Lean-seafood intake increases urinary iodine concentrations and plasma selenium levels: a randomized controlled trial with crossover design.

PURPOSE: Iodine deficiency due to insufficient nutritional intake is a public health challenge in several European countries, including Norway. Lean-seafood has a high iodine and arsenic (As) content and is a good source of selenium (Se). Evidence of a direct effect of increased intake of lean-seafood on iodine status is limited. The main aims were to determine the iodine status at baseline and to investigate possible dietary effects on urinary iodine concentration (UIC) after intervention with lean-seafood versus non-seafood. Plasma Se, and plasma and urinary As concentrations were also measured. METHODS: A randomized controlled crossover study comprising two 4 weeks experimental periods with two balanced diets varied in main proteins (60% of total dietary proteins) of lean-seafood and non-seafood, separated by a 5 week washout period. RESULTS: Twenty participants (7 males, 13 females) were included and the mean ± SD age was 50.6 ± 15.3 years for all participants. Fasting UIC was median (25th, 75th percentile) 70 (38, 110) and 79 (49, 94) µg/L in the lean-seafood and non-seafood intervention at baseline, respectively. UIC increased after 4 weeks of the lean-seafood intervention to 135 (110, 278) µg/L, but not after the non-seafood intervention [58 (33, 91) µg/L] (P diet-effect < 0.001). Fasting plasma Se increased in the lean-seafood intervention and decreased in the non-seafood intervention (P diet-effect = 0.001). Fasting urinary and plasma As increased in the lean-seafood intervention and was unchanged in the non-seafood intervention (P diet-effect < 0.001). CONCLUSION: The participant's UIC was below the recommended median (100 µg/L) at baseline, but increased sufficiently after a 4 week intervention with lean-seafood.

Dietary Intake and Biomarkers of Folate and Cobalamin Status in Norwegian Preschool Children: The FINS-KIDS Study.

BACKGROUND: Folate and cobalamin (vitamin B-12) are essential for growth and development. However, few population-based studies have investigated B-vitamin status in children. OBJECTIVES: This study aimed to assess biomarkers of folate and vitamin B-12 status and to explore their dietary determinants in healthy Norwegian children. METHODS: Using baseline data obtained from a randomized controlled trial on the effect of fish intake on neurodevelopment in children aged 4-6 y, we measured the plasma concentrations of folate, cobalamin, total plasma homocysteine (tHcy), and methylmalonic acid (MMA). Food-frequency questionnaires (FFQs) were used to assess dietary intake. We used unadjusted and multiple linear regression models to explore the determinants of biomarker concentrations. RESULTS: The median (IQR) of plasma folate (n = 197) and plasma cobalamin (n = 195) concentrations were 15.2 (12.2-21.1) nmol/L and 785 (632-905) pmol/L, respectively. Plasma folate concentrations of <10 nmol/L were observed in 13% of the children. No child had a cobalamin concentration <148 pmol/L. Two children were identified with elevated plasma MMA concentrations (>0.26 µmol/L) and 8 children had elevated tHcy concentrations (>6.5 µmol/L). Plasma folate concentration was inversely correlated with tHcy (ρ = -0.24, P < 0.001); we found no correlation between tHcy and cobalamin (ρ = -0.075, P = 0.30). Children who consumed vitamin supplements had 51% higher plasma folate concentrations (P < 0.0001) than those who did not. Consumption of red meat for dinner more than twice a week was associated with 23% lower plasma folate (P < 0.01). No other significant associations between dietary intake and the biomarkers were observed. CONCLUSIONS: The Norwegian preschool children from this cohort had adequate vitamin B-12 status. Poor folate status was common and associated with elevated tHcy. The implications of poor folate status during childhood should be a prioritized research question. This trial was registered at ClinicalTrials.gov as NCT02331667.

Seafood intake and the development of obesity, insulin resistance and type 2 diabetes.

