Corresponding Author:
Elizabeth N. Pearce, MD, MSc
Boston University Medical Center
88 East Newton Street
Evans 201
Boston, MA 02118
Tel 617-414-1348
Fax 617-638-7221
elizabeth.pearce@bmc.org

INTRODUCTION
Iodine is critical for the synthesis of thyroid hormone, and deficiency may result in goiter, impaired cognition, developmental abnormalities, and cretinism. Iodine deficiency is the most common cause of preventable mental retardation worldwide and poses an important public health issue in many areas. In this review of iodine nutrition in North America, we will focus on the state of iodine nutrition in the U.S., as there have been no recent assessments of iodine nutrition in Canada and only limited data from Mexico. Dedicated efforts to eliminate iodine deficiency and varying consumption of iodine-containing foods have influenced the status of the North America iodine supply dramatically over the last century.

The status of North American dietary iodine deficiency before the 1920s
Endemic iodine deficiency disorders occur commonly in areas where iodine in the soil is depleted by erosion and other natural processes. In North America, iodine deficiency was prevalent in the Great Lakes, Appalachian, and Northwestern U.S. regions and in most of Canada up until the 1920s. Goiter was present in 26-70% of children living in this “goiter belt”, and mental retardation and hypothyroidism were common (1). In 1917 midwesterner David Marine performed studies in schoolgirls that demonstrated that goiter could be eradicated by iodine supplementation (2). Based primarily on his work, voluntary salt iodization was initiated in the U.S. in 1924, resulting in the elimination of the goiter belt. Salt iodization was also begun in Canada in the 1920s. A survey in 1950 demonstrated that the goiter prevalence across 8 states of Mexico ranged from 5 to 46 percent (3). Mandatory iodized salt was introduced in some regions of Mexico in 1963, but salt iodization programs were not consistently maintained.

What are the recommendations for iodine intake?
The U.S. Institute of Medicine has established Recommended Daily Allowances (RDA) for iodine in U.S. and Canadian infants, children and adolescents, pregnant women, lactating women, and other adults range from 110 – 290 mcg/L. For infants less than one year of age, a recommended iodine daily intake has not been established, and an Adequate Intake (AI) level is instead utilized (Table 1).
In the population subset of women of childbearing age, iodine nutrition is particularly important, given the importance of iodine in the development of the central nervous system. The American Thyroid Association has recently recommended that all U.S. and Canadian women receive 150 µg iodine supplements above their dietary intake during pregnancy and lactation, and that the iodine content in all prenatal vitamins should be standardized at 150 µg (4).

What is the current status of iodine nutrition in North America?
The median urinary iodine concentration in the first U.S. National Health and Nutrition Examination Survey (NHANES I, 1971-1974) was 320 µg/L, which is consistent with adequate to excessive dietary iodine intake (5). However, the median urinary iodine decreased by more than 50 percent to 145 µg/L, by NHANES III (1988-1994). It is reassuring that data from the most recent NHANES survey (2001-2002) found that the median U.S. urinary iodine concentration has stabilized at 168 µg/L (6) (Figure 1A). In Mexico, there have been no surveys examining iodine nutrition across the population. However, several small studies, mostly in schoolchildren, in the last decade have suggested likely iodine sufficiency. The median urinary iodine level in a 2006 study of 100 schoolchildren was adequate at 125 µg/L, with only 6% of these children having median urinary iodine levels < 50 µg/L (7). In contrast to the U.S., where both iodized and non-iodized salt are available, all table salt in Canada is iodized; both the U.S. and Canada fortify table salt with 100 ppm potassium iodide, which corresponds to approximately 77 µg iodine per gram of salt. Although no recent studies in Canada have examined measures of iodine status across the general population, it is considered likely to be an iodine sufficient region (8).

Women of childbearing age

Women of childbearing age (15-44 years) and their infants are especially susceptible to iodine deficiency. This is because thyroid hormone, requiring adequate maternal iodine intake, is critical for neural development in utero. Between NHANES I and III, the most pronounced decline in U.S. median urinary iodine values occurred in women of childbearing age (Figure 1B). The median urinary iodine value in pregnant women (n = 208) from NHANES I was 327 µg/L, with 1% of the women sampled having urinary iodine levels < 50 µg/L. The median urinary iodine level among pregnant women from NHANES III (n = 348) was 141 µg/L, with 6.9% having urinary iodine levels ‹50 µg/L (5). The most recent NHANES survey (2000-2001) demonstrated that urinary iodine values in pregnant women appear to have stabilized since NHANES III. The median urinary iodine value was 173 µg/L for the 126 pregnant women sampled, with 7.3% having urinary iodine levels ‹50 µg/L (6). We assessed spot urine specimens from 100 healthy pregnant Boston-area women in 2004 and found a median urinary iodine of 149 µg/L (range, 13 – 1200 µg/L), but 9% were ‹50 µg/L (9).

