2023 Volume 70 Issue 4 Pages 393-401
Metabolic syndrome (MetS) is considered very important because of the increased risk for cardiovascular diseases. Identifying modifiable factors may help prevent MetS. We aimed to investigate the relationship between iodine intake as a dietary factor and MetS in euthyroid adult in an iodine-replete area. A total of 4,277 adult aged ≥19 years from the Korea National Health and Nutrition Examination Survey VI (2013–2015) with urinary iodine concentration (UIC) results and normal thyroid function were included. Participants were grouped according to their iodine nutrition status based on the WHO recommendations and modifications: insufficient (<100 μg/L), adequate (100–299 μg/L), and excessive (≥300 μg/L) iodine intake. We estimated the odds ratios (ORs) for MetS according to the UIC groups using logistic regression models. Of the study participants, 27.2% men and 23.9% women had MetS. Men with excessive iodine intake had a significantly lower risk of elevated triglycerides [OR 0.733, 95% confidence interval (CI) 0.603–0.890, p = 0.010], as compared to those with adequate iodine intake. Women with insufficient iodine intake had a significantly greater risk of elevated blood glucose (OR 1.519, 95% CI 1.011–2.282, p = 0.044), as compared to those with adequate iodine intake. In women, insufficient iodine intake was a significant risk factor for MetS compared to adequate iodine intake, even after adjusting for confounding variables including age, smoking, alcohol consumption, walking activity, serum thyroid-stimulating hormone, free thyroxine, and anti-thyroid peroxidase antibody (OR 1.544, 95% CI 1.031–2.311, p = 0.035). There was no association between iodine intake and risk of MetS in men. In conclusion, insufficient iodine intake was associated with an increased risk of MetS only in euthyroid adult women. Our data support that sex differences may influence the relationship between iodine intake as a dietary pattern and MetS.
METABOLIC SYNDROME (MetS), characterized by a cluster of metabolic abnormalities including central obesity, dyslipidemia, hypertension and glucose intolerance, is considered very important because it increases the risk of cardiovascular morbidity and mortality [1]. The prevalence of MetS has increased markedly with socioeconomic development and an increase in sedentary lifestyles [2, 3]. The prevalence of MetS varies considerably depending on age, sex, region and the diagnostic definition [2, 4]. These differences in the epidemiology and in regional prevalence suggest that local environmental and cultural factors influence the pathogenesis of MetS. Thus, identifying the related modifiable factors may help prevent MetS.
Iodine, a trace element essential for thyroid function, plays a crucial role in human development, growth and metabolism. Recently, it has been reported that iodine is one of the dietary factors associated with MetS [5] and its components [5-10]. A cross-sectional study conducted in China demonstrated that the relationship between urinary iodine concentration (UIC) and MetS and its components exhibits a U-shaped curve [5]. Data from the United States National Health and Nutrition Examination Survey (NHANES) showed that low UIC was associated with an increased risk of dyslipidemia [6] and coronary artery disease [7]. In a randomized controlled trial on overweight or obese women who were iodine insufficient, iodine supplementation could reduce the risk of dyslipidemia [8]. As for blood pressure (BP), UIC was found to be negatively correlated with systolic BP, and iodine insufficiency was more prevalent among participants with hypertension [9]. In addition, UIC was markedly decreased in patient with type 2 diabetes compared to control participants and was inversely associated with triglycerides, fasting glucose and insulin levels in type 2 diabetes [10].
According to the Korean National Health and Nutrition Examination Survey (KNHANES), the prevalence of MetS has rapidly increased in the Korean population [11]. The results of a meta-analysis have indicated that MetS might be a stronger risk factor for cardiovascular disease in women than in men [11, 12]. Sex differences could affect the relationship between dietary patterns and MetS in the Korean population [13]. Therefore, we sought to elucidate the relationship between iodine intake as a dietary factor and MetS according to sex in euthyroid adult in Korea, an iodine-replete area.
