|Year : 2013 | Volume
| Issue : 4 | Page : 239-244
"Iodized salt, a boon or bane?": A retrospective study
Eswar Ganti1, Seshaiah Venkata Kurada1, Srijana Pakalapati1, Srinivasa Rao Dana1, Madhavi Pothukuchi2
1 Department of Medicine, Government Siddhartha Medical College, Vijayawada, Andhra Pradesh, India
2 Department of Community Medicine, Government Siddhartha Medical College, Vijayawada, Andhra Pradesh, India
|Date of Web Publication||26-Nov-2013|
Seshaiah Venkata Kurada
Department of Medicine, Government Siddhartha Medical College, Vijayawada - 520 008, Andhra Pradesh
Background: Iodine is an essential micronutrient. Its daily requirement for adults is placed at 150 μg/day. This amount is normally supplied by well-balanced diets and drinking water, except in areas where food and water are deficient in iodine. Iodine is essential for production of thyroid hormones, which are essential for normal growth and development and for regulation of a number of homeostatic functions. Inadvertent use of iodized salt can lead to hypothyroidism.
Aim: To study the association of hypothyroidism a) with excess iodized salt usage; and b) with hypertension and diabetes.
Settings and Design: Multispecialty hospital located in municipal corporation of Vijayawada, Andhra Pradesh. The subjects included in this study were selected from outpatient section, using random sampling technique.
Materials and Methods: This cross-sectional study was conducted from November 2011 to August 2012, for a period of 10 months and included 120 subjects with hypothyroidism and 339 non-hypothyroid subjects.
Statistical Analysis: All statistical analyses were performed using MS Excel 2007 software and appropriate tests of statistical significance including chi-square test, P-values, odds ratios (ORs), and confidence intervals (CIs) were applied.
Results: There was statistically significant association of hypothyroidism with excess usage of iodized salt, with hypertension and diabetes.
Conclusion: Excess iodine, through global iodization of table salt can lead to hypothyroidism, which is more associated with hypertension and diabetes, the two most important diseases commonly encountered in the community. So, iodine supplementation should be restricted to pockets of iodine deficiency only.
Keywords: Antibody, autoimmunity, endemicity, goiter, hypothyroidism, iodized salt, thyroglobulin, thyrotropin, urinary iodine excretion
|How to cite this article:|
Ganti E, Kurada SV, Pakalapati S, Dana SR, Pothukuchi M. "Iodized salt, a boon or bane?": A retrospective study. J NTR Univ Health Sci 2013;2:239-44
|How to cite this URL:|
Ganti E, Kurada SV, Pakalapati S, Dana SR, Pothukuchi M. "Iodized salt, a boon or bane?": A retrospective study. J NTR Univ Health Sci [serial online] 2013 [cited 2014 Oct 31];2:239-44. Available from: http://www.jdrntruhs.org/text.asp?2013/2/4/239/122157
| Introduction|| |
Introduction of dietary iodine in the form of fortification of table salt with iodine as a public health measure in the early 20 th century eliminated endemic goiter in many countries including US, but appears spawned a new problem related to thyroid health in the form of hypothyroidism. 
Iodine compounds are mainly found in sea water and soil. Vegetables grown in these soils also contain some amount of iodine. In certain mountainous parts of the world such as the Andes, the Himalayas, and the Central Africa, there is a dietary deficiency of iodine and many people in these areas have endemic goiter. The distribution of iodine in soil and water is not uniform. It is low in northern hilly regions and elevated near southern basins. Soil iodine determination in Deccan Syneclise identified some pockets with high iodine values. There is also a considerable variation in iodine content both in surface and ground water. 
There is increased usage of table salt fortified with iodine all over the world and in some countries its usage has been made compulsory through national legislation, irrespective of regional differences in the endemicity for iodine deficiency. By 2002, more than 170 countries had committed themselves to universal iodization of table salt. As per United Nations Children's Fund (UNICEF) reports, most of the population in more than 87 countries (65% of the world's population) already had access to iodized salt. Once started it has become permanent in many countries. Large populations are no longer iodine deficient. China is one of the great success stories. There is significant reduction in goiter rate in several countries. By 2002 percentage of world's population using adequate iodized salt was 69%. The report of National Rural Health Mission (Iodine Deficiency Disorders (IDD) and Nutrition Cell) of India in 2006 has revealed that, the sample surveys conducted in 324 districts identified that only 263 are endemic for iodine deficiency.
Other sources of dietary iodine include iodine additives to bread, floor, preservatives, and red coloring; therapeutics (amiodarone, vitamins, Lugol's iodine, etc.); topical antiseptics; and contrast dyes.
