Comparison of two formulations of intravenous lipid emulsions in pediatric intestinal failure.

PURPOSE: The effect of different types of lipid emulsion may guide therapy of patients with intestinal failure (IF) to limit morbidity such as intestinal failure-associated liver disease (IFALD). METHODS: A retrospective chart review of pediatric patients with IF who received soybean oil lipid emulsion (SL) or mixed oil lipid emulsion (ML) was performed. Data over 1 year were collected. RESULTS: Forty-five patients received SL and 34 received ML. There were no differences in the incidence (82 versus 74%, P = 0.35) or resolution (86 versus 92%, P = 0.5) of IFALD between the cohorts. The median dose of ML was higher compared to SL (2 versus 1 g/kg/day, P < 0.001). If resolved, IFALD resolved rapidly in the ML cohort compared to the SL cohort (67 versus 37 days, P = 0.01). Weight gain was higher in the ML compared to the SL cohort at resolution of IFALD or 1 year from diagnosis of IF (P = 0.009). CONCLUSION: The administration of ML did not alter the incidence or resolution of IFALD compared to SL in pediatric IF. There was rapid resolution of IFALD and enhanced weight gain in the ML cohort compared to SL in pediatric IF.

Fish oil supplementation during pregnancy, anthropometrics, and metabolic health at age ten: A randomized clinical trial.

BACKGROUND: We previously reported that children of mothers who received fish oil supplementation during pregnancy had higher body mass index [BMI (in kg/m2)] at 6 y of age as well as a concomitant increase in fat-, muscle, and bone mass, but no difference in fat percentage. OBJECTIVES: Here, we report follow-up at age 10 y including assessment of metabolic health. METHODS: This is a follow-up analysis of a randomized clinical trial conducted among 736 pregnant females and their offspring participating in the Copenhagen Prospective Studies on Asthma in Childhood mother-child cohort. The intervention was 2.4 g n-3 (ω-3) Long-Chain PolyUnsaturated Fatty Acid (n-3 LCPUFA) or control daily from pregnancy week 24 until 1 wk after birth. Outcomes were anthropometric measurements, body composition from Bioelectrical Impedance Analysis, blood pressure, concentrations of triglycerides, cholesterol, glucose, and C-peptide from fasting blood samples, and a metabolic syndrome score was calculated. Anthropometric measurements and body composition were prespecified secondary endpoints of the n-3 LCPUFA trial, and others were exploratory. RESULTS: Children in the n-3 LCPUFA group had a higher mean BMI at age 10 year compared to the control group: 17.4 (SD: 2.44) compared with 16.9 (2.28); P = 0.020 and a higher odds ratio of having overweight (odds ratio: 1.53; 95% CI: 1.01, 2.33; P = 0.047). This corresponded to differences in body composition in terms of increased lean mass (0.49 kg; 95% CI: -0.20, 1.14; P = 0.17), fat mass (0.49 kg; 95% CI: -0.03, 1.01; P = 0.06), and fat percent (0.74%; 95% CI: -0.01, 1.49; P = 0.053) compared to the control group. Children in the n-3 LCPUFA group had a higher metabolic syndrome score compared to the control (mean difference: 0.19; 95% CI: -0.02, 0.39; P = 0.053). CONCLUSIONS: In this randomized clinical trial, children of mothers receiving n-3 LCPUFA supplementation had increased BMI at age 10 y, increased risk of being overweight, and a tendency of increased fat percentage and higher metabolic syndrome score. These findings suggest potential adverse health effects from n-3 LCPUFA supplementation during pregnancy and need to be replicated in future independent studies. This trial was registered at clinicaltrials.gov as NCT00798226.

Unexpected omega-3 activities in intracellular lipolysis and macrophage foaming revealed by fluorescence lifetime imaging.

Omega-3 polyunsaturated fatty acids (PUFA) found primarily in fish oil have been a popular supplement for cardiovascular health because they can substantially reduce circulating triglyceride levels in the bloodstream to prevent atherosclerosis. Beyond this established extracellular activity, here, we report a mode of action of PUFA, regulating intracellular triglyceride metabolism and lipid droplet (LD) dynamics. Real-time imaging of the subtle and highly dynamic changes of intracellular lipid metabolism was enabled by a fluorescence lifetime probe that addressed the limitations of intensity-based fluorescence quantifications. Surprisingly, we found that among omega-3 PUFA, only docosahexaenoic acid (DHA) promoted the lipolysis in LDs and reduced the overall fat content by approximately 50%, and consequently helped suppress macrophage differentiation into foam cells, one of the early steps responsible for atherosclerosis. Eicosapentaenoic acid, another omega-3 FA in fish oil, however, counteracted the beneficial effects of DHA on lipolysis promotion and cell foaming prevention. These in vitro findings warrant future validation in vivo.