Data from the KNHANES VI (2013–2015) were used in the present study. The KNHANES is a nationwide, cross-sectional survey conducted by the Korean Centers for Disease Control (KCDC) and Prevention to assess the health and nutritional status of the Korean population. The study participants were selected using stratified, multistage cluster sampling of the population and housing census data. Among them, approximately 2,400 individuals were selected for laboratory tests of serum thyroid-stimulating hormone (TSH), free thyroxine (fT4), anti-thyroid peroxidase antibody (TPOAb) and UIC using stratified subsampling according to sex and age in each year. We initially analyzed 6,561 participants whose data of thyroid function tests (TSH, fT4 and TPOAb) and UIC were available in KNHANES VI. Participants were excluded for the following reasons: under the age of 19, pregnant, absence of data (questionnaires about smoking, alcohol or exercise and history of diabetes, hypertension, dyslipidemia, thyroid disease, cancer, chronic kidney disease or liver cirrhosis); abnormal thyroid function; positive TPOAb; a history of thyroid disease; taking medication that could influence thyroid function; and a history of severe chronic disease, such as any type of cancer, chronic kidney disease or liver cirrhosis. Several participants met more than two criteria. A total of 4,277 participants were eligible for our study (Fig. 1).
Flow chart of the study population. KNHANES, Korean National Health and Nutrition Examination Survey.
All participants voluntarily participated in the survey and written informed consent was obtained from all individuals. All survey protocols were approved by the Institutional Review Board of the KCDC (approval numbers: 2013-07CON-03-4C, 2013-12EXP-03-5C, and 2015-01-02-6C).
DefinitionsAccording to the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III) [14], MetS was defined as the presence of three or more of the following five risk criteria: (1) abdominal obesity, waist circumference ≥90 cm in men and ≥80 cm in women according to the Asia-Pacific criteria [15]; (2) triglycerides levels ≥150 mg/dL; (3) high-density lipoprotein (HDL) cholesterol <40 mg/dL in men and <50 mg/dL in women; (4) BP ≥130/85 mmHg or undergoing treatment with antihypertensive medication; and (5) fasting glucose levels ≥100 mg/dL, glycated hemoglobin (HbA1c) ≥6.5% or currently on antidiabetic medication.
Euthyroidism was defined as serum TSH (reference range, 0.62–6.68 mIU/L) [16] and fT4 (reference range, 0.89–1.76 ng/dL) levels within the normal reference ranges.
The study participants were categorized into three groups according to iodine nutrition status based on the World Health Organization (WHO) recommendations and modifications [17, 18]: insufficient (<100 μg/L), adequate (100–299 μg/L), and excessive (≥300 μg/L) iodine intake.
Clinical and laboratory measurementsHealth-related behaviors, such as smoking, alcohol consumption and walking activity, were assessed using a self-reported questionnaire. Smoking status was categorized as current, former, or never smoker [19]. Alcohol consumption was classified as excessive (>21 drinks/week in men and >14 drinks/week in women) [20], moderate (≤21 drinks/week in men and ≤14 drinks/week in women), or never drinkers [21]. Walking activity was categorized active or inactive. Active was defined as walking for at least 5 days/week and at least 10 min/day [22]. Physical examination was performed by trained medical staff following standardized procedures. Using a tape measure (SECA 200, SECA GmbH, Hamburg, Germany), the waist circumference was measured to the nearest 0.1 cm in a horizontal plane at the level of the midpoint between the iliac crest and the costal margin at the end of expiration [23]. BP was measured on the right arm using a standard mercury sphygmomanometer (Baumanometer Desk Model 0320; WA Baum Co., Copiague, NY, USA) with the participants in a sitting position. All BP measurements were taken in triplicate, and the mean of the second and third measured values was used in the analyses [23].
