Iodine excretion has decreased in Denmark between 2004 and 2010--the importance of iodine content in milk.

Fortification with the essential trace element iodine is widespread worldwide. In the present study, results on iodine excretion and intake of iodine-rich foods from a cross-sectional study carried out in 2004-5, 4 to 5 years after the implementation of mandatory iodine fortification, were compared with data in a study carried out in 2008-10. The 2008-10 study was a follow-up of a cross-sectional study carried out before iodine fortification was implemented. Participants in the cross-sectional studies were randomly selected. Both studies were carried out in the cities of Aalborg and Copenhagen in Denmark. The median urinary iodine concentration decreased in women from 97 µg/l (n 2862) to 78 µg/l (n 2041) (P< 0.001). The decrease persisted after adjustment for age, city and education, and if expressed as estimated 24 h iodine excretion. The prevalence of users of iodine containing dietary supplements increased from 29.4 to 37.3 % (P< 0.001). The total fluid intake increased in women (P< 0.001), but the intake of other iodine-rich foods did not change. The median urinary iodine concentration did not change in men (114 µg/l (n 708) and 107 µg/l (n 424), respectively), while the total fluid intake decreased (P= 0.001). Iodine content was measured in milk sampled in 2000-1 and in 2013. The iodine content was lower in 2013 (12 (sd 3) µg/100 g) compared with that in 2000-1 (16 (sd 6) µg/100 g) (P< 0.001). In conclusion, iodine excretion in women has decreased below the recommended level. The reason might probably, at least partly, be a decreased content of iodine in milk.

Vitamin D status and its determinants in children and adults among families in late summer in Denmark.

The impact of the familial relationship on vitamin D status has not been investigated previously. The objective of the present cross-sectional study was to assess serum 25-hydroxyvitamin D (25(OH)D) concentration and its determinants in children and adults among families in late summer in Denmark (56°N). Data obtained from 755 apparently healthy children (4-17 years) and adults (18-60 years) recruited as families (n 200) in the VitmaD study were analysed. Blood samples were collected in September-October, and serum 25(OH)D concentration was measured by liquid chromatography-tandem MS. Information on potential determinants was obtained using questionnaires. The geometric mean serum 25(OH)D concentration was 72·1 (interquartile range 61·5-86·7) nmol/l (range 9-162 nmol/l), with 9 % of the subjects having 25(OH)D concentrations < 50 nmol/l. The intra-family correlation was 0·27 in all subjects, 0·24 in the adults and 0·42 in the children. Serum 25(OH)D concentration was negatively associated with BMI (P< 0·001) and positively associated with dietary vitamin D intake (P= 0·008), multivitamin use (P= 0·019), solarium use (P= 0·006), outdoor stay (P= 0·001), sun preference (P= 0·002) and sun vacation (P< 0·001), but was not associated with lifestyle-related factors in the adults when these were assessed together with the other determinants. In conclusion, the majority of children and adults among the families had serum 25(OH)D concentrations >50 nmol/l in late summer in Denmark. Both dietary and sun-related factors were determinants of vitamin D status and the familial component was stronger for the children than for the adults.

The influence of early exposure to vitamin D for development of diseases later in life.

BACKGROUND: Vitamin D deficiency is common among otherwise healthy pregnant women and may have consequences for them as well as the early development and long-term health of their children. However, the importance of maternal vitamin D status on offspring health later in life has not been widely studied. The present study includes an in-depth examination of the influence of exposure to vitamin D early in life for development of fractures of the wrist, arm and clavicle; obesity, and type 1 diabetes (T1D) during child- and adulthood. METHODS/DESIGN: The study is based on the fact that in 1961 fortifying margarine with vitamin D became mandatory in Denmark and in 1972 low fat milk fortification was allowed. Apart from determining the influences of exposure prior to conception and during prenatal life, we will examine the importance of vitamin D exposure during specific seasons and trimesters, by comparing disease incidence among individuals born before and after fortification. The Danish National databases assure that there are a sufficient number of individuals to verify any vitamin D effects during different gestation phases. Additionally, a validated method will be used to determine neonatal vitamin D status using stored dried blood spots (DBS) from individuals who developed the aforementioned disease entities as adults and their time and gender-matched controls. DISCUSSION: The results of the study will contribute to our current understanding of the significance of supplementation with vitamin D. More specifically, they will enable new research in related fields, including interventional research designed to assess supplementation needs for different subgroups of pregnant women. Also, other health outcomes can subsequently be studied to generate multiple health research opportunities involving vitamin D. Finally, the results of the study will justify the debate of Danish health authorities whether to resume vitamin D supplementation policies.

