Iodine Nutrition and the Impact of Dietary Sodium Reduction

Release Date: September 1, 2011

Expiration Date: September 30, 2013

FACULTY:

Andrea F. Fus, PharmD
ORISE Fellow*
United States Food and Drug Administration
College Park, Maryland

*At the time this article was written.

FACULTY DISCLOSURE STATEMENTS:

Dr. Andrea F. Fus has no actual or potential conflicts of interest in relation to this activity.

Postgraduate Healthcare Education, LLC does not view the existence of relationships as an implication of bias or that the value of the material is decreased. The content of the activity was planned to be balanced, objective, and scientifically rigorous. Occasionally, authors may express opinions that represent their own viewpoint. Conclusions drawn by participants should be derived from objective analysis of scientific data.

ACCREDITATION STATEMENT:

Pharmacy
acpePostgraduate Healthcare Education, LLC is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.
UAN: 0430-0000-11-025-H01-P
Credits: 2.0 hours (0.20 ceu)
Type of Activity: Knowledge

TARGET AUDIENCE:

This accredited activity is targeted to pharmacists. Estimated time to complete this activity is 120 minutes.

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DISCLAIMER:

Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patients' conditions and possible contraindications or dangers in use, review of any applicable manufacturer's product information, and comparison with recommendations of other authorities.

GOAL:

To educate community pharmacists about healthy iodine nutritional status and risk factors for deficiency.

OBJECTIVES:

After completing this activity, the participant should be able to:

  1. Describe the role of dietary iodine.
  2. Specify risk factors for iodine deficiency disorders.
  3. Discuss the status of iodine sufficiency in the U.S., sources of dietary and nondietary iodine, and whether dietary sodium reduction will affect iodine intake in Americans.
  4. Explain the pharmacist's role in educating the public about preventing iodine deficiency.

Iodine is an essential element for normal mammalian development and function. Although iodine deficiency disorders (IDDs) are less prevalent in the United States, they are a common problem in many countries. Iodine deficiency is a leading cause of preventable childhood brain damage and a serious public health problem. Because salt (sodium chloride) is consumed in most diets and is relatively inexpensive to fortify with iodine, universal salt iodization (USI) programs are embraced by most countries. Efforts to prevent iodine deficiency through USI are being made concurrently with campaigns to reduce added sodium in our food, as excessive sodium intake is associated with a risk of cardiovascular and other morbidities. While reducing the salt added to foods is not expected to impact global efforts toward iodine fortification of populations, it may be necessary to educate pregnant women and parents of young children to ensure adequate iodine consumption through improved food choices (including selection of iodized salt for home food preparation) or supplements. Pharmacists answer many questions about iodine consumption and the iodine content of medicines, supplements, foods, and other sources, and they can recommend steps for maintaining a healthy iodine level.

Extensive research about negative cardiovascular and other health effects of excessive dietary sodium intake has prompted recommendations by the Institute of Medicine of the National Academies to broadly reduce sodium content in the U.S. food supply.1 Sodium chloride, or common salt, is the primary source of sodium in the U.S. diet. Daily, the average American consumes more than 3,400 mg of sodium, which equals about 8.5 g (1.5 tsp) of salt.2 The 2010 U.S. Dietary Guidelines for Americans developed by the Department of Agriculture and the Department of Health and Human Services recommend a maximum daily intake of 2,300 mg of sodium (5.8 g of salt) and further advise that specific subpopulations amounting to about half of the U.S. population should reduce daily intake to 1,500 mg.

Concerns have been raised that the general reduction of sodium, primarily through foods with added salt, could have unintended effects. The most sustainable long-term strategy to control iodine deficiency and resultant disorders is to fortify food. Iodized salt is preferred because of its ubiquitous nature and low cost. Issues that impact healthy nutritional iodine status, including dietary sodium reduction, are discussed below.

An Essential Element

The element iodine exists naturally as a gas, and the solid form can sublime without melting.3 Iodine is widely and irregularly distributed in the environment, mainly in ocean water and generally as iodide. Environmental iodine fluctuates by means of atmospheric-terrestrial-aquatic interactions.4 Iodine cycling occurs when oxidation of seawater iodide salts releases iodine into the atmosphere, after which precipitation returns the element to earth surfaces. Iodine and other substances in soil and groundwater are subsequently incorporated into food and water. Depletion of iodine in the earth’s soil occurs through glacier melts, floods, erosion, and other influences.

