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Background: Intrahepatic triacylglycerol (liver TG) content is associated with hepatic insulin resistance and dyslipidemia. Liver TG content can be modulated within days under hypocaloric conditions., Objectives: We hypothesized that 4 d of eucaloric low-carbohydrate/high-fat (LC) intake would decrease liver TG content, whereas a high-carbohydrate/low-fat (HC) intake would increase liver TG content, and further that alterations in liver TG would be linked to dynamic changes in hepatic glucose and lipid metabolism., Methods: A randomized crossover trial in males with 4 d + 4 d of LC and HC, respectively, with ≥2 wk of washout. 1 H-magnetic resonance spectroscopy ( 1 H-MRS) was used to measure liver TG content, with metabolic testing before and after intake of an LC diet (11E% carbohydrate corresponding to 102 ± 12 {mean ± standard deviation [SD]) g/d, 70E% fat} and an HC diet (65E% carbohydrate corresponding to 537 ± 56 g/d, 16E% fat). Stable [6,6- 2 H 2 ]-glucose and [1,1,2,3,3-D5]-glycerol tracer infusions combined with hyperinsulinemic-euglycemic clamps and indirect calorimetry were used to measure rates of hepatic glucose production and lipolysis, whole-body insulin sensitivity and substrate oxidation., Results: Eleven normoglycemic males with overweight or obesity (BMI 31.6 ± 3.7 kg/m 2 ) completed both diets. The LC diet reduced liver TG content by 35.3% (95% confidence interval: -46.6, -24.1) from 4.9% [2.4-11.0] (median interquartile range) to 2.9% [1.4-6.9], whereas there was no change after the HC diet. After the LC diet, fasting whole-body fat oxidation and plasma beta-hydroxybutyrate concentration increased, whereas markers of de novo lipogenesis (DNL) diminished. Fasting plasma TG and insulin concentrations were lowered and the hepatic insulin sensitivity index increased after LC. Peripheral glucose disposal was unchanged., Conclusions: Reduced carbohydrate and increased fat intake for 4 d induced a marked reduction in liver TG content and increased hepatic insulin sensitivity. Increased rates of fat oxidation and ketogenesis combined with lower rates of DNL are suggested to be responsible for lowering liver TG. This trial was registered at clinicaltrials.gov as NCT04581421., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Detailed knowledge regarding the associations between intake of different types of seafood and meat and the risk of type 2 diabetes (T2D), and insight into possible mechanisms are warranted. In this study we aimed to evaluate the associations between intake of different types of seafood and meat and the subsequent risk of T2D using the Norwegian Mother, Father, and Child Cohort Study (MoBa), and furthermore, by using a mouse model to gain further insight into possible molecular mechanisms contributing to the associated metabolic changes. Women in MoBa who were free of pharmacologically treated diabetes at baseline (n = 60,777) were prospectively evaluated for incident T2D, identified on the basis of medication usages > 90 days after delivery, ascertained by the Norwegian Prescription Database. Dietary intake was obtained with a validated 255-item food frequency questionnaire which assessed habitual diet during the first 4-5 months of pregnancy. Metabolic phenotypes and plasma metabolome were investigated in female mice fed isocaloric diets with different types of seafood and meat mimicking the dietary intake in the human cohort. During maximum 10-year and mean (SD) 7.2 (1.6) years follow-up time, 681 (1.1%) women developed pharmacologically treated T2D. All statistical models identified a higher risk of T2D with increased shellfish intake, whereas no associations were observed for total seafood, fatty fish, total meat and red meat in the adjusted models. In mice, the shellfish-based western diet induced reduced glucose tolerance and insulin secretion compared to the diet based on lean fish, and we identified a number of metabolites elevated in plasma from shellfish-fed mice that correlated with glucose intolerance. Mice fed a western diet based on meat also exhibited reduced glucose tolerance in comparison to lean fish fed mice, whereas mice fed fatty fish, total seafood or red meat did not differ from lean fish fed mice. We observed a diet-specific metabolic signature in plasma demonstrating five distinct metabolite profiles in mice fed shellfish, fatty fish, total seafood/lean fish, a mixed diet and meat. In conclusion, these findings demonstrate that different types of seafood have different outcome on T2D risk. In women, intake of shellfish was associated with higher risk of T2D. In female mice, a shellfish enriched diet reduced glucose tolerance and altered the abundance of several distinct plasma metabolites correlating with glucose tolerance., (© 2024. The Author(s).)

