Category Archives: Iodine and selenium

Mario Renato Iwakura’s guest series on the place of iodine and selenium supplementation in treatment of hypothyroidism continues. This is part 2. Thank you Mario! – Paul

UPDATE November 2023: Since this article was written, PHD recommendations for iodine have become firm. We recommend consistent daily supplementation in the range of 150 to 225 micrograms (not milligrams) per day, plus frequent seafood consumption. The supplementation (a) ensures a healthful supply of iodine and (b) accustoms the thyroid to the presence of iodine which minimizes the risk of thyroid injury from intake of a large amount of iodine at once, possibly at a time of selenium deficiency, for example from an all-you-can-eat crab buffet. Supplementation of >1 mg high doses of iodine carries a high risk of thyroid injury, making some parts of the thyroid hypothyroid and possibly also creating nodules with hyperthyroid activity. … Although our recommendations are not in line with Mario’s, nevertheless Mario’s article is fascinating, and a few people have reported benefit from high-dose iodine. Please read his article and judge for yourself! Best, Paul

In Part I (Iodine and Hashimoto’s Thyroiditis, Part I, May 24, 2011) we looked at evidence from animal studies that iodine is dangerous to the thyroid only when selenium is deficient or in excess, and that optimizing selenium status allows the thyroid to tolerate a wide range of iodine intakes. In fact, there were some hints (such as an improved CD4+/CD8+ T cell ratio) that high iodine, if coupled with optimal selenium, might actually diminish autoimmunity.

If that holds in humans too, we should expect that populations with healthy selenium intakes should see a low incidence of thyroid disease and no effect from iodine intake on the incidence of Hashimoto’s thyroiditis. Is that the case?

Korean Study

Dr. K [1] quotes a Korean study [3] of Hashimoto’s patients. Half restricted iodine intake to less than 100 mcg/day, the other half ate their normal seaweed and iodine. Of the 23 patients who restricted iodine, 18 (78%) became euthyroid in the sense of having TSH below 4.43 mIU/L, while only 10 (46%) of the 22 that did not restrict iodine became euthyroid. There was no measurement of symptoms at all, and no report of thyroid antibody titers after iodine restriction, so we don’t know if the iodine restriction relieved the underlying autoimmune disorder.

The selection of subjects for the two groups was odd. Group 1, the iodine restricted patients, had an extremely wide range of starting TSH, averaging 38 mIU/L but with a standard deviation of 82 mIU/L. Since all subjects began with TSH above 5 mIU/L, it’s clear that many of the Group 1 members had TSH near 5 and others had TSH well over 100 mIU/L. In comparison, Group 2, the controls, averaged a TSH of 11 mIU/L with a standard deviation of 11 mIU/L – less than 1/7 the standard deviation of Group 1. Few Group 2 members had a TSH above 30.

Table 2 presents the results. Mean TSH in Group 1 was reduced a little, but it did not even come close to normal. Since 78.3% of Group 1 had TSH below 4.43 mIU/L after 3 months, the other 21.7% had to have averaged a TSH above 102.2 mIU/L at the conclusion of the study. The standard deviation of Group 1 TSH at the end of 3 months of iodine restriciton was 71 mIU/L.

Meanwhile, Group 2 members still had a much lower standard deviation at the end of the study: 19 mIU/L.

A conclusion of this study was that “the initial serum TSH concentration was significantly lower in the recovered patients than in the non-recovered patients, which suggests that the possibility of recovvery is increasingly rare as the initial hypothyroidism becomes more severe.” Since Group 1 originally had a much larger fraction of members with very low TSH than Group 2 (plus a few with extremely high TSH to raise the average TSH), and the definition of recovery was a reduction of TSH to 4.43, perhaps it is not surprising that a higher fraction of Group 1 recovered.

Further calling into question the conclusion that lower iodine intake is beneficial is another observation. Looking at Table 1, we see that Group 2 (controls) had, at baseline, much higher iodine intake and higher urinary iodine excretion. Despite this, goiter size, TSH, antimicrosomal (MSAb) and antithyroglobulin (TGAb) antibodies were all lower!

A Japanese Study

A similar study with similar results was done in Japan [4].

In Asia, high iodine intake is due to high consumption of seaweed. Seaweed is high in naturally produced bromine compounds [5][6][7], arsenic [9][12][13], and mercury [9], and can accumulate radioactive iodine [8][9][10][11]. All these substances are known to interfere with thyroid function.

Bromide levels in urine in Asia are very high and are associated with seaweed consumption [6][7]. Values of 5 to 8.1 mg/l have been observed among Japanese, and 8 to 12 mg/l among Koreans.

It is quite possible that any benefits from “iodine restriction,” i.e. seaweed restriction, were due to reduced intake of bromine, arsenic, mercury, and radioactive iodine.

A China Study

Dr. Kharrazian [2] cites a study done in China [14] comparing three different areas: one with iodine deficiency (Panshan), another where iodine is more than adequate (Zhangwu) and a third where iodine is excessive (Huanghua). More than adequate and excessive iodine was associated with increased risk for subclinical and overt hypothyroidism.

But, another study [15], done in the same regions, showed that, coincidentally, Huanghua, the region with excessive iodine, and Zhangwu, the region with more than adequate iodine, had lower median serum selenium concentrations than Panshan, where iodine was deficient. Blood selenium concentrations were 83.2, 89.1 and 91.4 microg/L, respectively. So iodine consumption was inversely related to selenium consumption. Was it lower iodine, or higher selenium, that was beneficial?

