By Chris D. Meletis, ND
Iodine is a trace element required by the body for an increasing number of identified physiologic functions. This element belongs to the halogen family of elements, a group of highly reactive nonmetals that includes fluorine, chlorine, bromine, and astatine.
Most iodine intake in the United States still occurs as a result of the intake of iodized table salt. Indeed in the 1920’s iodation of salt was established as a health mandate due to a growing number of iodine deficiency diseases including goiters and hormone altering thyroid disease such as hypo- and hyper-thyroidism. The genesis of this mandate arose from upper Midwest and Great Lakes region, where the incidence of goiter was as high as 30–40% in 1922, was aptly named the “goiter belt.”1
The recommended daily allowance (RDA) of iodine for adults is 150 μg/day, for pregnant women 220 μg/day, and for lactating women 290 μg/day, and although some studies indicate that Americans’ iodine intake is adequate, many other studies suggest a prevalence of sub-clinical iodine deficiency. The thinking that iodine levels are sufficient are resonant of the concept that vitamin D levels have been adequate over the years. As with the vitamin D paradigm that is now being challenged after decades of insufficiency and resultant progressive disease, iodine deficits are also contributing to further human suffering.
Blind Health Policy
The vitamin D awakening must trigger us to look at other nutrients that have through health policy been created. We were told to not go in the sun, for fear of skin cancer, indeed a reasonable consideration; yet with this recommended avoidance behavior or the incorporation of using high SPF sunscreens that can block in excess over 90% of UV inducing vitamin D creation within the body, health policy set society up for increased and varied diseases, including autoimmune disease, osteoporosis, cancer and depression to name a few. Likewise, blind health policy suggesting the avoidance of salt (sodium chloride) that may be protective against high blood pressure and heart disease, has led to decreased use of salt for the last couple of generations. Well, if in 1920, healthy policy tried to solved a health crisis by adding iodine to the diet, the new health policy without regard or warning of the public, took the iodine back out of the diet with no regard to the health effects.
Even under the best circumstance when iodized salt is used, research suggests that only 10% of the iodide in iodized salt is bioavailable.2 Moreover, with cautionary recommendations that Americans limit their sodium intake, an adequate intake of iodine is of concern because iodine deficiency is associated with numerous anomalies including hypothyroidism, goiter, cretinism, cognitive disorders, neurological disorders, and breast disease. Iodine deficiency is especially hazardous in pregnant women, developing fetuses, and newborn infants because of its ability to cause irreversible damage to fetuses and newborns.
The World Health Organization (WHO) has established that the mean urine iodine concentration should exceed 10 μg/dL, and should be less than 5 μg/dL in no more than 20% percent of a population. Sadly though the United States has demonstrated clearly that we are failing to meet the minimal standars of the WHO, as discovered by The National Health and Nutrition Examination Surveys (NHANES). It was determined via the NHANES I (1971–1974) and NHANES III (1988–1994), Americans’ median urine iodine concentration decreased by 50%, while a low urine excretory level of iodine of less than 5 μg/dL increased by 4.5-fold in this same period. Monitoring of high-risk groups showed that 6.7% of pregnant women and 14.9% of women of childbearing age had a urine excretory level of less than 5 μg/dL of iodine.3 Furthermore, it was demonstrated by the NHANES IV: 2001–2002 no improvement in iodine levels have occurred since NHANES III.4
An Artificial Sense of Adequacy: RDA for Iodine
The minimal iodine recommendation of 150 μg/day per the RDA for iodine according to many of the leaders in the field of nutrition are overtly too low. Much like the concept that an RDA of 60 mg for vitamin C is far too inadequate for anything other than the prevention of overt scurvy. The fear of triggering autoimmune thyroid disease are scattered in the scientific literature 5,6 but such autoimmune disease has been increasing during the same period in which iodine intake has been decreasing in the United States.7 From a practical perspective, one must only look to the East, to be reassured on the long term safety of higher levels of iodine, in the traditional Japanese populace, the typical dietary intake of elemental iodine is said to be as high as 13.8 mg.8
Throughout the US and Europe physicians have prescribed iodine in a dose of 0.1–0.3 mL of Lugol’s solution, a 5% solution containing 50 mg of iodine and 100 mg of potassium iodide per milliliter, thus providing 12.5–37.5 mg of the elemental iodine needed to treat iodine deficiency disorders and promote overall well-being.8,9 This prescribing practice began to decrease after the use of iodized salt. Now, that people have moved away from the use of iodized salt either due to health concerns, the realization that excess non-iodized salt have been introduced in the processed food supply, or the desire to become more holistic, hence leading to the use Sea Salt that is not typically iodized. Thus it makes sense, that we may revisit the practice of prescribing iodine, while practicing cautionary medicine that includes monitoring iodine levels and thyroid function.
