Weight loss induced by a hypocaloric diet with or without fish oil supplementation re-established iron and omega-3 fatty acid homeostasis in middle-aged women with obesity: A post-hoc analysis of a randomized controlled trial.

OBJECTIVE: Middle-aged women with obesity are at increased risk of iron overload and iron disorder is known to disrupt n-3 polyunsaturated fatty acid homeostasis. We evaluated relationships between pretreatment hemoglobin and n-3 polyunsaturated fatty acid levels, and tested whether pretreatment hemoglobin contributed to inter-individual variability in weight loss with special focus on changes in body weight, iron and n-3 polyunsaturated fatty acid profiles. STUDY DESIGN: 117 middle and older aged women with obesity and more than two metabolic abnormalities were randomized to a 12-week hypocaloric diet without or with fish oil supplementation. Blood iron biomarker and erythrocyte membrane phospholipid profiles were evaluated. MAIN OUTCOME: The absolute change from baseline to week 12 in serum iron and erythrocyte n-3 polyunsaturated fatty acid levels according to pretreatment hemoglobin tertiles and fish oil supplementation. RESULTS: A Pearson correlation analysis showed that pretreatment hemoglobin levels were negatively correlated with linoleic acid (r = -0.231), α-linoleic acid (r = -0.279), and n-3 polyunsaturated fatty acid (r = -0.217) (all p < 0.05). Dietary weight loss markedly enhanced erythrocyte membrane lipids of linoleic acid, α-linoleic acid, and n-6 and n-3 polyunsaturated fatty acid only in those women with the highest pretreatment hemoglobin levels (tertile 3) (all p < 0.05). Fish oil supplementation increased bioavailable iron in women with moderate pretreatment hemoglobin levels (tertile 2) (p < 0.05) and, to a lesser extent, prevented a reduction in circulating iron in those with the lowest hemoglobin levels (tertile 1). CONCLUSION: Dietary weight loss is an effective treatment program to manage obesity-related iron and n-3 polyunsaturated fatty acid disorders, particularly for middle-aged women with obesity and iron overload.

Dietary n-3 polyunsaturated fatty acids alter the number, fatty acid profile and coagulatory activity of circulating and platelet-derived extracellular vesicles: a randomized, controlled crossover trial.

BACKGROUND: Extracellular vesicles (EVs) are proposed to play a role in the development of cardiovascular diseases (CVDs) and are considered emerging markers of CVDs. n-3 PUFAs are abundant in oily fish and fish oil and are reported to reduce CVD risk, but there has been little research to date examining the effects of n-3 PUFAs on the generation and function of EVs. OBJECTIVES: We aimed to investigate the effects of fish oil supplementation on the number, generation, and function of EVs in subjects with moderate risk of CVDs. METHODS: A total of 40 participants with moderate risk of CVDs were supplemented with capsules containing either fish oil (1.9 g/d n-3 PUFAs) or control oil (high-oleic safflower oil) for 12 wk in a randomized, double-blind, placebo-controlled crossover intervention study. The effects of fish oil supplementation on conventional CVD and thrombogenic risk markers were measured, along with the number and fatty acid composition of circulating and platelet-derived EVs (PDEVs). PDEV proteome profiles were evaluated, and their impact on coagulation was assessed using assays including fibrin clot formation, thrombin generation, fibrinolysis, and ex vivo thrombus formation. RESULTS: n-3 PUFAs decreased the numbers of circulating EVs by 27%, doubled their n-3 PUFA content, and reduced their capacity to support thrombin generation by >20% in subjects at moderate risk of CVDs. EVs derived from n-3 PUFA-enriched platelets in vitro also resulted in lower thrombin generation, but did not alter thrombus formation in a whole blood ex vivo assay. CONCLUSIONS: Dietary n-3 PUFAs alter the number, composition, and function of EVs, reducing their coagulatory activity. This study provides clear evidence that EVs support thrombin generation and that this EV-dependent thrombin generation is reduced by n-3 PUFAs, which has implications for prevention and treatment of thrombosis. CLINICAL TRIAL REGISTRY: This trial was registered at clinicaltrials.gov as NCT03203512.

