Stine Marie Ulven

• Holven, Kirsten Bjørklund; Dahl, Tuva Børresdatter; Bålsrud, Pia; Christensen, Jacob Juel; Ottestad, Inger Olaug & Rundblad, Amanda [Show all 15 contributors for this article] (2026). Cetoleic acid rich fish oil increases plasma levels of eicosapentaenoic and docosapentaenoic acids in healthy volunteers: a double-blinded, randomised, controlled trial. British Journal of Nutrition. ISSN 0007-1145. p. 1–28. doi: 10.1017/S0007114526107958. Full text in Research Archive Show summary

  Intake of fish and supplementation with n-3 polyunsaturated fatty acids (PUFA) are associated with reduced incidence of cardiovascular disease (CVD). Cetoleic acid promotes n-3 PUFA generation in salmon and human HepG2 cells, but data in humans are scarce. To explore the effect of cetoleic acid on n-3 PUFA levels, we performed a double-blinded randomised controlled trial in healthy adults (37 females and 12 males) for four weeks. The participants were randomised to consume either capsules with mackerel oil, naturally rich in cetoleic acid, or a control oil, both with a similar concentration of n-3 PUFA. Clinicaltrials.gov (NCT04841044). Supplements with mackerel oil resulted in higher plasma levels of the n-3 PUFAs 20:4n-3 (Eicosatetraenoic acid) and 20:5n-3 (Eicosapentaenoic acid) as compared with those receiving control oil. In addition, those who received the cetoleic-rich capsules had higher levels of 20:4n-3 in the RBC membrane and a decrease in expression of elongation of very long chain fatty acids protein 5 in peripheral blood mononuclear cells. We found no differences in lipid, glucose or C-reactive protein between the two treatment groups, consisting of healthy subjects. Our data suggests that supplementation with cetoleic-rich mackerel oil may result in increased levels of certain n-3 PUFAs. Further studies should include patients with or at risk for metabolic and CVD.

• Jensen, Silje Marie; Holven, Kirsten Bjørklund; Ulven, Stine Marie; Anfinsen, Åslaug Matre; Dierkes, Jutta & Lysne, Vegard [Show all 7 contributors for this article] (2026). Lipoprotein metabolism and inflammation in healthy young subjects – exploring the postprandial and postabsorptive phases following intake of a standardized meal. Atherosclerosis Plus. ISSN 2667-0909. 65. doi: 10.1016/j.athplu.2026.100572. Full text in Research Archive Show summary

  Background and aims: Commonly measured cardiometabolic biomarkers have not been systematically characterized across the long-term continuum of the postprandial and postabsorptive phases. The aim of the present study was to evaluate how the exact time since last meal impacts test results for lipoprotein particles and inflammatory biomarkers. Methods: We used data from a trial where 34 normal-weighted males and females aged 20-30 y were included. Subjects fasted 12 h, had blood sampled at baseline, then consumed a standardized, habitual breakfast meal, and had blood sampled 13 more times over the next 24 h. NMR metabolomics was used to quantify lipoprotein subclasses and various biomarkers, and ELISA to analyze VCAM-1, ICAM-1, E-selectin, and IL-6. We characterized the postprandial and postabsorptive responses using visualizations and non-linear mixed effects models. Results: Six VLDL subclasses increased by 11-429% within 2-4 h postprandially before returning to baseline levels, followed by another increase 8-10 h after intake of the breakfast meal. IDL and three LDL subclasses increased around 10-12% over 24 h. Four HDL subclasses showed an inverse association with VLDL subclasses, reaching their lowest levels about 1 h after the meal and peaking after 8-10 h with a 5-15% increase from baseline. Participants had an average increase of 325% in IL-6 10 h after breakfast, while other inflammatory biomarkers showed little change over time. For most biomarkers, males generally exhibited higher baseline concentrations compared to females, however the responses over time remained similar. Conclusions: Baseline levels and time of return to baseline varied between individuals, with some sex-specific differences in responses. TG-rich lipoproteins and VLDL increased postprandially and normalized by 12-24 h, whereas IDL and LDL showed minor early changes but increased by 24 h. IL-6 increased markedly during the first 10 h and returned to baseline by 12-24 h, while other inflammatory markers changed little.

• Limani, Naman; Henriksen, Hege Berg; Minge, Mina Marie; Sandoval, Viviana; Landberg, Rikard & Lindqvist, Helen M. [Show all 9 contributors for this article] (2026). Effect of different sources of saturated and polyunsaturated fatty acids on postprandial inflammation: A double-blind randomized crossover trial. Clinical Nutrition ESPEN. ISSN 2405-4577. 74. doi: 10.1016/j.clnesp.2026.103335. Full text in Research Archive
• Bålsrud, Pia; Ulven, Stine Marie; Hjartåker, Anette; Ottestad, Inger Olaug; Retterstøl, Kjetil & Schwab, Ursula [Show all 9 contributors for this article] (2026). Association between dietary protein intake and frailty index among home-dwelling older adults; an 8-year follow-up study. The Journal of Nutrition, Health & Aging. ISSN 1279-7707. 30(6). doi: 10.1016/j.jnha.2026.100850. Full text in Research Archive
• Melnes, Torunn; Bogsrud, Martin Prøven; Christensen, Jacob J.; Rundblad, Amanda; Retterstøl, Kjetil & Narverud, Ingunn [Show all 10 contributors for this article] (2025). LDL cholesterol burden in elderly patients with familial hypercholesterolemia: Insights from real-world data. American Journal of Preventive Cardiology. 22. doi: 10.1016/j.ajpc.2025.100986. Full text in Research Archive Show summary

  Background and aims Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated low-density lipoprotein cholesterol (LDL-C) and increased risk of premature coronary heart disease (CHD). While current LDL-C levels usually guides therapy, the cumulative exposure to LDL-C (the LDL-C burden) is suggested to offer a more precise estimate of cardiovascular risk in people with FH. Therefore, using real-world data, this study aimed to estimate the LDL-C burden at different ages in elderly FH patients with and without CHD, and to assess the LDL-C burden at CHD onset. Methods Data was retrospectively collected from the medical records of elderly (>60 years) FH patients at the Lipid Clinic in Oslo. The LDL-C burden (mM-years) was estimated based on repeated LDL-C measurements and information on lipid-lowering medication. Time-weighted average (TWA) LDL-C was calculated as LDL-C burden divided by years. Results We included 112 FH patients, of which 55 (49 %) had experienced at least one CHD-event, and 58 (52 %) were females. Median age at first and last visit were 50 years and 68 years, respectively, with a median of 9 (range; 2–14) available LDL-C measurements. Subjects with CHD had higher LDL-C burden at all ages tested (45, 50 and 60 years) compared with the non-CHD group (p < 0.01, also after adjusting for sex), and had higher TWA LDL-C before treatment at the Lipid Clinic (p = 0.004), but not during follow-up (p = 0.6). There were no sex differences in LDL-C burden at all ages tested, also after adjusting for CHD (p > 0.1). However, women had higher TWA LDL-C during follow-up at the Lipid Clinic (p = 0.01). Median LDL-C burden at CHD onset was 352 mM-years; numerically lower in women than in men (320 vs. 357 mM-years, respectively. p = 0.1). Conclusion Elderly FH patients with CHD had higher estimated LDL-C burden compared with FH patients without CHD, due to higher burden prior to treatment, highlighting the importance of early detection and treatment.

• Rundblad, Amanda; Das, Siddhartha; Ginos, Bigina N.R; Matthews, Jason; Holven, Kirsten Bjørklund & Voortman, Trudy [Show all 7 contributors for this article] (2025). Exposure to fine particulate matter in adults is associated with immune cell gene expression related to inflammation, the electron transport chain, and cell cycle regulation. Environmental Epigenetics. 11(1). doi: 10.1093/eep/dvaf008. Full text in Research Archive Show summary

  Exposure to air pollution and an unhealthy built environment increase disease risk by impacting metabolic risk factors and inflammation, potentially via epigenetic modifications and effects on gene expression. We aimed to explore associations between fine particulate matter (PM2.5), black carbon, ozone, nitrogen dioxide, distance to nearest water body, normalized difference vegetation index, and impervious surface and gene expression profiles in adults. This study is a part of the LongITools project and includes cross-sectional data from the Rotterdam Study, a population-based cohort study, and NoMa, a randomized controlled trial. Environmental exposures were assigned using land-use regression (LUR) models and satellite data. Gene expression was assessed with whole blood RNA sequencing (Rotterdam Study, n = 758) and microarray analyses in peripheral blood mononuclear cells (NoMa, n = 100). We analysed transcriptomic profiles and enriched pathways associated with each of the environmental exposures. PM2.5 had the strongest gene expression associations, while only a few significant associations were observed for the other environmental exposures. In both populations, exposure to PM2.5 was associated with genes and pathways related to inflammation, oxidative stress, DNA metabolism, cell cycle regulation, histones, electron transport chain, oxidative phosphorylation, and neural signalling. This study is limited by different methods for RNA quantification, a cross-sectional design, and a small sample size. However, in both populations, exposure to PM2.5 resulted in the maximum number of associations with gene expression. In conclusion, PM2.5 is strongly associated with various gene expression profiles, which provide information about the underlying mechanisms of the detrimental health effects of exposure to PM2.5.

• Melnes, Torunn; Bogsrud, Martin Prøven; Christensen, Jacob Juel; Rundblad, Amanda; Narverud, Ingunn & Retterstøl, Kjetil [Show all 10 contributors for this article] (2024). Gene expression profiling in elderly patients with familial hypercholesterolemia with and without coronary heart disease. Atherosclerosis. ISSN 0021-9150. 392. doi: 10.1016/j.atherosclerosis.2024.117507. Full text in Research Archive Show summary

  Background and aims Elderly familial hypercholesterolemia (FH) patients are at high risk of coronary heart disease (CHD) due to high cholesterol burden and late onset of effective cholesterol-lowering therapies. A subset of these individuals remains free from any CHD event, indicating the potential presence of protective factors. Identifying possible cardioprotective gene expression profiles could contribute to our understanding of CHD prevention and future preventive treatment. Therefore, this study aimed to investigate gene expression profiles in elderly event-free FH patients. Methods Expression of 773 genes was analysed using the Nanostring Metabolic Pathways Panel, in peripheral blood mononuclear cells (PBMCs) from FH patients ≥65 years without CHD (FH event-free, n = 44) and with CHD (FH CHD, n = 39), and from healthy controls ≥70 years (n = 39). Results None of the genes were differentially expressed between FH patients with and without CHD after adjusting for multiple testing. However, at nominal p < 0.05, we found 36 (5%) differentially expressed genes (DEGs) between the two FH groups, mainly related to lipid metabolism (e.g. higher expression of ABCA1 and ABCG1 in FH event-free) and immune responses (e.g. lower expression of STAT1 and STAT3 in FH event-free). When comparing FH patients to controls, the event-free group had fewer DEGs than the CHD group; 147 (19%) and 219 (28%) DEGs, respectively. Conclusions Elderly event-free FH patients displayed a different PBMC gene expression profile compared to FH patients with CHD. Differences in gene expression compared to healthy controls were more pronounced in the CHD group, indicating a less atherogenic gene expression profile in event-free individuals. Overall, identification of cardioprotective factors could lead to future therapeutic targets.

• Torfadóttir, Johanna E. & Ulven, Stine Marie (2024). Fish - a scoping review for nordic nutrition recommendations 2023. Food & Nutrition Research (FNR). ISSN 1654-6628. 68. doi: 10.29219/fnr.v68.10485. Full text in Research Archive Show summary

  The aim of this scoping review was to conduct evidence-based documentation between fish intake and health outcomes for food-based dietary guidelines (FBDGs) in the Nordic Nutrition Recommendations (NNR) 2023. For most health outcomes, the evidence for fish oil and n-3 long chain (LC) polyunsaturated fatty acids (PUFA) supplementation was included when examining evidence between fish intake and health. In this review, conclusions from qualified systematic reviews (qSR) approved by NNR2023 are included. In addition, conclusions of a de novo systematic reviews on the topic of n-3 LC-PUFA, asthma, and allergy are included. Finally, a systematic literature search was performed limited to systematic reviews and meta-analysis published between 2011 and September 2021. In total, 21 papers from the systematic literature search, four qSR, and eight reports were included addressing the association between fish intake, fish oil, and n-3 LC-PUFA supplementation on several health outcomes. These included cardiovascular disease (CVD), type 2 diabetes, cancers (colorectal, breast, and prostate), metabolic syndrome, obesity, mortality, cognition and mental health, pregnancy-related outcomes (preterm birth and birth weight), and outcomes specific for children (neurodevelopment, and risk of food allergies, and asthma). In addition, intermediate risk factors such as blood lipids, glucose, C-reactive protein, and blood pressure were reviewed. Based on current evidence, fish consumption can have beneficial effects to prevent coronary heart disease (CHD) and stroke incidence, and lower mortality from CVD, CHD, myocardial infarction (MI), and stroke, as well as total mortality risk. In addition, fish consumption is beneficial for preventing cognitive decline in adults (e.g. dementia and Alzheimer’s disease). Fish intake may also prevent metabolic syndrome, supported by an observed association between fish intake and reduction in plasma triglycerides and increase in high-density lipoprotein (HDL) cholesterol levels. Data from fish oil and n-3 LC-PUFA supplementation studies supports the conclusions on the effects of fish consumption on most of the health outcomes.

• Das, Siddhartha; Rundblad, Amanda; Marques, Irene Fontes; Soares, Ana Goncalves; Jaddoe, Vincent W. & Vrijheid, Martine [Show all 14 contributors for this article] (2024). Air pollution exposure is associated with gene expression in children. Environmental Epigenetics. 10(1). doi: 10.1093/eep/dvae025. Full text in Research Archive Show summary

  Environmental exposures, including air pollutants and lack of natural spaces, are associated with suboptimal health outcomes in children. We aimed to study the associations between environmental exposures and gene expression in children. Associations of exposure to particulate matter (PM) with diameter <2.5 (PM2.5) and < 10 (PM10) micrometers, nitrogen dioxide, green spaces, and blue space, with whole-blood gene expression were explored in children from the Dutch Generation R Study (n = 172). Analyses were adjusted for age, sex, batch, maternal education, and area socioeconomic status. Follow-up analysis was carried out using lymphoblastoid cell line gene expression in children from the ALSPAC Study (n = 946). Gene set enrichment analysis (GSEA) using hallmark and immune gene sets from the molecular signature database was carried out to identify significantly over-represented gene sets for insights into biological mechanisms Exposure to PM2.5 was associated with expression of 86 genes in discovery analyses in the Generation R Study [false discovery rate (FDR)-adjusted P-value < .25]. Of these, PM2.5 was also associated with GNG11 expression in the same direction in follow-up analysis (FDR-adjusted P-value < .05). The remaining exposures showed much fewer associations in the discovery analyses. GSEA using PM2.5 association results for both cohorts indicated suppression of gene sets related to interferon response and response to bacterial and viral exposure. In conclusion, gene expression analysis performed in two independent cohorts suggests that PM2.5 exposure in children may be involved in interferon and microbial infection responses.

• Bålsrud, Pia; Ulven, Stine Marie; Ottestad, Inger; Retterstøl, Kjetil; Schwab, Ursula & Holven, Kirsten Bjørklund (2024). Association between inflammatory markers, body composition and frailty in home-dwelling elderly: an 8-year follow-up study. GeroScience. ISSN 2509-2715. 46, p. 5629–5641. doi: 10.1007/s11357-024-01279-w. Full text in Research Archive Show summary

  Frailty has been linked to inflammation and changes in body composition, but the findings are inconsistent. To explore this, we used the Frailty Index (FI) definition to (1) investigate the association between levels of inflammatory markers (baseline) and change in FI score after 8 years of follow-up and (2) investigate the longitudinal associations between inflammatory markers, body composition, and frailty. Home-dwelling elderly (≥ 70 years) were invited to participate in the study and re-invited to a follow-up visit 8 years later. This study includes a total of 133 participants. The inflammatory markers included were high-sensitive C-reactive protein (hs-CRP), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), and glycoprotein acetyls (Gp-acetyls). We used the body composition markers fat mass, fat-free mass, and waist circumference. The FI score consisted of 38 variables. Additional clinical assessments such as blood pressure and body mass index (BMI), as well as information about daily medications, were collected at both visits. Linear regression model and Spearman’s rank correlation were used to investigate associations. We showed that the FI score increased after 8 years, and participants with higher hs-CRP levels at baseline had the largest change in the FI score. Changes in fat mass were significantly correlated with changes in hs-CRP and IL-6, and changes in waist circumference were significantly correlated with changes in TNF-α. The use of drugs increased during the 8 years of follow-up, which may have attenuated the associations between inflammation and frailty. However, elevated concentrations of hs-CRP in the elderly may be associated with an increased risk of frailty in subsequent years.

