Iodine status in the Nordic countries – past and present

REVIEW ARTICLE Iodine status in the Nordic countries  past and present Helena Filipsson Nystro ¨m 1,2 *, Anne Lise Brantsæter 3 , Iris Erlund 4 , Ingibjo ¨rg Gunnarsdottir 5 , Lena Hulthe´n 6 , Peter Laurberg 7,8 , Irene Mattisson 9 , Lone Banke Rasmussen 10 , Suvi Virtanen 4,11 and Helle Margrete Meltzer 3 1 Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 2 Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden; 3 Norwegian Institute of Public Health, Oslo, Norway; 4 National Institute for Health and Welfare, Helsinki, Finland; 5 Unit for Nutrition Research, University of Iceland and Landspitali National University Hospital, Reykjavik, Iceland; 6 Department of Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 7 Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark; 8 Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; 9 National Food Agency, Uppsala, Sweden; 10 Department of Endocrinology, Bispebjerg University Hospital, Copenhagen, Denmark; 11 School of Health Sciences, University of Tampere, Finland Abstract Background: Adequate iodine nutrition is dependent on ground water content, seafood, and, as many countries use iodized cow fodder, dairy products. In most countries, salt fortification programs are needed to assure adequate iodine intake. Objectives: The objectives are threefold: 1) to describe the past and present iodine situation in the Nordic countries, 2) to identify important gaps of knowledge, and 3) to highlight differences among the Nordic countries’ iodine biomonitoring and fortification policies. Design: Historical data are compared with the current situation. The Nordic countries’ strategies to achieve recommended intake and urine iodine levels and their respective success rates are evaluated. Results: In the past, the iodine situation ranged from excellent in Iceland to widespread goiter and cretinism in large areas of Sweden. The situation was less severe in Norway and Finland. According to a 1960 World Health Organization (WHO) report, there were then no observations of iodine deficiency in Denmark. In Sweden and Finland, the fortification of table salt was introduced 5075 years ago, and in Norway and Finland, the fortification of cow fodder starting in the 1950s helped improve the population’s iodine status due to the high intake of milk. In Denmark, iodine has been added to household salt and salt in bread for the past 15 years. The Nordic countries differ with regard to regulations and degree of governmental involvement. There are indications that pregnant and lactating women, the two most vulnerable groups, are mildly deficient in iodine in several of the Nordic countries. Conclusion: The Nordic countries employ different strategies to attain adequate iodine nutrition. The situation is not optimal and is in need of re-evaluation. Iodine researchers, Nordic national food administrations, and Nordic governmental institutions would benefit from collaboration to attain a broader approach and guarantee good iodine health for all. Keywords: iodine;goiter;history;thyroid;fortification;Iceland;Norway;Sweden;Denmark;Finland Received: 18 April 2016; Revised: 8 May 2016; Accepted: 9 May 2016; Published: 8 June 2016 Adequate iodine intake is necessary for the normal production of the thyroid hormones tetraiodothyronine (T4) and triiodothyronine (T3). In 1952, the World Health Organization (WHO) stated that in order to assure normal thyroid metabolism, the average adult iodine intake should be 150 mg/day. Low iodine intake may result in hypothyroidism and goiter (1). Pregnant and lactating women have greater need of iodine and the recommended dose is 175250 mg iodine/day to target a median urinary iodine concentration (UIC) of 150249 mg/L during pregnancy and 100 mg/L during lactation (25). Thyroid hormones are especially important during fetal life and early years for the development of the brain (2, 6, 7). Severe iodine deficiency (ID) in pregnancy may result in physical and mental retardation  cretinism (8, 9). Studies also indicate that moderate to research food & nutrition æ Food & Nutrition Research 2016. #2016 Helena Filipsson Nystro ¨m et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material for any purpose, even commercially, provided the original work is properly cited and states its license. 1 Citation: Food & Nutrition Research 2016, 60: 31969 - http://dx.doi.org/10.3402/fnr.v60.31969 (page number not for citation purpose) mild ID may impact neuropsychological development in school-aged children and impair growth and motor function (10, 11). A longitudinal study in the United Kingdom showed that inadequate maternal iodine status, assessed by means of UIC in early pregnancy, was associated with lower verbal IQ in their 8-year-old children (12). In a similar study in Australia, mild ID in pregnancy was associated with lower educational outcomes in children at age 9 years (13). These studies indicate that moderate to mild ID may have a long-term, adverse impact on fetal neurodevelopment, but convincing evidence is lacking. Yet, these findings, as well as reports that suboptimal iodine intake is found in countries that have for decades been considered iodine-sufficient, have raised concerns that ID is overlooked as a public health concern in developed countries, including the Nordic countries (1419). The balance between too little and too much iodine The daily iodine intake is mostly a sum of the population’s dietary habits of fish and other seafood, dairy products (if the cow fodder is iodized), the water iodine content, and the current