Fish consumption and supplementation with n-3 fatty acids reduce CVD risk. Krill oil is an alternative source of marine n-3 fatty acids and few studies have investigated its health effects. Thus, we compared krill oil supplementation with the intake of fish with similar amounts of n-3 fatty acids on different cardiovascular risk markers. In an 8-week randomised parallel study, thirty-six healthy subjects aged 18–70 years with fasting serum TAG between 1·3 and 4·0 mmol/l were randomised to receive either fish, krill oil or control oil. In the fish group, subjects consumed lean and fatty fish, according to dietary guidelines. The krill and control group received eight capsules per d containing 4 g oil per d. The weekly intake of marine n-3 fatty acids from fish given in the fish group and from krill oil in the krill group were 4103 and 4654 mg, respectively. Fasting serum TAG did not change between the groups. The level of total lipids (P = 0·007), phospholipids (P = 0·015), cholesterol (P = 0·009), cholesteryl esters (P = 0·022) and non-esterified cholesterol (P = 0·002) in the smallest VLDL subclass increased significantly in response to krill oil supplementation. Blood glucose decreased significantly (P = 0·024) in the krill group and vitamin D increased significantly in the fish group (P = 0·024). Furthermore, plasma levels of marine n-3 fatty acids increased significantly in the fish and krill groups compared with the control (all P ≤ 0·0003). In conclusion, supplementation with krill oil and intake of fish result in health-beneficial effects. Although only krill oil reduced fasting glucose, fish provide health-beneficial nutrients, including vitamin D.

Marine n-3 (omega-3) fatty acids alter gene expression by regulating the activity of transcription factors. Krill oil is a source of marine n-3 fatty acids that has been shown to modulate gene expression in animal studies; however, the effect in humans is not known. Hence, we aimed to compare the effect of intake of krill oil, lean and fatty fish with a similar content of n-3 fatty acids, and high-oleic sunflower oil (HOSO) with added astaxanthin on the expression of genes involved in glucose and lipid metabolism and inflammation in peripheral blood mononuclear cells (PBMC) as well as circulating inflammatory markers. In an 8-week trial, healthy men and women aged 18–70 years with fasting TAG of 1·3–4·0 mmol/l were randomised to receive krill oil capsules (n 12), HOSO capsules (n 12) or lean and fatty fish (n 12). The weekly intakes of marine n-3 fatty acids from the interventions were 4654, 0 and 4103 mg, respectively. The mRNA expression of four genes, PPAR γ coactivator 1A (PPARGC1A), steaoryl-CoA desaturase (SCD), ATP binding cassette A1 (ABCA1) and cluster of differentiation 40 (CD40), were differently altered by the interventions. Furthermore, within-group analyses revealed that krill oil down-regulated the mRNA expression of thirteen genes, including genes involved in glucose and cholesterol metabolism and β-oxidation. Fish altered the mRNA expression of four genes and HOSO down-regulated sixteen genes, including several inflammation-related genes. There were no differences between the groups in circulating inflammatory markers after the intervention. In conclusion, the intake of krill oil and HOSO with added astaxanthin alter the PBMC mRNA expression of more genes than the intake of fish.

Scope To explore the effect of a healthy Nordic diet on the global transcriptome profile in peripheral blood mononuclear cells (PBMCs) of subjects with metabolic syndrome. Methods and results Subjects with metabolic syndrome undergo a 18/24 week randomized intervention study comparing an isocaloric healthy Nordic diet with an average habitual Nordic diet served as control (SYSDIET study). Altogether, 68 participants are included. PBMCs are obtained before and after intervention and total RNA is subjected to global transcriptome analysis. 1302 probe sets are differentially expressed between the diet groups (p‐value < 0.05). Twenty‐five of these are significantly regulated (FDR q‐value < 0.25) and are mainly involved in mitochondrial function, cell growth, and cell adhesion. The list of 1302 regulated probe sets is subjected to functional analyses. Pathways and processes involved in the mitochondrial electron transport chain, immune response, and cell cycle are downregulated in the healthy Nordic diet group. In addition, gene transcripts with common motifs for 42 transcription factors, including NFR1, NFR2, and NF‐κB, are downregulated in the healthy Nordic diet group. Conclusion These results suggest that benefits of a healthy diet may be mediated by improved mitochondrial function and reduced inflammation.

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 large inter-individual differences in the TG-lowering effect of omega-3 supplementation. Genotype differences partly explain this variation, but gene-environment interactions leading to gene expression differences may also be important. In this study, 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-3 fatty 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 having a 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 lipoprotein subclasses 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 defined as 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 four of 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 and PBMC gene expression profiles at baseline and different lipoprotein subclass and PBMC gene expression responses to omega-3 supplementation. These gene expression differences may partially explain the variability in TG response observed after omega-3 supplementation. Graphical abstract Based on free images from Servier Medical Art (Creative Commons Attribution License) and image from www.colourbox.com . Electronic supplementary material The online version of this article (10.1186/s12263-019-0633-y) contain...

Fish oil (FO) supplementation reduces the risk of CVD. However, it is not known if FO of different qualities have different effects on lipoprotein subclasses in humans. We aimed at investigating the effects of oxidised FO and high-quality FO supplementation on lipoprotein subclasses and their lipid concentrations in healthy humans. In all, fifty-four subjects completed a double-blind randomised controlled intervention study. The subjects were randomly assigned to receive high-quality FO (n 17), oxidised FO (n 18) or high-oleic sunflower oil capsules (HOSO, n 19) for 7 weeks. The concentration of marine n-3 fatty acids was equal in high-quality FO and oxidised FO (1·6 g EPA+DHA/d). The peroxide value (PV) and anisidine value (AV) were 4 mEq/kg and 3 in high-quality FO and HOSO, whereas the PV and AV in the oxidised FO were 18 mEq/kg and 9. Blood samples were collected at baseline and end of study. NMR spectroscopy was applied for the analysis of lipoprotein subclasses and their lipid concentrations. High-quality FO reduced the concentration of intermediate-density lipoprotein (IDL) particles and large, medium and small LDL particles, as well as the concentrations of total lipids, phospholipids, total cholesterol, cholesteryl esters and free cholesterol in IDL and LDL subclasses compared with oxidised FO and HOSO. Hence, high-quality FO and oxidised FO differently affect lipid composition in lipoprotein subclasses, with a more favourable effect mediated by high-quality FO. In future trials, reporting the oxidation levels of FO would be useful.

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.

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. Methods and results: Healthy subjects (n = 47) consume four different high-fat meals composed of either butter, cheese, whipped cream, or sour cream 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 amino acid changes correlate with several of the differentially altered genes. 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.

Fish consumption is associated with reduced risk of cardiovascular disease (CVD), which may be partly mediated by alterations in plasma lipids, such as high-density lipoprotein cholesterol (HDL-C). 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 emphasis on HDL. We performed a comprehensive plasma metabolite profiling in 517 healthy adults, using a targeted high-throughput nuclear magnetic resonance spectroscopy platform. The participants were divided into tertiles based on consumption of fatty fish, reported through a validated food frequency questionnaire. 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 (>223 g/week, median intake 294 g/week) had higher particle concentrations and content of total lipids, and phospholipids in large and extra-large HDL particles, and higher content of total cholesterol, free cholesterol, cholesteryl esters and triglycerides in large HDL particles, than low-consumers (<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-C-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.