• Rønning, Sissel Beate; Carlsen, Harald; Rocha, Sergio Domingos Cardoso; Rud, Ida; Solberg, Nina & Høst, Vibeke [Show all 18 contributors for this article] (2024). Dietary intake of micronized avian eggshell membrane in aged mice reduces circulating inflammatory markers, increases microbiota diversity, and attenuates skeletal muscle aging. Frontiers in Nutrition. 10, p. 1–19. doi: 10.3389/fnut.2023.1336477. Full text in Research Archive Show summary

  Introduction: Avian eggshell membrane (ESM) is a complex extracellular matrix comprising collagens, glycoproteins, proteoglycans, and hyaluronic acid. We have previously demonstrated that ESM possesses anti-inflammatory properties in vitro and regulates wound healing processes in vivo. The present study aimed to investigate if oral intake of micronized ESM could attenuate skeletal muscle aging associated with beneficial alterations in gut microbiota profile and reduced inflammation. Methods: Elderly male C57BL/6 mice were fed an AIN93G diet supplemented with 0, 0.1, 1, or 8% ESM. Young mice were used as reference. The digestibility of ESM was investigated using the static in vitro digestion model INFOGEST for older people and adults, and the gut microbiota profile was analyzed in mice. In addition, we performed a small-scale pre-clinical human study with healthy home-dwelling elderly (>70 years) who received capsules with a placebo or 500 mg ESM every day for 4 weeks and studied the effect on circulating inflammatory markers. Results and discussion: Intake of ESM in elderly mice impacted and attenuated several well-known hallmarks of aging, such as a reduction in the number of skeletal muscle fibers, the appearance of centronucleated fibers, a decrease in type IIa/IIx fiber type proportion, reduced gene expression of satellite cell markers Sdc3 and Pax7 and increased gene expression of the muscle atrophy marker Fbxo32. Similarly, a transition toward the phenotypic characteristics of young mice was observed for several proteins involved in cellular processes and metabolism. The digestibility of ESM was poor, especially for the elderly condition. Furthermore, our experiments showed that mice fed with 8% ESM had increased gut microbiota diversity and altered microbiota composition compared with the other groups. ESM in the diet also lowered the expression of the inflammation marker TNFA in mice and in vitro in THP-1 macrophages. In the human study, intake of ESM capsules significantly reduced the inflammatory marker CRP. Altogether, our results suggest that ESM, a natural extracellular biomaterial, may be attractive as a nutraceutical candidate with a possible effect on skeletal muscle aging possibly through its immunomodulating effect or gut microbiota.

• Bålsrud, Pia; Ulven, Stine Marie; Christensen, Jacob J.; Ottestad, Inger & Holven, Kirsten Bjørklund (2024). Inflammatory markers and frailty in home-dwelling elderly, a cross-sectional study. BMC Geriatrics. 24(1), p. 1–11. doi: 10.1186/s12877-024-04690-2. Full text in Research Archive Show summary

  Background Low-grade, chronic inflammation during ageing, (“inflammageing”), is suggested to be involved in the development of frailty in older age. However, studies on the association between frailty, using the frailty index definition, and inflammatory markers are limited. The aim of this study was to investigate the relationship between inflammatory markers and frailty index (FI) in older, home-dwelling adults. Method Home-dwelling men and women aged ≥ 70 years old, living in South-East Norway were recruited and included in a cross-sectional study. The FI used in the current study was developed according to Rockwood’s frailty index and included 38 variables, resulting in an FI score between 0 and 1 for each participant. Circulating inflammatory markers (IL-6, CRP, IGF-1, cystatin C, cathepsin S, and glycoprotein Acetyls) were analyzed from non-fasting blood samples using ELISA. Whole-genome PBMC transcriptomics was used to study the association between FI score and inflammation. Results The study population comprised 403 elderly (52% women), with a median age of 74 years and a mean BMI of 26.2 kg/m2. The mean FI score for the total group was 0.15 (range 0.005–0.56). The group was divided into a frail group (FI score ≥ 0.25) and non-frail group. After adjusting for BMI, age, sex, and smoking in the whole group, IL-6, cathepsin S, cystatin C, and Gp-acetyls remained significant associated to FI score (IL-6: 0.002, 95% CI: 0.001, 0.002, cathepsin S: 6.7e-06, 95% CI 2.44e-06, 0.00001, cystatin C: 0.004, 95% CI: 0.002, 0.006, Gp- Acetyls: 0.09, 95% CI: 0.05, 0.13, p < 0.01 for all), while CRP and IGF-1 were not (0.0003, 95% CI: -00001, 0.0007, p = 0.13, (-1.27e-06), 95% CI: (-0.0003), 0.0003, p = 0.99). There was a significant association between FI score and inflammatory markers, and FI score and monocyte-specific gene expression. Conclusions We found an association between FI score and inflammatory markers, and between FI score and monocyte-specific gene expression among elderly subjects above 70 years of age. Whether inflammation is a cause or consequence of frailty and whether the progression of frailty can be attenuated by reducing inflammation remains to be clarified.

• Myhrstad, Mari Charlotte Wik; Ruud, Emilia; Gaundal, Line; Gjøvaag, Terje; Rud, Ida & Retterstøl, Kjetil [Show all 10 contributors for this article] (2024). Gut microbiota, physical activity and/or metabolic markers in healthy individuals - towards new biomarkers of health. Frontiers in Nutrition. 11, p. 1–8. doi: 10.3389/fnut.2024.1438876. Full text in Research Archive Show summary

  Background: The global prevalence of the metabolic disease Type 2 Diabetes (T2D) is increasing. Risk factors contributing to the development of T2D include overweight and obesity, lack of physical activity (PA), and an unhealthy diet. In addition, the gut microbiota has been shown to affect metabolic regulation. Since T2D is preventable, efforts should be put into the discovery of new biomarkers for early detection of individuals at risk of developing the disease. Objective: The objective of the cross-sectional study was to explore the relationship between gut microbiota and physical activity (PA) and/or metabolic markers such as selected amino acids (AA), markers of glycaemic regulation and lipid metabolism and anthropometric measures. Design: Healthy adults (18 and 65 years) with BMI between 18.5 and 27.5 kg/m2 originally recruited to a randomised controlled trial (RCT) (n = 17: six males, eleven females), were included in this exploratory cross-sectional study. Physical activity data was calculated based on a 3-days registration, and blood metabolome, gut microbiota analyses and anthropometric measures from one visit of the intervention were used in this cross-sectional study. Results: Of the 47 gut bacteria analysed, there were a total of 87 significant correlations with AA, PA, body composition and/or metabolic markers. Several of the gut bacteria correlated with both PA, metabolic or anthropometric markers. Conclusion: In this study, we demonstrate associations between gut bacteria and PA and/or metabolic markers including AA in healthy individuals. The results may guide future studies aiming at identifying new and early biomarkers of metabolic health and diseases.

• Henriksen, Hege Berg; Henriksen, Christine; Sousa, Ana Rita Sequeira de; Alavi, Dena Helene; Augestad, Elin Maria Sandstad & Rising, Russell [Show all 12 contributors for this article] (2023). Validity and reproducibility of a whole-room indirect calorimeter for the estimation of VO<inf>2</inf>, VCO<inf>2</inf>, and resting metabolic rate. Physiological Reports. 11(7). doi: 10.14814/phy2.15658. Full text in Research Archive Show summary

  Abstract Whole‐room indirect calorimeters (WRICs) provide accurate instruments for the measurement of respiratory exchange, energy expenditure, and macronutrient oxidation. Here, we aimed to determine the validity and reproducibility of a 7500 L WRIC for the measurement of ventilation rates and resting metabolic rate (RMR). Technical validation was performed with propane combustion tests ( n  = 10) whereas biological reproducibility was tested in healthy subjects (13 women, 6 men, mean ± SD age 39.6 ± 15.3) in two 60 min measurements separated by 24 h. Subjects followed a run‐in protocol prior to measurements. The coefficient of variation (CV) and intraclass correlation coefficient (ICC) were calculated for ventilation rates of O2 (VO2), CO2 (VCO2), the respiratory quotient (RQ; VCO2/VO2), and RMR. Technical validation showed good validity with CVs ranging from 0.67% for VO 2 to 1.00% for energy expenditure. For biological reproducibility, CVs were 2.89% for VO 2 ; 2.67% for VCO 2 ; 1.95% for RQ; and 2.68% for RMR. With the exception of RQ (74%), ICCs were excellent for VO 2 (94%), VCO 2 (96%) and RMR (95%). Excluding participants that deviated from the run‐in protocol did not alter results. In conclusion, the 7500 L WRIC is technically valid and reproducible for ventilation rates and RMR.

• Das, Siddhartha; Somisetty, Venkata Satheesh; Ulven, Stine Marie & Matthews, Jason (2023). Resveratrol and 3,3′-Diindolylmethane Differentially Regulate Aryl Hydrocarbon Receptor and Estrogen Receptor Alpha Activity through Multiple Transcriptomic Targets in MCF-7 Human Breast Cancer Cells. International Journal of Molecular Sciences. ISSN 1661-6596. 24(19). doi: 10.3390/ijms241914578. Full text in Research Archive Show summary

  Inhibitory crosstalk between estrogen receptor alpha (ERα) and aryl hydrocarbon receptor (AHR) regulates 17β-estradiol (E2)-dependent breast cancer cell signaling. ERα and AHR are transcription factors activated by E2 and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), respectively. Dietary ligands resveratrol (RES) and 3,3′diindolylmethane (DIM) also activate ERα while only DIM activates AHR and RES represses it. DIM and RES are reported to have anti-cancer and anti-inflammatory properties. Studies with genome-wide targets and AHR- and ERα-regulated genes after DIM and RES are unknown. We used chromatin immunoprecipitation with high-throughput sequencing and transcriptomics to study ERα as well as AHR coregulation in MCF-7 human breast cancer cells treated with DIM, RES, E2, or TCDD alone or E2+TCDD for 1 and 6 h, respectively. ERα bound sites after being DIM enriched for the AHR motif but not after E2 or RES while AHR bound sites after being DIM and E2+TCDD enriched for the ERE motif but not after TCDD. More than 90% of the differentially expressed genes closest to an AHR binding site after DIM or E2+TCDD also had an ERα site, and 60% of the coregulated genes between DIM and E2+TCDD were common. Collectively, our data show that RES and DIM differentially regulate multiple transcriptomic targets via ERα and ERα/AHR coactivity, respectively, which need to be considered to properly interpret their cellular and biological responses. These novel data also suggest that, when both receptors are activated, ERα dominates with preferential recruitment of AHR to ERα target genes.

• Sousa, Ana Rita Sequeira de; Ottestad, Inger; Gjevestad, Gyrd Omholt; Holven, Kirsten Bjørklund; Ulven, Stine Marie & Christensen, Jacob J. (2023). Associations between PBMC whole genome transcriptome, muscle strength, muscle mass, and physical performance in healthy home-dwelling older women. GeroScience. ISSN 2509-2715. 45, p. 3175–3186. doi: 10.1007/s11357-023-00819-0. Full text in Research Archive Show summary

  Abstract Increasing age is accompanied by many changes, including declining functional skeletal muscle health and immune dysfunction. Peripheral blood mononuclear cells (PBMCs) are circulating cells that assemble an immune response, but their whole genome transcriptome has not been studied in the context of age-related muscle health. Consequently, this article explored associations between three muscle variables indicative of functional muscle health — maximum handgrip strength (muscle strength), appendicular skeletal muscle mass index (ASMI, muscle mass), and gait speed (physical performance) — and two groups of bioinformatics-generated PBMC gene expression features (gene expression–estimated leukocyte subset proportions and gene clusters). We analyzed cross-sectional data from 95 home-dwelling healthy women ≥ 70 years, using “cell-type identification by estimating relative subsets of RNA transcripts” (CIBERSORT) to estimate leukocyte subset proportions and “weighted correlation network analysis” (WGCNA) to generate gene clusters. Associations were studied using linear regression models and relevant gene clusters were subjected to gene set enrichment analysis using gene ontology. Gait speed and ASMI associated with CIBERSORT-estimated monocyte proportions ( β  =  − 0.090, 95% CI = (− 0.146, − 0.034), p -value = 0.002 for gait speed, and β  =  − 0.206, 95% CI = (− 0.385, − 0.028), p -value = 0.024 for ASMI), and gait speed associated with CIBERSORT-estimated M2 macrophage proportions ( β  =  − 0.026, 95% CI = (− 0.043, − 0.008), p -value = 0.004). Furthermore, maximum handgrip strength associated with nine WGCNA gene clusters, enriched in processes related to immune function and skeletal muscle cells ( β in the range − 0.007 to 0.008, p -values &lt; 0.05). These results illustrate interactions between skeletal muscle and the immune system, supporting the notion that age-related functional muscle health and the immune system are closely linked.

• Johansen, Anja Katrin; Bogsrud, Martin Prøven; Christensen, Jacob J.; Rundblad, Amanda; Narverud, Ingunn & Ulven, Stine Marie [Show all 9 contributors for this article] (2023). Young women with familial hypercholesterolemia have higher LDL-cholesterol burden than men: Novel data using repeated measurements during 12-years follow-up. Atherosclerosis Plus. ISSN 2667-0909. 51, p. 28–34. doi: 10.1016/j.athplu.2023.01.001. Full text in Research Archive Show summary

  Background and aims The concentration and the duration of exposure to low-density lipoprotein cholesterol (LDL-C) (LDL-C burden) is an important determinant of risk for cardiovascular disease and thresholds has recently been estimated. Individuals with familial hypercholesterolemia (FH) have increased risk of premature cardiovascular disease. The overall aim of the present study was to describe differences in LDL-C level and LDL-C burden in females and males with FH visiting an outpatient lipid clinic from a young age, using multiple LDL-C measurements during a follow-up time of 12 years. First, we aimed to study if the LDL-C concentration and the LDL-C burden is different between females and males at ages 0–10, 10–20, 20–30 and >30 years. Second, we aimed to estimate the subject-specific LDL-C burden at age 19 and 30 years, and the proportion of female and male patients that reach suggested LDL-C thresholds indicating high risk of ASCVD. Methods Data was retrospectively collected from medical records of 438 subjects (207 girls and 231 boys) with FH, referred to the Lipid Clinic, Oslo University Hospital below the age of 19 years. The LDL-C burden was estimated based on repeated LDL-C measurements over time. Results Subjects were followed over a period of mean 12.0 (SD 7.0) years, with median 10 years (7–17; 25–75 percentiles, minimum 2), with median 6 (4–9; 25–75 percentiles, minimum 2) available LDL-C measurements, starting at mean age 11 (SD 3.9) years. There was a difference in both LDL-C and LDL-C burden between sexes at different ages. On average, males had lower LDL-C over time, although this difference was less pronounced with age and males also had lower estimated LDL-C burden over time, and this difference was further exacerbated with age. Conclusion Our study shows that young women with FH have a higher LDL-C burden than their male counterparts, potentially explaining the increased excess CVD risk seen among these. It underscores the importance of careful-follow up and early treatment initiation both prior to and after pregnancies in order to limit statin-free periods.

• Rundblad, Amanda; Sandoval, Viviana Paz Sandoval; Holven, Kirsten Bjørklund; Ordovás, José M. & Ulven, Stine Marie (2023). Omega-3 fatty acids and individual variability in plasma triglyceride response: A mini-review. Redox Biology. 63, p. 1–9. doi: 10.1016/j.redox.2023.102730. Full text in Research Archive Show summary

  Cardiovascular disease (CVD) is a leading cause of death worldwide. Supplementation with the marine omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is associated with lower CVD risk. However, results from randomized controlled trials that examine the effect of omega-3 supplementation on CVD risk are inconsistent. This risk-reducing effect may be mediated by reducing inflammation, oxidative stress and serum triglyceride (TG) levels. However, not all individuals respond by reducing TG levels after omega-3 supplementation. This inter-individual variability in TG response to omega-3 supplementation is not fully understood. Hence, we aim to review the evidence for how interactions between omega-3 fatty acid supplementation and genetic variants, epigenetic and gene expression profiling, gut microbiota and habitual intake of omega-3 fatty acids can explain why the TG response differs between individuals. This may contribute to understanding the current controversies and play a role in defining future personalized guidelines to prevent CVD.

