Friday, June 28, 2013

Iodine Induced Reduction in Hepatic Deiodinase Activity Leads to Hypothyrodism and the Accumulation of Liver Fat That May Eventually Pave the Way to Diabesity

While us Westerners think of goitre mostly as a result of iodine deficiency, the Chinese have learned by hard that the opposite is about as likely - goitre in response to iodine in the drinking water is a huge health problem in certain parts of the country (Zheng. 2000)
As colorful as the web may have become, it is still full of paradigmatic black-and-white thinking: The world is either black or white and if you browse the blogosphere, it would appear that iodine would certainly belong to the white part of our world. That in exactly those people who are often referred to as an example of the multitude of beneficial health effects, namely the Japanese, a high intake of iodine has repeatedly been shown to be associated with low thyroid function and even full-blown hypothyroidism, on the other hand, is something you will probably not learn from the tons of unreferenced stuff you'll find on the Internet about how good, if not essential it was for your health to take copious amounts of iodine everyday (about the same amount you would take if the nuclear powerplant next to you exploded to saturate and shut down your thyroid and prevent it from taking up the radioactive iodine).

The Ying and Yang of high and low iodine intake

A recently published rodent study from the Huazhong University of Science and Technology, the Binzhou Medical University and the Shen Zhen Center for Chronic Disease Control, in China (Xia. 2013) does now shed some light onto the underlying mechanisms of the well-known thyroid disrupting effects of the structural backbone of all mammalian thyroid hormones, iodine. While the whole spectrum of disorders of iodine excess includes hypothyroidism, hyperthyroidism, autoimmune thyroiditis,embryo toxicity, and depression of brain development (Guo. 2006; Rose. 2001; Roti. 2001; Yang. 2006) Yun Xia et al. are probably the first to investigate its hazardous effects of iodine excess on the liver.

To this end, the Chinese researchers supplemented rats on a standard diet containing a baseline level of 365μg/kg iodine with different doses of iodine in the form of potassium iodate (KIO3) in the drinking water for 3 months:
"In 2000, the Chinese Nutrition Society stated that the recommended nutrient intake (RNI) of iodine of adults is 150μg/day and the tolerable upper intake level (UL) is 1,000μg/day.
Conversely, intake of iodine at about sixfold of its RNI may induce injury. In addition, many excess iodine animal experimental data indicate that ten times the normal iodine intake in mice for about 3 months can cause damage. Moreover,the results of our previous experiment show that drinking 1.2 mg I/L iodine water for 1 month had no significant effect on serum lipid metabolism, while prolonged exposure for 3 months induced an increase of serum cholesterol." (Xia. 2013)
According to these results, the mice in the study were randomized to receiver either 0, 0.3, 0.6, 1.2, 2.4, and 4.8 mg I/L iodine, corresponding to 0-, 1-, 2-, 4-, 8-, and 16-fold of the adequate/normal iodine intake for 3 months to explore the dose-dependent effect of iodine on hepatic steatosis. In the course of the trial, dood consumption, water consumption of each group, were recorded meticulously and the weight gain of each mouse was recorded daily.

Additionally, another 60 weaning female Balb/c mice were randomly assigned to six groups and given iodine at different levels (0, 0.3, 0.6, 1.2, 2.4, and 4.8 mg I/ml) for 1 month just for
measuring the oxidative stress parameters in serum and liver.
Figure 1: Triglyceride content in liver and serum, as well as SREBP-1c and fatty acid syntethase (FAS) activity after 3 months on diets with additional iodine (Xia. 2013)
While neither food intake, nor water consumption or weight gain differed significantly between the groups (data not shown), a brief glance at the data in figure 1 should suffice to see that there was a dose-dependent increase in hepatic triglyceride levels (=fatty liver disease) that was accompanied by corresponding increases in serum triglyceride, when the liver was clogged up to the max - as it appears to be the case with 8x or 16x higher than normal levels in the diet (for humans that would thus be ~1.6g or 3.2g of potassium iodiate).

