Effects of Two Weekly Servings of Cod for 16 Weeks in Pregnancy on Maternal Iodine Status and Infant Neurodevelopment: Mommy's Food, a Randomized-Controlled Trial.

Background: Mild-to-moderate iodine deficiency is still present in many countries, particularly in pregnant women. Observational studies suggest that mild-to-moderate iodine deficiency during pregnancy may be associated with impaired thyroid function and child neurodevelopment. Randomized-controlled food trials to increase iodine status are scarce. We assessed the impact of an increased intake of cod during pregnancy on maternal iodine status and infant neurodevelopment. Methods: In this randomized-controlled trial, pregnant women in Bergen, Norway, recruited through Haukeland University Hospital, were randomly assigned (1:1) to an intervention of 200 g of cod twice a week for 16 weeks (gestational week 20-36) or to continue with their standard diet (control group). Randomization was done by lottery. Primary outcome was urinary iodine concentration (UIC) (spot samples from six consecutive days) measured postintervention. Secondary outcome was infant neurodevelopment assessed by the cognitive, language, and motor scales of the Bayley Scales of Infant and Toddler Developmental third edition (Bayley-III) at 11 months of age. In addition, maternal thyroid function was measured (thyrotropin [TSH], free triiodothyronine [fT3], free thyroxine [fT4]) at baseline and postintervention. Results: Between January 2016 until February 2017, 137 women were recruited. Postintervention UIC was higher in the intervention group (n = 61) [median (interquartile range, IQR) 98 (64-145) µg/L], compared with control (n = 61) [median (IQR) 73 (52-120) µg/L] (p = 0.028), also after adjusting for baseline UIC (p = 0.048). Infants of mothers in the intervention group had a lower cognitive composite score on the Bayley-III compared with the control group (p = 0.045). There were no group differences in the Bayley III language- or motor composite scores. Maternal thyroid hormones (TSH, fT3, fT4) did not differ between the groups postintervention. Conclusions: Increased cod intake during pregnancy improved the iodine status in women with mild-to-moderate iodine deficiency, however, did not affect thyroid function. The negative effect on cognition should be followed up to assess whether this is a stable effect over time. More studies are warranted to enable good health advice on iodine nutrition in pregnancy. ClinicalTrials.gov NCT02610959. Registered November 20, 2015.

Iodine and Mercury Content in Raw, Boiled, Pan-Fried, and Oven-Baked Atlantic Cod (Gadus morhua).

There is a lack of scientific evidence regarding the stability of iodine and mercury during cooking and processing of seafood. In this study, the iodine and mercury content were determined after thawing frozen fillets of Atlantic cod (Cadus morhua), and further in raw compared to boiled, pan-fried, and oven baked fillets. Iodine was determined by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) and mercury by atomic absorption spectrophotometry with Direct Mercury Analyzer (DMA-80). Thawing of the cod resulted on average in a 12% loss of iodine to the thawing water. Boiling significantly decreased the total content of iodine per slice of cod fillet corresponding to the concentration of iodine found in the boiling water. Pan-frying and oven-baking did not cause any significant changes of the total iodine content per slice of cod fillet, although iodine content per 100 g increased due to weight reduction of the cod slices from evaporation of water during preparation. For mercury, we found minimal changes of the different cooking methods. In summary, the findings in our study show that boiling had the greatest effect on the iodine content in the cod fillets. Type of cooking method should be specified in food composition databases as this in turn may influence estimation of iodine intake.

Belly flap from Norwegian spring-spawning herring (Clupea harengus L.): A potentially new product with high content of vitamin D, EPA and DHA.