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.

Association of Plasma n-3 Polyunsaturated Fatty Acid Levels and the Prevalence of Frailty in Older Adults: A Cross-Sectional Analysis of UK Biobank.

BACKGROUND: Circulating levels of n-3 polyunsaturated fatty acids (PUFAs) have been associated with frailty among Koreans (a population with a high intake of fish), but whether this association exists in Western populations with low fish intake is unknown. The present study examined the hypothesis that the prevalence of frailty was inversely associated with plasma levels of n-3 PUFAs, with the intake of oily fish, and with fish oil supplementation in older adults in the United Kingdom. METHODS: UK Biobank including 79 330 adults aged ≥65 years with dietary data, and 18 802 participants with plasma fatty acid data were used. Frailty was defined using the Cardiovascular Health Study index, plasma levels of n-3 PUFAs were measured by nuclear magnetic resonance, and intake of oily fish and/or fish oil supplements was collected via food frequency questionnaire. RESULTS: Frailty prevalence was inversely associated with n-3 PUFA levels [odds ratios (OR) per SD: 0.86, 95% confidence interval (CI) 0.79-0.94; p < .001], with oily fish intake (never vs ≥2 servings per week; OR 0.59, 95% CI 0.52-0.68, p < .001), and with the use of fish oil supplements (OR 0.72; 95% CI 0.66-0.78; p < .001) after adjusting for confounding factors. All 3 exposures were also associated with each frailty criterion, particularly low physical activity and walking pace. CONCLUSIONS: Inverse associations between plasma n-3 PUFA levels and measures of frailty suggest that higher intakes of oily fish or the use of fish oil supplements may help prevent frailty in older adults in the United Kingdom.

A ketogenic diet rich in fish oil is superior to other fats in preventing NNK-induced lung cancer in A/J mice.

Given that ketogenic diets (KDs) are extremely high in dietary fat, we compared different fats in KDs to determine which was the best for cancer prevention. Specifically, we compared a Western and a 15% carbohydrate diet to seven different KDs, containing either Western fats or fats enriched in medium chain fatty acids (MCTs), milk fat (MF), palm oil (PO), olive oil (OO), corn oil (CO) or fish oil (FO) for their ability to reduce nicotine-derived nitrosamine ketone (NNK)-induced lung cancer in mice. While all the KDs tested were more effective at reducing lung nodules than the Western or 15% carbohydrate diet, the FO-KD was most effective at reducing lung nodules. Correlating with this, mice on the FO-KD had low blood glucose and the highest ß-hydroxybutyrate level, lowest liver fatty acid synthase/carnitine palmitoyl-1a ratio and a dramatic increase in fecal Akkermansia. We found no liver damage induced by the FO-KD, while the ratio of total cholesterol/HDL was unchanged on the different diets. We conclude that a FO-KD is superior to KDs enriched in other fats in reducing NNK-induced lung cancer, perhaps by being the most effective at skewing whole-body metabolism from a dependence on glucose to fats as an energy source.

Thermodynamic Analysis to Evaluate the Effect of Diet on Brain Glucose Metabolism: The Case of Fish Oil.

Inefficient glucose metabolism and decreased ATP production in the brain are linked to ageing, cognitive decline, and neurodegenerative diseases (NDDs). This study employed thermodynamic analysis to assess the effect of fish oil supplementation on glucose metabolism in ageing brains. Data from previous studies on glucose metabolism in the aged human brain and grey mouse lemur brains were examined. The results demonstrated that Omega-3 fish oil supplementation in grey mouse lemurs increased entropy generation and decreased Gibbs free energy across all brain regions. Specifically, there was a 47.4% increase in entropy generation and a 47.4 decrease in Gibbs free energy in the whole brain, indicating improved metabolic efficiency. In the human model, looking at the specific brain regions, supplementation with Omega-3 polyunsaturated fatty acids (n-3 PUFAs) reduced the entropy generation difference between elderly and young individuals in the cerebellum and particular parts of the brain cortex, namely the anterior cingulate and occipital lobe, with 100%, 14.29%, and 20% reductions, respectively. The Gibbs free energy difference was reduced only in the anterior cingulate by 60.64%. This research underscores that the application of thermodynamics is a comparable and powerful tool in comprehending the dynamics and metabolic intricacies within the brain.