The term iodine is used to refer to the element itself, as well as to its salts. Iodine is present in foods as inorganic iodine, iodide, or iodate. Iodide is well absorbed in the stomach and small intestine, whereas iodate is reduced in the gastrointestinal tract and absorbed as iodide. Absorbed iodine is concentrated in vertebrates’ thyroid gland and is used to synthesize the thyroid hormones thyroxine and triiodothyronine.5 These hormones regulate metabolic and enzymatic processes, affecting the development and function of the brain, muscle tissues, pituitary gland, kidney, and nearly all other cells. Excess iodine is excreted in the urine.

In addition to its nutrient functions, iodine is an antimicrobial agent in certain surface disinfectants for human and animal use. Iodine salts can be protective, as in the case of perchlorate exposure or as demonstrated after the Chernobyl nuclear reactor radiation emergency in 1986.6 While iodized table salt is not indicated for radiation protection, it became a scarce commodity in Japan when the recent earthquake and tsunami caused panic about a potential nuclear crisis at the Fukushima Daiichi plant.7

The body cannot synthesize iodine, so this trace element must be obtained through the diet. Populations living in areas with poor access to marine-derived foods, whose drinking water has a low iodine content, or whose diet primarily contains foods grown in iodine-deficient soils are at risk for developing iodine deficiency. This was evidenced by a relatively high prevalence of goiter (an often noticeably enlarged thyroid) in the inland intermountain, Midwestern, and Great Lakes areas of the U.S. in the early 1900s, leading to the region being termed the “goiter belt.”8,9

The association between goiter and environmental iodine deficiency has since been questioned.10 The effects of iodine deficiency on the development of goiter and thyroid function vary between individuals and population groups and are influenced by dietary, environmental, and genetic factors.8

Regardless of its precise origin, goiter associated with iodine deficiency is common globally and often can be corrected if treated in time.8,9 Conversely, cretinism—a severe irreversible condition of diminished physical and mental growth following maternal and fetal iodine deficiency—is uncommon in the U.S. and other developed countries. Goiter and cretinism, along with hypothyroidism, test scores indicating low cognitive ability, and other developmental and growth disorders, are termed IDDs. Americans are among the highest users of iodized salt and constitute the group with least insufficient iodine intake.9 However, data from 1994 to 2006 suggest that almost 2 billion people, or about one-third of the world population, are iodine deficient, including 98 million individuals in the Americas.9 While severe iodine deficiency is uncommon in the U.S., there is concern for some subgroups of reproductive-age women who do not consume dairy products.11 Iodine deficiency is the main cause of preventable childhood brain damage and a major public health problem throughout the world, including areas or groups in developed countries.

The World Health Organization (WHO) recommends USI to prevent and treat IDD. The WHO advocates individualized regional programs based on factors such as population urinary iodine status, goiter prevalence, and mean dietary salt intake.8 Excessive iodine can lead to abnormal thyroid and metabolic activity and is associated with hypothyroidism and autoimmune thyroiditis.12 Hypothyroid and other individuals can be hypersensitive to the actions of an extraphysiological supply of iodine.13 Coexisting deficiencies of selenium, iron, and vitamin A can exacerbate the effects of iodine deficiency.14,15

Intervention

After research demonstrated a benefit from iodine supplementation, Switzerland and the U.S. were the first countries to establish population iodine supplementation through salt fortification.16 The Akron Experiment was an important study in the early 20th century that evaluated the effects of iodine supplementation in more than 4,000 girls in grades 5 and above.17 Girls with parental consent to participate received water with sodium iodide on 10 consecutive schooldays every 6 months for 2.5 years. Girls whose parents did not consent served as controls. In girls with enlarged thyroid at baseline, 60.3% of those receiving iodine had a smaller thyroid, compared with 13.8% of controls. For girls with normal thyroid size at baseline, enlargement occurred in 0.2% of those treated with iodine versus 27.6% of controls.

Based on these results, iodized salt was first sold commercially in grocery stores in 1924, and all salt used for food, manufactured, or brought into Michigan State contained iodine.17,18 Iodized salt was quickly adopted, and large distributors sold the new product nationally. Originally, potassium iodide was added to U.S. table salt in an amount based on an average dietary sodium intake of 6.5 g per day.16 (Interestingly, this average was determined by a Michigan physician, David Murray Cowie, upon observing his family’s intake.) The intent was to provide a conservative excess of dietary iodine compared with the then-required range.

