Micronutrient Information Center

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Summary

• Iodine is a key component of thyroid hormones, which are required throughout life for normal growth, neurological development, and metabolism. (More information)
• Insufficient iodine intake impairs the production of thyroid hormones, leading to a condition called hypothyroidism. Iodine deficiency results in a range of adverse health disorders with varying degrees of severity, from thyroid gland enlargement (goiter) to severe physical and mental retardation known as cretinism. (More information)
• Iodine deficiency-induced hypothyroidism has adverse effects in all stages of development but is most damaging to the developing brain. Maternal iodine deficiency during pregnancy can result in maternal and fetal hypothyroidism, as well as miscarriage, preterm birth, and neurological impairments in offspring. (More information)
• Even in areas with voluntary/mandatory iodization programs and in iodine-replete countries, pregnant women, lactating mothers, and young infants are among the most vulnerable to iodine deficiency due to their special requirements during these life stages. (More information)
• The recommended dietary allowance (RDA) for iodine intake is 150 micrograms (μg)/day in adults, 220 μg/day in pregnant women, and 290 μg/day in breast-feeding women. During pregnancy and lactation, the fetus and infant are entirely reliant on maternal iodine intake for thyroid hormone synthesis. (More information)
• Thyroid accumulation of radioactive iodine (¹³¹I) increases the risk of developing thyroid cancer, especially in children. In case of radiation emergencies, current preventive measures include the distribution of pharmacologic doses of potassium iodide that would reduce the risk of significant uptake of ¹³¹I by the thyroid gland. (More information)
• Seafood is an excellent source of dietary iodine. Dairy products, grains, eggs, and poultry contribute substantially to dietary iodine intakes in the US. (More information)
• More than 120 countries worldwide have introduced programs of salt fortification with iodine in order to correct iodine deficiency in populations. (More information)
• In iodine-deficient populations, a rapid increase in iodine intake may precipitate iodine-induced hyperthyroidism. The risk of iodine-induced hyperthyroidism is especially high in older people with multi-nodular goiter. (More information)
• In iodine-sufficient adults, long-term iodine intake above the tolerable upper intake level (UL) of 1,100 μg/day may increase the risk of thyroid disorders, including iodine-induced goiter and hypothyroidism. (More information)

Iodine (I), a non-metallic trace element, is required by humans for the synthesis of thyroid hormones. Iodine deficiency is an important health problem throughout much of the world. Most of the Earth's iodine, in the form of the iodide ion (I^-), is found in oceans, and iodine content in the soil varies with region. The older an exposed soil surface, the more likely the iodine has been leached away by erosion. Mountainous regions, such as the Himalayas, Atlas, Andes, and Alps; flooded river valleys, such as the Ganges River plain in India; and many inland regions, such as central Asia and Africa, central and eastern Europe, and the Midwestern region of North America are among the most severely iodine-deficient areas in the world (1). 

Function

Iodine is an essential component of the thyroid hormones, triiodothyronine (T₃) and thyroxine (T₄), and is therefore essential for normal thyroid function. To meet the body's demand for thyroid hormones, the thyroid gland traps iodine from the blood and incorporates it into the large (660 kDa) glycoprotein thyroglobulin. The hydrolysis of thyroglobulin by lysosomal enzymes gives rise to thyroid hormones that are stored and released into the circulation when needed. In target tissues, such as the liver and the brain, T₄ (the most abundant circulating thyroid hormone) can be converted to T₃ by selenium-containing enzymes known as iodothyronine deiodinases (DIOs) (Figure 1; see also Nutrient interactions). T₃ is the physiologically active thyroid hormone that can bind to thyroid receptors in the nuclei of cells and regulate gene expression. In this manner, thyroid hormones regulate a number of physiologic processes, including growth, development, metabolism, and reproductive function (2).

[Figure 1 - Click to Enlarge]

The regulation of thyroid function is a complex process that involves the hypothalamus and the pituitary gland. In response to thyrotropin-releasing hormone (TRH) secretion by the hypothalamus, the pituitary gland secretes thyroid-stimulating hormone (TSH), which stimulates iodine trapping, thyroid hormone synthesis, and release of T₄ and T₃ by the thyroid gland. The presence of adequate circulating T₄ and T₃ feeds back at the level of both the hypothalamus and pituitary, decreasing TRH and TSH production (Figure 2). When circulating T₄ levels decrease, the pituitary gland increases its secretion of TSH, resulting in increased iodine trapping, as well as increased production and release of both T₃ and T₄. Iodine deficiency results in inadequate production of T₄. In response to decreased blood T₄ concentrations, the pituitary gland increases its output of TSH. Persistently elevated TSH levels may lead to hypertrophy (enlargement) of the thyroid gland, also known as goiter (see Deficiency) (3).