• Øyri, Linn K. L.; Christensen, Jacob J.; Sebert, Sylvain; Thoresen, Magne; Michelsen, Trond M. & Ulven, Stine M. [Show all 12 contributors for this article] (2023). Maternal prenatal cholesterol levels predict offspring weight trajectories during childhood in the Norwegian Mother, Father and Child Cohort Study. BMC Medicine. 21. doi: 10.1186/s12916-023-02742-9. Full text in Research Archive Show summary

  Background Numerous intrauterine factors may affect the offspring’s growth during childhood. We aimed to explore if maternal and paternal prenatal lipid, apolipoprotein (apo)B and apoA1 levels are associated with offspring weight, length, and body mass index from 6 weeks to eight years of age. This has previously been studied to a limited extent. Methods This parental negative control study is based on the Norwegian Mother, Father and Child Cohort Study and uses data from the Medical Birth Registry of Norway. We included 713 mothers and fathers with or without self-reported hypercholesterolemia and their offspring. Seven parental metabolites were measured by nuclear magnetic resonance spectroscopy, and offspring weight and length were measured at 12 time points. Data were analyzed by linear spline mixed models, and the results are presented as the interaction between parental metabolite levels and offspring spline (age). Results Higher maternal total cholesterol (TC) level was associated with a larger increase in offspring body weight up to 8 years of age (0.03 ≤ Pinteraction ≤ 0.04). Paternal TC level was not associated with change in offspring body weight (0.17 ≤ Pinteraction ≤ 0.25). Higher maternal high-density lipoprotein cholesterol (HDL-C) and apoA1 levels were associated with a lower increase in offspring body weight up to 8 years of age (0.001 ≤ Pinteraction ≤ 0.005). Higher paternal HDL-C and apoA1 levels were associated with a lower increase in offspring body weight up to 5 years of age but a larger increase in offspring body weight from 5 to 8 years of age (0.01 ≤ Pinteraction ≤ 0.03). Parental metabolites were not associated with change in offspring height or body mass index up to 8 years of age (0.07 ≤ Pinteraction ≤ 0.99). Conclusions Maternal compared to paternal TC, HDL-C, and apoA1 levels were more strongly and consistently associated with offspring body weight during childhood, supporting a direct intrauterine effect.

• Øhman, Elisabeth Adolfsen; Fossli, Maria; Ottestad, Inger; Holven, Kirsten Bjørklund; Ulven, Stine Marie & Løland, Beate Fossum [Show all 7 contributors for this article] (2023). Dietary treatment postpartum in women with obesity reduces weight and prevents weight gain: a randomised controlled trial. BMC Pregnancy and Childbirth. 23. doi: 10.1186/s12884-023-05976-w. Full text in Research Archive Show summary

  Background Women with pre-pregnancy obesity have an increased risk of retaining or gaining weight postpartum and may benefit from weight loss treatment. However, evidence is lacking for weight loss strategies in women with BMIs in the higher obesity classes. A dietary treatment for postpartum weight loss resulted in a 10% weight reduction in lactating women with a mean BMI of 30 kg/m2. We aimed to examine the effects of this dietary treatment on changes in weight, markers of lipid and glucose metabolism, waist and hip circumference and postpartum weight retention (PPWR) in postpartum women with higher BMIs than tested previously. Methods At baseline, approximately 8 weeks postpartum, 29 women with a mean (SD) BMI = 40.0 (5.2) kg/m2 were randomised to a 12-week dietary treatment (n 14) or to a control treatment (n 15). Measurements were made at baseline and after 3 and 12 months. Data was analysed using mixed model. Results The mean weight change in the diet group was -2.3 (3.1) kg compared to 1.7 (3.1) kg in the control group after 3 months (P = 0.003) and -4.2 (5.6) kg compared to 4.8 (11.8) kg in the control group after 12 months (P = 0.02). The dietary treatment led to reduced waist circumference (P < 0.04) and PPWR (P < 0.01) compared to the control treatment at both time points. The treatment lowered fasting blood glucose at 12 months (P = 0.007) as the only effect on markers of lipid and glucose metabolism. Conclusion The dietary treatment postpartum reduced weight and prevented weight retention or weight gain in women with obesity. Trial registration The trial was retrospectively registered at ClinicalTrials.gov (NCT03579667) 06/07/2018. Graphical Abstract In a randomised, controlled trial, 29 postpartum women with obesity were allocated to a dietary treatment or a control treatment. The dietary treatment reduced weight and prevented postpartum weight retention or weight gain after 12 months. Reference: Adapted from “Randomized, Placebo-Controlled, Parallel Study Design (2 Arms, Graphical)”, by BioRender.com (2022). Retrieved from https://app.biorender.com/biorender-templates .

• Rundblad, Amanda; Christensen, Jacob J.; Hustad, Kristin Solheim; Bastani, Nasser Ezzatkhah; Ottestad, Inger & Holven, Kirsten Bjørklund [Show all 7 contributors for this article] (2023). Associations between dietary intake and glucose tolerance in clinical and metabolomics-based metabotypes. Genes & Nutrition. ISSN 1555-8932. 18(3). doi: 10.1186/s12263-023-00721-6. Full text in Research Archive Show summary

  Background Metabotyping is a novel concept to group metabolically similar individuals. Different metabotypes may respond differently to dietary interventions; hence, metabotyping may become an important future tool in precision nutrition strategies. However, it is not known if metabotyping based on comprehensive omic data provides more useful identification of metabotypes compared to metabotyping based on only a few clinically relevant metabolites. Aim This study aimed to investigate if associations between habitual dietary intake and glucose tolerance depend on metabotypes identified from standard clinical variables or comprehensive nuclear magnetic resonance (NMR) metabolomics. Methods We used cross-sectional data from participants recruited through advertisements aimed at people at risk of type 2 diabetes mellitus (n = 203). Glucose tolerance was assessed with a 2-h oral glucose tolerance test (OGTT), and habitual dietary intake was recorded with a food frequency questionnaire. Lipoprotein subclasses and various metabolites were quantified with NMR spectroscopy, and plasma carotenoids were quantified using high-performance liquid chromatography. We divided participants into favorable and unfavorable clinical metabotypes based on established cutoffs for HbA1c and fasting and 2-h OGTT glucose. Favorable and unfavorable NMR metabotypes were created using k-means clustering of NMR metabolites. Results While the clinical metabotypes were separated by glycemic variables, the NMR metabotypes were mainly separated by variables related to lipoproteins. A high intake of vegetables was associated with a better glucose tolerance in the unfavorable, but not the favorable clinical metabotype (interaction, p = 0.01). This interaction was confirmed using plasma concentrations of lutein and zeaxanthin, objective biomarkers of vegetable intake. Although non-significantly, the association between glucose tolerance and fiber intake depended on the clinical metabotypes, while the association between glucose tolerance and intake of saturated fatty acids and dietary fat sources depended on the NMR metabotypes. Conclusion Metabotyping may be a useful tool to tailor dietary interventions that will benefit specific groups of individuals. The variables that are used to create metabotypes will affect the association between dietary intake and disease risk.

• Christensen, Jacob J.; Arnesen, Erik Kristoffer; Rundblad, Amanda; Telle-Hansen, Vibeke; Narverud, Ingunn & Blomhoff, Rune [Show all 10 contributors for this article] (2023). Dietary fat quality, plasma atherogenic lipoproteins, and atherosclerotic cardiovascular disease: An overview of the rationale for dietary recommendations for fat intake. Atherosclerosis. ISSN 0021-9150. 389. doi: 10.1016/j.atherosclerosis.2023.117433. Full text in Research Archive Show summary

  The scientific evidence supporting the current dietary recommendations for fat quality keeps accumulating; however, a paradoxical distrust has taken root among many researchers, clinicians, and in parts of the general public. One explanation for this distrust may relate to an incomplete overview of the totality of the evidence for the link between fat quality as a dietary exposure, and health outcomes such as atherosclerotic cardiovascular disease (ASCVD). Therefore, the main aim of the present narrative review was to provide a comprehensive overview of the rationale for dietary recommendations for fat intake, limiting our discussion to ASCVD as outcome. Herein, we provide a core framework – a causal model – that can help us understand the evidence that has accumulated to date, and that can help us understand new evidence that may become available in the future. The causal model for fat quality and ASCVD is comprised of three key research questions (RQs), each of which determine which scientific methods are most appropriate to use, and thereby which lines of evidence that should feed into the causal model. First, we discuss the link between low-density lipoprotein (LDL) particles and ASCVD (RQ1); we draw especially on evidence from genetic studies, randomized controlled trials (RCTs), epidemiology, and mechanistic studies. Second, we explain the link between dietary fat quality and LDL particles (RQ2); we draw especially on metabolic ward studies, controlled trials (randomized and non-randomized), and mechanistic studies. Third, we explain the link between dietary fat quality, LDL particles, and ASCVD (RQ3); we draw especially on RCTs in animals and humans, epidemiology, population-based changes, and experiments of nature. Additionally, the distrust over dietary recommendations for fat quality may partly relate to an unclear understanding of the scientific method, especially as applied in nutrition research, including the process of developing dietary guidelines. We therefore also aimed to clarify this process. We discuss how we assess causality in nutrition research, and how we progress from scientific evidence to providing dietary recommendations.

• Melnes, Torunn; Bogsrud, Martin Prøven; Thorsen, Ida; Fossum, Julie; Christensen, Jacob J. & Narverud, Ingunn [Show all 9 contributors for this article] (2022). What characterizes event-free elderly FH patients? A comprehensive lipoprotein profiling. NMCD. Nutrition Metabolism and Cardiovascular Diseases. ISSN 0939-4753. 32(7), p. 1651–1660. doi: 10.1016/j.numecd.2022.03.028. Full text in Research Archive Show summary

  Familial hypercholesterolemia (FH) is a genetic disorder characterized by lifelong elevated low-density lipoprotein cholesterol (LDL-C) and increased risk of pre- mature coronary heart disease (CHD). Cholesterol-lowering therapy (statins) reduces CHD risk, but have been available only in the last 25 years, thus, elderly FH patients have been exposed to elevated LDL-C levels most of their life. Surprisingly, some of these have never experienced any CHD event, raising the question whether they present CHD resistant characteristics. Identifying possible cardioprotective biomarkers could contribute to future CHD preventive treatment, therefore, we aimed to identify metabolic markers in event-free elderly FH subjects. Methods and results: We used a high-throughput nuclear magnetic resonance (NMR) spectroscopy platform to quantify a large number of metabolites in serum samples from 83 FH patients >65 years, and analyze differences between subjects with (n = 39) and without (n = 44) CHD. Mean age was 70 years in both groups (57% and 38% female in the event-free group and CHD group, respectively). The event-free group had significantly higher levels of large and extra-large high-density lipoprotein (HDL) particles, and higher concentration of Apolipoprotein A1 (ApoA1) and cholesterol in HDL and HDL2 particles, compared to the CHD group (p < 0.05 for all). Conclusion: CHD resistant elderly FH patients have higher levels of large HDL particles. The mechanisms behind the event-free survival among these patients remain unclear; hence, a deeper understanding of the metabolic profile in event-free elderly FH subjects may lead to development of novel preventive therapies.

• Pigsborg, Kristina; Gürdeniz, Gözde; Rangel-Huerta, Oscar Daniel; Holven, Kirsten Bjørklund; Dragsted, Lars Ove & Ulven, Stine Marie (2022). Effects of changing from a diet with saturated fat to a diet with n-6 polyunsaturated fat on the serum metabolome in relation to cardiovascular disease risk factors. European Journal of Nutrition. ISSN 1436-6207. 61, p. 2079–2989. doi: 10.1007/s00394-021-02796-6. Full text in Research Archive Show summary

  Abstract Purpose Replacing saturated fatty acids (SFA) with polyunsaturated fatty acids (PUFA) is associated with a reduced risk of cardiovascular disease. Yet, the changes in the serum metabolome after this replacement is not well known. Therefore, the present study aims to identify the metabolites differentiating diets where six energy percentage SFA is replaced with PUFA and to elucidate the association of dietary metabolites with cardiometabolic risk markers. Methods In an 8-week, double-blind, randomized, controlled trial, 99 moderately hyper-cholesterolemic adults (25–70 years) were assigned to a control diet (C-diet) or an experimental diet (Ex-diet). Both groups received commercially available food items with different fatty acid compositions. In the Ex-diet group, products were given where SFA was replaced mostly with n-6 PUFA. Fasting serum samples were analysed by untargeted ultra-performance liquid chromatography high-resolution mass spectrometry (UPLC-HRMS). Pre-processed data were analysed by double cross-validated Partial Least-Squares Discriminant Analysis (PLS-DA) to detect features differentiating the two diet groups. Results PLS-DA differentiated the metabolic profiles of the Ex-diet and the C-diet groups with an area under the curve of 0.83. The Ex-diet group showed higher levels of unsaturated phosphatidylcholine plasmalogens, an unsaturated acylcarnitine, and a secondary bile acid. The C-diet group was characterized by odd-numbered phospholipids and a saturated acylcarnitine. The Principal Component analysis scores of the serum metabolic profiles characterizing the diets were significantly associated with low-density lipoprotein cholesterol, total cholesterol, and triglyceride levels but not with glycaemia. Conclusion The serum metabolic profiles confirmed the compliance of the participants based on their diet-specific metabolome after replacing SFA with mostly n-6 PUFA. The participants' metabolic profiles in response to the change in diet were associated with cardiovascular disease risk markers. This study was registered at clinicaltrials.gov as NCT 01679496 on September 6th 2012.

• Hustad, Kristin Solheim; Ottestad, Inger; Olsen, Thomas; Sæther, Thomas; Ulven, Stine Marie & Holven, Kirsten Bjørklund (2022). Salmon fish protein supplement increases serum vitamin B12 and selenium concentrations: secondary analysis of a randomised controlled trial. European Journal of Nutrition. ISSN 1436-6207. 61(6), p. 3085–3093. doi: 10.1007/s00394-022-02857-4. Full text in Research Archive Show summary

  Abstract Purpose The main aim of the present study was to examine the effect of a fish protein supplement made from by-products from production of Atlantic salmon, on blood concentration of micronutrients. Methods We conducted an 8-week double-blind parallel-group randomised controlled trial. In total, 88 adults were randomised to a salmon fish protein supplement or placebo, and 74 participants were included in the analysis of vitamin D, omega-3, vitamin B12, selenium, folate, zinc, homocysteine and mercury. Results During the intervention period, geometric mean (GSD) of serum vitamin B12 concentrations increased from 304 (1.40) to 359 (1.42) pmol/L in the fish protein group ( P vs. controls = 0.004) and mean (SD) serum selenium increased from 1.18 (0.22) to 1.30 (0.20) μmol/L ( P vs. controls = 0.002). The prevalence of low vitamin B12 status (B12 &lt; 148–221 &gt; pmol/L) decreased from 15.4 to 2.6% in the fish protein group, while increasing from 5.9 to 17.6% in the placebo group ( P  = 0.045). There was no difference between the groups in serum levels of the other micronutrients measured. Conclusion Including a salmon fish protein supplement in the daily diet for 8 weeks, increases serum vitamin B12 and selenium concentrations. From a sustainability perspective, by-products with high contents of micronutrients and low contents of contaminants, could be a valuable dietary supplement or food ingredient in populations with suboptimal intake. Trail Registration The study was registered at ClinicalTrials.gov (ID: NCT03764423) on June 29th 2018.

• Gaundal, Line; Myhrstad, Mari; Rud, Ida; Gjøvaag, Terje; Byfuglien, Marte G. & Retterstøl, Kjetil [Show all 9 contributors for this article] (2022). Gut microbiota is associated with dietary intake and metabolic markers in healthy individuals. Food & Nutrition Research (FNR). ISSN 1654-6628. 66. doi: 10.29219/fnr.v66.8580. Full text in Research Archive Show summary

  Background: Metabolic diseases have been related to gut microbiota, and new knowledge indicates that diet impacts host metabolism through the gut microbiota. Identifying specific gut bacteria associated with both diet and metabolic risk markers may be a potential strategy for future dietary disease prevention. However, studies investigating the association between the gut microbiota, diet, and metabolic markers in healthy indi-viduals are scarce.Objective: We explored the relationship between a panel of gut bacteria, dietary intake, and metabolic and anthropometric markers in healthy adults.Design: Forty-nine volunteers were included in this cross-sectional study. Measures of glucose, serum tri-glyceride, total cholesterol, hemoglobin A1c (HbA1c), blood pressure (BP), and body mass index (BMI) were collected after an overnight fast, in addition to fecal samples for gut microbiota analyzes using a targeted approach with a panel of 48 bacterial DNA probes and assessment of dietary intake by a Food Frequency Questionnaire (FFQ). Correlations between gut bacteria, dietary intake, and metabolic and anthropometric markers were assessed by Pearson’s correlation. Gut bacteria varying according to dietary intake and metabolic markers were assessed by a linear regression model and adjusted for age, sex, and BMI.Results: Of the 48 gut bacteria measured, 24 and 16 bacteria correlated significantly with dietary intake and metabolic and/or anthropometric markers, respectively. Gut bacteria including Alistipes, Lactobacillus spp., and Bacteroides stercoris differed according to the intake of the food components, fiber, sodium, saturated fatty acids, and dietary indices, and metabolic markers (BP and total cholesterol) after adjustments. Notably, Bacteroides stercoris correlated positively with the intake of fiber, grain products, and vegetables, and higher Bacteroides stercoris abundance was associated with higher adherence to Healthy Nordic Food Index (HNFI) and lower diastolic BP after adjustment.Conclusion: Our findings highlight the relationship between the gut microbiota, diet, and metabolic mark-ers in healthy individuals. Further investigations are needed to address whether these findings are causally linked and whether targeting these gut bacteria can prevent metabolic diseases.