iodine fortification programs. The single most important iodine issue globally is avoiding ID and the resulting deleterious consequences for fetal and child brain development. When a population is living under conditions of mild ID, the thyroid maintains normal hormone production, but compensation mechanisms result in goiter and a higher frequency of hyperthyroidism with autonomous areas in a toxic multinodular goiter (TMNG) with secondary health consequences (2, 20, 21). When iodine intake levels are changed over time, this affects the incidence and prevalence of thyroid diseases. When a population goes from moderate or mild ID to normal iodine levels, the incidence of TMNG decreases and more young people develop Graves’ disease (GD), as iodine sufficiency results in an increased incidence of autoimmune thyroid disease. The increased incidence of GD is probably temporary and the incidence of autoimmune hypothyroidism rises in line with iodine level increments (22). High iodine intake can generate both hypothyroidism and hyperthyroidism. Iodine prophylaxis is therefore a complex issue that must be handled with care and detail. Socioand health economic consequences of iodine deficiency The access to iodine varies in different parts of the world because of different levels of iodine in ground water (23) and soils. The use of fish and other seafood (24) and of iodine-rich dairy products (25) varies and so does the degree of iodized salt use. In many areas with iodine-poor soils far from the sea, ID continues to be a significant health issue (26). Goiter is the obvious and visible manifestation of ID, but severe health and socioeconomic consequences are also apparent through other expressions of ID: cretinism, neurological disability, mental retardation, hypothyroidism, and TMNG. Therefore, the term iodine deficiency disorders (IDD) was introduced in 1983 (27). There is an association between goiter prevalence and the number of cretins born. When the goiter prevalence is 3040%, few cretins are born, but if it increases to 7080%, 10% of all children born are cretins. On a continuum of consequences for mental development, cretinism is the most severe form. The prevalence of mental retardation in ID areas may exceed the prevalence of cretinism by 10 times (27), making combatting IDD the most cost-effective measure. Iodine prophylaxis From Chinese and Hindu writings, we know that the use of seaweed to combat goiter has been known for thousands of years and was still in use at the beginning of the 19th century; after iodine was found in seaweed in 1811 by Courtois, the first prophylactic attempts began in the 1820s. Iodine prophylaxis was established in 1921 after Marine and Kimball’s classical experiment in which they treated schoolgirls in the United States (US) with iodine, leading to a dramatic reduction in the prevalence of goiter. After some debate, iodine prophylaxis was introduced in Switzerland in 1922. In 19231924, iodine fortification of table salt and tap water was tried in several communities in the Great Lakes region in the US. Over the following decades, goiter prophylaxis programs were introduced worldwide (27). In 1986, the International Council for Control of Iodine Deficiency Disorders (ICCIDD) was founded (27). In 2014, the ICCIDD became the Iodine Global Network (IGN). The IGN has initiated and improved many iodine prophylaxis programs. The IGN also sets up monitoring guidelines and encourages national and subcontinental reporting. The iodization of salt is the most commonly used tool for iodine prophylaxis, but the amount of iodine added to table salt varies from country to country (27). In developing countries, the use of iodized oil has been proven a safe and easy form of administering iodine to the population (28). Mandatory iodine prophylaxis programs are more likely to deliver a sustained source and, in turn, a public health benefit (29). The importance of political decisions and continuous surveillance must, however, be emphasized, all the more so due to factors such as migration and changes in food consumption over time. The objectives of this article are 1) to describe past and present iodine status in the five Nordic countries, 2) to identify important gaps of knowledge, and 3) to highlight differences between the Nordic countries’ iodine fortification policies that need to be adapted to ensure adequate iodine status in the general population and in groups at risk of ID. Helena Filipsson Nystro ¨m et al. 2 (page number not for citation purpose) Citation: Food & Nutrition Research 2016, 60: 31969 - http://dx.doi.org/10.3402/fnr.v60.31969 Present investigation The five Nordic countries Geological and climatic conditions of importance for intake levels There is a cycle of iodine in nature. Most iodine resides in the world’s oceans. Large amounts of iodine were leached from surface soil by glaciations, snow, and rain and carried by rivers and floods into the sea. Therefore, many mountainous areas, but also lowlands far from the oceans, are depleted of iodine (30). During the last Ice Age, the Nordic countries, Iceland, Norway, Denmark, Sweden, and Finland, were covered with ice. Iceland is located in the sea on the transatlantic rift with continuous volcanic activity. Norway and Sweden are on the same peninsula, with mountain areas in Norway and the northwestern parts of Sweden. The south of Sweden is lowland and was partly covered by the sea when the ice receded. Finland and Denmark are separated from the peninsula by the Baltic Sea and have no mountain areas; Denmark and parts of Finland were seabed long ago. After