Too Much Versus Too Little: The Implications of Current Iodine Intake in the United States

Special Article June 1999: 177-181

Too Much Versus Too Little: The Implications of Current Iodine Intake in the United States Kelly Lee, M.S., R.D., Robert Bradley, M.S., R.D., Johanna Dwyer, D.Sc., R.D., and Stephanie L. Lee, M.D., Ph.D.

lodine intake influences the health of Americans todaH but in different ways than it has in the past. In the early 7900s, iodine deficiency was responsible for widespread endemic goiter in the United States. The incidence of goiter was markedly reduced by the introduction of iodine supplementation of salt and other foods in the 7920s. By the middle of this century iodine-related problems in the Unites States were more likely to be aasoci- ated with too much rather than too little of this essential nutrient. Recent and disturbing new data suggest that there has been a sharp decline in iodine intake during the last 20 years, especially in women of reproductive age. A brief compari- son of thyroid response to insufficient and excessive intakes in normal and diseased thyroid tissue is presented. The population affected and the implications for therapy are also reviewed.

Introduction

At the turn of this century iodine deficiency disorders (IDD) were epidemic in many parts of the United States, with consequent morbidities that included endemic goiter.' Iodine deficiency occurs in regions where the topsoil has been depleted of iodine by erosion caused by glacier movement, rain, wind, and flooding. The most profound iodine deficiency and goiter occurred in several regions of the United States including the length of the Appala- chian range, the states bordering the Great Lakes, and

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Ms. Lee and Mr. Bradley are with the Frances Stern Nutrition Center, New England Medical Center, and Tufts University School of Nutrition Science and Policy; Dr. Dwyer is Director of the Frances Stern Nutrition Center, New England Medical Center, and Professor of Medicine and Community Health, Tufts University School of Medicine and School of Nutrition Science and Policy; Dr. Lee is Assistant Professor of Medicine, Tufts University School of Medicine, and Director of the Thyroid Disease Center, Division of Endocrinology, New England Medical Center, Boston, MA 021 11, USA. Reprint requests should be directed to Dr. Stephanie Lee.

westward to the Northwest and Rocky Mountain regions of the United States.

In the 1920s David Marine conducted initial studies of iodine supplementation in adolescent girls and demonstrated that sodium iodide supplementation reduced thyroid enlargement from 21% to 0.2%.2 Salt iodination has never been mandatory in the United States because salt manufacturers readily iodized their products to achieve marketing advantages over their competitors who did not add iodine. By the mid-1 900s preventive efforts had been so successful that IDD was no longer considered a public health problem in America. For the last 50 years the average American iodine intake3 exceeded the Recommended Dietary Alloyance (RDA)4 and the recommended level based on a consensus statement by UNICEF, the Interna- tional Council for the Control of Iodine Deficiency Disor- ders (ICCIDD), and the World Health Organization (WHO).' The importance of iodine in the prevention of goiter has nearly disappeared from the collective American con- sciousness owing to the widely held but erroneous belief that iodine deficiency has been permanently eliminated.

Iodine intake still influences the health ofAmericans today but in different ways than in past years. Today, iodine-related problems occur in subsets ofthe U.S. population that have either excessive or deficient intake of this essential nutrient.6 For most individuals the level of iodine in the American diet today is appropriate for good health, but small but significant groups of persons with disparate pathologies of the thyroid gland suffer adverse health effects from current iodine intake. Depending on underlying thyroid pathology, excessive iodine may cause hypothyroidism, goiter formation, or hyperthyroidism in these persons. Also, excessive iodine in the diet may im- pede the diagnosis and treatment of individuals with dis- eases of the thyroid who are about to undergo radioactive iodine administration. Iodine deficiency, especially in women, will cause an increase in goiter formation, with additional special concerns during pregnancy.

This article provides a review of the biologic effects of the spectrum of iodine intakes, which range from toxic- ity to deficiency, and their public health implications today.