TPOAb antibody levels were inversely associated with selenium levels. Patients with the highest TPOAb antibodies (>600 UI/ml) had lower selenium levels than patients with moderate and lower TPOAb antibodies (respectively 83.6, 95.6 and 92.9 UI/ml). [15]

Studies from Brazil, Sri Lanka, Turkey, and Greece

Dr K also cites a rise in Hashimoto’s incidence in Brazil, Sri Lanka, Turkey and Greece after salt iodinization began. Are these countries deficient in selenium? Well, lets see:

Brazil: The study was done in São Paulo, a city with a large Brazilian-Japanese population. Brazilian-Japanese have significant lower levels of Se than Japanese living in Japan [16].

Greece: Selenium status is one of the lowest of the Europe [17].

Turkey: Selenium status of Turkish children is found to be unusually low, only 65 ng/ml in boys and 71 ng/ml in girls [18]. Turkey is characterized by widespread iodine deficiency and marginal selenium deficiency [19].

Sri Lanka: Significant parts of the Sri Lankan female population may be selenium deficient [20].

One study, done in Egypt, measured iodine excretation in urine and its relation with thyroid peroxidase antibody (TPOAb) [21]. Although the abstract said that a significant correlation was found, this is far from reality, as we can see from Fig. 2.

Another study from Brazil [2] measured urinary iodine excretation and serum TPOAb and TgAb antibodies from 39 subjects with Hashimoto’s, none of whom were receiving treatment at the time of the study. Both antibody titers had no obvious correlation with urinary iodine.

Two discordant epidemiological studies

From the Netherlands, we have a prospective observational study looking at whether the female relatives of 790 autoimmune thyroid disease patients would progress to overt hypothyroidism or hyperthyroidism [22].

Although the relationship was not considered statistically significant, they found that women with high iodine intake (assessed through questionnaires) were 20% less likely to develop thyroid disorders.

Another study from western Australia (a region that has previously been shown to be iodine replete) measured urinary iodine concentration (UIC) of 98 women at 6 months postpartum and checked their thyroid status both postpartum and 12 years later [23]. UIC at 6 months postpartum predicted both postpartum thyroid dysfunction and hypothyroidism  12 years later:

The researchers concluded:

The odds ratio (OR) of hypothyroid PPTD with each unit of decreasing log iodine was 2.54, (95%CI: 1.47, 4.35), and with UIC < 50 lg/l, OR 4.22, (95%CI: 1.54, 11.55). In the long term, decreased log UIC significantly predicted hypothyroidism at 12-year follow-up (p = 0.002) … The association was independent of antibody status.

In short, the more iodine being excreted (and thus, presumably, the more in the diet and in the body), the less likely were hypothyroid disorders – not only at the time, but also 12 years later.

Dangers of selenium supplementation in iodine deficiency.

Selenium supplementation when iodine and selenium deficiencies are both present  can be dangerous, as the experience in northern Zaire, one of the most severely iodine and selenium deficient population in the world, shows [25].

Schoolchildren and cretins were supplemented for 2 months with a physiological dose of selenium (50 mcg Se per day as selenomethionine). Serum selenium was was very low at the beggining of the study and was similar in schoolchildren and in cretins (343 +- 190 nmil/L in schoolchildren, n=23, and 296 +- 116 nmol/L in cretins, n=9). After 2 months of selenium supplementation, the massive decrease in serum T4 in virtually every subject can be seen in fig. 4 below:

In schoolchildren, serum free thyroxin (fT4) decreased from 11.8 +- 6.7 nmol/L to 8.4 +- 4.1 nmol/L (P<0.01); serum reverse triiodothyronine (rT3) decreased from 12.4 +- 11.5 nmol/L to 9.0 +- 7.2 nmol/L; mean serum T3 and mean TSH remained stable. In cretins, serum fT4 remained the same or decreased to an undetectable level in all nine cretins; mean serum T3 decreased from 0.98 +- 0.72 nmol/L to 0.72 +- 0.29 nmol/L, and two cretins who were initially in a normal range of serum  T3 (1.32-2.9 nmol/L) presented T3 values outside the lower limit of normal after selenium supplementation; mean serum TSH increased significantly from 262 mU/L to 363 mU/L (p<0.001).

Another previous similar trial, this time done in 52 schoolchildren, reached the same results: a marked reduction in serum T4 [26][27]. This previous trial “was shown to modify the serum thyroid hormones parameters in clinically euthyroid subjects and to induce a dramatic fall of the already impaired thyroid function in clinically hypothyroid subjects” [27].

What stands out is the difference in the results between euthyroid schoolchildren and cretins/hypothyroids. Two months of selenium supplementation was probably not enough time to affect significantly the thyroid of the euthyroid schoolchildren (althougt already impacted T4 and fT4). But, in cretins and hypothyroids, where the thyroid was already more deficient, the impact was evident.

Conclusion and What I Do

Iodine and selenium are two extremely important minerals for human health, and are righly emphasized as such in the Perfect Health Diet book and blog. I believe they are fundamental to thyroid health and very important to Hashimoto’s patients.

A survey of the literature suggests that Hashimoto’s is largely unaffected by iodine intake. However, the literature may be distorted by three circumstances under which iodine increases may harm, and iodine restriction help, Hashimoto’s patients:

1. Selenium deficiency causes an intolerance of high iodine.
2. Iodine intake via seaweed is accompanied by thyrotoxic metals and halides.
3. Sudden increases in iodine can induce a reactive hypothyroidism.

All three of these negatives can be avoided by supplementing selenium along with iodine, using potassium iodide rather than seaweed as the source of iodine, and increasing iodine intake gradually.

It’s plausible that if iodine were supplemented in this way, then Hashimoto’s patients would experience benefits with little risk of harm. Anecdotally, a number have reported benefits from supplemental iodine.

Other evidence emphasizes the need for balance between iodine and selenium. Just as iodine without selenium can cause hypothyroidism, so too can selenium without iodine. Both are needed for good health.