the last Ice Age, approximately 14,000 years ago, Denmark was the first of today’s Nordic countries to be populated. People later migrated across the narrow sound to southern Sweden and over the North Sea to southern Norway. During the Viking age, in the ninth and tenth centuries AD, Norwegians (and Irish) inhabited Iceland. Icelandic, Danish, Norwegian, and Swedish people share a common genetic heritage, while Finland was populated from the east, a heritage that is evident today through the Finnish language, which is quite different from that of the other Nordic countries. However, Finland’s major genetic influence is from Europe. The Swedish influence in Finland has been significant, both genetically and culturally. Geographical and climatic conditions favored animal herding; in addition, the gene for lactase was preserved over multiple generations. Milk and dairy products thus became staple foods in all the Nordic countries. Coastal areas had more favorable conditions and were therefore more densely populated; inland or mountain areas were more sparsely populated. Fish intake was high in coastal areas and areas to which fish was transported, but in inland areas, saltwater fish, which has higher iodine content, was rarely consumed. The five Nordic neighbors employ different strategies to ensure adequate iodine intake (Table 1). Iceland Iceland has been known for its population’s good iodine status. In 1939, Sigurjonsson reported findings that the thyroid gland in the Icelandic population was smaller than was generally accepted in other countries at the time (31). This was attributed to the uniquely high consumption of fish, on average 200 g/day (32), but also to high iodine levels in haddock and cod, the most commonly consumed species (33, 34). Dairy products are another important source of iodine for the Icelandic people (3236), as dairy products have high iodine content because fish meal is used in cow fodder (37). In 1939, the average milk intake was 1 liter/person/day, resulting in an iodine contribution from fish and dairy products of 570 mg iodine/person/ day (32). In 19781979, the average iodine intake in Iceland was estimated to be 336 mg/person/day. In a follow-up study, urinary iodine excretion (UIE) was 395 mg/day in men and 270 mg/day in women (38). In 1990, the Icelandic Nutrition Council reported an average iodine intake of 299 mg/person/day (32). In that survey, for the first time, a subgroup that was potentially at risk of ID was identified: young women with a low intake of fish and dairy products and with an iodine intake in the range of 86130 mg/ day (32). In many countries, iodized salt is the primary source of iodine because the intake of fish and seafood is low, but in Iceland, iodized salt is not commonly used and the iodine content in water is low (ISGEM the Icelandic Food Composition www1.matis.is/ISGEM/details1.aspx? FAEDA0290 030116) (Table 1). Also, combined with a decline in the intake of products containing iodine, the iodine content in milk has almost halved since 1962 (38, 39). This is attributable to the reduced use of fishmeal in cow fodder. More iodine is now added to cow fodder, and the added iodine contributes more to the total iodine content of milk today. The fish meal content of cow fodder varies between 4.4 and 19.4% (40). Young women and their risk of ID were further highlighted in the Public Health Institute of Iceland’s survey in 2002. The fish intake in this group had decreased to 40 g/day and milk consumption had also declined. In a 1990 survey, young women only obtained two-thirds of the recommended iodine intake from their diet (32). Similar trends have been observed in children and adolescents (41), also in the last national survey from year 20102011 (36). Hence, the diet of young Icelanders has come to more closely resemble the diet of the other Nordic countries. Iceland exemplifies the fragility of iodine sufficiency at the national level and that there is a need to carefully monitor trends in iodine status. It is especially important to monitor women of child-bearing age to secure healthy brain development in their children. Norway Prior to 1950, there were several areas where goiter was endemic in Norway. In 1917, Dr Carl Schiøtz described his findings of goiter among 10,000 schoolchildren in the inland district of Hedmark (42) (Fig. 1). At the age of 14, the prevalence was 24% among girls and 10% among boys (Fig. 2). He gave a detailed account of cretins. Iodine in the Nordic countries Citation: Food & Nutrition Research 2016, 60: 31969 - http://dx.doi.org/10.3402/fnr.v60.31969 3 (page number not for citation purpose) Table 1. Comparisons of the Nordic countries regarding geological conditions, iodine levels in water, and historical data on iodine intake levels Iceland Norway Denmark Sweden Finland Covered by ice during Ice Age Yes Yes Yes Yes Yes Marine sediments No No Yes South Eastern parts Southern parts Water iodine level (median) 0.12 mg/L B2mg/L 12.298.3 mg/L (mean) 3.7 mg/L Dug wells: 2.12 (range B0.2761) mean 10.7926.8 mg (L Drilled wells 3.04 (range B0.2232) mean 6.78935.1 mg(L Iodine status before iodination Sufficient Severe to moderately deficient Moderate to mildly deficient Severely deficient Moderately deficient Degree of sea fish intake during 19001950 High High in the coastline low in the inland High in the coastline low in the inland High in the coastline low in the inland High in the coastline low in the inland Fortification of cow fodder historically (starting point) Fish meal used in cow fodder voluntary Mandatory from 1950, level: 2mg/g salt. Voluntary Voluntary