Fish oil supplement use modifies the relationship between dietary oily fish intake and plasma n-3 PUFA levels: an analysis of the UK Biobank.

Observational evidence linking dietary n-3 PUFA intake and health outcomes is limited by a lack of robust validation of dietary intake using blood n-3 PUFA levels and potential confounding by fish oil supplement (FOS) use. We investigated the relationship between oily fish intake, FOS use and plasma n-3 PUFA levels in 121 650 UK Biobank (UKBB) participants. Ordinal logistic regression models, adjusted for clinical and lifestyle factors, were used to quantify the contribution of dietary oily fish intake and FOS use to plasma n-3 PUFA levels (measured by NMR spectroscopy). Oily fish intake and FOS use were reported by 38 % and 31 % of participants, respectively. Increasing oily fish intake was associated with a higher likelihood of FOS use (P < 0·001). Oily fish intake ≥ twice a week was the strongest predictor of high total n-3 PUFA (OR 6·7 (95 % CI 6·3, 7·1)) and DHA levels (6·6 (6·3, 7·1). FOS use was an independent predictor of high plasma n-3 PUFA levels (2·0 (2·0, 2·1)) with a similar OR to that associated with eating oily fish < once a week (1·9 (1·8, 2·0)). FOS use was associated with plasma n-3 PUFA levels that were similar to individuals in the next highest oily fish intake category. In conclusion, FOS use is more common in frequent fish consumers and modifies the relationship between oily fish intake and plasma n-3 PUFA levels in UKBB participants. If unaccounted for, FOS use may confound the relationship between dietary n-3 PUFA intake, blood levels of n-3 PUFAs and health outcomes.

Selective Consumption of Fish Oil at End of the Day Increases the Physiological Fatty Acid Compositions of Eicosapentaenoic Acid and Docosahexaenoic Acid in Mice.

Diets with high daily fat consumption are associated with excess weight. However, the effects of fat type and consumption timing on excess weight remain unclear. We investigated the selection of a 30% (w/w) fat diet of soybean oil (SOY), lard (LARD), and fish oil (FISH) on the metabolic parameters of mice. Male C57BL/6 mice were divided into the double SOY-box (w-SOY), SOY-box/LARD-box (SOY-vs-LARD), or SOY-box/FISH-box (SOY-vs-FISH) groups and allowed to selectively consume for 8 weeks. The total energy intake was similar for all groups, but the mice selectively chose to consume LARD over SOY and SOY over FISH. Body weight in the SOY-vs-LARD group was significantly higher than that in the w-SOY and SOY-vs-FISH groups. Additionally, minimal but selective consumption of an omega-3 fatty-acid-rich FISH diet at the end of the active period increased the physiological fatty acid compositions of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the SOY-vs-FISH group; their metabolic parameters were also lower than the SOY-vs-LARD group. In conclusion, selectively consuming small amounts of fish oil at the end of the day may prevent excess weight compared with LARD consumption.

Fish oil ameliorates neuropsychiatric behaviors and gut dysbiosis by elevating selected microbiota-derived metabolites and tissue tight junctions in rats under chronic sleep deprivation.

Neuropsychiatric behaviors caused by sleep deprivation (SD) are severe public health problems in modern society worldwide. This study investigated the effect of fish oil on neuropsychiatric behaviors, barrier injury, microbiota dysbiosis, and microbiota-derived metabolites in SD rats. The rats subjected to SD had significantly elevated blood levels of corticosteroid and lipopolysaccharides and exhibited anxiety-like behavior in the open field test, depression-like behavior in the forced swim test, and cognitive impairment in the Morris water maize test. We observed that the upregulation of proinflammatory cytokines in the SD rats resulted in colonic epithelial barrier injury including a decreased number of goblet cells and increased expression of selected tight junction proteins in the gut and brain. The gut microbiome status revealed a significant decrease in the microbial diversity in the SD rats, especially in probiotics. By contrast, a fish oil-based diet reversed SD-induced behavioral changes and improved the epithelial barrier injury and dysbiosis of the microbiota in the colon. These findings could be attributable to the increase in probiotics and short-chain fatty acid (SCFAs) production, improvement in selected intestinal barrier proteins, increase in SCFA receptor expression, and decrease in blood circulation proinflammatory status due to fish oil supplementation.

