The Danish Investigation on Iodine Intake and Thyroid Disease (DanThyr): history and implications.

Due to mild to moderate iodine deficiency in Denmark, health authorities initiated a voluntary iodine fortification (IF) program in 1998, which became mandatory in 2000. In line with recommendations from WHO, the Danish Investigation on Iodine Intake and Thyroid Disease (DanThyr) was established to monitor the effect on thyroid health and diseases. The program involved different study designs and followed two Danish sub-populations in the years before IF and up till 20 years after. Results showed that the IF was successfully implemented and increased the level of iodine intake from mild-moderate iodine deficiency to low-adequacy. The level of thyroglobulin and thyroid volume decreased following IF and there was an indication of fewer thyroid nodules. The incidence of hyperthyroidism increased transiently following IF but subsequently decreased below the pre-fortification level. Conversely, thyroid stimulating hormone levels and the prevalence of thyroid autoimmunity increased along with an increase in the incidence of hypothyroidism. These trends were mirrored in the trends in treatments for thyroid disease. Most differences in thyroid health and disease between regions with different iodine intake levels before IF attenuated. This review illustrates the importance of a monitoring program to detect both beneficial and adverse effects and exemplifies how a monitoring program can be conducted when a nationwide health promotion program - as IF - is initiated.

Does iodine fortification affect the risk of atrial fibrillation in incident hyperthyroidism? A national register-based cohort.

OBJECTIVE: Iodine fortification (IF) induces an initial increase followed by a decrease in the incidence of hyperthyroidism in the general population. Within the population of hyperthyroid patients, the sex-, age- and subtype distribution changes after IF. The risk of atrial fibrillation (AF) in hyperthyroid patients may be influenced by these factors. Therefore, we aimed to examine how the association between incident hyperthyroidism and AF was affected by IF increasing the population iodine intake from moderate-mild iodine deficiency to low adequacy. DESIGN, PATIENTS AND MEASUREMENTS: Incident hyperthyroid patients were included at the date of first inpatient or outpatient diagnosis, and AF diagnoses within 3 months before to 6 months after the index date were identified in Danish nationwide registers, 1997-2018. The relative risk (RR) of AF each calendar year (reference: 1997; IF introduced: 2000) was analyzed in Poisson regression models adjusted for age, sex, educational level, geographic region, and comorbidities. RESULTS: Overall, in 62,201 patients with incident hyperthyroidism 7.9% were diagnosed with AF. There was a minor nonsignificantly increased risk of AF during the first years after IF followed by a gradual decrease to RR 0.76 (0.62-0.94) in 2017. There were no statistically significant differences in the development in the risk of AF by sex, age group, or geographic region. CONCLUSIONS: Results indicate that IF may reduce the risk of concomitant AF in hyperthyroid patients. If these results are confirmed, IF may not only reduce the population incidence of hyperthyroidism but also reduce the burden of morbidity in the remaining hyperthyroid patients.

Multicomponent (bio)markers for obesity risk prediction: a scoping review protocol.

INTRODUCTION: Despite international efforts, the number of individuals struggling with obesity is still increasing. An important aspect of obesity prevention relates to identifying individuals at risk at early stage, allowing for timely risk stratification and initiation of countermeasures. However, obesity is complex and multifactorial by nature, and one isolated (bio)marker is unlikely to enable an optimal risk stratification and prognosis for the individual; rather, a combined set is required. Such a multicomponent interpretation would integrate biomarkers from various domains, such as classical markers (eg, anthropometrics, blood lipids), multiomics (eg, genetics, proteomics, metabolomics), lifestyle and behavioural attributes (eg, diet, physical activity, sleep patterns), psychological traits (mental health status such as depression) and additional host factors (eg, gut microbiota diversity), also by means of advanced interpretation tools such as machine learning. In this paper, we will present a protocol that will be employed for a scoping review that attempts to summarise and map the state-of-the-art in the area of multicomponent (bio)markers related to obesity, focusing on the usability and effectiveness of such biomarkers. METHODS AND ANALYSIS: PubMed, Scopus, CINAHL and Embase databases will be searched using predefined key terms to identify peer-reviewed articles published in English until January 2024. Once downloaded into EndNote for deduplication, CADIMA will be employed to review and select abstracts and full-text articles in a two-step procedure, by two independent reviewers. Data extraction will then be carried out by several independent reviewers. Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews and Peer Review of Electronic Search Strategies guidelines will be followed. Combinations employing at least two biomarkers from different domains will be mapped and discussed. ETHICS AND DISSEMINATION: Ethical approval is not required; data will rely on published articles. Findings will be published open access in an international peer-reviewed journal. This review will allow guiding future directions for research and public health strategies on obesity prevention, paving the way towards multicomponent interventions.

