of leukocytes with thyroid-derived TG. Altogether, these observations demonstrate a novel insight on the effects of iodide on human immune cells and highlight leukocytes as a potential source for T4 in local tissues and peripheral blood.

 

[Jam]

Why some people may respond negatively to iodine supplementation:

"The subject of daily recommended iodine intake is extremely controversial even within functional medicine groups. Part of this controversy is due to the fact that a small population can respond negatively to high-dose (> 12-100 mg) iodine supplementation by amplifying autoimmune thyroiditis (increased thyroid antibodies). While this is true in some cases, it is not common and the missing link for that group is probably, in-part, deficient antioxidant defenses. This includes reduced levels of selenium, glutathione, and copper. Anytime iodine is ingested, the thyroid ramps up hydrogen peroxide production and reactive oxygen species. If there are no antioxidant defenses, well then the person is left defenseless against thyroid injury and autoimmune antibody production."

 

[Ismail]

Why some people may respond negatively to iodine supplementation:

"The subject of daily recommended iodine intake is extremely controversial even within functional medicine groups. Part of this controversy is due to the fact that a small population can respond negatively to high-dose (> 12-100 mg) iodine supplementation by amplifying autoimmune thyroiditis (increased thyroid antibodies). While this is true in some cases, it is not common and the missing link for that group is probably, in-part, deficient antioxidant defenses. This includes reduced levels of selenium, glutathione, and copper. Anytime iodine is ingested, the thyroid ramps up hydrogen peroxide production and reactive oxygen species. If there are no antioxidant defenses, well then the person is left defenseless against thyroid injury and autoimmune antibody production."

Very interesting and beneficial, thank you ?

 

[Ismail]

Why some people may respond negatively to iodine supplementation:

"The subject of daily recommended iodine intake is extremely controversial even within functional medicine groups. Part of this controversy is due to the fact that a small population can respond negatively to high-dose (> 12-100 mg) iodine supplementation by amplifying autoimmune thyroiditis (increased thyroid antibodies). While this is true in some cases, it is not common and the missing link for that group is probably, in-part, deficient antioxidant defenses. This includes reduced levels of selenium, glutathione, and copper. Anytime iodine is ingested, the thyroid ramps up hydrogen peroxide production and reactive oxygen species. If there are no antioxidant defenses, well then the person is left defenseless against thyroid injury and autoimmune antibody production."

Are you supplementing with iodine? If so, for how long? And have you noticed any benefits?

 

[Jam]

Are you supplementing with iodine? If so, for how long? And have you noticed any benefits?

I've been using iodine for several years, in the way it used to be used a century ago -- as a medicine, liberally. I do not "supplement" with it, in the way that vitamins and other minerals are supplemented. In my case, I have been using it primarily to treat a periodontal condition and related arthritis. I mainly use SSKI (saturated solution of potassium iodide).

 

[Ismail]

I've been using iodine for several years, in the way it used to be used a century ago -- as a medicine, liberally. I do not "supplement" with it, in the way that vitamins and other minerals are supplemented. In my case, I have been using it primarily to treat a periodontal condition and related arthritis. I mainly use SSKI (saturated solution of potassium iodide).

Amazing, thank you ?

 

[yerrag]

Thanks, Jam.

Good information. I like that you present them in morsels that are easy to digest.

 

[Dr. B]

Why some people may respond negatively to iodine supplementation:

"The subject of daily recommended iodine intake is extremely controversial even within functional medicine groups. Part of this controversy is due to the fact that a small population can respond negatively to high-dose (> 12-100 mg) iodine supplementation by amplifying autoimmune thyroiditis (increased thyroid antibodies). While this is true in some cases, it is not common and the missing link for that group is probably, in-part, deficient antioxidant defenses. This includes reduced levels of selenium, glutathione, and copper. Anytime iodine is ingested, the thyroid ramps up hydrogen peroxide production and reactive oxygen species. If there are no antioxidant defenses, well then the person is left defenseless against thyroid injury and autoimmune antibody production."

does that include vitamin C and E
which substances can we intake to boost antioxidant defenses and glutathione/glutathione peroxidase and catalase, besides selenium and copper.
that may mean vitamin C and zinc could actually hurt since those deplete copper. too much iron also depletes copper.

 

[Makrosky]

Amazing. Thanks Jam.

does that include vitamin C and E
which substances can we intake to boost antioxidant defenses and glutathione/glutathione peroxidase and catalase, besides selenium and copper.
that may mean vitamin C and zinc could actually hurt since those deplete copper. too much iron also depletes copper.

2gr. Vitamin C x day is often recommended on protocols for iodine supplementation.

E and C recycle each other so it can't hurt I guess.

Ideally Vit C should be taken away from other supps including iodine and copper since it may react with those and form who knows which compounds. It reacts with iodine that's for sure.

 

[Dr. B]

Amazing. Thanks Jam.


2gr. Vitamin C x day is often recommended on protocols for iodine supplementation.

E and C recycle each other so it can't hurt I guess.

Ideally Vit C should be taken away from other supps including iodine and copper since it may react with those and form who knows which compounds. It reacts with iodine that's for sure.

how does it react with iodine? i heard some people do use them together for the protocol

 

[Makrosky]

how does it react with iodine? i heard some people do use them together for the protocol

I don't know but you can try it yourself. You put a drop of Lugol on a glass of water, then put some vit C and it turns transparent. Exactly the same that happens with methylene blue.

 

[Jam]

how does it react with iodine? i heard some people do use them together for the protocol

The iodine oxidizes the ascorbic acid to DHAA and itself becomes reduced to iodide.

 

[Dr. B]

Amazing. Thanks Jam.


2gr. Vitamin C x day is often recommended on protocols for iodine supplementation.

E and C recycle each other so it can't hurt I guess.

Ideally Vit C should be taken away from other supps including iodine and copper since it may react with those and form who knows which compounds. It reacts with iodine that's for sure.

would orange juice recycle vitamin E too or only ascorbic acid supplements