Background: Choline is an essential nutrient for humans and is involved in various physiologic functions. Through its metabolite betaine, it is closely connected to the one-carbon metabolism, and the fat-soluble choline form phosphatidylcholine is essential for VLDL synthesis and secretion in the liver connecting choline to the lipid metabolism. Dietary recommendations for choline are not available in the Nordic countries primarily due to data scarcity., Objectives: The aim of this study was to investigate the dietary intake of total choline and individual choline forms, dietary sources, and the association of total choline intake with circulating one-carbon metabolites and lipids., Methods: We included 5746 participants in the Hordaland Health Study, a survey including community-dwelling adults born in 1925-1927 (mean age 72 y, 55% women) and 1950-1951 (mean age 48 y, 57% women). Dietary data were obtained using a 169-item FFQ, and choline content was calculated using the USDA Database for Choline Content of Common Foods, release 2. Metabolites of the one-carbon and lipid metabolism were measured in a nonfasting blood sample obtained at baseline, and the association with total choline intake was assessed using polynomial splines., Results: The geometric mean (95% prediction interval) energy-adjusted total choline intake was 260 (170, 389) mg/d, with phosphatidylcholine being the main form (44%). The major food items providing dietary choline were eggs, low-fat milk, potatoes, and leafy vegetables. Dietary total choline was inversely associated with circulating concentrations of total homocysteine, glycine, and serine and positively associated with choline, methionine, cystathionine, cysteine, trimethyllysine, trimethylamine-N-oxide, and dimethylglycine. A weak association was observed between choline intake and serum lipids., Conclusions: Phosphatidylcholine was the most consumed choline form in community-dwelling adults in Norway. Our findings suggest that choline intake is associated with the concentration of most metabolites involved in the one-carbon and lipid metabolism., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Objective: To investigate associations between intakes of total fish, lean fish, fatty fish, and long-chain n-3 polyunsaturated fatty acid (LC n -3PUFA) supplements and risk of type 2 diabetes in women after pregnancy. Furthermore, we sought to compare the estimated intakes of methylmercury (MeHg) and sum of dioxins and dioxin-like polychlorinated biphenyls ( dl -PCBs) with tolerable weekly intakes (TWI)., Research Design and Methods: Women free of diabetes at baseline ( n = 60,831) who participated in the population-based Norwegian Mother, Father and Child Cohort Study (MoBa) were prospectively evaluated for incident type 2 diabetes, identified on the basis of medication usage >90 days after delivery, ascertained through the Norwegian Prescription Database. Dietary intake data were obtained with a validated 255-item food-frequency questionnaire (FFQ), which assessed habitual diet during the first 4-5 months of pregnancy. Intakes of MeHg and sum of dioxins and dl -PCBs were derived with use of a contaminant database and the FFQ., Results: Median age was 31 years (interquartile range 27, 34) at time of delivery, and follow-up time was 7.5 years (6.5, 8.5). Type 2 diabetes occurred in 683 (1.1%) participants. Multivariable Cox regression analyses identified lower risk of type 2 diabetes with increasing energy-adjusted lean fish intake, 25 g/1,000 kcal (25 g/1,000 kcal: hazard ratio 0.71, 95% CI 0.53-0.95, P = 0.022). However, in stratified analyses, a lower risk was found only in women with prepregnancy BMI ≥25 kg/m 2 . There were no associations between intake of total fish, fatty fish, or LC n -3PUFA supplements and type 2 diabetes. MeHg intake was low, but the intake of the sum of dioxins and dl -PCBs (picograms of toxic equivalents/kilograms of body weight/week) exceeded the TWI set by the European Food Safety Authority (EFSA) for the majority of participants., Conclusions: Intake of lean fish, but not fatty fish or LC n -3PUFA supplements, was associated with lower risk of pharmacologically treated type 2 diabetes in Norwegian women who were overweight or obese. Fatty fish, which contain dioxins and dl -PCBs, did not increase the risk of type 2 diabetes, but the exceedance of the EFSA TWI for dioxins and dl -PCBs is a health concern., (© 2021 by the American Diabetes Association.)

Background: Biomarkers such as omega-3 (n-3) PUFAs, urinary iodine concentration (UIC), 1-methylhistidine (1-MH), and trimethylamine N-oxide (TMAO) have been associated with fish intake in observational studies, but data from children in randomized controlled trials are limited., Objectives: The objective of this exploratory analysis was to investigate the effects of fatty fish intake compared with meat intake on various biomarkers in preschool children., Methods: We randomly allocated (1:1) 232 children, aged 4 to 6 y, from 13 kindergartens. The children received lunch meals of either fatty fish (herring/mackerel) or meat (chicken/lamb/beef) 3 times a week for 16 wk. We analyzed 86 biomarkers in plasma (n = 207), serum (n = 195), RBCs (n = 211), urine (n = 200), and hair samples (n = 210). We measured the effects of the intervention on the normalized biomarker concentrations in linear mixed-effect regression models taking the clustering within the kindergartens into account. The results are presented as standardized effect sizes., Results: We found significant effects of the intervention on the following biomarkers: RBC EPA (20:5n-3), 0.61 (95% CI: 0.36, 0.86); DHA (22:6n-3), 0.43 (95% CI: 0.21, 0.66); total n-3 PUFAs, 0.41 (95% CI: 0.20, 0.64); n-3/n-6 ratio, 0.48 (95% CI: 0.24, 0.71); adrenic acid (22:4n-6, -0.65 (95% CI: -0.91, -0.40), arachidonic acid (20:4n-6), -0.54 (95% CI: -0.79, -0.28); total n-6 PUFAs, -0.31 (95% CI: -0.56, -0.06); UIC, 0.32 (95% CI: 0.052, 0.59); hair mercury, 0.83 (95% CI: 0.05, 1.05); and plasma 1-MH, -0.35 (95% CI: -0.61, -0.094)., Conclusions: Of the 86 biomarkers, the strongest effect of fatty fish intake was on n-3 PUFAs, UIC, hair mercury, and plasma 1-MH. We observed no or limited effects on biomarkers related to micronutrient status, inflammation, or essential amino acid, choline oxidation, and tryptophan pathways.The trial was registered at clinicaltrials.gov (NCT02331667)., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Choline is an essential nutrient involved in a wide range of physiological functions. It occurs in water- and lipid-soluble forms in the body and diet. Foods with a known high choline content are eggs, beef, chicken, milk, fish, and selected plant foods. An adequate intake has been set in the US and Europe, however, not yet in the Nordic countries. A higher intake of lipid-soluble choline forms has been associated with increased risk of acute myocardial infarction, highlighting the need for knowledge about food sources of the individual choline forms. In general, little is known about the habitual intake and food sources of choline, and individual choline forms. Objective: Investigate foods contributing to the intake of total choline and individual choline forms. Design: The study population consisted of 1,929 patients with stable angina pectoris from the Western Norway B Vitamin Intervention Trial. Dietary intake data was obtained through a 169-item food frequency questionnaire. Intake of total choline and individual choline forms was quantified using the USDA database, release 2. Results: The geometric mean (95% prediction interval) total choline intake was 287 (182, 437) mg/d. Phosphatidylcholine accounted for 42.5% of total choline intake, followed by free choline (25.8%) and glycerophosphocholine (21.2%). Phosphocholine and sphingomyelin contributed 4.2 and 4.5%, respectively. The main dietary choline sources were eggs, milk, fresh vegetables, lean fish, and bread. In general, animal food sources were the most important contributors to choline intake. Conclusion: This study is, to the best of our knowledge, the first to assess the intake of all choline forms and their dietary sources in a European population. Most choline was consumed in the form of phosphatidylcholine and animal food sources contributed most to choline intake. There is a need for accurate estimates of the dietary intake of this essential nutrient to issue appropriate dietary recommendations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Van Parys, Karlsson, Vinknes, Olsen, Øyen, Dierkes, Nygård and Lysne.)