A cautious iodization programme bringing iodine intake to a low recommended level is associated with an increase in the prevalence of thyroid autoantibodies in the population.

UNLABELLED: Autoantibodies against the thyroid gland with thyroid peroxidase antibody (TPO-Ab) and thyroglobulin antibody (Tg-Ab) as the most common can often be demonstrated in serum. The effect of public iodization programmes on antibody prevalence is uncertain. AIM: To measure the concentrations of thyroid autoantibodies in the Danish population before and after mandatory iodization of salt. METHODS: Two identical cross-sectional population studies were performed before (Cohort 1 (C1), year 1997-1998, n = 4649, median urinary iodine 61 µg/l) and 4-5 years after (Cohort 2 (C2), year 2004-2005, n = 3570, median urinary iodine 101 µg/l) mandatory iodine fortification of salt was implemented in Denmark. Blood tests were analysed for TPO-Ab and Tg-Ab using sensitive assays. RESULTS: Antibodies were more frequent in C2 than in C1: TPO-Ab > 30 U/ml, C1 vs C2: 14·3 vs 23·8% (P < 0·001) and Tg-Ab > 20 U/ml, C1 vs C2: 13·7 vs 19·9% (P < 0·001). The C2 vs C1 effect was confirmed in multivariate regression models (C1 reference): TPO-Ab: OR (95% CI): 1·80 (1·59-2·04) and Tg-Ab: 1·49 (1·31-1·69). The increase in the frequency of thyroid antibodies was most pronounced in young women and especially observed at low concentrations of antibodies. CONCLUSION: The prevalence of both TPO-Ab and Tg-Ab was higher 4-5 years after a cautious iodine fortification of salt was introduced in Denmark. The increase was most pronounced in young women and in the low concentrations of antibody. Further studies are needed to evaluate the long-term effects of increased iodine intake on thyroid autoimmunity in the population.

Lower prevalence of mild hyperthyroidism related to a higher iodine intake in the population: prospective study of a mandatory iodization programme.

OBJECTIVE: Marked differences in pattern of thyroid dysfunction are seen in populations with different iodine intakes. We evaluated the influence of a higher iodine intake on thyroid hormone levels and the prevalence of thyroid dysfunction in the Danish population. DESIGN: Two cross-sectional studies matched on a group level according to sex and age. PARTICIPANTS: In all, 8219 individuals were examined before (n = 4649) or after (n = 3570) the introduction of a mandatory iodization programme in 2000 in two regions with established mild and moderate iodine deficiency. Serum TSH, fT(4) and fT(3 )were measured. An ultrasonography of the thyroid was performed. RESULTS: We found a higher median serum TSH after the introduction of mandatory iodization of salt: 1.51 mU/l (10-90th percentiles: 0.72-3.00) vs. 1.30 mU/l (10-90th percentiles: 0.59-2.66) before iodization. The difference was found in both regions and across age groups. There was a lower prevalence of mild hyperthyroidism and a tendency towards a lower prevalence of overt hyperthyroidism. The prevalence of mild hypothyroidism increased, most pronounced among young women after iodization. Conversely, there was a lower prevalence of undiagnosed overt hypothyroidism. However, when currently treated participants were included, the prevalence of hypothyroidism increased after iodization in the area with formerly mild iodine deficiency. CONCLUSION: A change in pattern of thyroid dysfunction was seen in relation to mandatory iodization of salt. There was no rise in the prevalence of hyperthyroidism and the prevalence of mild hyperthyroidism was halved. Conversely, prevalence of hypothyroidism increased.

Validation of the Danish 7-day pre-coded food diary among adults: energy intake v. energy expenditure and recording length.