Effect of Dietary Supplementation with Omega-3 Fatty Acid on the Generation of Regulatory T Lymphocytes and on Antioxidant Parameters and Markers of Oxidative Stress in the Liver Tissue of IL-10 Knockout Mice.

INTRODUCTION: chronic low-grade inflammation, or inflammaging, emerges as a crucial element in the aging process and is associated with cardiovascular and neurological diseases, sarcopenia, and malnutrition. Evidence suggests that omega-3 fatty acids present a potential therapeutic agent in the prevention and treatment of inflammatory diseases, mitigating oxidative stress, and improving muscle mass, attributes that are particularly relevant in the context of aging. The objective of the present study was to evaluate the effectiveness of supplementation with omega-3 fish oil in improving the immune response and oxidative stress in knockout mice for interleukin IL-10 (IL-10-/-). MATERIAL AND METHODS: female C57BL/6 wild-type (WT) and interleukin IL-10 knockout (IL-10-/-) mice were fed during 90 days with a standard diet (control groups), or they were fed/supplemented with 10% of the omega-3 polyunsaturated fatty acid diet (omega-3 groups). Muscle, liver, intestinal, and mesenteric lymph node tissue were collected for analysis. RESULTS: the IL-10-/-+O3 group showed greater weight gain compared to the WT+O3 (p = 0.001) group. The IL-10-/-+O3 group exhibited a higher frequency of regulatory T cells than the IL-10-/- group (p = 0.001). It was found that animals in the IL-10-/-+O3 group had lower levels of steatosis when compared to the IL-10-/- group (p = 0.017). There was even greater vitamin E activity in the WT group compared to the IL-10-/-+O3 group (p = 0.001) and WT+O3 compared to IL-10-/-+O3 (p = 0.002), and when analyzing the marker of oxidative stress, MDA, an increase in lipid peroxidation was found in the IL-10-/-+O3 group when compared to the IL-10-/- group (p = 0.03). Muscle tissue histology showed decreased muscle fibers in the IL-10-/-+O3, IL-10-/-, and WT+O3 groups. CONCLUSION: the findings show a decrease in inflammation, an increase in oxidative stress markers, and a decrease in antioxidant markers in the IL-10-/-+O3 group, suggesting that supplementation with omega-3 fish oil might be a potential intervention for inflammaging that characterizes the aging process and age-related diseases.

Effect of Lifelong Exposure to Dietary Plant and Marine Sources of n-3 Polyunsaturated Fatty Acids on Morphologic and Gene Expression Biomarkers of Intestinal Health in Early Life.

Altered intestinal health is also associated with the incidence and severity of many chronic inflammatory conditions, which could be attenuated via dietary n-3 PUFA interventions. However, little is known about the effect of lifelong exposure to n-3 PUFA from plant and marine sources (beginning in utero via the maternal diet) on early life biomarkers of intestinal health. Harems of C57Bl/6 mice were randomly assigned to one of three isocaloric AIN-93G modified diets differing in their fat sources consisting of the following: (i) 10% safflower oil (SO, enriched in n-6 PUFA), (ii) 3% flaxseed oil + 7% safflower oil (FX, plant-based n-3 PUFA-enriched diet), or (iii) 3% menhaden fish oil + 7% safflower oil (MO, marine-based n-3 PUFA-enriched diet). Mothers remained on these diets throughout pregnancy and offspring (n = 14/diet) continued on the same parental diet until termination at 3 weeks of age. In ileum, villi:crypt length ratios were increased in both the FX and MO dietary groups compared to SO (p < 0.05). Ileum mRNA expression of critical intestinal health biomarkers was increased by both n-3 PUFA-enriched diets including Relmß and REG3γ compared to SO (p < 0.05), whereas only the FX diet increased mRNA expression of TFF3 and Muc2 (p < 0.05) and only the MO diet increased mRNA expression of ZO-1 (p < 0.05). In the proximal colon, both the FX and MO diets increased crypt lengths compared to SO (p < 0.05), whereas only the MO diet increased goblet cell numbers compared to SO (p < 0.05). Further, the MO diet increased proximal colon mRNA expression of Relmß and REG3γ (p < 0.05) and both MO and FX increased mRNA expression of Muc2 compared to SO (p < 0.05). Collectively, these results demonstrate that lifelong exposure to dietary n-3 PUFA, beginning in utero, from both plant and marine sources, can support intestinal health development in early life. The differential effects between plant and marine sources warrants further investigation for optimizing health.