• Hjorth, Marit; Galigniana, Natalia; Ween, Ola; Ulven, Stine Marie; Holven, Kirsten Bjørklund & Dalen, Knut Tomas [Show all 7 contributors for this article] (2022). Postprandial Effects of Salmon Fishmeal and Whey on Metabolic Markers in Serum and Gene Expression in Liver Cells. Nutrients. 14(8). doi: 10.3390/nu14081593. Full text in Research Archive Show summary

  Fish is considered an important part of a healthy diet, in part due to the content of long chain omega-3 fatty acids. However, both lean and fatty fish have beneficial health effects, suggesting that micronutrients and proteins may play a role. In a randomised, controlled, cross-over trial, five healthy male participants consumed 5.2 g of protein from either salmon fishmeal or whey. Blood samples were taken before and 30 and 60 min after intake. The concentration of glucose, lipids, hormones and metabolites, including 28 different amino acids and derivatives, were measured in serum or plasma. Cultured HepG2 cells were incubated with or without serum from the participants, and transcriptomic profiling was performed using RNA sequencing. The ingestion of both salmon fishmeal and whey reduced the glucose and triglyceride levels in serum. Protein intake, independent of the source, increased the concentration of 22 amino acids and derivatives in serum. Fishmeal increased the concentration of arginine, methionine, serine, glycine, cystathionine and 2-aminobutyric acid more than whey did. Incubation with postprandial serum resulted in large transcriptomic alterations in serum-fasted HepG2 cells, with the differential expression of >4500 protein coding genes. However, when comparing cells cultivated in fasting serum to postprandial serum after the ingestion of fishmeal and whey, we did not detect any differentially regulated genes, neither with respect to the protein source nor with respect to the time after the meal. The comparable nutrigenomic effects of fishmeal and whey do not change the relevance of fish by-products as an alternative food source.

• Telle-Hansen, Vibeke; Gaundal, Line; Bastani, Nasser Ezzatkhah; Rud, Ida; Byfuglien, Marte G. & Gjøvaag, Terje [Show all 10 contributors for this article] (2022). Replacing saturated fatty acids with polyunsaturated fatty acids increases the abundance of Lachnospiraceae and is associated with reduced total cholesterol levels-a randomized controlled trial in healthy individuals. Lipids in Health and Disease. 21, p. 1–13. doi: 10.1186/s12944-022-01702-1. Full text in Research Archive Show summary

  Improving dietary fat quality strongly affects serum cholesterol levels and hence the risk of cardiovascular diseases (CVDs). Recent studies have identified dietary fat as a potential modulator of the gut microbiota, a central regulator of host metabolism including lipid metabolism. We have previously shown a significant reduction in total cholesterol levels after replacing saturated fatty acids (SFAs) with polyunsaturated fatty acids (PUFAs). The aim of the present study was to investigate the effect of dietary fat quality on gut microbiota, short-chain fatty acids (SCFAs), and bile acids in healthy individuals. In addition, to investigate how changes in gut microbiota correlate with blood lipids, bile acids, and fatty acids.

• Gürdeniz, Gözde; Uusitupa, Matti; Hermansen, Kjeld; Savolainen, Markku J.; Schwab, Ursula & Kolehmainen, Marjukka [Show all 19 contributors for this article] (2022). Analysis of the SYSDIET Healthy Nordic Diet randomized trial based on metabolic profiling reveal beneficial effects on glucose metabolism and blood lipids. Clinical Nutrition. ISSN 0261-5614. 41(2), p. 441–451. doi: 10.1016/j.clnu.2021.12.031. Full text in Research Archive Show summary

  Background & aims Intake assessment in multicenter trials is challenging, yet important for accurate outcome evaluation. The present study aimed to characterize a multicenter randomized controlled trial with a healthy Nordic diet (HND) compared to a Control diet (CD) by plasma and urine metabolic profiles and to associate them with cardiometabolic markers. Methods During 18–24 weeks of intervention, 200 participants with metabolic syndrome were advised at six centres to eat either HND (e.g. whole-grain products, berries, rapeseed oil, fish and low-fat dairy) or CD while being weight stable. Of these 166/159 completers delivered blood/urine samples. Metabolic profiles of fasting plasma and 24 h pooled urine were analysed to identify characteristic diet-related patterns. Principal components analysis (PCA) scores (i.e. PC1 and PC2 scores) were used to test their combined effect on blood glucose response (primary endpoint), serum lipoproteins, triglycerides, and inflammatory markers. Results The profiles distinguished HND and CD with AUC of 0.96 ± 0.03 and 0.93 ± 0.02 for plasma and urine, respectively, with limited heterogeneity between centers, reflecting markers of key foods. Markers of fish, whole grain and polyunsaturated lipids characterized HND, while CD was reflected by lipids containing palmitoleic acid. The PC1 scores of plasma metabolites characterizing the intervention is associated with HDL (β = 0.05; 95% CI: 0.02, 0.08; P = 0.001) and triglycerides (β = −0.06; 95% CI: −0.09, −0.03; P < 0.001). PC2 scores were related with glucose metabolism (2 h Glucose, β = 0.1; 95% CI: 0.05, 0.15; P < 0.001), LDL (β = 0.06; 95% CI: 0.01, 0.1; P = 0.02) and triglycerides (β = 0.11; 95% CI: 0.06, 0.15; P < 0.001). For urine, the scores were related with LDL cholesterol. Conclusions Plasma and urine metabolite profiles from SYSDIET reflected good compliance with dietary recommendations across the region. The scores of metabolites characterizing the diets associated with outcomes related with cardio-metabolic risk. Our analysis therefore offers a novel way to approach a per protocol analysis with a balanced compliance assessment in larger multicentre dietary trials.

• Canet, Francisco; Christensen, Jacob J.; Victor, Victor M.; Hustad, Kristin Solheim; Ottestad, Inger & Rundblad, Amanda [Show all 11 contributors for this article] (2022). Glycated proteins, glycine, acetate, and monounsaturated fatty acids may act as new biomarkers to predict the progression of type 2 diabetes: Secondary analyses of a randomized controlled trial. Nutrients. 14(23), p. 1–19. doi: 10.3390/nu14235165. Full text in Research Archive Show summary

  Food protein or food-derived peptides may regulate blood glucose levels; however, studies have shown inconsistent results. The aim of the present study was to characterize subgroups of individuals with increased risk of type 2 diabetes (T2D) and to investigate the cardiometabolic effects of fish protein in the same subgroups. We first divided participants into high insuliniAUC and low insuliniAUC subjects based on their insulin incremental area under the curve (iAUC) levels after a 2 h oral glucose tolerance test (OGTT), and secondly based on whether they had received 5.2 g salmon fish protein or placebo for 8 weeks, in a previously conducted randomized controlled trial (RCT). We then profiled these groups by analyzing plasma metabolomics and peripheral blood mononuclear cell (PBMC) gene expression. Compared to the low insuliniAUC group, the high insuliniAUC group had higher plasma concentrations of monounsaturated fatty acids (MUFAs) and glycated proteins (GlycA) and lower concentrations of glycine and acetate. After intervention with fish protein compared to placebo, however, only acetate was significantly increased in the low insuliniAUC group. In conclusion, we identified metabolic biomarkers known to be associated with T2D; also, intervention with fish protein did not affect cardiometabolic risk markers in subgroups with increased risk of T2D.

• Andersen, Lene Frost; Berstad, Paula; Bukhvalova, Barbara Alexandra; Carlsen, Monica Hauger; Dahl, Lisbeth Jane & Goksøyr, Anders [Show all 35 contributors for this article] (2022). Benefit and risk assessment of fish in the Norwegian diet - Scientific Opinion of the Steering Committee of the Norwegian Scientific Committee for Food and Environment. VKM Report. 2022(17). Full text in Research Archive Show summary

  In 2006, VKM published “A comprehensive assessment of fish and other seafood in the Norwegian diet”. The assessment supported the recommendation from Norwegian Health authorities to eat more fish both for dinner and on sandwiches. In an update of the assessment in 2014 VKM concluded that “the benefits from fish consumption clearly outweigh the negligible risk presented by current levels of contaminants and other undesirable substances in fish”. Because of new knowledge available, the Norwegian Food Safety Authority requested a new benefit and risk assessment of fish in the Norwegian diet in 2019. In the assignment, they asked VKM to answer the following questions:<p> <p>Which health consequences will it have for the Norwegian population if they:<uli> <li>Continue with the same fish consumption levels as of today</li> <li>Increase the consumption of fish to match the recommendations given by the Norwegian Directorate of Health</li> </uli>

• Øhman, Elisabeth Adolfsen; Kirchner, Lisa; Winkvist, Anna; Bertz, Fredrik; Holven, Kirsten Bjørklund & Ulven, Stine Marie [Show all 7 contributors for this article] (2022). Effects of dietary and exercise treatments on HDL subclasses in lactating women with overweight and obesity: A secondary analysis of an RCT. British Journal of Nutrition. ISSN 0007-1145. 128, p. 2105–2114. doi: 10.1017/S0007114522000241. Full text in Research Archive Show summary

  Abstract Childbearing decreases HDL-cholesterol, potentially contributing to the increased risk of CVD in parous women. Large HDL particles (HDL-P) are associated with lower risk of CVD. In this secondary analysis of a randomised controlled trial, we investigated the effects of 12-week dietary and exercise treatments on HDL-P subclass concentration, size and apoA1 in lactating women with overweight/obesity. At 10–14 weeks postpartum, 68 women with pre-pregnant BMI 25–35 kg/m 2 were randomised to four groups using 2 × 2 factorial design: (1) dietary treatment for weight loss; (2) exercise treatment; (3) both treatments and (4) no treatment. Lipoprotein subclass profiling by NMR spectroscopy was performed in serum at randomisation and after 3 and 12 months, and the results analysed with two-way ANCOVA. Lipid concentrations decline naturally postpartum. At 3 months (5–6 months postpartum), both diet ( P = 0·003) and exercise ( P = 0·008) reduced small HDL-P concentration. Concurrently, exercise limited the decline in very large HDL-P ( P = 0·002) and the effect was still significant at 12 months (15 months postpartum) ( P = 0·041). At 12 months, diet limited the decline in very large HDL-P ( P = 0·005), large HDL-P ( P = 0·001) and apoA1 ( P = 0·002) as well as HDL size ( P = 0·002). The dietary treatment for weight loss and the exercise treatment both showed effects on HDL-P subclasses in lactating women with overweight and obesity possibly associated with lower CVD risk. The dietary treatment had more effects than the exercise treatment at 12 months, likely associated with a 10 % weight loss.

• Hjorth, Marit; Doncheva, Atanaska Ivanova; Norheim, Frode Amador; Ulven, Stine Marie; Holven, Kirsten Bjørklund & Sæther, Thomas [Show all 7 contributors for this article] (2022). Consumption of salmon fishmeal increases hepatic cholesterol content in obese C57BL/6 J mice. European Journal of Nutrition. ISSN 1436-6207. 61, p. 4027–4043. doi: 10.1007/s00394-022-02930-y. Full text in Research Archive Show summary

  Abstract Purpose By-products from farmed fish contain large amounts of proteins and may be used for human consumption. The purpose of this study was to investigate cardiometabolic effects and metabolic tolerance in mice consuming fishmeal from salmon by-products, salmon filet or beef. Methods Female C57BL/6J mice were fed chow, as a healthy reference group, or a high-fat diet for 10 weeks to induce obesity and glucose intolerance. Obese mice were subsequently given isocaloric diets containing 50% of the dietary protein from salmon fishmeal, salmon filet or beef for 10 weeks. Mice were subjected to metabolic phenotyping, which included measurements of body composition, energy metabolism in metabolic cages and glucose tolerance. Lipid content and markers of hepatic toxicity were determined in plasma and liver. Hepatic gene and protein expression was determined with RNA sequencing and immunoblotting. Results Mice fed fishmeal, salmon filet or beef had similar food intake, energy consumption, body weight gain, adiposity, glucose tolerance and circulating levels of lipids and hepatic toxicity markers, such as p-ALT and p-AST. Fishmeal increased hepatic cholesterol levels by 35–36% as compared to salmon filet (p = 0.0001) and beef (p = 0.005). This was accompanied by repressed expression of genes involved in steroid and cholesterol metabolism and reduced levels of circulating Pcsk9. Conclusion Salmon fishmeal was well tolerated, but increased hepatic cholesterol content. The high cholesterol content in fishmeal may be responsible for the effects on hepatic cholesterol metabolism. Before introducing fishmeal from salmon by-products as a dietary component, it may be advantageous to reduce the cholesterol content in fishmeal. Introduction

• Telle-Hansen, Vibeke; Gaundal, Line; Høgvard, Benedicte; Ulven, Stine Marie; Holven, Kirsten Bjørklund & Byfuglien, Marte Gjeitung [Show all 12 contributors for this article] (2022). A three-day intervention with granola containing cereal beta-glucan improves glycemic response and changes the gut microbiota in healthy individuals: A crossover study. Frontiers in Nutrition. 9, p. 1–16. doi: 10.3389/fnut.2022.796362. Full text in Research Archive Show summary

  Intake of soluble fibers including beta-glucan, is known to improve post-prandial glycemic response. The mechanisms have been attributed to the viscous gel forming in the stomach and small intestine, giving a longer absorption time. However, recent evidence suggests a link between intake of beta-glucan and improved glycemic regulation at subsequent meals through the gut microbiota. We investigated the short-term effect of granola with different amounts of cereal beta-glucan on glycemic response and gut microbiota. After a two-week run-in period (baseline), fourteen healthy, normal weight adults completed a dose-response dietary crossover study. Different amounts of cereal beta-glucan (low: 0.8 g, medium: 3.2 g and high: 6.6 g) were provided in granola and eaten with 200 ml low-fat milk as an evening meal for three consecutive days. Blood glucose and insulin were measured fasted and after an oral glucose tolerance test (OGTT) the following day, in addition to peptide YY (PYY) and glucagon-like peptide (GLP-2), fasting short chain fatty acids (SCFA) in blood, breath H2, and gut microbiota in feces. Only the intervention with medium amounts of beta-glucan decreased blood glucose and insulin during OGTT compared to baseline. Fasting PYY increased with both medium and high beta-glucan meal compared to the low beta-glucan meal. The microbiota and SCFAs changed after all three interventions compared to baseline, where acetate and butyrate increased, while propionate was unchanged. Highest positive effect size after intake of beta-glucan was found with Haemophilus, followed by Veillonella and Sutterella. Furthermore, we found several correlations between different bacterial taxa and markers of glycemic response. In summary, intake of granola containing 3.2 g cereal beta-glucan as an evening meal for three consecutive days reduced the glycemic response after an OGTT 0-180 min and changed gut microbiota composition. Since we cannot rule out that other fiber types have contributed to the effect, more studies are needed to further explore the effect of cereal beta-glucan on glycemic regulation.

• Ronkainen, Justiina; Nedelec, Rozenn; Atehortua, Angelica; Balkhiyarova, Zhanna; Cascarano, Anna & Dang, Vien Ngoc [Show all 73 contributors for this article] (2022). LongITools: Dynamic longitudinal exposome trajectories in cardiovascular and metabolic noncommunicable diseases. Environmental Epidemiology. 6(1). doi: 10.1097/EE9.0000000000000184. Full text in Research Archive Show summary

  The current epidemics of cardiovascular and metabolic noncommunicable diseases have emerged alongside dramatic modifications in lifestyle and living environments. These correspond to changes in our “modern” postwar societies globally characterized by rural-to-urban migration, modernization of agricultural practices, and transportation, climate change, and aging. Evidence suggests that these changes are related to each other, although the social and biological mechanisms as well as their interactions have yet to be uncovered. LongITools, as one of the 9 projects included in the European Human Exposome Network, will tackle this environmental health equation linking multidimensional environmental exposures to the occurrence of cardiovascular and metabolic noncommunicable diseases.