Processing Norwegian spring-spawning herring (NSSH) yields large amounts of rest raw material which currently is used mainly for production of fish oil and fish meal for feed in aquaculture. However, belly flaps from NSSH might be a profitable resource as a food product. This study investigates the nutritional composition of the belly flaps. NSSH was harvested in the main season between September and February. Chemical analyses of fatty acids, protein and vitamin A and D in belly flaps were conducted. Belly flaps from NSSH had a mean fat and protein content of 32.3 ± 6.9 g/100 g and 12.6 ± 0.9 g/100g, respectively. Mean vitamin D level was 53.5 ± 8.5 µg/100 g and mean eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) levels were 2.0 ± 0.8 g/100g and 2.3 ± 1.0 g/100g, respectively. Belly flap from NSSH contains twice the amount of vitamin D, EPA and DHA compared to NSSH fillet. There were large seasonal variations in the amount of both vitamin D, EPA and DHA. Mean level of vitamin A was 45.0 ± 8.9 µg/100 g. Belly flap from NSSH is a potential product for human consumption with a high nutritional value.

Effects of seafood consumption on mercury exposure in Norwegian pregnant women: A randomized controlled trial.

BACKGROUND: Seafood provides nutrients that are important for optimal development of the unborn child. However, seafood is also a source of contaminants including mercury (Hg) and methylmercury (MeHg) that may have adverse effects on neurodevelopment of the fetus. Humans are predominantly exposed to MeHg through seafood consumption, however, levels of MeHg vary considerably between species. OBJECTIVES: Investigate, in a randomized controlled trial (RCT) during pregnancy, if an increased intake of Atlantic cod (Gadus morhua), a fish species with relatively low levels of MeHg contamination, influences total hair Hg (THHg) concentrations in humans. METHODS: Pregnant women (n = 137) were enrolled in the RCT "Mommy's Food" (2016-2017), which was designed to increase iodine status. Participants were randomly assigned to intervention (400 g of cod fillets per week) or control (continued habitual diet) groups for 16 weeks (gestational week 20-36). THHg concentrations were measured at baseline and post-intervention using thermal decomposition, amalgamation, and atomic absorption spectrophotometry (US EPA method 7473). The trial is registered in ClinicalTrials.gov, NCT02610959. RESULTS: Post-intervention, the intervention group had median (inter-quartile range) THHg concentrations of 554 (392-805) µg/kg, and the control group 485 (341-740) µg/kg (p = 0.186). When adjusting for baseline THHg concentrations, there was a significant difference between the groups in those participants with baseline THHg concentrations below 534 µg/kg. Post-intervention, 8% of the study population exceeded the US EPA reference dose in hair (1,000 µg/kg) (intervention group: n = 6, control group: n = 4). CONCLUSION: THHg concentrations were generally low in both study groups of pregnant women, despite the relatively high seafood intake. While the intervention with 400 g of cod per week slightly increased THHg concentrations, it did not lead to an increase in number of subjects exceeding the US EPA reference dose; a dose level at which no adverse effects are expected to occur over a period of lifetime exposure.

Validation and reproducibility of a new iodine specific food frequency questionnaire for assessing iodine intake in Norwegian pregnant women.

BACKGROUND: Iodized salt is not mandatory in Norway, and the permitted level of iodine in table salt is low (5 µg/g). Thus, milk and dairy products, fish and eggs are the main dietary sources of iodine in Norway. Mild-to-moderate iodine deficiency in pregnant women has been described in several European countries, including Norway. There are few validated tools available to assess iodine intake in an efficient manner. The aim of the current study was to assess the validity and reproducibility of a new iodine-specific food frequency questionnaire (I-FFQ) in Norwegian pregnant women. METHODS: An I-FFQ consisting of a total of 60 food items and the use of supplements was developed to assess iodine intake and was administrated to 137 pregnant women at gestational week 18-19. Reference methods were a structured 6-days iodine specific food diary, urinary iodine concentration (UIC) (pooled sample of spot UIC from six consecutive days), and thyroid function tests. Correlation analyses, Cohen's weighted kappa, Bland-Altman plots, and linear regression analyses were used to assess validity. Reproducibility of the I-FFQ was assessed in a subgroup (n = 47) at gestational week 35-36. RESULTS: There was a strong correlation between estimated iodine intake from the I-FFQ and food diary (r = 0.62, P < 0.001) and an acceptable correlation between the I-FFQ and UIC (r = 0.21, P = 0.018). There was no significant association between the I-FFQ and thyroid function tests. The I-FFQ estimated higher iodine intake compared to the food diary with a mean absolute difference 33 µg/day. The limits of agreement from the Bland-Altman plots were large, however few participants fell outside the limits of agreement (5.2-6.5%). There was no difference between the estimated iodine intake from the I-FFQ assessed at gestational week 18-19, and gestational week 35-36 (P = 0.866), and there was a strong correlation between the two time points (r = 0.63, P < 0.001). CONCLUSION: In summary, this study suggests that the I-FFQ can be used as a valid tool to estimate and rank iodine intake among Norwegian pregnant women. We further suggest that this I-FFQ may also be valid in other populations with similarly dietary patterns and where salt is not iodized. TRIAL REGISTRATION: The study is registered in ClinicalTrials.gov (NCT02610959).