Children

Several studies have examined urinary iodine in samples of school-aged U.S. children. NHANES I reported that in children ages 6-11, the median urinary iodine was 421 µg/L, while by the time of NHANES III, this value had decreased to 237 µg/L (5). Since then, urinary iodine values in U.S. children, as for other groups, appear to have stabilized. The median urinary iodine in a 1996 sample of 302 Atlanta children was 282 µg/L (10). In a 2002 sample of 565 Boston-area children, median urinary iodine was 289 µg/L (11). Finally, in the most recent NHANES survey (2001-2002; n = 374) median urinary iodine was 249 µg/L (6). Interestingly, children’s urinary iodine values are consistently higher than those of U.S. adults and boys’ urinary iodine values are consistently higher than those for girls.

Breastfed infants

Infants who are breastfed are reliant on maternal iodine intake for adequate iodine nutrition (12). During lactation, iodine is avidly concentrated in the breast, due to increased expression of the sodium/iodide symporter in lactating mammary tissue (13). However, current data regarding iodine sufficiency among lactating U.S. women are very limited. The median breast milk iodide level in a 1984 sample of 37 U.S. women was 146 µg/L (14). In 2005, Kirk et al reported a substantially lower median breast milk iodide value of 33.5 µg/L in a sample of 23 U.S. women recruited via the internet (15). Finally, we reported a median urinary breast milk iodine concentration of 155 µg/L in a sample of 57 lactating Boston-area women (16). Forty-seven percent of women sampled may have been providing breast milk with insufficient iodine to meet infants’ requirements in this study (16).

What are common sources of iodine in the U.S. diet?
It has been difficult to identify sources of dietary iodine in the U.S. There are a wide range of potential sources, and varying dietary practices likely contribute to wide fluctuations in individual iodine intake. Food iodine levels are further affected by regional variations in topsoil content and irrigation practices. The U.S. Food and Drug Administration does not require iodine content to be listed on food packaging.

Salt
In 1990, the World Health Assembly adopted universal salt iodization as the route to eliminate iodine deficiency disorders. Though iodized salt was responsible for eliminating the goiter belt in the U.S. beginning in the 1920s, it has never been mandated in the U.S. 70% of salt sold for household use in the U.S. is fortified with 100 ppm potassium iodide (i.e. 400 µg iodine is present in one teaspoon of iodized table salt) (17), but household table salt accounts for only about 15% of daily salt intake in the U.S. Among the possible reasons for the decrease in U.S. iodine consumption between the early 1970s and the 1990s are recommendations for reduced salt intake for blood pressure control, and increasing use of non-iodized salt in processed foods (18). Finally, the salt used in manufacturing many processed foods may not be iodized and warrants further investigation. In Canada, all salt is required to be fortified with 77 ppm potassium iodide, while Mexico has mandated fortification of all salt with 20 ppm potassium iodide. Whether this is consistently so in Mexico is unclear.

Milk
Between 1965 and 1980, U.S. milk iodine content increased by 300-500%, primarily because of changes in cattle feeds (19). Then in 1986, the allowable amount of organic iodine ethylenediamine dihydroiodine (EDDI) in cattle feed was limited to 10mg per cow daily, resulting in decreases in the iodine content of U.S. cows’ milk, which accounts for another likely reason for the decrease in U.S. dietary iodine intake between the 1970s and 1990s. In addition, iodophor disinfectant pre- and post-milking teat dips and udder washes, which are widely used in the U.S., contain up to 1% available iodine, and are absorbed through the skin and subsequently incorporated into cows’ milk (20, 21) and may also directly contaminate milk during the milking process. The iodine content of 18 varieties of cows’ milk from Boston-area supermarkets was recently measured (22). The average iodine content of milk in this sample was 110 µg per cup (464 µg/L), with iodine content being slightly higher in the winter than in the summer. Another recent study examined 39 samples of cow’s milk from around the U.S. and found that the average iodide content was 89.2 µg/L (15).

Commercially-baked breads
Commercially-baked breads have been another major source of iodine in the U.S. diet. Iodate bread conditioners, added to bread to maintain freshness, were widely used starting in the 1940s. London et al reported in 1965 that bread was a source of large quantities of dietary iodine with iodine content as high as 150 µg per slice (23). This was considered to be a cause of decreasing radioactive iodine uptakes in the U.S. during the 1960s (24, 25). The use of iodate bread conditioners has decreased in recent decades, another probable contributing factor to the reduction in U.S. dietary iodine levels between the 1970s and the early 1990s. In 2002 we measured iodine content of 18 different breads from Boston-area supermarkets (). Three varieties of bread contained >300 µg iodine per slice (313.5 to 587.4 µg), while the average iodine content in the other 17 brands was 10 µg iodine/slice. We found that the labeling of bread packages did not accurately predict the content of iodine.