PPARγ antagonists induce aromatase transcription in adipose tissue cultures.

Aromatase is the rate-limiting enzyme in the biosynthesis of estrogens and a key risk factor for hormone receptor-positive breast cancer. In postmenopausal women, estrogens synthesized in adipose tissue promotes the growth of estrogen receptor positive breast cancers. Activation of peroxisome proliferator-activated receptor gamma (PPARγ) in adipose stromal cells (ASCs) leads to decreased expression of aromatase and differentiation of ASCs into adipocytes. Environmental chemicals can act as antagonists of PPARγ and disrupt its function. This study aimed to test the hypothesis that PPARγ antagonists can promote breast cancer by stimulating aromatase expression in human adipose tissue. Primary cells and explants from human adipose tissue as well as A41hWAT, C3H10T1/2, and H295R cell lines were used to investigate PPARγ antagonist-stimulated effects on adipogenesis, aromatase expression, and estrogen biosynthesis. Selected antagonists inhibited adipocyte differentiation, preventing the adipogenesis-associated downregulation of aromatase. NMR spectroscopy confirmed direct interaction between the potent antagonist DEHPA and PPARγ, inhibiting agonist binding. Short-term exposure of ASCs to PPARγ antagonists upregulated aromatase only in differentiated cells, and a similar effect could be observed in human breast adipose tissue explants. Overexpression of PPARG with or without agonist treatment reduced aromatase expression in ASCs. The data suggest that environmental PPARγ antagonists regulate aromatase expression in adipose tissue through two mechanisms. The first is indirect and involves inhibition of adipogenesis, while the second occurs more acutely.

Evaluating the health impact of increased linseed consumption in the Danish population.

Consumption of linseeds has been suggested to have beneficial effects on human health. However, toxic constituents of linseed may compromise these benefits. We conducted a quantitative risk-benefit assessment to evaluate the overall health impact of increasing linseed intake up to 45 g/day in the Danish population (15-74 years). We quantified the risks associated with increased cadmium exposure and the benefits associated with increased intake of dietary fibre. Increased intakes of alpha-linoleic acid (ALA) were included in a sensitivity analysis. The overall health impact of different linseed intake scenarios was estimated in terms of Disability-Adjusted Life Years (DALYs). We found that the beneficial effects of linseed due to increased intake of dietary fibre outweighed the adverse health effects due to increased cadmium exposure in all scenarios. Up to 670 DALYs/100,000 individuals could be averted per year by increasing linseed consumption in the Danish population. The estimated beneficial health impact increased further when including ALA in the assessment. Different sources of uncertainty might affect the results, and more research is needed on both the health effects associated with intake of linseed and its constituents, and the bioavailability of ALA and cadmium from linseed to further improve the risk-benefit assessment.

Orthogonal assay and QSAR modelling of Tox21 PPARγ antagonist in vitro high-throughput screening assay.

Disruption of signalling mediated by the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) is associated with risk of cancer, metabolic diseases, and endocrine disruption. The purpose of this study was to identify environmental chemicals acting as PPARγ antagonists. Data from the Tox21 PPARγ antagonism assay were replicated using a reporter system in HEK293 cells. Two quantitative structure-activity relationship (QSAR) models were developed, and five REACH-registered substances predicted positive were tested in vitro. Reporter assay results were consistent with Tox21 data since all conflicting results could be explained by assay interference. QSAR models showed good predictive performance, and follow-up experiments revealed two PPARγ antagonists out of three non-interfering chemicals. In conclusion, the developed QSAR models and follow-up experiments are important steps in the discovery of potential endocrine- and metabolism-disrupting chemicals.