• Brunvoll, Sonja Hjellegjerde; Nygaard, Anders Benteson; Ellingjord-Dale, Merete; Holland, Petter; Istre, Mette Stausland & Kalleberg, Karl Trygve [Show all 15 contributors for this article] (2022). Prevention of covid-19 and other acute respiratory infections with cod liver oil supplementation, a low dose vitamin D supplement: quadruple blinded, randomised placebo controlled trial. The BMJ. 378. doi: 10.1136/bmj-2022-071245. Full text in Research Archive Show summary

  Objective To determine if daily supplementation with cod liver oil, a low dose vitamin D supplement, in winter, prevents SARS-CoV-2 infection, serious covid-19, or other acute respiratory infections in adults in Norway. Design Quadruple blinded, randomised placebo controlled trial. Setting Norway, 10 November 2020 to 2 June 2021. Participants 34601 adults (aged 18-75 years), not taking daily vitamin D supplements. Intervention 5 mL/day of cod liver oil (10 µg of vitamin D, n=17278) or placebo (n=17323) for up to six months. Main outcome measures Four co-primary endpoints were predefined: the first was a positive SARS-CoV-2 test result determined by reverse transcriptase-quantitative polymerase chain reaction and the second was serious covid-19, defined as self-reported dyspnoea, admission to hospital, or death. Other acute respiratory infections were indicated by the third and fourth co-primary endpoints: a negative SARS-CoV-2 test result and self-reported symptoms. Side effects related to the supplementation were self-reported. The fallback method was used to handle multiple comparisons. Results Supplementation with cod liver oil was not associated with a reduced risk of any of the co-primary endpoints. Participants took the supplement (cod liver oil or placebo) for a median of 164 days, and 227 (1.31%) participants in the cod liver oil group and 228 (1.32%) participants in the placebo group had a positive SARS-CoV-2 test result (relative risk 1.00, multiple comparison adjusted confidence interval 0.82 to 1.22). Serious covid-19 was identified in 121 (0.70%) participants in the cod liver oil group and in 101 (0.58%) participants in the placebo group (1.20, 0.87 to 1.65). 8546 (49.46%) and 8565 (49.44%) participants in the cod liver oil and placebo groups, respectively, had ≥1 negative SARS-CoV-2 test results (1.00, 0.97 to 1.04). 3964 (22.94%) and 3834 (22.13%) participants in the cod liver oil and placebo groups, respectively, reported ≥1 acute respiratory infections (1.04, 0.97 to 1.11). Only low grade side effects were reported in the cod liver oil and placebo groups. Co nclusion Supplementation with cod liver oil in the winter did not reduce the incidence of SARS-CoV-2 infection, serious covid-19, or other acute respiratory infections compared with placebo. Trial registration ClinicalTrials.gov NCT04609423.

• Hustad, Kristin Solheim; Ottestad, Inger Olaug; Hjorth, Marit; Dalen, Knut Tomas; Sæther, Thomas & Sheikh, Navida Akhter [Show all 9 contributors for this article] (2021). No effect of salmon fish protein on 2-h glucose in adults with increased risk of type 2 diabetes: a randomised controlled trial. British Journal of Nutrition. ISSN 0007-1145. 126(9), p. 1304–1313. doi: 10.1017/S0007114521000040. Full text in Research Archive Show summary

  Abstract The association between fish consumption and decreased risk of CVD is well documented. However, studies on health effects of fish consumption suggest that other components than n -3 PUFA have beneficial cardiometabolic effects, including effects on glucose metabolism. The aim of the present study was to investigate effects of salmon fish protein on cardiometabolic risk markers in a double-blind, randomised controlled parallel trial. We hypothesised that daily intake of a salmon fish protein supplement for 8 weeks would improve glucose tolerance in persons with increased risk of type 2 diabetes mellitus (T2DM). Our primary outcome measure was serum glucose (s-glucose) 2 h after a standardised oral glucose tolerance test. In total, eighty-eight adults with elevated s-glucose levels were randomised to 7·5 g of salmon fish protein/d or placebo, and seventy-four participants were included in the analysis. We found no significant effect of salmon fish protein supplementation on our primary outcome or other markers related to glucose tolerance, serum lipids, weight or blood pressure compared with placebo. The present study does not support the hypothesis that daily intake of a salmon fish protein supplement for 8 weeks improves glucose tolerance in persons with increased risk of T2DM.

• Nordengen, Anne Lene; Øyri, Linn Kristin Lie; Ulven, Stine Marie; Raastad, Truls; Holven, Kirsten Bjørklund & Ottestad, Inger Olaug (2021). Comparison of methods to identify individuals with obesity at increased risk of functional impairment among a population of home-dwelling older adults. British Journal of Nutrition. ISSN 0007-1145. doi: 10.1017/S0007114521004128. Full text in Research Archive Show summary

  Obesity is associated with increased muscle mass and muscle strength. Methods taking into account the total body mass to reveal obese older individuals at increased risk of functional impairment are needed. Therefore, we aimed to detect methods to identify obese older adults at increased risk of functional impairment. Home-dwelling older adults (n 417, ≥ 70 years of age) were included in this cross-sectional study. Sex-specific cut-off points for two obesity phenotypes (waist circumference (WC) and body fat mass (FM %)) were used to divide women and men into obese and non-obese groups, and within-sex comparisons were performed. Obese women and men, classified by both phenotypes, had similar absolute handgrip strength (HGS) but lower relative HGS (HGS/total body mass) (P < 0·001) than non-obese women and men, respectively. Women with increased WC and FM %, and men with increased WC had higher appendicular skeletal muscle mass (P < 0·001), lower muscle quality (HGS/upper appendicular muscle mass) (P < 0·001), and spent longer time on the stair climb test and the repeated sit-to-stand test (P < 0·05) than non-obese women and men, respectively. Absolute muscle strength was not able to discriminate between obese and non-obese older adults. However, relative muscle strength in particular, but also muscle quality and physical performance tests, where the total body mass was taken into account or served as an extra load, identified obese older adults at increased risk of functional impairment. Prospective studies are needed to determine clinically relevant cut-off points for relative HGS in particular.

• Rodriguez-Borjabad, Celia; Narverud, Ingunn; Christensen, Jacob J.; Ulven, Stine Marie; Malo, Ana Irene & Ibarretxe, Daiana [Show all 13 contributors for this article] (2021). Dietary intake and lipid levels in Norwegian and Spanish children with familial hypercholesterolemia. NMCD. Nutrition Metabolism and Cardiovascular Diseases. ISSN 0939-4753. 31(4), p. 1299–1307. doi: 10.1016/j.numecd.2020.12.002. Full text in Research Archive
• Larsen, Sunniva Veen; Holven, Kirsten B.; Christensen, Jacob J.; Flatberg, Arnar; Rundblad, Amanda & Leder, Lena [Show all 13 contributors for this article] (2021). Replacing Saturated Fat with Polyunsaturated Fat Modulates Peripheral Blood Mononuclear Cell Gene Expression and Pathways Related to Cardiovascular Disease Risk Using a Whole Transcriptome Approach. Molecular Nutrition & Food Research. ISSN 1613-4125. 65(24). doi: 10.1002/mnfr.202100633. Full text in Research Archive Show summary

  The aim of this study is to explore the molecular mechanisms underlying the effect of replacing dietary saturated fat (SFA) with polyunsaturated fat (PUFA) on cardiovascular disease (CVD) risk using a whole transcriptome approach. Methods and Results Healthy subjects with moderate hypercholesterolemia (n = 115) are randomly assigned to a control diet (C-diet) group or an experimental diet (Ex-diet) group receiving comparable food items with different fatty acid composition for 8 weeks. RNA isolated from peripheral blood mononuclear cells (PBMCs) at baseline and after 8 weeks of intervention is analyzed by microarray technology (n = 95). By use of a linear regression model (n = 92), 14 gene transcripts are differentially altered in the Ex-diet group compared to the C-diet group. These include transcripts related to vascular smooth muscle cell proliferation, low-density lipoprotein receptor folding, and regulation of blood pressure. Furthermore, pathways mainly related to immune response and inflammation, signal transduction, development, and cytoskeleton remodeling, gene expression and protein function, are differentially enriched between the groups. Conclusion Replacing dietary SFA with PUFA for 8 weeks modulates PBMC gene expression and pathways related to CVD risk in healthy subjects with moderate hypercholesterolemia.

• Øyri, Linn Kristin Lie; Bogsrud, Martin Prøven; Christensen, Jacob J.; Ulven, Stine Marie; Brantsæter, Anne Lise & Retterstøl, Kjetil [Show all 13 contributors for this article] (2021). Novel associations between parental and newborn cord blood metabolic profiles in the Norwegian Mother, Father and Child Cohort Study. BMC Medicine. 19(19). doi: 10.1186/s12916-021-01959-w. Full text in Research Archive Show summary

  Background:More than one third of Norwegian women and men between 20 and 40 years of age have elevated cholesterol concentration. Parental metabolic health around conception or during pregnancy may affect the offspring’s cardiovascular disease risk. Lipids are important for fetal development, but the determinants of cord blood lipids have scarcely been studied. We therefore aimed to describe the associations between maternal andpaternal peri-pregnancy lipid and metabolic profile and newborn cord blood lipid and metabolic profile. Methods:This study is based on 710 mother–father–newborn trios from the Norwegian Mother, Father and ChildCohort Study (MoBa) and uses data from the Medical Birth Registry of Norway (MBRN). The sample included in thisstudy consisted of parents with and without self-reported hypercholesterolemia the last 6 months before pregnancy and their partners and newborns. Sixty-four cord blood metabolites detected by nuclear magnetic resonance spectroscopy were analyzed by linear mixed model analyses. The false discovery rate procedure wasused to correct for multiple testing. Results:Among mothers with hypercholesterolemia, maternal and newborn plasma high-density lipoproteincholesterol, apolipoprotein A1, linoleic acid, docosahexaenoic acid, alanine, glutamine, isoleucine, leucine, valine,creatinine, and particle concentration of medium high-density lipoprotein were significantly positively associated(0.001≤q≤0.09). Among mothers without hypercholesterolemia, maternal and newborn linoleic acid, valine,tyrosine, citrate, creatinine, high-density lipoprotein size, and particle concentration of small high-density lipoproteinwere significantly positively associated (0.02≤q≤0.08). Among fathers with hypercholesterolemia, paternal andnewborn ratio of apolipoprotein B to apolipoprotein A1 were significantly positively associated (q= 0.04). Amongfathers without hypercholesterolemia, no significant associations were found between paternal and newbornmetabolites. Sex differences were found for many cord blood lipids. Conclusions:Maternal and paternal metabolites and newborn sex were associated with several cord bloodmetabolites. This may potentially affect the offspring’s long-term cardiovascular disease risk.Keywords:MoBa, the Norwegian Mother, Father and Child Cohort Study, MBRN, Medical Birth Registry of Norway,Cholesterol, Metabolic profiling, Cord blood, Sex differences

• Christensen, Jacob J.; Narverud, Ingunn; Ruuth, Maija; Heier, Martin; Jauhiainen, Matti & Ulven, Stine Marie [Show all 14 contributors for this article] (2021). Children with familial hypercholesterolemia display changes in LDL and HDL function: A cross-sectional study. Journal of Internal Medicine. ISSN 0954-6820. 290(5), p. 1083–1097. doi: 10.1111/joim.13383. Full text in Research Archive
• Milić, Mirta; Ceppi, Marcello; Bruzzone, Marco; Azqueta, Amaya; Brunborg, Gunnar & Godschalk, Roger [Show all 90 contributors for this article] (2021). The hCOMET project: International database comparison of results with the comet assay in human biomonitoring. Baseline frequency of DNA damage and effect of main confounders. Mutation research. Reviews in mutation research. ISSN 1383-5742. 787. doi: 10.1016/j.mrrev.2021.108371. Full text in Research Archive Show summary

  The alkaline comet assay, or single cell gel electrophoresis, is one of the most popular methods for assessing DNA damage in human population. One of the open issues concerning this assay is the identification of those factors that can explain the large inter-individual and inter-laboratory variation. International collaborative initiatives such as the hCOMET project - a COST Action launched in 2016 - represent a valuable tool to meet this challenge. The aims of hCOMET were to establish reference values for the level of DNA damage in humans, to investigate the effect of host factors, lifestyle and exposure to genotoxic agents, and to compare different sources of assay variability. A database of 19,320 subjects was generated, pooling data from 105 studies run by 44 laboratories in 26 countries between 1999 and 2019. A mixed random effect log-linear model, in parallel with a classic meta-analysis, was applied to take into account the extensive heterogeneity of data, due to descriptor, specimen and protocol variability. As a result of this analysis interquartile intervals of DNA strand breaks (which includes alkali-labile sites) were reported for tail intensity, tail length, and tail moment (comet assay descriptors). A small variation by age was reported in some datasets, suggesting higher DNA damage in oldest age-classes, while no effect could be shown for sex or smoking habit, although the lack of data on heavy smokers has still to be considered. Finally, highly significant differences in DNA damage were found for most exposures investigated in specific studies. In conclusion, these data, which confirm that DNA damage measured by the comet assay is an excellent biomarker of exposure in several conditions, may contribute to improving the quality of study design and to the standardization of results of the comet assay in human populations.

• Nelson, Josefine; Ulven, Stine Marie; Gjertsson, Inger; Sjöblom, Helen; Lindqvist, Helen M. & Bärebring, Linnea (2020). Do interventions with diet or dietary supplements reduce the disease activity score in rheumatoid arthritis? A systematic review of randomized controlled trials. Nutrients. 12:2991(10), p. 1–23. doi: 10.3390/nu12102991. Full text in Research Archive Show summary

  The aim was to compile the evidence from Randomized Controlled Trials (RCTs) of diet or dietary supplements used to reduce disease activity in adults with Rheumatoid Arthritis (RA). Searches were performed in the databases PubMed, Scopus and Cochrane. Only RCT studies of diets, foods or dietary supplements, looking at effects on the Disease Activity Score in 28 joints (DAS28) among adults with RA, published in peer-reviewed journals, were included. A total of 27 articles were included—three of whole diets (Mediterranean diet, raw food and anti-inflammatory diet), five of food items, five of n-3 fatty acids, five of single micronutrient supplements, four of single antioxidant supplements and five of pre-, pro- or synbiotics. Studies that showed moderate strength evidence for positive effects on disease activity in RA included interventions with a Mediterranean diet, spices (ginger powder, cinnamon powder, saffron), antioxidants (quercetin and ubiquinone), and probiotics containing Lactobacillus Casei. Other diets or supplements had either no effects or low to very low strength of evidence. In conclusion, RCT studies on diet or dietary supplements are limited in patients with RA, but based on the results in this review there is evidence that some interventions might have positive effects on DAS28.

• Christensen, Jacob Juel; Ulven, Stine Marie; Thoresen, Magne; Westerman, Kenneth; Holven, Kirsten Bjørklund & Andersen, Lene Frost (2020). Associations between dietary patterns and gene expression pattern in peripheral blood mononuclear cells: a cross-sectional study (preprint). BioRxiv. ISSN 0362-4331. doi: 10.1101/2020.01.25.20018465. Full text in Research Archive
• Gaundal, Line; Myhrstad, Mari; Leder, Lena; Byfuglien, Marte Gjeitung; Gjøvaag, Terje & Rud, Ida [Show all 10 contributors for this article] (2020). Beneficial effect on serum cholesterol levels, but not glycaemic regulation, after replacing SFA with PUFA for three days: a randomised crossover trial. British Journal of Nutrition. ISSN 0007-1145. p. 1–11. doi: 10.1017/S0007114520003402. Full text in Research Archive Show summary

  Replacing intake of SFA with PUFA reduces serum cholesterol levels and CVD risk. The effect on glycaemic regulation is, however, less clear. The main objective of the present study was to investigate the short-term effect of replacing dietary SFA with PUFA on glycaemic regulation. Seventeen healthy, normal-weight participants completed a 25-d double-blind, randomised and controlled two-period crossover study. Participants were allocated to either interventions with PUFA products or SFA products (control) in a random order for three consecutive days, separated by a 1·5-week washout period between the intervention periods. Glucose, insulin and TAG were measured before and after an oral glucose tolerance test. In addition, fasting total cholesterol, NEFA and plasma total fatty acid profile were measured before and after the 3-d interventions. Fasting and postprandial glucose, insulin, and TAG levels and fasting levels of NEFA and plasma fatty acid profile did not differ between the groups. However, replacing dietary SFA with PUFA significantly reduced total cholesterol levels by 8 % after 3 d (P = 0·002). Replacing dietary SFA with PUFA for only 3 d has beneficial cardio-metabolic effects by reducing cholesterol levels in healthy individuals.