[Figure 2 - Click to Enlarge]

Deficiency

The thyroid gland of a healthy adult concentrates 70-80% of a total body iodine content of 15-20 mg and utilizes about 80 μg of iodine daily to synthesize thyroid hormones. In contrast, chronic iodine deficiency can result in a dramatic reduction of the iodine content in the thyroid well below 1 mg (1). Iodine deficiency is recognized as the most common cause of preventable brain damage in the world. The spectrum of iodine deficiency disorders (IDD) includes mental retardation, hypothyroidism, goiter, and varying degrees of other growth and developmental abnormalities (4). The World Health Organization (WHO) estimated that over 30% of the world’s population (2 billion people) have insufficient iodine intake as measured by median urinary iodine concentrations below 100 μg/L (5). Moreover, about one-third of school-age children (6-12 years old) worldwide (241 million children in 2011) have insufficient iodine intake (6, 7). Major international efforts have produced dramatic improvements in the correction of iodine deficiency in the 1990s, mainly through the use of iodized salt in iodine-deficient countries (4). Although about 70% of households in the world now have access to iodized salt (8), mild-to-moderate iodine deficiency remains a public health concern in at least 30 countries; there are no iodine excretion data available for 42 other countries, including Israel, Syria, and Sierra Leone (7). For more information on the international effort to eradicate iodine deficiency, visit the websites of the Iodine Global Network (formerly the International Council for the Control of Iodine Deficiency Disorders) and the WHO.

Biomarkers of iodine status

More than 90% of ingested iodine is excreted in the urine within 24-48 hours such that daily iodine intakes in a population can be extrapolated from measures of median spot urinary iodine concentrations (9, 10). According to WHO criteria, population iodine deficiency is defined by median urinary iodine concentrations lower than 150 micrograms (μg)/L for pregnant women and 100 μg/L for all other groups (Table 1). Adequate intakes correspond to median urinary iodine concentrations of 100-199 μg/L in school-age children and 150-249 μg/L in pregnant women (Table 1). While median urinary iodine concentration is a population indicator of recent dietary iodine intake, multiple collections of 24-hour urinary iodine are preferable to estimate intake in individuals (9-11).

In many countries, serum TSH concentration is used in the screening for congenital hypothyroidism in newborns. Newborn TSH can be used as an indicator of population iodine status. Yet, in older children and adults, serum TSH is not a sensitive indicator of iodine status as concentrations are usually maintained within a normal range despite frank iodine deficiency (12). Serum thyroglobulin concentration in school-age children is a sensitive marker of iodine status in populations (13). In areas of endemic goiter, changes in thyroid size reflect long-term iodine nutrition (months to years). Assessment of the goiter rate in a population is used to define the severity of iodine deficiency, as well as to monitor the long-term impact of sustained salt iodization programs (4, 10). Finally, serum thyroid hormone concentrations do not adequately reflect iodine nutrition in populations (1).

Iodine deficiency disorders

All the adverse effects of iodine deficiency in animals and humans are collectively termed iodine deficiency disorders (reviewed in 1). Thyroid enlargement, or goiter, is one of the earliest and most visible signs of iodine deficiency. It is a physiologic adaptation of the thyroid gland in response to persistent stimulation by TSH (see Function). In mild iodine deficiency, thyroid enlargement may be enough to maximize the uptake of available iodine and provide the body with sufficient thyroid hormones. Yet, large goiters can obstruct the trachea and esophagus and damage the recurrent laryngeal nerves.

More severe cases of iodine deficiency result in impaired thyroid hormone synthesis known as hypothyroidism. Adequate iodine intake will generally reduce the size of goiters, but the reversibility of the effects of hypothyroidism depends on an individual's life stage. Iodine deficiency-induced hypothyroidism has adverse effects in all stages of development but is most damaging to the developing brain. In addition to regulating many aspects of growth and development, thyroid hormones are important for the migration, proliferation, and differentiation of specific neuronal populations, the overall architecture of the brain’s cortex, the formation of axonal connections, and the myelination of the central nervous system, which occurs both before and shortly after birth (reviewed in 14).

The effects of iodine deficiency at different life stages are discussed below.

Pregnancy and lactation

Daily iodine requirements are significantly increased in pregnant and breast-feeding women because of (1) the increased thyroid hormone production and transfer to the fetus in early pregnancy before the fetal thyroid gland becomes functional, (2) iodine transfer to the fetus during late gestation, (3) increased urinary iodine excretion, and (4) iodine transfer to the infant via breast milk (see also The RDA) (12, 15).

During pregnancy, the size of the thyroid gland is increased by 10% in women residing in iodine-sufficient regions and increased by 20%-40% in those living in iodine-deficient regions (16). Iodine deficiency during pregnancy can result in hypothyroidism in women. Maternal hypothyroidism has been associated with increased risk for preeclampsia, miscarriage, stillbirth, preterm birth, and low-birth-weight infants (reviewed in 16). In addition, severe iodine deficiency during pregnancy may result in congenital hypothyroidism and neurocognitive deficits in the offspring (see Prenatal development) (12).