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Current Intakes more than 20% of the population should have a urinary

Virtually all iodine intake occurs via dietary ingestion. The effects of low iodine intakes and the prevalence of IDD have not been considered a major public health issue in this country for the last 50 years because of a well-estab- lished voluntary program of fortification of table salt with iodine. Iodized salt in the United States contains one part iodine to 10,000 parts salt (sodium chloride) by weight. Therefore, 1 g iodized salt contains approximately 100 pg iodine. Also, there is a relatively high level of iodine in the American food supply from other sources: Iodine products are commonly used as ingredients in or in the processing of bread and dairy products, and the diets of cattle and chickens are often supplemented with kelp, resulting in significant but variable amounts of iodine in meats, milk, and eggs. As a result, iodine intake in the United States in the recent past has been higher than both mini- mal average requirements and the RDA l e ~ e l . ~ . ~ - ~

Previously published data regarding iodine consumption in the United States is from the Food and Drug Ad- ministration Total Diet Study 1991. The estimated daily intake of iodine from food is between 150 and 550 &day, with many people getting more than the dietary allowances of 150 pglday for adolescents and adults and 200 &day for pregnant or lactating w0men~9~ recommended by the Food and Nutrition Board ofthe U.S. National Re- search Council. The Total Diet Study underestimates iodine intake because it does not include the contributions of iodine from iodized salt, drinking water, prepared or “fast” foods, and medications. Some but not all daily mul- tiple vitamins contain 150 pg iodine per tablet. Kelp or seaweed supplements available at natural food or nutrition stores may contain many thousands of micrograms of iodine per tablet. It is impossible to analyze every food on the market, and there is considerable variation in iodine content by region and by processing technique. Therefore, it is possible that significant sources of iodine have yet to be identified and that intakes may be higher than current estimates. Iodine intake levels of this magni- tude are not a problem for the general population. How- ever, high intake levels in those with previous iodine deficiency, diffuse or nodular nontoxic goiter, thyroiditis and hyperthyroidism, and in those who require radioactive iodine (I131) treatment for thyroid cancer or thyrotoxicosis are at risk for complications.

Trends in dietary habits and food selection were not taken into account in the Total Diet Study. Iodine excretion data from the first National Health and Nutrition Ex- amination Survey (NHANES I)’ collected across the country fiom 197 1 to 1974 confirmed the Total Diet Study data showing that the average urinary iodine concentration was relatively high at 293.3 pgfg creatinine. The median urinary iodine concentration of an iodine-sufficient population should be greater than 100 pglg creatinine, and no

iodine concentration below 50 pgfg creatinine. Significant iodine deficiency occurs with urinary iodine excretion of less than 50 pgfg creatinine. At the end of 1998, data from NHANES I11 (1 988-1 994) demonstrated a surprising and significant reduction in the average American dietary iodine intake to 124.6 pg/g ~reatinine.~ Although this average intake is considered sufficient, the size of the population with iodine deficiency (urinary iodine concentration less than 50 pg/g creatinine) rose 1 0-fold from NHANES I to 8.1 % of men and 15.1 % of women. At high risk are Caucasian females between ages 40 and 49 years, who had the highest incidence of iodine deficiency (25.5%). In fact, approximately 19-23% of women between ages 30 and 60 years were iodine deficient. Thus, iodine deficiency is again becoming significant, especially in women in the United States. This observed reduction in iodine intake must be monitored carefully and confirmed with additional independent studies because iodine deficiency is associated with goiter formation, with increased risk of miscar- riages, and possibly with reduced intelligence in offspring of iodine-deficient mother^.^,^^^^

The recent reduction in dietary iodine may be owing to several factors, including the dairy industry’s effort to reduce iodine in milk, the replacement of iodine with bro- mine salts as the dough conditioner in commercial bread production, reduced intake of eggs (especially the iodine- rich yolks) for cholesterol concerns, reduced use of table salt for hypertension concerns, and the use of salt not supplemented with iodine in manufactured foods. Another factor that must be taken into account is the low public awareness of the importance of using iodized salt to main- tain an adequate iodine intake for good thyroid health.

