Long-term iodine nutrition is associated with longevity in older adults: a 20 years' follow-up of the Randers-Skagen study.

Iodine intake affects the occurrence of thyroid disorders. However, the association of iodine intake with longevity remains to be described. This led us to perform a 20 years' follow-up on participants from the Randers-Skagen (RaSk) study. Residents in Randers born in 1920 (n 210) and Skagen born in 1918-1923 (n 218) were included in a clinical study in 1997-1998. Mean iodine content in drinking water was 2 µg/l in Randers and 139 µg/l in Skagen. We collected baseline data through questionnaires, performed physical examinations and measured iodine concentrations in spot urine samples. Income data were retrieved from Danish registries. We performed follow-up on mortality until 31 December 2017 using Danish registries. Complete follow-up data were available on 428 out of 430 of participants (99·5 %). At baseline, the median urinary iodine concentration was 55 µg/l in Randers and 160 µg/l in Skagen residents. Participants were long-term residents with 72·8 and 92·7 % residing for more than 25 years in Randers and Skagen, respectively. Cox regression showed that living in Skagen compared with Randers was associated with a lower hazard ratio (HR) of death in both age- and sex-adjusted analyses (HR 0·60, 95 % CI 0·41, 0·87, P = 0·006), but also after adjustment for age, sex, number of drugs, Charlson co-morbidity index, smoking, alcohol and income (HR 0·60, 95 % CI 0·41, 0·87, P = 0·008). Residing in iodine-replete Skagen was associated with increased longevity. This indicates that long-term residency in an iodine-replete environment may be associated with increased longevity compared with residency in an iodine-deficient environment.

Thyroglobulin in smoking mothers and their newborns at delivery suggests autoregulation of placental iodide transport overcoming thiocyanate inhibition.

BACKGROUND: Placental transport of iodide is required for fetal thyroid hormone production. The sodium iodide symporter (NIS) mediates active iodide transport into the thyroid and the lactating mammary gland and is also present in placenta. NIS is competitively inhibited by thiocyanate from maternal smoking, but compensatory autoregulation of iodide transport differs between organs. The extent of autoregulation of placental iodide transport remains to be clarified. OBJECTIVE: To compare the impact of maternal smoking on thyroglobulin (Tg) levels in maternal serum at delivery and in cord serum as markers of maternal and fetal iodine deficiency. METHODS: One hundred and forty healthy, pregnant women admitted for delivery and their newborns were studied before the iodine fortification of salt in Denmark. Cotinine in urine and serum classified mothers as smokers (n=50) or nonsmokers (n=90). The pregnant women reported on intake of iodine-containing supplements during pregnancy and Tg in maternal serum at delivery and in cord serum were analyzed. RESULTS: In a context of mild-to-moderate iodine deficiency, smoking mothers had significantly higher serum Tg than nonsmoking mothers (mean Tg smokers 40.2 vs nonsmokers 24.4 µg/l, P=0.004) and so had their respective newborns (cord Tg 80.2 vs 52.4 µg/l, P=0.006), but the ratio between Tg in cord serum and maternal serum was not significantly different in smokers compared with nonsmokers (smoking 2.06 vs nonsmoking 2.22, P=0.69). CONCLUSION: Maternal smoking increased the degree of iodine deficiency in parallel in the mother and the fetus, as reflected by increased Tg levels. However, placental iodide transport seemed unaffected despite high thiocyanate levels, suggesting that thiocyanate-insensitive iodide transporters alternative to NIS are active or that NIS in the placenta is autoregulated to keep iodide transport unaltered.

Iodine deficiency influences thyroid autoimmunity in old age--a comparative population-based study.

OBJECTIVE: To assess thyroid autoimmunity among elderly people living in an area with low iodine intake compared to the sustained recommended iodine intake from a natural source, and to estimate the importance of migration. DESIGN AND SETTING: Iodine content of drinking water is highly different in the Danish towns Randers and Skagen. We collected blood and spot urine samples from 430 long-term Randers and Skagen dwellers aged 75-80 years, who filled in a questionnaire. We measured thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TGAb) in serum and iodine and creatinine in urine. RESULTS: Participation rate was 47% (n=212 (men/women 82/130) in Randers; 218 (84/134) in Skagen). Iodine deficiency prevailed in Randers while Skagen dwellers were iodine replete (median urinary iodine 74 µg/24h vs. 184 µg/24h, p<0.001). Thyroid antibodies were more frequent in Randers than in Skagen residents (42% vs. 32%; p=0.006) and more likely with iodine excretion <50 µg/24h (OR, 95%CI: 1.9, 1.1-3.4). Differences between towns increased with longer duration of residence as trends in the occurrence of TGAb and TPOAb were opposite (p<0.001; p=0.007). CONCLUSIONS: Thyroid autoantibodies were common in old age, influenced by the iodine intake level, and the lowest frequency was found at the recommended iodine intake level.

Naturally occurring iodine in humic substances in drinking water in Denmark is bioavailable and determines population iodine intake.