Comparison of treatment efficacy of omega-3 fish oil and montelukast in ovalbumin-protease-induced allergic rhinitis model in rats.

OBJECTIVES: Montelukast is a well-known leukotriene receptor antagonist commonly used in treating allergic rhinitis and asthma. Omega-3 fatty acid is also known as an antiallergic and immunomodulator molecule. This study aimed to elucidate the efficacy of systemic montelukast and omega-3 fatty acid treatment in allergic rhinitis models in Wistar Hannover rats. METHODS: This research was conducted on 28 healthy Wistar Hannover rats weighing 250-350 g. After establishing the allergic rhinitis model, nasal symptoms were observed and scored, and the nasal mucosa of all rats was investigated histologically. Light microscopy was utilized to evaluate the degree of ciliary loss, goblet cell hyperplasia, vascular congestion, vascular proliferation, inflammatory cell infiltration, eosinophil infiltration, and hypertrophy in chondrocytes. RESULTS: As a result of the analysis of the data obtained from the study, it was determined that typical allergic rhinitis symptoms such as nasal scratching and sneezing were significantly reduced in the rats in the montelukast and omega-3 treated group, and these symptoms did not increase after repeated intranasal OVA-protease applications. Histological examinations after fish oil treatment did not reveal typical inflammatory changes in allergic rhinitis. None of the rats in the montelukast and omega-3 groups had any increase in goblet cells, whereas 14.3% of the rats in the control group and 28.6% of the rats in the allergic rhinitis group had mild increase. Last but not least, 71.4% of rats in the allergic rhinitis group had a moderate increase. The difference between the groups was statistically significant (p < 0.001). CONCLUSION: Regarding the outcomes of this research, it was observed that w-3 fatty acids had antiallergic effects, both histopathological and clinical, in the allergic rhinitis model. We believe that further randomized controlled trials incorporating larger cohorts are warranted to verify the use of omega-3 fatty acids in treating allergic rhinitis. The level of evidence of this article is Level 2.

Amelioration of obesity induction by a high-fat diet and related inflammation by Phasa fish (Setipinna phasa) oil in BALB/c mice.

We have extracted and characterized Phasa fish (Setipinna phasa) oil for the first time to evaluate the anti-obesity and related anti-inflammatory effects on obese mice. Inbred male albino BALB/c mice were segregated into three categories: control (C), Obese control group (OC), and Phasa fish oil treated group (TX). To establish the potentiality of Setipinna phasa oil for its anti-obesity and anti-inflammatory properties, it was extracted and characterized using GC-MS method. To evaluate the anti-obesity effect, different parameters were considered, such as body weight, lipid composition, obesity, and obesity associated inflammation. The physicochemical characteristics of Phasa fish oil revealed that the oil quality was good because acid value, peroxide value, p-anisidine value, Totox value, refractive index, and saponification value were within the standard value range. The GC-MS study explored the presence of fatty acids beneficial to health such as Hexadec-9-enoic acid; Octadec-11-enoic acid; EPA, DHA, Methyl Linolenate, etc. The application of Setipinna phasa oil on the treated mice group acutely lowered body weight and serum lipid profile compared to the obese group. In connection with this, leptin, FAS, and pro-inflammatory cytokines TNF-α genes expression were downregulated in the treated group compared to the obese group. The Phasa oil treated group had an elevated expression of PPAR-α, adiponectin, LPL gene, and anti-inflammatory markers IL-10 and IL-1Ra compared to the obese group. This study suggests that Phasa fish oil, enriched with essential fatty acid, might be used as an anti-obesity and anti-inflammatory supplement.

Feasibility of replacing fish oil with sunflower oil on the growth, body composition, fatty acid profile, antioxidant activity, stress response, and blood biomarkers of Labeo rohita.