Infant formula
We recently measured the iodine content of 17 varieties of infant formula sold in the Boston area, which ranged from 84-224 µg/L, similar to concentrations found in breast milk (16).

Other sources
Other important sources of dietary iodine in North America include eggs, meat, and poultry. The iodine in eggs is found primarily in the yolk, and a large egg contains about 29 µg of iodine (26). The amount of iodine in meat and poultry is highly variable, depending largely on the amount of iodine supplementation of animals’ feed. Seafood can also be a large source of dietary iodine and may contain 2 –10 times as much iodine as meats (27). However, iodine content varies widely depending on the type of seafood and location (28). In general, saltwater seafood contains more iodine than freshwater seafood. Edible seaweeds may contain up to 2500 µg iodine per gram (29), but are not a major component of the North American diet. Erythrosine dye (FDC Red #3) is sometimes described as a major contributor to U.S. dietary iodine intake, but this is untrue. First, this colorant is no longer widely used in U.S. foods. Second, the iodine contained in erythrosine is not readily bioavailable, as only about 1% of iodine in ingested erythrosine is actually absorbed (30).

Multivitamins
Multivitamins, in both adult and infant formulations, may be an important source of iodine in the U.S. Only 51% of the adult multivitamin formulations on the U.S. market contain iodine (generally 150 µg iodine daily) (31). 45% of the types of U.S. children’s multivitamin formulations contain iodine, and importantly, none of the infant liquid multivitamin formulations marketed in the U.S. contain iodine (31). Based on concerns about adequate iodine intake in the perinatal period, the National Academy of Sciences recently recommended that consideration be given to adding iodine to all prenatal vitamins (32). However, only 44 of 69 (64%) prenatal multivitamins marketed in the U.S. currently contain any iodine; of those, only 15% contain more than 150 µg, and most contain less than the 220 µg daily recommended for pregnancy or the 290 µg daily recommended during lactation (31).

Medications
Although they do not contribute to North American dietary sufficiency overall, in some individuals, medications can be an important source of ingested daily iodine (Table 2). Amiodarone is an antiarrythmic agent frequently used in the U.S. (33), Canada, and Mexico, and contains 75 mg iodine per 200mg tablet. Iodinated intravenous radiographic contrast agents contain up to 380 mg of iodine per mL. Some topical antiseptic contain iodine, but systemic absorption of these agents is generally not clinically significant except in patients with severe burns (34), those treated with betadine irrigation for severe wound infections (35), and in preterm infants (36). Use of iodine-containing vaginal douches has declined over the last 15 years, but remains a common practice among some groups of U.S. women (37); frequent use has been shown to increase serum and urine iodine concentrations (38). In the past, there were several iodine-containing anti-asthmatic medications and expectorants on the U.S. market, however these are no longer available. Finally, some dietary supplements may contain large amounts of iodine; these are not regulated by the U.S. Food and Drug Administration and the prevalence of such supplement use is unknown.

What are the assessments used to ensure iodine adequacy in North America?
The U.S. Total Diet Study in the 1980s was a market basket study that assessed iodine consumption in a wide variety of common foods. The estimated individual daily iodine intake was 150 – 550 µg/day. The NHANES studies have measured trends by urinary iodine concentrations across the U.S. population since the early 1970s. Larger and systematic studies examining iodine nutrition in different population subgroups, and the assessment of the iodine content in different foods and other sources, are warranted to ensure iodine sufficiency in the future. There have been no recent systematic assessments of the status of iodine nutrition in Canada or Mexico.

CONCLUSIONS
Iodine deficiency was prevalent in the Great Lakes, Appalachian, and Northwestern U.S. regions and in most of Canada until the 1920s, when efforts to eliminate endemic goiter with the use of iodized salt were introduced. However, the most significant routes of iodine exposure are difficult to determine, and further studies are needed to assess the role of other foods and other sources with large iodine loads. Although assessments of U.S. iodine nutritional status in the last 40 years have shown a decreasing trend of urinary iodine values, the U.S. population remains generally iodine sufficient. Despite this, achieving stable adequate iodine levels in pregnant women and those of childbearing age may remain an area worthy of public health concern. We feel there needs to be increased awareness of the importance of adequate iodine nutrition especially in this particularly susceptible population, and that iodine-containing multivitamins should be recommended for pregnant and non-pregnant women of childbearing age. There have been no recent systematic assessments of iodine intake in Canada and Mexico, though these countries are likely iodine sufficient. Studies are needed to determine the status of iodine nutrition in these areas and in population subgroups across the U.S.