A few months after I was diagnosed with Hashimoto’s I started 50 mg/day iodine plus 200 mcg/day selenium. If I were starting today, I would follow Paul’s recommendation to start with selenium and a low dose of iodine, and increase the iodine dose slowly. I would not take any kelp, because of potential thyrotoxic contaminants.

Currently I’m doing the following to try to reverse my Hashimoto’s:

1. PHD diet and follow PHD book and blog advices to enhance immunity against infections, since infections seems to be implicated in Hashimoto’s pathology [28][29][30]. I give special attention to what Chris Masterjohn calls “traditional superfoods”: liver and other organs, bones and marrow, butter and cod liver oil, egg yolks and coconut, because these foods are high in minerals, like iodine, zinc, selenium, copper, chromium, manganese and vanadium, all of which seems to play a role in thyroid health [31];
2. High dose iodine (50mg of Lugol’s) plus 200 mcg selenium daily. These I supplement because of their vital importance to thyroid and immune function;
3. 3 mg LDN (low dose naltrexone) every other day to further increase immunity. LDN resources are listed below [32][33][34][35][36];
4. Avoiding mercury and other endocrine disruptors. When I removed 9 amalgams (mercury), my TPO antibodies increased for 3 months and took another 6 months to return to previous values. I also avoid fish that have high and medium concentrations of mercury. Cod consumption increased my TPO antibodies;
5. 1g of vitamin C daily. Since it seems to confer some protection against heavy metal thyroid disfunction [37], improve thyroid medication absorption [38] and there is some evidence that it could improve a defective cellular transport for iodine [39];
6. Donating blood 2 to 3 times per year. In men, high levels of iron seems to impact thyroid function [40].

Final Thanks

I would like to make a special thanks to Paul Jaminet for giving me the opportunity to write this essay, for gathering many, many papers for me, and for having the patience to revise both posts and suggest many changes that made the text clearer; and to Emily Deans who kindly sent me one key study that Paul could not get.

References:

[1] Dr Datis Kharrazian. Iodine and Autoimmune Thyroid — References.  http://drknews.com/some-studies-on-iodine-and-autoimmune-thyroid-disease/.

[2] Marino MA et al. Urinary iodine in patients with auto-immune thyroid disorders in Santo André, SP, is comparable to normal controls and has been steady for the last 10 years. Arq Bras Endocrinol Metabol. 2009 Feb;53(1):55-63. http://pmid.us/19347186.

[3] Yoon SJ et al. The effect of iodine restriction on thyroid function in patients with hypothyroidism due to Hashimoto’s thyroiditis. Yonsei Med J. 2003 Apr 30;44(2):227-35. http://pmid.us/12728462.

[4] Kasagi K et al. Effect of iodine restriction on thyroid function in patients with primary hypothyroidism. Thyroid. 2003 Jun;13(6):561-7. http://pmid.us/12930600.

[5] Gribble GW. The natural production of organobromine compounds. Environ Sci Pollut Res Int. 2000 Mar;7(1):37-47. http://pmid.us/19153837.

[6] Zhang ZW et al. Urinary bromide levels probably dependent to intake of foods such as sea algae. Arch Environ Contam Toxicol. 2001 May;40(4):579-84. http://pmid.us/11525503.

[7] Kawai T, Zhang ZW et al. Comparison of urinary bromide levels among people in East Asia, and the effects of dietary intakes of cereals and marine products. Toxicol Lett. 2002 Aug 5;134(1-3):285-93. http://pmid.us/12191890.

[8] Leblanc C et al. Iodine transfers in the coastal marine environment: the key role of brown algae and of their vanadium-dependent haloperoxidase. Biochimie. 2006 Nov;88(11):1773-85. http://pmid.us/17007992.

[9] van Netten C et al. Elemental and radioactive analysis of commercially available seaweed. Sci Total Environ. 2000 Jun 8;255(1-3):169-75. http://pmid.us/10898404.

[10] Hou X et al. Iodine-129 in human thyroids and seaweed in China. Sci Total Environ. 2000 Feb 10;246(2-3):285-91. http://pmid.us/10696729.

[11] Toh Y et al. Isotopic ratio of 129I/127I in seaweed measured by neutron activation analysis with gamma-gamma coincidence. Health Phys. 2002 Jul;83(1):110-3. http://pmid.us/12075675.

[12] Miyashita S, Kaise T. Biological effects and metabolism of arsenic compounds present in seafood products. Shokuhin Eiseigaku Zasshi. 2010;51(3):71-91. http://pmid.us/20595788.

[13] Cleland B et al. Arsenic exposure within the Korean community (United States) based on dietary behavior and arsenic levels in hair, urine, air, and water. Environ Health Perspect. 2009 Apr;117(4):632-8. Epub 2008 Dec 8. http://pmid.us/19440504.

[14] Chong W, Shit Xg, Teng WP, et al. Multifactor analysis of relationship between the biological exposure to iodine and hypothyroidism. Zhongua Yi Za Zhi. 2004 Jul 17:84(14):1171-4. http://pmid.us/15387978.

[15] Tong YJ et al. An epidemiological study on the relationship between selenium and thyroid function in areas with different iodine intake. Zhonghua Yi Xue Za Zhi. 2003 Dec 10;83(23):2036-9. http://pmid.us/14703411.

[16] Karita K et al. Comparison of selenium status between Japanese living in Tokyo and Japanese brazilians in São Paulo, Brazil. Asia Pac J Clin Nutr. 2001;10(3):197-9. http://pmid.us/11708308.

[17] Thorling EB et al. Selenium status in Europe–human data. A multicenter study. Ann Clin Res. 1986;18(1):3-7. http://pmid.us/3717869.