Impact of Co-Delivery of EGCG and Tuna Oil within a Broccoli Matrix on Human Gut Microbiota, Phenolic Metabolites and Short Chain Fatty Acids In Vitro.

(-)-Epigallocatechin gallate (EGCG) and tuna oil (TO) are beneficial bioactive compounds. EGCG, TO or a combination of, delivered by broccoli by-products (BBP), were added to an in vitro anaerobic fermentation system containing human fecal inocula to examine their ability to generate short-chain fatty acids (SCFA), metabolize EGCG and change the gut microbiota population (assessed by 16 S gene sequencing). Following 24 h fermentation, EGCG was hydrolyzed to (-)-epigallocatechin and gallic acid. EGCG significantly inhibited the production of SCFA (p < 0.05). Total SCFA in facal slurries with BBP or TO-BBP (48-49 µmol/mL) were significantly higher (p < 0.05) than the negative control with cellulose (21 µmol/mL). EGCG-BBP and TO-EGCG-BBP treatment increased the relative abundance of Gluconacetobacter, Klebsiella and Trabulsiella. BBP and TO-BBP showed the greatest potential for improving gut health with the growth promotion of high butyrate producers, including Collinsella aerofaciens, Bacillus coagulans and Lactobacillus reuteri.

Sex Differences in Fish Oil and Olanzapine Effects on Gut Microbiota in Diet-Induced Obese Mice.

Children are prescribed second-generation antipsychotic (SGA) medications, such as olanzapine (OLZ) for FDA-approved and "off-label" indications. The long-term impact of early-life SGA medication exposure is unclear. Olanzapine and other SGA medications are known to cause excessive weight gain in young and adult patients, suggesting the possibility of long-term complications associated with the use of these drugs, such as obesity, diabetes, and heart disease. Further, the weight gain effects of OLZ have previously been shown to depend on the presence of gut bacteria and treatment with OLZ, which shifts gut bacteria toward an "obesogenic" profile. The purpose of the current study was to evaluate changes in gut bacteria in adult mice following early life treatment with OLZ and being fed either a high-fat diet or a high-fat diet supplemented with fish oil, which has previously been shown to counteract gut dysbiosis, weight gain, and inflammation produced by a high-fat diet. Female and male C57Bl/6J mice were fed a high fat diet without (HF) or with the supplementation of fish oil (HF-FO) and treated with OLZ from postnatal day (PND) 37-65 resulting in four groups of mice: mice fed a HF diet and treated with OLZ (HF-OLZ), mice fed a HF diet and treated with vehicle (HF), mice fed a HF-FO diet and treated with OLZ (HF-FO-OLZ), and mice fed a HF-FO diet and treated with vehicle (HF-FO). Following euthanasia at approximately 164 days of age, we determined changes in gut bacteria populations and serum LPS binding protein, an established marker of gut inflammation and dysbiosis. Our results showed that male HF-FO and HF-FO-OLZ mice had lower body weights, at sacrifice, compared to the HF group, with a comparable body weight across groups in female mice. HF-FO and HF-FO-OLZ male groups also exhibited lower serum LPS binding protein levels compared to the HF group, with no differences across groups in female mice. Gut microbiota profiles were also different among the four groups; the Bacteroidetes-to-Firmicutes (B/F) ratio had the lowest value of 0.51 in the HF group compared to 0.6 in HF-OLZ, 0.9 in HF-FO, and 1.1 in HF-FO-OLZ, with no differences in female mice. In conclusion, FO reduced dietary obesity and its associated inflammation and increased the B/F ratio in male mice but did not benefit the female mice. Although the weight lowering effects of OLZ were unexpected, FO effects persisted in the presence of olanzapine, demonstrating its potential protective effects in male subjects using antipsychotic drugs.

The effects of fish oil plus vitamin D3 intervention on non-alcoholic fatty liver disease: a randomized controlled trial.