Blood samples were processed and transported to the central certified laboratory, and analyzed within 24 h. Triglycerides, HDL cholesterol and fasting glucose levels were measured using a Hitachi Automatic Analyzer 7600-210 (Hitachi Ltd, Tokyo, Japan) [23]. HbA1c levels were measured using high-performance liquid chromatography with a Tosoh G8 analyzer (Tosoh Co., Tokyo, Japan). For thyroid function tests, approximately 15 mL of blood was collected from each participant. After separating of the serum within 30 min, the samples were sent to a central certified laboratory and analyzed. Serum TSH, fT4, and TPOAb levels were measured with an electrochemiluminescence immunoassay (Roche Diagnostics, Mannheim, Germany) [16]. Serum TSH levels were measured using an E-TSH kit (Roche Diagnostics). In this study, a reference TSH interval of 0.62–6.68 mIU/L was used as the reference range for the Korean population [16]. Serum fT4 levels were measured using an E-Free T4 kit (Roche Diagnostics), with a laboratory reference range of 0.89–1.76 ng/dL. TPOAb levels were measured with an E-Anti-TPO kit (Roche Diagnostics) with a reference range of <34.0 IU/mL [16]. UIC was measured by inductively coupled plasma mass spectrometry (ICP-MS) (PerkinElmer Inc, Waltham, MA, USA) using an iodine standard (Inorganic Venture, Christiansburg, VA, USA) [16].
Statistical analysisTo produce an unbiased national estimate, a sample weight was assigned for the participating individuals to represent the Korean population considering the stratified multistage probability sampling design of KNHANES VI. Due to a skewed distribution, a logarithmic transformation of TSH values was used in the analysis. Continuous variables are expressed as means (standard error) or medians (with their 25th and 75th percentiles). Categorical variables are expressed as weighted percentages (%). The differences in demographic and biochemical characteristics were evaluated using general linear model or chi-square test. Complex samples logistic regression analyses were used to estimate odds ratios (ORs) with their 95% confidence interval (CIs) for the risk of each MetS component and MetS itself. All p values and 95% CIs for ORs were corrected using the Bonferroni method due to multiple comparisons. Model 1 was age-adjusted. All ORs of Model 2 were adjusted for age, smoking, alcohol consumption, walking activity, TSH, fT4, and TPO Ab.
All statistical analyses were performed using SPSS Statistics version 26.0 (IBM Corp., Chicago, IL, USA). Analysis items with two-sided p value <0.05 were considered statistically significant.
The baseline clinical and biochemical characteristics of the 4,277 participants according to sex are summarized in Table 1. The prevalence rate of MetS in this cohort was 27.2% in men and 23.9% in women (p = 0.036). In both men and women, participants with MetS were older and had higher body mass indexes, waist circumferences, systolic and diastolic BPs, total cholesterol, triglycerides, fasting glucose, and HbA1c levels, but had lower HDL cholesterol and fT4 levels, than those without MetS. In men, participants with MetS were current smokers, excessive drinkers, and more likely to be inactive than those without MetS. Women participants with MetS did not consume alcohol, and there were no significant differences in the percentage of smoking and walking activity in women with or without MetS.