Iodine-deficient women who are breast-feeding may not be able to provide sufficient iodine to their infants who are particularly vulnerable to the effects of iodine deficiency (see Newborns and infants) (17). A daily prenatal supplement of 150 μg of iodine, as recommended by the American Thyroid Association (ATA) (16), will help to ensure that US pregnant and breast-feeding women consume sufficient iodine during these critical periods. In iodine-deficient areas where iodized salt is not available, the Iodine Global Network (IGN; formerly the International Council for the Control of Iodine Deficiency Disorders), the World Health Organization (WHO), and UNICEF recommend that lactating women receive a single annual dose of 400 mg of iodine (or 250 μg/day) and exclusively breast-feed for at least six months. When breast-feeding is not possible, direct supplementation of the infant (<2 years old) with a single annual dose of 200 mg of iodine (or 90 μg/day) is advised (4). A randomized and placebo-controlled trial recently demonstrated that maternal supplementation (with a single 400-mg dose of iodine) improved the iodine status of breast-fed infants more efficiently than direct infant supplementation (with a single 100 mg-dose of iodine) for a period of at least six months (18). Yet, supplementation of lactating women failed to increase maternal urinary iodine concentrations above 100 μg/L, suggesting that supplemented mothers remained deficient in iodine (18).

Prenatal development

Fetal iodine deficiency is caused by iodine deficiency in the mother (see Pregnancy and lactation). During pregnancy, before the fetal thyroid gland becomes functional at 16-20 weeks’ gestation, maternal thyroxine (T₄) crosses the placenta to promote normal embryonic and fetal development. Hence, maternal iodine deficiency and hypothyroidism can result in adverse pregnancy complications, including fetal loss, placental abruption, preeclampsia, preterm delivery, and congenital hypothyroidism in the offspring (16). The effects of maternal hypothyroidism on the offspring depend on the timing and severity of in utero iodine deficiency. A severe form of congenital hypothyroidism may lead to cretinism, a condition associated with irreversible mental retardation. The clinical picture of neurological cretinism in the offspring includes severe mental and physical retardation, deafness, mutism, and motor spasticity.

A myxedematous form of cretinism has been associated with coexisting iodine and selenium deficiency in central Africa (see Nutrient interactions) and is characterized by a less severe degree of mental retardation than in neurological cretinism. Yet, affected individuals exhibit all the features of severe hypothyroidism, including severe growth retardation and delayed sexual maturation (12). Two longitudinal cohort studies (one in the UK and one in Australia) recently observed that even mild-to-moderate iodine deficiency during pregnancy was associated with reduced scores of IQ and various measures of literacy performance in children 8 to 9 years of age (19, 20). 

Newborns and infants (up to one year of age)

Infant mortality is higher in areas of severe iodine deficiency than in iodine-replete regions, and several studies have demonstrated an increase in childhood survival upon correction of the iodine deficiency (8, 21, 22). Infancy is a period of rapid brain growth and development. Sufficient thyroid hormone, which depends on adequate iodine intake, is essential for normal brain development. Even in the absence of congenital hypothyroidism, iodine deficiency during infancy may result in abnormal brain development and, consequently, impaired intellectual development (23, 24).

Children and adolescents

Iodine deficiency in children and adolescents is often associated with goiter. The incidence of goiter peaks in adolescence and is more common in girls than boys. School-age children in iodine-deficient areas show poorer school performance, lower IQs, and a higher incidence of learning disabilities than matched groups from iodine-sufficient areas. Three meta-analyses of mainly cross-sectional studies concluded that chronic iodine deficiency was associated with reduced mean IQ scores by 7-13.5 points in participants (primarily children) (25-27). However, these observational studies did not distinguish between iodine deficiency during pregnancy and during childhood, and such observational studies may be confounded by social, economic, and educational factors that influence child development.

Adults

Inadequate iodine intake may also result in goiter and hypothyroidism in adults. Although the effects of hypothyroidism are more subtle in the brains of adults than children, research suggests that hypothyroidism results in poor social and economic achievements due to low educability, apathy, and reduced work productivity (28). Other symptoms of hypothyroidism in adults include fatigue, weight gain, cold intolerance, and constipation.

Finally, because iodine deficiency induces an increase in the iodine trapping capacity of the thyroid, iodine-deficient individuals of all ages are more susceptible to radiation-induced thyroid cancer (see Disease Prevention), as well as to iodine-induced hyperthyroidism after an increase in iodine intakes (see Safety) (2).

Individuals and populations at risk of iodine deficiency

While the risk of iodine deficiency for populations living in iodine-deficient areas without adequate iodine fortification programs is well recognized, concerns have been raised that certain subpopulations in countries considered iodine-sufficient may not consume adequate iodine (7, 29). The greater use of methods assessing iodine status (see Biomarkers of iodine status) has shown that iodine deficiency also occurs in areas where the prevalence of goiter is low, in coastal areas, in highly developed countries, and in regions where iodine deficiency was previously eliminated (4).