In the 1920s, most food consumed by Americans was homemade, and means of distributing certain foods rich in iodine, such as ocean foods, were limited. Salts were used to cure or dehydrate foods to prevent spoilage. Also at that time, it was realized that sodium nitrite (saltpeter) not only preserved food and the red color of meat, but inhibited Clostridium botulinum.19 Consistent with Dr. Cowie’s observations, dietary sodium—although at higher levels than those recommended now—was mostly consumed in foods prepared at home or added at the table. The contribution of dietary iodine intake from iodized salt has varied over time, and it has trended downward as packaged foods, which typically do not contain iodized salt, have increasingly replaced many meals and snacks formerly prepared at home. Indeed, only about 5% of average U.S. dietary sodium intake is added by the consumer as table salt, and the Salt Institute, a nongovernmental organization, estimates that only about 70% of households use iodized salt.20,21 On average, based on a dietary sodium intake of 3,400 mg, iodized salt probably accounts for only 3.5% of the daily sodium intake of most Americans.

USI was embraced by the World Health Assembly almost two decades ago.22 Iodization of salt for both human and livestock consumption was based on assumptions about average dietary salt intake and potential iodine losses before product consumption. Worldwide iodine-fortification programs are tailored to address the extent of regional iodine deficiency, estimated iodine losses, and factors such as deficiency of other dietary microelements or consumption of goitrogenic foods.22,23

A panel of experts representing the International Council for the Control of Iodine Deficiency Disorders, the U.S. Agency for International Development, Health Canada, the Pan American Health Organization, the FDA, and the International Life Sciences Institute affirmed the compatibility of the global campaign to iodize salt with concomitant efforts in many countries to lower sodium intake to moderate levels.24

Regulation

The use and availability of iodized salt in the U.S. are voluntary, and the use of iodized salt has practically eliminated goiter. Chemical forms of an iodide or iodate of potassium, copper, calcium, or sodium are used when iodine is added to foods.25 Potassium iodide is not stable, and moisture, light, heat, and other environmental conditions reduce the available iodine content.4,26

Potassium iodide and cuprous iodide are considered Generally Recognized as Safe (GRAS) for iodine fortification of salt in the U.S., whereas potassium and calcium iodate are listed as food additives for technical effects in dough.25 Manufacturers add potassium iodide to table salt by spraying it onto the salt as it passes on a conveyor belt or by mixing the dry powder with salt crystals at concentrations from 0.006% to the regulatory limit of 0.01%, which is equivalent to 0.0046% to 0.0077% (77 mcg/1 g, or just under one-fourth tsp of iodized table salt) iodine.27,28 Additionally, food-grade salt usually is not pure sodium chloride. Salt is a hygroscopic crystalline product, and humid storage conditions can cause the crystals to clump. Voluntary standards allow up to 2% (total) of suitable food-grade anticaking or conditioning agents such as calcium silicate, sodium thiosulfate, dextrose, sodium bicarbonate, sodium carbonate, or sodium thiosulfate to be added—singly or in combination—to improve product flow, increase alkalinity, stabilize the potassium iodide, and reduce oxidation and volatilization of iodine from the product.29 Potassium iodate, which is more stable, is one of 10 sources of iodine listed for use in U.S. animal feed, but it is not explicitly identified as GRAS for general human food use.29 U.S. food manufacturers are not required to list iodine content on food labels unless the food has been fortified. The amount of iodine in infant formula must be stated and must be between 5 mcg and 75 mcg per 100 kcal of formula as prepared for consumption.

Iodine fortification of foods is mandatory in many countries. Australia and New Zealand have required manufacturers to use iodized salt in bread manufacturing since 2009.13 Iodization of table salt was made mandatory in Canada in 1949 (with the exception of specialty salts).30

Recommended Intakes

A variety of Dietary Reference Intakes (DRIs) are used by governments and interest groups to estimate the dietary adequacy of iodine.9,31 Estimated Average Requirements (EARs) meet the requirements of about half of the U.S. population in a particular life stage and are used as a reference intake recommendation to establish Recommended Dietary Allowances (RDAs). For iodine, recommendations are estimated based on thyroid iodine accumulation and turnover in euthyroid subjects with adequate iodine status. RDAs for iodine are based on the EAR, such that intake meets the requirements of about 97% to 98% of individuals in various life stages. Adequate Intakes (AIs) are set when there is insufficient evidence to determine an EAR. For iodine, the AI is set at 95 mcg/person/day, which is the AI for all children and for all adults who are not pregnant or lactating.

