Iodine is a hot topic of debate in the thyroid conversation. Here are the facts behind the iodine/thyroid connection.
Bring up the relationship between iodine and thyroid disorders, and people inevitably put the gloves on and get scrappy—not just an intellectual back and forth banter, supported by exchange of peer-reviewed scientific studies and empirically validated literature—but a throw-down, knock-out fight, where claims are made on the basis of anecdotal evidence based on what so-and-so blogger said, without a single primary or secondary source citation. This, I cannot endorse.
Despite clear trends in the scientific literature, there is rampant misinformation in the integrative medical community when it comes to iodine supplementation for Hashimoto’s thyroiditis in particular. I have heard many high profile functional medicine leaders advocate consumption of iodine-rich seaweed or high dose iodine supplementation for those of us with Hashimoto’s…without a single evidence-based resource to substantiate their recommendation. Because one autoimmune condition can beget another, it is reckless and irresponsible to give recommendations to autoimmune cohorts without so much as a literature search. Thus, a disimpassioned examination of the science is warranted.
Iodine, the heaviest of the halogens, is required in proper quantities as an essential precursor to thyroid hormone synthesis. The thyroid gland converts the amino acid tyrosine into thyroglobulin,and attaches one to four iodine atoms to create T4 (thyroxine), the inactive storage hormone, T3 (triidothyronine), or metabolically active thyroid hormone, and two thyroid hormones whose clinical significance is less known, T2 and T1.
Mandatory salt iodization programs, to which 70% of the world’s population are subject, have by and large eliminated iodine deficiency in most industrialized countries (1). For instance, after the development of the universal salt iodization initiative in China, median urinary iodine escalated from 164.8 μg/L in 1995 to 238.6 μg/L in 2011, well beyond the 100.0 to 199.0 μg/L levels recommended by the World Health Organization (WHO) from prevention of iodine deficiency disorders (IDD) (2). Meanwhile, however, “The spectrum of thyroid diseases has undergone a significant change ranging from simple goiter to toxic nodular goiter, Hashimoto’s thyroiditis, and thyroid cancer accompanied by the increase in iodine intake, especially for thyroid cancer with an annual increase of 14.51% in China” (3).
The Epidemic of Thyroid Cancer
While increased incidence of Hashimoto’s thyroiditis, the autoimmune disease responsible for the majority of cases of hypothyroidism, is part of a larger epidemic of autoimmune disorders, the skyrocketing rates of thyroid cancer are likely a consequence of over-diagnosis due to an unprecedented increase in thyroid imaging. Most of these thyroid cancers are being re-classified as benign morphological variations, or papillary lesions of indolent course (PLICs), “which do not evolve to cause metastatic disease or death” (4). According to Brito and colleagues (2014), the majority of these growths constitute the most indolent type of thyroid cancer, called small papillary cancers, with a mortality of less than 1% after 20 years of post-surgical follow-up (4). The researchers elucidate, “Now new risk factors, but one, can completely explain the surge of these lesions: the exponential increase in the use of diagnostic imaging” (4, p.1).
Volmer (2014) concluded similarly that, “The results of this study support the notion that many thyroid cancers are part of a reservoir of nonfatal tumors that are increasingly being overdetected and overdiagnosed” (5, p. 128). Devastatingly, standard of care for patients with these conditions is thyroidectomy—surgical removal of one of the most essential glands in the body—followed by carcinogenic radiation, lifelong synthetic thyroid hormone replacement, and surveillance for ‘cancer’ recurrence. Brito and colleagues (2014) state that, as evidenced by autopsies, many of us harbor these thyroid ‘cancers’ in our thyroid glands (4). In fact, studies suggest that if all thyroids were subjected to biopsy, pathologists would find these microscopic thyroid ‘cancers’ to be ubiquitous in the population (6). The authors of these post-mortem studies state that these occult papillary carcinomas (OPCs), which arise from normal follicular cells, should be “regarded as a normal finding which should not be treated when incidentally found” (6, p. 531). Researchers further state that, “The great majority of the tumors remain small and circumscribed and even from those few tumors that grow larger and become invasive OPCs only a minimal proportion will ever become a clinical carcinoma” (6, p. 531).
Iodine and the Epidemic of Hashimoto’s Thyroiditis
On the other hand, iodine may be one of the potential culprits in the dramatic surge in diagnoses of Hashimoto’s thyroiditis, also known as autoimmune thyroiditis or chronic lymphocytic thyroiditis, which has occurred in recent years.