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.

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., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

High plasma choline has been associated with the metabolic syndrome and risk of chronic diseases, including cardiovascular disease. However, dietary choline is not correlated with choline plasma concentrations, and there are few studies and contradictory evidence regarding dietary choline and cardiovascular events. In addition, a recommended dietary allowance for choline has not been established and remains a point of contention. This study assessed the association between dietary choline, including choline forms, and risk of incident acute myocardial infarction (AMI) in patients with suspected stable angina pectoris (SAP). In total 1981 patients (80% men, median age 62) from the Western Norway B Vitamin Intervention Trial were included in this analysis. Information on dietary choline was obtained using a 169-item food frequency questionnaire. The Cardiovascular Disease in Norway project provided data on AMI. Risk associations were estimated using Cox-regression analysis using energy-adjusted choline intake. Median (25th, 75th percentile) total energy-adjusted choline intake was 288 (255, 326) mg/d. During a median (25th, 75th percentile) follow-up of 7.5 (6.3, 8.8) years, 312 (15.7%) patients experienced at least one AMI. Increased intakes of energy-adjusted choline (HR [95% CI] per 50 mg increase 1.11 [1.03, 1.20]), phosphatidylcholine (HR per 50 mg increase 1.24 [1.08, 1.42]) and sphingomyelin (HR per 5 mg increase 1.16 [1.02, 1.31]) were associated with higher AMI risk. In conclusion, higher dietary intakes of total choline, phosphatidylcholine and sphingomyelin were associated with increased risk of AMI in patients with SAP. Future studies are necessary to explore underlying mechanisms for this observation., Competing Interests: Declaration of competing interest No conflict of interest reported by any of the authors., (Copyright © 2019 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)

Objectives: The aims of this study were to determine vitamin D status (serum 25-hydroxyvitamin D 3 [s-25(OH)D 3 ]) and examine possible associations between vitamin D status and vitamin D-rich dietary sources, sun exposure, and body mass index in preschool children ages 4 to 6 y., Methods: This is a cross-sectional study based on baseline data (collected in January-February 2015) from the two-armed randomized controlled trial Fish Intervention Studies-KIDS (FINS-KIDS) conducted in Bergen, Norway. S-25(OH)D 3 concentration was determined by liquid chromatography-tandem mass spectrometry. Information regarding habitual dietary intake, recent sun vacations, and body mass index were assessed with questionnaires answered by the children's caregivers., Results: The children (n = 212) had a mean (standard deviation) s-25(OH)D 3 of 60.7 (13.8) nmol/L; 18.9% had s-25(OH)D 3 ≤50 nmol/L. In logistic regression models, non-overweight versus overweight status was inversely associated with s-25(OH)D 3 ≤50 nmol/L (odds ratio: 0.41; 95% confidence interval, 0.18-0.95; P = 0.037). Non-sun versus sun vacations were associated with s-25(OH)D 3 ≤75 nmol/L (odds ratio: 5.33; 95% confidence interval, 1.93-14.77; P = 0.001)., Conclusions: The majority of the preschool children (81%) had s-25(OH)D 3 >50 nmol/L. Children with overweight status had an increased risk of s-25(OH)D 3 ≤50 nmol/L, and children who had not been on sun vacations were at a greater risk of s-25(OH)D 3 ≤75 nmol/L., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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., (Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

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.

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.

Low-fat diets and energy restriction are recommended to prevent obesity and to induce weight loss, but high-protein diets are popular alternatives. However, the importance of the protein source in obesity prevention and weight loss is unclear. The aim of this study was to investigate the ability of different animal protein sources to prevent or reverse obesity by using lean or obese C57BL/6J mice fed high-fat/high-protein or low-fat diets with casein, cod or pork as protein sources. Only the high-fat/high-protein casein-based diet completely prevented obesity development when fed to lean mice. In obese mice, ad libitum intake of a casein-based high-fat/high-protein diet modestly reduced body mass, whereas a pork-based high-fat/high-protein diet aggravated the obese state and reduced lean body mass. Caloric restriction of obese mice fed high-fat/high-protein diets reduced body weight and fat mass and improved glucose tolerance and insulin sensitivity, irrespective of the protein source. Finally, in obese mice, ad libitum intake of a low-fat diet stabilized body weight, reduced fat mass and increased lean body mass, with the highest loss of fat mass found in mice fed the casein-based diet. Combined with caloric restriction, the casein-based low-fat diet resulted in the highest loss of fat mass. Overall, the dietary protein source has greater impact in obesity prevention than obesity reversal.

High protein diets have become popular for body weight maintenance and weight loss despite controversies regarding efficacy and safety. Although both weight gain and weight loss are determined by energy consumption and expenditure, data from rodent trials consistently demonstrate that the protein:carbohydrate ratio in high fat diets strongly influences body and fat mass gain per calorie eaten. Here, we review data from rodent trials examining how high protein diets may modulate energy metabolism and the mechanisms by which energy may be dissipated. We discuss the possible role of activating brown and so-called beige/BRITE adipocytes including non-canonical UCP1-independent thermogenesis and futile cycles, where two opposing metabolic pathways are operating simultaneously. We further review data on how the gut microbiota may affect energy expenditure. Results from human and rodent trials demonstrate that human trials are less consistent than rodent trials, where casein is used almost exclusively as the protein source. The lack of consistency in results from human trials may relate to the specific design of human trials, the possible distinct impact of different protein sources, and/or the differences in the efficiency of high protein diets to attenuate obesity development in lean subjects vs. promoting weight loss in obese subjects.