The US is currently considered to be iodine-sufficient. Yet, in recent years, dietary intakes of iodine in the US population have decreased. Data from the latest US National Health and Nutrition Examination Survey (NHANES 2009-2010) indicated that the median urinary iodine concentration for the general population was 144 μg/L compared to 164 μg/L reported in previous assessments (NHANES 2005-2006 and 2007-2008) (30, 31). In addition to regional differences across the US, ethnic variations have been found. In all age groups, median urinary iodine concentrations were shown to be lower in African Americans than in Hispanics and Caucasians.

In addition, median urinary iodine concentrations in nonpregnant women of childbearing age and pregnant women indicate that mild iodine deficiency has re-emerged in the US in recent years (31).

Nonpregnant women

Data from US NHANES 2007-2010 indicated that 37.3% of nonpregnant women (ages 15-44 years) had urinary iodine concentrations lower than 100 μg/L, reflecting potentially insufficient iodine intakes (see Biomarkers of iodine status) (31). Only one-fifth of nonpregnant women reported using iodine-containing supplements in an earlier NHANES (2001-2006) (32). Yet, adequate intakes of iodine in women of childbearing age (150 μg/day; see The RDA) are essential for optimum stores of iodine, especially if they are considering pregnancy. Some experts suggested a daily consumption of 250 μg of iodine before conception to ensure adequate thyroid hormone production and iodine supply to the embryo and fetus during pregnancy (see Pregnancy and lactation) (12).

Pregnant women

There are no statistics on the global burden of iodine deficiency in pregnant women, but national and regional data suggest that this group is especially vulnerable. Given the increased iodine requirements during pregnancy, the median urinary iodine concentration should be at least of 150 μg/L (see Biomarkers of iodine status). Pooled data from NHANES 2005-2010 reported that US pregnant women had a median urinary iodine concentration of 129 μg/L, and the lowest median concentration (109 μg/L) was observed during the first trimester of gestation, when the embryo/fetus relies exclusively on maternal thyroid hormones (31).

Breast-feeding women

While data regarding the iodine status of breast-feeding women in the US are limited, dietary intakes that were inadequate during pregnancy are likely to be insufficient in a significant fraction of breast-feeding women (33, 34). A systematic review of the literature recently reported suboptimal dietary iodine intakes in breast-feeding women in some countries with a mandatory fortification program, including Denmark, Australia, and India (35). The American Thyroid Association (ATA) recommends that all North American women who are pregnant or breast-feeding supplement their dietary iodine intake with 150 μg/day of iodine (36).

Breast-fed and weaning infants

The body of a healthy newborn contains only about 300 μg of iodine, which makes newborns extremely vulnerable to iodine deficiency (28), and breast-fed infants are entirely reliant on maternal iodine intakes for thyroid hormone synthesis. Even in areas covered by a salt iodization program, weaning infants are at high risk of iodine deficiency, especially if they are not receiving iodine-containing infant formula (17).

Individuals consuming special diets

Diets that exclude iodized salt, fish, and seaweed have been found to contain very little iodine (9). Individuals consuming branded weight-loss foods may also be at risk of inadequate intakes (37). A small US cross-sectional study in 78 vegetarians and 63 vegans reported median urinary iodine concentrations of 147 μg/L and 78.5 μg/L, respectively, suggesting inadequate iodine intakes among vegans (38). Two cases of goiter and/or hypothyroidism have also been recently reported in children following restrictive diets to control esophageal inflammation (eosinophilic esophagitis) (39) or allergies (40).

Patients requiring parenteral nutrition

Although iodine is usually not added to parenteral nutrition (PN) solutions, topical iodine-containing disinfectants and other adventitious sources provide substantial amounts of iodine to some PN patients such that the occurrence of iodine deficiency is unlikely. Yet, deficiency might occur, especially in preterm infants with limited body stores, if chlorhexidine-based antiseptics replace iodinated antiseptics (28, 41).

Nutrient interactions

Concurrent deficiencies in selenium, iron, or vitamin A may exacerbate the effects of iodine deficiency (reviewed in 42).

Selenium

While iodine is an essential component of thyroid hormones, the selenium-containing iodothyronine deiodinases (DIOs) are enzymes (or selenoenzymes) required for the conversion of T₄ to the biologically active thyroid hormone, T₃ (see the article on Selenium). DIO1 activity may also be involved in regulating iodine homeostasis (43). In addition, glutathione peroxidases are selenoenzymes that protect the thyroid gland from hydrogen peroxide-induced damage during thyroid hormone synthesis (44). A randomized, placebo-controlled study in 151 pregnant women at risk of developing autoimmune thyroid disease found that selenium supplementation (200 μg/day in the form of selenomethionine) at 12 weeks of gestation until 12 months’ postpartum reduced the risk of thyroid dysfunction and permanent hypothyroidism (45). However, another trial (the Selenium in Pregnancy Intervention Trial) found no benefit of selenium supplementation (60 μg/day from 12-14 weeks of gestation to delivery) over placebo on circulating autoantibody concentrations in pregnant women mildly deficient in iodine (46).