Iodine Metabolism

The only known function of iodine in the human body is as an essential component of the thyroid hormones thy- roxine (T,) and triiodothyronine (T3). T, contains four at- ums (59% by weight) and T, contains three atoms (65% by weight) of iodine per molecule. Severe iodine deficiency results in reduced thyroid hormone levels and hypothyroidism. The biologic functions of the thyroid hormones include binding to nuclear receptors to influence gene expression in target tissues resulting in biologic effects on neuronal development, adrenergic receptor sensitiv- ity, oxygen consumption, resting metabolic rate, heat production, and fatty acid release from adipose tissue.

Iodine is absorbed completely and rapidly from the gut in the form of iodide, which is the most common form of dietary iodine. Once iodine is in the blood stream, it is transported both as free and protein-bound iodine and is distributed throughout the body’s extracellular compart- ments. A sodium-iodate symporter concentrates the iodine in a saturable and energy-dependent process into

178 Nutrition Reviews@, Vol. 57, NO. 6

High iodine intake

Normal thyroid Pathology: Thyroiditis

Graves’ thyrotoxicosis Hashimoto’s hypothyrodism

Wolff-Chaikoff Shut down

.1 Escape and return

to normal

.1 Wolff-Chaikoff

Shut down

-1 No escape and hypothyroidism

Pathology: Thyroid autonomy

Toxic adenoma Toxic and non-toxic multinodular goiter

-1 lodineinduced

Hyperthyroidism (Jod-Basedow thyrotoxicosis)

Figure 1. Thyroid pathology and effect of high-iodine intake on thyroid function. Figure generated from information from references 6 and 12.

the thyroid hormone producing follicle cells of thethyroid gland. Thyroid stores account for approximately 8000 pg of body iodine stores. Other extracellular iodine in the body is present mainly in the salivary, gastric, and mam- mary glands, adding 250 pg to body stores.lO.”

The body recycles iodine when intake is low by deiodinating thyroid hormones in the liver and releasing the iodine into the circulation for reuptake by the thyroid.” Iodine excretion occurs mainly through the kidneys, which lack any significant means of iodine conservation or resorption. Thus, urinary loss is a reliable measurement of blood level of iodine and the status of iodine intake. When the mean urinary iodine level of a population is less than 50 pg/g creatinine, endemic thyroid enlargement or goiter is likely to o c c ~ r . ~ - ~ I

Iodine Excess

The effects of high iodine intake on thyroid function are variable and depend chiefly on the health of the thyroid gland. The three possible responses to high iodine intake are illustrated in Figure 1. In the normal, healthy thyroid, high levels of iodine intake have little lasting effect even when loads are large (1 000-2000 pdday). Under such cir- cumstances the normal thyroid temporarily ceases production of thyroid hormone. This shut-down of hormone production is called the Wolff-Chaikoff effect. The normal thyroid ceases thyroid hormone synthesis until the thyroid tissue can adapt to the high intercellular level of iodine, then the production of thyroid hormone resumes to normal in the face of the new, higher level of iodine intake.6,12 Thyroid functions remain normal in this population. This process is known as “escape from the Wolff- Chaikoff effect.”

In patients with thyroiditis, most typically caused by

Graves’ or Hashimoto’s disease, the diseased thyroid stops producing thyroid hormone when exposed to elevated intakes for a variable length of time and hypothyroidism may occur. Excessive iodine intake has also been associated with the increased incidence of autoimmune thyroiditis or Hashimoto’s thyroiditis, the primary cause of adult hypothyroidism.