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., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Mental health and sleep problems are prevalent in children during preschool years. The aim of the current study was to investigate if increased intake of fatty fish compared with meat improves mental health and sleep in four- to six-year-old children. The children ( n = 232) in the two-armed randomized controlled trial, Fish Intervention Studies-KIDS (FINS-KIDS), 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 in grams (dietary compliance). Mental health problems were assessed by the strengths and difficulties questionnaire (SDQ) and sleep by parent report pre- and post-intervention. There was no significant statistical difference between changes in mental health and sleep for the fish eating group compared with the meat eating group, neither in the crude analysis nor after adjusting for intake of fish or meat (dietary compliance).

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.

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.

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.

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.

There is a growing body of evidence linking fish consumption and n-3 LCPUFAs to mental health. Still, the results from randomized trials with n-3 LCPUFAs show conflicting results, and it is possible that the combined effect of several nutrients in fish may explain the observed associations. To aim of the present study was to investigate if school meals with fatty fish three times per week for 12 weeks could alter mental health in a sample of typically developing adolescents. In the Fish Intervention Studies-TEENS (FINS-TEENS), adolescents from eight secondary schools (n=425) in Norway, were randomized to receive school meals with fatty fish, meat or n-3 LCPUFA supplements. Mental health was assessed with the Strengths and Difficulties Questionnaire (SDQ) and the differences between the groups were assessed with linear mixed effect models, unadjusted and adjusted for baseline and dietary compliance. The results showed no effects of school meals with fatty fish compared to similar meals with meat or n-3 LCPUFAs on the adolescents' self-reported symptom scores for mental health. Among adolescents scoring above the SDQ cut-offs (high-scorers), the fish- improved less than the meat group in the self-reported symptom scores for total difficulties- and emotional problems. However, the findings should be regarded as preliminary, as the analyses for the high-scorer group were underpowered. In conclusion, serving school meals with fatty fish did not alter mental health in a typically developing sample of adolescents. It is possible that serving healthy school meals with meat is more beneficial than similar meals with fatty fish in adolescents scoring high on mental health problems. However, the results should be seen as preliminary, as the dietary compliance in the fish group was low and the analyses in the high score group underpowered. Thus, further studies should investigate the associations between fish consumption and adolescents' mental health.

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 .

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.

Background: Choline is an important nutrient either obtained from a variety of foods or synthesized endogenously, and it is the precursor of betaine. We previously reported positive associations between plasma free choline and bone mineral density (BMD). Animal studies suggest an impact of dietary choline on bone metabolism, but the role of dietary intake of choline and betaine for human bone health is unknown. Objectives: The main aims were to examine the associations of dietary choline, choline species, and betaine with BMD and to study the relations between dietary and plasma free choline and betaine. Methods: Study subjects were participants in the Hordaland Health Study, including 2649 women and 1983 men (aged 46-49 or 71-74 y). BMD was measured by dual-energy X-ray absorptiometry, and dietary intake was obtained by using a validated 169-item food-frequency questionnaire. Risk associations were assessed by logistic regression and correlations by ρ (Spearman's bivariate rank order correlation). Results: Subjects in the lowest compared with the highest tertile of dietary total choline, free choline, glycerophosphocholine, phosphocholine, phosphatidylcholine, and sphingomyelin had a higher risk of low-femoral neck BMD, defined as the lowest BMD quintile. Particularly strong associations were found among middle-aged men for intake of free choline (OR: 1.83; 95% CI: 1.24, 2.69; P = 0.002) and glycerophosphocholine (OR: 2.13; 95% CI: 1.43, 3.16; P < 0.001) and among elderly women for total choline (OR: 1.96; 95% CI: 1.33, 2.88; P = 0.001) and phosphatidylcholine (OR: 1.94; 95% CI: 1.33, 2.84: P = 0.001) intake. No significant associations were observed between dietary betaine and BMD. Dietary total choline, free choline, glycerophosphocholine, phosphatidylcholine, and sphingomyelin correlated weakly with plasma free choline (ρ: 0.07, 0.05, 0.07, 0.07, and 0.05, respectively; P < 0.01). Dietary betaine correlated with plasma betaine (ρ: 0.23; P < 0.001). Conclusion: Dietary choline was positively associated with BMD in middle-aged and elderly participants., (© 2017 American Society for Nutrition.)

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.

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.

Assessment of adolescents' dietary habits is challenging. Reliable instruments to monitor dietary trends are required to promote healthier behaviours in this group. The purpose of this cross-sectional study was to assess adolescents' adherence to Norwegian dietary recommendations with a diet score and to report results from, and test-retest reliability of, the score. The diet score involved seven food groups and one physical activity indicator, and was applied to answers from a semi-quantitative food frequency questionnaire (FFQ) administered twice. Reproducibility of the score was assessed with Cohen's Kappa (κ statistics) at an interval of three months. The setting was eight lower-secondary schools in Hordaland County, Norway, and subjects were adolescents (n = 472) aged 14-15 years and their caregivers. Results showed that the proportion of adolescents consistently classified by the diet score was 87.6% (κ = 0.465). For food groups, proportions ranged from 74.0% to 91.6% (κ = 0.249 to κ = 0.573). Less than 40% of the participants were found to adhere to recommendations for frequencies of eating fruits, vegetables, added sugar, and fish. Highest compliance to recommendations was seen for choosing water as beverage and limit the intake of red meat. The score was associated with parental socioeconomic status. The diet score was found to be reproducible at an acceptable level. Health promoting work targeting adolescents should emphasize to increase the intake of recommended foods to approach nutritional guidelines.