Impaired Abcb1a function and red meat in a translational colitis mouse model induces inflammation and alters microbiota composition.

Inflammatory Bowel Disease (IBD) affects approximately 0.3% of the global population, with incidence rates rising dramatically worldwide. Emerging evidence points to an interplay between exposome factors such as diet and gut microbiota, host genetics, and the immune system as crucial elements in IBD development. ATP-binding cassette (ABC) transporters, including human p-glycoprotein encoded by the Abcb1 gene, influence intestinal inflammation, and their expression may interact with environmental factors such as diet and gut microbes. Our study aimed to examine the impact of protein sources on a genetic colitis mouse model. Methods: Abcb1a-deficient colitis mice were fed either casein or red meat-supplemented diets to investigate potential colitis-aggravating components in red meat and their effects on host-microbiota interactions. We conducted deep label free quantitative proteomic inflammation profiling of gastrointestinal tissue (colon, ileum) and urine, and determined the overall microbiome in feces using 16S rRNA gene sequencing. Microbiota shifts by diet and protein transporter impairment were addressed by multivariate statistical analysis. Colon and systemic gut inflammation were validated through histology and immune assays, respectively. Results: A quantitative discovery based proteomic analysis of intestinal tissue and urine revealed associations between ileum and urine proteomes in relation to Abcb1a deficiency. The absence of Abcb1a efflux pump function and diet-induced intestinal inflammation impacted multiple systemic immune processes, including extensive neutrophil extracellular trap (NET) components observed in relation to neutrophil degranulation throughout the gastrointestinal tract. The colitis model's microbiome differed significantly from that of wild-type mice, indicating the substantial influence of efflux transporter deficiency on microbiota. Conclusion: The proteomic and microbiota analyzes of a well-established murine model enabled the correlation of gastrointestinal interactions not readily identifiable in human cohorts. Insights into dysregulated biological pathways in this disease model might offer translational biomarkers based on NETs and improved understanding of IBD pathogenesis in human patients. Our findings demonstrate that drug transporter deficiency induces substantial changes in the microbiota, leading to increased levels of IBD-associated strains and resulting in intestinal inflammation. GRAPHICAL ABSTRACT.

Toxicity of repeated oral intake of organic selenium, inorganic selenium, and selenium nanoparticles: A review.

BACKGROUND: To protect from toxicity at supra-essential doses of selenium, it is important to determine dose levels at which adverse effects occur. METHODS: We identified relevant literature on the repeated dosage of selenium and extracted dose descriptors on reported endpoints, except on genotoxicity/carcinogenicity. RESULTS: Selenium forms with toxicological data were organic ones: selenomethionine, selenocystine/selenocysteine; and inorganic ones, including selenite (SeO32-), selenate (SeO42-), selenium sulphide (SeS2), selenide (Se2-) and selenium nanoparticles. Clinical signs of selenium toxicity in humans include a garlicky-smelling breath, hair loss, and nail changes. One human study showed increased mortality following daily ingestion of 300 µg Se per day for 5 years, equal to a lowest-observed-adverse-effect level (LOAEL) of ∼4.3 µg/kg bw/days. The corresponding no-observed-adverse-effect level (NOAEL) was ∼2.9 µg Se/kg bw/day. One study reported an increased risk of type 2 diabetes after ∼2.9 µg Se/kg bw/day, but other studies with similar doses found no increases in mortality or incidence of type 2 diabetes. NOAELs on affected body weight in animal studies were 0.24-1.2 mg Se/kg bw/day. Other endpoints of selenium toxicity in animals include hepatotoxicity with a NOAEL as low as 2 µg/kg bw/day in rats, as well as gastrointestinal, cardiovascular, and reproductive toxicities with NOAELs of 0.6 (gastrointestinal), 0.08, and 0.4 (cardiovascular) and ≥ 0.04 mg Se/kg bw/day (reproductive), respectively. CONCLUSIONS: Dose descriptors describing selenium toxicity were as low as 2-3 µg Se/kg bw/day.

Effect of School-Based Educational Intervention on Promoting Healthy Dietary Habits in Danish Schoolchildren: The FOODcamp Case Study.