Iodine status in Norwegian preschool children and associations with dietary iodine sources: the FINS-KIDS study.

PURPOSE: Iodine is an essential trace element necessary for thyroid hormone synthesis. Iodine deficiency is a continuing public health problem despite international efforts to eliminate it. Studies on iodine status in preschoolers are scarce. Thus, the aims of the current study were to determine the iodine status and to investigate possible associations between urinary iodine concentration (UIC) and estimated 24 h iodine extraction (UIE) and iodine-rich foods. METHODS: Data are cross-sectional baseline data, obtained from the two-armed randomized controlled dietary trial "Fish Intervention Studies-KIDS" (FINS-KIDS) conducted in Bergen, Norway. UIC was determined by inductively coupled plasma-mass spectrometry in spot urine samples. Inadequate UIC was defined as median < 100 µg/L, and low estimated 24 h UIE as < 65 µg/day. Habitual dietary intake was assessed by a short food frequency questionnaire. Logistic regression models were used to investigate possible associations between UIC and estimated 24 h UIE and iodine-rich dietary sources including seafood, dairy products and eggs. Iodine/creatinine ratio (I/Cr) was also estimated. RESULTS: Urinary spot samples were obtained from 220 children. The median (interquartile range) UIC and estimated 24 h UIE was 132 (96) µg/L, and 65 (55) µg/day, respectively. The majority of children had an estimated I/Cr ratio within 100-199 µg/g. Intake of sweet milk < 2 times/day versus ≥ 2 times/day was associated with UIC < 100 µg/L (OR 2.17, 95% CI 1.07-4.38, p = 0.031). Intake of dairy products (OR 3.59, 95% CI 1.13-11.43, p = 0.031) and sweet milk (OR 2.77, 95% CI 1.37-5.61, p = 0.005) < 2 times/day versus ≥ 2 times day was associated with estimated 24 h UIE < 65 µg/day. CONCLUSIONS: The preschoolers had adequate iodine status. Low intake of sweet milk and dairy products were associated with low iodine status.

Fatty fish, hair mercury and cognitive function in Norwegian preschool children: Results from the randomized controlled trial FINS-KIDS.

BACKGROUND: The toxic effects of prenatal methylmercury (MeHg) include neurological abnormalities and developmental delay of which infants and children are particular susceptible. Studies on the effects of low and moderate exposure show conflicting results. Seafood is the main dietary source of MeHg, but also contributes with nutrients regarded as beneficial for development. OBJECTIVES: To measure the change in total hair mercury concentration (THHg) after an intervention of lunch meals with fatty fish or meat in Norwegian preschool children, and to examine the associations between THHg and cognitive function. METHODS: Children (n = 232) 4-6 years old were randomized to lunch meals with fatty fish (n = 114) or meat (n = 118) three times a week for 16 weeks. THHg was determined using a Direct Mercury Analyzer, and cognitive function was assessed by the Wechsler Preschool and Primary Intelligence Scale-III (WPPSI-III) pre- and post-intervention. Linear mixed effect models were used to analyze changes in THHg and WPPSI-III scores. RESULTS: The mean (SD) THHg pre-intervention was 0.373 (0.204) mg kg-1. Children in the fish group had an increase in THHg (change 0.162, 95% CI 0.111, 0.213 mg kg-1), whereas children in the meat group had decreased THHg (-0.053, 95% CI -0.103, -0.002 mg kg-1). There were no notable associations between THHg and the WPPSI-III raw scores at baseline or after 16 weeks of the fish/meat intervention. CONCLUSIONS: Lunch meals including fatty fish led to a significant increase in THHg, but the values remain below the point of departures used for risk assessment by the EFSA, WHO and US-EPA. We observed no associations between THHg and cognitive function.

