Introduction
Iodine is an essential micronutrient, primarily obtained from the diet, indispensable to thyroid hormone production and key for the metabolism regulation of mammals [
1]. Both, low and high iodine intake can lead to thyroid dysfunction [
2]. In children, the adverse effects of its deficiency include intellectual impairments and growth retardation, while in adults it has been linked to goiter, increased risk of thyroid cancer and clinical manifestations of hypothyroidism, such as reduced metabolic rate, cold intolerance, weight gain, puffy face, edema, hoarse voice and mental sluggishness. Excessive iodine intake, on the other hand, can also induce thyroid dysfunction resulting in both hyper- and hypothyroidism, increased risk of cancer and thyroid autoimmunity [
3].
Iodine deficiency disorder (IDD) is still an ongoing worldwide recognized problem, with over two billion individuals having inadequate iodine intake [
2]. Although often seen as a problem in developing countries, IDD has re-emerged in the industrialized world, including regions previously iodine sufficient [
3]. Despite the global effort to tackle the problem, recently a high number of European countries (44%) have been reported as iodine deficient, and updated data regarding the status of iodine in different populations remains insufficient [
4,
5].
In Portugal, studies reported that the median urinary iodine concentration (UIC) is generally adequate in school-aged children [
5‐
7]. Nevertheless, iodine inadequacy was found in pregnant women more than a decade ago [
8], and although a recent supplementation approach was implemented, iodine adequacy has not yet been achieved [
5,
9]. Unfortunately, the current iodine status of the broad Portuguese population is not available.
Since about 90% of ingested iodine is excreted in the urine, the median UIC is recognized as a good biomarker of short-term iodine status in groups [
10]. According to the World Health Organization (WHO) criteria, iodine nutrition status in school-age children and non-pregnant adults is insufficient when median UIC is below 100 μg/L, adequate when between 100 and 199 μg/L (and < 20% of the population with UIC ≤ 50 μg/L), more than adequate when between 200 and 300 μg/L, and excessive when higher than 300 μg/L [
1].
The main sources of iodine in the human diet are marine foodstuffs—fish, shellfish, algae and sea salt. Water, milk, vegetables and processed foods, such as bread and margarine, are also potential iodine sources [
2]. The WHO recommends a daily iodine intake of 90 μg for children 0–5 years, 120 μg for children 6–12 years, 150 μg for adolescents and adults, and 250 μg for pregnant and lactating women [
10].
Universal salt iodization is preconized by the WHO, the United Nations Children's Fund (UNICEF) and the Iodine Global Network (IGN) as a safe, cost-effective and sustainable way to tackle IDD [
1]. Worldwide, 88.7% of the population uses iodized salt, even though there is no data concerning the current situation in most European countries [
11]. Portugal lacks a mandatory salt iodization policy, with iodization being optional for household and industry salt since 1996 [
12]. Due to the IDD challenges and the lack of a regulatory framework, the use of fortified salt in Portuguese school canteens has been recommended since 2013 [
6,
13]. Presently, additional concern arose in the vein of the WHO recommendation to reduce salt intake to 5 g of per day, to prevent hypertension and cardiovascular disease [
14], and the potential impact of this policy on the iodine nutritional status.
Therefore, the aim of this study was to evaluate the iodine nutritional status of the public University of Porto staff, as a proxy for the Portuguese adult working population. Additionally, it was intended to demonstrate the potential of occupational health appointments in the education and monitoring of the iodine subject.
Discussion
To the best of our knowledge, this is the first study on the iodine status of Portuguese working adults, using gold standard methodology.
Based on previous epidemiological studies performed in school-aged children [
5‐
7,
11], Portugal could be classified as iodine sufficient. However, even though school-aged children are a priority target group and logistically the ideal population to study, they are not representative of the overall population, because differences in diet and metabolism are expected between subpopulations [
5]. To what the broad Portuguese population is concerned, no recent data concerning the iodine status are available [
5].