The present study aimed to evaluate the effect of the school-based educational intervention "FOODcamp" on dietary habits among 6th-7th graders (aged 11-13 years), focusing on the food groups: fruits and vegetables, fish, meat, discretionary food, and sugar-sweetened beverages. In this cluster-based quasi-experimental controlled intervention study, 16 intervention classes (322 children) and 16 control classes (267 children) from nine schools were recruited during the school year 2019-2020. The children were asked to record their food intake for four consecutive days (Wednesday to Saturday) before (baseline) and after (follow-up) attending FOODcamp, using a validated self-administered web-based dietary record. Eligible dietary intake registrations from 124 and 118 children from the control and interventions classes, respectively, were included in the final statistical analysis. Hierarchical mixed model analysis was used to evaluate the effect of the intervention. No statistically significant effects of participating in FOODcamp were found on the average food intake of the food groups eaten regularly (vegetables, fruit, vegetables/fruit/juice combined, or meat) (p > 0.05). Among the food groups not eaten regularly (fish, discretionary foods, and sugar-sweetened beverages), a non-significant tendency to lower odds of consuming sugar-sweetened beverages from baseline to follow-up (OR = 0.512; 95% CI: 0.261-1.003; p = 0.0510) was seen among FOODcamp participants compared to control participants. In conclusion, this study found no effect of the educational intervention FOODcamp on the dietary intake of vegetables, fruit, vegetable/fruit/juice combined, meat, fish, or sugar-sweetened beverages. The intake frequency of sugar-sweetened beverages tended to decrease among FOODcamp participants.

Vitamin D Food Fortification Strategies on Population-Based Dietary Intake Data Using Mixed-Integer Programming.

The dietary vitamin D intake of the Danish population is low, and food fortification is a strategy to increase intake. This paper explores the possibility of vitamin D fortification on the current population food intake in Denmark, such that the population receives adequate amounts of vitamin D without having to change current dietary patterns. A mixed-integer programming approach is used to arrive at a solution for the optimal fortification required at each food group level so that the majority of the population receive the minimum intake of average requirement (AR) and do not exceed the tolerable upper intake level (UL). The method shows a significant increase in vitamin D intake compared to the current scenario, keeping a neutral approach towards preferences of one food group over others. The method can also be fine-tuned in different scenarios where certain food group preferences are known, which can be encoded into the model in the form of constraints.

A Data Driven Approach to Identify Safe and Adequate Schemes for Vitamin D Fortification.

Food fortification is a strategy to increase low vitamin D intake. In order to avoid the intake of a population exceeding the upper tolerable intake level, the right choice of food groups to fortify is of crucial importance. An automated fortification tool was developed based on dietary intake data from the Danish National Survey of Dietary Habits and Physical Activity 2011-2013 (DANSDA), taking into account the energy contribution of the fortified food. The fortification of food group is a variant in the linear modelling, where the optimization ensures the lowest possible variation in deviation of the calculated intake and the target intake. The resulting tool demonstrated that the lowest limit of fortification, where the model works, is 12 µg/10 MJ, when fortification of any food group is allowed. The tool also demonstrated that, by increasing the allowed upper level of fortification from 12 µg/10 MJ up to 30 µg/10 MJ, the food groups selected for fortification and the level of fortification in those food groups may change. Specifically, fewer food groups seem to be needed as the upper level of fortification is increased. The optimized scenarios, using the food groups, including milk, cheese, cereals, fats, and juice, were tested on dietary-survey data and demonstrated that all the projected scenarios manage to lift the median vitamin D intake to the targeted intake safely. A data-driven approach was used to develop a simple, fast, and automated fortification tool to test different vitamin D food fortification strategies.

Intake of Food Supplements, Caffeine, Green Tea and Protein Products among Young Danish Men Training in Commercial Gyms for Increasing Muscle Mass.