Iodine content of six fish species, Norwegian dairy products and hen's egg.

Iodine is a trace element required for the production of thyroid hormones, essential for metabolism, growth and brain development, particularly in the first trimester of pregnancy. Milk and lean fish are the main dietary sources of iodine in the Norwegian diet. Thus, the aim of the present study was to provide updated analysed values of iodine concentration in six fish species, 27 selected Norwegian iodine-rich dairy foods and Norwegian hen's eggs. The iodine concentrations in the wild fish species varied between 18 µg/100 g (Atlantic halibut) and 1,210 µg/100 g (pollack). The iodine concentration of cow milk varied between 12 and 19 µg/100 g and the iodine concentration of the eggs varied between 23 and 43 µg/100 g. The results in this study deviate somewhat from the current iodine concentrations in the Norwegian Food Composition Table. This deviation may have a large impact on the assessment of the iodine intake. Hence, updated knowledge about the variation in iodine level of fish, milk, dairy products and hen's egg are of great importance when estimating the iodine intake in the population. These data will contribute substantially to future estimations of dietary iodine intake and will be made available for the public Norwegian Food Composition Table.

Fatty fish intake and cognitive function: FINS-KIDS, a randomized controlled trial in preschool children.

BACKGROUND: Marine resources including fatty fish are important sources of n-3 long chain polyunsaturated fatty acids (n-3 LC-PUFAs), which are important for brain development. To our knowledge, this is the first randomized controlled trial (RCT) investigating the impact of fatty fish on cognition in preschool children. The purpose of the trial was to investigate whether an increased intake of fatty fish compared to meat improves cognitive function in children 4-6 years old. METHODS: The children (n = 232) in this two-armed RCT, Fish Intervention Studies-KIDS (FINS-KIDS) were recruited from 13 kindergartens in Bergen, Norway. They were randomly assigned to lunch meals with fatty fish (herring/mackerel) or meat (chicken/lamb/beef) three times a week for 16 weeks. The fish and meat were weighed before and after the meals to record the exact consumption (dietary compliance). The primary outcome was cognitive function measured by the Wechsler Preschool and Primary Scale of Intelligence, 3rd edition (WPPSI-III) and fine-motor coordination measured by the 9-Hole Peg Test (9-HPT) at pre- and post-intervention. Biological samples (blood, urine, hair), and questionnaires to the caregivers were included at both time points. Linear mixed effect models with a random intercept for kindergarten were used to analyze changes from pre- to post-intervention in the primary outcome variables. RESULTS: There were 218 children included in the trial (105 in the fish, and 113 in the meat group). The children consumed a mean (standard deviation) of 2070 (978) g fish or 2675 (850) g meat from the study meals (p < 0.0001). The fish group had a significant increase of red blood cell n-3 LC-PUFAs. The intervention had no effect on the WPPSI-III scores (mean change total raw score; fish group 17.7, 95% confidence interval (CI) 14.8-20.7 vs meat group 17.8, 95% CI 15.0-20.6, p = 0.97) in the main analyses. In the sub-analyses, adjusting for dietary compliance, the fish group showed a higher improvement on total raw score (20.4, 95% CI 17.5-23.3) compared to the meat group (15.2, 95% CI 12.4-18.0, p = 0.0060); docosahexaenoic acid mediated this effect. CONCLUSIONS: There was no beneficial effect of fatty fish compared to meat on cognitive functioning in the preschool children. When considering dietary compliance, we found a beneficial effect of fatty fish on cognitive scores. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02331667 December 17, 2014.