The most recent DRIs for iodine, which were set by the National Academies in 2001, are summarized in TABLE 1.31 The RDA for adult men and women is 150 mcg/day. However, the recommended intake for iodine during pregnancy is 220 mcg/day and during lactation is 290 mcg/day, and the 2001 Micronutrients Report workshop panel recommended further research on iodine requirements for lactating women.32 A Tolerable Upper Intake Level (UL) is determined for nutrients that may have harmful effects when consumed in excessive amounts. The UL for iodine is estimated as the highest value that is not likely to cause adverse health effects in most individuals in a population. The UL for iodine for adults is 1,100 mcg/day, which is based on serum thyrotropin concentration in response to varying levels of ingested iodine.

tbl1

Iodine Sources

Much of the iodine in today’s diet comes from nonsalt sources in processed foods, such as iodine-containing food additives, processing aids, and foods grown in iodine-rich soil. The iodine content of foods can vary tremendously. Seaweed, such as the nori sheets used to make certain types of sushi, may have very high levels of iodine. Finfish, shellfish, crustaceans, and sea-based additives, including carrageenan, agar-agar, algin, and alginate, contain iodine. Dairy products, particularly milk, yogurt, eggs, and some cheeses, have moderate amounts of iodine. Iodates have been used as dough conditioners in enriched breads and as additives in macaroni products; however, many manufacturers now use noniodine-containing additives. Some food sources of iodine and their approximate iodine content are listed in TABLE 2.33

tbl2

In a survey of the iodine content of bread, milk, and infant formula, 20 breads sampled in the U.S. from 2001 to 2002 had an iodine content ranging from 2.2 mcg to 587 mcg per slice (weight per slice ranged from 25.3-51.2 g, with one outlier of 13.9 mcg iodine in a 132.1-g sample).34 Iodized salt was not listed on any package as an ingredient. Some packages listed iodated dough conditioners, but their presence in the formula did not always correlate with the measured iodine content. The iodine content of 18 samples of cow’s milk and infant formula had a tighter range: 88 mcg to 168 mcg per 250 mL. The iodine content in eight different infant formulas ranged from 16.2 mcg to 56.8 mcg per 148 mL.

Significant losses of naturally occurring iodine or iodine-containing food additives may be caused by environmental factors in transportation and storage by the producer and consumer, and also by processing and cooking. An analysis of the effects of cooking on the iodine content of fish found that boiling, grilling, or frying haddock fillets resulted in iodine losses of 58%, 23%, and 20%, respectively.35 The amount of iodine in cow’s milk has been linked to the amount of iodine supplemented in the cows’ diet.36 Iodine is present, but at lower concentrations, in the skeletal muscle of farm animals given iodine-fortified feed or salt licks as a component of their diet.

Estimating Nutritional Iodine Status

Urinary Iodine: Because the iodine content of food products can vary greatly and about 90% of iodine is excreted in the urine, urinary iodine (UI) concentration, rather than dietary intake, is used to monitor nutritional iodine status. UI is often expressed as micrograms (excreted per day), and spot urine samples are often used for population estimates. A median value, rather than a mean, is used for interpretation because UI values are not normally distributed.37 The WHO assesses sustainable IDD elimination by surveying children aged 6 to 12 years, a close age group with available data, or specific population groups. The WHO advises that no more than half of a population fall below a UI of 100 mcg/L; that a median UI of 100 mcg to 199 mcg/L for a general population indicates sufficient nutritional iodine status; and that the median in pregnant women is 150 mcg/L to 249 mcg/L.8 Low population UI values suggest an overall risk for developing thyroid disorders and are considered with other factors, such as goiter rate, neonatal serum thyroid-stimulating hormone, and serum thyroglobulin.

The median UI concentration for the general U.S. population in the early 1970s was estimated to be 320 mcg/L, suggesting excessive iodine intake.38 Concerns about the use of iodophor cleaning agents in dairy-product production, high levels of iodine in animal feed, red dyes containing iodine, and iodate baking conditioners in breads led to decreased use.39 The median UI concentration reported by the National Health and Nutrition Examination Survey (NHANES) for 2005 through 2008 was 164 mcg/L, which is considered optimal.40

Iodine Intake: The Total Diet Study (TDS) has determined levels of various contaminants and nutrients in foods for over 50 years, and it is one of the few sources of information on nutritional iodine status in the American diet. Analysis of iodine in food as prepared for eating (e.g., a peeled banana) has been included since 2003. The TDS reports annual information for more than 280 foods and beverages that has been aggregated from 6,000 survey foods and beverages sampled from four regions of the country. Iodine was detectable in at least one sample in 59% of TDS foods and was undetected in the remaining 41%.41

Based on TDS food data and consumption data from the NHANES for 2003 through 2004, the estimated average iodine intake by males and females aged 2 to 74 years in 14 life-stage groups ranged from 138 mcg to 353 mcg (values adjusted for uncertainty in detection).41 These levels exceed estimated requirements for children and nonpregnant and nonlactating adults. However, the average daily intake for women of reproductive age in the TDS (14-16 years and 25-45 years) was 178 mcg to 214 mcg and 145 mcg to 197 mcg, respectively, revealing that many females in these populations would need iodine supplementation if they became pregnant or started lactating and did not change their diet. The TDS does not include iodine intake from iodized salt added by the consumer, tap water, or dietary supplements.