Sixty-three men (15-35 years of age) regularly training in Danish gyms and supplement users were interviewed about the use of supplemental protein and food supplements, intake of caffeine- and (-)-epigallocathechin-3-gallate (EGCG)-containing supplements and beverages and any experienced adverse effects. Protein powder (60%), fish oil (54%) and multivitamin/mineral supplements (41%) were the most popular products. The daily supplementary protein intake (mean 0.42 g/kg body weight, users only) in adult men contributed substantially to their protein intake and exceeded the recommended allowance (0.83 g/kg body weight) for six adult participants (14%). Thirty-eight percent of the adult men exceeded the daily caffeine intake presumed to be safe (400 mg) with coffee as the main contributor. Thirty percent drank green tea and among this percentage, two participants had an extreme daily intake (1.5 and 2 -L). EGCG intake could not be estimated from the food supplements due to the lack of label information. Eighteen participants (29%) reported having experienced adverse effects but seventeen did not consult a physician or report the adverse effect to the Danish food authority. The most common adverse effects were insomnia, shaking, headache and palpitations, itching of the skin and stinging. Pre-workout products accounted for 53% of the adverse effects. Three adverse effects came after intake of two brands of supplements known to have contained substances such as 1,3-dimethylamine or derivatives of phenylethylamines previously having caused serious adverse effects.

Risk-Benefit Assessment of an Increase in the Iodine Fortification Level of Foods in Denmark-A Pilot Study.

Iodine deficiency is one of the most common nutritional disorders worldwide. In Denmark, the mandatory iodine fortification of salt of 13 ppm was introduced in 2000 to eradicate mild to moderate iodine deficiency and the fortification level was increased to 20 ppm in 2019. However, the optimal iodine intake is a narrow interval, and the risk of disease increases with intakes both below and above this interval. In this study, we quantified the risk-benefit balance in the Danish adult population by increasing the mandatory fortification level. We applied a risk-benefit assessment approach in which population-level iodine intakes before and after the increase in fortification were integrated with epidemiological evidence of the association between iodine nutrition status and risk of relevant diseases to estimate the number of cases caused or prevented and estimated health impact in terms of disability-adjusted life years (DALY). We estimated an overall beneficial health impact and prevention of 34.9 (95% UI: -51.6; -21.7) DALY per 100,000 adults in the population annually with the increase in fortification level. Prevention of low IQ in children due to maternal iodine deficiency was the primary contributor to overall health gain. The gain in healthy life years comes at the expense of extra cases of goiter due to iodine excess. Due to lack of data, hypo- and hyperthyroidism related to iodine status were not included. Neither were children as a population group. Because of this, as well as uncertainties inherent in the model and data used, results should be interpreted with caution. We argue that nation-specific, quantitative assessments of the public health impact of fortification programs provide transparent, evidence-based decision support. Future research should aim to enable the inclusion of all relevant health effects as well as children in the assessment.

Assessment of iodine fortification of salt in the Danish population.

PURPOSE: We assessed the effect of the current iodine fortification level (20 µg/g household salt and salt included in bread and bakery products) on inadequate and excessive intake in the general Danish population. Intake models with/without the contribution from food supplements and effects of excluding specific food groups were evaluated. METHOD: Data from the Danish National Survey of Dietary Habits and Physical Activity in 2011-13 (N = 3946, aged 4-75 years) stratified by age-group and sex were used to estimate habitual dietary iodine intakes, and compared with established dietary reference values. RESULTS: The proportion with an estimated inadequate iodine intake was ≤ 3% for males and ≤ 5% for females, except for 15-17-year-old girls, where the probable prevalence of an inadequate intake was 11%. Including the contribution from food supplements gave similar results (10%). High intakes (as defined by 95th percentile) from food sources generally did not exceed the tolerable upper intake level (UL). However, for the youngest age-groups (4-6-year-old boys/girls and 7-10-year-old boys), the 95th percentiles exceeded the UL with 11%, 4% and 7%, respectively, when food supplements were included in the estimates. Especially exclusion of dairy products and bread led to an inadequate intake for both boys and girls. CONCLUSION: The current fortification level may provide an inadequate iodine intake for some females and on the other hand lead to excessive intakes in the youngest age-groups. The study shows the importance of choosing iodine-rich alternatives when excluding major sources of iodine in the Danish diet.

Improved food literacy among schoolchildren as an effect of a food camp intervention: Results of a controlled effectiveness trial.