With a median 24-h UIC of 66 μg/L, 30% of the population showing 24-h UIC below 50 μg/L, and a daily iodine intake of 112 μg/day, this study revealed that the adult working population had a mild iodine deficiency according to the WHO guidelines for iodine status (median UIC < 100 μg/L plus > 20% of the population with a UIC ≤ 50 μg/L), and the EFSA iodine intake threshold of 150 μg/L. In the literature is argued that the extrapolation from the observed correlation between increasing goiter and a UIE < 100 µg/day to a spot sample UIC below 100 µg/L, as indicative of ID, may have been applicable in children but was not correct for adults [
11]. When the urine volume is higher, approximately 1.5 L/day, the UIC in spot samples is usually about 60–65% of the amount excreted in 24 h. In this study, the median 24-h UIE was 94 µg/day, below the threshold value identified in the correlation between UIE and goiter. Unlike other studies, here all the biomarkers and methodologies used to assess the iodine nutritional status agreed on the same classification. Moreover, the median 24-h UIC revealed the same trend reported in adults in other European countries, such as Finland (96 μg/L, [
25]), Germany (65 μg/L, [
26]), Italy (66 μg/L, [
27]), and Norway (88 μg/L, [
28]). Indeed, the EUthyroid project corroborated our results, demonstrating that in European countries iodine status is generally adequate in school-aged children, but iodine deficiency may still be present in adults and pregnant women [
5]. Also, one possible explanation for the 18% lower iodine intake observed in women in our study may result from higher food consumption by men, including discretionary salt. This iodine intake pattern in what sex is concerned was also noticed in other European studies [
27‐
29].
From a public health perspective, the mild iodine deficiency found in this study reinforces the need to implement supplementation strategies for the whole, but especially for women of childbearing age to meet the increased needs in a future pregnancy and secure a normal development of the fetus. Indeed, iodine inadequacy was found in Portuguese pregnant women more than a decade ago [
8], leading to guidelines from the Directorate-General for Health (no. 011/2013), for supplementation in preconception, pregnancy, and breastfeeding. Currently, there is a lack of knowledge concerning the efficiency of the policy implementation. The most recent studies available indicated that the minimum median UIC threshold for iodine adequacy in pregnant women is yet to be achieved [
5,
9].
Despite the lower value displayed by the 24-h recall approach, both methodologies applied to estimate the daily iodine intake correlated well. The discrepancy found could be explained by incomplete information on iodine content in foods in the national databases and the self-reported 24-h recall. The 24-h dietary recall indicated that 56.7% of the total iodine intake comes from ingested food. Although the intestinal absorption of ingested iodine is considered to be high (more than 90%), the iodine concentration in water and foods is highly variable [
23]. In the present study, the most relevant food sources were dairy, cereals, fruit, and legumes. Milk and dairy are recognized as good sources of iodine, and several studies [e.g.,
30‐
32] reported higher iodine intake in populations with higher consumption levels, including in Portuguese pregnant women [
9]. Indeed, iodine content in Portuguese milk and yogurt has been estimated to average 200 and 180 μg/L, respectively [
33]. Despite several factors being associated with the iodine concentration in milk, such as farm management, feeding, or seasonality [
34,
35], and in accordance with the value found in our study (55%), milk and dairy contribution was reported to be 13–64% of the daily iodine requirement [
36].
Cereals, fruit, vegetables, and legumes are generally poor iodine sources, and the levels present depend on the amount of iodine in the soil where the plants are grown. Worldwide, 30% of the population lives in areas with iodine-deficient soil [
37], with an average global content of 2.6 mg/kg [
38]. The iodine concentration in food crops can be as low as 10 μg/kg [
39]. In recent years, to tackle IDD, the biofortification of crops and agricultural soil have been explored [
40‐
44]. The contribution of cereals found in this study can be justified by the consumption of bread and the salt associated with its production. Despite decreasing in recent years, the consumption of bread in the Portuguese population is around 45 kg per year [
45], with efforts to reduce the salt content from 10–21 to 11 g/kg in 2021 [
46]. Taking the average bread consumption, the aimed value for salt in its production, and the average iodine content in salt found in this study, bread alone can represent a daily iodine intake of nearly 18 µg (12.2% of the daily requirement). Strategies of using iodized salt in bread production have been successfully applied to increase iodine intake adequacy elsewhere [
47,
48]. The contribution to the daily iodine intake of fruits, vegetables, and legumes observed in this study is in line with the previously reported iodine content of Portuguese foods [
18] and already demonstrated in the literature [
49,
50]. An additional problem concerning iodine deficiency is the presence of goitrogens in some popular crops, such as broccoli, cabbage, cauliflower, sweet potato, or soy, with the consequent association of higher consumption to lower iodine status [
51,
52].