PURPOSE: The present study aimed to investigate fish oil plus vitamin D3 (FO + D) supplementation on biomarkers of non-alcoholic fatty liver disease (NAFLD). METHODS: In a 3-month randomized controlled trial, 111 subjects with NAFLD, aged 56.0 ± 15.9 y, were randomized into FO + D group (n = 37), fish oil group (FO, n = 37) or corn oil group (CO, n = 37). The subjects consumed the following capsules (3 g/day), which provided 2.34 g/day of eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) + 1680 IU vitamin D3 (FO + D group), or 2.34 g/day of EPA + DHA (FO group), or 1.70 g/d linoleic acid (CO group). RESULTS: Using multivariable-adjusted general linear model, there were significant net reductions in serum alanine aminotransferase (ALT), and triacylglycerol (TAG) and TNF-α levels in the FO + D and FO groups, compared with the control group (P < 0.05). The supplemental FO + D also showed significant reductions in insulin (- 1.58 ± 2.00 mU/L vs. - 0.63 ± 1.55 mU/L, P = 0.050) and IL-1ß (- 6.92 ± 7.29 ng/L vs. 1.06 ± 5.83 ng/L, P < 0.001) in comparison with control group. Although there were no significant differences between FO + D and FO groups regarding biochemical parameters, supplemental FO + D showed decreases in ALT (from 26.2 ± 13.5 U/L to 21.4 ± 9.6 U/L, P = 0.007), aspartate aminotransferase (AST, from 22.5 ± 7.0 U/L to 20.2 ± 4.0 U/L, P = 0.029), HOMA-IR (from 3.69 ± 1.22 to 3.38 ± 1.10, P = 0.047), and TNF-α (from 0.43 ± 0.38 ng/L to 0.25 ± 0.42 ng/L, P < 0.001) levels following the intervention. CONCLUSION: The present study demonstrated that groups supplemented with FO + D and FO had similar beneficial effects on biomarkers of hepatocellular damage and plasma TAG levels in subjects with NAFLD, while in the FO + D group, there were some suggestive additional benefits compared with FO group on insulin levels and inflammation. TRIAL REGISTRATION: ChiCTR1900024866.

Omega-3 fatty acid, carotenoid and vitamin E supplementation improves working memory in older adults: A randomised clinical trial.

BACKGROUND & AIMS: Accumulating evidence suggests that omega-3 fatty acids (ω-3FAs), carotenoids and vitamin E can improve cognitive performance. However, their collective impact on cognition has not yet been investigated in healthy individuals. This study investigated the combined effect of ω-3FA, carotenoid and vitamin E supplementation on the cognitive performance of older adults. METHODS: Cognitively healthy individuals aged ≥65 years consumed daily 1 g fish oil (of which 430 mg docosahexaenoic acid, 90 mg eicosapentaenoic acid), 22 mg carotenoids (10 mg lutein, 10 mg meso-zeaxanthin, 2 mg zeaxanthin) and 15 mg vitamin E or placebo for 24 months in a double-blind, placebo-controlled, randomised clinical trial. RESULTS: Following 24-month supplementation, individuals in the active group (n = 30; aged 69.03 ± 4.41 years; 56.7% female) recorded significantly fewer errors in working memory tasks than individuals receiving placebo (n = 30; aged 69.77 ± 3.74 years; 70% female) (point estimate effect sizes ranged 0.090-0.105). Interestingly, as the cognitive load of the working memory tasks increased, the active group outperformed the placebo group. Statistically significant improvements in tissue carotenoid concentrations, serum xanthophyll carotenoid concentrations and plasma ω-3FA concentrations were also observed in the active group versus placebo (point estimate effect sizes ranged 0.078-0.589). Moreover, the magnitude of change of carotenoid concentrations in tissue, and ω-3FA and carotenoid concentrations in blood were related to the magnitude of change in working memory performance. CONCLUSION: These results support a biologically plausible rationale whereby these nutrients work synergistically, and in a dose-dependent manner, to improve working memory in cognitively healthy older adults. Increasing nutritional intake of carotenoids and ω-3FAs may prove beneficial in reducing cognitive decline and dementia risk in later life. STUDY ID NUMBER: ISRCTN10431469; https://doi.org/10.1186/ISRCTN10431469.

Association between fish oil supplementation and cancer risk according to fatty fish consumption: A large prospective population-based cohort study using UK Biobank.