[18] Mengüba? K et al. Selenium status of healthy Turkish children. Biol Trace Elem Res. 1996 Aug;54(2):163-72. http://pmid.us/8886316.

[19] Hincal F. Trace elements in growth: iodine and selenium status of Turkish children. J Trace Elem Med Biol. 2007;21 Suppl 1:40-3. http://pmid.us/18039495.

[20] Fordyce FM et al. Selenium and iodine in soil, rice and drinking water in relation to endemic goitre in Sri Lanka. Sci Total Environ. 2000 Dec 18;263(1-3):127-41. http://pmid.us/11194147.

[21] Alsayed A et al. Excess urinary iodine is associated with autoimmune subclinical hypothyroidism among Egyptian women. Endocr J. 2008 Jul;55(3):601-5. Epub 2008 May 15. http://pmid.us/18480555.

[22] Strieder TG et al. Prediction of progression to overt hypothyroidism or hyperthyroidism in female relatives of patients with autoimmune thyroid disease using the Thyroid Events Amsterdam (THEA) score. Arch Intern Med. 2008 Aug 11;168(15):1657-63. http://pmid.us/18695079.

[23] Stuckey BG et al. Low urinary iodine postpartum is associated with hypothyroid postpartum thyroid dysfunction and predicts long-term hypothyroidism. Clin Endocrinol (Oxf). 2011 May;74(5):631-5. doi: 10.1111/j.1365-2265.2011.03978.x. http://pmid.us/21470286.

[24] American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the Evaluation and Treatment of Hyperthyroidism and Hypothyroidism. https://www.aace.com/sites/default/files/hypo_hyper.pdf.

[25] Vanderpas JB et al. Selenium deficiency mitigates hypothyroxinemia in iodine-deficient subjects. Am J Clin Nutr. 1993 Feb;57(2 Suppl):271S-275S. http://pmid.us/8427203.

[26] Contempré B et al. Effect of selenium supplementation on thyroid hormone metabolism in an iodine and selenium deficient population. Clin Endocrinol (Oxf). 1992 Jun;36(6):579-83. http://pmid.us/1424183.

[27] Contempré B et al. Effect of selenium supplementation in hypothyroid subjects of an iodine and selenium deficient area: the possible danger of indiscriminate supplementation of iodine-deficient subjects with selenium. J Clin Endocrinol Metab. 1991 Jul;73(1):213-5. http://pmid.us/2045471.

[28] Benvenga S et al. Homologies of the thyroid sodium-iodide symporter with bacterial and viral proteins. J Endocrinol Invest. 1999 Jul-Aug;22(7):535-40. http://pmid.us/10475151.

[29] Wasserman EE et al. Infection and thyroid autoimmunity: A seroepidemiologic study of TPOaAb. Autoimmunity. 2009 Aug;42(5):439-46. http://pmid.us/19811261.

[30] Tozzoli R et al. Infections and autoimmune thyroid diseases: parallel detection of antibodies against pathogens with proteomic technology. Autoimmun Rev. 2008 Dec;8(2):112-5. http://pmid.us/18700170.

[31] Neve J. Clinical implications of trace elements in endocrinology. Biol Trace Elem Res. 1992 Jan-Mar;32:173-85. http://pmid.us/1375054.

[32] David Gluck, MD. Low Dose Naltrexone information site. http://www.lowdosenaltrexone.org/.

[33] LDN Yahoo Group. http://groups.yahoo.com/group/lowdosenaltrexone/.

[34] LDN World Database. Where LDN users share their experience with various diseases. http://www.ldndatabase.com/.

[35] Those Who Suffer Much Know Much. A colection of LDN users testimonies. http://www.ldnresearchtrustfiles.co.uk/docs/2010.pdf.

[36] Elaine A. More. The Promise Of Low Dose Naltrexone Therapy: Potential Benefits in Cancer, Autoimmune, Neurological and Infectious Disorder. http://www.amazon.com/Promise-Low-Dose-Naltrexone-Therapy/dp/0786437154.

[37] Gupta P, Kar A. Role of ascorbic acid in cadmium-induced thyroid dysfunction and lipid peroxidation. J Appl Toxicol. 1998 Sep-Oct;18(5):317-20. http://pmid.us/9804431.

[38] Absorption of thyroid drug levothyroxine improves with vitamin C. The Endocrine Society. News Room. http://www.endo-society.org/media/ENDO-08/research/Absorption-of-thyroid-drug.cfm.

[39] Abraham, G.E., Brownstein, D.. Evidence that the administration of Vitamin C improves a defective cellular transport mechanism for iodine: A case report. The Original Internist, 12(3):125-130, 2005. http://www.optimox.com/pics/Iodine/IOD-11/IOD_11.htm.

[40] Edwards CQ et al. Thyroid disease in hemochromatosis. Increased incidence in homozygous men. Arch Intern Med. 1983 Oct;143(10):1890-3. http://pmid.us/6625774.

Mario Renato Iwakura is a Brazilian engineer and Hashimoto’s thyroiditis patient who is intimately familiar with the hypothyroidism literature. Mario has graciously agreed to do a guest series on the place of iodine and selenium supplementation in treatment of hypothyroid disorders. I’m very excited to have Mario’s thoughts, as he’s extremely smart and passionately engaged with the science. — Paul

Most doctors believe that iodine supplementation will aggravate autoimmune (Hashimoto’s) thyroiditis. This view is supported by observations that the incidence of Hashimoto’s hypothyroidism tends to increase in populations that increase their iodine intake. (The incidence of hyperthyroidism, on the other hand, increases as iodine intake decreases.). However not all epidemiological studies support this association [1][2][3][4].