The contribution of the discretionary salt to the daily iodine intake was 43% (52 μg), estimated by the difference between the total daily intake (mean 121 μg/day based on UIE), and the iodine amount provided by food (mean 69 μg/L based on the 24-h dietary recall). In the IMC Salt study, the average salt intake at baseline was 8 g/day [
15], of which about 3.3 g per day was discretionary salt (41% [
53]). Taking into account the average iodine concentration found in the studied household salt (14 mg I/kg), the discretionary salt accounted for 47 µg of the daily iodine intake (38%). To note that, when the contribution of discretionary salt is added to the contribution of ingested food based on the 24-h dietary recall, the gap between approaches applied is minimum (121 μg/day based on UIE, and 116 μg/day based on the 24-h dietary recall plus discretionary salt contribution). Thus, the discretionary salt contribution and the daily iodine intake determined by the two data sets collected in this study seem to agree well, conferring reliability and robustness to the results. Also, the mean iodine content in household salt was similar to the reported in a previous study concerning commercially available salt in the same area (13.8 mg I/kg, [
20]. Moreover, this percentage of discretionary salt contribution to the daily iodine intake is in line with the values reported for other studies in European countries, such as Italy and Germany [
54,
55].
Considering the sodium-healthy diet, as preconized by WHO [
56], which recommends the consumption of up to 5 g of salt per day, the iodine intake from salt would be around 56 µg/day, 23 µg of which was from discretionary salt. Taking the contribution of food estimated in this study, the daily iodine intake would be 92 µg, far from the recommended 150 µg. Even taking the estimated 11 g/day average salt intake by Portuguese adults described in the literature [
57], retaining the highest percentage of discretionary salt use reported (25–50%, [
19,
58]), and assuming no loss during cooking, the iodine intake (144 µg/day) would not be sufficient to meet the guidelines.
The iodization of the salt used in households is the primary strategy to prevent iodine deficiency at a population level [
1]. In Portugal, most salt used at the household level and in the food industry is of marine origin (sea salt). In the country, the iodine fortification of salt is not mandatory, with the consumption being limited, in the range of 2–8.8% [
6,
59], owing to the higher sales price compared to non-iodized sea salt. However, the non-mandatory iodine fortification Portuguese law established a salt fortification range between 19 and 27 mg I/kg in the iodide form [
12].
If an iodoprophylaxis was followed, with the fortification of the household and food industry salt, and retaining the average contribution of iodine from food estimated in this study, the daily iodine intake would be 168–199 µg in a sodium-healthy diet, already accounting for the inevitable 20% lost during cooking [
1]. In this scenario, the population would be iodine sufficient according to the WHO and EFSA threshold for iodine intake. Moreover, since the mean concentration of iodine in Portuguese marine salt is already close to the WHO-recommended iodine threshold of 15 mg I/kg [
60], the associated production costs of fortification would be smaller.
Study strengths and limitations
The iodine intake was estimated simultaneously from both the 24-h urinary iodine excretion and a detailed 24-h dietary recall for each participant. Although cumbersome, the 24-h urinary iodine excretion is considered the best biomarker to assess and monitor the recent iodine intake of a given population [
61]. Also, the concurrent creatinine content analysis allowed the exclusion of incomplete urine collections, making the results more robust. The use of the 24-h dietary recall enabled the estimation of the amount of iodine derived from food as well as the indirect contribution of discretionary salt. Moreover, the iodine direct quantification in household salt was also important to understand the current role of salt in iodine intake and the potential impact of the consumption reduction. Additionally, since most iodine comes from food, the comparison between methodologies allowed us to understand if the approaches were interchangeable. A major strength of this study was to demonstrate the potential of the mandatory occupational health appointments in the education and monitoring of the iodine subject, increasing the quality of life, and consequent productivity of the working population and associated households.
A major limitation of the study was the relatively small sample size. The data collection was performed during the COVID-19 pandemic, and despite the efforts made to solve the inherent implications, it was impossible to achieve the sample size initially estimated [
16]. Moreover, the study population was not nationally representative, since participants were primarily recruited among the university staff, mainly from coastal urban areas, with a high level of education, and included fewer smokers than the general population. Regional divergence, with proximity to the coastal zone and rural areas associated with the iodine status, has been reported, including in Portugal [
6,
7,
62,
63]. Also, participants with a higher level of education were more likely to have better socio-economic status and therefore be more prone to a healthy diet. Although being a controversial topic, several studies linked IDD with lower socio-economic status and the associated access to iodine-rich foods [e.g.,
64‐
66]. Another limitation can be the use of a single 24-h urine collection, since it is known that several collections are required to reduce the day-to-day variation and estimate the iodine intake accurately [
67]. Also, the 24-h dietary recall data are self-reported, and the daily iodine intake estimation relies on iodine content in foods found in traditionally incomplete national databases, which can lead to under- or overestimation of iodine intake. Finally, the lack of direct information about the amount of discretionary salt or the use of iodized salt in the household of the participants limited the understanding of the salt contribution to the daily iodine intake.