Purpose: To evaluate the long-term clinical outcome after microfracture treatment of focal chondral defects of the knee and to investigate possible early determinants of the outcome., Methods: A prospective cohort of 110 patients, treated with microfracture, was evaluated at a median of 12 years (range 10-14) by Lysholm score, VAS of knee function and VAS of knee pain. Pre- and perioperative information was collected, and additional surgery to the same knee during the follow-up period was recorded. Analysis of variance and paired t test were used for comparison of the long-term data to results from the baseline examination and a former 5-year (midterm) follow-up evaluation., Results: Forty-three patients needed additional surgery to the knee including seven knee replacements. Fifty had a poor long-term outcome-defined as a knee replacement surgery or Lysholm score below 64. A poor result was more common in subgroups with mild degenerative changes in the cartilage surrounding the treated defect, concurrent partial meniscectomy, poor baseline Lysholm score or long-standing knee symptoms. The Lysholm score, function VAS and pain VAS all significantly improved from the baseline values to the mean scores of 65 (SD 24), 65 (SD 24) and 31 (SD 24), respectively, at the long-term evaluation. The long-term scores did not differ significantly from the midterm scores., Conclusions: The outcome scores improved significantly from baseline to the long-term evaluation and were not different from the midterm outcome. Still, a normal knee function was generally not achieved, and many patients had further surgery. The results call for more research and, at present, caution in recommending microfracture in articular cartilage defects, especially in subgroups with worse prognosis., Level of Evidence: Case series, Level IV.

Purpose: To compare the outcome of 2 arthroscopic techniques for treating recalcitrant lateral epicondylitis., Methods: The study included patients undergoing arthroscopic treatment of lateral epicondylitis during 2 different time periods: April 2005 to October 2007 (tenotomy) and May 2009 to June 2010 (debridement). By using a patient-administered form, baseline information including QuickDASH (disabilities of the arm, shoulder and hand) score (primary outcome), visual analog scale (VAS) of pain, and VAS of function was recorded prospectively. To have the same follow-up period of minimum 4 years in the 2 groups, the follow-up was conducted at 2 different points of time., Results: Of a total of 326 patients fulfilling the requirements for inclusion in the study, 283 patients (87%) were followed up (144 male and 139 female, median age 46 [21 to 65] years), 204 (87%) in the tenotomy group and 79 (88%) in the debridement group. In both groups, a significant improvement in the QuickDASH was found at the follow-up compared with baseline: from 60 to 12 in the debridement group (P < .001) and from 59 to 13 in the tenotomy group (P < .001). No statistically significant difference was found in baseline or follow-up QuickDASH, VAS of pain, VAS of function, or failure (reoperation) rate between the 2 groups. The mean length of sick leave was 2 weeks shorter in the debridement only group (P = .007)., Conclusions: Both arthroscopic methods lead to a significant improvement of pain and function, and no statistically significant difference was found in any outcome parameters between the 2 techniques at this minimum 4-year evaluation. The results indicate that tenotomy of the extensor carpi radialis brevis may be an unnecessary step in the arthroscopic treatment of lateral epicondylitis Debridement only is a potentially less costly procedure, and the current finding of a mean 2 weeks shorter sick leave in the debridement only group proposes a substantial cost saving in a societal perspective., Level of Evidence: Level IV, therapeutic case series., (Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Aim: To investigate whether plasma dimethylglycine was associated with and improved risk prediction of mortality among patients with coronary heart disease (CHD)., Methods: By Cox modelling, we explored the association between plasma dimethylglycine and mortality in two independent cohorts of patients with suspected stable angina pectoris (SAP) (n = 4156) and acute myocardial infarction (AMI) (n = 3733). We also assessed any improvement in risk prediction by adding plasma dimethylglycine to established CHD risk factors., Results: Median follow-up time was 4.7 and 7.0 years among patients with SAP and AMI, respectively. Across both cohorts, elevated plasma dimethylglycine levels were linearly associated with increased risk of all-cause mortality (age and gender adjusted hazard ratios (95% confidence interval, CI) were 1.72 (1.21-2.46) and 1.76 (1.42-2.18) when comparing the fourth versus the first plasma dimethylglycine quartile in patients with SAP and AMI, respectively). There was a particularly strong risk association between plasma dimethylglycine and cardiovascular, as compared with non-cardiovascular, mortality (age and gender adjusted hazard ratios (95% CI) 1.94 (1.21-3.11) and 1.43 (0.83-2.47) among patients with SAP and 1.97 (1.50-2.59) and 1.44 (1.02-2.04) among patients with AMI, respectively). The relationship between dimethylglycine and all-cause and cardiovascular mortality was only slightly attenuated in analyses adjusted for established CHD risk factors. Plasma dimethylglycine also improved risk prediction for all-cause and cardiovascular mortality, and especially among patients with AMI., Conclusions: Elevated plasma dimethylglycine was associated with and improved risk prediction of mortality in patients with suspected or verified CHD. This relationship was stronger for death from cardiovascular, as compared with non-cardiovascular, causes., (© The European Society of Cardiology 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Background: Data from recent meta-analyses question an association between dietary intake of saturated fatty acids (SFAs) and risk of cardiovascular disease (CVD). Moreover, the prognostic effect of dietary SFA in patients with established CVD treated with modern conventional medication has not been extensively studied., Objective: We investigated the associations between self-reported dietary SFA intake and risk of subsequent coronary events and mortality in patients with coronary artery disease (CAD)., Methods: This study included patients who participated in the Western Norway B-Vitamin Intervention Trial and completed a 169-item semiquantitative food-frequency questionnaire after coronary angiography. Quartiles of estimated daily intakes of SFA were related to risk of a primary composite endpoint of coronary events (unstable angina pectoris, nonfatal acute myocardial infarction, and coronary death) and separate secondary endpoints (total acute myocardial infarction, fatal coronary events, and all-cause death) with use of Cox-regression analyses., Results: This study included 2412 patients (81% men, mean age: 61.7 y). After a median follow-up of 4.8 y, a total of 292 (12%) patients experienced at least one major coronary event during follow-up. High intake of SFAs was associated with a number of risk factors at baseline. However, there were no significant associations between SFA intake and risk of coronary events [age- and sex-adjusted HR (95% CI) was 0.85 (0.61, 1.18) for the upper vs. lower SFA quartile] or any secondary endpoint. Estimates were not appreciably changed after multivariate adjustments., Conclusions: There was no association between dietary intake of SFAs and incident coronary events or mortality in patients with established CAD., (© 2015 American Society for Nutrition.)