Dr. Datis Kharrazian (“Dr. K”), whose 2010 book “Why Do I Still Have Thyroid Symptoms?”[5] is popular among Hashimoto’s patients, vehemently opposes the use of iodine in Hashimoto’s [5][6][7]. Chris Kresser of The Healthy Skeptic [8] has argued this point of view in his post “Iodine for hypothyroidism: like gasoline on a fire?”. And there’s little doubt that some patients have experienced bad consequences from high-dose iodine.

On the other side, doctors such as Dr. Guy E. Abraham [9], Dr. David Brownstein [10], Jorge D. Flechas [11] and Dr. David Derry [12] have claimed success prescribing high doses of iodine for Hashimoto’s and for breast and thyroid cancers.

Can these experiences by reconciled? What we will try to do is demonstrate that iodine acts synergistically with selenium, and that it is imbalances between the two that damage the thyroid.

First, Some Background

Thyroid peroxidase or thyroperoxidase (TPO) is an enzyme expressed mainly in the thyroid that liberates iodine for addition onto tyrosine residues on thyroglobulin (TG) for the production of the thyroid hormones thyroxine (T4) or triiodothyronine (T3).

The human body normally has low levels of auto-antibodies against both TG and TPO, which serve some physiological function. Autoimmune thyroiditis features high levels of these auto-antibodies, leading to immune attacks on the thyroid.

High levels of  thyroid auto-antibodies are positively associated with hypothyroidism symptoms [13][14]. TPO antibodies and TSH levels are strongly associated with progression of subclinical hypothyroidism to overt hypothyroidism [3], as can be see in Table 3 below:

Selenium Can Cure An Iodine Excess

Dr. K said in his book and site that “iodine stimulates the production and activity of the thyroid peroxidase (TPO) enzyme” [5][7]. Since TPO is a target of autoimmune attack in Hashimoto’s patients, this might worsen the disease [5][6][7]. In his book he also states that excessive iodine will shut down TPO activity [5], but he neither cites a reference nor states what level of iodine intake will cause this to happen.

In fact, excess iodine combined with selenium insufficiency will reduce (not increase, not shut down) TPO activity [15]. Let’s look at a study that had seven groups: normal iodine and lab-chow selenium only (NI), excess iodine and lab-chow selenium only (EI), and five groups with excess iodine and steadily increasing levels of selenium added to water (IS1 to IS5). TPO activity was reduced by excess iodine (EI), but returned to control levels (NI) with moderate selenium (IS1 and IS2). With excess iodine and excessive selenium (IS3 to IS5), TPO activity was also decreased, as we can see from table 2 below.

Some other studies have also demonstrated this reduced TPO activity at high iodine intakes [23][24].

This study [15] also showed a picture (fig. 1) of thyroid follicles from rats receiving normal iodine diet (NI), excessive iodine (EI) and excessive iodine plus 0.2 mg/L selenium (IS2). Thyroid follicles from the excessive iodine group (EI) are enlarged, a characteristic of goiter. But, there is virtually no difference between the first and last picture! If selenium and iodine are increased together, no goiter occurred.

Note that the IS2 level of selenium, which protects against iodine toxicity, corresponds in a person who drinks 1-2 liters per day to a selenium dose of 200 to 400 mcg per day – which happens to be the Perfect Health Diet “plateau range” for selenium.

Selenium Can Cure Autoimmunity

Another paper, also from China, looked at the effects of selenium in an animal model of iodine induced autoimmune thyroiditis [16].

There were three groups of mice, a healthy control group, and groups with iodine induced autoimmune thyroiditis without (AIT) and with (AIT+Se) selenium. The AIT+Se group was given high iodine (AIT only) for 8 weeks to induce the disease, and then, for 8 weeks more, they were given iodine plus selenium. After 8 weeks of selenium supplementation their thyroid follicles were almost fully recovered, as we can see below, even though high-dose iodine had continued:

The AIT group has enlarged cells characteristic of goiter and dead tissue; the AIT-Se group thyroid section resembles a normal thyroid. Thyroid weight doubled in the AIT group, proof of goiter, but returned to normal after selenium supplementation.

Before selenium was given to the AIT+Se group, serum TgAb antibodies were elevated, but they returned to normal after selenium supplementation:

An interesting aspect of this study was the changing population of immune cells. A specialized subpopulation of T cells, negative regulatory T cells or Tregs, helps establish and maintain self-tolerance by suppressing response to self-antigens and suppressing excessive immune responses deleterious to the host. Deficits in Treg cell numbers or function lead to autoimmune diseases [17].

In this study, CD4⁺CD25⁺Foxp3⁺ Treg Cells were reduced by high iodine, but returned much of the way toward normal after 8 weeks of selenium even though high iodine intake continued. The implication is that selenium-iodine balance may be needed to maintain proper Treg cell populations, and that selenium supplementation may restore normal regulation of autoimmunity.

The researchers concluded:

“In the present study, we observed that Se supplementation increased the frequency  of CD4+CD25+Foxp3+ T cells and enhanced expression of Foxp3 in vivo. These changes were accompanied by suppressed TgAb titers and reduced thyroiditis. Thus the benefit of Se treatment may be due to the increase of CD4+CD25+ regulatory T cells.”

Under What Circumstances Does Excess Iodine Induce Autoimmunity?

In the previous study high doses of iodine were used to induce autoimmune thyroiditis. Let’s look more closely into the circumstances in which that happens.

It’s often said that excessive iodine in Hashimoto’s triggers an immune response characterized by proliferation of T lymphocytes, a disrupted Th1/Th2 axis, and altered CD4/CD8 levels. Pathogenesis of autoimmune disease is believed to begin with the activation of T cell autoaggression (turning them into “allergized T cells”).

