Iodine Prescribing Update

Abstract

Thirteen years ago, IMCJ published editorial 11.1, “How Much Iodine Should We Prescribe?” We explored the controversy around the safety and efficacy of supplemental iodine. We looked at the incidence of deficiency, epidemiological population studies of thyroid disorders, safety of various dosages, the need of special populations for larger dosages, and the unreliability of laboratory measures to determine an individual’s iodine deficiency. We also sought the guidance of several highly experienced doctors of nutritional/integrative/functional/natural medicine. Their opinions ranged from conservative recommendations to aggressive supplementation in those with specific conditions. In this editorial we reviewed the research to help advance our understanding of iodine supplementation.

Introduction

Iodine deficiency is becoming more common in the West and is an issue worldwide. However, iodine supplementation is highly controversial and clearly associated with adverse drug reactions in specific populations. Thirteen years ago, JP wrote an editorial (11.1) on iodine supplementation and asked the perspectives of well-known and respected experts in our medicine, Jeffrey Bland, PhD, Peter D’Adamo, ND, Alan Gaby, MD, Michael Murray, ND, and Jonathan Wright, MD. Their guidance was remarkably diverse. This editorial provides an update.

Iodine Supplementation Safety

Iodine is Harmful for Thyroid Function in Specific Populations

Iodine intake, even at recommended dietary allowance (RDA) levels, may adversely affect thyroid function in individuals with preexisting thyroid conditions, such as multinodular thyroid disease, goitrous nodules, autoimmune thyroiditis (Hashimoto’s or Graves disease), thyroid nodules or cysts, or previous thyroid-removal surgery to remove them.¹

These conditions are indications of thyroid dysfunction, which is more likely to include impaired autoregulation, such as an inability to escape from the Wolff-Chaikoff effect (a temporary downregulation of the sodium iodide transporter in the thyroid, triggering hypothyroidism), or an inability to activate the Wolff-Chaikoff effect, referred to as Jod-Basedow syndrome, which triggers hyperthyroidism.^1,2

In healthy individuals, a daily intake of iodine/iodide at a level of 200-300 μg appears to not only be safe but have anti-inflammatory effects.³ A safe level of iodine intake in adolescents and adults with preexisting thyroid conditions is ≤150 μg/day; that is, no more than the RDA, possibly less, at least until thyroid function has normalized.

Restoring normal thyroid function requires more than just adequate iodine intake. It also requires addressing many other nutritional factors as well as environmental toxins known to impair thyroid metabolism. Response to nutritional and detoxification interventions can take many months and requires careful assessment and monitoring. Here are important factors to consider:

1. There must be sufficiency of the micronutrients required to support optimal thyroid function. Deficiency of selenium, iron, zinc, copper, magnesium, vitamin A, and vitamin D are common.⁴

2. Excessive intake of goitrogens can aggravate iodine insufficiency. Cruciferous vegetables’ glucosinolates can inhibit the sodium/iodide symporter (NIS) and interfere with thyroid peroxidase activity, a problem only when crucifer intake is excessive and iodine intake is insufficient.⁵ (JP: This is not just theoretical. I saw a patient several years ago with overt hypothyroidism, including a visually obvious goiter. He was consuming 1 head of cabbage a day! Unfortunately, he was not willing to change his diet and sought a doctor to prescribe him thyroid.)

3. Millet contains flavonoids that can inhibit thyroid peroxidase.⁶

4. Excessive saturated fat intake increases production of thyroid autoantibodies.⁷

5. Highly processed foods can promote insulin resistance and metabolic syndrome; food preparation practices are important, as advanced glycation end products promote oxidative stress and increase risk of Hashimoto’s disease.⁸

6. A lack of resistant starch reduces microbiome support⁷; gluten intake is important, as celiac disease and gluten sensitivity are associated with thyroid dysfunction.⁹

7. Exposure to endocrine-disrupting environmental toxins impairs thyroid function. These toxins include plastics, pesticides, polychlorinated biphenyls, flame retardants (polybrominated diphenyl ethers and organophosphates), perfluoroalkyl substances, bisphenols, heavy metals (cadmium, mercury, and lead), perchlorate (binds iodine), dioxins, and even mold and air pollution. These toxins interfere with thyroid function in many ways: they impair transport of iodine into the thyroid, triiodothyronine (T3) and thyroxine (T4) production, conversion of T4 to the physiologically 4-fold more active T3, and cellular response to thyroid hormones, and they mimic thyroid hormone activity independently of regulatory mechanisms or even directly affect transport proteins and enzymes.⁷