Under-reporting of energy intake (EI) is a well-known problem when measuring dietary intake in free-living populations. The present study aimed at quantifying misreporting by comparing EI estimated from the Danish pre-coded food diary against energy expenditure (EE) measured with a validated position-and-motion instrument (ActiReg). Further, the influence of recording length on EI:BMR, percentage consumers, the number of meal occasions and recorded food items per meal was examined. A total of 138 Danish volunteers aged 20-59 years wore the ActiReg and recorded their food intake for 7 consecutive days. Data for 2504 participants from the National Dietary Survey 2000-2 were used for comparison of characteristics and recording length. The results showed that EI was underestimated by 12 % on average compared with EE measured by ActiReg (PreMed AS, Oslo, Norway). The 95 % limits of agreement for EI and EE were - 6.29 and 3.09 MJ/d. Of the participants, 73 % were classified as acceptable reporters, 26 % as under-reporters and 1 % as over-reporters. EI:BMR was significantly lower on 1-3 consecutive recording days compared with 4-7 recording days (P < 0.03). Percentage consumers of selected food items increased with number of recording days. When recording length was 7 d, the number of reported food items per meal differed between acceptable reporters and under-reporters. EI:BMR was the same on 4 and 7 consecutive recording days. This was, however, a result of under-reporting in the beginning and the end of the 7 d reporting. Together, the results indicate that EI was underestimated at group level and that a 7 d recording is preferable to a 4 d recording period.

Iodine intake before and after mandatory iodization in Denmark: results from the Danish Investigation of Iodine Intake and Thyroid Diseases (DanThyr) study.

Iodine deficiency is still common in some European countries. In Denmark an iodine fortification programme was introduced in 1998 and a monitoring programme was established prior to iodization. This study reports the change in urinary iodine excretion caused by fortification and investigates determinants of iodine intake after fortification. Iodine excretion in casual urine samples was assessed in 4649 subjects in 1997-8 and in 3570 comparable subjects in 2004-5 in women 18-22, 25-30, 40-45 and 60-65 years of age and in men 60-65 years of age living in Aalborg (western part of Denmark) or Copenhagen (eastern part of Denmark). These areas had moderate and mild iodine deficiency, respectively, before iodine fortification. All subjects filled in a FFQ and a questionnaire regarding lifestyle factors. Iodine excretion, expressed as the estimated 24 h urinary iodine excretion and as urinary iodine concentration, increased significantly in all age and sex groups. However, the iodine intake was still below the recommended in the youngest age groups in both cities and in women 40-45 years of age living in Aalborg. Intake of milk and salt had strong significant direct associations with iodine excretion (P < 0.001). It is concluded that although the median iodine intake in the whole study population is at the recommended level, some groups still have an intake below the recommended. It is important to have a moderate milk intake to obtain a sufficient iodine intake in Denmark.

Effect of a mandatory iodization program on thyroid gland volume based on individuals' age, gender, and preceding severity of dietary iodine deficiency: a prospective, population-based study.

OBJECTIVE: We aimed to evaluate prospectively the effect of 4 yr of mandatory iodization of salt (13 ppm iodine) on thyroid volume in two regional areas with respectively mild and moderate iodine deficiency. METHODS: Two separate cross-sectional studies were performed before (n=4649) and after (n=3570) the iodization in year 2000 in two areas with mild and moderate iodine deficiency. Women aged 18-22, 25-30, 40-45, and 60-65 yr and men aged 60-65 yr were examined. Thyroid ultrasonography was performed. RESULTS: A lower median thyroid volume was seen in all age groups after iodization. The largest relative decline was found among the younger females from the area with previous, moderate iodine deficiency. Only a minor decrease was seen among the youngest participants in the area with previous, mild iodine deficiency. After iodization, there were no regional differences in median thyroid volume in the age groups younger than 45 yr. When adjusted for confounders, a lower mean volume was seen among those with multiple nodules in both areas and in the group with diffuse structure in the area with moderate iodine deficiency. Before the iodization, 17.6% of the total cross-section had thyroid enlargement; after the iodization, 10.9% of the cross-section had thyroid enlargement. CONCLUSION: In this prospective study, we demonstrated a lower thyroid volume in all age groups after iodization of salt. The decline was largest in the area with former, moderate iodine deficiency. The equal volumes in the regions among the younger age groups indicate approximation to an optimal iodine intake.