| Variables | Men (n = 2,291) | Women (n = 1,986) | ||||
|---|---|---|---|---|---|---|
| No MetS (n = 1,647, 72.8%) |
MetS (n = 644, 27.2%) |
p value | No MetS (n = 1,550, 76.1%) |
MetS (n = 436, 23.9%) |
p value | |
| Age (years) | 41.12 (0.37) | 48.83 (0.55) | <0.001 | 41.32 (0.41) | 56.09 (0.61) | <0.001 |
| Smoking (%) (current/former/never) |
40.2/31.8/28.0 | 43.7/38.2/18.1 | <0.001 | 5.7/5.4/88.9 | 6.6/5.0/88.4 | 0.774 |
| Alcohol consumption (%) (excessive/moderate/never) |
13.8/83.4/2.9 | 22.3/75.2/2.4 | <0.001 | 4.3/84.4/11.3 | 3.2/77.8/19.0 | 0.002 |
| Walking activity (%) (active/inactive) |
57.6/42.4 | 50.5/49.5 | 0.006 | 56.4/43.6 | 51.1/48.9 | 0.086 |
| BMI (kg/m2)a | 23.44 (0.08) | 26.82 (0.16) | <0.001 | 22.25 (0.09) | 26.33 (0.18) | <0.001 |
| <18.5 kg/m2 (%) | 3.1 | 0.1 | <0.001 | 8.5 | 0.0 | <0.001 |
| 18.5–24.9 kg/m2 (%) | 70.3 | 30.5 | 74.4 | 40.4 | ||
| 25–29.9 kg/m2 (%) | 24.8 | 54.4 | 15.6 | 44.1 | ||
| ≥30 kg/m2 (%) | 1.9 | 15.0 | 1.6 | 15.5 | ||
| Waist circumference (cm) | 81.79 (0.23) | 92.44 (0.38) | <0.001 | 74.74 (0.26) | 86.50 (0.46) | <0.001 |
| Systolic BP (mmHg) | 115.31 (0.43) | 126.84 (0.65) | <0.001 | 109.16 (0.43) | 127.26 (1.08) | <0.001 |
| Diastolic BP (mmHg) | 76.08 (0.27) | 83.15 (0.45) | <0.001 | 70.99 (0.26) | 78.52 (0.62) | <0.001 |
| Total cholesterol (mg/dL) | 186.19 (0.95) | 193.67 (1.68) | <0.001 | 186.83 (1.00) | 197.47 (2.19) | <0.001 |
| HDL cholesterol (mg/dL) | 50.36 (0.29) | 41.38 (0.42) | <0.001 | 57.71 (0.30) | 45.01 (0.56) | <0.001 |
| Triglycerides (mg/dL) | 125.95 (2.54) | 261.62 (8.85) | <0.001 | 88.08 (1.35) | 183.14 (6.69) | <0.001 |
| Fasting glucose (mg/dL) | 94.72 (0.41) | 113.77 (1.32) | <0.001 | 91.61 (0.44) | 110.42 (1.55) | <0.001 |
| HbA1c (%) | 5.58 (0.02) | 6.14 (0.05) | <0.001 | 5.52 (0.16) | 6.21 (0.06) | <0.001 |
| TSH (mIU/L) | 2.01 (0.02) | 1.93 (0.04) | 0.630 | 2.26 (0.04) | 2.26 (0.07) | 0.961 |
| fT4 (ng/dL) | 1.30 (0.01) | 1.24 (0.01) | <0.001 | 1.20 (0.00) | 1.17 (0.01) | 0.003 |
| UIC (μg/L)b | 274.5 (160.0, 601.3) |
256.6 (157.4, 584.8) |
0.238 | 277.0 (142.4, 642.0) |
250.4 (124.6, 575.7) |
0.022 |
| <100 μg/L (%) | 11.6 | 9.9 | 0.140 | 12.7 | 17.9 | 0.066 |
| 100–299 μg/L (%) | 40.5 | 45.7 | 39.9 | 36.4 | ||
| ≥300 μg/L (%) | 47.9 | 44.4 | 47.4 | 45.7 | ||
MetS, metabolic syndrome; BMI, body mass index; BP, blood pressure; HDL, high-density lipoprotein; HbA1c, glycated hemoglobin; TSH, thyroid-stimulating hormone; fT4, free thyroxine; UIC, urinary iodine concentration.
a BMI category according to the WHO classification: underweight (<18.5 kg/m2), normal weight (18.5–24.9 kg/m2), overweight (25–29.9 kg/m2), and obese (≥30 kg/m2); b UIC category according to the WHO classification and modification: insufficient (<100 μg/L), adequate (100–299 μg/L), and excessive (≥300 μg/L) iodine intakes.
Data are presented as means (standard error), medians (with their 25th and 75th percentiles) or weighted percentages as appropriate for the variable. Demographic and biochemical characteristics of the study population with respect to the metabolic syndrome were compared using general linear model for continuous variables and chi-square test for categorical variables.