• Christensen, Jacob J.; Narverud, Ingunn; Ruuth, Maija; Heier, Martin; Ulven, Stine Marie & Bogsrud, Martin Prøven [Show all 12 contributors for this article] (2020). Children with familial hypercholesterolemia display changes in LDL and HDL function: a cross-sectional study. medRxiv. doi: 10.1101/2020.11.11.20214247. Full text in Research Archive Show summary

  Background The functional status of lipoprotein particles contributes to atherogenesis. The tendency of plasma LDL particles to aggregate and the ability of HDL particles to induce and mediate reverse cholesterol transport associate with high and low risk for cardiovascular disease in adult patients, respectively. However, it is unknown whether children with familial hypercholesterolemia (FH) display lipoprotein function alterations. Hypothesis We hypothesized that FH children had disrupted lipoprotein function. Methods We analyzed LDL aggregation susceptibility and HDL-apoA-I exchange to apoA-I ratio (HAE/apoA-I ratio), and activity of four proteins that regulate lipoprotein metabolism (CETP, LCAT, PLTP and PON1) in plasma samples derived from children with FH (n = 47) and from healthy children (n = 56). Potential biological mechanisms behind any variation in lipoprotein functionalities were explored using an NMR-based metabolomics profiling approach. Results LDL aggregation was higher and HAE/apoA-I ratio was lower in FH children than in healthy children. LDL aggregation associated positively with LDL-C and negatively with triglycerides, and HAE/apoA-I ratio associated negatively with LDL-C. Generally, the metabolomic profile for LDL aggregation was a mirror image of that for HAE/apoA-I ratio. Conclusions FH children displayed increased atherogenicity of LDL and disrupted HDL function. These newly observed functional alterations in LDL and HDL may increase the risk for atherosclerotic cardiovascular disease in FH children.

• Christensen, Jacob Juel; Ulven, Stine Marie; Thoresen, Magne; Westerman, Kenneth; Holven, Kirsten Bjørklund & Andersen, Lene Frost (2020). Associations between dietary patterns and gene expression pattern in peripheral blood mononuclear cells: A cross-sectional study. NMCD. Nutrition Metabolism and Cardiovascular Diseases. ISSN 0939-4753. 30(11), p. 2111–2122. doi: 10.1016/j.numecd.2020.06.018. Full text in Research Archive Show summary

  Background and aims Diet may alter gene expression in immune cells involved in atherosclerotic cardiovascular disease susceptibility. However, we still lack a robust understanding of the association between diet and immune cell-related gene expression in humans. Therefore, we examined associations between dietary patterns (DPs) and gene expression profiles in peripheral blood mononuclear cells (PBMCs) in a population of healthy, Norwegian adults (n = 130 women and 105 men). Methods and results We used factor analysis to define a posteriori DPs from food frequency questionnaire-based dietary assessment data. In addition, we derived interpretable features from microarray-based gene expression data (13 967 transcripts) using two algorithms: CIBERSORT for estimation of cell subtype proportions, and weighted gene co-expression network analysis (WGCNA) for cluster discovery. Finally, we associated DPs with either CIBERSORT-predicted PBMC leukocyte distribution or WGCNA gene clusters using linear regression models. We detected three DPs that broadly reflected Western, Vegetarian, and Low carbohydrate diets. CIBERSORT-predicted percentage of monocytes associated negatively with the Vegetarian DP. For women, the Vegetarian DP associated with a large gene cluster consisting of 600 genes mainly involved in regulation of DNA transcription, whereas for men, the Western DP inversely associated with a smaller cluster of 36 genes mainly involved in regulation of metabolic and inflammatory processes. A subsequent protein–protein interaction network analysis suggested that genes within these clusters might physically interact in biological networks. Conclusions Although the present findings are exploratory, our analysis pipeline serves as a useful framework for studying the association between diet and gene expression.

• Svendsen, Karianne; Olsen, Thomas; Rusvik, Tove Caroline Nordstrand; Ulven, Stine Marie; Holven, Kirsten Bjørklund & Retterstøl, Kjetil [Show all 7 contributors for this article] (2020). Fatty acid profile and estimated desaturase activities in whole blood are associated with metabolic health. Lipids in Health and Disease. 19. doi: 10.1186/s12944-020-01282-y. Full text in Research Archive Show summary

  Background: The aim was to investigate if fatty acid profile and estimated desaturase activities; stearoyl CoAdesaturase (SCD), delta-5-desaturase and delta-6-desaturase (D5D; D6D), differ between individuals with metabolically healthy (MH) and unhealthy (MU) phenotypes. We also explored these associations according to BMI categories. Methods: Men and women at moderately elevated risk of cardiovascular disease were included in this crosssectional study (n=321). If subjects met ≥4 out of 5 criteria (elevated triglycerides, total and LDL-cholesterol, HbA1c and low HDL-cholesterol), they were classified as MU (n=52). If levels were within reference ranges for ≥3 of the same criteria, subjects were classified as MH (n=150). Utilizing the entire population, a score ranging from 0 to 5 denoting the number of MU criteria met was computed. Estimated desaturase activities were calculated as productto-precursor ratio of fatty acids in whole blood (SCD16 [16:1n7/16:0], SCD18 [18:1n9/18:0], D5D [18:3n6/18:2n6], D6D [20:4n6/20:3n6]). Results: Individuals with MH had lower estimated SCD16 and SCD18 activities, whereas estimated D6D activity was higher compared to MU. Similar, SCD16 and SCD18 increased, whereas D6D decreased with increasing criteria of MU. Trends were similar across BMI categories. Conclusions: This study supports the notion of estimated desaturase activities as possible novel biomarkers of metabolic health irrespectively of BMI.

• Rundblad, Amanda; Holven, Kirsten Bjørklund; Øyri, Linn Kristin Lie; Hansson, Patrik; Ivan, Ingvild Hansen & Gjevestad, Gyrd Omholt [Show all 8 contributors for this article] (2020). Intake of fermented dairy products induces a less pro-inflammatory postprandial peripheral blood mononuclear cell gene expression response than non-fermented dairy products: A randomized controlled cross-over trial. Molecular Nutrition & Food Research. ISSN 1613-4125. 64(21), p. 1–11. doi: 10.1002/mnfr.202000319. Full text in Research Archive Show summary

  Scope: It is aimed to investigate how intake of high-fat meals composed of different dairy products with a similar fat content affects postprandial peripheral blood mononuclear cell (PBMC) expression of inflammation-related genes, as well as circulating inflammatory markers and metabolites.<p>Methods and results: Healthy subjects (n = 47) consume four different high-fat meals composed of either butter, cheese, whipped cream, or sourcream in a randomized controlled cross-over study. Fasting and postprandial PBMC gene expression, plasma metabolites, and circulating inflammatory markers are measured. Using a linear mixed model, it is found that expression of genes related to lymphocyte activation, cytokine signaling, chemokine signaling, and cell adhesion is differentially altered between the four meals. In general, intake of the fermented products cheese and sour cream reduces,while intake of the non-fermented products butter and whipped cream increases, expression of these genes. Plasma amino acid concentrations increase after intake of cheese compared to the other meals, and the aminoacid changes correlate with several of the differentially altered genes.<p>Conclusion: Intake of fermented dairy products, especially cheese, induces a less inflammatory postprandial PBMC gene expression response than non-fermented dairy products. These findings may partly explain inconsistent findings in studies on health effects of dairy products.

• Henjum, Sigrun; Brantsæter, Anne Lise; Holvik, Kristin; Lillegaard, Inger Therese Laugsand; Mangschou, Bente & Parr, Christine Louise [Show all 14 contributors for this article] (2020). Benefit and risk assessment of iodization of household salt and salt used in bread and bakery products. Scientific opinion of the Panel on Nutrition, Dietetic Products, Novel Food and Allergy of the Norwegian Scientific Committee for Food and Environment. VKM Report. 2020(5), p. 1–312. Full text in Research Archive
• Telle-Hansen, Vibeke; Christensen, Jacob J.; Formo, Gulla Aase; Holven, Kirsten Bjørklund & Ulven, Stine Marie (2020). A comprehensive metabolic profiling of the metabolically healthy obesity phenotype. Lipids in Health and Disease. 19, p. 1–12. doi: 10.1186/s12944-020-01273-z. Full text in Research Archive Show summary

  Background: The ever-increasing prevalence of obesity constitutes a major health problem worldwide. A subgroup of obese individuals has been described as “metabolically healthy obese” (MHO). In contrast to metabolically unhealthy obese (MUO), the MHO phenotype has a favorable risk profile. Despite this, the MHO phenotype is still sub-optimally characterized with respect to a comprehensive risk assessment. Our aim was to increase the understanding of metabolic alterations associated with healthy and unhealthy obesity. Methods: In this cross-sectional study, men and women (18–70years) with obesity (body mass index (BMI)≥30kg/ m2) or normal weight (NW) (BMI≤25kg/m2) were classified with MHO (n=9), MUO (n=10) or NW (n=11) according to weight, lipid profile and glycemic regulation. We characterized individuals by comprehensive metabolic profiling using a commercial available high-throughput proton NMR metabolomics platform. Plasma fatty acid profile, including short chain fatty acids, was measured using gas chromatography. Results: The concentrations of very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL) and low density lipoprotein (LDL) subclasses were overall significantly higher, and high density lipoprotein (HDL) subclasses lower in MUO compared with MHO. VLDL and IDL subclasses were significantly lower and HDL subclasses were higher in NW compared with MHO. The concentration of isoleucine, leucine and valine was significantly higher in MUO compared with MHO, and the concentration phenylalanine was lower in NW subjects compared with MHO. The fatty acid profile in MHO was overall more favorable compared with MUO. Conclusions: Comprehensive metabolic profiling supports that MHO subjects have intermediate-stage cardiovascular disease risk marker profile compared with NW and MUO subjects. Clinical trial registration number: NCT01034436, Fatty acid quality and overweight (FO-study).

• Ulven, Stine Marie & Holven, Kirsten Bjørklund (2020). Metabolomic and gene expression analysis to study the effects of dietary saturated and polyunsaturated fats. Current Opinion in Lipidology. ISSN 0957-9672. 31(1), p. 15–19. doi: 10.1097/MOL.0000000000000651. Full text in Research Archive Show summary

  Purpose of review Give an update on recent dietary intervention studies that have used peripheral blood mononuclear cell gene expression analysis and/or metabolic profiling to understand how intake of polyunsaturated and saturated fat affects and biological pathways linked to cardiovascular disease. Recent findings Several studies showed that intake of fish oil and vegetable oil, high in omega-3 fatty acids, reduced expression level of genes involved in inflammation. One intervention study showed that gene transcripts encoding genes involved inflammation and lipid metabolism increased after intake of polyunsaturated fat (mainly omega-6 fatty acids) compared to saturated fat. Additionally, using targeted metabolomics, the concentrations of atherogenic lipoprotein particles and several metabolites including palmitoylcarnitine, myristoylcarnitine, and kynurenine were reduced after intake of polyunsaturated fat compared to saturated fat, whereas acetate and acetoacetate were increased. The use of targeted metabolomics showed that overfeeding with polyunsaturated fat reduced the serum concentration of ceramides, dihydroceramides, glucosylceramides, and lactosylceramides, whereas overfeeding with saturated fat increased serum concentration of these metabolites. Summary The use of gene expression profiling and metabolomics are promising tools to identify possible new biomarkers linking fat quality to cardiovascular disease risk.

• Fan, Qiong; Nørgaard, Rikke Christine; Grytten, Ivar; Ness, Cecilie; Lucas, Christin & Vekterud, Kristin [Show all 15 contributors for this article] (2020). LXRα Regulates ChREBPα Transactivity in a Target Gene-Specific Manner through an Agonist-Modulated LBD-LID Interaction. Cells. 9(5), p. 1–26. doi: 10.3390/cells9051214. Full text in Research Archive Show summary

  The cholesterol-sensing nuclear receptor liver X receptor (LXR) and the glucose-sensing transcription factor carbohydrate responsive element-binding protein (ChREBP) are central players in regulating glucose and lipid metabolism in the liver. More knowledge of their mechanistic interplay is needed to understand their role in pathological conditions like fatty liver disease and insulin resistance. In the current study, LXR and ChREBP co-occupancy was examined by analyzing ChIP-seq datasets from mice livers. LXR and ChREBP interaction was determined by Co-immunoprecipitation (CoIP) and their transactivity was assessed by real-time quantitative polymerase chain reaction (qPCR) of target genes and gene reporter assays. Chromatin binding capacity was determined by ChIP-qPCR assays. Our data show that LXRα and ChREBPα interact physically and show a high co-occupancy at regulatory regions in the mouse genome. LXRα co-activates ChREBPα and regulates ChREBP-specific target genes in vitro and in vivo. This co-activation is dependent on functional recognition elements for ChREBP but not for LXR, indicating that ChREBPα recruits LXRα to chromatin in trans. The two factors interact via their key activation domains; the low glucose inhibitory domain (LID) of ChREBPα and the ligand-binding domain (LBD) of LXRα. While unliganded LXRα co-activates ChREBPα, ligand-bound LXRα surprisingly represses ChREBPα activity on ChREBP-specific target genes. Mechanistically, this is due to a destabilized LXRα:ChREBPα interaction, leading to reduced ChREBP-binding to chromatin and restricted activation of glycolytic and lipogenic target genes. This ligand-driven molecular switch highlights an unappreciated role of LXRα in responding to nutritional cues that was overlooked due to LXR lipogenesis-promoting function.

• Hustad, Solheim Kristin; Rundblad, Amanda; Ottestad, Inger; Christensen, Jacob J.; Holven, Kirsten Bjørklund & Ulven, Stine Marie (2020). Comprehensive lipid and metabolite profiling in healthy adults with low and high consumption of fatty fish: A cross-sectional study. British Journal of Nutrition. ISSN 0007-1145. p. 1–9. doi: 10.1017/S0007114520002305. Full text in Research Archive Show summary

  Abstract Fish consumption is associated with reduced risk of CVD, which may be partly mediated by alterations in plasma lipids, such as HDL-cholesterol. However, comprehensive analyses of associations between fatty fish consumption and lipoprotein subclass profile are limited and show inconsistent results. Therefore, the aim of the present exploratory study was to investigate the association between fatty fish consumption and lipoprotein subclass particle concentrations and composition, with an emphasis on HDL. We performed a comprehensive plasma metabolite profiling in 517 healthy adults, using a targeted high-throughput NMR spectroscopy platform. The participants were divided into tertiles based on consumption of fatty fish, reported through a validated FFQ. We compared the concentration of metabolites between the participants in the lowest and highest tertiles of fatty fish consumption. We show that high consumers of fatty fish (&gt;223 g/week, median intake 294 g/week) had higher particle concentrations and content of total lipids, free cholesterol and phospholipids in large and extra-large HDL particles and higher content of total cholesterol, cholesteryl esters and TAG in large HDL particles than low consumers (&lt;107 g/week, median intake 58 g/week). Using fatty fish consumption as a continuous variable, we found that fatty fish consumption was associated with lower levels of the inflammation marker glycoprotein acetyls. In conclusion, high consumers of fatty fish seem to have a more favourable HDL-cholesterol-related lipoprotein profile and anti-inflammatory phenotype than low consumers of fatty fish. Thus, these data support the current Norwegian dietary recommendations for fish consumption regarding CVD risk.

• Christensen, Jacob J.; Bakke, Siril Skaret; Ulven, Stine Marie; Retterstøl, Kjetil; Henriksen, Tore & Bollerslev, Jens [Show all 10 contributors for this article] (2019). Serum Omega-6 Fatty Acids and Immunology-Related Gene Expression in Peripheral Blood Mononuclear Cells: A Cross-Sectional Analysis in Healthy Children. Molecular Nutrition & Food Research. ISSN 1613-4125. 63(7). doi: 10.1002/mnfr.201800990. Full text in Research Archive Show summary

  Scope Some studies suggest that a high dietary intake of omega‐6 fatty acids is pro‐inflammatory. However, whether omega‐6 fatty acids actually cause pathogenic inflammation in humans is debated. Therefore, the associations between expression of immunology‐related genes in peripheral blood mononuclear cells (PBMCs) and serum total omega‐6 PUFA status are investigated. Methods and results Serum fatty acid profile and expression of 460 immunology‐related genes in PBMCs from 58 healthy children (6–13 years) is measured, and examined the expression differences between children with high or low total omega‐6 PUFA status (upper vs lower tertile). Taken together, both univariate analyses and integrated omics analyses support that while high omega‐6 PUFA level associated with higher expressing of genes related to innate immune responses, it also associated with lower expression of several genes related to adaptive immune responses. Conclusion Omega‐6 PUFA status associated both positively and negatively with expression of specific immunology‐related genes in PBMCs in healthy children. The results may suggest a nuanced role for omega‐6 fatty acids in the interphase of lipids and inflammation, and warrants further examination in gene‐environment studies and randomized controlled trials.