Age modifies the pituitary TSH response to thyroid failure.

OBJECTIVE: To investigate the association between serum TSH, total T4 and various patient characteristics when hypothyroidism is diagnosed in a population, and to study how age, sex and serum T4 levels influenced pituitary TSH response. DESIGN: A computer-based register linked to laboratory databases prospectively identified all patients with new, biochemically overt hypothyroidism (n = 685) in an open cohort in Denmark. The diagnosis was verified in each patient, and disease was classified into nosological type. Serum TSH and total T4 were recorded at the time of diagnosis in untreated patients with spontaneous autoimmune hypothyroidism (n = 578). MAIN OUTCOME: In untreated primary, spontaneous autoimmune hypothyroidism, we observed a four fold difference in average serum TSH levels between the youngest (0-20 years: TSH = 100 mU/l) and the oldest (80+ years: TSH = 24.4 mU/l) group of patients. No age dependent variation was observed in serum total T4. Log TSH showed an inverse linear correlation with age. An inverse linear correlation was present between log TSH and total T4 in both young and old patients, but for all total T4 values we observed lower median serum TSH values in elderly patients. CONCLUSIONS: For the same degree of thyroid failure, the serum TSH is lower among the elderly. This is most likely caused by a decrease in the hypothalamic/pituitary response to low serum T4. A certain increase in serum TSH may indicate more severe hypothyroidism in an old than in a young patient, and longer time may be needed after thyroid hormone withdrawal before elderly patients with thyroid cancer reach sufficiently high TSH values to allow for an effective radio-iodine treatment.

The association between hypoechogenicity or irregular echo pattern at thyroid ultrasonography and thyroid function in the general population.

OBJECTIVE: Patients with overt hypothyroidism show decreased echogenicity of the thyroid at ultrasonography (US). The aim of this study was to investigate the association between echogenicity of the thyroid/irregular echo pattern, and thyroid function in the general population, i.e. subjects without overt thyroid disease. DESIGN: A cross-sectional investigation of 4649 randomly selected adult subjects. METHODS: Blood samples were analysed for serum TSH, thyroid hormones and thyroid autoantibodies. US of the thyroid was performed. RESULTS: Participants with decreased echogenicity (n=379) had a higher mean TSH (1.65 mU/l) compared with subjects with normal echogenicity (1.21 mU/l, P<0.0001). The association was stronger in subjects with markedly decreased echogenicity (4.20 mU/l, P<0.0001). A similar association was seen when the subjects were divided into subgroups according to the level of TSH; more subjects with high levels of TSH had decreased echogenicity (P<0.0001). Likewise, more subjects with high levels of TSH had an irregular echo pattern (P<0.0001). Subjects with decreased echogenicity had a higher risk of having thyroid autoantibodies than subjects without decreased echogenicity (P<0.0001). This association was stronger when echogenicity was markedly decreased. CONCLUSIONS: We demonstrated an association between hypoechogenicity at thyroid US and higher levels of serum TSH even in subjects without overt thyroid disease, suggesting decreased echogenicity as an early sign of thyroid dysfunction. Irregular echo pattern, whether accompanied by hypoechogenicity or not, was another possible marker of thyroid failure. This indicates a possible use of thyroid US in detecting early and subclinical thyroid dysfunction.

The Danish investigation on iodine intake and thyroid disease, DanThyr: status and perspectives.