Metabolism of Iodine
The human body concentrates iodide in the salivary glands, breast tissue, gastric mucosa, and choroid plexus, among other sites demonstrating the global importance of “sufficient” levels of iodine to more than just the thyroid gland. The body possesses a specific mechanism, the sodium/iodide transporters—protein molecules also known as “symporters” that uptake iodide from the blood into the thyroid gland and other tissues across a concentration gradient that may be as high as 50-fold, and concentrate the iodide in cells.
It has long been understood that iodide/iodine are essential for thyroxine (T4) which is converted in peripheral tissues to the hormone tri-iodothyronine (T3), which regulates growth and cellular metabolism. Additionally, vitamin A and iron deficiency, as well as the selenium deficiency noted earlier, can exacerbate iodine deficiency.10 Intake of particular elements that compete with iodine for uptake and utilization, such as chlorine, fluorine, and bromine, may also be a factor.
Diagnosis of Iodine Deficiency
Based on the research studies that demonstrate 90% of ingested iodine is excreted in the urine. According to the WHO, median urine iodine levels should exceed 10 μg/dL in “iodine sufficient” populations. Urinary iodine excretion may also be expressed in relation to creatinine excretion, as μg of iodine per gram of creatinine. There remains debate amongst researchers as to the best measure of iodine sufficiency, which should not be surprising, considering the level of entrenchment in the status quo that so many researcher adhere to as they develop and test hypotheses.12, 13 The Iodine Loading test is becoming an ever growing popularity of functional testing that a 24-hour urinary excretion after a 50mg iodine load.
The Halide Wars: Bromine, Chlorine and Fluoride
There are many competing halides that exacerbate the current inadequate dietary iodine intake. Not surprisingly, in the 1970’s when iodine levels began to drop in the US as documented by the NHANES surveys, during the same time bromine replaced iodine for use as a dough softener in bread–making. Studies of thyroid function in rats indicate that with increased intake, bromine replaces iodine in this organ.14 Animal studies also suggest that in the presence of an iodine-deficient state, bromine may induce hypothyroid symptoms of decreased thyroxine synthesis and increased thyroid gland size, as well as decreasing iodine concentrations in the skin.14 Studies with pregnant and lactating rats have demonstrated that increased bromine intake decreases the iodine content of mammary tissue, decreases T4 in both mothers and offspring, and decreases the body weight of offspring. Bromine also increases the renal excretion of iodine in these animals.14 Treating rats with bromine has been shown to induce goiter and decrease the thyroid iodine concentration, while supplementation with iodine and selenium has been found to reduce by 50% the amount of bromine taken up by the thyroid as compared to that in rats without such supplementation.15
Perchlorate, an environmental contaminant, is a known competitive inhibitor of the iodine/sodium symporter and decreases thyroid function by inhibiting iodine uptake by the thyroid at doses of 200 mg/day or more.16 Perchlorate is found in fireworks, explosives, solid jet and rocket fuel, and is a contaminate found in some fertilizers. Perchlorate is often consumed in plants such as lettuce and leafy greens, drinking water, and milk, generally accumulated from contaminated ground water. Studies have found that the majority of dairy milk samples and all samples of breast milk tested contained perchlorate. A recent study demonstrated a mean perchlorate level in breast milk of 10.5 μg/L, suggesting that the average breast-fed infant consumes more than twice the recommended maximum daily level of perchlorate established by the National Academy of Sciences.17 Studies of perchlorate levels in drinking water and their relation to diseases in the United States have provided conflicting results. Several studies have measured thyroid hormone values as indicators of the health effects of perchlorate in drinking water, and have found no effect.18