• Hansson, Patrik; Holven, Kirsten Bjørklund; Øyri, Linn Kristin Lie; Brekke, Hilde Kristin; Gjevestad, Gyrd Omholt & Thoresen, Magne [Show all 7 contributors for this article] (2019). Sex differences in postprandial responses to different dairy products on lipoprotein subclasses: A randomised controlled cross-over trial. British Journal of Nutrition. ISSN 0007-1145. 122(7), p. 780–789. doi: 10.1017/S0007114519001429. Full text in Research Archive Show summary

  Men have earlier first-time event of CHD and higher postprandial TAG response compared with women. The aim of this exploratory sub-study was to investigate if intake of meals with the same amount of fat from different dairy products affects postprandial lipoprotein subclasses differently in healthy women and men. A total of thirty-three women and fourteen men were recruited to a randomised controlled cross-over study with four dairy meals consisting of butter, cheese, whipped cream or sour cream, corresponding to 45 g of fat (approximately 60 energy percent). Blood samples were taken at 0, 2, 4 and 6 h postprandially. Lipoprotein subclasses were measured using NMR and analysed using a linear mixed model. Sex had a significant impact on the response in M-VLDL (P=0·04), S-LDL (P=0·05), XL-HDL (P=0·009) and L-HDL (P=0·001) particle concentration (P), with women having an overall smaller increase in M-VLDL-P, a larger decrease in S-LDL-P and a larger increase in XL- and L-HDL-P compared with men, independent of meal. Men showed a decrease in XS-VLDL-P compared with women after intake of sour cream (P&amp;lt;0·01). In men only, XS-VLDL-P decreased after intake of sour cream compared with all other meals (v. butter: P=0·001; v. cheese: P=0·04; v. whipped cream: P=0·006). Meals with the same amount of fat from different dairy products induce different postprandial effects on lipoprotein subclass concentrations in men and women.

• Ulven, Stine Marie; Christensen, Jacob J.; Nygård, Ottar; Svardal, Asbjørn M.; Leder, Lena & Ottestad, Inger [Show all 14 contributors for this article] (2019). Using metabolic profiling and gene expression analyses to explore molecular effects of replacing saturated fat with polyunsaturated fat-a randomized controlled dietary intervention study. American Journal of Clinical Nutrition. ISSN 0002-9165. 109(5), p. 1239–1250. doi: 10.1093/ajcn/nqy356. Full text in Research Archive Show summary

  Background: Replacing dietary saturated fatty acids (SFAs) with polyunsaturated fatty acids (PUFA) reduces the plasma low-density lipoprotein (LDL) cholesterol and subsequently the risk of cardiovascular disease. However, beyond changes in LDL cholesterol, we lack a complete understanding of the physiologic alterations that occur when improving dietary fat quality. Objectives: The aim of this study was to gain knowledge of metabolic alterations paralleling improvements in the fat quality of the diet. Methods: We recently conducted an 8-wk, double-blind, randomized controlled trial replacing SFAs with PUFAs in healthy subjects with moderate hypercholesterolemia (n = 99). In the present substudy, we performed comprehensive metabolic profiling with multiple platforms (both nuclear magnetic resonance- and mass spectrometry-based technology) (n = 99), and analyzed peripheral blood mononuclear cell gene expression (n = 95) by quantitative real-time polymerase chain reaction. Results: A large number of lipoprotein subclasses, myristoylcarnitine and palmitoylcarnitine, and kynurenine were reduced when SFAs were replaced with PUFAs. In contrast, bile acids, proprotein convertase subtilisin/kexin type 9, acetate, and acetoacetate were increased by the intervention. Some amino acids were also altered by the intervention. The mRNA levels of LXRA and LDLR were increased, in addition to several liver X receptor α target genes and genes involved in inflammation, whereas the mRNA levels of UCP2 and PPARD were decreased in peripheral blood mononuclear cells after replacing SFAs with PUFAs. Partial least squares-discriminant analysis showed that the 30 most important variables that contributed to class separation spanned all classes of biomarkers, and was in accordance with the univariate analysis. Conclusions: Applying metabolomics in randomized controlled dietary intervention trials has the potential to extend our knowledge of the biological and molecular effects of dietary fat quality. This study was registered at clinicaltrials.gov as NCT 01679496.

• Narverud, Ingunn; Christensen, Jacob J.; Bakke, Siril Skaret; Ulven, Stine Marie; Rundblad, Amanda & Aukrust, Pål [Show all 12 contributors for this article] (2019). Profiling of immune-related gene expression in children with familial hypercholesterolaemia. Journal of Internal Medicine. ISSN 0954-6820. p. 1–12. doi: 10.1111/joim.13001. Full text in Research Archive Show summary

  Background Innate and adaptive immune responses are pivotal in atherosclerosis, but their association with early‐stage atherosclerosis in humans is incompletely understood. In this regard, untreated children with familial hypercholesterolaemia may serve as a human model to investigate the effect of elevated low‐density lipoprotein (LDL)‐cholesterol. Objectives We aimed to study the immunological and inflammatory pathways involved in early atherosclerosis by examining mRNA molecules in peripheral blood mononuclear cells (PBMCs) from children with FH. Methods We analysed the level of 587 immune‐related mRNA molecules using state‐of‐the‐art Nanostring technology in PBMCs from children with (n = 30) and without (n = 21) FH, and from FH children before and after statin therapy (n = 10). Results 176 genes (30%) were differentially expressed between the FH and healthy children at P < 0.05. Compared to healthy children, the dysregulated pathways in FH children included the following: T cells (18/19); B cells (5/6); tumour necrosis factor super family (TNFSF) (6/8); cell growth, proliferation and differentiation (5/7); interleukins (5/9); toll‐like receptors (2/5); apoptosis (3/7) and antigen presentation (1/7), where the ratio denotes higher expressed genes to total number of genes. Statin therapy reversed expression of thirteen of these mRNAs in FH children. Conclusion FH children display higher PBMC expression of immune‐related genes mapped to several pathways, including T and B cells, and TNFSF than healthy children. Our results suggest that LDL‐C plays an important role in modulating expression of different immune‐related genes, and novel data on the involvement of these pathways in the early atherosclerosis may represent future therapeutic targets for prevention of atherosclerotic progression.

• Rundblad, Amanda; Larsen, Sunniva; Myhrstad, Mari; Ottestad, Inger; Thoresen, Magne & Holven, Kirsten Bjørklund [Show all 7 contributors for this article] (2019). Differences in peripheral blood mononuclear cell gene expression and triglyceride composition in lipoprotein subclasses in plasma triglyceride responders and non-responders to omega-3 supplementation. Genes & Nutrition. ISSN 1555-8932. 14(10), p. 1–13. doi: 10.1186/s12263-019-0633-y. Full text in Research Archive Show summary

  Background:Intake of the marine omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)reduces fasting triglyceride (TG) levels and may thereby lower cardiovascular disease risk. However, there are largeinter-individual differences in the TG-lowering effect of omega-3 supplementation. Genotype differences partly explainthis variation, but gene-environment interactions leading to gene expression differences may also be important. In thisstudy, we aimed to investigate baseline differences and differences in the change in peripheral blood mononuclear cell(PBMC) gene expression and lipoprotein subclass TG levels between TG responders and non-responders to omega-3fatty acid supplementation.Methods:In a previous randomized controlled trial, healthy normotriglyceridemic subjects (n= 35, 71% women)received 1.6 g EPA + DHA/day for 7 weeks. In this exploratory sub-study, we defined TG responders as subjects havinga TG reduction beyond the 20% day-to-day variation and non-responders as having a TG change between−20% and+ 20% after omega-3 supplementation. PBMC gene expression was measured using microarray, and lipoproteinsubclasses were measured using nuclear magnetic resonance spectroscopy.Results:Eight subjects were defined as responders with a median TG reduction of 37%, and 16 subjects were definedas non-responders with a median TG change of 0%. At baseline, responders had higher TG levels in two of four high-density lipoprotein (HDL) subclasses and 909 gene transcripts (p≤0.05) were differentially expressed compared to non-responders. During the intervention, the plasma TG reduction among responders was reflected in TG reductions in fourof six different very low-density lipoprotein subclasses and three of four different HDL subclasses. Compared to non-responders, the expression of 454 transcripts was differentially altered in responders (p≤0.05). Pathway analyses revealed that responders had altered signaling pathways related to development and immune function. In addition,two of the top 10 enriched pathways in responders compared to non-responders were related to lysophosphatidic acid signaling.Conclusion:TG responders and non-responders to omega-3 supplementation have different lipoprotein subclass andPBMC gene expression profiles at baseline and different lipoprotein subclass and PBMC gene expression responses toomega-3 supplementation. These gene expression differences may partially explain the variability in TG response observed after omega-3 supplementation.

• Wedervang-Resell, Kirsten; Friis, Svein; Lonning, Vera Louise Hiorth; Smelror, Runar; Johannessen, Cecilie Haggag & Agartz, Ingrid [Show all 10 contributors for this article] (2019). Lipid alterations in adolescents with early-onset psychosis may be independent of antipsychotic medication. Schizophrenia Research. ISSN 0920-9964. p. 1–7. doi: 10.1016/j.schres.2019.11.039. Full text in Research Archive Show summary

  Background Dyslipidemia and insulin resistance (HOMA-IR) are cardiovascular risk factors prevalent in patients with psychosis. Whether these factors are intrinsic or affected by lifestyle or antipsychotic medication (AP) is unclear. Therefore, we investigated lipid profiles, HOMA-IR, and psychotic phenotypes in patients aged 12–18 years with early-onset psychosis (EOP) with and without AP exposure. Method We measured fasting total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), triglycerides (TG), insulin, and glucose in patients with EOP (n = 39) and healthy controls (HC) (n = 66). Diet information was not available. Negative symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). We used univariate analysis of variance to compare TC/HDL-C ratios and TG and HOMA-IR values, controlling for body mass index (BMI) and AP exposure. We assessed the explained variance of having EOP using multiple regression analysis. Results Patients with and without AP exposure had significantly higher TC/HDL-C (p = 0.003, p = 0.029) and TG values (p < 0.001, p = 0.021) than HC. Significantly increased HOMA-IR scores were found only in AP-exposed patients (p = 0.037). EOP significantly increased the explained variance for TC/HDL-C and TG, but not for HOMA-IR. Patients with a PANSS negative score > 21 had significantly higher levels of TG than those with low scores (p = 0.032). Conclusion Our results suggest that lipid alterations predate AP treatment in adolescents with EOP. Higher levels of negative symptoms and AP further increase metabolic risk. The preliminary findings propose that subclinical dyslipidemia may be intrinsic to EOP.

• Ulven, Stine Marie; Holven, Kirsten Bjørklund; Gil, Angel & Rangel-Huerta, Oscar Daniel (2019). Milk and dairy product consumption and inflammatory biomarkers: an updated systematic review of randomized clinical trials. Advances in Nutrition. ISSN 2161-8313. 10(2), p. S239–S250. doi: 10.1093/advances/nmy072. Full text in Research Archive
• Ulven, Stine Marie; Holven, Kirsten Bjørklund; Rundblad, Amanda; Myhrstad, Mari; Leder, Lena & Dahlman, Ingrid [Show all 25 contributors for this article] (2019). An isocaloric nordic diet modulates RELA and TNFRSF1A gene expression in peripheral blood mononuclear cells in individuals with metabolic syndrome - a SYSDIET sub-study. Nutrients. 11:2932(12), p. 1–11. doi: 10.3390/nu11122932. Full text in Research Archive Show summary

  A healthy dietary pattern is associated with a lower risk of metabolic syndrome (MetS) and reduced inflammation. To explore this at the molecular level, we investigated the effect of a Nordic diet (ND) on changes in the gene expression profiles of inflammatory and lipid-related genes in peripheral blood mononuclear cells (PBMCs) of individuals with MetS. We hypothesized that the intake of an ND compared to a control diet (CD) would alter the expression of inflammatory genes and genes involved in lipid metabolism. The individuals with MetS underwent an 18/24-week randomized intervention to compare a ND with a CD. Eighty-eight participants (66% women) were included in this sub-study of the larger SYSDIET study. Fasting PBMCs were collected before and after the intervention and changes in gene expression levels were measured using TaqMan Array Micro Fluidic Cards. Forty-eight pre-determined inflammatory and lipid related gene transcripts were analyzed. The expression level of the gene tumor necrosis factor (TNF) receptor superfamily member 1A (TNFRSF1A) was down-regulated (p = 0.004), whereas the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) subunit, RELA proto-oncogene, was up-regulated (p = 0.016) in the ND group compared to the CD group. In conclusion, intake of an ND in individuals with the MetS may affect immune function.

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• Telle-Hansen, Vibeke; Rundblad, Amanda; Rud, Emilia; Gaundal, Line; Rud, Ida & Retterstøl, Kjetil [Show all 9 contributors for this article] (2025). Metabolic profiling and gene transcription analyses in healthy individuals after exchanging SFA with PUFA: secondary analyses of a randomized controlled trial. Full text in Research Archive Show summary

  Background and objectives: The underlying molecular mechanisms by which diet influences metabolic health are still to be elucidated. In secondary analyses of an RCT, we aimed to investigate the effect on cardiometabolic risk markers in healthy individuals after a short-term intervention with PUFA compared to SFA by using metabolomics and transcriptomics. Materials and methods: Seventeen healthy, normal-weight participants completed a double-blind, crossover RCT. Participants were allocated to receive interventions with PUFA and SFA products in a random order for three consecutive days, separated by a 10-day washout period. We analyzed the effect of the intervention on 155 metabolites mainly related to lipoproteins using nuclear magnetic resonance (NMR) spectroscopy, and the expression of 748 genes related to metabolic pathways using NanoString. Results: The particle concentration of the smallest very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL) and all low-density lipoprotein (LDL) subclasses were reduced after intake of PUFA for three days compared to SFA. We found the same pattern for the particle content of cholesterol, but not triglyceride, in these lipoprotein subclasses. Moreover, the concentration of other atherogenic lipoprotein measures were reduced after intake of PUFA compared to SFA. The expression of 45 genes were significantly altered by PUFA compared to SFA. Several of these genes were related to lipid metabolism and energy homeostasis (such as ALOX15, SLC3A2, ECHS1, STK11, SREBF2, FABP5, and ACACA). Conclusions: This study demonstrated that a three-day intervention with PUFA significantly reduced several atherogenic lipoprotein subclass measures, and the expression of genes related to lipid metabolism in young healthy individuals. This highlights that the dietary fat quality is important to improve the cardiovascular disease risk profile, even in a young healthy population.