We provide an overview of studies on seafood intake in relation to obesity, insulin resistance and type 2 diabetes. Overweight and obesity development is for most individuals the result of years of positive energy balance. Evidence from intervention trials and animal studies suggests that frequent intake of lean seafood, as compared with intake of terrestrial meats, reduces energy intake by 4-9 %, sufficient to prevent a positive energy balance and obesity. At equal energy intake, lean seafood reduces fasting and postprandial risk markers of insulin resistance, and improves insulin sensitivity in insulin-resistant adults. Energy restriction combined with intake of lean and fatty seafood seems to increase weight loss. Marine n-3 PUFA are probably of importance through n-3 PUFA-derived lipid mediators such as endocannabinoids and oxylipins, but other constituents of seafood such as the fish protein per se, trace elements or vitamins also seem to play a largely neglected role. A high intake of fatty seafood increases circulating levels of the insulin-sensitising hormone adiponectin. As compared with a high meat intake, high intake of seafood has been reported to reduce plasma levels of the hepatic acute-phase protein C-reactive protein level in some, but not all studies. More studies are needed to confirm the dietary effects on energy intake, obesity and insulin resistance. Future studies should be designed to elucidate the potential contribution of trace elements, vitamins and undesirables present in seafood, and we argue that stratification into responders and non-responders in randomised controlled trials may improve the understanding of health effects from intake of seafood.

The effect of Atlantic salmon consumption on the cognitive performance of preschool children - A randomized controlled trial.

BACKGROUND AND AIMS: Long chain polyunsaturated n-3 fatty acids (LC-PUFA) are of functional and structural importance for brain development. Observational studies have shown positive relations between fatty fish consumption and cognitive performance in children, but Results from intervention studies using supplementary n-3 LC-PUFA are conflicting. Salmon is a good source of n-3 LC-PUFA, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). We tested the hypothesis that an increased dietary salmon intake results in better cognitive outcomes than a meat based diet. METHODS: Children (n = 205, age 4-6 years) in this trial were individually randomized to eating meals containing farmed Atlantic salmon or meat three times weekly for 16 weeks. Pre- and post-intervention a cognitive test (Wechsler Preschool and Primary Scale of Intelligence, 3rd edition, WPPSI-III) and a fine-motor coordination test (Nine Hole Peg Test, 9-HPT) were performed. Biochemical analyses included glycerophospholipid fatty acid profiles in plasma and cheek cells, serum 25-hydroxyvitamin D, and urinary iodine concentration. Dietary intake before and during the study were determined using food frequency questionnaires. RESULTS: Intakes of EPA, DHA, vitamin D and iodine were higher in the salmon than the meat group, but on biomarker level only EPA and DHA increased significantly in the salmon group compared to the meat group (p < 0.001). In general linear models no significant differences between the intervention groups were found in the scale scores of the WPPSI-III tests and the 9-HPT. In analyses of the raw scores, the salmon group showed significantly better improvement in two of the eight raw scores compared to the meat group (symbol search p = 0.038, picture concepts p = 0.047). CONCLUSIONS: Intake of farmed Atlantic salmon led to a greater increase of the raw scores of the picture concept and symbol search subtests, while in the six other subtests raw scores were not different between the groups. This might indicate a modest positive association of salmon intake with the performance of preschool children in some subtests evaluating fluid intelligence but does not suggest an influence on global IQ development. CLINICAL TRIAL REGISTRY NUMBER AND WEBSITE: ClinicalTrials.gov registration number: NCT01951937.

Maternal Iodine Status is Associated with Offspring Language Skills in Infancy and Toddlerhood.

Inadequate iodine status affects the synthesis of the thyroid hormones and may impair brain development in fetal life. The aim of this study was to explore the association between maternal iodine status in pregnancy measured by urinary iodine concentration (UIC) and child neurodevelopment at age 6, 12 and 18 months in a population-based cohort. In total, 1036 families from nine locations in Norway were enrolled in the little in Norway cohort. The present study includes n = 851 mother-child pairs with singleton pregnancies, no use of thyroid medication in pregnancy, no severe genetic disorder, data on exposure (UIC) in pregnancy and developmental outcomes (Bayley Scales of Infant and Toddler Development, third edition). Data collection also included general information from questionnaires. We examined associations between UIC (and use of iodine-containing supplements) and repeated measures of developmental outcomes using multivariable mixed models. The median UIC in pregnancy was 78 µg/L (IQR 46⁻130), classified as insufficient iodine intake according to the WHO. Eighteen percent reported use of iodine-containing multisupplements. A UIC below ~100 was associated with reduced receptive (p = 0.025) and expressive language skills (p = 0.002), but not with reduced cognitive or fine- and gross motor skills. Maternal use of iodine-containing supplements was associated with lower gross motor skills (b = -0.18, 95% CI = -0.33, -0.03, p = 0.02), but not with the other outcome measures. In conclusion, an insufficient iodine intake in pregnancy, reflected in a UIC below ~100 µg/L, was associated with lower infant language skills up to 18 months. The use of iodine-containing supplements was not associated with beneficial effects.

The effects of fatty fish intake on adolescents' nutritional status and associations with attention performance: results from the FINS-TEENS randomized controlled trial.