Our next study, also from China, showed that excess iodine can indeed cause such an autoimmune pathology, but only if there is a deficiency in selenium [18].

Mice in 5 groups were orally administrated different combinations of iodine and selenium for 30 days. Four groups had no selenium but varying amounts of iodine in their water:  0 μg/L (group I), 1500 μg/L (group II), 3000 μg/L (group III), and 6000 μg/L (group IV). The fifth group had 6000 μg/L iodine plus 0.3 mg/L selenium (group V).

In Group IV, high-dose iodine at 6000 μg/L caused a proliferation of lymphocytes. But this was completely abolished by the addition of selenium to water in Group V:

Normally there are relatively stable population of T cells and their subgroups in tissue till immune function is in disorder. As we can see from Fig. 1, increasing iodine increased T lymphocytic reproductive activity, and was clearly high in group IV. But group V, which also received selenium, had the same values as the control group (I).

Subjects with Hashimoto’s also have a lower ratio of CD4⁺ to CD8⁺ lymphocytes than controls [19][20]. From fig. 2, we can see that iodine supplementation in groups II and III actually increased the CD4⁺ to CD8⁺ ratio, until the onset of autoimmune symptoms at very high doses in Group IV when the ratio decreased. However, group V, which had the highest iodine intake but with selenium as well, had the highest CD4⁺ to CD8⁺ ratio of all groups.  This suggests that high-dose iodine and selenium together may actually diminish the autoimmune syndrome compared to the low levels in the controls.

Another marker of autoimmune thyroiditis is the relative strength of the Th1 and Th2 responses, as indicated by the markers interferon-gamma and interleukin-4 (Th2). Th1(IFN-γ)/Th2(IL-4) ratios are increased in Hashimoto patients [21][22], and related with severity of Hashimoto’s disease [22].

As we can see from Fig. 3, the group with the highest iodine intake but no selenium (IV) was the only group that had clearly higher Th1/Th2 ratio. High iodine plus selenium in group V had similar Th1/Th2 ratios than control group (I).

The researchers concluded:

“The results revealed that there was no significant difference in the immunotoxicity between interventional group (group V) and control group (group I), indicating that adequate selenium has a favorable interventional effect on excessive iodine intake.”

Conclusion

Excess iodine intake can cause an autoimmune thyroiditis that bears all the characteristics of Hashimoto’s. However, in animal studies this occurs only if selenium is deficient or in excess. Similarly, in animal studies very high iodine intake can exacerbate a pre-existing autoimmune thyroiditis, but only if selenium is deficient or in excess.

With optimal selenium status, thyroid follicles are healthy, goiter is eliminated, and autoimmune markers like Th1/Th2 ratio and CD4+/CD8+ ratio are normalized over a wide range of iodine intake. It seems that optimizing selenium intake provides powerful protection against autoimmune thyroid disease, and provides tolerance of a wide range of iodine intakes.

In the next post in this series (Iodine and Hashimoto’s Thyroiditis, Part 2, May 26, 2011), we’ll transition from animals to humans. Does epidemiological evidence suggest that these animal findings are transferable to humans?

References:

[1] F. Aghini-Lombardi et al. The spectrum of thyroid disorders in an iodine-deficient community: the Pescopagano Survey. J. Clin. Endocrinol. Metab. 84, 561–566 (1999). http://pmid.us/10022416.

[2] Marino MA et al. Urinary iodine in patients with auto-immune thyroid disorders in Santo André, SP, is comparable to normal controls and has been steady for the last 10 years. Arq Bras Endocrinol Metabol. 2009 Feb;53(1):55-63. http://pmid.us/19347186.

[3] Strieder TG et al. Prediction of progression to overt hypothyroidism or hyperthyroidism in female relatives of patients with autoimmune thyroid disease using the Thyroid Events Amsterdam (THEA) score. Arch Intern Med. 2008 Aug 11;168(15):1657-63. http://pmid.us/18695079.

[4] Stuckey BG et al. Low urinary iodine postpartum is associated with hypothyroid postpartum thyroid dysfunction and predicts long-term hypothyroidism. Clin Endocrinol (Oxf). 2011 May;74(5):631-5. doi: 10.1111/j.1365-2265.2011.03978.x. http://pmid.us/21470286.

[5] Dr. Datis  Kharrazian. Why Do I Still Have Thyroid Symptoms? When My Lab Tests Are Normal: A Revolutionary Breakthrough In Understanding Hashimoto’s Disease and Hypothyroidism.

[6] Dr. Datis  Kharrazian. Iodine and Autoimmune Thyroid — References. http://drknews.com/some-studies-on-iodine-and-autoimmune-thyroid-disease/.

[7] Dr. Datis  Kharrazian. Iodine and Hashimoto’s. http://drknews.com/iodine-and-hashimotos/.

[8] Chris Kresser. Iodine for hypothyroidism: like gasoline on a fire?. http://thehealthyskeptic.org/iodine-for-hypothyroidism-like-gasoline-on-a-fire.

[9] Dr. Guy E. Abraham. http://www.optimox.com/.

[10] Dr. Brownstein. Iodine, Why You Need It. https://www.drbrownstein.com/homePage.php.

[11] Dr. Jorge D. Flechas. http://cypress.he.net/~bigmacnc/drflechas/index.htm.

[12] Dr. David Derry. Breast Cancer and Iodine : How to Prevent and How to Survive Breast Cancer.

[13] Ott J et al. Hashimoto’s thyroiditis affects symptom load and quality of life unrelated to hypothyroidism: a prospective case-control study in women undergoing thyroidectomy for benign goiter. Thyroid. 2011 Feb;21(2):161-7. Epub 2010 Dec 27. http://pmid.us/21186954.