Figure 2: Total antioxidant capacity, glutathione peroxidase, SOD, and lipid peroxidation (MDA) after 1 and 3 months expressed relative to untreated control (Xia. 2013)
The fatty acid accumulation in the liver was accompanied by profound changes in total antioxidant and SOD and glutathione status, as well as significant increases in lipid oxidation (as indicated by the +61% and +85% increase in MDA in the groups with the highest intake of supplemental iodine). Contrary to the commonly propagated myth that tons of supplemental iodine would increase the thyroid function these changes were accompanied by profound decreases in D1 deiodinase activity and correspondingly decreased conversion of T4 to T3 (see figure 3).
Figure 3: Changes in thyroid hormone and deiodinase levels; expressed. rel. to control (Xia. 2013)
It should thus not surprise you, that the levels of TSH and T4 in the rodents increased, while those of T3 decreased (no conversion = hypothyroism, no matter how much T4 you got floating around).

Low D1 => Low T3 => fatty liver disease

In fact, the reduced local conversion of T4 to T3, is also behind the accumulation of triglycerides in the liver and blood of the animals, as the
"[r]educed plasma T3 level resulted in the upregulation of SREBP-1c mRNA and FAS mRNA that ultimately led to the accumulation of triglycerides in the liver. [...] Evident hepatic steatosis was observed in mice challenged with 2.4 and 4.8 mg I/L iodine in drinking water. " (Xia. 2013)
As a SuppVersity student you know about the downstream effects, but I guess it makes sense to reiterate them for the newbies: Since the liver plays a, if not the pivotal role in systemic lipid homeostasis the reduced oxidation of triglycerides and the increased storage will sooner or later lead to an increased secretion of triglyceride-rich lipoprotein (VLDL) as a compensatory response by which the liver will desperately try to spread the lipid burdon to other organs and tissues. Overwhelmed with the sudden onslaught of triglyceride laden VLDL particles which are easily oxidized during their voyage through your blood stream, this opens the door to a narrowing of the arteries, cardiovascular disease and stroke.

For the majority of you, overtraining and undereating is probably a much greater threat, when it comes to hypothyrodism (learn more about "self-inflicted hypothyrodism"). However, contrary to excess iodine intake that will not clog up your liver and arteries and eventually cause heart disease and stroke.
Bottom line: If we assume based on the available epidemiological data that the general mechanism was identical in human beings, the ingestion of large amounts of iodine which are often touted as a remedy to all sorts of metabolic syndroms may in fact exert the exact opposite effects.

Yet, although I would be cautious about extrapolating the exact cut-off levels, it appears that dietary intakes in the 800µg range and thus 4-6x more than the RDA can still be considered relatively save. So if you are neither taking high dose supplements or living on tons of seaweed, this is probably not much of a concern for most of you. In addition it would warrant investigation if / to which extent the addition of extra selenium would ameliorate these effects. After all, the latter has been shown to have protective effects against iodine intoxication in the very same rodent model in a 2006 study by Xu et al. (Xu. 2006).

References:
  • Guo H, Yang X et al. Effect of selenium on thyroid hormone metabolism in filial cerebrum of mice with excessive iodine exposure. Biol Trace Elem Res. 2006; 113:281–295. 
  • Rose NR, Bonita R et al. Iodine: an environmental trigger of thyroiditis. Autoimmun Rev. 2002;  1:97–103.
  • Roti E, Uberti ED. Iodine excess and hyperthyroidism. Thyroid. 2001;11:493–500.
  • Xia Y, Qu W, Zhao LN, Han H, Yang XF, Sun XF, Hao LP, Xu J. Iodine Excess Induces Hepatic Steatosis Through Disturbance of Thyroid Hormone Metabolism Involving Oxidative Stress in BaLB/c Mice. Biol Trace Elem Res. 2013 May 28. 
  • Xu, J, Yang, XF., Guo, HL, Hou, XH Liu, LG, & Sun, XF. Selenium supplement alleviated the toxic effects of excessive iodine in mice. Biological trace element research; 2006 111(1-3), 229-238. 
  • Yang XF, Xu J et al. Developmental toxic effects of chronic exposure to high doses of iodine in the mouse. Reprod Toxicol. 2006: 22:725–730. 
  • Zhao J, Wang P, Shang L, Sullivan KM, van der Haar F, Maberly G. Endemic goiter associated with high iodine intake. Am J Public Health. 2000 Oct;90(10):1633-5. 

13 comments:

  1. This comment has been removed by the author.

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  2. >800mg range and thus 4-6x more than the RDA
    Typo. should be mcg.

    There is Iodoral tablets, which are very popular in some circles. Every tablet contains either 12.5 or 50 mg mixture of elemental iodine and iodide as the potassium salt. Now thats doses. :)

    Any studies on brazil nuts (selenium) toxicity among locals?