BACKGROUND: Adolescence involves changes in dietary habits that may induce imbalances in the intake of different nutrients. Fish is an important dietary source of omega-3 (n-3) long-chain polyunsaturated fatty acids (LCPUFAs), vitamin D, several minerals and high-quality protein. By using secondary outcomes and exploratory analyses, the aims of this paper were to evaluate if nutritional biomarkers (red blood cell fatty acids, serum (s)-25(OH)D, s-ferritin and urinary iodine concentration (UIC)) were altered during a dietary intervention, and if they mediated previously reported changes in attention performance. In addition, to examine the status of the biomarkers and explore associations between dietary pattern, biomarkers and attention performance cross-sectionally at baseline. METHODS: The Fish Intervention Studies-TEENS (FINS-TEENS) was a three-armed intervention trial, including adolescents from eight secondary schools (n = 415; age: 14-15y) in Bergen, Norway. Participants were individually randomized to receive either fish meals, meat meals or n-3 LCPUFA supplements, three times a week for a total of 12 weeks. Blood and urine samples were collected pre and post intervention and attention performance was assessed with the d2 test of attention. Analyses of covariance (ANCOVA) assessed differences between groups in changes of biomarkers and linear mixed models were applied in analyses of attention performance and biomarkers. The trial is registered in ClinicalTrials.gov (NCT02350322). RESULTS: At baseline, the mean omega-3 index was 5.8 ± 1.3% and deficient status were identified for s-25(OH)D (54%), s-ferritin (10%) and UIC (40%). The intervention resulted in an increase in DHA and the omega-3 index which was larger in the supplement group compared to the fish and meat group (P < 0.01), and in the fish group compared to the meat group (P < 0.01). No differences between the groups were observed for changes in 25(OH)D, s-ferritin or UIC. None of the biomarkers mediated performance in the d2 test. The intake of fatty fish and a healthy dietary pattern was associated with scores in processing speed at baseline. CONCLUSIONS: These results show that Norwegian adolescents have insufficient status of important nutrients, which may be improved with fatty fish consumption or n-3 LCPUFA supplements. However, nutritional status was not associated with scores in the d2 test of attention.

Fatty fish intake and attention performance in 14-15 year old adolescents: FINS-TEENS - a randomized controlled trial.

BACKGROUND: Fatty fish is the dominant dietary source of n-3 LCPUFAs but it also contains other micronutrients considered important for brain development and function. To our knowledge, the effect of fatty fish intake on cognitive function in adolescents has not been investigated in randomized controlled trials (RCTs) previously. The aim of the present trial was to investigate whether consumption of fatty fish meals three times per week for 12 weeks could alter attention performance in adolescents compared to similar meals with meat or n-3 LCPUFA supplements. METHODS: In the Fish Intervention Studies-TEENS (FINS-TEENS), adolescents from eight secondary schools (n = 426; age: 14-15y) were individually randomized. Attention performance was assessed with the d2 test of attention. Differences between groups from pre to post intervention were assessed with linear mixed effect models and general estimates equation. The fish group was set as reference. Dietary compliance was recorded for each meal throughout the trial and controlled for in the adjusted analyses. RESULTS: The improvement in processing speed was significantly lower in the meat (-11.8; 95% CI: -23.3, -0.4) and supplement (-13.4; 95% CI: -24.9, -1.8) group compared to the fish group (reference). The supplement group also showed inferior improvement in total performance (-10.4; 95% CI: -20.0, -0.7) compared to the fish group (reference). The results were slightly affected when controlling for dietary compliance. Omission errors decreased in the meat group compared to the fish group (Incidence rate ratio = 0.85; 95% CI: 0.74, 0.98), but the difference disappeared when controlling for dietary compliance. CONCLUSIONS: We observed a small beneficial effect of fatty fish, compared to meat meals and supplements on processing speed. However, these results are difficult to interpret due to low dietary compliance. This study shows that different taste preferences among participants is challenging in intervention trials with food. A prospective cohort design may be a better alternative when studying diet in the future. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov registration number: NCT02350322 .

Design of the FINS-TEENS study: A randomized controlled trial assessing the impact of fatty fish on cognitive performance in adolescents.