Voluntary Start of iodination to the population Late 1930s 2000 1936 1946 Type of iodination Table salt for household use only Household salt and salt for commercial bread production Table salt Household salt and cow fodder Level of iodine added 5 mg/g salt 13 mg/g salt 50 mg/g salt 25 mg/g salt Type of legislation Voluntary Mandatory Voluntary Voluntary Monitoring by authorities No No Yes No Some Actual cow milk iodine concentration (mg/L) 2006: 85283 (average 145) Before year 2000: 150 20002012: 100150 20122015: 190 2015: 200 2001: 160 2009: 117 2015: 150 Mean amount of fish by adults (gram per day per person) National dietary survey in 20102011: fish and seafood 46 National dietary survey in 2011: fish and seafood: 67 fish: 52 National dietary survey 20112013: 37 National diet survey 20102011 fish and shellfish, women 37, men 43 National diet survey 2012 40 Major source for iodine in the population Fish Milk Milk and salt Salt Milk Iodine sufficiency in the adult general population Yes Yes/Mild ID (depending on milk intake) Mild ID Yes Mild ID The ongoing iodization program, regulations, and monitoring and the current iodine sources and iodine status in the normal population are also presented. Helena Filipsson Nystro ¨m et al. 4 (page number not for citation purpose) Citation: Food & Nutrition Research 2016, 60: 31969 - http://dx.doi.org/10.3402/fnr.v60.31969 The well-known goiter district of Modum was extensively studied in 19341935 (43) (Fig. 1). The prevalence of goiter was very high, especially among school children in the community (80%). Also, the prevalence of goiter was higher among subjects who did not consume fish than among those who ate fish (43). From 1950 onwards, the iodine fortification of cow fodder became mandatory (2 mg/g) to improve livestock reproductive performance (44), a measure that resulted in a dramatic increase in iodine concentrations in milk and dairy products in Norway. Interestingly, this was paralleled in the United Kingdom (45). In the reinvestigation of school children in Modum in 1977, the goiter rate was found to have dropped to 1.5% and goiter was no longer considered a problem among Norwegian children (46). The sufficient iodine intake was attributed to the high iodine content of milk, but also to the fact that saltwater fish was more widely consumed in the 1970s (46). Studies carried out in men from 10 locations sampled in 19711972 (47, 48) and in 1985 pointed at satisfactory UIE; the dietary intake of iodine of Norwegians was suggested to be 150250 mg iodine/person/day (44). Based on these publications, Norwegian health authorities have since 1950s considered Norwegians to be iodine-replete (Table 1). The only study carried out so far which has calculated the iodine intake in a representative group of Norwegians was conducted in 1997, the NORKOST 2 study (49). The mean dietary intake of iodine was within the recommended dose for men (176 mg/day), while in women the intake was slightly below the recommended dose (136 mg/ day). Only 7% of the adult population had a daily intake of iodine below the lowest recommended intake level of 70 mg iodine/day, which is a threshold for normal thyroid function. None exceeded 1,000 mg/day. However, vitamins and/or mineral supplements were not included in the estimations in this study. Currently, the largest study of iodine intake in the world is the Norwegian Mother and Child Cohort Study (MoBa) (19, 50). Iodine intake from food and supplements was estimated using a food frequency questionnaire and validated by means of comparison with 24-h UIE in a subsample of 119 participants (19, 51). Of 61,904 women, 16% had an iodine intake B100 mg/day, 54% had iodine intake below the Nordic recommendation of 175 mg/day, and only 22% reached the WHO/ UNICEF/ICCIDD recommendation of 250 mg/day. The insufficient iodine intake levels shown in pregnant women have set alarm bells ringing at the Norwegian Directorate of Health, and an Iodine Committee is now trying to assess the situation and has been commissioned to present proposals for the alleviation of ID in vulnerable groups. In Norway, the fortification of salt with iodine is voluntary and very few brands contain iodine. The permitted level is 5 mg iodine/g salt, which is too low to impact the iodine intake of those who use this salt. The food industry is not allowed to use iodine-fortified salt in Norway. The amount of iodine in drinking water is influenced by geological conditions. In samples from 12 different sites, the average water iodine content was found to be 1.7 mg/L in 2002. Samples from coastal cities had higher concentrations than samples from inland towns (range 0.6 mg/L (Rjukan) to 5.5 mg/L (Stavanger) (Table 1). An increasing number of Norwegians take dietary supplements, and today many multivitamin-mineral supplements Sweden Denmark Norway Finland Modum The Swedish Goitre belt Hedmark Fig. 1. Map of the Nordic countries (except Iceland) in 1960 (55). Dark gray represents mountain areas and striped areas are goiter regions. Sweden still has large areas of goiter 24 years after the start of the iodization program and the salt iodine content was increased in 1966. Goitrous areas are also seen in Norway and Finland. (Children with academic parents) (Farmers not owing their own land) Fig. 2. Social factors that influenced the goiter frequency in Norway. This is a handwritten note by Carl Schiøtz, who investigated the prevalence of goiter in the Norwegian inland county Hedmark in 1914. In the figure, he indicates the prevalence according to social class: the lowest prevalence was among children of academics, the