Whether regular fish oil supplementation is associated with cancer risk is controversial. We aimed to evaluate the association of fish oil supplementation on cancer risk according to fatty fish consumption patterns. From the UK Biobank cohort, 470 804 participants with fish oil supplementation data were included. A total of 147 316 individuals with fish oil supplementation were in the exposed group; the other 323 488 were in the unexposed group. No association was found between self-report regular fish oil supplementation and overall cancer risk (hazard ratio [HR] = 0.97, 95% confidence intervals [CIs] = 0.95-1). Stratified by fatty fish consumption level, we found the association between fish oil supplementation and lower cancer risk in participants who consumed fatty fish less than two times per week, with association noted for both overall cancer (HR = 0.96, 95% CI = 0.94-0.99) and some specific cancers (colon cancer: HR = 0.84, 95% CI = 0.75-0.94; hepatobiliary cancer: HR = 0.74, 95% CI = 0.58-0.96; lung cancer: HR = 0.87, 95% CI = 0.78-0.98). On the contrary, a higher risk of breast cancer was observed (HR = 1.16, 95% CI = 1.01-1.32) in participants who consumed fatty fish at least two times per week. In conclusion, our findings underscore the need to refine recommendations for nutritional supplements according to inherent diet habits.

Erythrocyte fatty acid membrane composition in children on long-term parenteral nutrition enriched with ω-3 fatty acids.

BACKGROUND: Composite lipid emulsions containing soybean oil (30%), medium-chain triglycerides (30%), olive oil (25%), and fish oil (15%) (SMOF) are now widely used. OBJECTIVES: We aimed to evaluate the tolerance, the efficiency, and the erythrocyte fatty acid (FA) profile for children on long-term home parenteral nutrition (HPN) receiving a composite fish oil-based emulsion (FOLE). METHODS: At baseline, children (n = 46) with severe intestinal failure highly dependent on parenteral nutrition (PN) for ≥1 y were included in the study when they had received the composite FOLE for >6 mo. Out of this baseline group, only 25 children remained highly PN-dependent (SMOF1, n = 25) and could be assessed a second time, 2.4 y later (SMOF2, n = 25). An independent control group ("weaned off PN" group; n = 24) included children who had been weaned off PN for >2 y (median: 4 y). RBC-FA composition was established by GC-MS. Growth parameters, plasma citrulline, conjugated bilirubin, FA profiles, and the Holman ratio (20:3ω-9/20:4ω-6) were compared between groups. RESULTS: No difference for growth parameters, citrulline, and bilirubin was observed between the SMOF groups after 2.4 y (0.2 < P < 0.8). The weaned-off group did not differ from the SMOF groups for growth parameters (0.2 < P < 0.4) but citrulline was higher (P < 0.0001) and conjugated bilirubin lower (P < 0.01). The composite FOLE induced higher proportions of EPA (20:5n-3) (8.4% ± 2.9%) and DHA (22:6n-3) (11.7% ± 2.2%) than what was observed in weaned-off children (0.8% ± 0.4% and 6.6% ± 2.3%, respectively) but lower proportions of arachidonic acid (20:4n-6). However, the Holman ratio did not vary between groups (P = 0.9), whereas the PUFA concentrations varied widely. CONCLUSIONS: Long-term use of the composite FOLE was well tolerated in HPN-dependent children. The RBC-FA profile alterations were consistent with the ω-3 PUFA-enriched composition of this emulsion without evidence of essential FA deficiency.

Fish oil supplementation and physical exercise during the development period increase cardiac antioxidant capacity in Wistar rats