With respect to certain constructs, the natural medicine community often adopts a group-think mentality and becomes an echo chamber of reverberating ideas, a choir with one unanimous voice and little substantive discourse. However, as Benjamin Franklin stated, “If everyone is thinking alike, then no one is thinking”. Thus, the assertion that is frequently cited in alternative medical communities that we are in the midst of a massive iodine deficiency due to inundation with chlorinated, fluoridated, and brominated compounds, which displace iodine in the thyroid gland, is worthy of examination.
While these halogens are indisputably cause for concern, this theoretical iodine deficiency in Western nations does not materialize in the literature. According to a 2013 study, 10 countries have iodine excess, 111 countries have sufficient iodine intake, 9 countries are moderately deficient, 21 are mildly deficient, and none are considered severely deficient, as defined by a median urinary iodine concentration of 100-299 μg/L in school-aged children (1). According to studies, approximately 71% to 74% or more of the world’s population is now iodine sufficient, illuminating that the risk of iodine deficiency is overstated (1, 7). The most recent Food and Drug Administration’s Total Diet Study also revealed that the U.S. population has adequate dietary iodine, with estimated average daily iodine intake ranging from 138 to 353 micrograms per person (8). Canada and Mexico are likewise iodine sufficient (1).
Importantly, iodine is a narrow therapeutic index or “Goldilocks” nutrient. It exhibits a biphasic U-shaped dose-response curve, where too much and too little is problematic for the thyroid. Iodine deficiency can create endemic goiter, growth retardation, neonatal hypothyroidism, intellectual impairments, cretinism, pregnancy loss, and infant mortality (9). On the other hand, excess iodine can induce hypothyroidism in euthyroid patients who have had previous episodes of subacute thyroiditis, in patients with a history of postpartum thyroiditis, in euthyroid patients with Hashimoto’s thyroiditis, and in some patients with chronic, systemic diseases (10). The Jod-Basedow phenomenon, also known as iodine-induced hyperthyroidism or thyrotoxicosis, can also occur in those with a history of autonomous multinodular or non-toxic goiter (1).
Evidence that Iodine Can Induce Hashimoto’s thyroiditis
Although iodine prophylaxis programs may decrease goiter prevalence, epidemiological research in China and Denmark has elucidated that excess iodine increases incidence of Hashimoto’s thyroiditis and hypothyroidism (11). Slovenia likewise showed an increase in Hashimoto’s thyroiditis incidence in the ten years after it became an iodine-replete country (12). Similarly, salt iodization was associated with increased frequency of thyroid autoantibodies and hypothyroidism in Great Britain, Denmark, and Iceland (13, 14, 30). Another study demonstrated an increased incidence of Hashimoto’s and positive thyroid autoantibodies when Italy improved its low iodine intake between 1995 and 2010 (15). Hypothyroidism and increases in serum thyroid autoantibodies also occurred with the introduction of iodine prophylaxis in Pescopagano (15). Furthermore, mean thyroid stimulating hormone (TSH), a biomarker for hypothyroidism, escalated significantly after a mandatory salt iodization program was implemented in a longitudinal DanThyr study (16). Astonishingly, in one study, 42.8% of subjects tested positive for thyroid autoantibodies after just three and six months of treatment with iodized oil (17).
In individuals with anti-thyroid peroxidase (TPO) or anti-thyroglobulin (TG) antibodies, the incidence of elevated TSH increased with greater levels of iodine intake (18). In addition, TG antibodies have been found more frequently in users of iodized salt (19). Zhao et al. (2014) found a significant correlation between excess iodine intake and thyroid disease incidence (3). Thyroid autoantibodies, specifically TG and TPO, were statistically higher in those with greater iodine intake (3). Researchers concluded that excess iodine intake can induce production of TPO and TG antibodies, both of which have positive predictive value for Hashimoto’s thyroiditis (3). In fact, positive anti-thyroid antibodies equate to an odds ratio of 8 for women and 25 for men for development of clinical hypothyroidism (13).
Lastly, the effect of iodine in Hashimoto’s is most dramatically demonstrated by a study by Yoon and colleagues (2003), where 78.3% of patients with Hashimoto’s regained euthyroid status (reversing their Hashimoto’s thyroiditis) after three months of restricting iodine to less than 100 micrograms/day (versus 45.5% who recovered in an iodine non-restriction group) (24).