Increased mortality rates in patients sustaining hip and vertebral fractures are well documented; however in distal radius fracture patients the results are conflicting. The aim of this study was to examine short- and long-term mortality in distal radius fracture patient in comparison with the background population. Patients aged ≥ 50 years with distal radius fracture living in Southern Norway who suffered a fracture in the two year period 2004 and 2005 were included in the study. The mortality risk of the standard Norwegian population was used to calculate the standardized mortality ratio (SMR). The number of distal radius fractures was 883 (166 men and 717 women). Mean age was 69 years (men 65 years and women 70 years). After one year the overall mortality rate was 3.4% (men 5.4% and women 2.9%) and after five years 4.6% (men 4.0% and women 4.8%). The SMR for men and women compared to the Norwegian population for the first year was 1.6 (95% confidence interval (CI): 0.6, 2.7) and 0.9 (95% CI: 0.4, 1.2), respectively, and after five years 1.7 (95% CI: 0.3, 3.0) and 2.0 (95% CI: 1.2, 2.7). Stratified on age groups (50-70 and >70 years) an increased SMR was only seen in female patients aged >70 years five years after the fracture (SMR: 1.9, 95% CI: 1.1, 2.6). In conclusion, increased SMR was found in female patients aged >70 years five years after the distal radius fracture, but not in men or in women younger than 70 years.

There is lack of studies investigating the association between bodyweight changes and health related quality of life (HRQL). The aim was to study the effect of relative changes in bodyweight over time on HRQL. In the Hordaland Health Study, 9276 men and 10433 women aged 40-47 years were included. Weight and height were measured and information on bodyweight changes during the last 5 years, physical activity and smoking was obtained from self-administered questionnaires including the Medical Outcomes Study MOS short form-12 including a Physical health Composite Score (PCS) and a Mental health Composite Score (MCS). Increasing bodyweight changes were associated with marked reduced scores in PCS and MCS also after adjustment for body mass index (BMI), physical activity and smoking. Men and women with a variation in weight with more than 15% during the last 5 years reported a mean score of MCS that was 0.48 standard deviation (SD) (3.9/8.1) and 0.35 SD (3.1/8.9) lower than those reporting a variation in weight less than 5%. No major differences were found between those who at date of examination were at the lower and higher end of the reported weight interval. There were no significant differences in the associations between men and women. Our findings confirm that increasing bodyweight changes are associated with reduced physical and mental health beyond what is related to BMI itself.

Background: Nutritional care for hospital in-patients is potentially important but challenging., Objective: To investigate the association between nutritional status and clinical outcomes., Methods: Eight prevalence surveys were performed at Haukeland University Hospital, Norway, during 2008-2009. In total 3279 patients were classified as being at nutritional risk or not according to the Nutritional Risk Screening (NRS 2002) tool. The initial four questions of NRS 2002 assess dietary intake, weight loss, body mass index (BMI) and illness severity., Results: The overall prevalence of nutritional risk was 29%. Adjusted mean days for hospitalisation was 8.3 days for patients at nutritional risk and 5.0 days for patients not at risk (p < 0.001). In adjusted models, patients at nutritional risk had increased one-year mortality (OR 4.07, 95% CI 2.90-5.70), morbidity (OR 1.59, 95% CI 1.18-2.13), and were 1.24 (95% CI 1.16-1.32) times more likely to have had a new admission during the three previous years and the one subsequent year, compared to patients not at risk. A 'positive' response to the initial four questions was associated with increased risk of morbidity and mortality. Patients with a reduced dietary intake during the last weeks had OR 1.72 (95% CI 1.03-2.85) for one-year mortality. Patients with a positive answer on all the initial four questions had ten times increased risk for mortality the following year, OR 13.0 (95% CI 4.52-37.6)., Conclusion: The four initial questions of the NRS 2002 robustly identify nutritional risk and were strong predictors of hospitalisation, morbidity and most importantly mortality among hospitalised patients. Thus, these simpler and short questions are robust indicators for subsequent poor outcomes., (Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Lower bone mineral density (BMD) in smokers may be attributable to lower body weight or fat mass, rather than to a direct effect of smoking. We analyzed the effects of smoking exposure, assessed by plasma cotinine, and body fat on BMD and the risk of subsequent hip fracture. In the community-based Hordaland Health Study (HUSK), 3003 participants 46-49 years and 2091 subjects 71-74 years were included. Cotinine was measured in plasma and information on health behaviors was obtained from self-administered questionnaires. BMD and total body soft tissue composition were measured by dual X-ray absorptiometry. Information on hip fracture was obtained from computerized records containing discharge diagnoses for hospitalizations between baseline examinations 1997-2000 through December 31st, 2009. In the whole cohort, moderate and heavy smokers had stronger positive associations between fat mass and BMD compared to never smokers (differences in regression coefficient (95% CI) per % change in fat mass = 1.38 (0.24, 2.52) and 1.29 (0.17, 2.4), respectively). In moderate and heavy smokers there was a nonlinear association between BMD and fat mass with a stronger positive association at low compared to high levels of fat mass (Davies segmented test, p<0.001). In elderly women and men, heavy smokers had an increased risk of hip fracture compared to never smokers (hazard ratio = 3.31, 95% CI: 2.05, 5.35; p<0.001). In heavy smokers there was a tendency of a lower risk of hip fracture with higher percentage of fat mass. The deleterious effect of smoking on bone health is stronger in lean smokers than in smokers with high fat mass.