Effects of cod intake in pregnancy on iodine nutrition and infant development: study protocol for Mommy's Food - a randomized controlled trial.

BACKGROUND: Iodine is a key component of thyroid hormones that are critical for normal development of the brain and nervous system in utero. Recent results indicate that two thirds of pregnant women in Europe have sub-optimal iodine nutrition. In Norway, milk and seafood are the most important dietary iodine sources and contributes to about 80% of the intake. METHOD: Two-armed randomized trial where 137 pregnant women were randomized to either receiving cod twice weekly, or continue with habitual diet for 16 weeks (pregnancy week 20-36). Socioeconomic- and demographic factors, dietary information and biological (urine, blood, and hair) samples are collected pre- and post-intervention, and at six weeks, three-, six-, and eleven months postpartum. Biological samples (urine, blood, and hair) of the infant are collected at six weeks, three-, six-, and eleven months postnatal. Child development is assessed by The Bayley Scale of Infant and Toddler Development, 3rd edition, at eleven months, and by parent report on the Ages and Stages Questionnaire, 3rd edition, and Ages and Stages Questionnaire: Social Emotional at three-, six-, and eleven months. DISCUSSION: The Mommy's Food study will provide knowledge on changes in iodine nutrition when consuming iodine rich fish during pregnancy and contribute to the understanding of the impact of iodine status in pregnancy on infant neurodevelopment. TRIAL REGISTRATION: This study is registered in ClinicalTrials.gov (NCT02610959). Registered November 17, 2015.

High-fat feeding rather than obesity drives taxonomical and functional changes in the gut microbiota in mice.

BACKGROUND: It is well known that the microbiota of high-fat (HF) diet-induced obese mice differs from that of lean mice, but to what extent, this difference reflects the obese state or the diet is unclear. To dissociate changes in the gut microbiota associated with high HF feeding from those associated with obesity, we took advantage of the different susceptibility of C57BL/6JBomTac (BL6) and 129S6/SvEvTac (Sv129) mice to diet-induced obesity and of their different responses to inhibition of cyclooxygenase (COX) activity, where inhibition of COX activity in BL6 mice prevents HF diet-induced obesity, but in Sv129 mice accentuates obesity. RESULTS: Using HiSeq-based whole genome sequencing, we identified taxonomic and functional differences in the gut microbiota of the two mouse strains fed regular low-fat or HF diets with or without supplementation with the COX-inhibitor, indomethacin. HF feeding rather than obesity development led to distinct changes in the gut microbiota. We observed a robust increase in alpha diversity, gene count, abundance of genera known to be butyrate producers, and abundance of genes involved in butyrate production in Sv129 mice compared to BL6 mice fed either a LF or a HF diet. Conversely, the abundance of genes involved in propionate metabolism, associated with increased energy harvest, was higher in BL6 mice than Sv129 mice. CONCLUSIONS: The changes in the composition of the gut microbiota were predominantly driven by high-fat feeding rather than reflecting the obese state of the mice. Differences in the abundance of butyrate and propionate producing bacteria in the gut may at least in part contribute to the observed differences in obesity propensity in Sv129 and BL6 mice.

Macronutrient composition determines accumulation of persistent organic pollutants from dietary exposure in adipose tissue of mice.