OBJECTIVE: Denmark was an area of iodine deficiency, and mandatory iodine fortification of table salt and salt in bread (13 p.p.m. iodine) was initiated in 2000/2001. The Danish investigation on iodine intake and thyroid disease (DanThyr) is the monitoring of the iodine fortification program. DESIGN AND METHODS: DanThyr consists of three main parts: a study of population cohorts initialized before (n=4649) and after (n=3570) iodization of salt, a prospective identification of incident cases of overt hyper- and hypothyroidism in a population of around 550,000 people since 1997, and compilation of data from the national registers on the use of thyroid medication, thyroid surgery, and radioiodine therapy. Studies were carried-out in parallel in subcohorts living in areas with differences in iodine content of ground water. RESULTS: The study showed profound effects of even small differences in iodine intake level on the prevalence of goiter, nodules, and thyroid dysfunction. Mild and moderate iodine deficiency was associated with a decrease in serum TSH with age. Other environmental factors were also important for goiter development (increase in risk, smoking and pregnancy; decrease in risk, oral contraception and alcohol consumption), and the individual risk depended on the genetic background. Environmental factors had only a minor influence on the prevalence of thyroid autoantibodies in the population. There were more cases of overt hypothyroidism in mild than in moderate iodine deficiency caused by a 53% higher incidence of spontaneous (presumably autoimmune) hypothyroidism. On the other hand, there were 49% more cases of overt hyperthyroidism in the area with moderate iodine deficiency. The cautious iodine fortification program, aiming at an average increase in iodine intake of 50 mug/day has been associated with a 50% increase in incidence of hyperthyroidism in the area with the most severe iodine deficiency. The incidence is expected to decrease in the future, but there may be more cases of Graves' hyperthyroidism in young people. CONCLUSION: A number of environmental factors influence the epidemiology of thyroid disorders, and even relatively small abnormalities and differences in the level of iodine intake of a population have profound effects on the occurrence of thyroid abnormalities. Monitoring and adjustment of iodine intake in the population is an important part of preventive medicine.

Iodine excretion in school children in Copenhagen.

INTRODUCTION: Studies of dietary habits show a high iodine intake in children in Denmark. Iodine excretion in children has not previously been assessed. Iodine excretion in adults is below the recommended threshold, and it is therefore being discussed to increase the fortification level. The main objective of this study was to assess iodine excretion in children living in Copenhagen to establish whether a moderate increase in iodine fortification would lead to excess iodine intake in this group. METHODS: Children in first and fifth grade were recruited through schools in Copenhagen. In total, 244 children de-ivered a urine sample. Urine samples were analysed for iodine and creatinine, and the results were expressed as urinary iodine concentration (UIC) and as estimated 24-h iodine excretion. Iodine excretion in children was also compared with that of adults living in the same area, investigated in a prior study. RESULTS: The median UIC was within the recommended level; 145 (range: 116-201) µg/l for boys and 128 (range: 87-184) µg/l for girls, and was lower in fifth grade students than in first grade students. Estimated 24-h iodine excretion was higher in boys than in girls, but did not differ according to grade. The UIC was higher in children than in adults from the same area. CONCLUSIONS: The iodine excretion among schoolchildren in Copenhagen, an area with a relatively high iodine content in tap water, was within the recommended range as assessed by the UIC. An increased iodine fortification will not have negative consequences for this group. FUNDING: The Ministry of Food, Agriculture and Fisheries. TRIAL REGISTRATION: not relevant.

Small differences in thyroid function may be important for body mass index and the occurrence of obesity in the population.

CONTEXT: Increasing prevalence of overweight in the population is a major concern globally; and in the United States, nearly one third of adults were classified as obese at the end of the 20th century. Few data have been presented regarding an association between variations in thyroid function seen in the general population and body weight. OBJECTIVE: The aim of this study was to investigate the association between thyroid function and body mass index (BMI) or obesity in a normal population. DESIGN: A cross-sectional population study (The DanThyr Study) was conducted. PARTICIPANTS: In all, 4649 participants were investigated, and 4082 were eligible for these analyses after exclusion of subjects with previous or present overt thyroid dysfunction. MAIN OUTCOME MEASURES: The study examined the association between category of serum TSH or serum thyroid hormones and BMI or obesity in multivariate models, adjusting for possible confounding. RESULTS: We found a positive association between BMI and category of serum TSH (P < 0.001) and a negative association between BMI and category of serum free T(4) (P < 0.001). No association was found between BMI and serum free T(3) levels. The difference in BMI between the groups with the highest and lowest serum TSH levels was 1.9 kg/m(2), corresponding to a difference in body weight of 5.5 kg among women. Similarly, the category of serum TSH correlated positively with weight gain during 5 yr (P = 0.04), but no statistically significant association was found with weight gain during 6 months (P = 0.17). There was an association between obesity (BMI > 30 kg/m(2)) and serum TSH levels (P = 0.001). CONCLUSIONS: Our results suggest that thyroid function (also within the normal range) could be one of several factors acting in concert to determine body weight in a population. Even slightly elevated serum TSH levels are associated with an increase in the occurrence of obesity.