highest prevalence among farmers not owning their own land (a cotter) (English translation in brackets). Iodine in the Nordic countries Citation: Food & Nutrition Research 2016, 60: 31969 - http://dx.doi.org/10.3402/fnr.v60.31969 5 (page number not for citation purpose) contain iodine. In the MoBa Study, 32% of the pregnant women took iodine-containing supplements which on average contributed 100 mg iodine/day to these women’s diet (19). Hence, in Norway, the iodine fortification of cow fodder had unintended positive effects on the human population. Milk, in combination with the intake of other dairy products, has made this food category the major source of iodine in the Norwegian diet (49, 52) However, the consumption of milk, yoghurt, and lean fish has declined over the past decades in some groups and explains why suboptimal iodine intake is becoming more prevalent in Norway (19, 51). Denmark Cretinism may develop when iodine intake is B25 mg/day, and goiter may appear when iodine intake is B100 mg/day. Endemic goiter is defined as either goiter found in 10% of the adult population or found in 5% among school children (53). In Denmark, neither cretinism nor endemic goiter has been reported in the population. Small local studies in the 1920s subsequently reported an incidence of goiter of 15%, but high goiter frequency was not confirmed in a national study of 350,101 Danish school children performed in 19721973 (54). In 1960, Denmark was among the few countries reporting no endemic goiter (55) and was not, until recently, considered to be an ID area. However, when the focus shifted from school children to other population groups, the consequences of ID became apparent. First, the incidence rate of TMNG was high with clinical and subclinical hyperthyroidism particularly common in the elderly (22). Second, by the end of their pregnancies, pregnant women did not have sufficient iodine levels (56). In 1969, the population in Denmark had UIE levels of 64 mg/person/day, with variations within the country (57). Lower UIE was detected in Jutland, with 50 mg/person/day than in Zealand with 70100 mg/person/ day (58). Also, in a national Danish dietary survey from 1985, the average intake was calculated to be 114 mg iodine/day (59), which was below the level of 150 mg/day recommended by the WHO. Available data in Denmark suggested that the iodine situation had been stable for 35 years until the Ministry of Health in Denmark decided to initiate a nationwide iodization program in 1997 (53). Before the iodization program, 27.8% of the population was taking multivitamins containing iodine (53). Iodized salt had been on the Danish market for a long time (kelp salt tablets containing 1020 mg iodine/g salt) and, in the 1970s, at least three table salts containing iodine were supplied to the market (iodine content 1040 mg/g), but they only covered a few per cent points of the market. Also, from 1974 until June 1998, the sale of iodized salt and other iodized products was illegal in Denmark, similar to the ban on other fortified food products with no proven health benefits. Before the iodization of salt began, a monitoring program, the Danish Investigation of Iodine Intake and Thyroid Diseases (DanThyr), was initiated. The aim was to investigate iodine intake, the prevalence of goiter, and the incidence of thyroid diseases in Aalborg, with moderate ID, and Copenhagen, with mild ID. The main reason for the difference in iodine status in these cities was differences in the water iodine content (60, 61). In Copenhagen, the iodine concentration in tap water is 19 mg/L, and in Aalborg, it is 5 mg/L (61). In general, western Denmark has lower water iodine concentrations than those in eastern Denmark (Table 1). The intake of milk represented 44% of the total iodine intake; the intake of fish accounted for 15% of the iodine intake in the Danish population (62). The most prominent determinants for high iodine intake were the use of multivitamins containing iodine, eating at least 200 g fish/week, and having a milk intake of more than 0.5 liter/day (62). The results showed that individuals in Aalborg did not reach the recommended intake levels even if they followed the advice regarding intake of fish and milk. This finding highlighted that dietary changes could not redress the ID problems in Denmark and that an iodization program was needed (62). First, the Danish Veterinary and Food Administration introduced a voluntary program of universal salt iodization. As this turned out to be ineffective, it was replaced in 20002001 by a mandatory program of iodine fortification of household salt and salt in bread produced in Denmark (13 mg iodine/g salt) (21) (Table 1). Even though the iodine program was cautious and increased the iodine intake with 50 mg/day, the DanThyr monitoring program has observed effects on prevalence of goiter, nodules, and thyroid dysfunctionality. The incidence of overt hypothyroidism increased more in those areas that had previously had mild ID than in areas with moderate ID; there was a 53% higher incidence of spontaneous (presumably autoimmune) hypothyroidism. On the other hand, in previously moderate ID areas, there were initially 49% more cases of overt hyperthyroidism; however, this proved a temporary phenomenon, and the incidence of hyperthyroidism is now considerably below the periodization level. One phenomenon under surveillance is whether GD is becoming more common in young people (21, 63). Denmark has demonstrated that small changes in iodine intake can have dramatic effects on the spectra of thyroid diseases. In the last DanThyr