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    1. sorry, corrected the typo.. see comment on brazil nuts below and add this > "No evidence of selenosis from a selenium-rich diet in the Brazilian Amazon" (http://www.sciencedirect.com/science/article/pii/S0160412011001917) > "although [selenium levels] surpassed concentrations considered toxic [...] no dermal or breath signs or symptoms of Se toxicity were associated with the biomarkers of Se status."

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  3. Yes, selenium deficiency is common enough in China.
    I have searched the internet many times for a case report of selenium toxicity from Brazil nuts without success.

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    1. same here... there is no peer-reviewed research that actually proves you can intoxicate yourself with brazil nuts only warnings in every other paper about selenium that they got plenty of it and COULD be a problem

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  4. the high iodine researchers start at 50mg of molecular iodine/potassium iodide. http://www.optimox.com/pics/Iodine/opt_Research_I.shtml

    i would love it if someone not associated with Optimox, the makers of Iodoral, would do some peer-reviewed articles... however, high iodine requires a number of co-nutrients: http://breastcancerchoices.org/iprotocol.html

    more iodine research: http://iodineresearch.com/research.html

    and yet, i wonder about the role of magnesium deficiency in the whole picture.

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    1. sounds to me like you were reading all the popular "scientific" stuff google will turn out when you type in stuff

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  5. is that a typo at the bottom of the article? 800mg? does it mean 800ug?

    ive been using the idoral at 12.5mg, selenium and tyrosine combo for a while now. I've never been diagnosed hypo but my TSH levels were always up there (2.9-3.2), my last test came in at 2.4 which was the smallest level ever, although not ignoring the lab error margin.

    I'll probably knock it down to a more 800ug dose or there abouts.

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    1. oh yeah, sorry. That's a typo. And wrt to TSH, you got to get your fT4 and fT3 levels to see what the iodine does; to cut back is a good idea anyway

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  6. Why is this not happening to Japanese who take milligram amounts of iodine? In the coast region they reach 100 mg or more.

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    1. that is the wrong question because it DOES happen => "»ENDEMIC COAST GOITRE« IN HOKKAIDO, JAPAN" http://www.eje-online.org/content/50/2/161.abstract

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  7. It's very easy to provide references, like that one. But that IS FAR FROM BEING CONCLUSIVE, just like the possible "issues" with green tea and many other hard conclusions reached.

    The study you cite, has been debunked to different degrees by Iodine Doctors AND even those who don't "sell" anything or work with iodine.


    "The Japanese authors investigating the Hokkaido goiter did not think iodide was the cause of the thyroid enlargement"

    "Kelp-induced endemic goiter was reported to occur in the coastal regions of Hokkaido nearly 30 years ago. Such goiter has now **** disappeared *****."

    "Please note that Konno, et al called it "kelp-induced goiter" whereas Wolff called it "iodide-goiter," without any evidence that iodide was the cause. Wolff blamed iodide for the Hokkaido goiter without any scientific data, and further, he stated that this iodide goiter was probably caused by the W-C effect, a double assumption."

    " Seaweed also concentrates other halides such as bromide, which possess goitrogenic, carcinogenic and narcoleptic properties (1). Seawater is very poor in iodide and relatively rich in bromide with 0.05 PPM iodide and 70 PPM bromide. There is 1400 times more bromide than iodide in seawater. "

    http://www.optimox.com/pics/Iodine/IOD-04/IOD_04.html
    http://optimox.com/pics/Iodine/IOD-12/IOD_12.htm

    Yes I KNOW what optimox is, no need to mention it. But there's plenty of references in there, dozens.

    Despite being "popular "scientific" content" on the internet, THAT IS WHAT HAS TO BE DEBUNKED.

    I agree that the internet is a two edged sword: good and bad. Too much people selling things and also the interests from "evil" organizations with bigger interests than people's wellness.

    BEWARE! Research, be objective before jumping to conclusions. That goes for common lay persons, they should be more like Dr. Andro so they don't harm themselves OR lose the opportunity to reach optimal health!

    BTW there's much more to Idoine than just the thyroid, like cancer, antioxidant protection, immune system, etc.

    Not criticizing SuppVersity or Dr. Andro, I'm a big fan of them, just felt like mentioning that there's much more to this problem than just a rodent study.


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  8. Curiously this doesn't get debated.

    BTW, I forgot to say that selenium increases deiodonase.

    http://mikemutzel.com/debunking-the-anti-iodine-myth-the-role-of-selenium/

    Don't drop the iodine.

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