The opposite response, iodine-induced hyperthyroidism, or Jod-Basedow Thyrotoxicosis, occurs in patients with thyroid nodules that are “autonomous” or “overactive.” Autonomous nodules produce thyroid hormone in direct correlation with iodine intake without regard to thyroid hormone levels. These nodules produce excess thyroid hormone because they lack feedback controls and do not shut down like normal thyroid tissue does in the face of high iodine intakes. Single toxic nodules or adenomas are monoclonal expansion of an overactive thyroid follicle cell. Many of these autonomous nodules contain muta- tions of the thyroid-stimulating hormone (TSH) receptor that cause the cells to produce excessive levels of thyroid hormones. Polyclonal thyroid nodules or a multinodular goiter can be caused by prior iodine deficiency, but in some cases they may be hereditary, endemic, or idio- pathic.13 Autonomous nodules normally develop over de- cades in a multinodular goiter, and iodine-induced thyrotoxicosis therefore often occurs in older individuals who have a long-standing goiter. Thyrotoxicosis may occur among populations who move from iodine-deficient areas to areas of high iodine intake. When autonomous nodules are present, the more iodine that is available the greater the amount of thyroid hormone is produced. When previously iodine-deficient populations are supplemented with iodine or move to iodine-sufficient areas, some individuals develop thyrotoxicosis because they have developed


autonomous thyroid nodules.l”16 This condition, a toxic multinodular goiter, is a common diagnosis in the United States among immigrants from iodine-deficient areas in Asia, for example. By interfering with the synthesis of thyroid hormone, antithyroid thionamide drugs such as propylthiouracil and methimazole are used to treat thyrotoxicosis caused by conditions such as Graves’ disease and toxic multinodular g0iter.I’

Iodine Deficiency

There are three levels of iodine deficiency based on urinary iodine levels: mild (50-100 pg/g creatinine), moderate (20-49 pg/g creatinine), and severe (< 20 pg/g creatinine). The average urinary excretion of creatinine is approximately 1 g/day in adults but depends on the renal function and muscle mass of the person. In areas with severe deficiency, side effects in addition to goiter formation are observed, including hypothyroidism, endemic mental retardation, cretinism, and decreased fertility. Io- dine deficiency is the most common preventable cause of mental retardation in the world.

When iodine intake is even just mildly deficient, the first sign is thyroid enlargement or goiter formation. The body is not able to produce adequate levels of T,. In response, TSH is released from the pituitary gland and the thyroid gland produces increased numbers of thyroid follicle cells and it enlarges.I0The enlarged gland is able to trap available iodine more efficiently and thus can produce more thyroid hormone. Mild to moderate iodine deficiency results in endemic goiter without hypothyroidism. The thyroid hormone levels remain in the normal range but at the expense of developing an enlarged thyroid gland or goiter.

Although there are many causes of goiter, adaptation to chronic low iodine intakes is one common cause of formation in large populations. Over time the goitrous thyroid develops autonomous nodules, which increase the risk of hyperthyroidism from a high iodine intake. When several autonomous nodules form in a goiter, the patient may become thyrotoxic from a “toxic multinodular goiter” even with a normal iodine intake. These patients may ex- perience a marked worsening of thyrotoxicosis if exposed to large amounts of iodine.

Goitrogens may worsen the effects of iodine deficiency. Cassava meal, a dietary staple in many areas of the world, contains linamarin which is metabolized to thiocy- anate that can interfere with iodine trapping and thyroid hormone production. Goitrogens are also found in millet, kelp, maize, bamboo shoots, sweet potatoes, lima beans, and vegetables of the genus Brassica, including cabbages, turnips, kale, rutabaga, and mustard. Selenium deficiency worsens iodine deficiency because of the decrease in the activity of enzymes required for thyroid hormone synthesis.

4

Also, dietary iodine may influence the type and incidence of thyroid carcinoma. It has been observed that aggressive follicular thyroid cancer is common in areas of iodine deficiency, whereas the more indolent papillary thyroid cancer is more common in areas of iodine sufficiency. The causal relationship is supported by the observation that in regions of iodine deficiency that have been supplemented with iodine, the incidence of follicular thyroid carcinoma falls concomitant with a rise in papillary thyroid carcinoma.

