Introduction
Iodine is essential for thyroid hormone production [
1]. Suboptimal iodine status is a public health concern worldwide, and despite efforts to increase the dietary iodine intake, Europe is still the continent with the highest prevalence of iodine deficiency [
2]. This is a particular concern for women that are pregnant and/or at childbearing age [
3‐
7].
Dietary sources of iodine are limited. Hence, to cope with iodine insufficiency, iodized salt programmes are recommended [
4,
8]. Such programmes have a high impact globally, but several European countries have not followed this strategy. The impact of iodized salt in Norway is limited as the amount of iodine in the iodized salt is low (5 mg iodine/kg salt), and the food industry is not allowed to use iodized salt. However, the cow feed has been fortified with iodine since the 1950s. Thus, milk and dairy products are the major sources of iodine in Norway [
9,
10], and contributes with about 55% of the iodine intake [
11]. Seawater fish and seafood are the food items where iodine is occurring at the highest concentrations [
10,
12]. Although the concentration of iodine is higher in seafood than milk and dairy products there is lack of associations between intake of seafood and adequate UIC in Danish and Icelandic populations [
13,
14]. However, a direct effect of increased intake of lean-seafood on UIC has to our knowledge been demonstrated in one intervention study [
15]. Unlike iodized salt, intake of lean-seafood will also provide other components. Lean-seafood contains undesirable substances such as Hg [
16], but also essential nutrients, such as selenium (Se), B vitamins, trace elements and some long chain n-3 polyunsaturated fatty acids [
17]. Additionally, lean fish also provide high quality marine proteins and taurine [
18].
UIC in spot urine samples is the recommended method to assess iodine status by World Health Organization (WHO), United Nations children’s fund (UNICEF) and Iodine Global Network (IGN). Importantly, however, UIC reflects the last 24 h of iodine intake. Hence, even if seafood is consumed 2–3 times a week as recommended, associations between seafood intake and UIC would necessarily be more difficult to reveal than associations with intake of items often consumed on a daily basis, such as milk and dairy. Thus, as lean-seafood is rarely consumed daily and UIC reflects the last day of iodine intake, the contribution of seafood for maintenance of sufficient iodine status may be underestimated in population-based studies.
To document the effect of lean-seafood on iodine status, we measured iodine in urine collected from participants in an intervention study, with a crossover design where lean-seafood was consumed every day and intake of milk and dairy were restricted. As lean-seafood also is the main contributor of dietary arsenic (As) and represents an important source for Se, we concurrently measured plasma levels of Se and As, as well as urinary As.
Discussion
Lean-seafood has the highest natural iodine content, but evidence of a direct impact of increased intake of lean-seafood on UIC is limited. We therefore aimed to measure UIC after intervention with lean-seafood and non-seafood in an intervention study with crossover design. The participant’s UIC was below the recommended median at baseline, but after 4 weeks of the lean-seafood intervention median UIC was above 100 µg/L.
The present investigation demonstrated that a 28 day lean-seafood intervention increased median UIC by 65 µg/L, whereas the UIC was unchanged after the non-seafood intervention. Lean-seafood is a well-known source of iodine, but to our knowledge, this is the second intervention study directly demonstrating an effect of intake of lean-seafood on UIC. In a Norwegian 14 day semi-controlled study by Molin et al. [
15], 38 participants were randomized into four groups for daily portions of 150 g cod, salmon, blue mussels or potato (control). The participants in the cod and blue mussel groups increased significantly their UIC from median 80–220 µg/L and 85–155 µg/L, respectively, compared to the control group with unchanged UIC from pre- to post-intervention (95 µg/L). Increases in UIC have also been demonstrated with cow milk [
27], seaweed [
28], and supplements [
29]. Given the high iodine levels in lean-seafood, our result was expected. Further, the historically good iodine status in the Icelandic population has, at least in part, been attributed to a high intake of fish [
30,
31]. Still, although seafood is suggested to contribute to iodine status, UIC has been associated with intake of milk and dairy, and not seafood, in population-based studies from for example Iceland [
32], Norway [
33,
34], and Italy [
35]. Additional, in a Danish crossover study including a random sample of inhabitants living in Alborg and Copenhagen, estimated 24 h UIC increased with increased seafood intake in participants living in Alborg, but not in Copenhagen, whereas increased milk intake was associated with increased UIC in both cities. However, even though the intake of seafood was above 75 g/d in the group of Alborg participants who consumed most, the UIC was inadequate (median 71 µg/L), and adequate UIC was detected only in those living in Copenhagen who consumed more than two glasses of milk daily [
14]. Unlike seafood, with a recommended intake of 2–3 times a week, milk and dairy are often consumed daily. As UIC reflects intake of iodine the last 24 h, associations between seafood and UIC may be more difficult to detect, and therefore the overall contribution of seafood to iodine status may be underestimated.