Food literacy (FL) refers to an individual's prerequisites for their engagement with food. Schoolchildren's FL has been defined in terms of five competencies: "to know"(e.g food-related knowledge), "to do" (e.g cooking skills), "to sense" (e.g. less well-explored sensory experiences), "to care" (e.g. taking care of oneself and others) and "to want" (e.g. willingness to take a stand and act). A cluster-based quasi-experimental effectiveness trial on the effects of a school-based intervention, "FOODcamp," on FL, health literacy, and school well-being was conducted. A total of 640 school children in grades 6 and 7 (mean age = 12 years) attended this one-week camp and participated in different food-related classes and activities. Linear mixed models controlling for the nested structure of data showed small but significant effects for the following FL dimensions: "to do (E = 0.098, CI (0.035-0.161), p = 0.002), "to sense" (E = 0.152, CI (0.073-0.232), p < 0.001), and "to know" (E = 0.086, CI (0.022-0.150), p = 0.009) as well as for overall FL (E = 0.078, CI (0.034-0.122), p = 0.001). No effects were found for the dimensions "to want" or "to care". The intervention also had a small but significant effect on children's health literacy but not on school well-being. These findings demonstrate the value of FOODcamp and the positive impacts of a relatively brief intervention on children's FL.

Approaches for Health Effect Characterization in Risk-Benefit Assessment of Foods: A Comparative Case Study.

One of the challenges in quantitative risk-benefit assessment (RBA) of foods is the choice of approach for health effect characterization to estimate the health impact of dietary changes. The purpose of health effect characterization is to describe an association between intake of a food or food component and a health effect in terms of a dose-response relationship. We assessed the impact of the choice of approach for health effect characterization in RBA in two case studies based on substitution of (i) white rice by brown rice and (ii) unprocessed red meat by vegetables. We explored this by comparing the dose-response relations linking a health effect with (i) a food component present in the food, (ii) a food based on non-specified substitution analyses, and (iii) a food based on specified substitution analyses. We found that the choice of approach for health effect characterization in RBA may largely impact the results of the health impact estimates. Conducting the calculations only for a food component may neglect potential effects of the food matrix and of the whole food on the diet-disease association. Furthermore, calculations based on associations for non-specified substitutions include underlying food substitutions without specifying these. Data on relevant specified substitutions, which could reduce this type of bias, are unfortunately rarely available. Assumptions and limitations of the health effect characterization approaches taken in RBA should be documented and discussed, and scenario analysis is encouraged when multiple options are available.

Absorption, distribution, metabolism and excretion (ADME) of oral selenium from organic and inorganic sources: A review.

BACKGROUND: Selenium is a trace element traditionally ingested either in its organic form via food or in its inorganic form through nutritional supplements, while selenium formulated as nanoparticles is a putative long-acting alternative. To understand the physiology and toxicology of the different selenium formulations, it is important to determine how their selenium content is absorbed, distributed, metabolised and excreted; therefore, we reviewed their biokinetics following oral exposure. METHODS: We retrieved and reviewed the literature on the absorption, distribution, metabolism, and excretion of oral exposure to different forms of selenium. RESULTS: Selenium in both the organic form (containing carbon to selenium chemical bonds) and the inorganic form is absorbed into the blood in humans. The mean normal blood level of many studies was 139 µg/L. There are indications that selenium from organic sources is more bioavailable than selenium from inorganic sources. Selenium is distributed throughout the body, including in breast milk. The elimination of selenium mainly involves the faecal and urinary pathways, whereas breath, saliva and hair are minor contributors. Urinary metabolites include trimethylselenium ions, selenosugars and Se-methylselenoneine. CONCLUSION: Selenium is absorbed to a high extent, and selenium from organic sources is more bioavailable than from inorganic sources. Selenium, as expected as an essential trace element, is distributed throughout the body. Selenium is extensively metabolised, and various excretion metabolites have been identified in both urine and breath, while some selenium is also excreted via faeces.

Sequential transfer learning based on hierarchical clustering for improved performance in deep learning based food segmentation.