The epidemiology of coexisting iodine and selenium deficiencies in central Africa has been linked to the prevalence of myxedematous cretinism, a severe form of congenital hypothyroidism accompanied by mental and physical retardation. Selenium deficiency may be only one of several undetermined factors that might exacerbate the detrimental effects of iodine deficiency (42). Besides, results from randomized controlled intervention trials have shown that correcting only the selenium deficiency may have a deleterious effect on thyroid hormone metabolism in school-age children with co-existing selenium and iodine deficiency (47, 48). Finally, selenium deficiency in rodents was found to have little impact on DIO activities as it appears that selenium is being supplied in priority for adequate synthesis of DIOs at the expense of other selenoenzymes (44). 

Iron

Severe iron-deficiency anemia can impair thyroid metabolism in the following ways: (1) by altering the TSH response of the pituitary gland; (2) by reducing the activity of thyroid peroxidase that catalyzes the iodination of thyroglobulin for the production of thyroid hormones; and (3) in the liver by limiting the conversion of T₄ to T₃, increasing T₃ turnover, and decreasing T₃ binding to nuclear receptors (49). It is estimated that goiter and iron-deficiency anemia coexist in up to 25% of school-age children in west and north Africa (42). A randomized controlled study in iron-deficient children with goiter showed a greater reduction in thyroid size following the consumption of iodized salt together with 60 mg/day of iron four times per week compared to placebo (50). Additional interventions have confirmed that correcting iron-deficiency anemia improved the efficacy of iodine supplementation to mitigate thyroid disorders (reviewed in 42, 49).

Vitamin A

In north and west Africa, vitamin A deficiency and iodine deficiency-induced goiter may coexist in up to 50% of children. Vitamin A status, like other nutritional factors, appears to influence the response to iodine prophylaxis in iodine-deficient populations (51). Vitamin A deficiency in animal models was found to interfere with the pituitary-thyroid axis by (1) increasing the synthesis and secretion of thyroid-stimulating hormone (TSH) by the pituitary gland, (2) increasing the size of the thyroid gland, (3) reducing iodine uptake by the thyroid gland and impairing the synthesis and iodination of thyroglobulin, and (4) increasing circulating concentrations of thyroid hormones (reviewed in 52). A cross-sectional study of 138 children with concurrent vitamin A and iodine deficiencies found that the severity of vitamin A deficiency was associated with higher risk of goiter and higher concentrations of circulating TSH and thyroid hormones (51). These children received iodine-enriched salt together with vitamin A (200,000 IU at baseline and at 5 months) or a placebo in a randomized, double-blind, 10-month trial. Vitamin A supplementation significantly decreased TSH concentration and thyroid volume compared to placebo (51). In another trial, vitamin A supplementation alone (without iodine) to iodine-deficient children reduced the volume of the thyroid gland, as well as TSH and thyroglobulin concentrations (53). Yet, supplemental vitamin A had no additional effect on thyroid function/hormone metabolism when children were also given iodized oil.

Goitrogens

Some foods contain substances that interfere with iodine utilization or thyroid hormone production; these substances are called goitrogens. The occurrence of goiter in the Democratic Republic of Congo has been related to the consumption of cassava, which contains linamarin, a compound that is metabolized to thiocyanate and blocks thyroidal uptake of iodine (1). In iodine-deficient populations, tobacco smoking has been associated with an increased risk for goiter (54, 55). Cyanide in tobacco smoke is converted to thiocyanate in the liver, placing smokers with low iodine intake at risk of developing a goiter. Moreover, thiocyanate affects iodine transport into the lactating mammary gland, leading to low iodine concentrations in breast milk and impaired iodine supply to the neonates/infants of smoking mothers (2). Some species of millet, sweet potatoes, beans, and cruciferous vegetables (e.g., cabbage, broccoli, cauliflower, and Brussels sprouts) also contain goitrogens (1). Further, the soybean isoflavones, genistein and daidzein, have been found to inhibit thyroid hormone synthesis (56). Most of these goitrogens are not of clinical importance unless they are consumed in large amounts or there is coexisting iodine deficiency. Industrial pollutants, such as perchlorate (see Safety), resorcinol, and phthalic acid, may also be goitrogenic (1, 57).

The Recommended Dietary Allowance (RDA)

The RDA for iodine was reevaluated by the Food and Nutrition Board (FNB) of the Institute of Medicine (IOM) in 2001 (Table 2). The recommended amounts were calculated using several methods, including the measurement of iodine uptake in the thyroid glands of individuals with normal thyroid function (9). Similar recommendations have been made by several organizations, including the American Thyroid Association (ATA) (16, 58), the World Health Organization (WHO), the Iodine Global Network (IGN; formerly the International Council for the Control of Iodine Deficiency Disorders), and the United Nations Children’s Fund (UNICEF) (4). Of note, the WHO, IGN, and UNICEF recommend daily intakes of 250 μg of iodine for both pregnant and breast-feeding women (4).