Common variants in CYP2R1 and GC genes are both determinants of serum 25-hydroxyvitamin D concentrations after UVB irradiation and after consumption of vitamin D3-fortified bread and milk during winter in Denmark.

BACKGROUND: Little is known about how the genetic variation in vitamin D modulating genes influences ultraviolet (UV)B-induced 25-hydroxyvitamin D [25(OH)D] concentrations. In the Food with vitamin D (VitmaD) study, we showed that common genetic variants rs10741657 and rs10766197 in 25-hydroxylase (CYP2R1) and rs842999 and rs4588 in vitamin D binding protein (GC) predict 25(OH)D concentrations at late summer and after 6-mo consumption of cholecalciferol (vitamin D3)-fortified bread and milk. OBJECTIVES: In the current study, called the Vitamin D in genes (VitDgen) study, we analyzed associations between the increase in 25(OH)D concentrations after a given dose of artificial UVB irradiation and 25 single nucleotide polymorphisms located in or near genes involved in vitamin D synthesis, transport, activation, or degradation as previously described for the VitmaD study. Second, we aimed to determine whether the genetic variations in CYP2R1 and GC have similar effects on 25(OH)D concentrations after artificial UVB irradiation and supplementation by vitamin D3-fortified bread and milk. DESIGN: The VitDgen study includes 92 healthy Danes who received 4 whole-body UVB treatments with a total dose of 6 or 7.5 standard erythema doses during a 10-d period in winter. The VitmaD study included 201 healthy Danish families who were given vitamin D3-fortified bread and milk or placebo for 6 mo during the winter. RESULTS: After UVB treatments, rs10741657 in CYP2R1 and rs4588 in GC predicted UVB-induced 25(OH)D concentrations as previously shown in the VitmaD study. Compared with noncarriers, carriers of 4 risk alleles of rs10741657 and rs4588 had lowest concentrations and smallest increases in 25(OH)D concentrations after 4 UVB treatments and largest decreases in 25(OH)D concentrations after 6-mo consumption of vitamin D3-fortified bread and milk. CONCLUSION: Common genetic variants in the CYP2R1 and GC genes modify 25(OH)D concentrations in the same manner after artificial UVB-induced vitamin D and consumption of vitamin D3-fortified bread and milk.

Relations between various measures of iodine intake and thyroid volume, thyroid nodularity, and serum thyroglobulin.

BACKGROUND: Iodine intake can be measured in various ways, and each method may have advantages and disadvantages. OBJECTIVE: We sought to investigate the potential associations of various measures of iodine intake with thyroid volume, prevalence of thyroid nodules, and serum thyroglobulin. We also sought to identify, if possible, groups at risk of thyroid disease because of their food choices. DESIGN: This cohort study included 4649 randomly selected subjects with mild-to-moderate iodine deficiency; the subjects lived in 2 cities in Denmark. Iodine intake was estimated by using a food-frequency questionnaire and by measuring iodine excretion in spot urine samples. Thyroid volume and nodularity were measured with ultrasonography. RESULTS: In multiple linear regression models, significant inverse relations were found between thyroid volume and estimated 24-h iodine excretion, iodine intake from diet plus supplements, iodine intake from diet/kg body wt, and milk intake (P = 0.001 for all), but not urinary iodine excretion measured as a concentration (P = 0.40). All measures of iodine intake were significantly related to serum thyroglobulin concentration (P

Mandatory iodine fortification of bread and salt increases iodine excretion in adults in Denmark - a 11-year follow-up study.