One study did find a statistically significant increase in newborns’ TSH levels in an area where all samples of drinking water were contaminated with perchlorate, as compared to the TSH levels of newborns in an area without such contamination.19 Some researchers suggest that the combination of perchlorate with other competitors of the iodine/sodium symporter, such as nitrates and thiocyanate, as well as the combination of perchlorate with iodine itself, increases the risk of thyroid-related disease.20 A further study examining the incidence of attention-deficit/hyperactivity disorder (ADHD), autism, and the academic performance of fourth graders in areas with and without perchlorate contamination did not find a statistically significant difference in these conditions in the two groups. However, this study did not take into account the residence locations of mothers at the time of gestation, or their individual perchlorate exposure.21 Also, one study showed that higher levels of perchlorate excretion were associated with increased levels of TSH and decreased levels of T4 in iodine-deficient women.22
Fluorine, often in the form of fluoride, a halogen like bromine and chlorine, is commonly added to drinking water and used as a component of dental products for decreasing the risk of caries. However, some animal studies have shown that increased intake of fluoride can decrease serum T3 and T4 levels in iodine-deficient mice.23
Iodine Deficiency and Thyroid Disease
There is abundant scientific and medical literature demonstrating that hypothyroidism during pregnancy can result in miscarriage, abnormal fetal growth, perinatal morbidity, and neonatal death. Of particular note, it is essential to recognize that early brain development begins around the 15th week of gestation relies on thyroxine, hence iodine status of the mother. Indeed maternal hypothyroidism and iodine insufficiency can produce fetal brain damage, cretinism, and a decreased intelligence quotient. Cretinism, a severe neuropathology caused by iodine deficiency, is marked by gross mental retardation along with varying degrees of shortness of stature, deaf-mutism, and spasticity. Because of decreased iodine retention, preterm infants, in whom renal function is not fully developed, require twice the daily intake of iodine for normal infants. To decrease these risks, the WHO in 2001 suggested an increased iodine intake for infants and an increased iodine content in infant formula.24
The bigger question must be posed with such a huge drop in iodine status in the US since the 1970’s, would it not be prudent the population in general be encouraged to increase iodine levels, just as the healthy policy suggests for vitamin D, upon our new enlightenment on yet another nutrient.
Beyond Thyroid Disease-The Breast Health Link
Beyond thyroid function, iodine is required for the normal growth and development of breast tissue. The high level of iodine intake by Japanese women, noted earlier, has been associated with a low incidence of both benign and cancerous breast disease in this population. Evidence links iodine deficiency with an elevated risk of breast, endometrial, and ovarian cancer.25 Antiproliferative iodolactones in the thyroid may be responsible for this effect.26 Although autoimmune antibodies directed against thyroid peroxidase have been associated with a better prognosis in breast cancer,27 thyroid supplementation may increase the risk of breast cancer, especially if an underlying iodine insufficiency is not addressed, though this is still a point of great debate.28 In vitro studies have found that molecular iodine inhibits induction and proliferation and induces apoptosis in some human breast cancer cell lines, as well as exhibiting antioxidant activity.29 Benign, fibrocystic breast disease is also associated with iodine deficiency. Blocking of iodine with perchlorate in the mammary tissue of rats has been found to cause histologic changes indicative of fibrocystic breast disease, as well as precancerous lesions.30 Of clinical note, iodine supplementation has been shown to ease mastalgia. Supplementation with 3 or 6 mg/day of molecular iodine significantly decreased pain reported by patients, as well as physicians’ assessments of pain, tenderness, and nodularity in benign breast disease, with a dose of 6 mg/day providing significant reduction of pain in more than 50% of patients.31
Brain Development and IQ- The Iodine Factor
T3 and T4 are particularly important for myelination of the developing brain, and in turn iodine is critical for thyroid hormone production, with 3 iodine molecules incorporated in T3 and 4 iodine molecules on T4. Hypothyroidism during pregnancy and lactation causes numerous neurologic and cognitive deficits. A study of schoolchildren with mild iodine deficiency found that urine iodine levels above 100 μg/L were associated with significantly higher IQ scores, while levels below 100 μg/L increased the risk of an IQ below 70.32 The same study also found that consuming noniodized salt and drinking milk less than once daily increased the risk of an IQ below the 25th percentile.33 Another study found that children from severely iodine-deficient areas had IQ scores that were 12.45 points below average.33