AIMS: To describe the rationale, study design, population and dietary compliance in a randomized controlled trial (RCT) investigating the effect of fatty fish on cognitive performance and mental health in adolescents. METHOD: In the Fish Intervention Studies-TEENS (FINS-TEENS) study we individually randomized 478 adolescents (14-15-year-olds) from eight secondary schools in Norway to receive school meal lunches with fatty fish or meat or n-3 supplements three times a week for 12 weeks. Demographic factors, psychological tests and biological measures were collected pre-and post-intervention. Duplicate portions of lunch meals were collected and individual intake recorded throughout the study. RESULTS: In total, 481 out of 785 adolescents (61%) agreed to participate and 34 (7%) dropped out. Breakfast consumption was the only group difference in background characteristics. Analyses of selected nutrients in the lunch meals showed higher levels of n-3 fatty acids, vitamin D and n-6 fatty acids in the fish compared to the meat meals. Dietary compliance (score 0-144) revealed that the intake in the Fish group (mean = 59, standard deviation (SD) = 35) were lower than in the Meat group (mean = 83, SD = 31, p < 0.01) and Supplement group (mean = 105, SD = 25, p < 0.01). CONCLUSIONS: The results show that it is possible to conduct a RCT with fatty fish in a school-based setting. The results also emphasize the importance of collecting detailed records of dietary compliance, as this information is important when interpreting and analysing the outcome of dietary interventions.

Associations between intake of fish and n-3 long-chain polyunsaturated fatty acids and plasma metabolites related to the kynurenine pathway in patients with coronary artery disease.

PURPOSE: Enhanced tryptophan degradation via the kynurenine pathway has been related to several pathological conditions. However, little is known about the effect of diet on individual metabolites of this pathway. We investigated cross-sectional associations between reported intake of fish and omega-3 (n-3) long-chain PUFA (LC-PUFA) and plasma metabolites related to the kynurenine pathway. METHODS: Participants were 2324 individuals with coronary artery disease from the Western Norway B Vitamin Intervention Trial. Fish and n-3 LC-PUFA intakes were assessed using a food frequency questionnaire. Plasma concentrations of tryptophan, kynurenine, kynurenic acid, anthranilic acid, 3-hydroxykynurenine, xanthurenic acid, 3-hydroxyanthranilic acid, neopterin, and kynurenine-to-tryptophan ratio (KTR) were analyzed. Associations were investigated using partial Spearman's rank correlations and multiple linear regressions. RESULTS: Median age at inclusion was 62 years (80 % males), and 84 % had stable angina pectoris. Intake of fatty fish and n-3 LC-PUFA was inversely associated with plasma 3-hydroxykynurenine. Consumption of total fish, lean fish, and n-3 LC-PUFA was inversely associated with plasma neopterin. Intake of total fish, fatty fish, and n-3 LC-PUFA was inversely associated with KTR. All these correlations were weak (ρ between -0.12 and -0.06, P < 0.01). In 306 patients with diabetes, lean fish intake was positively associated with plasma 3-hydroxyanthranilic acid (ρ = 0.22, P < 0.001, P for interaction = 0.01), and total fish intake was inversely associated with KTR (ρ = -0.17, P < 0.01, P for interaction = 0.02). CONCLUSION: Fish intake was not an important determinant of individual metabolites in the kynurenine pathway. However, some correlations were stronger in patients with diabetes. The inverse associations of fish or n-3 LC-PUFA with neopterin and KTR may suggest a slightly lower IFN-γ-mediated immune activation with a higher intake.

Reduced bone resorption by intake of dietary vitamin D and K from tailor-made Atlantic salmon: A randomized intervention trial.

Suboptimal vitamin D status is common among humans, and might increase bone resorption with subsequent negative effects on bone health. Fatty fish, including Atlantic salmon, is an important dietary vitamin D source. However, due to a considerable change in fish feed composition, the contribution of vitamin D from salmon fillet has been reduced. The main objective was to investigate if intake of vitamin D3 enriched salmon or vitamin D3 tablets decreased bone biomarkers (urinary N-telopeptides, deoxypyridinoline, serum bone-specific alkaline phosphatase, and osteocalcin) compared to a low vitamin D3 intake. The 122 healthy postmenopausal women included in this 12 weeks intervention trial were randomized into four groups: three salmon groups (150 grams/two times/week) and one tablet group (800 IU vitamin D and 1000 mg calcium/day). The salmon groups also received calcium supplements. The salmon had three different vitamin D3/vitamin K1 combinations: high D3+high K1, low D3+high K1, or high D3+low K1. Increased intake of salmon containing high levels of vitamin D3 (0.35-0.38 mg/kg/fillet) and supplements with the same weekly contribution had a positive influence on bone health as measured by bone biomarkers in postmenopausal women. Consequently, an increased level of vitamin D3 at least to original level in feed for salmonids will contribute to an improved vitamin D3 status and may improve human bone health.