Implications for Therapy

The public health implications of iodine intake in the United States have moved from the historical problem of endemic iodine deficiency to concerns about the health effects of high levels of iodine in some individuals, with specific risks of either increased or insufficient intake on different thyroid pathologies. As the new millennium arrives there are new public health concerns about a trend of iodine deficiency in certain subsets of the U.S. population. Of particular concern is iodine deficiency in young women of reproductive age, which could lead to goiter formation and potentially reduced mental intellect of children born to mothers with severe iodine deficiency. It is predicted that mild iodine deficiency contributes to thyroid enlargement and goite? formation. During the last decade, it has been recognized that thyroid nodules occur in 50% of the elderly, which may reflect goiter formation from insufficient iodine intake. It is important for health care profes- sionals to consider iodine deficiency as a cause of nodular goiter in the United States and to watch for an increas- ing incidence, especially in women. It is very important that the public understand that the use of iodized salt is necessary for normal thyroid function.

More than 14,000 patients are diagnosed with thyroid cancer each year.I8 In addition, approximately 1% of the U.S. population-2.7 million people4evelop thyrotoxicosis during their lifetime. Patients with this diagnosis are often treated with radioactive iodine. The main concern for them is that the uptake of radioactive iodine will be decreased when dietary iodine intake is high.I9”O There is good reason to believe that this is so. In the United States, uptake of II3’ by the thyroid has progressively decreased during the last 50 years. By the late 1960s the normal 24- hour thyroid uptakes had already decreased from approximately 20-30% to between 5 and 10% of the administered dose of radioactive iodine.2I To increase the uptake of for radioiodine therapy it is customary to prescribe a low- iodine diet to patients to increase iodine uptake by the thyroid tissue, thereby creating a temporary dietary deficiency state.

A major challenge for clinicians is to make sure that medical nutrition therapy prior to radioactive iodine therapy maximizes II3I uptake by the diseased thyroid tissue. Be-

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cause iodine intake in the United States is very high in some patients, 5- to 14-day low-iodine diets are prescribed for patients prior to radioactive iodine therapy. The goal is to create a temporary dietary deficiency of iodine so the thyroid tissue will avidly take up the administered radioactive iodine and will receive a maximally effective radia- tion dose.

Conclusion

Food processing practices and the use of iodized salt since the 1920s have created a food supply in the United States that can be high in iodine. Health care providers must be aware of the interaction of high-iodine intakes with sus- ceptible individuals with thyroid dysfunction. Iodine intake, although sufficient on average, has decreased dra- matically during the last 20 years, as illustrated by recent NHANES I11 data. Although the reduction in iodine intake in subsets of the population is moderate, there is no concern for severe deficiency associated with cretinism and growth and mental retardation. It therefore appears that, similar to the start of the 20th century, the UnitedStates at the start of the 2 1 st century is again faced with iodine deficiency, at least in certain subsets of the population. It is unclear whether the trend toward use of prepared foods that do not contained iodized salt or avoidance of added iodized salt at the table is responsible, but until it is deter- mined what dietary pattern or patterns have contributed to this change clinicians must be aware of the effects of too little and too much iodine on thyroid physiology. The United States has a unique set of public health concerns regarding both iodine deficiency, especially in women, which may result in goiter formation, and the effects of too much iodine on certain individuals who are at risk because of pre-existing thyroid pathology.

Acknowledgments. This research was funded in part by contract number 53/3-K06-5-10 ofthe U.S. Department of Agriculture and by the Gerber Foundation, which provided partial salary support to Dr. Dwyer for preparation of this manuscript. Support was also provided through the General Clinical Research Center, funded by the Divi- sion of Research Resources of the NIH under grant number MO 1 -RR00054.

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Too Much Versus Too Little: The Implications of Current Iodine Intake in the United States