Molecular Mechanisms For Iodine-Induced Hashimoto’s
At a mechanistic level, thyroid autoimmunity induced by iodine is associated with synthesis of TG antibodies and the unmasking of a cryptic epitope of thyroglobulin, which is normally sequestered and unavailable to the immune system (19). According to Fiore, Latrofa, and Vitti (2015), “Thyroglobulin (TG) is an important target in iodine-induced autoimmune response due to post-translational modifications of iodinated TG,” as thyroglobulin is the only self-antigen subject to post-translational alterations resulting from exogenous iodine supply (9, p. 26). Enhanced iodination of TG alters its antigenicity and up-regulates presentation of its cryptic peptide to antigen-presenting cells (20; 21). Iodinated thyroglobulin is more antigenic because T cells that pass thymic selection, the process whereby self-reactive T cells are deleted, only recognize non-iodinated thyroglobulin motifs as belonging to self (22). Animal models strongly support this pathophysiological mechanism whereby iodine induces thyroid autoimmunity, as, “Excessive iodine intake can precipitate spontaneous thyroiditis in genetically predisposed animals, by increasing the immunogenicity of thyroglobulin (TG)” (19).
According to Topliss (2016), “Iodine supplementation is believed to increase the prevalence of circulating anti-TPO. The underlying mechanism is yet to be elucidated; however, more highly iodinated TG is more antigenic in experimental autoimmune thyroiditis” (11, p. 494). Experimental models of autoimmune thyroiditis have underscored that loss of B-cell self-tolerance occurs first for thyroglobulin and then secondarily for thyroid peroxidase, in line with these observations (23). Moreover, at a biochemical level, iodine may inhibit thyroid hormone synthesis and secretion, which is known as the Wolff-Chaikoff effect (10). According to Markou and colleagues (2001), “It is proposed that iodopeptide(s) are formed that temporarily inhibit thyroid peroxidase (TPO) mRNA and protein synthesis and, therefore, thyroglobulin iodinations. The Wolff-Chaikoff effect is an effective means of rejecting the large quantities of iodide and therefore preventing the thyroid from synthesizing large quantities of thyroid hormones” (10, p. 501).
The authors clarify that, “The acute Wolff-Chaikoff effect lasts for a few days and then, through the so-called “escape” phenomenon, the organification of intrathyroidal iodide resumes and the normal synthesis of thyroxine (T4) and triiodothyronine (T3) returns” (10, p. 501). However, in euthyroid patients with Hashimoto’s thyroiditis, this escape phenomenon from the inhibitory effect of iodine is impaired, resulting in subclinical or clinical hypothyroidism (10).
Another potential mechanism through which iodine exacerbates or induces Hashimoto’s is by up-regulating Th17 cells, the immune cell subset responsible for tissue destruction in autoimmune disease, and by suppressing development of regulatory T cells, the population that invokes oral tolerance to arrest autoimmune responses (31). Duntas (2015) articulates, “In susceptible individuals, iodine excess increases intra-thyroid infiltrating Th17 cells and inhibits T regulatory (Treg) cells development, while it triggers an abnormal expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in thyrocytes, thus inducing apoptosis and parenchymal destruction” (31, p. 721). Also relevant to this phenomenon is the ratio of iodine to selenium, since selenoproteins mediate antioxidant, anti-inflammatory, and redox-related processes (31). “Selenostasis”, which is found to be compromised in Hashimoto’s thyroiditis and Graves’ disease, is critical to counterbalance iodine, because “Selenium enhances CD4+/CD25 FOXP3 and T regulatory cells activity while suppressing cytokine secretion, thus preventing apoptosis of the follicular cells and providing protection from thyroiditis” (31, p. 721).
Caveats for Iodine Supplementation
Based on a review of the literature, the only people who should be supplementing with iodine are those with lab-validated iodine deficiency. 90% of ingested iodine is excreted via renal pathways, such that median spot urinary iodine concentrations (UIC) will serve as a biomarker for recent dietary iodine intake (1). Iodine sufficiency is defined as median UIC of 100-299 micrograms per liter in school-aged children and greater than or equal to 140 micrograms per liter in pregnant women (32). However, some authors maintain that these tests are sufficient only at the population level and should not be applied to individuals due to the large day-to-day variation in iodized salt intake (1).