Upon classifying all participants according to iodine nutrition status based on the WHO recommendations and modifications [17, 18], 41.9% men and 39.1% women had an adequate iodine intake. Approximately half of the participants (47.0% men and 47.0% women) belonged to the category of excessive iodine intake. The proportion of participants with insufficient iodine intake was 11.1% in men and 14.0% in women. In men, there was no statistically significant difference in the median UIC according to the presence or absence of MetS (256.6 vs. 274.5 μg/L, p = 0.238), but in women, participants with MetS had a lower median UIC than those without MetS (250.4 vs. 277.0 μg/L, p = 0.022). When we further subdivided the participants according to iodine nutrition status as shown Fig. 2A and Fig. 2B, men with MetS were more likely to be within the groups with adequate iodine intake than those without MetS, and women with MetS were more likely to be within the groups with insufficient iodine intake than those without MetS.
Distribution of participants with or without metabolic syndrome according to iodine nutrition status. (A) Men. (B) Women.
We further explored the prevalence and risk of each MetS component according to iodine nutrition status (Table 2). In men, there was significant difference in the prevalence of elevated triglycerides among the three iodine groups (p = 0.012), and participants with elevated triglycerides were more likely to be classified into the group with adequate iodine intake than in other groups. In the analysis of the risk for each MetS component, participants with excessive iodine intake had significantly lower risks of elevated triglycerides (OR 0.733, 95% CI 0.603–0.890, p = 0.010), as compared to those with adequate iodine intake.
| Variables | Men (n = 2,291) | Women (n = 1,986) | ||||||
|---|---|---|---|---|---|---|---|---|
| UIC <100 μg/L (n = 269, 11.1%) |
UIC 100–299 μg/L (n = 970, 41.9%) |
UIC ≥300 μg/L (n = 1,052, 47.0%) |
p value | UIC <100 μg/L (n = 276, 14.0%) |
UIC 100–299 μg/L (n = 788, 39.1%) |
UIC ≥300 μg/L (n = 922, 47.0%) |
p value | |
| Abdominal obesitya | ||||||||
| Prevalence (%) | 26.7 | 27.7 | 27.1 | 0.940 | 40.3 | 35.8 | 38.2 | 0.466 |
| OR (95% CI) | 0.947 (0.665–1.349) |
1.000 | 0.969 (0.771–1.218) |
1.209 (0.880–1.659) |
1.000 | 1.108 (0.870–1.412) |
||
| Elevated triglyceridesb | ||||||||
| Prevalence (%) | 36.2 | 42.0 | 34.7 | 0.012 | 23.2 | 18.3 | 20.6 | 0.364 |
| OR (95% CI) | 0.784 (0.557–1.104) |
1.000 | 0.733 (0.603–0.890)* |
1.344 (0.874–2.068) |
1.000 | 1.156 (0.850–1.570) |
||
| Low HDL cholesterolc | ||||||||
| Prevalence (%) | 21.7 | 25.7 | 21.6 | 0.155 | 40.7 | 36.4 | 36.3 | 0.484 |
| OR (95% CI) | 0.803 (0.540–1.193) |
1.000 | 0.799 (0.629–1.015) |
1.199 (0.872–1.649) |
1.000 | 0.996 (0.794–1.249) |
||
| Elevated BPd | ||||||||
| Prevalence (%) | 39.2 | 36.0 | 38.9 | 0.461 | 30.1 | 25.7 | 28.2 | 0.409 |
| OR (95% CI) | 1.144 (0.815–1.606) |
1.000 | 1.132 (0.932–1.374) |
1.247 (0.863–1.802) |
1.000 | 1.136 (0.887–1.454) |
||
| Elevated blood glucosee | ||||||||
| Prevalence (%) | 31.4 | 37.0 | 33.4 | 0.183 | 30.5 | 23.1 | 25.8 | 0.151 |
| OR (95% CI) | 0.782 (0.574–1.065) |
1.000 | 0.854 (0.689–1.059) |
1.519 (1.011–2.282)* |
1.000 | 1.158 (0.877–1.528) |
||
UIC, urinary iodine concentration; BP, blood pressure; HDL, high-density lipoprotein.
a Waist circumference ≥80 cm; b Triglycerides ≥150 mg/dL; c HDL cholesterol <40 mg/dL; d Blood pressure ≥130/85 mmHg or antihypertensive medication; e Fasting glucose ≥100 mg/dL, glycated hemoglobin (HbA1c) ≥6.5% or antidiabetic medication.