Iodine intake is important for thyroid function. Iodine content of natural waters is high in some areas and occurs bound in humic substances. Tap water is a major dietary source but bioavailability of organically bound iodine may be impaired. The objective was to assess if naturally occurring iodine bound in humic substances is bioavailable. Tap water was collected at Randers and Skagen waterworks and spot urine samples were collected from 430 long-term Randers and Skagen dwellers, who filled in a questionnaire. Tap water contained 2 microg/l elemental iodine in Randers and 140 microg/l iodine bound in humic substances in Skagen. Median (25; 75 percentile) urinary iodine excretion among Randers and Skagen dwellers not using iodine-containing supplements was 50 (37; 83) microg/24 h and 177 (137; 219) microg/24 h respectively (P < 0.001). The fraction of samples with iodine below 100 microg/24 h was 85.0 % in Randers and 6.5 % in Skagen (P < 0.001). Use of iodine-containing supplements increased urinary iodine by 60 microg/24 h (P < 0.001). This decreased the number of samples with iodine below 100 microg/24 h to 67.3 % and 5.0 % respectively, but increased the number of samples with iodine above 300 microg/24 h to 2.4 % and 16.1 %. Bioavailability of iodine in humic substances in Skagen tap water was about 85 %. Iodine in natural waters may be elemental or found in humic substances. The fraction available suggests an importance of drinking water supply for population iodine intake, although this may not be adequate to estimate population iodine intake.

Reliability of studies of iodine intake and recommendations for number of samples in groups and in individuals.

The iodine intake level in a population is determined in cross-sectional studies. Urinary iodine varies considerably and the reliability of studies of iodine nutrition and the number of samples needed is unsettled. We performed a longitudinal study of sixteen healthy men living in an area of mild to moderate iodine deficiency. Iodine and creatinine concentrations were measured in spot urine samples collected monthly for 13 months. From these data we calculated the number of urine samples needed to determine the iodine excretion level for crude urinary iodine and for 24 h iodine excretion estimated from age- and gender-specific creatinine excretions. We found that mean urinary iodine excretion varied from 30 to 87 microg/l (31 to 91 microg/24 h). Sample iodine varied from 10 to 260 microg/l (20 to 161 microg/24 h). Crude urinary iodine varied more than estimated 24 h iodine excretion (population standard deviation 32 v. 26; individual standard deviation 29 v. 21; Bartlett's test, P < 0.01 for both). The number of spot urine samples needed to estimate the iodine level in a population with 95 % confidence within a precision range of +/- 10 % was about 125 (100 when using estimated 24 h iodine excretions), and within a precision range of +/- 5 % was about 500 (400). A precision range of +/- 20 % in an individual required twelve urine samples or more (seven when using estimated 24 h iodine excretions). In conclusion, estimating population iodine excretion requires 100-500 spot urine samples for each group or subgroup. Less than ten urine samples in an individual may be misleading.

Sources of circulating 3,5,3'-triiodothyronine in hyperthyroidism estimated after blocking of type 1 and type 2 iodothyronine deiodinases.

CONTEXT: Graves' hyperthyroidism and multinodular toxic goiter lead to high serum T(3) compared with serum T(4). The source of this high T(3) has not been clarified. OBJECTIVE: Our objective was to assess the role of iodothyronine deiodinase type 1 (D1) and type 2 (D2) for T(3) production and to estimate the sources of T(3) in hyperthyroidism. DESIGN AND SETTING: The study was a prospective, randomized, open-labeled study in a secondary care setting. PATIENTS AND METHODS: Consecutive patients with hyperthyroidism caused by Graves' disease or by multinodular toxic goiter were randomized to be treated with high-dose propylthiouracil (PTU) to block D1, PTU plus KI, or PTU plus sodium ipodate to additionally block D2. T(3) and T(4) were measured in serum, and we estimated the sources of T(3). RESULTS: PTU reduced the T(3)/T(4) in serum to 47.7 +/- 2.5% (mean +/- sem) of the initial value on d 4 of therapy in patients with Graves' disease. The addition of KI to PTU led to a greater fall in T(3) and T(4), but the balance was unaltered. After PTU plus ipodate, T(3)/T(4) on d 4 was lower, 34.1 +/- 1.2% of the initial value. Similar variations were observed in patients with multinodular toxic goiter. Thus, the major source of the excess T(3) was D1-catalyzed T(4) deiodination, with a minor role for D2. It was estimated that the majority of this D1-catalyzed T(3) production takes place in the hyperactive thyroid gland. CONCLUSION: Although thyroidal T(3) contributes only around 20% of total T(3) production in normal individuals, this is much higher in patients with a hyperactive thyroid, ranging up to two thirds. The major part is produced from T(4) deiodinated in the thyroid.

Iodine nutrition in breast-fed infants is impaired by maternal smoking.

Lack of iodine for thyroid hormone formation during the fetal stage and/or the first years of life may lead to developmental brain damage. During the period of breastfeeding, thyroid function of the infant depends on iodine in maternal milk. We studied healthy, pregnant women admitted for delivery and their newborn infants. Cotinine in urine and serum was used to classify mothers as smokers (n = 50) or nonsmokers (n = 90). Smoking and nonsmoking mothers had identical urinary iodine on d 5 after delivery, but smoking was associated with reduced iodine content in breast milk (smokers 26.0 micro g/liter vs. nonsmokers 53.8 micro g/liter; geometric mean, P < 0.001) and in the infants' urine (smokers 33.3 micro g/liter, vs. nonsmokers 50.4 micro g/liter, P = 0.005). Results were consistent in multivariate linear models and by logistic regression analysis. The odds ratio for smoking vs. nonsmoking mothers to have lower breast milk than urinary iodine content was 8.4 (95% confidence interval, 3.5-20.1). In smokers, iodine transfer into breast milk correlated negatively to urinary cotinine concentration. Smoking mothers had significantly higher serum levels of thiocyanate, which may competitively inhibit the sodium-iodide symporter responsible for iodide transport in the lactating mammary gland. Smoking during the period of breastfeeding increases the risk of iodine deficiency-induced brain damage in the child. Women who breastfeed should not smoke, but if they do, an extra iodine supplement should be considered.