8. Some prescription medications affect thyroid function. For example, lithium can increase risk of hypothyroidism via changing the structure of thyroglobulin, weakening the iodination of tyrosine and disrupting their coupling, which reduces the clearance of free T4 in the serum, thereby indirectly reducing the activity of 5-deiodinase type 1 and 2 and reducing the deiodination of these hormones in the liver. Another example is amiodarone, which contains high amounts of iodine and can increase risk of both hypo- and hyperthyroidism.¹⁰

9. Finally, and not surprisingly, chronic stress increases cortisol, which inhibits deiodinase enzymes, preventing conversion of T4 to T3.¹¹

Although prevalence of iodine toxicity in the general population is low (<1% according to data collected 2008-2015), a prospective pregnancy cohort found a prevalence of inadequate iodine intake to be 23%).¹² Individuals with preexisting thyroid conditions may still be at risk of iodine toxicity even at RDA levels due to dysfunctional autoregulation resulting in increased susceptibility for failure to escape the Wolff-Chaikoff effect, which can lead to iodine-induced hypothyroidism, or resulting in an inability to induce the Wolff-Chaikoff effect (aka Jod-Basedow syndrome), which can lead to iodine-induced hyperthyroidism.

Thyroid nodules are surprisingly common

In addition to preexisting thyroid conditions, Jod-Basedow syndrome, while supposedly rare, is thought to be frequently missed and is also associated with repeated exposure to iodinated contrast media used in conjunction with computed tomography scans, angiography, and other imaging studies.² Iodinated contrast media are common triggers for iodine-induced hyperthyroidism. The large iodine load from a single imaging scan can precipitate thyrotoxicosis in a person with underlying nodular thyroid disease, and thyroid nodules are not uncommon. Although physical examination alone shows a prevalence of thyroid nodules of 5% to 7% in adults, ultrasonography shows a prevalence of 20% to 76%.

A study published January 2024 using ultrasonography rather than physical examination to detect thyroid nodules reported an overall prevalence of 38.3% in healthy Chinese individuals, with significantly higher rates in women (44.4%) than men (30.2%), increasing with age.¹³

In another study conducted in China that included 1697 participants (539 men and 1158 women) aged 18-60 years, 355 were diagnosed with thyroid nodules. Overall prevalence was 20.9% with 21.9% in iodine-deficient areas, 25.8% in iodine-adequate areas, and 18.0% in iodine-excess areas. Prevalence was significantly higher in women than men (24.5% vs 13.2%, respectively) and increased with age. Risk factors were female sex (OR, 1.67 [1.21-2.30]), old age (>41 years; OR, 2.00 [1.14-3.50]), and smoking, likely due to cadmium exposure in cigarette smoke.¹⁴ In the most recent papers, prevalence of thyroid nodules is shown to increase with metabolic syndrome.¹⁵

Autoimmune thyroid disease is surprisingly common

Autoimmune thyroid disease (primarily Hashimoto’s disease) is common in the United States, particularly in older adult women. According to the American Thyroid Association, the combined prevalence of subclinical and overt hypothyroidism in the US population could be as high as 10% to 20%, with higher rates in adults aged 65 years and older, particularly women.¹⁶ However, women diagnosed with subclinical hypothyroidism should be closely followed, as higher concentrations of thyroid-stimulating hormone and the presence of thyroid peroxidase antibodies are linked to a higher risk of progression to overt hypothyroidism.¹⁷

Individuals with autoimmune thyroid disease (Hashimoto’s or Graves disease) treated for iodine deficiency or nodular goiter may be at increased risk of adverse effects from iodine intake. Young adults with simple goiter and iodine deficiency supplemented with iodine at a dose of 200 μg/day developed either mild transient hyperthyroidism or hypothyroidism, positive antibodies, and reversible histological changes of lymphocytic thyroiditis. Although the sensitivities of these distinct subgroups do not fall within the range of sensitivities expected for the healthy population, it may be important to note that these young adults’ actual iodine intake may have been far greater if an estimate including dietary intake and the use of a multiple vitamin supplement had been included.¹⁸ Data from the Total Diet Study collected between 2008 and 2012 indicated that the average daily iodine intake from food in the US was 216 μg/day and did not account for iodine derived from the use of iodized salt or iodine-containing supplements.¹⁹ The 1999-2004 National Health and Nutrition Examination Survey reported iodine-containing supplements were being taken by 28% to 29% of adults.¹⁹

A sudden increase in iodine intake can worsen Hashimoto’s disease by stimulating the immune system to produce thyroid autoantibodies; that is, anti-thyroid peroxidase or anti-thyroglobulin antibodies. In susceptible individuals, high iodine levels can also increase reactive oxygen species production, damaging thyroid follicular cells. Iodine in excess can increase T_H17 cells while decreasing Treg cells within the thyroid, an imbalance typically seen in autoimmune thyroiditis that promotes thyroid damage.²⁰

Indications for Iodine Supplementation

As discussed, a substantial portion of the general population can be harmed by even modest levels of supplemental iodine. However, some populations significantly benefit from additional iodine. When dietary consumption of iodine is adequate, only 10% of iodine is retained by the thyroid gland, with the excess rapidly eliminated in urine. This process helps explain why spot testing is not reliable and why a 24-hour urine iodine test is needed to determine iodine sufficiency. Importantly, thyroid function may be impaired more by deficiencies in other nutrients. Thus, we discuss here the need for iodine supplementation as well as other factors to consider.