[14] Díez JJ, Iglesias P. Relationship between thyrotropin and body mass index in euthyroid subjects. Exp Clin Endocrinol Diabetes. 2011 Mar;119(3):144-50. Epub 2010 Nov 17. http://pmid.us/21086247.

[15] Xu J et al. Supplemental Selenium Alleviates the Toxic Effects of Excessive Iodine on Thyroid. Biol Trace Elem Res. 2010 Jun 2. http://pmid.us/20517655.

[16] Xue H et al. Selenium upregulates CD4(+)CD25(+) regulatory T cells in iodine-induced autoimmune thyroiditis model of NOD.H-2(h4) mice. Endocr J. 2010 Jul 30;57(7):595-601. Epub 2010 Apr 27. http://pmid.us/20453397.

[17] Sakaguchi S et al. Foxp3⁺CD25⁺CD4⁺ natural regulatory T cells in dominant self-tolerance and autoimmune disease. Immunol Rev. 2006 Aug;212:8-27. http://pmid.us/16903903.

[18] Chen X et al. Effect of excessive iodine on immune function of lymphocytes and intervention with selenium. J Huazhong Univ Sci Technolog Med Sci. 2007 Aug;27(4):422-5. http://pmid.us/17828501.

[19] Gopalakrishnan S et al. The role of T-lymphocyte subsets and interleukin-5 blood levels among Indian subjects with autoimmune thyroid disease. Hormones (Athens). 2010 Jan-Mar;9(1):76-81. http://pmid.us/20363725.

[20] Zeppa P et al. Flow cytometry phenotypization of thyroidal lymphoid infiltrate and functional status in Hashimoto’s thyroiditis. Anal Quant Cytol Histol. 2006 Jun;28(3):148-56. http://pmid.us/16786724.

[21] Colin IM et al. Functional lymphocyte subset assessment of the Th1/Th2 profile in patients with autoimmune thyroiditis by flowcytometric analysis of peripheral lymphocytes. J Biol Regul Homeost Agents. 2004 Jan-Mar;18(1):72-6. http://pmid.us/15323363.

[22] Nanba T et al. Increases of the Th1/Th2 cell ratio in severe Hashimoto’s disease and in the proportion of Th17 cells in intractable Graves’ disease. Thyroid. 2009 May;19(5):495-501. http://pmid.us/19415997.

[23] Müller K et al. Effect of iodine on early stage thyroid autonomy. Genomics. 2011 Feb;97(2):94-100. http://pmid.us/21035537.

[24] Man N et al. Long-term effects of high iodine intake: inhibition of thyroid iodine uptake and organification in Wistar rats. Zhonghua Yi Xue Za Zhi. 2006 Dec 26;86(48):3420-4. http://pmid.us/17313856.

We have friends in Japan, living both north and south of the damaged reactors, and Shou-Ching asked me to do a post about how to protect against radiation.

The Concern

The radioactive substances released by the Chernobyl nuclear power plant meltdown are represented in this chart:

(Source. If you’re wondering what the other radioactive elements are, or why radioactive iodine is a byproduct of uranium fission, a possible place to start is Wikipedia, “Fission products by element” ).

Note first of all that the chart presents percentages of radioactive substances, not amounts. The amounts are highest on the first day and then decline rapidly. The great danger comes in the first few days.

During these dangerous first days, iodine-131 is, along with tellurium-132 and its decay product iodine-132, the dominant source of radioactivity. These radioactive iodine species account for over 50% of the radiation.

Not only its abundance, but also its effectiveness at causing biological damage make iodine far and away the greatest danger. Iodine radiation is highly effective at causing cellular damage:

Due to its mode of beta decay, iodine-131 is notable for causing mutation and death in cells which it penetrates, and other cells up to several millimeters away. [Source: Wikipedia, Iodine-131]

Worse, iodine is an important biological molecule that gets concentrated in the thyroid. So the dose of radiation becomes very high in the thyroid, and this leads to DNA damage producing a high risk for thyroid cancer.

Thyroid cancer is “the only unequivocal radiological effect of the Chernobyl accident on human health.” [1] Since Chernobyl released a great deal more radiation than the Japanese reactor meltdowns are likely to do, it’s likely that this will be the case in Japan also.

The rate of thyroid cancer after Chernobyl was higher the younger the age at time of exposure. Children and infants are at greatest risk:

It is now well documented that children and adolescents exposed to radioiodines from Chernobyl fallout have a sizeable dose-related increase in thyroid cancer, with the risk greatest in those youngest at exposure and with a suggestion that deficiency in stable iodine may increase the risk. [2]

The last point is crucial – iodine deficiency increases the risk.

Iodine deficiency and radiation risk

In iodine deficiency, the thyroid gland has difficulty generating enough thyroid hormone. T4 thyroid hormone, manufactured in the thyroid and so named because it has 4 iodine atoms, is 65.4% iodine by weight, so iodine is the key ingredient in thyroid hormone.

To compensate for an iodine deficiency, the body does two things:

• The thyroid gland grows, so that it can more aggressively scan the blood for iodine. An enlarged thyroid is called a goiter.
• The pituitary gland issues thyroid stimulating hormone (TSH), which induces the thyroid to aggressively scavenge iodine from the blood and turn it into thyroid hormone.

So in iodine deficiency the thyroid is aggressively scavenging all available iodine. This means that when a large dose of iodine-131 or iodine-132 arrives during radiation fallout, these radioactive iodine atoms are quickly picked up by the thyroid. There, they release their radiation and damage the thyroid.