Disease Prevention

Radiation-induced thyroid cancer

Radioactive iodine, especially iodine 131 (¹³¹I), may be released into the environment as a result of nuclear reactor accidents, such as the 1986 Chernobyl nuclear accident in Ukraine and the 2011 Fukushima Daiichi nuclear accident in Japan. Thyroid accumulation of radioactive iodine increases the risk of developing thyroid cancer, especially in children (59). The increased iodine trapping activity of the thyroid gland in iodine deficiency results in increased thyroid accumulation of radioactive iodine (¹³¹I). Thus, iodine-deficient individuals are at increased risk of developing radiation-induced thyroid cancer because they will accumulate greater amounts of radioactive iodine. Potassium iodide administered in pharmacologic doses (up to 130 mg for adults) within 48 hours before or eight hours after radiation exposure from a nuclear reactor accident can significantly reduce thyroid uptake of ¹³¹I and decrease the risk of radiation-induced thyroid cancer (60). The prompt and widespread use of potassium iodide prophylaxis in Poland after the 1986 Chernobyl nuclear reactor accident may explain the lack of a significant increase in childhood thyroid cancer compared to fallout areas where potassium iodide prophylaxis was not widely used (61). In the US, the Nuclear Regulatory Commission (NRC) requires that consideration be given to potassium iodide as a protective measure for the general public in the case of a major release of radioactivity from a nuclear power plant (62). See also the US FDA’s Potassium Iodide Information.

Disease Treatment

Fibrocystic breast changes

Fibrocystic breast changes constitute a benign (non-cancerous) condition of the breasts, characterized by lumpiness and discomfort in one or both breasts. Cyst formation and fibrous changes in the appearance of breast tissue occur in at least 50% of premenopausal women and are not usually associated with an increased risk of breast cancer (63). The cause of fibrocystic changes is not known, but variations in hormonal stimulation during menstrual cycles may trigger changes in breast tissue (63).

A few observational studies also suggested an association between benign breast diseases (including but not limited to fibrocystic changes) and thyroid disorders. Recently, a small case-control study (166 cases vs. 72 controls) showed that the frequency of benign breast diseases was greater in women with nodular goiter (54.9%) or Hashimoto thyroiditis (47.4%) than in euthyroid controls (29.2%) (64). Conversely, the prevalence of anti-thyroid autoimmunity and hypothyroidism was found to be significantly higher in women with benign breast diseases compared to controls (65, 66). Interestingly, correcting hypothyroidism with supplemental T₄ was found to improve some of the benign breast disease symptoms, including breast pain (mastalgia) and nipple discharge (65).

In estrogen-treated rats, iodine deficiency leads to changes similar to those seen in fibrocystic breasts, while iodine repletion reverses those changes (67). An uncontrolled study of 233 women with fibrocystic changes found that treatment with aqueous molecular iodine (I₂) at a dose of 0.08 mg of I₂/kg of body weight daily over 6 to 18 months was associated with improvement in pain and other symptoms in over 70% of participants (68). About 10% of the study participants reported side effects that were described by the investigators as minor. A double-blind, placebo-controlled trial of aqueous molecular iodine (0.07-0.09 mg of I₂/kg of body weight daily for six months) in 56 women with fibrocystic changes found that 65% of the women taking molecular iodine reported improvement compared to 33% of those taking the placebo (68). A double-blind, placebo-controlled trial in 87 women with documented breast pain reported that molecular iodine (1.5, 3, or 6 mg/day) for six months improved overall pain (69). In this study, 38.5% of the women receiving 1.5 mg/day, 37.9% of those receiving 3 mg/day, and 51.7% of those receiving 6 mg/day reported at least a 50% reduction in self-assessed breast pain compared to 8.3% in the placebo group.

Large-scale, controlled clinical trials are needed to determine the therapeutic value of molecular iodine in fibrocystic breasts. Besides, the doses of iodine used in these studies (1.5 to 6 mg/day for a 60 kg person) are higher than the tolerable upper intake level (UL) recommended by the Food and Nutrition Board of the Institute of Medicine and should only be used under medical supervision (see Safety).

Sources

Food sources

Data from the ongoing US Total Diet Study, which monitors the levels of some contaminants and nutrients in food products, indicates that dietary iodine intakes in adults range between 138 and 268 micrograms (μg)/day. Considerably higher average intakes (304-353 μg/day of iodine) were reported for boys 14 to 16 years of age (70).

Seafood is rich in iodine because marine animals can concentrate the iodine from seawater. Certain types of edible seaweed (e.g., wakame) are also very rich in iodine (71). The iodine content of food that is grown or raised on a particular soil depends on the iodine content of this soil. In the US, dairy products contribute up to 90% of total estimated iodine intakes in infants, at least 70% in children (ages, 2-10 years), 53%-63% in adolescents (ages, 14-16 years), and about 50% in adults (70). In the UK and northern Europe, iodine levels in dairy products tend to be lower in summer when cattle are allowed to graze in pastures with low soil iodine content (9).