BACKGROUND & AIMS: Iodine fortification is widespread. Systematic monitoring of iodine fortification programs should be carried out to secure an optimal fortification level. Our aim was to investigate the effectiveness of the Danish iodine fortification program by comparing iodine excretion at baseline and at 11-year follow-up, and to study determinants for any change in iodine intake including dietary habits, education, life style factors and health parameters. METHODS: A follow-up study based on the Danish DanThyr cohort examined in 1997-1998 just before iodine fortification was introduced, and reexamined in 2008-2010. In total, 2465 (59.1%) adult participants were reexamined. RESULTS: Median (IQR) iodine concentration in urine had increased by 19 (-25-68) µg/L to 83 (47-133) µg/L. Estimated 24-h iodine excretion had increased by 36 (-21-95) µg/24-h to 134 (93-206), and calculated total iodine intake (diet plus supplements) had increased by 16 (-18-48) µg/day. Iodine excretion had increased significantly in all age and gender groups, but was still below the recommended amount at follow-up. The increase in iodine excretion was positively associated with changes in milk intake, with changes in the use of iodine supplements, and with bread intake at follow-up. Salt intake, education, self-rated health, smoking, alcohol intake and physical activity were not associated with the increase in iodine excretion. CONCLUSIONS: The strategy to combat iodine deficiency in Denmark seems to be working because the fortification led to increased urinary iodine excretion in (almost) all participants. However, the level of iodine fortification of salt is too low.

Real-life use of vitamin D3-fortified bread and milk during a winter season: the effects of CYP2R1 and GC genes on 25-hydroxyvitamin D concentrations in Danish families, the VitmaD study.

Common genetic variants rs10741657 and rs10766197 in CYP2R1 and rs4588 and rs842999 in GC and a combined genetic risk score (GRS) of these four variants influence late summer 25-hydroxyvitamin D (25(OH)D) concentrations. The objectives were to identify those who are most at risk of developing low vitamin D status during winter and to assess whether vitamin D3-fortified bread and milk will increase 25(OH)D concentrations in those with genetically determined low 25(OH)D concentrations at late summer. We used data from the VitmaD study. Participants were allocated to either vitamin D3-fortified bread and milk or non-fortified bread and milk during winter. In the fortification group, CYP2R1 (rs10741657) and GC (rs4588 and rs842999) were statistically significantly associated with winter 25(OH)D concentrations and CYP2R1 (rs10766197) was borderline significant. There was a negative linear trend between 25(OH)D concentrations and carriage of 0-8 risk alleles (p < 0.0001). No association was found for the control group (p = 0.1428). There was a significant positive linear relationship between different quintiles of total vitamin D intake and the increase in 25(OH)D concentrations among carriers of 0-2 (p = 0.0012), 3 (p = 0.0001), 4 (p = 0.0118) or 5 (p = 0.0029) risk alleles, but not among carriers of 6-8 risk alleles (p = 0.1051). Carriers of a high GRS were more prone to be vitamin D deficient compared to carriers of a low GRS. Furthermore, rs4588-AA carriers have a low but very stable 25(OH)D concentration, and interestingly, also low PTH level.

Randomized controlled trial of the effects of vitamin D­fortified milk and bread on serum 25-hydroxyvitamin D concentrations in families in Denmark during winter: the VitmaD study.

BACKGROUND: Vitamin D intakes are lower than dietary recommendations in most populations, and thus, a low vitamin D status is widespread, especially during winter. OBJECTIVE: We investigated the effects of increasing vitamin D intake to the recommended amount by fortification of milk and bread on serum 25-hydroxyvitamin D [25(OH)D] concentrations in families during winter in Denmark. DESIGN: The study was a randomized controlled trial in 782 children and adults (4-60 y old) recruited as 201 families. Families were randomly assigned to vitamin D-fortified or nonfortified milk and bread for 6 mo starting in September. The milk and bread replaced the participants' usual consumptions of products. RESULTS: Median (IQR) vitamin D intakes (habitual diet plus fortified products) were 9.4 mg/d (6.5, 12.3 mg/d) and 2.2 mg/d (1.5, 3.0 mg/d) in fortification and control groups, respectively. Geometric mean (IQR) serum 25(OH)D concentrations decreased from 73.1 nmol/L (61.9, 88.5 nmol/L) to 67.6 nmol/L (56.2, 79.4 nmol/L) in the fortification group and from 71.1 nmol/L (61.2, 85.9 nmol/L) to 41.7 nmol/L (29.5, 58.9 nmol/L) in the control group (both P , 0.001). The final 25(OH)D concentration was significantly higher in the fortification group than in the control group (P , 0.001). By the end of the study, ,1% of subjects in the fortification group and 25% of subjects in the control group had 25(OH)D concentrations ,30 nmol/L and 16% and 65% of subjects, respectively, had 25(OH)D concentrations ,50 nmol/L. CONCLUSION: Vitamin D fortification of milk and bread reduces the decrease in serum 25(OH)D concentrations during winter and ensures 25(OH)D concentrations .50 nmol/L in children and adults in Denmark.