monitoring study in 20082010, the UIC levels were again found to have decreased (64). The exact reason for this is unknown; there was no reduction in the use of multivitamin supplements containing iodine, fish intake, fluid intake, egg consumption, Helena Filipsson Nystro ¨m et al. 6 (page number not for citation purpose) Citation: Food & Nutrition Research 2016, 60: 31969 - http://dx.doi.org/10.3402/fnr.v60.31969 or milk intake; however, the content of iodine in milk had decreased. Sweden In Sweden, goiter was first described by Carl von Linne´in 17461747 (65) (Fig. 3) and by the end of the 19th century, goiter was observed among 2030% of the children in Ga ¨strikland and Dalarna counties (66). Twenty years later, the prevalence of goiter had increased to 6065% in these areas (6770). A national investigation was undertaken in 1929 that confirmed endemic goiter and cretinism in Dalarna, Ga ¨strikland, mid-Norrland, and in Sma˚land (25, 71, 72) (Fig. 1), areas at a distance from the western seas’ salty winds (25) and thus far from the principal product contributing to iodine intake: herring. As herring was transported to the larger cities (73, 74), urban populations and those living along the roads were well supported (75). During the 19th century, several factors contributed to a higher frequency of goiter. 1) The introduction of potatoes to the popular diet not only saved many from starvation but also led to a less iodine-rich diet. 2) The herring disappeared for long periods. 3) The rise in population meant that new areas were being cultivated, areas that were less fertile compared with the land that had once been the seabed. The areas with a high incidence of goiter were known as the goiter belt (Fig. 1), inside of which, the ground water iodine content may have been lower than in outside areas (unpublished observation). The iodization of table salt was introduced in Sweden in 1936. Initially, 10 mg iodine was added per gram of salt (76), but in 1966 the amount was increased to 50 mg iodine per gram of salt (77), as goiter continued to be prevalent in some areas (7881) (Table 1). Today, WHO considers the Swedish population to be iodine-sufficient because the population has been subject to almost lifelong iodization (26, 82, 83). Smaller studies support this assumption (79, 84, 85), and it was confirmed in a national study in 20062007, in which 889 Swedish school children aged 612 years from 30 schools participated (73, 74). Median UIC was 125 mg/L with a low proportion of children with UIC B100 mg/L and 200 mg/l, indicating an optimal intake of iodine (73). Also, the old goiter belt had disappeared (74). Hypoand hyperthyroidism are the most widespread forms of thyroid diseases in Sweden. Autoimmune hypothyroidism is common, but the incidence of hyperthyroidism in Sweden is lower than the ranges indicated in international reports. Seventy-five percent of patients Struma glanulae thyroideae Glandula thyroidea kallas den körtel som sier där halsen begynner, och är alld större på barn än på stort folk, då denna blir Obstruerad, blir det en struma, som kalas Broncocele eller struma …….Dea är det wi kalla Sweitzerhalsar, och är allmänt i Sweitz, hwilket kommer af deras wan, som rinner ut för ällarne, och har någon besynnerlig sten art u sig, den wi icke ha oss bekant som förordsakar denna sjukdomen. Det är så allmänt i Sweitz ha tjocka halsar, a de le åt dem som ha smal hals. Icke kommer det av kalkkwanet som somlige mena, ty då skulle den vara på Gotland. Ej heller av kritwanet; ty då borde den wara gångbar i Paris, icke heller endast av kalla wanet, då skulle wåra Lappar ha den mer, än någon annan naon. Utan där måste ges någon stenart i wanet, som wi ännu icke weta hwad det är för slag. Woro en stor sak om någon som kommer dit kunde utransaka hwad det är för en sten som wanet håller. Sjukdomen är utom Sweitz ganska rar, och ser den sällan hos oss. …. Linneaus har dock se honom på e frunmmer här i Swerike, som druckit nog wan. Sweitzarne har många symppaemaner här emot. Bland andra , a de skola gå bort och låta konungen i Frankrike ta på sig. Man observerar noga, a om de ha en sådan struma, och dricka mycket hetsiga drycker, så kan där bli kräfwetan utav. Struma glanulae thyroideae Glandula thyroidea is the gland called that is located where the neck begins, and it is always larger in children than in larger people, when this is congested it will be a goiter, called Broncocele or goiter ???. This is what we call “Sweitzer necks”, and is common in Switzerland, that is derived from their water, drained from the mountains, and have something peculiar in it, that we do not know and that causes this disease. It is so frequent in Switzerland to have thick necks, that they smile at those with thin necks. It is not derived from calcium in the water as some says, as they would have it in Gotland. Not either from water with chalk as it would be common in Paris. Neither from the cold water, as it would be frequent among our same than in any other naon. It has to be some kind of stone in the water, even though we do not know what it is, It would be a large issue if somebody could invesgate what kind of stone that is in the water. Outside Switzerland the disease is rare and is seldom seen among us. Linneaus has however seen him in a women in Sweden that has probably been drinking water. The Suisse people may have opinions against. Among other, they shall let the king in France take it on. It is carefully observed that if they have such goiter and drink a lot of strong beverages, a cancer can be developed. Fig. 3. Goiter as it was first described in