Abstract Aim: To investigate if treadmill exercise (Ex) associated with fish oil (FO) supplementation during lactation would influence the biochemical profile as well as the oxidative balance in the hearts of male juvenile rats. Methods: Fifteen days-old rats were submitted to a daily moderate Ex training (based on their maximal running capacity) and FO supplementation for 4 weeks. Forty-eight hours after the last exercise session, blood fasting glucose and lipid profile were assessed according to the manufacturer's recommendations, while the oxidative status of the hearts was evaluated via colorimetric and absorbance-based assays. Results: FO associated with Ex decreased triglycerides (TG-79.27 ± 5.75 to 60.24 ± 6.25 mg/dL) and very-low-density lipoprotein cholesterol levels (VLDL-15.85 ± 1.15 to 12.05 ± 1.25 mg/dL) when compared to sedentary animals. FO, alone, reduced atherogenic index (AI- 1.14 ± 0.03 vs. 1.01 ± 0.04 a.u) while increased high-density lipoprotein cholesterol (HDL-43.90 ± 2.50 vs. 59.43 ± 3.15 mg/dL) of sedentary animals. Additionally, both Ex (67.3 ± 13.5 nmol/mg prot) and FO supplementation (56.6 ± 5.5 nmol/mg prot) decreased the oxidative damage to lipids in non-trained animals (105.8 ± 10.8 nmol/mg prot). The interventions also protected the protein content from oxidative stress (Ex- 5.15 ± 0.46; FO- 4.5 ± 0.5; and vehicle sedentary-7.3 ± 0.6 µmol/mg prot), while increasing the antioxidant defense and oxidative metabolism. Conclusion: Our findings suggest that intervention in juvenile rats can improve cardiac metabolism. These are the first findings to show the positive effects of the association between FO and moderate treadmill Ex during the critical period of development. We believe these results can drive early-life origins of heart disease through different avenues and, possibly, assist the development of a heart disease prevention program as well as an adjunctive therapeutic resource.

Krill-Oil-Dependent Increases in HS-Omega-3 Index, Plasma Choline and Antioxidant Capacity in Well-Conditioned Power Training Athletes.

There is evidence that both omega-3 polyunsaturated fatty acids (n-3 PUFAs) and choline can influence sports performance, but information establishing their combined effects when given in the form of krill oil during power training protocols is missing. The purpose of this study was therefore to characterize n-3 PUFA and choline profiles after a one-hour period of high-intensity physical workout after 12 weeks of supplementation. Thirty-five healthy power training athletes received either 2.5 g/day of Neptune krill oilTM (550 mg EPA/DHA and 150 mg choline) or olive oil (placebo) in a randomized double-blind design. After 12 weeks, only the krill oil group showed a significant HS-Omega-3 Index increase from 4.82 to 6.77% and a reduction in the ARA/EPA ratio (from 50.72 to 13.61%) (p < 0.001). The krill oil group showed significantly higher recovery of choline concentrations relative to the placebo group from the end of the first to the beginning of the second exercise test (p = 0.04) and an 8% decrease in total antioxidant capacity post-exercise versus 21% in the placebo group (p = 0.35). In conclusion, krill oil can be used as a nutritional strategy for increasing the HS-Omega-3 Index, recover choline concentrations and address oxidative stress after intense power trainings.

A Mixed-Lipid Emulsion Containing Fish Oil for the Parenteral Nutrition of Preterm Infants: No Impact on Visual Neuronal Conduction.

Fish oil is rich in omega-3 fatty acids and essential for neuronal myelination and maturation. The aim of this study was to investigate whether the use of a mixed-lipid emulsion composed of soybean oil, medium-chain triglycerides, olive oil, and fish oil (SMOF-LE) compared to a pure soybean oil-based lipid emulsion (S-LE) for parenteral nutrition had an impact on neuronal conduction in preterm infants. This study is a retrospective matched cohort study comparing preterm infants <1000 g who received SMOF-LE in comparison to S-LE for parenteral nutrition. Visual evoked potentials (VEPs) were assessed longitudinally from birth until discharge. The latencies of the evoked peaks N2 and P2 were analyzed. The analysis included 76 infants (SMOF-LE: n = 41 and S-LE: n = 35) with 344 VEP measurements (SMOF-LE: n= 191 and S-LE n = 153). Values of N2 and P2 were not significantly different between the SMOF-LE and S-LE groups. A possible better treatment effect in the SMOF-LE group was seen as a trend toward a shorter latency, indicating faster neural conduction at around term-equivalent age. Prospective trials and follow-up studies are necessary in order to evaluate the potential positive effect of SMOF-LE on neuronal conduction and visual pathway maturation.

Multi-Omics Interpretation of Anti-Aging Mechanisms for ω-3 Fatty Acids.