A small study comparing the prevalence of ADHD in children from a mildly iodine-deficient area and a moderately iodine-deficient area found that 68.7% of those from the latter area had a diagnosis of ADHD, as compared with an absence of this diagnosis in the children from the mildly iodine deficient area, and that IQ scores were lower in the moderately deficient area. Of the children with ADHD, 63.6% were born to mothers who had become hypothyroxinemic in early gestation.34 Studies have also suggested that iodine deficiency affects hearing. Children in a mildly iodine-deficient area who had elevated serum thyroglobulin levels had higher auditory thresholds for sound of higher frequencies than did children with lower thyroglobulin levels.35
Another comparative study examining children from a severely iodine-deficient and a mildly iodine-deficient region found that the former group had lower thyroxine levels, higher TSH levels, and lower scores on achievement motivation tests, and were slower learners than the latter group.36 Research on endemic cretinism from congenital iodine deficiency has shown specific severe neurologic deficits including deaf-mutism and a varying degree of bilateral hearing loss, as well as dysarthria, mental deficiency, spasticity of the proximal lower extremities, rigidity, and bradykinesia. In some cases strabismus and kyphoscoliosis were also present.37 Thus the question of whether subclinical cases of iodine insufficiency may also contribute to the wide myriad of the above mentioned common complaints seen in daily clinical practice.
Gastric Disease on the Rise—Iodine Correlation
There is no question that clinicians are barraged by a sheer volume of patients with gastric ailments. There is no question from a historical perspective that since the 1970’s and a drop in iodine sufficiency in the US that stomach disease and in particular dyspepsia continues to rise. Certainly there are many co-morbid factors, yet we also know that iodine deficiency has been linked to an increased risk of gastric carcinoma. One study demonstrated an increased prevalence of gastric cancer and an increased risk of atrophic gastritis in areas with a greater-than-average prevalence of iodine-deficiency related goiter. The researchers also reported that competitive inhibitors of intracellular iodine transport, such as nitrates, thiocyanate, and salt increased the risk of gastric cancer.38 Another study found a significant correlation between decreased mean urinary iodine levels and prevalence of stomach cancer, as well as a greater frequency of severe iodine deficiency in stomach cancer than in controls.39 There is also evidence for lower levels of iodine in cancerous gastric tissue than in surrounding normal tissue.40
Treatment of Iodine Deficiency
The American Thyroid Association (ATA) recommends that iodine supplementation of 150 μg/day be given to all pregnant and lactating women, and suggests that all prenatal vitamin supplements contain 150 μg of iodine.41 Based on this recommendation; it may be possible to extrapolate this increased need to the general population. It is time to start thinking beyond the 1940s RDA approach of dosing so marginally that survival is the targeted threshold opposed to true human thriving.
Iodine deficiency is a worldwide concern with serious consequences to health. With the increased presence of other halogens in our environment, food and water supplies, relative iodine deficiency is an ever growing concern. As with vitamin D, omega-3 fatty acids, and other key nutrients recognized as deficient in the Western diet, sub-clinical iodine deficiency may then become a thing of the past. Incorporating iodine into clinical practice makes good sense and with testing and monitoring it can be done safely and most importantly can serve as a proactive intervention to help prevent undue human suffering.
Author: Dr. Chris D. Meletis is an educational consultant for Complementary Prescriptions. He is an international author and lectures nationally on topics of family practice, nutrition, botanical medicine and healthy aging and wellness. Many of his articles and books can be found at www.DrMeletis.com An update compilation of 39 health topics with evidence based references can be found in Dr. Meletis’ co-authored with Dr. Robert Rountree 17th book called Clinical Natural Medicine Handbook, published by MaryAnn Liebert Publishing.