Data are expressed as weighted percentages. Prevalence of metabolic syndrome components according to the urinary iodine concentration was compared using chi-square test. OR and 95% CI for risk of metabolic syndrome components were estimated using complex samples logistic regression. All p values and 95% CI for OR were corrected by Bonferroni method due to multiple testing.
* p < 0.05.
Women participants with each MetS component were more likely to be classified into the group with insufficient iodine intake than in other UIC groups, but there were no significant differences in the prevalence of each MetS component among the three groups. In the analysis of the risk of each MetS component, participants with insufficient iodine intake had significantly greater risks of elevated blood glucose (OR 1.519, 95% CI 1.011–2.282, p = 0.044), as compared to those with adequate iodine intake.
There were no significant differences among the groups with respect to the following components: abdominal obesity, low HDL cholesterol levels, elevated BP, and elevated blood glucose in men, and abdominal obesity, elevated triglycerides, low HDL cholesterol levels, and elevated BP in women.
Risk of metabolic syndrome according to urinary iodine concentrationThe proportions of participants with MetS based on the UIC were 24.2, 29.6, and 25.7%, respectively, in men and 30.7, 22.3, and 23.2%, respectively, in women among those with insufficient, adequate, and excessive iodine intake, respectively (Table 3).
| Men (n = 2,291) | Women (n = 1,986) | |||||
|---|---|---|---|---|---|---|
| UIC <100 μg/L (n = 269, 11.1%) |
UIC 100–299 μg/L (n = 970, 41.9%) |
UIC ≥300 μg/L (n = 1,052, 47.0%) |
UIC <100 μg/L (n = 276, 14.0%) |
UIC 100–299 μg/L (n = 788, 39.1%) |
UIC ≥300 μg/L (n = 922, 47.0%) |
|
| MetS (%) | 24.2 | 29.6 | 25.7 | 30.7 | 22.3 | 23.2 |
| Unadjusted | 0.757 (0.472–1.213) |
1.000 | 0.820 (0.633–1.063) |
1.548 (1.042–2.300)* |
1.000 | 1.056 (0.799–1.394) |
| Model 1a | 0.724 (0.448–1.172) |
1.000 | 0.799 (0.614–1.039) |
1.529 (1.022–2.288)* |
1.000 | 0.992 (0.740–1.331) |
| Model 2b | 0.725 (0.450–1.168) |
1.000 | 0.794 (0.608–1.036) |
1.544 (1.031–2.311)* |
1.000 | 1.001 (0.745–1.344) |
UIC, urinary iodine concentration; MetS, metabolic syndrome.
a Model 1, adjusted for age; b Model 2, adjusted for age, smoking, alcohol consumption, walking activity, thyroid-stimulating hormone, free thyroxine and thyroid-peroxidase antibody.
Data are presented as weighted percentages. OR and 95% CI for risk of metabolic syndrome were estimated using complex samples logistic regression. All p values and 95% CI for OR were corrected by Bonferroni method due to multiple testing.
* p < 0.05.
We performed logistic regression analyses of the risk of MetS among participants, using the group with adequate iodine intake as the reference category (Table 3). In women, UIC was found to be an independent predictor of MetS. Women with insufficient iodine intake had a significantly greater risk of MetS than those with adequate iodine intake (OR 1.548, 95% CI 1.042–2.300, p = 0.031). Additional adjustments were made for confounding variables such as age, smoking, alcohol consumption, walking activity, TSH, fT4 and TPOAb. Insufficient iodine intake was a significant risk factor for MetS in women even after such adjustments (OR 1.544, 95% CI 1.031–2.311, p = 0.035). However, there was no association between iodine intake and risk of MetS in men.