Accurately segmenting foods from optical images is a challenging task, yet becoming possible with the help of recent advances in Deep Learning based solutions. Automated identification of food items opens up possibilities of useful applications like nutrition intake monitoring. Given large variations in food choices, Deep Learning based solutions still struggle to generate human level accuracy. In this work, we propose a novel Sequential Transfer Learning method using Hierarchical Clustering. This novel approach simulates a step by step problem solving framework based on clustering of similar types of foods. The proposed approach provides up to 6% gain in accuracy compared to traditional network training and generated a robust model performing better in challenging unseen cases. This approach is also tested for segmenting foods in Danish school children meals for dietary intake monitoring as an application.

Influence of educational level on test and treatment for incident hypothyroidism.

OBJECTIVE: The incidence of hypothyroidism is not expected to differ by socioeconomic factors. However, the decision to test and initiate treatment may differ. We aimed to examine whether educational level influences the probability of thyroid stimulation hormone (TSH)-measurement and initiation of levothyroxine treatment. DESIGN: Citizens in the greater Copenhagen Area during 2001-2015 were included. Individual-level data on educational level, diagnoses, GP-contact, TSH-measurement and medication were derived from administrative and healthcare registers. The relative risks (RR) between educational levels of annual TSH-measurement and treatment initiation following a TSH-measurement were analysed in Poisson regression models with generalized estimation equations. RESULTS: A TSH-measurement was performed in 19% of 9,390,052 person years. The probability of TSH-measurement was higher with short (RR 1.16 [95% CI 1.15-1.16]) and medium (RR 1.11 [95% CI 1.06-1.12]) compared with long education. Treatment was initiated after 0.8% of 2,049,888 TSH-measurements. For TSH < 5 mIU/L, RR for treatment initiation ranged between 0.47 (95%CI 0.39-0.57) and 0.78 (95%CI 0.67-0.91) for short and medium compared with long education. For TSH 5-10 mIU/L, there was no statistically significant difference. For TSH > 10 mIU/L, RR was 1.07 (95% CI 1.02-1.12) for short and 1.08 (95% CI 1.03-1.13) for medium compared with long education. CONCLUSION: The probability of TSH-measurement was higher with shorter education, and the probability of treatment initiation with TSH > 10 mIU/L was marginally higher with short-medium education compared with long education. However, the probability of treatment initiation with TSH < 5 mIU/L, that is treatment incongruous with guidelines, was substantially higher in persons with long education.

Increasing Seaweed Consumption in the Netherlands and Portugal and the Consequences for the Intake of Iodine, Sodium, and Exposure to Chemical Contaminants: A Risk-Benefit Study.

Background: Seaweed has a high potential for nourishing the future planet. However, besides being beneficial, it also contains adverse components; this poses the question whether consumption of seaweed foods overall contributes beneficially or detrimentally to human health, and hence if their consumption should be promoted or restricted. Methods: This study evaluated the impact of substituting regular foods with seaweed foods in the diet, both in terms of nutritional quality (via iodine and sodium) and food safety (via arsenic, cadmium, lead, and mercury). Food consumption data from the Netherlands and Portugal (adults aged >18 years) were used, in which 10% of the amounts of pasta, bacon, and lettuce consumed were replaced by seaweed-derived products made from kelp (Saccharina latissima). Using Monte Carlo Risk Assessment software (MCRA), long-term nutrient intake and exposure to contaminants were assessed. The results obtained for the Netherlands and Portugal were compared with data from Japan, a country that has a high natural consumption of seaweed. Results: This low-tier risk-benefit study reveals that an increased seaweed consumption (as assessed by the 10% replacement with seaweed products) has no consequences in terms of intake of sodium and exposure to cadmium, lead, and mercury, and the associated (absence of) adverse health aspects. The alternative scenario almost doubled the mean iodine intake in the Netherlands (to 300 µg/day) and Portugal (to 208 µg/day) and increased the average exposure to arsenic levels in the Netherlands (to 1.02 µg/kg bw/day) and Portugal (to 1.67 µg/kg bw/day). Conclusion: The intake of iodine and exposure to arsenic in the Netherland and Portugal were certainly higher due to the modeled increase of seaweed foods. If seaweed consumption increases close to the 10% substitution, the public health consequences thereof may trigger further research.