1. Markel H. “When it rains it pours”: Endemic goiter, iodized salt, and David Murray Cowie, M.D. Am J Public Health 1987;77:219–229.
2. Abraham GE. The concept of orthoiodosupplementation and its clinical implications. Original Internist 2004;11:29–38.
3. Hollowell JG, Staehling NW, Hannon WH, et al. Iodine nutrition in the United States: Trends and public health implications. Iodine excretion data from National Health and Nutrition Examination Surveys I and III (1971–1974 and 1988–1994) J Clin Endocrinol Metab 1998;83:3401–3408.
4. Blackburn GL. National Health and Nutrition Examination Survey: Where nutrition meets medicine for the benefit of health. Am J Clin Nutr 2003;78:197–198.
5. Prummel MF, Strieder T, Wiersinga WM. The environment and autoimmune thyroid diseases. Eur J Endocrinol 2004;150:605–618.
6. Zois C, Stavrou I, Svarna E, et al. Natural course of autoimmune thyroiditis after elimination of iodine deficiency in northwestern Greece. Thyroid 2006;16:289–293.
7. Abraham GE, Flechas JD, Hakala JC. Orthoiodosupplementation: Iodine sufficiency of the whole human body. Original Internist 2002;9:30–41.
8. Abraham GE, Brownstein D. A rebuttal of Dr. Gaby’s editorial on iodine. Townsend Letter for Doctors & Patients, October 2005. Online document at: www.townsendletter.com/Oct2005/gabyrebuttal1005.htm Accessed on April 1, 2007.
9. Jamieson A, Semple CG. Successful treatment of Graves’ disease in pregnancy with Lugol’s iodine. Scott Med J 2000;45:20–21.
10. National Academies Press. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. 2000. Online document at: www.nap.edu/openbook.php?record_id=10026&page=268 Accessed on April 1, 2007.
11. Gaitan E, Cooksey RC, Legan J. Antithyroid effects in vivo and in vitro of vitexin: A C-glucosylflavone in millet. J Clin Endocrinol Metab 1995;80:1144–1147.
12. Simsek E, Safak A, Yavuz O, et al. Sensitivity of iodine deficiency indicators and iodine status in Turkey. J Pediatr Endocrinol Metab 2003;16:197–202.
13. Soldin OP, Tractenberg RE, Pezzullo JC. Do thyroxine and thyroidstimulating hormone levels reflect urinary iodine concentrations? Ther Drug Monit 2005;27:178–185.
14. Pavelka S. Metabolism of bromide and its interference with the metabolism of iodine. Physiol Res 2004;53(suppl1):S81–S90.
15. Kotyzova D, Eybl V, Mihaljevic M, Glattre E. Effect of long-term administration of arsenic (III) and bromine with and without selenium and iodine supplementation on the element level in the thyroid of rat. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2005;149:329–333.
16. Crump C, Michaud P, Tellez R. Does perchlorate in drinking water affect thyroid function in newborns or school-age children? J Occup Environ Med 2000;42:603–612.
17. Kirk AB, Martinelango PK, Tian K, et al. Perchlorate and iodide in dairy and breast milk. Environ Sci Technol 2005;39:2011–2017.
18. Li Z, Li FX, Byrd D, et al. Neonatal thyroxine level and perchlorate in drinking water. J Occup Environ Med 2000;42:200–205.
19. Brechner RJ, Parkhurst GD, Humble WO, et al. Ammonium perchlorate contamination of Colorado River drinking water is associated with abnormal thyroid function in newborns in Arizona. J Occup Environ Med 2000;42:777–782.
20. De Groef B, Decallonne BR, Van der Geyten S, et al. Perchlorate versus other environmental sodium/iodide symporter inhibitors: Potential thyroid-related health effects. Eur J Endocrinol 2006;155:17–25.
21. Chang S, Crothers C, Lai S, Lamm S. Pediatric neurobehavioral diseases in Nevada counties with respect to perchlorate in drinking water: An ecological inquiry. Birth Defects Res [A] Clin Mol Teratol 2003;67:886–892.