Accumulation of persistent organic pollutants (POPs) has been linked to adipose tissue expansion. As different nutrients modulate adipose tissue development, we investigated the influence of dietary composition on POP accumulation, obesity development and related disorders. Lifespan was determined in mice fed fish-oil-based high fat diets during a long-term feeding trial and accumulation of POPs was measured after 3, 6 and 18months of feeding. Further, we performed dose-response experiments using four abundant POPs found in marine sources, PCB-153, PCB-138, PCB-118 and pp'-DDE as single congeners or as mixtures in combination with different diets: one low fat diet and two high fat diets with different protein:sucrose ratios. We measured accumulation of POPs in adipose tissue and liver and determined obesity development, glucose tolerance, insulin sensitivity and hepatic expression of genes involved in metabolism of xenobiotics. Compared with mice fed diets with a low protein:sucrose ratio, mice fed diets with a high protein:sucrose ratio had significantly lower total burden of POPs in adipose tissue, were protected from obesity development and exhibited enhanced hepatic expression of genes involved in metabolism and elimination of xenobiotics. Exposure to POPs, either as single compounds or mixtures, had no effect on obesity development, glucose tolerance or insulin sensitivity. In conclusion, this study demonstrates that the dietary composition of macronutrients profoundly modulates POP accumulation in adipose tissues adding an additional parameter to be included in future studies. Our results indicate that alterations in macronutrient composition might be an additional route for reducing total body burden of POPs.

Intake of farmed Atlantic salmon fed soybean oil increases hepatic levels of arachidonic acid-derived oxylipins and ceramides in mice.

Introduction of vegetable ingredients in fish feed has affected the fatty acid composition in farmed Atlantic salmon (Salmo salar L). Here we investigated how changes in fish feed affected the metabolism of mice fed diets containing fillets from such farmed salmon. We demonstrate that replacement of fish oil with rapeseed oil or soybean oil in fish feed had distinct spillover effects in mice fed western diets containing the salmon. A reduced ratio of n-3/n-6 polyunsaturated fatty acids in the fish feed, reflected in the salmon, and hence also in the mice diets, led to a selectively increased abundance of arachidonic acid in the phospholipid pool in the livers of the mice. This was accompanied by increased levels of hepatic ceramides and arachidonic acid-derived pro-inflammatory mediators and a reduced abundance of oxylipins derived from eicosapentaenoic acid and docosahexaenoic acid. These changes were associated with increased whole body insulin resistance and hepatic steatosis. Our data suggest that an increased ratio between n-6 and n-3-derived oxylipins may underlie the observed marked metabolic differences between mice fed the different types of farmed salmon. These findings underpin the need for carefully considering the type of oil used for feed production in relation to salmon farming.

Intake of farmed Atlantic salmon fed soybean oil increases insulin resistance and hepatic lipid accumulation in mice.

BACKGROUND: To ensure sustainable aquaculture, fish derived raw materials are replaced by vegetable ingredients. Fatty acid composition and contaminant status of farmed Atlantic salmon (Salmo salar L.) are affected by the use of plant ingredients and a spillover effect on consumers is thus expected. Here we aimed to compare the effects of intake of Atlantic salmon fed fish oil (FO) with intake of Atlantic salmon fed a high proportion of vegetable oils (VOs) on development of insulin resistance and obesity in mice. METHODOLOGY/PRINCIPAL FINDINGS: Atlantic salmon were fed diets where FO was partly (80%) replaced with three different VOs; rapeseed oil (RO), olive oil (OO) or soy bean oil (SO). Fillets from Atlantic salmon were subsequently used to prepare Western diets (WD) for a mouse feeding trial. Partial replacement of FO with VOs reduced the levels of polychlorinated biphenyls (PCB) and dichloro-diphenyl-tricloroethanes (DDT) with more than 50% in salmon fillets, in WDs containing the fillets, and in white adipose tissue from mice consuming the WDs. Replacement with VOs, SO in particular, lowered the n-3 polyunsaturated fatty acid (PUFA) content and increased n-6 PUFA levels in the salmon fillets, in the prepared WDs, and in red blood cells collected from mice consuming the WDs. Replacing FO with VO did not influence obesity development in the mice, but replacement of FO with RO improved glucose tolerance. Compared with WD-FO fed mice, feeding mice WD-SO containing lower PCB and DDT levels but high levels of linoleic acid (LA), exaggerated insulin resistance and increased accumulation of fat in the liver. CONCLUSION/SIGNIFICANCE: Replacement of FO with VOs in aqua feed for farmed salmon had markedly different spillover effects on metabolism in mice. Our results suggest that the content of LA in VOs may be a matter of concern that warrants further investigation.