Choline, obtained from diet and formed by biosynthesis, is the immediate precursor of betaine. Animal studies suggest an impact of choline on bone metabolism. We examined the associations of plasma choline and betaine with bone mineral density (BMD), the risk of hip fractures, and possible effect-modification by nicotine exposure. The Hordaland Health Study (1998 to 2000) included 7074 women and men (ages 46 to 49 or 71 to 74 years). In 5315, BMD was measured. The oldest (n = 3311) were followed for hip fractures through 2009. Risk associations were studied by logistic and Cox regression by comparing the lowest and middle tertiles with the highest, as well as trends across tertiles of plasma choline and betaine. In analyses adjusted for sex and age, participants in the lowest (odds ratio [OR] = 2.00, 95% confidence interval [CI] 1.69-2.37) and middle (OR = 1.39, CI 1.17-1.66) tertiles of plasma choline had an increased risk of low BMD (lowest quintile) (p trend < 0.001). Separate analyses for sex and age groups revealed the strongest relations in elderly women (lowest tertile: OR = 2.84, CI 1.95-4.14; middle tertile: OR = 1.80, CI 1.22-2.67, p trend < 0.001), and highest OR among those in the lowest tertile who were exposed to nicotine (OR = 4.56, CI 1.87-11.11). Low plasma choline was also associated with an increased risk of hip fracture in elderly women and men (lowest tertile: hazard ratio [HR] = 1.45, CI 1.08-1.94; middle tertile: HR = 1.13, CI 0.83-1.54, p trend = 0.012). In elderly women, the HR for hip fracture was 1.90 (CI 1.32-2.73) and 1.36 (CI 0.92-1.99) (p trend < 0.001) for lowest and middle tertiles of choline, and the highest HR was found among women in the lowest tertile exposed to nicotine (HR = 2.68, CI 1.16-6.19). Plasma betaine was not related to BMD or hip fracture. Low plasma choline was associated with low BMD in both sexes and increased the risk of hip fracture in elderly women. These results should motivate further studies on choline, nicotine exposure, and bone metabolism., (© 2014 American Society for Bone and Mineral Research.)

Purpose: The aim of this study was to evaluate the medium-term (5-9 years) and long-term (10-14 years) outcomes of mosaicplasty in the knee and identify possible risk factors for poor outcome., Methods: We included patients 60 years or younger with symptomatic focal full-thickness chondral lesions. Seventy-three patients (87%) with median age of 34 years were available for analyses. Clinical outcome was evaluated by Lysholm score and VAS of pain., Results: Both the mean Lysholm score and mean VAS pain score improved significantly from baseline, 49 (SD 17) and 58 (SD 23), respectively, to both the mid-term follow-up, 72 (SD18, p<0.001) and 27 (SD 20, p<0.001), respectively, and the long-term follow-up, 72 (SD 21, p<0.001) and 33 (SD 23, p<0.001), respectively. A poor outcome at the long-term follow-up - defined as a Lysholm score of 64 or less or having had a knee replacement - was found in 40%. A poor outcome was more frequent in patients 40 years or older (59%), in women (61%) and in defects with an area of 3 cm(2) or more (57%). Conversely, in a subgroup of male individuals younger than 40 years with defect size less than 3 cm(2) the failure rate was 12.5% and the mean Lysholm score was 82 (SD 16)., Conclusion: We conclude that the long-term clinical outcome after mosaicplasty varies greatly depending on age, gender and the size of the lesion., Level of Evidence: IV-Retrospective Case Series., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Purpose: The purpose of this study was to compare the outcome of arthroscopic and open tendon release in tennis elbow (TE)., Methods: We compared the outcome of patients treated by an open tendon release in the period from 2002 to 2005 (n = 80) with that of patients treated by an arthroscopic release of the extensor carpi radialis brevis in the period from 2005 to 2008 (n = 225). In both groups the inclusion criteria were symptomatic TE refractory to conservative care for a minimum of 6 months and a clinical follow-up of at least 3 years. The diagnosis was based on a typical history and positive clinical findings. Patients with previous surgery in the elbow, chondral or osteochondral lesions, osteoarthritis, or free bodies were excluded. To have a similar follow-up period in the 2 groups (median, 4 years), the follow-up was conducted at 2 different time points., Results: The groups did not differ significantly with regard to the age of the patients, distribution of gender, distribution of affected side, duration of symptoms, or baseline score on the short version of Disabilities of the Arm, Shoulder and Hand questionnaire (QuickDASH). We did not observe any major complications. The failure rate was not significantly different between the 2 groups. At follow-up, the mean QuickDASH score was statistically significantly better (P = .004) in the arthroscopic group (11.6 points; SD, 15.6 points) compared with that in the open group (17.8 points; SD, 19.4 points). The percentage of elbows with an excellent outcome at follow-up (QuickDASH score <20 points) was significantly higher in the arthroscopic group (78%) than in the open group (67%) (P = .04)., Conclusions: Both a traditional open approach and the newer arthroscopic method provide an effective treatment of recalcitrant TE without major complications. The arthroscopic method offers a small, but not insignificant, improvement in the outcome as evaluated by the QuickDASH score., Level of Evidence: Level III, therapeutic case-control study., (Copyright © 2013 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Purpose: The objectives of this study were to evaluate the results in the outpatient treatment of recalcitrant lateral epicondylitis with release of the common extensor origin according to Hohmann and to determine any prognostic factors., Methods: Eighty tennis elbows in 77 patients with a characteristic history of activity-related pain at the lateral epicondyle interfering with the activities of daily living refractory to conservative care for at least 6 months and a confirmatory physical examination were included. Clinical outcome was evaluated using the QuickDASH score system. Data were collected before the operation and at the medians of 18 months (range 6-36 months; short term) and 4 years (range 3-6 years; medium term) postoperatively., Results: The mean QuickDASH was improved both at the short- and the medium-term follow-ups and did not change significantly between the follow-ups. At the final follow-up, the QuickDASH was improved in 78 out of 80 elbows and 81% was rated as excellent or good (QuickDASH<40 points). We found a weak correlation between residual symptoms (a high QuickDASH score) at the final follow-up and high level of baseline symptoms (r=0.388), acute occurrence of symptoms (r=0.362), long duration of symptoms (r=0.276), female gender (r=0.269) and young age (r=0.203), whereas occurrence in dominant arm, a work-related cause or strenuous work did not correlate significantly with the outcome., Conclusion: Open lateral extensor release performed as outpatient surgery results in improved clinical outcome at both short- and medium-term follow-ups with few complications. High baseline disability, sudden occurrence of symptoms, long duration of symptoms, female gender and young age were found to be weak predictors of poor outcome., Level of Evidence: Case series, Level IV.