Sweden; lecture notes by Per Osbeck that attended one of Carl von Linne´’s classes, 17461747’s copy from the Hagstro ¨mer Library; Stockholm, Sweden. Iodine in the Nordic countries Citation: Food & Nutrition Research 2016, 60: 31969 - http://dx.doi.org/10.3402/fnr.v60.31969 7 (page number not for citation purpose) with hyperthyroidism had GD and the intensity of the disease decreased by age (86, 87). Sweden is a country in which severe ID avoidance relies heavily on an adequate iodization program which, in turn, requires a satisfactory long-term monitoring strategy. However, the milk iodine concentration has decreased lately (88) and salt consumption is switching from iodized salt to salt with no added iodine, highlighting the need for future monitoring, especially of vulnerable groups. Finland The first known observations of goiter in Finland were made 180 years ago in some communities in the eastern parts of the country (89). In 1928, Adlercreutz reported that the water iodine content was low in Finland. The levels were lower in eastern Finland than in the west, and there was an inverse association between goiter and water iodine content (90). In 1938, Finland was classified as a country with endemic goiter, with most of the disease burden being found in eastern Finland (91) (Fig. 1). In reports from 19281929, the goiter frequency in school children from some areas was 1015%, but in 19531954, it was 3040% in others. The mean incidence in all elementary Finnish school children was, however, 4.4%. As late as in the 1950s, the entire country was moderately iodine-deficient, also now with endemic goiter being observed mainly in eastern Finland. However, there was considerable discussion about whether other goitrogenic factors might have additional effects on the ID population in the east, as iodine intake levels were not, in fact, very different. The goitrogenic effects of 5-vinyl-2-thiooxazoliodone (VTO, goitrin), a thionamid that blocks the intrathyroidal hormonal synthesis in milk, was much discussed (27). No distinct consensus was reached, but goitrogenic plants were eradicated from the pastures. Iodized salt was available as early as 1949, but the use of salt with iodine was very low and the iodine content in salt was insufficient. Only 20% (or 15 mg) of the iodine intake came from iodized salt (89, 92). The first attempts to interest the medical authorities in an iodine prophylaxis program were made in the 1930s and 1940s but was met with little response. In the late 1950s, a voluntary salt iodization program was initiated. In response to the initiative of A.I. Virtanen, the State Commission of Nutrition agreed with Finnish packing and importing firms that only import of salt containing 25 mg KI/g would be permitted. The use of iodized salt steadily increased and, in 1969, it was used in 75% of households, reaching 95% of households in 1979. However, the overall use of salt has decreased (89) and, in the 1980s, the fortification of table salt represented only one-third of the total iodine intake, while the intake of dairy products provided two-thirds of the Finns’ iodine intake, thanks to the active iodization of livestock fodder (92). In areas with endemic goiter, domestic animals also suffered from goiter and ID. After the decision to iodize table salt and cow fodder in Finland in the 1950s (Table 1), milk production increased (27), along with an increase of the iodine content in milk, from 30 mg/L in 1950 to 180 mg/L in the 1970s (89, 93, 94). Dairy products became the main iodine source (50%) as early as the 1950s. In the 1980s, when the iodine intake in Finland was 300 mg/d, 60 mg was derived from table salt and 200 mg from dairy products and eggs (27, 93). In the 1980s, the iodine intake in Finland was the highest in Europe (89) and, in 1986, it was stated that the use of iodized salt was no longer necessary because of the very active iodization strategy in household animals (89). After the iodine prophylaxis program in humans and animals, the frequency of goiter declined. In 19651966, the mean prevalence was 0.25% and in the areas that had previously had the highest prevalence, it was 0.7% (89). Over the course of 1520 years, the proportion of TMNG among patients with hyperthyroidism decreased from 80 to 10% (95) and, in the mid-1980s, GD dominated (89). For decades, Finland had a very effective iodization strategy, which rested heavily on the iodine content in dairy products and iodized salt, and on unchanged consumption patterns. In the last decade or so, iodine levels have decreased in the general population to the extent that it has resulted in mild ID (96). Similarly, a decrease in milk and iodized salt consumption is noted. Therefore, a working group was initiated with representatives from the Ministry of Health and Social Affairs, the Ministry of Agriculture, the Finnish Food and Drink Industries’ Federation, the National Institute for Health and Welfare, and the National Nutrition Council to do the necessary groundwork for new iodine recommendations and find practical new solutions that could be implemented especially by the food industry and mass catering services. A new recommendation was launched by the National Nutrition Council in 2015 (96). Finland is an example of a country with a very effective iodization strategy that relied heavily on the iodine content of dairy products and on unchanged consumption patterns. Iodine status in populations at risk of ID in the Nordic countries Pregnant women As already mentioned, in Iceland, fish and milk intake has recently decreased among younger women (32). It is well known that the