In the present cross-sectional study of 4,277 euthyroid adult based on data from the KNHANES VI, we found that insufficient iodine intake (UIC <100 μg/L) was associated with unfavorable profiles of MetS components of blood glucose in women and excessive iodine intake (UIC ≥300 μg/L) was associated with favorable profiles of MetS components of triglycerides in men. Moreover, in women, UIC independently predicted MetS, and insufficient iodine intake was associated with an increased probability of MetS after adjusting for age, smoking, alcohol consumption, walking activity, TSH, fT4 and TPOAb. However, there was no association between iodine intake and risk of MetS in men.
Korea is an iodine-replete area, and the population here consumes iodine-rich food, such as seaweed [24]. According to a report on the nationwide iodine nutrition status of Korea, the median UIC in the general population was 293.9 μg/L [25]. Similarly, the median UIC among euthyroid adult in the present study was 270.6 μg/L in men and 272.3 μg/L in women. In this study, the prevalence of MetS in adults with normal thyroid function was 27.2% for men and 23.9% for women, showing a statistically significant difference according to sex as reported in the previous study [4]. The effect of iodine intake on the risk of MetS was found to be sex-specific, and insufficient iodine intake (UIC <100 μg/L) was shown to be associated with the risk of MetS only in women. We observed that insufficient iodine intake was associated with an increased probability of MetS in women, compared to adequate iodine intake (UIC 100–299 μg/L). However, there was no association between iodine intake and risk of MetS in men. The relation between sex, iodine intake as a dietary factor, and MetS is not clearly explained. A recent study showed that sex differences could influence the association between dietary patterns and MetS risk factors in Korean population [13]. Another research reported that alcohol consumption as a part of dietary pattern was identified as a major risk factors for MetS components, such as elevated triglycerides, elevated BP and high blood glucose in Korean adult men [26].
Few studies have evaluated the association between iodine intake and MetS. Recently, Jin et al. [5] demonstrated a relationship between iodine intake and MetS and its components with U-shaped curves. The authors showed that there was an association between UIC and MetS components among persons with iodine insufficiency (UIC <100 μg/L) and excess (UIC ≥500 μg/L) [5]. The inconsistencies between the results obtained in our study and those of Jin et al. [5] are likely due to regional differences in iodine intake and different cut-off values of iodine nutrition status as well as ethnic and sex differences in the participants included in the analyses.
Recent cross-sectional studies using the NHANES data reported that low UIC was associated with an increased risk of dyslipidemia [6] and coronary artery disease [7]. In a randomized controlled trial conducted on overweight or obese women with iodine insufficiency, iodine supplementation was found to reduce the risk of dyslipidemia [8]. In adolescents with iodine insufficiency and euthyroid goiter, iodine treatment resulted in a decreased lipid levels [27]. Similarly, we also observed that women participants with elevated triglycerides or low HDL cholesterol were more likely to be classified into the group with a UIC <100 μg/L rather than other UIC groups. However, there were no significant differences among the groups with respect to elevated triglycerides or low HDL cholesterol levels. On the other hand, in men, the prevalence of elevated triglycerides was higher in the group with adequate iodine intake (UIC 100–299 μg/L) compared to other groups, and the risk of elevated triglycerides was significantly lower in the group with excessive iodine intake (UIC ≥300 μg/L). Our additional analyses (Supplementary Table 1 and Supplementary Table 2) showed that the proportion of excessive drinkers was relatively low in excessive iodine intake group (UIC ≥300 μg/L) than in other groups (p = 0.023), and excessive drinking was associated with an increased risk of MetS (OR 1.927, 95% CI 1.004–3.699, p = 0.049). Although it has not been established with certainty, these findings are believed to be due to the effect of excessive alcohol on food intake in Korean men [26, 28, 29]. Also, though it is difficult to define optimal iodine intake in Korean population which chronically consumes iodine-rich foods [30], excessive iodine intake to a certain extent may have the effect of lowering triglycerides. Animal experiments have suggested that insufficient iodine intake is associated with the risks of dyslipidemia, atherosclerosis and coronary artery disease [31-33]. Particularly, iodine insufficiency was shown to be associated with increased levels of triglycerides and low-density lipoprotein cholesterol in mice [31]. In a study conducted on rabbits, aortic atherosclerosis was prevented by iodine supplementation [32]. Furthermore, iodine infusion reduced the occurrence of cardiac reperfusion injury in a murine model of acute myocardial infarction [33]. The exact mechanisms underlying the association between iodine intake and dyslipidemia remain unclear. The anti-inflammatory and anti-proliferative activities of iodine may have a protective effect against dyslipidemia. Further research is required in the future to elucidate these mechanism.