Although the iodine content of prenatal vitamins is unregulated, the American Thyroid Association recommends that pregnant and lactating women receive prenatal vitamins containing 150 mcg of iodine.42 Of 19 supplements listed specifically for prenatal use in the 2006 Physicians’ Desk Reference, only one contained 150 mcg of iodine; the others did not list any iodine content. Alarmingly, a more recent analysis of 223 prescription and nonprescription prenatal vitamins showed that 49% did not contain iodine.43 For products with labeling stating that they contained 150 mcg per daily dose, the measured iodine ranged from 33 mcg to 610 mcg per daily dose. Pharmacists may guide both prescribers and patients in choosing products that help pregnant women meet their overall iodine intake goals.

Dairy products make the greatest contribution to daily iodine intake in males and females older than 14 years, ranging from 45% to 63%; grains contribute 16% to 23%.41 Mixed meals contribute 5% to 8% of iodine intake for any age/sex group, and egg, meat, poultry, and fish contribute 5% or less. Dairy products contribute about 70% of the total estimated daily intake of iodine in children aged 2 to 6 years. When asked to recommend vitamins for children, the pharmacist should ask whether the child consumes a vegan or low- or no-dairy diet and should probe to determine whether the selection of a vitamin with iodine is appropriate.

It is not possible to estimate the contribution of iodized salt that is not consumed at home and added while cooking or at the table. Food manufactured for individual sale in the U.S. must list ingredients on the label; this can assist in determining whether a particular brand of bread contains iodine as an additive. While there is no single database of all packaged food labels marketed in the U.S. at any given time, an analysis of 228,895 new variants of food and drink products introduced between June 1996 and April 2011 and tracked by Mintel International’s Global New Products Database listed iodine from any source in 1,034 (0.45%) new product variants, and 916 products (0.40%) listed iodized salt on the ingredient label.44 While the database captures label information only from new product introductions, these data corroborate findings that iodized salt is not a major source of dietary iodine intake from packaged foods, which make up the majority of the average American diet.

There is no standard method of determining whether restaurants use iodized salt. Bulk packages of food-grade iodized salt are available in the U.S., and this salt may be used in packaged or restaurant food or for filling salt shakers at food establishments. It is believed that noniodized salt is used by most food-processing manufacturers and food-service providers.26

Iodine from nonfood sources and unintentional iodine residues can contribute to iodine intake status. Nonfood sources of iodine include cosmetics, vitamins, supplements, medication, and external disinfectants. Some of these products can be a concern for individuals prescribed a restricted iodine diet prior to certain medical procedures, but they are not part of usual estimates of iodine intake. Erythrosine (FD&C Red No. 3, which contains four iodine molecules) has been banned for use generally except as a straight color in foods and dietary supplements.45 Medical products containing iodine include water-purification tablets, radiographic contrast media, medicines such as amiodarone (Cordarone) and some red- and pink-colored oral solutions, and iodophor dermal disinfectants such as povidone-iodine. Povidone-iodine is a stable chemical complex of polyvinylpyrrolidone (povidone) and elemental iodine that contains 9% to 12% iodine. Common names of medications containing iodine include tincture of iodine, Lugol’s solution, and Betadine. Iodophor preparations are also used by brewers, winemakers, and the dairy industry to sanitize bottles and equipment.46

Conclusion

The introduction of iodized table salt has dramatically reduced the incidence of goiter in the U.S. compared with a century ago. Since that time, the availability of foods prepared outside the home and the American lifestyle have undergone major changes. Decades of evidence have linked excessive dietary sodium consumption with cardiovascular risk, and most sodium in the American diet comes from sodium chloride. Because the average person’s diet consists primarily of packaged and prepared foods, reducing sodium in the U.S. food supply is considered a primary strategy to reduce excessive consumption. The contribution of iodized salt to the average dietary sodium intake is small, and sodium reduction in packaged and prepared foods would not be expected to change the population’s iodine status. Some individuals, including pregnant and lactating women, may be at risk for iodine deficiency and can benefit from education by pharmacists regarding a diet that includes foods or supplements containing sufficient iodine or the selection of iodized salt for home use.

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