Normal average intake of salt by an adult is 10 g/day, so that the iodized salt must contain at least 15 ppm of iodine to meet the daily requirement of 150 μg/day. As per the Indian Prevention of Food Adulteration Law of September 1987, fortification must be of 30 ppm at manufacturing point to compensate for the loss during transport and storage. As per the recent national family survey adequate usage of iodized salt has increased by 20% in rural households of India as against survey results in 2005-2006. According to International Council for the Control of IDD (INCC IDD), map reveals that while most areas of western hemisphere tend to be sufficient in iodine, Europe, Russia, Asia, Australia, and Africa have areas at varying risks of deficiency with uneven distribution of endemicity.
Iodine is the major cofactor and stimulator for thyroid peroxidase (TPO). The acute response to increased iodine intake with a normal underlying thyroid is, reduced hormone production and release, the Wolff-Chaikoff effect.  In a few apparently normal individuals, in newborns and fetuses, in some patients with systemic diseases, in euthyroid patients with autoimmune thyroiditis, in Graves' disease patients previously treated with drugs or radioiodine, in patients with postpartum thyroidits, and in patients treated with recombinant interferon-α, the escape from this effect is not achieved and clinical or subclinical hypothyroidism ensues. The patients who develop transient iodine induced hypothyroidism must be followed long-term thereafter, because many will develop permanent primary hypothyroidism. 
The adverse effects of excess iodine also depend upon the extent and duration of iodine exposure.  More than adequate and excessive iodine exposure is independent risk factor of hypothyroidism. The risk of hypothyroidism goes up and thyroid dysfunction becomes more serious with the increase in biological exposure to iodine. 
| Materials and Methods|| |
This retrospective study was carried out in a multispecialty hospital, located in municipal corporation area of Vijayawada, Andhra Pradesh. The subjects in this study were selected from the outpatient section, using random sampling technique, with 120 hypothyroid subjects as well as 339 non-hypothyroid subjects who attended to hospital for other problems. Written informed consent was taken from all the subjects, after carefully explaining all the study protocols to them. This study was approved by the Institutional Ethics Committee. An oral questionnaire was administered to each person. The questionnaire elicited data on the eating habits, type of salt used, amount of salt ingested per day and personal and family history of thyroid diseases. Subjects with associated comorbidities were excluded from the study. Serum levels of thyrotropin, free triiodothyronine (FT 3 ), free thyroxine (FT 4 ), TPO antibody, and Tg antibody were measured in all subjects by chemiluminiscence immunoassay. The reference range for the serum thyrotropin level (0.3-4.8 μIU/ml) was determined from 2.5-97.5 th percentile values for the 300 subjects without known clinical thyroid disease, without thyroid antibodies, and without goiter. The limit of detection of serum thyrotropin was 0.002 μIU/ml. An oral glucose tolerance test was done to determine the glycemic status. Blood samples were collected after 10 h of fasting for estimation of plasma glucose. Mean of two blood pressure (BP) readings taken 5 min apart in resting state were used. Cut-off values for diabetes and BP were followed according to American Diabetes Association, 2011 (ADA) and Joint National Committee 7 (JNC 7) criteria, respectively.
All statistical analyses were performed with MS Excel 2007 software. Comparisons between hypothyroid and non-hypothyroid groups were performed with the use of percentages, chi-square test, and P-values. Strength of associations was assessed with odds ratios (ORs) and confidence intervals (CIs).
| Results|| |
Average age of the thyroid group was 49.31 ± 15.24 years, with duration of hypothyroidism as 5.19 ± 0.66 years. Average age of the non-thyroid group was 44.07 ± 14.99 years. Male and female distribution, demographic, and clinical data are shown in [Table 1].
|Table 1: Demographic and Clinical Profile of Hypothyroid and Non-Hypothyroid Groups|
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Percentage distribution of males and females, users of iodized salt in hypothyroid group, users of iodized salt in non-hypothyroid group, users of excess iodized salt, hypertensives, and diabetics in both the groups are depicted in [Figure 1],[Figure 2],[Figure 3],[Figure 4],[Figure 5] and [Figure 6], respectively.
|Figure 1: Sex distribution among thyroid (n = 120) and nonhypothyroid (n = 339) groups|
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|Figure 3: Consumption of iodized salt in non-hypothyroid group (n = 339)|
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|Figure 4: Consumption of excess iodized salt in hypothyroid (n = 120) and non-hypothyroid (n = 339)|
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|Figure 5: Percentage of hypertensives in hypothyroid (n = 120) and non-hypothyroid (n = 339) groups|
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|Figure 6: Percentage of diabetics in hypothyroid (n = 120) and non-hypothyroid (n = 339) groups|
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There was statistically significant association of hypothyroidism with usage of only iodized salt (χ2 = 7.16, P ≤ 0.01, OR 2.11; 95% CI = 1.21-3.68); with excess usage of iodized salt (χ2 = 35.55, P ≤ 0.001, OR 3.61; 95% CI = 2.34-5.57); with hypertension (χ2 = 27.91, P ≤ 0.005, OR 3.34; 95% CI = 2.11-5.30); and with diabetes (χ2 = 15.39, P ≤ 0.001, OR 1.76; 95% CI = 1.07-2.88).
| Discussion|| |
Our study has shown that excess usage of iodized salt can lead to hypothyroidism and its associated complications hypertension and diabetes. Excess iodine intake is associated with highly iodinated thyroglobulin (Tg), which is more immunogenic than poorly iodinated Tg. Increased binding of iodine to tyrosyl residues enhances the stability of Tg and reduces its susceptibility to prophylactic cathepsins of the thyroid. Increased iodination of Tg can thus heighten its autoimmunogenic potential by changes in antigen processing, alterations in stereochemical shape, production of novel iodine containing determinants, or appearance of cryptic epitopes.  Other mechanisms include a direct toxic effect of iodine in the thyroid cells via free oxygen radical generation and immune stimulation of iodine. 