• Øhman, Elisabeth Adolfsen; Fossli, Maria; Ottestad, Inger Olaug; Holven, Kirsten Bjørklund; Ulven, Stine Marie & Løland, Beate Fossum [Show all 7 contributors for this article] (2024). Dietary treatment postpartum in women with obesity reduces weight and prevents weight gain: a randomised controlled trial. Full text in Research Archive
• Øhman, Elisabeth Adolfsen; Fossli, Maria; Ottestad, Inger; Holven, Kirsten Bjørklund; Ulven, Stine Marie & Løland, Beate Fossum [Show all 7 contributors for this article] (2023). Effect of a postpartum weight loss intervention in women with obesity: a randomized controlled trial. Full text in Research Archive
• Øhman, Elisabeth Adolfsen; Fossli, Maria; Ottestad, Inger; Holven, Kirsten Bjørklund; Ulven, Stine Marie & Løland, Beate Fossum [Show all 7 contributors for this article] (2023). Kostprogram postpartum reduserer vekt og forebygger vektoppgang blant kvinner med fedme – en randomisert kontrollert studie. Full text in Research Archive
• Melnes, Torunn; Bogsrud, Martin Prøven; Christensen, Jacob J.; Rundblad, Amanda; Narverud, Ingunn & Retterstøl, Kjetil [Show all 10 contributors for this article] (2023). Difference in PBMC gene expression between elderly event-free FH patients and FH patients with CHD. Full text in Research Archive
• Melnes, Torunn; Bogsrud, Martin Prøven; Christensen, Jacob J.; Rundblad, Amanda; Narverud, Ingunn & Retterstøl, Kjetil [Show all 10 contributors for this article] (2023). Difference in PBMC gene expression between elderly event-free FH patients and FH patients with CHD. Full text in Research Archive
• Melnes, Torunn; Bogsrud, Martin Prøven; Thorsen, Ida; Fossum, Julie; Christensen, Jacob J. & Narverud, Ingunn [Show all 9 contributors for this article] (2023). What characterizes event-free elderly FH patients? A comprehensive lipoprotein profiling. Full text in Research Archive
• Rundblad, Amanda; Hansen, Anna Lena; Christensen, Jacob Juel; Melnes, Torunn; Ottestad, Inger Olaug & Narverud, Ingunn [Show all 12 contributors for this article] (2023). Patients with familial hypercholesterolemia have shorter telomeres than controls in older, but not in young subjects: a cross-sectional study. Full text in Research Archive
• Rundblad, Amanda; Christensen, Jacob Juel; Hustad, Kristin Solheim; Bastani, Nasser Ezzatkhah; Holven, Kirsten Bjørklund & Ulven, Stine Marie (2023). Associations between dietary intake and glucose tolerance in  clinical and metabolomics-based metabotypes. Full text in Research Archive
• Rundblad, Amanda; Das, Siddhartha; Matthews, Jason; Ginos, Gina; Kavousi, Maryam & Holven, Kirsten Bjørklund [Show all 7 contributors for this article] (2023). Air pollution, built environment and associations with gene expression and CVD risk markers in adults. Full text in Research Archive
• Ulven, Stine Marie; Ottestad, Inger Olaug; Christensen, Jacob Juel & Holven, Kirsten Bjørklund (2023). Inflammatory markers and frailty in home-dwelling elderly, a cross-sectional study. Full text in Research Archive
• Øhman, Elisabeth Adolfsen; Fossli, Maria; Ottestad, Inger; Holven, Kirsten Bjørklund; Ulven, Stine Marie & Løland, Beate Fossum [Show all 7 contributors for this article] (2023). Effect of a postpartum weight loss intervention in women with obesity: a randomized controlled trial. Full text in Research Archive
• Melnes, Torunn; Bogsrud, Martin Prøven; Christensen, Jacob J.; Rundblad, Amanda; Narverud, Ingunn & Retterstøl, Kjetil [Show all 10 contributors for this article] (2023). Difference in PBMC gene expression between elderly event-free FH patients and FH patients with CHD. Full text in Research Archive
• Holven, Kirsten Bjørklund; Ulven, Stine Marie; Ottestad, Inger Olaug & Christensen, Jacob Juel (2023). Inflammatory markers and frailty markers in home-dwelling elderly, a cross-sectional study. Full text in Research Archive
• Holven, Kirsten Bjørklund; Ulven, Stine Marie; Christensen, Jacob Juel & Ottestad, Inger Olaug (2023). Betydning av kosten for endring i skrøpelighet hos hjemmeboende eldre etter 8 års oppfølging. Full text in Research Archive
• Rønning, Sissel Beate; Carlsen, Harald; Rocha, Sergio Domingos Cardoso; Solberg, Nina; Høst, Vibeke & Veiseth-Kent, Eva [Show all 14 contributors for this article] (2022). Intake of avian Eggshell membrane powder can reduce inflammation and attenuate skeletal muscle aging. Full text in Research Archive
• Hjorth, Marit; Doncheva, Atanaska Ivanova; Norheim, Frode Amador; Ulven, Stine Marie; Holven, Kirsten Bjørklund & Sæther, Thomas [Show all 7 contributors for this article] (2022). Consumption of salmon fishmeal increases hepatic cholesterol content in obese C57BL/6J mice. Full text in Research Archive
• Telle-Hansen, Vibeke; Christensen, Jacob J.; Formo, Gulla Aase; Holven, Kirsten Bjørklund & Ulven, Stine Marie (2022). Do All People With Obesity Have Increased Risk of Disease? Frontiers for Young Minds. 10. doi: 10.3389/frym.2022.792630. Full text in Research Archive
• Melnes, Torunn; Bogsrud, Martin Prøven; Thorsen, Ida; Fossum, Julie; Christensen, Jacob J. & Narverud, Ingunn [Show all 9 contributors for this article] (2022). What characterizes event-free elderly FH patients? A comprehensive lipoprotein profiling. Full text in Research Archive
• Øhman, Elisabeth Adolfsen; Fossli, Maria; Brekke, Hilde Kristin; Holven, Kirsten Bjørklund; Ulven, Stine Marie & Ottestad, Inger [Show all 7 contributors for this article] (2022). Dietary treatment prevents postpartum weight gain in women with obesity: a randomised controlled trial. Full text in Research Archive Show summary

  Background: Women with pre-pregnancy obesity have an increased risk of retaining or gaining weight postpartum. Previously, we performed a dietary treatment which resulted in sustained weight loss and improved cardiometabolic risk factors in lactating women with a mean BMI=30 kg/m2. However, evidence is lacking for higher BMI classes. The aim of this study was to examine the effects of the dietary treatment on change in weight and markers of lipid- and glucose metabolism as well as postpartum weight retention (PPWR) and change in waist-and-hip-circumference in postpartum women with obesity. Methodology: At baseline, approximately 8 weeks postpartum, 29 women were randomised to a 12-week dietary treatment for weight loss (n=14) or to a control treatment (n=15) receiving a brochure on healthy eating. Measurements were made at baseline and 3 and 12 months later. Data was analysed using mixed model. Results: Mean BMI at baseline was 40.0 ± 5.2 kg/m2. Weight change after 3 months was -2.3 ± 3.1 kg in the diet group compared to 1.7 ± 3.1 kg in the control group (P=0.025), and -4.2 ± 5.6 kg in the diet group compared to 4.8 ± 11.8 kg in the control group after 12 months (P=0.010). The dietary treatment led to reduced waist circumference (P<0.032) and PPWR (P<0.002) compared to the control treatment at both time points. There were no effects of the treatment on markers of lipid- and glucose metabolism. Conclusion: The dietary treatment prevented postpartum women with obesity from retaining or gaining weight, and may even reduce weight.

• Melnes, Torunn; Bogsrud, Martin Prøven; Thorsen, Ida; Fossum, Julie; Christensen, Jacob J. & Narverud, Ingunn [Show all 9 contributors for this article] (2021). Event-free FH patients ≥65 years of age are characterized by higher concentration of large HDL particles. Full text in Research Archive
• Christensen, Jacob Juel; Narverud, Ingunn; Ruuth, Maija; Heier, Martin; Jauhiainen, Matti & Ulven, Stine Marie [Show all 14 contributors for this article] (2021). Children with FH display changes in LDL and HDL function: a cross-sectional study. Full text in Research Archive
• Ulven, Stine Marie (2021). Dietary fat, metabolomics and inflammation assessed by gene expression profiling. Full text in Research Archive
• Ulven, Stine Marie (2021). Betydningen av exposomet i persontilpasset ernæring. Full text in Research Archive
• Christensen, Jacob Juel; Telle-Hansen, Vibeke; Ulven, Stine Marie; Kovanen, Petri T.; Jauhiainen, Matti & Öörni, Katariina [Show all 7 contributors for this article] (2021). The homeoviscous adaptation to dietary lipids (HADL) hypothesis is probably incorrect. American Journal of Clinical Nutrition. ISSN 0002-9165. 113(6), p. 1711–1712. doi: 10.1093/ajcn/nqab110. Full text in Research Archive
• Melnes, Torunn; Bogsrud, Martin Prøven; Thorsen, Ida; Fossum, Julie; Christensen, Jacob J. & Narverud, Ingunn [Show all 9 contributors for this article] (2021). Event-free FH patients >65 years of age are characterized by higher concentration of large HDL particles. Full text in Research Archive
• Øhman, Elisabeth Adolfsen; Kirchner, Lisa; Winkvist, Anna; Bertz, Fredrik; Holven, Kirsten Bjørklund & Ulven, Stine Marie [Show all 7 contributors for this article] (2020). Effects of dietary and exercise treatments on HDL subclasses in lactating women with overweight and obesity: a secondary analysis of a randomised controlled trial. Full text in Research Archive
• Øhman, Elisabeth Adolfsen; Kirchner, Lisa; Winkvist, Anna; Bertz, Fredrik; Holven, Kirsten Bjørklund & Ulven, Stine Marie [Show all 7 contributors for this article] (2020). Effects of dietary and exercise treatments on HDL subclasses in lactating women with overweight and obesity: a secondary analysis of a randomised controlled trial. Full text in Research Archive
• Øhman, Elisabeth Adolfsen; Kirchner, Lisa; Winkvist, Anna; Bertz, Fredrik; Holven, Kirsten Bjørklund & Ulven, Stine Marie [Show all 7 contributors for this article] (2020). Effects of dietary and exercise treatments on HDL subclasses in lactating women with overweight and obesity: a secondary analysis of a randomised controlled trial. Full text in Research Archive
• Gaundal, Line; Myhrstad, Mari; Leder, Lena; Byfuglien, Marte Gjeitung; Gjøvaag, Terje & Rud, Ida [Show all 10 contributors for this article] (2020). Beneficial effect on serum cholesterol levels, but not glycaemic regulation, after replacing SFA with PUFA for 3 days: a randomized crossover trial. Full text in Research Archive
• Narverud, Ingunn; Christensen, Jacob Juel; Bakke, Siril Skaret; Ulven, Stine Marie; Rundblad, Amanda & Aukrust, Pål [Show all 12 contributors for this article] (2020). Profiling of immune‐related gene expression in children with familial hypercholesterolaemia. Full text in Research Archive
• Christensen, Jacob Juel; Ulven, Stine Marie; Thoresen, Magne; Westerman, Kenneth; Holven, Kirsten Bjørklund & Andersen, Lene Frost (2020). Associations between dietary patterns and gene expression pattern in PBMCs: a cross-sectional study. Full text in Research Archive
• Myhrstad, Mari; Gaundal, Line; Stegelvik, Tina; Høgvard, Benedicte; Byfuglien, marthe & Rieder, Anne [Show all 12 contributors for this article] (2019). Intake of beta-glucan and changes in plasma metabolic profile. A short-term intervention in healthy subjects. Full text in Research Archive
• Rundblad, Amanda; Larsen, Sunniva Veen; Myhrstad, Mari; Ottestad, Inger; Thoresen, Magne & Holven, Kirsten Bjørklund [Show all 7 contributors for this article] (2019). Characterization of PBMC gene expression and lipoprotein subclasses among plasma TG responders and non-responders. Full text in Research Archive
• Holven, Kirsten Bjørklund; Sæther, Thomas; Hjorth, Marit; Dalen, Knut Tomas; Ulven, Stine Marie & Ottestad, Inger [Show all 7 contributors for this article] (2019). Kan fisk utnyttes enda mer og samtidig fremme folkehelsen? Norsk tidsskrift for ernæring (NTFE). ISSN 1503-5034. 17(2), p. 20–22. Full text in Research Archive
• Andersen, Lene Frost; Berstad, Paula; Carlsen, Monica Hauger; Dahl, Lisbeth Jane; Goksøyr, Anders & Knutsen, Helle Katrine [Show all 32 contributors for this article] (2020). Protocol and description of literature searches for the risk-benefit assessment of fish in the Norwegian diet. The Steering Committee of the Norwegian Scientific Committee for Food and Environment. The Norwegian Scientific Committee for Food Safety. ISSN 9788282593359. Full text in Research Archive Show summary

  Fish contains nutrients that are positive for our health. At the same time, it contains varying levels of undesirable substances that can have a negative effect on health. Undesirable substances can be found in different levels in most types of food. In a risk-benefit assessment, both the nutrients and the undesirable substances are assessed and it is evaluated whether it in total gives a more positive effect to eat certain foodstuff than not, and possibly how much one should eat to achieve optimal use of the positive health effects.

• Løvik, Martinus; Dahl, Lisbeth; Mangschou, Bente; Ulven, Stine Marie; Andersen, Lene Frost & Dalen, Knut Tomas [Show all 10 contributors for this article] (2019). Assessment of dietary intake of fluoride and maximum limits of fluoride in food supplements. Opinion of the Panel on Nutrition, Dietetic Products, Novel Food and Allergy of the Norwegian Scientific Committee for Food and Environment. Norwegian Scientific Committee for Food and Environment (VKM). ISSN 9788282593281. Full text in Research Archive Show summary

  The Norwegian Scientific Committee for Food and Environment (Vitenskapskomiteen for mat og miljø, VKM) has, at the request of the Norwegian Food Safety Authority (Mattilsynet, NFSA), evaluated the intake of fluoride in the diet, together with intake of fluoride from dental hygiene and caries prevention products. VKM has also evaluated suggested maximum limits for fluoride in food supplements at 0.5, 1, 5 and 7 mg/day in relation to established tolerable upper intake levels (ULs). The former maximum limit for fluoride of 0.5 mg/day in food supplements was repealed 30 May 2017. Fluorine is a gaseous halogen which occurs naturally only in anionic form as fluoride (F-). Fluorides are ubiquitous in air, water and the lithosphere. Fluoride is found naturally in all water sources. The highest levels are found in groundwater. Surface water usually has lower concentrations of fluoride than groundwater, most often under 0.5 mg/L. Major dietary fluoride sources are water and tea. An important non-dietary source is dental hygiene products such as toothpaste and tablets for caries prevention. There is no fluoridation of drinking water or salt in Norway. Fluoride is not an essential nutrient. Caries is not a fluoride deficiency disease. However, because of the beneficial effects for caries prevention, an adequate intake (AI) of 0.05 mg per kg body weight per day has been set for fluoride by the European Food Safety Authority (EFSA). Readily soluble fluorides (sodium- and potassium fluoride) are rapidly and almost completely absorbed by passive diffusion in the stomach and the small intestine. Absorption is influenced by acidity and concomitant food intake. Absorbed fluoride is rapidly distributed in blood plasma, but is retained only in calcified tissues, that are bones and teeth. Consequently, 99% of the total fluoride content of the body is found in bone and teeth. Absorbed fluoride which is not deposited in calcified tissues is excreted almost exclusively via the kidneys. Whereas skeletal bone and dentine accumulate fluoride throughout life, enamel of teeth incorporate fluoride only at the time of tooth formation. Fluoride substitutes for hydroxyl groups in the apatite, increasing the resistance to caries. In permanent teeth enamel maturation is completed at the age of seven to eight years, except in the third molars. Posteruptive fluoride uptake by enamel occurs only in the outer layer and depends on local oral fluoride levels. A linear relationship between fluoride exposure and caries resistance has been demonstrated. Over the years, the view has shifted from systemic fluoride being most effective for caries prevention to local oral exposure being most important. Acute toxic effects may be provoked by fluoride, and deaths have been reported after intake of very large doses from fluoride tablets. The main adverse outcomes from intake of excess doses of fluoride over time, are enamel fluorosis in children up to eight years of age, and bone fluorosis in older children and adults. Dental fluorosis causing mottled teeth is largely a cosmetic effect, whereas bone fluorosis causes stiff joints and a greater tendency to fractures. Tolerable upper intake levels (UL) for fluoride have been set by the American Institute of Medicine (IOM) and by the European Food Safety Authority (EFSA). In this report, we relate estimated fluoride intakes to the upper level set by EFSA. Intakes of the main dietary fluoride sources, water and tea, in different age groups were obtained from Norwegian dietary surveys. High fluoride intakes were estimated by applying the 95 percentile of fluoride concentrations in water obtained from 2001 fluoride analyses from Norwegian waterworks in the period between 2010 and 2018 and in tea obtained from a Polish study to the daily volume consumed. Fluoride intakes from recommended use of dental hygiene and caries prevention products were then added, plus a small fixed value for undescribed sources. The estimated 95 percentile fluoride exposure calculated this way was compared to the upper level, and scenarios with additional fluoride supplementation of 0.5, 1, 5 or 7 mg/day were developed. The estimated 95-percentile of fluoride exposure from water, tea and dental hygiene products alone (before fluoride from the suggested food supplement doses at 0.5, 1, and 7 mg/day were added) was found to exceed the upper level for 2-year old children and for adults. VKM concludes that all the suggested food supplement doses considered will cause the tolerable upper intake level to be exceeded in all age groups, except for the supplement doses of 0.5 in 9- and 13-year olds and 1 mg/day in 9 year olds. VKM emphasises that the current assessment of maximum limits for fluoride in food supplements is merely based on published reports concerning upper levels from the IOM (USA, 2001), Scientific Committee on Food (EU, 2003), Expert Group on Vitamins and Minerals (UK, 2003) and Nordic Nutrition Recommendations (Nordic Countries, 2012). VKM has not conducted any review of the literature for the current opinion, as this was outside the scope of the terms of reference from the NFSA.

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