According to Konig and colleagues, (2011), “~10 repeat spot urine collections are needed to estimate individual iodine intakes with acceptable precision” (29, p. 524). On the other hand, the World Health Organization recommends urine iodine concentration (UIC) to monitor an individual’s iodine status (2). Because a single measurements serves only as an isolated snapshot in time, and may not be reflective of total body iodine status, repeat testing may be necessary before conclusions about iodine deficiency can be drawn.
Moreover, because thyroid hormone is critical for fetal and infant neurodevelopment in utero and post-partum, and since iodine deficiency can result in neurological and psychological deficits, using a multivitamin containing iodine may be indicated during pregnancy and breastfeeding. Although Prete, Paragliola, and Corsello (2015) caution against use of iodine in Hashimoto’s thyroiditis at levels above 100 micrograms per day, they note that one exception is use of iodine supplementation during pregnancy to avoid damage to the newborn (25). Topliss (2016) also mentions, “Discouraging iodine mega-supplementation may not preclude appropriate physiological supplementation in pregnancy to a total intake of 250 µg/day” (11, p. 495). The post-partum period is a high-risk time for the development of thyroid autoimmunity due to Th1 dominance; however, researchers discuss that the risk of developmental retardation and intellectual deficits outweighs the risk of Hashimoto’s onset.
Conclusions Regarding Iodine Supplementation in Hashimoto’s
When it comes to iodine, I have no dog in the fight. If the literature demonstrates that any natural food or nutraceutical helps Hashimoto’s, I’m all for it, having the condition myself—but this is just not the case with iodine. Barring any lab-validated iodine deficiency, restriction of iodine seems to be warranted in Hashimoto’s thyroiditis, and use of iodized salts and supplements containing high doses of iodine would appear to be contraindicated. Thus, if your functional medicine practitioner, nutritionist, naturopathic doctor, or alternative medicine provider recommends that you supplement with supra-physiological doses of iodine—or that you incorporate massive sea vegetables into your diet to boost thyroid function—ask them for the peer-reviewed study supporting this practice. My bet is that they will come up empty.
So, why are people so invested in iodine? According to the Thyroid Pharmacist, Dr. Isabella Wentz, people may experience a short-term artificial increase in energy after beginning an iodine supplement (26). Dr. Wentz fleshes out a probable mechanism, whereby their newfound energy is derived from iodine-induced thyroid tissue destruction and the liberation of thyroid hormone into the circulation (26).
In summary, an across-the-board recommendation for iodine supplementation in people with Hashimoto’s thyroiditis is not evidence-based. Studies have rather supported the contrary notion, that, “high iodine intake [is] likely to lead to occurrence of thyroid diseases, such as Hashimoto’s thyroiditis, nodular goiter, and hyperthyroidism, through a long-term mechanism” (3). In fact, groups with the aforementioned thyroid diseases, as well as individuals with positive TG or TPO antibodies, have been demonstrated to exhibit significantly higher levels of urinary iodine, the main indicator of iodine nutritional status, compared to healthy controls (3).
What’s more, individuals with a family history of Hashimoto’s thyroiditis should be especially cautious about iodine intake, since the autoimmune reaction induced by iodine is particularly likely in genetically susceptible individuals. Besides promoting immunogenicity of the thyroglobulin molecule, dietary iodine can enhance levels of reactive oxygen species (ROS), which lead to expression of cell adhesion molecules (ICAM-1) that are crucial to the early phases of thyroid follicular inflammatory responses (3). Lastly, excessive iodine can generate high levels of hydrogen peroxide (H2O2), which damages thyrocytes and perpetuates thyroid autoimmunity (27).
The role of iodine in triggering Hashimoto’s thyroiditis should not be taken lightly, as an increased prevalence of thyroid autoantibodies was discovered even after cautious iodization programs were implemented (14, 28). According to researchers, this data cumulatively substantiates the notion that even small increases in supplemental iodine may increase risk for thyroid autoimmunity (9).
Caution should therefore be heeded before adding supplemental iodine to the regimen of any patient with thyroid autoimmunity, since, “Iodine intake modulates the pattern of thyroid diseases, even in cases of slight differences in intake and doses below 150 μg daily recommended for preventing IDD” (9).
*Article originally appeared at Green Med Info.