Background: In general there is a lack of data on osteoporosis and fracture in men; this also includes low-energy distal radius fractures. The objectives of this study were to examine BMD and identify factors associated with distal radius fractures in male patients compared with controls recruited from the background population., Methods: In a 2-year period, 44 men 50 years or older were diagnosed with low-energy distal radius fractures, all recruited from one hospital. The 31 men who attended for osteoporosis assessment were age-matched with 35 controls. Demographic and clinical data were collected and BMD at femoral neck, total hip and spine L2-4 was assessed by dual energy X-ray absorptiometry., Results: Apart from weight and living alone, no significant differences were found between patient and controls for demographic variables (e.g. height, smoking) and clinical variables (e.g. co-morbidity, use of glucocorticoids, osteoporosis treatment, falls and previous history of fracture). However, BMD expressed as T-score was significant lower in patients than in controls at all measurement sites (femoral neck: -2.24 vs. -1.15, p < 0.001; Total hip: -1.65 vs. -0.64, p < 0.001; Spine L2-4: -1.26 vs. 0.25, p = 0.002). Among the potential risk factors for fracture evaluated, only reduced BMD was found to be significantly associated with increased risk for low-energy distal radius fractures in men., Conclusion: The results from our study indicate that reduced BMD is an important risk factor for low-energy distal radius fracture in men. This suggests that improvement of BMD by both pharmacological and non-pharmacological initiatives may be a strategy to reduce fracture risk in men.

We compared the results of microfracture in single versus multiple symptomatic articular cartilage defects in the knee in 110 patients with a median age of 38 years (range 15-60). Cases of reoperation of the cartilage defect were classified as failures. Clinical outcome in non-failures was evaluated by the Lysholm score and grading of knee pain and function of the knee by the use of patient-administered visual analog scales (VAS; 0-100). Data were prospectively collected before the operation and at the 2- to 9-year follow-up. The single lesion or the largest of multiple lesions were located on the medial femoral condyle (n = 62), trochlea (n = 18), lateral tibia (n = 11), patella (n = 10) or lateral femoral condyle (n = 9). We treated one (n = 76), two (n = 27) or three (n = 7) lesions with a median total area of 4 cm(2) (range 1-15). A total of 24 failures (22%) were registered-18% in the single-defect subgroup and 29% in the multiple-defects subgroup. In the remaining group of patients (n = 86), the mean Lysholm score, mean pain-score (0 = no pain; 100 = worst possible pain) and mean function-score (0 = useless; 100 = full function) improved from 51, 52 and 41, respectively, to 71 (P < 0.001), 30 (P < 0.001) and 69 (P < 0.001) at the follow-up. The pain-score was significant lower (P = 0.042), and the function-score significantly higher (P = 0.001) in the group of patients with a single lesion compared to the group with 2 or 3 lesions. The Lysholm score did not differ significantly between the two subgroups (P = 0.06).

Background: Frozen shoulder is a debilitating, long-lasting condition. At Bergen Surgical Hospital we have performed arthroscopic capsular release since 2003 in patients where conservative treatment has failed. The procedure is done as day surgery. The purpose of this study was to evaluate our results., Patients and Methods: From June 2003 until October 2005 arthroscopic capsular and ligament release was performed in 66 patients (70 shoulders) with primary frozen shoulder. Oxford shoulder score and range of motion were recorded prospectively. Follow-up was done during autumn 2005 and included subjective evaluation of symptoms, function, satisfaction with the result of the procedure, Oxford shoulder score and clinical examination., Results: 62 out of 66 patients would agree to have the same procedure done again. Degree of satisfaction with the result of the procedure (0 = worst, 10 = best) was 8.6 +/- 1.8 (SD) on average. Ability to work, physical activity and quality of night's sleep improved significantly (p < 0.001). Oxford shoulder score (12 = best, 60 = worst) decreased significantly from 41.0 +/- 7.5 (SD) to 18.4 +/- 7.3 (SD) (p < 0.001). External rotation, abduction and flexion increased significantly (p < 0.001)., Interpretation: The results from treatment of frozen shoulder with arthroscopic capsular release are good and suggest that the the condition shoulder is shortened. The procedure may be done safely as day surgery. We feel that more patients may benefit from the procedure.