A 90-day study was conducted to investigate the effects of substituting sunflower oil (SFO) for fish oil (FO) on various parameters in Labeo rohita (initial weight 18.21 ± 0.22 g). Five experimental diets with different levels of SFO (up to 7%) substitution for FO (0%, 25%, 50%, 75%, and 100%) were formulated, ensuring equal levels of nitrogen and lipids. The results indicated that even with 100% substitution of SFO with FO, there were no significant differences (P>0.05) were observed in growth performance. The survival rate (SR), hepato-somatic index (HSI), and viscero-somatic index (VSI) as well as whole-body composition were also nonsignificant by SFO substitution. However, the fatty acid profiles in both muscle and liver were influenced (P<0.05) by dietary substitution. Saturated fats (SFA) decreased, while monounsaturated fats (MUFA), and linoleic acid (LA) increased (P<0.05). On the other hand, the contribution of linolenic acid (ALA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) decreased (P<0.05) as the amount of SFO in the diet increased. Hematology parameters, including red blood cells (RBCs), hemoglobin (Hb), and hematocrit (Hct), were not affected. Globulin (GLO) levels decreased significantly (P<0.05), while alanine transaminase (ALT) and aspartate transaminase (AST) activity showed nonsignificant increases (P>0.05). Total protein (TP) increased (P<0.05) at 100% SFO inclusion in the diet, and albumin (ALB) levels increased (P<0.05) at 75% and 100% SFO inclusion in the diet. Cholesterol (CHOL), triacylglycerol (TG), and high-density lipids (HDL) were not significantly affected (P>0.05), while low-density lipids (LDL) were significantly increased (P<0.05) compared to the control group. Cortisol (CORT) and glucose (GLU) levels showed nonsignificant (P>0.05) changes. Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities in the liver and serum were not significantly (P>0.05) affected, while malondialdehyde (MDA) status was significantly (P<0.05) reduced. In conclusion, the fatty acid profile of the muscle and liver of fish was modified by the diets, and FO can be substituted with SFO up to 100% for L. rohita, which is beneficial for growth and immunity while marinating the lipid contents in fish. Our study revealed that fully replacing fish oil with SFO shows promise in fully replacing FO without compromising the growth and overall health status of the fish.

Polychlorinated Biphenyl Concentrations and Estimated Intakes in Fish Oil Supplements on the Japanese Market.

Polychlorinated biphenyls (PCBs) are synthetic organic contaminants that are widespread in the environment. There are 209 PCB congeners. Fish oil produced from marine fish is widely used as a health supplement. PCB contamination of fish oil is of concern. We determined the concentrations of all 209 PCB congeners in commercially available fish oil supplements from Japan and estimated PCB intakes for humans consuming the supplements. We determined the concentrations of non-dioxin-like PCBs separately. The total PCB concentrations in 37 fish oil supplements purchased in Japan were 0.024-19 ng/g whole weight, and the non-dioxin-like PCB concentration range was also 0.024-19 ng/g whole weight. The total PCB intakes calculated for a 50 kg human consuming the supplements were 0.039-51 ng/day (0.00078-1.0 ng/(kg body weight per day)) and the non-dioxin-like PCB intake range was also 0.039-51 ng/day (0.00078-1.0 ng/(kg body weight per day)). The total PCB intakes were much lower than the tolerable daily intake of 20 ng/(kg body weight per day) recommended by the WHO. The results indicated that PCBs in the fish oil supplements pose acceptable risks to humans consuming the fish oil supplements daily.

Toxicological evaluation of a fish oil concentrate containing Very Long Chain Fatty Acids.

Very long chain fatty acids (VLCFA) have a chain length ≥24 carbons. Fish contain low levels of these fatty acids. A commercial oil called EPAX® Evolve 05 with an up-concentration of VLCFAs of approximately 10 times, has been developed as a dietary supplement by Epax Norway AS. A series of toxicological studies were performed using mice and rats to determine the safety and toxicity of repeat dosing with a gavage administered VLCFA formulation. The results suggest transient lipid accumulation in kidneys and liver. Lipid accumulation was seen with the test item and with the soya control but was not dose related. Liver and kidney lipid accumulation, whilst present in 14- day repeat dose study, was absent in a 90-day rat study. No treatment-effect was seen in urine analysis in any of the studies. No treatment-related effects were seen with a functional observation battery, ophthalmological examination, haematology, urine analysis, oestrus cycle, thyroid hormones, organ weight, or histopathology. In the 90-day study the liver enzymes ALP, AST and ALT were statistically significantly increased with test item but within control values. There were no associated histological findings in the liver suggesting there was no toxic effect and the normalisation of values for all liver enzymes in the recovery groups suggests an adaptive response rather than a prevailing toxic response. The no-observed-adverse-effect level (NOAEL) was determined as 1200 mg VLCFA/kg b.w./day.