The immune response is specific for Tg in both terms of antibody response and T cell proliferation. In fact the appearance of lesions can be predicted by the presence of Tg specific IgG2b antibody. The disease can be transferred adoptively, using spleen cells from iodine fed donors treated in vitro with iodinated Tg. Excess iodine changes immunogenicity of Tg molecule and upregulates intracellular adhesion molecule (ICAM-1), reactive oxygen species (ROS) in the thyrocyte itself.  It was identified that murine monoclonal antibody raised against human Tg (MOAb 42C3), recognized Tg differently depending upon its level of iodination. Iodinated thyromine, a derivative of tyrosine, an amino acid unique to Tg, determines the binding specificity of certain antibodies. 
In a study, restriction of dietary iodine reversed hypothyroidism in 12 of 22 subjects. When seven of the patients with reversed hypothyroidism were refed iodine, all of them became hypothyroid.  In another study, 78% of subjects with Hashimoto's disease regained normal thyroid function with iodine restriction alone.  High iodine intake has been reported to initiate and excaberate infiltration of thyroid by lymphocytes in genetically susceptible BB/W rats and NOD.H-2h4 mice. ,
A study in 2004 in Andhra Pradesh (India) has reflected adequate iodine nutriture (urinary iodine excretion level >100 μg/l) in all the districts except Rangareddy and Cuddapah.  A study on school children from Delhi, India reported direct correlation between urinary iodine excretion (UIE) and autoimmunity with goiter and autoimmunity with thyroid dysfunction. 
A prospective study was done on the effect of iodine intake on thyroid diseases in China, in which 3,760 subjects were enrolled at base line and 3,018 participated in 1999, and during the 5 year follow-up through 2004, the effect of regional differences in iodine intake on the incidence of thyroid disease was examined. This study concluded that more than adequate or excessive iodine intake may lead to hypothyroidism and autoimmune thyroiditis.  A Sri Lankan study has identified the evolution of thyroid autoimmune markers during the course of iodine prophylaxis for a period of 3 years.  Silent iodine prophylaxis in Greece resulted in elimination of iodine deficiency, but increased prevalence of autoimmune thyroiditis.  A research study in Turkey concluded that iodine supplementation has resulted in the elimination of iodine deficiency in the Eastern Black Sea region, but has been accompanied by an increase in the prevalence of autoimmune thyroiditis and thyroid dysfunction.  A Brazilian 5 year study documented that excess iodine intake was associated with chronic autoimmune thyroiditis and hypothyroidsm in subjects generally predisposed to thyroid autoimmune diseases. 
CUPS-19, a south Indian study revealed that incidence rate of diabetes was 20.2 per 1,000 person years, and that of prediabetes was 13.1 among subjects with normal glucose tolerance, while it was 64.8 among prediabetics at baseline; and also obesity, abdominal obesity, and hypertension were associated with diabetes.  Iodide-induced hypothyroidism can appear even in subjects with no underlying thyroid disease and it is not strictly correlated with the presence of thyroid autoimmunity.  As India is now predominantly iodine sufficient, we are nearing the peak prevalence of autoimmune epidemic.  Endemicity of iodine deficiency is not uniform in any country including India. Although iodine supplementation should be implemented to prevent and treat iodine deficiency disorders (IDD), supplementation should be maintained at a safe level. Global iodine supplementation should differ from Global Immunization Program. Supplementation programs should be tailored to iodine deficient areas. Surveys should not simply depend on presence of goiter for identification of iodine deficiency, because excess iodine can also cause goiter. Thus, more than adequate iodine intake might not be recommended for the general population in terms of keeping a normal function of thyroid.  Nevertheless, further population-based studies taking large sample size are required to identify areas of iodine deficiency and to save the residents of iodine sufficient areas from hypothyroidism.
| Conclusion|| |
We suggest that pockets of iodine deficiency should be identified by estimating median urinary iodine excretion. Areas with more than normal urinary iodine excretion should be excluded from iodine supplementation programs. Preventing high iodine-induced hypothyroidism is as important as preventing iodine deficiency induced hypothyroidism. Awareness must be created among the public regarding the harmful effects of excess iodine and facility for urinary iodine estimation must be made available in all district headquarters hospitals and for all individuals at request.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]