Other good sources of dietary iodine include eggs, fruit, grain products, and poultry (70). Processed foods can contribute to iodine intake if iodized salt or food additives, such as calcium iodate and potassium iodate, are added during production. Yet, in the US, virtually no iodized salt is used in the manufacturing of processed food and fast food products, and the food industry is not required to list the iodine content on food packaging (72). Table 3 lists the iodine content of some iodine-rich foods in micrograms (μg). Because the iodine content of foods can vary considerably, these values should be considered approximate (73).

Supplements

Over-the-counter iodine supplements

Potassium iodide is available as a nutritional supplement, typically in combination products, such as multivitamin/mineral supplements. Iodine makes up approximately 77% of the total weight of potassium iodide (56). A multivitamin/mineral supplement that contains 100% of the daily value (DV) for iodine provides 150 μg of iodine. Although most people in the US consume sufficient iodine in their diets (see Sources), an additional 150 μg/day is unlikely to result in excessive iodine intake. The American Thyroid Association (ATA) recommends prenatal supplementation with 150 μg/day of iodine and advises against the ingestion of ≥500 μg/day of iodine from iodine, potassium iodine, and kelp supplements for children and adults, and during pregnancy and lactation (see also Safety) (36, 74).

Iodine fortification programs

The fortification of salt with iodine is a feasible and inexpensive method to eliminate iodine deficiency, and salt iodization programs have been implemented in almost all countries. In North America, salt fortification with iodine is mandated in Canada and some parts of Mexico, but only voluntary in the US such that only 52% of US table salt is iodized and only one-fifth of the total salt consumed in the US is iodized (72, 75). Potassium iodide (KI), cuprous iodide (CuI), and potassium iodate (KIO₃) are used to iodize salt. The US Food and Drug Administration (FDA) recommends between 46 and 76 μg of iodine per gram of salt in iodized salt. However, the recent analysis of 88 US iodized food-grade salt samples revealed that the iodine content was below the recommended range in 52% of the samples and above the range in 7% of the samples (76).

In other countries, salt commonly contains 20-50 μg of iodine per gram of salt, depending on local regulations (76). In countries like Denmark (77), Australia (78, 79), and New Zealand (80), the use of iodized salt in the bread-making process is mandated. Additional approaches have been explored, including sugar fortification (81), egg fortification (82), use of iodized salt in the preparation of fermented fish and fish sauce (83), and use of iodine-rich crop fertilizers (84). In addition, fortification of livestock feeds with iodine and the use of iodophors for sanitation during milking contribute to increasing iodine content in dairy products (85). Finally, annual doses of iodized vegetable oil are administered orally or intramuscularly to individuals in iodine-deficient populations who do not have access to iodized salt (4, 56).

Safety

Acute toxicity

Acute iodine poisoning is rare and usually occurs only with doses of many grams. Symptoms of acute iodine poisoning include burning of the mouth, throat, and stomach, fever, nausea, vomiting, diarrhea, a weak pulse, cyanosis, and coma (1).

Excessive iodine intakes

Risk of iodine-induced hyperthyroidism in iodine-deficient individuals

Iodine supplementation programs in iodine-deficient populations have been associated with an increased incidence of iodine-induced hyperthyroidism (IIH), especially in older people with multi-nodular goiter (86). Iodine intakes of 150-200 μg/day have been found to increase the incidence of IIH in iodine-deficient populations. Iodine deficiency increases the risk of developing autonomous thyroid nodules that are unresponsive to TSH control (see Function). These autonomous nodules may then overproduce thyroid hormones in response to sudden iodine supply. IIH symptoms include weight loss, tachycardia (high pulse rate), muscle weakness, and skin warmth. IIH can be dangerous in individuals with underlying heart disease. Yet, because the primary cause of nodular goiter and IIH is chronic iodine deficiency, the benefit of iodization programs largely outweighs the risk of IIH in iodine-deficient populations (1).

Risk of hypothyroidism in iodine-sufficient individuals

In iodine-sufficient individuals, excess iodine intake is most commonly associated with elevated blood concentrations of thyroid stimulating hormone (TSH) that inhibit thyroid hormone production, leading to hypothyroidism and goiter. A slightly elevated serum TSH concentration without a decrease in serum T₄ or T₃ is the earliest sign of abnormal thyroid function when iodine intake is excessive. In iodine-sufficient adults, elevated serum TSH has been found at chronic iodine intakes of ≥750 μg/day in children and ≥1,700 μg/day in adults. Because various edible seaweed species substantially contribute to traditional Asian meals, average Japanese dietary intakes are estimated to range between 1,000 and 3,000 μg of iodine/day (71). Iodine-induced goiter and hypothyroidism are not uncommon in Japan and can be reversed by restricting seaweed intake (71). Prolonged intakes of more than 18,000 μg/day (18 mg/day) increase the incidence of goiter in adults. In newborns, iodine-induced goiter and hypothyroidism can be due to either high maternal intakes or high exposure to iodized antiseptics (87). In order to minimize the risk of adverse health effects, the Food and Nutrition Board of the US Institute of Medicine set a tolerable upper intake level (UL) for iodine that is likely to be safe in almost all individuals. The UL values for iodine are listed in Table 4 by age group; the UL does not apply to individuals who are being treated with iodine under medical supervision (74).