intake of fish and dairy products is linked to iodine status (2527), but the recommendation to the population to consume fish at least twice a week and at least two portions of dairy products daily is based on concern for bone health and cardiovascular risk (21); iodine status was not an issue when the advice was issued. However, this recommendation also serves to promote Helena Filipsson Nystro ¨m et al. 8 (page number not for citation purpose) Citation: Food & Nutrition Research 2016, 60: 31969 - http://dx.doi.org/10.3402/fnr.v60.31969 adequate iodine intake. In Iceland, pregnant women in the second and third trimesters had UIC 180 mg/L (97), which is within the levels recommended during pregnancy by the WHO (Table 2). However, also the women that consumed fish and dairy products below the recommended levels had sufficient UIC levels at 160 mg/L, even if this value may be questioned because of the small size of the sample (97). Half of the women in this investigation took multivitamins, possibly containing iodine during pregnancy. Multivitamins with or without iodine can be bought, but giving information about iodine is not prioritized by health care workers at the Icelandic maternal health centers. As already mentioned, a large percentage of the pregnant women in the Norwegian MoBa study had insufficient iodine intake, and only 21.7% reached the WHO/UNICEF/ICCIDD iodine intake recommendation of 250 mg/day (19, 51). The use of supplements containing iodine was reported by 31.6% of mothers-to-be (Table 2). The primary source of iodine from food was dairy products, contributing 67% of daily iodine intake in non-supplement and 43% in iodine-supplement users. The median intake of iodine from food was 141 mg/day and the additional contribution from supplements in iodinesupplement users was 107 mg/day. Dietary behaviors associated with the risk of low and suboptimal iodine intake were no use of iodine-containing supplements and low intake of milk/yoghurt, seafood, and eggs (19). After the introduction of an iodine fortification program, the situation for Danish women has improved, but mild to moderate ID continues among pregnant women, especially for the women who are among the 12.7% that do not take multivitamin tablets also containing iodine (98) (Table 2). In Sweden, no specific attention is given to the iodine question during pre-natal care, as the pregnant population in Sweden has appeared to be iodine-sufficient (99, 100). However, recently concerns have arisen regarding the truth of these assumptions, due to the following trends in Swedish society, which are 1) changes in food consumption patterns tending to a lower dairy product intake; 2) reduced iodine content in dairy products (88, 101); 3) a rise in the use of non-iodized salts, such as flake and gourmet salt; 4) low use of iodized salt in processed foods, promoting a lower iodine intake in the population; and 5) the salt reduction program launched by the National Food Agency (NFA) to lower the incidence of hypertension. This will affect pregnant and lactating women in particular. Retrospective local data have recently been published from Uppsala and Karlstad showing a median UIC of 99 mg/L in the third trimester in 469 women (102), further underlining these assumptions. Young women in Sweden have an intake of fish of 30 g/day, milk 230 g/day, and cheese 25 g/day (103); this may not be enough to cover the increased need of iodine. Hence, ID in pregnancy in Sweden may be imminent and there is an urgent need for monitoring studies to enable decision-making on future strategies to ensure adequate iodine nutrition (Table 2). In Finland, there are no data on women during pregnancy, but studies are ongoing (Table 2). Lactation There is a large knowledge gap regarding the iodine situation for mothers and children during lactation in most Nordic countries (Table 2). The only country with available data is Denmark. Here, the use of multivitamins containing iodine during the lactation period drops to almost half compared to the use of such supplements during pregnancy, falling from 83 to 47%. Regardless of whether women take supplements containing iodine or not, Danish women do not attain the WHO target levels during breastfeeding (104). The situation is further aggravated for smokers, as smoking halves the milk iodine Table 2. Comparison of risk populations in the Nordic countries according to available data Success in risk groups Iceland Norway Denmark Sweden Finland Pregnant women Sufficient Mild ID Mild ID Mild ID Unknown To be analyzed Percentage of pregnant women using iodine-containing multivitamins Unknown 32% 87% Unknown To be analyzed Unknown Lactating women Unknown Unknown Mild ID Unknown To be analyzed Unknown To be analyzed Percentage of lactating women using iodine-containing multivitamins Unknown Unknown 47% Unknown Unknown Children B1 year To be analyzed Unknown Unknown Unknown To be analyzed Adolescents Sufficient To be analyzed Unknown Unknown study planned Unknown This table also illustrates the lack of data (unknown) in several areas in all the countries, but also that several ongoing studies will address some of the lack of knowledge (to be analyzed). The situation during pregnancy is unsatisfactory and none of the countries are aware of an optimal situation during lactation. Data are lacking in small children, and Iceland is the only country with known sufficient levels in adolescents. IDiodine deficiency. Iodine in the Nordic countries Citation: Food & Nutrition Research 2016, 60: 31969 - http://dx.doi.org/10.3402/fnr.v60.31969 9 (page number not for citation purpose)