As autoimmune thyroiditis appears to be the most common cause of thyroid disease in the US, we need to focus more on the causes of autoimmune reactions rather than simply prescribing levothyroxine to treat hypothyroidism. Identifying and treating these autoimmune reactions could be key to restoring thyroid function. We now know that environmental toxins are primary drivers of the rampant thyroid dysfunction we are seeing. According to current research, hypothyroidism prevalence in the US grew from 9.6% during 2009-2012 to 11.7% during 2012-2019, and untreated hypothyroidism increased from 11.8% to 14.4% during 2012-2019.^21,22

Patients presenting with goiter are often also deficient in iron, which means iron intake must be checked, particularly in vegetarians and vegans. And as mentioned earlier, intake of many other nutrients must be considered, such as vitamin D, zinc, and magnesium. But we also have to consider other factors than just thyroid hormone production. For example, antioxidants and (essential) fatty acids improve thyroid function by reducing thyroid inflammation.

Iodine intake insufficiency may be more common than recognized

A further complication of determining who needs supplemental iodine is the conflicting information regarding the sufficiency of iodine intake in the US. Although iodine insufficiency is the leading cause of hypothyroidism worldwide, in the West, iodized salt is supposed to prevent this, and the most common cause of hypothyroidism is autoimmune thyroiditis (Hashimoto’s disease).⁴ Some researchers assert iodine deficiency is rare.²³ While this may still be true for the population overall, recent reports indicate that iodine intake in the US is inadequate in certain groups; that is, girls and young women. A study published May 2023 reported median dietary iodine intake of 108.8 μg/day among pregnant women, with 63% falling below the estimated average requirement.²⁴ Another article, published March 2024, reported a significant decline in dietary iodine intake in girls and women of reproductive age (15-49 years) between 2011 and 2020. Iodine intake insufficiency estimated from urine iodine concentrations was close to 50% for nonpregnant girls and women and greater than 50% for pregnant women.²⁵

In 2015, Elizabeth Pearce, MD, published a commentary entitled “Is Iodine Deficiency Reemerging in the United States?”²⁶ Her concerns were supported by a review published in 2022, summarizing recently published studies reporting the reemerging issue of iodine deficiency among populations in developed countries. A quote from this review: “In the U.S., in spite of salt-iodization policies, mild-to-moderate iodine deficiency is common and appears to be increasing.”²⁷

Iodine is Helpful for Fibrocystic Breast Disease

Other groups of women for whom iodine insufficiency may be an issue and whose needs for iodine may be significantly increased are those with fibrocystic breast disease and/or breast cancer.^28-30 Over the years, a number of researchers have suggested that treatment with iodine may provide significant benefit, with doses ranging from 75 μg (Mansel et al³¹) to 3-6 mg/day (Patrick³²). For decades, integrative medicine pioneer Jonathan Wright, MD, has recommended high-dose iodine supplementation for women with fibrocystic breast disease. Alan Gaby, MD (who used to practice with Wright), summarized studies supporting this intervention.³³ (JP: I have successfully helped women with fibrocystic breast disease using topical iodine combined with contrast hydrotherapy. Although no apparent adverse events occurred, in retrospect I wish I had been aware of the thyroid nodule problem, as this could have been a contraindication or indication of the need for more careful monitoring.)

Conclusion

Iodine deficiency is surprisingly common, especially in young women, but more worrisome in pregnant women. Unfortunately, this does not mean a blanket recommendation for iodine supplementation due to the also surprisingly common problem of thyroid nodules. In addition, some specific groups clearly benefit from higher levels of supplementation. However, due to the high risk of adverse drug reactions, every patient being considered for iodine supplementation must be carefully screened for thyroid nodules (as well as other relevant but much less likely potential issues), and other causes of impaired thyroid function must be addressed before simply supplementing with iodine. Nonetheless, those needing iodine greatly benefit from supplementation.

Biographies

Joseph Pizzorno, ND, Editor in Chief, IMCJ; co-author, Textbook of Natural Medicine; Founding President, Bastyr University; Founding Member, Board of Directors, Institute for Functional Medicine.

Lara Pizzorno, MDiv, MA, LMT, MSN(c), co-author of Healthy Bones, Healthy You and a prolific writer on bone health.