Individuals with increased sensitivity to excess iodine intake

Individuals with iodine deficiency and those with preexisting thyroid disease, including nodular goiter, autoimmune Hashimoto thyroiditis, Graves disease, and a history of partial thyroidectomy, may be sensitive to iodine intake levels considered safe for the general population and may not be protected by the UL for iodine (9). Infants, the elderly, and pregnant and lactating women may also be more susceptible to excess iodine (see Supplements) (74).

Do elevated and/or insufficient iodine intakes increase the risk of thyroid cancer?

Over the past decades, the incidence of thyroid cancer has increased worldwide. In the US, the incidence of thyroid cancer — representing 4% of all newly diagnosed cancers — has increased from 4.9 cases per persons in 1983 to 14.7 cases per 100,000 persons in 2011, but mortality rate from thyroid cancer has remained low (about 0.5 per 100,000 persons) (88). Accounting for over 80% of all thyroid cancers, thyroid papillary cancer is less aggressive and has a better prognosis than thyroid follicular cancer or anaplastic thyroid cancer. The increasing incidence of thyroid cancer worldwide is likely due at least in part to the improved screening and diagnosis activities. However, because it has coincided with the introduction of iodine fortification programs, a possible contribution of increased iodine intakes has been hypothesized. Yet, in the US, the increasing incidence of thyroid cancers (primarily papillary cancer) over the last few decades was paralleled with a reduction in average iodine intake (89).

Ecologic studies also suggested that iodine prophylaxis in populations that were previously iodine deficient was associated with an increased incidence of the papillary rather than the follicular cancer subtype, and with a reduced incidence of the more aggressive anaplastic thyroid cancer (89). While changes in iodine intakes appear to affect the histological type of thyroid cancer, it is not yet clear whether iodine deficiency and/or iodine excess increase the risk of thyroid cancer (88).

Drug interactions

Amiodarone, a medication used to prevent abnormal heart rhythms, contains high levels of iodine and may affect thyroid function (90). Antithyroid drugs used to treat hyperthyroidism, such as propylthiouracil (PTU), methimazole, and carbimazole, may increase the risk of hypothyroidism. Additionally, the long-term use of lithium to treat mood disorders may increase the risk of hypothyroidism (91). Further, the use of pharmacologic doses of potassium iodide may decrease the anticoagulant effect of warfarin (coumarin) (92).

Contaminants

Perchlorate is an oxidizing agent found in rocket propellants, airbags, fireworks, herbicides, and fertilizer. Mainly as a result of human activity, perchlorate has been found to contaminate drinking water and many foods (57). Chronic exposure to perchlorate concentrations at levels greater than 20 μg per kg body weight (bw) per day interferes with iodine uptake by the thyroid gland and may lead to hypothyroidism (93). The US Environment Protection Agency (EPA) recommends that daily oral exposure to perchlorate should not exceed 0.7 μg/kg bw to protect the most sensitive population, i.e., the fetuses of pregnant women who might be deficient in iodine and/or hypothyroid (94). Among all age groups, children aged two years have the highest estimated perchlorate intakes per day with 0.35-0.39 μg/kg bw/day. Average estimated intakes of perchlorate in US adults range between 0.08 and 0.11 μg/kg bw/day (70).

Linus Pauling Institute Recommendation

The RDA for iodine is sufficient to ensure normal thyroid function. There is presently no evidence that iodine intakes higher than the RDA are beneficial. Most people in the US consume sufficient iodine in their diets, making supplementation unnecessary.

Pregnant and breast-feeding women

Given the importance of sufficient iodine during prenatal development and infancy, pregnant and breast-feeding women should take a supplement that provides 150 μg of iodine per day (see Deficiency).

Older adults (>50 years)

Because aging has not been associated with significant changes in the requirement for iodine, the LPI recommendation for iodine intake is not different for older adults.

Authors and Reviewers

Originally written in 2001 by:
Jane Higdon, Ph.D.
Linus Pauling Institute
Oregon State University

Updated in April 2003 by:
Jane Higdon, Ph.D.
Linus Pauling Institute
Oregon State University

Updated in July 2007 by:
Victoria J. Drake, Ph.D.
Linus Pauling Institute
Oregon State University

Updated in March 2010 by:
Victoria J. Drake, Ph.D.
Linus Pauling Institute
Oregon State University

Updated in August 2015 by:
Barbara Delage, Ph.D.
Linus Pauling Institute
Oregon State University

Reviewed in August 2015 by:
Elizabeth N. Pearce, M.D., M.Sc.
Associate Professor of Medicine
Boston University School of Medicine

Copyright 2001-2018  Linus Pauling Institute 

References