22. Blount BC, Pirkle JL, Osterloh JD, Valentin-Blasini L, Caldwell KL. Urinary perchlorate and thyroid hormone levels in adolescent and adult men and women living in the United States. Environ Health Perspect 2006 Dec;114(12):1865-71.
23. Zhao W, Zhu H, Yu Z, et al. Long-term effects of various iodine and fluorine doses on the thyroid and fluorosis in mice. Endocr Regul 1998;32:63–70.
24. World Health Organization and Food and Agriculture Organization Vitamin and Mineral Requirements in Human Nutrition, 2nd ed. 2004. Online document at: http://whqlibdoc.who.int/publications/2004/9241546123_chap16.pdf Accessed April 1, 2007.
25. Stadel BV. Dietary iodine and risk of breast, endometrial, and ovarian cancer. Lancet 1976;1:890–891.
26. Aceves C, Anguiano B, Delgado G. Is iodine a gatekeeper of the integrity of the mammary gland? J Mammary Gland Biol Neoplasia 2005;10:189–196.
27. Smyth PP. The thyroid, iodine and breast cancer. Breast Cancer Res 2003;5:235–238.
28. Kapdi CC, Wolfe JN. Breast cancer: Relationship to thyroid supplements for hypothyroidism. JAMA 1976;236:1124–1127.
29. Shrivastava A, Tiwari M, Sinha RA. Molecular iodine induces caspase-independent apoptosis in human breast carcinoma cells involving the mitochondria-mediated pathway. J Biol Chem 2006;281:19762–19771. Epub 2006 May 5.
30. Eskin BA, Shuman R, Krouse T, Merion JA. Rat mammary gland atypia produced by iodine blockade with perchlorate. Cancer Res 1975;35:2332–2339.
31. Kessler JH. The effect of supraphysiologic levels of iodine on patients with cyclic mastalgia. Breast J 2004;10:328–336.
32. Santiago-Fernandez P, Torres-Barahona R, Muela-Martinez JA, et al. Intelligence quotient and iodine intake: A cross-sectional study in children. J Clin Endocrinol Metab 2004;89:3851–3857.
33. Qian M, Wang D, Watkins WE, et al. The effects of iodine on intelligence in children: A meta-analysis of studies conducted in China. Asia Pac J Clin Nutr 2005;14:32–42.
34. Vermiglio F, Lo Presti VP, Moleti M, et al. Attention deficit and hyperactivity disorders in the offspring of mothers exposed to mild–moderate iodine deficiency: A possible novel iodine deficiency disorder in developed countries. J Clin Endocrinol Metab 2004;89:6054–6060.
35. van den Briel T, West CE, Hautvast JG, Ategbo EA. Mild iodine deficiency is associated with elevated hearing thresholds in children in Benin. Eur J Clin Nutr 2001;55:763–768.
36. Tiwari BD, Godbole MM, Chattopadhyay N, et al. Learning disabilities and poor motivation to achieve due to prolonged iodine deficiency. Am J Clin Nutr 1996;63:782–786.
37. DeLong GR, Stanbury JB, Fierro-Benitez R. Neurological signs in congenital iodine-deficiency disorder (endemic cretinism). Dev Med Child Neurol 1985;27:317–324.
38. Venturi S, Venturi A, Cimini D, et al. A new hypothesis: Iodine and gastric cancer. Eur J Cancer Prev 1993;2:17–23.
39. Behrouzian R, Aghdami N. Urinary iodine/creatinine ratio in patients with stomach cancer in Urmia, Islamic Republic of Iran. East Mediterr Health J 2004;10:921–924.
40. Gulaboglu M, Yildiz L, Celebi F, et al. Comparison of iodine contents in gastric cancer and surrounding normal tissues. Clin Chem Lab Med 2005;43:581–584.
41. Becker DV, Braverman LE, Delange F, et al. Iodine supplementation for pregnancy and lactation—United States and Canada: Recommendations of the American Thyroid Association. Thyroid 2006;16:949–951.