Aging is one of the hottest topics in biomedicine. Previous research suggested that ω-3 fatty acids have preventive effects on aging. However, most of previous studies on the anti-aging effects of ω-3 fatty acids are focused on clinical observations, and the anti-aging mechanisms of ω-3 fatty acids have not been fully elucidated. This stimulated our interest to use multi-omics data related to ω-3 fatty acids in order to interpret the anti-aging mechanisms of ω-3 fatty acids. First, we found that ω-3 fatty acids can affect methylation levels and expression levels of genes associated with age-related diseases or pathways in humans. Then, a Mendelian randomization analysis was conducted to determine whether there is a causal relationship between the effect of ω-3 fatty acids on blood lipid levels and variation in the gut microbiome. Our results indicate that the impact of ω-3 fatty acids on aging is partially mediated by the gut microbiome (including Actinobacteria, Bifidobacteria and Streptococcus). In conclusion, this study provides deeper insights into the anti-aging mechanisms of ω-3 fatty acids and supports the dietary supplementation of ω-3 fatty acids in aging prevention.

Impact of combined consumption of fish oil and probiotics on the serum metabolome in pregnant women with overweight or obesity.

BACKGROUND: If a pregnant woman is overweight, this can evoke metabolic alterations that may have health consequences for both mother and child. METHODS: Pregnant women with overweight/obesity (n = 358) received fish oil+placebo, probiotics+placebo, fish oil+probiotics or placebo+placebo from early pregnancy onwards. The serum metabolome was analysed from fasting samples with a targeted NMR-approach in early and late pregnancy. GDM was diagnosed by OGTT. FINDINGS: The intervention changed the metabolic profile of the women, but the effect was influenced by their GDM status. In women without GDM, the changes in nine lipids (FDR<0.05) in the fish oil+placebo-group differed when compared to the placebo+placebo-group. The combination of fish oil and probiotics induced changes in more metabolites, 46 of the lipid metabolites differed in women without GDM when compared to placebo+placebo-group; these included reduced increases in the concentrations and lipid constituents of VLDL-particles and less pronounced alterations in the ratios of various lipids in several lipoproteins. In women with GDM, no differences were detected in the changes of any metabolites due to any of the interventions when compared to the placebo+placebo-group (FDR<0.05). INTERPRETATION: Fish oil and particularly the combination of fish oil and probiotics modified serum lipids in pregnant women with overweight or obesity, while no such effects were seen with probiotics alone. The effects were most evident in the lipid contents of VLDL and LDL only in women without GDM. FUNDING: State Research Funding for university-level health research in the Turku University Hospital Expert Responsibility Area, Academy of Finland, the Diabetes Research Foundation, the Juho Vainio Foundation, Janssen Research & Development, LLC.

New Insights into Depressive Disorder with Respect to Low-Grade Inflammation and Fish Oil Intake.

Unipolar depression has been recognized as one of the major diseases by the World Health Organization in the 21st century. The etiology of depression is complicated and includes genetic factors, stress, aging, and special physical status (pregnancy, metabolic syndrome, and trauma). Numerous animal and human studies have demonstrated that n-3 polyunsaturated fatty acids (n-3 PUFAs) are highly correlated to cognition and depression. These nutritional antidepressants, including EPA and DHA, have a range of neurobiological activities contributing to their potential antidepressant effects. Our preclinical and clinical studies have indicated that n-3 PUFA supplementation in addition to standard antidepressant medications may provide synergistic neuroprotective and antioxidant/inflammatory effects. To translate our preliminary findings into clinical application, this paper reviews the existing evidence on the antidepressant effects of n-3 PUFAs and the potential underlying mechanisms, which include modulation of chronic lowgrade inflammation and the corresponding changes in peripheral blood immune biomarkers.

Short-Term Intake of Yellowstripe Scad versus Salmon Did Not Induce Similar Effects on Lipid Profile and Inflammatory Markers among Healthy Overweight Adults despite Their Comparable EPA+DHA Content.