Fish oil supplementation and risk of dementia among diabetic patients: a prospective study of 16,061 older patients.

BACKGROUND: Although n-3 Polyunsaturated fatty acids (PUFAs) may benefit cognitive performance, the association of n-3 PUFA intake with dementia risk under dysglycemia has not been examined. We aimed to evaluate the relationship between fish oil supplement use or fish consumption and dementia risk among older patients with diabetes. METHOD: A total of 16,061 diabetic patients aged over 60 years were followed up in the UK Biobank. Fish oil supplements use (yes or no) was collected by the touch screen questionnaire. The diagnosis of dementia was ascertained by the UK Biobank Outcome Adjudication Group. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated using Cox proportional hazards models. RESULTS: A total of 337 cases of dementia were confirmed after a mean duration of 7.7 years (123,486 person-years) of follow-up. Habitual use of fish oil supplements showed a 24% lower dementia risk among older diabetic patients [HRs (95% CIs): 0.76 (0.60-0.98) (P = 0.031)] compared with non-users. Such inverse association was not modified by the APOE ε4 genotype. However, the consumption of both oily fish (≥2 times/week) and non-oily fish (≥2 times/week) had no significant association with dementia risk (p-trend = 0.271 and p-trend = 0.065) compared with non-consumers. CONCLUSION: In summary, fish oil supplementation may play a protective role in cognitive function across all APOE genotypes, while non-oily fish and oily fish consumption have no protective association among older diabetic patients.

High Dose Fish Oil Added to Various Lipid Emulsions Normalizes Superoxide Dismutase 1 Activity in Home Parenteral Nutrition Patients.

(1) Objectives: Intestinal failure in home parenteral nutrition patients (HPNPs) results in oxidative stress and liver damage. This study investigated how a high dose of fish oil (FO) added to various lipid emulsions influences antioxidant status and liver function markers in HPNPs. (2) Methods: Twelve HPNPs receiving Smoflipid for at least 3 months were given FO (Omegaven) for a further 4 weeks. Then, the patients were randomized to subsequently receive Lipoplus and ClinOleic for 6 weeks or vice versa plus 4 weeks of Omegaven after each cycle in a crossover design. Twelve age- and sex-matched healthy controls (HCs) were included. (3) Results: Superoxide dismutase (SOD1) activity and oxidized-low-density lipoprotein concentration were higher in all baseline HPN regimens compared to HCs. The Omegaven lowered SOD1 compared to baseline regimens and thus normalized it toward HCs. Lower paraoxonase 1 activity and fibroblast growth factor 19 (FGF19) concentration and, on the converse, higher alkaline phosphatase activity and cholesten concentration were observed in all baseline regimens compared to HCs. A close correlation was observed between FGF19 and SOD1 in baseline regimens. (4) Conclusions: An escalated dose of FO normalized SOD1 activity in HPNPs toward that of HCs. Bile acid metabolism was altered in HPNPs without signs of significant cholestasis and not affected by Omegaven.

Comparison of fish oil supplements and corn oil effects on serum lipid profile: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The present study aimed to investigate the effects of fish oil supplements compared to corn oil on serum lipid profiles by performing a meta-analysis of randomized controlled trials (RCTs). METHODS: Online databases including PubMed, Web of Science, and Scopus were searched until 30 December 2022. Pooled effect sizes were reported as the weighted mean difference (WMD) with 95% confidence intervals (CI). The Cochrane Collaboration's risk-of-bias tool was utilized to evaluate the quality of the studies. Lipid parameters, including triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL), and high-density lipoprotein cholesterol (HDL), were assessed in the meta-analysis. RESULTS: Overall, 16 eligible trials were included in this systematic review and meta-analysis. The results revealed that the fish oil supplements significantly reduced TG (WMD: - 25.50 mg/dl, 95% CI: - 42.44, - 8.57, P = 0.000) levels compared to corn oil. Also, in this study, fish oil supplements had a positive and significant effect on HDL (WMD: 2.54 mg/dl, 95% CI: 0.55, 4.52). There were no significant changes in TC and LDL. CONCLUSIONS: Our findings showed the effects of fish oil supplements on reducing TG and increasing HDL-c compared to corn oil. Further larger and well-designed RCTs are required to confirm these data.