In relation to BP, UIC was negatively correlated with systolic BP, and iodine insufficiency was more prevalent among hypertensive participants [9]. Empirical evidence from clinical studies has demonstrated the beneficial effects of iodine in participants with cardiovascular disease and high BP [34]. The role of iodine in anti-inflammation, vasodilatation and reducing blood viscosity has been suggested as an important mechanism for BP control and overall cardiovascular health [34]. In the present study, women participants with insufficient iodine intake (UIC <100 μg/L) were more likely to have elevated BP than other groups, but there was no statistically significant difference in both men and women.
A recent investigation of patients with diabetes showed that UIC was negatively correlated with triglycerides, fasting glucose and insulin levels [10]. In addition, the UIC was markedly decreased in patients with diabetes compared to that in healthy control participants [10]. Mild iodine insufficiency (UIC 100–150 μg/L) in pregnant women is associated with an elevated risk of gestational diabetes [35]. Dietary supplementation of goats with iodine was found to reduce glucose levels and improve insulin sensitivity [36]. Similar to the results of previous studies, a relationship between insufficient iodine intake (UIC <100 μg/L) and elevated glucose levels was demonstrated in women participants in our study.
This evidence suggests that an association between iodine intake and MetS is biologically plausible. Oxidative stress, also referred to as reactive oxygen species-antioxidant imbalance, is thought to play a major role in the pathogenesis of MetS components [37]. Glucose and fatty acid overload lead to oxidative stress in multiple organs and tissues, including beta cells [38]. It has been reported that iodine can reduce damage caused by free oxygen radicals by acting as an electron donor in the presence of hydrogen peroxide, peroxidase and some polyunsaturated fatty acids [39]. A previous study showed that 15 μM of sodium iodide had the same level of antioxidant activity as 50 μM of ascorbic acid [40]. The antioxidant role of iodine in oxidative stress could, thus, explain the association between UIC and MetS in the present study.
Our study had several strengths. The present study included a nationally representative sample of the KNHANES, which allowed us to generalize the findings to the Korean population. We were able to control for the potentially confounding effects of risk factors for MetS, including smoking, alcohol consumption, physical activity, thyroid dysfunction and additional comorbid conditions, in examining the relationship between UIC and MetS. However, owing to its cross-sectional nature, our study has several limitations. We could not determine a causal relationship between iodine intake and MetS. In addition, although UIC in this study was measured by ICP-MS, which has been demonstrated to be extremely accurate in measuring urine iodine [41], repeated measurement of spot-urine iodine samples could have been more reliable. A single measurement of UIC could be subject to time-dependent variation in the measurement according to diet and urine volume. Additional prospective, high-quality randomized controlled trials are needed to further clarify the link between iodine intake and MetS.
In conclusion, insufficient iodine intake was associated with an increased risk of MetS in euthyroid adult women. The relationship between iodine intake as a dietary pattern and MetS, with respect to sex differences was revealed. Further research into the potential mechanisms underlying the relationship between iodine intake and metabolic profiles may provide additional insights into the etiology of MetS and potentially important modifiable risk factors for MetS prevention.
The authors thank the Korea National Health and Nutrition Examination Survey for providing public access to its data. This study was supported by Soonchunhyang University Research Fund.
The authors declare no conflict of interest.