Yellowstripe scad (YSS) have comparable eicosapentaenoic acid and docosahexaenoic acid (EPA+DHA) content to salmon. We aimed to compare the effects of YSS and salmon on lipid profile and inflammatory markers. A randomized crossover trial with two diet periods was conducted among healthy overweight (with BMI 23.0-27.4 kg/m2) Malaysian adults aged 21-55 years. Steamed whole YSS fish (≈385 g whole fish/day) or salmon fillets (≈246 g fillet/day) were given for eight weeks (3 days per week), retaining approximately 1000 mg EPA+DHA per day. Diets were switched after an 8-week washout period. Fasting blood samples were collected before and after each diet period. A total of 49 subjects participated in the intervention (35% male and 65% female; mean age 29 (7) years). YSS did not induce any significant changes in outcome measures. However, the consumption of salmon as compared with YSS was associated with reduction in triglycerides (between-group difference: -0.09 mmol/1, p = 0.01), VLDL-cholesterol (between-group difference: -0.04 mmol/1, p = 0.01), atherogenic index of plasma (between-group difference: -0.05 mmol/1, p = 0.006), and IL-6 (between-group difference: -0.01 pg/mL, p = 0.03). Despite their comparable EPA+DHA content, short-term consumption of salmon but not YSS induced significant changes in lipid profile and inflammatory markers. Larger clinical trials are needed to confirm the findings.

Effects of a Fish Oil Rich in Docosahexaenoic Acid on Cardiometabolic Risk Factors and Oxidative Stress in Healthy Rats.

Omega-3 polyunsaturated fatty acids are associated with a lower risk of cardiometabolic diseases. However, docosahexaenoic acid (DHA) is easily oxidized, leading to cellular damage. The present study examined the effects of an increased concentration of DHA in fish oil (80% of total fatty acids) on cardiometabolic risk factors and oxidative stress compared to coconut oil, soybean oil, and fish oil containing eicosapentaenoic acid (EPA) and DHA in a balanced ratio. Forty healthy male Sprague-Dawley rats were supplemented with corresponding oil for 10 weeks. Supplementation with the fish oil containing 80% DHA decreased plasma fat, plasma total cholesterol and muscle fat compared to the coconut oil and the soybean oil. Increasing concentrations of DHA induced incorporation of DHA and EPA in cell membranes and tissues along with a decrease in ω-6 arachidonic acid. The increase in DHA promoted lipid peroxidation, protein carbonylation and antioxidant response. Taken together, the increased concentration of DHA in fish oil reduced fat accumulation compared to the coconut oil and the soybean oil. This benefit was accompanied by high lipid peroxidation and subsequent protein carbonylation in plasma and in liver. In our healthy framework, the slightly higher carbonylation found after receiving fish oil containing 80% DHA might be a protecting mechanism, which fit with the general improvement of antioxidant defense observed in those rats.

Lipidomic changes of LDL after consumption of Camelina sativa oil, fatty fish and lean fish in subjects with impaired glucose metabolism-A randomized controlled trial.

BACKGROUND: There is little knowledge on the effects of alpha-linolenic acid (ALA) and n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) on the LDL lipidome and aggregation of LDL particles. OBJECTIVE: We examined if consumption of Camelina sativa oil (CSO) as a source of ALA, fatty fish (FF) as a source of n-3 LCPUFA and lean fish (LF) as a source of fish protein affect the lipidome of LDL as compared to a control diet. METHODS: Participants with impaired glucose tolerance (39 women and 40 men) were randomized to 4 study groups (CSO providing 10 g/d ALA, FF and LF [both 4 fish meals/wk] and control limiting their fish and ALA intake) in a 12-week, parallel trial. Diets were instructed and dietary fats were provided to the participants. The lipidome of LDL particles isolated from samples collected at baseline and after intervention was analyzed with electrospray ionization-tandem mass spectrometry. RESULTS: In the CSO group, the relative concentrations of saturated and monounsaturated cholesteryl ester species in LDL decreased and the species with ALA increased. In the FF group, LDL phosphatidylcholine (PC) species containing n-3 LCPUFA increased. There was a significant positive correlation between the change in total sphingomyelin and change in LDL aggregation, while total PC and triunsaturated PC species were inversely associated with LDL aggregation when all the study participants were included in the analysis. CONCLUSION: Dietary intake of CSO and FF modifies the LDL lipidome to contain more polyunsaturated and less saturated lipid species. The LDL surface lipids are associated with LDL aggregation.