At baseline, the median UIC was below 100 µg/L and hence, iodine status in the participants comprising 20 healthy adult Norwegians may be considered suboptimal. The number of participants is small, but our finding that about 70% of the participants had UIC below 100 µg/L at study start corroborate the suggestion that iodine deficiency or sub-optimal iodine status is a re-emerging condition in Norway. For instance, recent studies have reported median UIC of 68 µg/L [
3] and 85 µg/L [
36] in pregnant women, and 75 µg/L in non-pregnant Norwegian women [
37]. In addition, a small Norwegian cross-sectional study detected inadequate UIC and iodine intake in elderly (62 µg/L), pregnant women (84 µg/L), non-pregnant women of childbearing age (71 µg/L), and in vegans (46 µg/L) [
38]. Due to introduction of iodine fortification of cow fodder in the 1950s and traditionally high intake of milk and dairy with subsequent high iodine concentrations, health authorities used to consider Norwegians to be iodine-replete [
39]. The possible re-emergence of sub-optimal iodine levels in Norway may be linked to the recorded declining intake of both milk, dairy and seafood [
40].
Concomitant with increased UIC after the lean-seafood intervention, we also observed increased urinary As levels and increased fasting plasma As and Se levels, similar to the findings by Molin et al. [
15]. These results were expected, as lean-seafood will also provide other essential nutrients, such as Se, as well as undesirable substances. Seafood consumption is a predictor of elevated urinary As in several population studies and may be used as a biomarker [
41]. Seafood and cereals appear to be the most important contributor to adequate blood Se in adolescent Icelandic girls [
42]. The relatively high content of As and other heavy metals, such as mercury (Hg), may be of concern. However, in lean-seafood the major As form is the arsenobetaine, considered to be non-toxic [
43]. Several risk benefit evaluations of seafood have concluded that the beneficial effects of the essential nutrients in seafood outweighs potential harmful effects of undesirable substances, including mercury [
44‐
46]. In this respect, the content of Se may be of particular importance. First, low Se intake is reported in several countries [
47], and lean finfish species are good dietary sources for Se [
16,
48]. Second, Se is also known to antagonize the toxic effects of heavy metals, including Hg [
49], and a molar ratio of Se: Hg above 1.0 is suggested to provide protection against MeHg toxicity in humans [
50].
The strengths of this study include the crossover design and the balanced diets and accurate recordings of the seafood intake. The UIC measured in spot urine samples is the recommended method [
4], but it reflects recent dietary intake and there is debated whether this is the best estimate of measuring iodine status. Thus, it is a strength that the participants consumed lean-seafood daily. Milk and dairy are major sources for iodine. Importantly, only very small amounts of dairy products were included in the non-seafood diet and all participants were instructed to not drink milk during any of the interventions.
This study has some limitations. The diets with 60% of dietary proteins from lean-seafood or non-seafood sources does not reflect a normal dietary protein intake for most people and the generalizability of our findings are thus limited. The comprehensive design limited the number of subjects willing to participate and led to a rather high drop-out (26%). This was, however, accounted for in the power analysis. The power calculation was, however, not based on UIC as the primary endpoint, but on cardiovascular lipid risk markers. Further, only Caucasians were included.
We conclude that 4 weeks of the lean-seafood intervention increased UIC from sub-optimal levels to adequate levels above 100 µg/L. Iodized salt programmes have had a high impact globally, but several European countries have not followed this strategy and a sub-optimal iodine level is evident among subpopulations in Europe. Unlike iodized salt, iodine rich food items, such as lean-seafood will provide essential nutrients and undesirable substances, such as Se and As.