Nationwide trends in surgery and radioiodine treatment for benign thyroid disease during iodization of salt.

OBJECTIVE: Iodization of salt was introduced in Denmark in 1998 because of mild-to-moderate iodine deficiency (ID). The aim of this study was to analyze the utilization rate of surgery and radioiodine therapy for benign thyroid disorders before and after the introduction of iodization, and to study a possible association between the changes and the raised iodine intake. DESIGN: A nationwide register study. METHODS: Information on operations and radioiodine treatments for benign thyroid disorders was extracted from nationwide registers in the years 1990 to 2007. Treatment rates are presented for surgery and for radioiodine separately, and as a combined rate, both nationwide and split by the regions of prior mild and moderate ID. RESULTS: A total of 65 605 treatments were identified: 26 456 operations and 39 149 radioiodine treatments. In the first years of iodization (1998-2000; rate ratio 2000/1997), the combined treatment rate increased with 2.5% (95% confidence interval (CI): -1.8-7.1). Split by prior ID level, the increase was seen in the region of moderate ID, but a decrease was seen in the region of mild ID. After 2000, the combined rate decreased, and ended up being 11.1% (95% CI: 7.1-15.0) lower in 2007 than before iodization (rate ratio 2007/1997). The changes were primarily due to changes in the use of radioiodine therapy as the surgery rates remained almost constant. CONCLUSIONS: Iodization seemed to be associated with a temporary increase in the utilization rate of surgery and radioiodine therapy in the region of prior moderate ID, probably as a result of treatment of iodine-induced hyperthyroidism, but the rates ended up being lower than before iodization.

Estimation of iodine intake from various urinary iodine measurements in population studies.

BACKGROUND: Iodine intake is often measured by a surrogate measure, namely urine iodine excretion as almost all ingested iodine is excreted in the urine. However, the methods for urine collection and the reporting of the results vary. These methods, and their advantages and disadvantages, are considered in this article. SUMMARY: There are two main ways in which urine can be collected for iodine measurement. The first is the collection of urine over a period, usually 24 hours. The second is the collection of a spot urinary sample. Urinary iodine values can be expressed as the content or concentration and reported without modification or as a function of creatinine in the same sample. The 24-hour urine for iodine measurement is often considered as the "reference standard" for giving a precise estimate of the individual iodine excretion and thereby iodine intake. As 24-hour collections are difficult to perform for large number of persons, single spot urinary samples are preferable to the 24-hour urinary collections in population studies. The iodine concentration in urine depends on the intake of both iodine and fluid. This, and the fact that there is a considerable variability in the daily iodine intake, makes the iodine measurement in spot urine samples unreliable for evaluating individuals for iodine deficiency, though they can be used to screen for exposure to large amounts of iodine from sources such as amiodarone and certain radiographic contrast agents. In populations of at least 500 subjects, the median value of spot urinary iodine concentration is a reliable measure of the iodine intake in the population as there is a leveling out of the day-to-day variation in iodine intake and urinary volume. Expressing the urinary iodide concentration as a function of urinary creatinine is useful in correcting for the influence of fluid intake. When doing so, it is recommended to adjust for the age- and sex-specific creatinine excretion in the given population. CONCLUSION: In studies of iodine intake, the correct choice of the method for collecting urine and the format for expressing the results of urine iodine measurement is essential to avoid misinterpretation of data on the iodine status of a population or individuals.