On the other hand, in thyroid replete persons, the thyroid has all the iodine it needs and takes up little iodine from the blood. In this case, iodine that enters the body is distributed throughout the body, or excreted. Doses in any single cell are much lower. The danger to the thyroid is not much greater than that to other organs – which, the Chernobyl experience tells us, is not detectable to epidemiology. (There is even a theory that low-level radiation may be beneficial through hormesis.)

How can the thyroid be made replete with iodine?

The best way, which we recommend in our book, is to supplement with iodine and gradually build up the dose over a four to six month period. Start below 1 mg/day, take that for a month, then double the dose. After a month, double the dose again. Continue doubling until you reach your desired maintenance dose; we recommend at least 3 mg/day (a quarter Iodoral tablet), with 12.5 mg/day a reasonable dose. Some people taking as much as 50 mg/day.

At 12.5 mg/day, it can take a year or more to become replete with iodine in all tissues and to fully drive out other halogens, such as bromine, from the body. This has great benefits for immune function. So, it is best to get started!

Risks of high-dose iodine supplementation

If a person’s thyroid gland is adapted for iodine scarcity and the person takes a large dose of (non-radioactive) iodine, the likely course of events is:

1.      Hyperthyroidism. The thyroid, aggressively scavenging for iodine to repair a deficiency of thyroid hormone, scoops up all the iodine and makes a large amount of thyroid hormone. The person develops symptoms of hyperthyroidism (too much thyroid hormone): anxiety, intolerance of heat, muscle aches, hyperactivity, irritability, hypoglycemia, elevated body temperature, palpitations, hair loss, difficulty sleeping.

2.      Wolff-Chaikoff effect. As thyroid hormone levels become too high, the body induces mechanisms for suppressing thyroid hormone production. Simply reducing TSH output is not effective to suppress thyroid hormone production if a very large iodine influx is received. Fortunately there is another mechanism for suppressing thyroid hormone formation, mediated by iodine itself: the formation of iodine-rich proteins (iodopeptides) in the thyroid that inhibt synthesis of the thyroid peroxidase (TPO) enzyme. Normally, this mechanism operates for a few days and wears off, restoring normal thyroid function. [3]

3.      Reactive hypothyroidism? Usually, everything will normally return to normal after a few days. But sometimes in previously iodine-deficient adults and more commonly in newborns and fetuses and some diseased persons, after very high doses of iodine the Wolff-Chaikoff effect can persist. In this case the early hyperthyroidism is followed by a period of hypothyroidism (too little thyroid hormone). This “hypothyroidism is transient and thyroid function returns to normal in 2 to 3 weeks after iodide withdrawal, but transient T4 replacement therapy may be required in some patients.” [3]

4.      Risk for lasting hypothyroidism. People who develop a reactive hypothyroidism following a large dose of iodine are at high risk for later development of persistent hypothyroidism. [3]

So most people will experience transient hyperthyroid symptoms for a few days and then do fine. Some will develop a reactive hypothyroidism lasting a few weeks and then be OK, save for an elevated risk of hypothyroidism later which may or may not be due to the reactive episode.

Advice of the authorities to fallout victims

The advice from public health authorities is a compromise between the protective effects of high-dose iodine and the risk of messing up the thyroid.

A US Center for Disease Control (CDC) fact sheet explains the recommendations. A single large dose of iodine offers protection for about 24 hours. Recommended intakes are:

• Adults should take 130 mg/day while exposure persists.
• Children older than 3 and smaller than adults should take 65 mg/day while exposure persists.
• Infants and toddlers aged 1 month to 3 years should take 32 mg/day.
• Newborns should take 16 mg/day.

Our advice

The CDC dosage advice strikes us as very reasonable.

If you are not currently exposed to fallout, but think you may be exposed in the near future, you should consider beginning with small doses of iodine now – say, 3 mg/day. If that does not produce any symptoms, then try 6 mg/day; if it does, back off to half that dose. This will begin the adaptation process for your thyroid gland and help minimize hyperthyroid or hypothyroid reactions if you do have to take high doses.

Also, obtain your iodine tablets in advance. If fallout does occur, it may be hard to find iodine pills. NukePills.com says they are out of stock and have a large order backlog. I saw a story the other day that a 14-dose packet of potassium iodide was being sold at one site for $200, up from the normal $10 list price.

We recommend Iodoral 12.5 mg tablets. This is a good size for supplemental use; to reduce it to a 3 mg dose, cut the tablet in quarters with a razor blade. If fallout arrives, you can use ten Iodoral tablets to get a 125 mg adult dose.

For doses below 3 mg, smaller iodine tablets or liquid iodine solutions may be best; you can dilute liquid solutions to your desired dose. Some brands were recommended by readers in comments on our Supplement Recommendations page.

Conclusion

Outside of Japan, the risk is minimal, and even in Japan those who are replete with iodine are unlikely to develop thyroid cancer from exposure. After Chernobyl, thyroid cancer rates were high in Russia, the Ukraine, and Belarus which did not distribute iodine, but low in Poland which did. Fortunately, Japan has one of the highest iodine intakes in the world thanks to its high seaweed consumption. With that preparation plus proactive distribution of iodine tablets, we can expect and hope that the health effects of the reactor meltdowns will be minimal.

References

[1] Thomas GA et al. Integrating Research on Thyroid Cancer after Chernobyl-The Chernobyl Tissue Bank. Clin Oncol (R Coll Radiol). 2011 Feb 22. [Epub ahead of print] http://pmid.us/21345659.

[2] Cardis E, Hatch M. The Chernobyl Accident-An Epidemiological Perspective. Clin Oncol (R Coll Radiol). 2011 Mar 9. [Epub ahead of print] http://pmid.us/21396807.

[3] Markou K et al. Iodine-Induced hypothyroidism. Thyroid. 2001 May;11(5):501-10. http://pmid.us/11396709.