Polyunsaturated Fatty Acid Supplementation Research Articles

N-3 fatty acids and the risk of atrial fibrillation, review.

Atrial fibrillation (AF) is the most frequent type of cardiac arrhythmia that affects over six million individuals in Europe. The incidence and prevalence of AF rises with age, and often occurs after cardiac surgery. Other risk factors correlated with AF comprise high blood pressure, diabetes mellitus, left atrial enlargement, ischemic heart disease, and congestive heart failure. Considering the high prevalence of AF in aging societies, strategies to prevent serious complications, such as stroke or heart failure, are important because they are correlated with high morbidity and mortality. The supplementation of sea-derived n-3 polyunsaturated fatty acids (PUFA) is widely discussed in this context, but the results of experimental and observational studies are in contrast to randomized placebo-controlled intervention trials (RCTs). Specifically, larger placebo-controlled n-3 PUFA supplementation studies with long follow-up showed a dose-dependent rise in incident AF. Daily n-3 PUFA doses of≥1 g/d are correlated with a 50 % increase in AF risk, whereas a daily intake of <1 g/d causes AF in only 12 %. Individuals with a high cardiovascular risk (CVD) risk and high plasma-triglycerides seem particularly prone to develop AF upon n-3 PUFA supplementation. Therefore, we should exercise caution with n-3 PUFA supplementation especially in patients with higher age, CVD, hypertriglyceridemia or diabetes. In summary, existing data argue against the additive intake of n-3 PUFA for preventative purposes because of an incremental AF risk and lacking CVD benefits. However, more clinical studies are required to disentangle the discrepancy between n-3 PUFA RCTs and observational studies showing a lower CVD risk in individuals who regularly consume n-3 PUFA-rich fish.

Synergistic effects of Ω-3 polyunsaturated fatty acid supplementation and programmed cell death protein 1 blockade on tumor growth and immune modulation in a xenograft model of esophageal cancer

Synergistic effects of Ω-3 polyunsaturated fatty acid supplementation and programmed cell death protein 1 blockade on tumor growth and immune modulation in a xenograft model of esophageal cancer

Therapeutic advantages of omega-3 fatty acid supplementation in patients with schizophrenia – a systematic review

Introduction and aim. In patients with schizophrenia, omega-3 (n-3) polyunsaturated fatty acids (PUFAs) treatment was found to ameliorate the cardiovascular, metabolic, and inflammatory problems caused by antipsychotic medication and even reduce the need for medication by 20%. In this study, we evaluated the potential therapeutic effects of n-3 PUFA supplementation in patients with schizophrenia. Material and methods. The PRISMA guidelines were followed in conducting this systematic review. The Embase, MEDLINE, Web of Science, and Google Scholar databases were searched electronically. The first search yielded 50 papers in total. Subse quently, 43 publications that did not meet our eligibility requirements were removed, and seven articles were selected. Analysis of the literature. The analysis showed that n-3 PUFA supplementation and the placebo group both decreased their psychotic (PANSS and GAF scales) and Calgary Depression Scale symptomatology and boosted their functional ability (GAF) when used as an adjuvant to antipsychotic medication. When administered as a monotherapy with a metabolic antioxidant, n-3 PUFA supplementation proved beneficial for treating schizophrenia. In patients with schizophrenia, n-3 PUFAs have thera peutic benefits as adjuvant treatments to medications, although not for different variables or patient groups. Conclusion. In many studies, patients with chronic schizophrenia who received n-3 PUFA supplementation showed no improvement in their clinical condition.

Abstract 438: Inhibition of de novo lipogenesis with PUFA supplementation induces ferroptosis in advanced prostate cancer

Abstract Background: Metabolic alterations are recognized as a hallmark of cancer progression. In prostate cancer (PCa), in particular, a notable lipid reprogramming occurs with increased expression levels of multiple enzymes involved in the fatty acid synthesis pathway to fulfill the metabolic and structural demands of cancer cells. Fatty acids are vital for membrane building, ATP production through B-oxidation, and storage in lipid droplets for high-energy demands. In castration-resistant prostate cancer (CRPC), the aberrant overexpression of Fatty Acid Synthase (FASN), the rate-limiting enzyme in de novo lipogenesis (DNL), results in synthesis of saturated (palmitate) and monounsaturated fatty acids (SFA and MUFA). If DNL is inhibited, polyunsaturated fatty acids (PUFAs) are taken up from the environment. These could undergo lipid peroxidation generating reactive oxygen species (ROS) and contribute to ferroptosis. We hypothesize that combining the inhibition of DNL with the addition of exogenous PUFAs could increase cell death by ferroptosis. Methods: PCa cells (LNCaP, 22Rv1 and C4-2) and human organoids were exposed to pharmacologic FASN inhibition and PUFAs for 6 days. Cell viability, lipid peroxidation, superoxide production and, protein carbonylation as a measure of intracellular ROS as well as lipidomic profiling, were assessed. Results: FASN inhibition significantly increased lipid peroxidation and intracellular ROS, with subsequent membrane potential hyperpolarization in prostate cancer cells. These effects were partially rescued by palmitate, while FASNi supplemented with PUFA potentiated protein carbonylation. Expression levels of GPX4, the main regulator of ferroptosis, were reduced after DNL inhibition and rescued with palmitate addition. Suppression of DNL combined with supplemental addition of PUFAs resulted in significant cell growth inhibition in prostate cancer cells and organoids. Finally, lipid profiling demonstrated that the suppression of DNL triggers increased acyl chain length in phospholipid and several other lipid classes. Again, this effect was significantly potentiated when combining FASN inhibition with PUFA supplementation. Conclusion: FASN inhibition produces a cascade of intracellular events, including lipid remodeling, increased ROS production and ferroptosis, all potentiated by PUFAs. These findings provide compelling evidence for the use a combined approach involving DNL inhibition and PUFA supplementation as a novel therapeutic avenue to treat advanced prostate cancer. Citation Format: Silvia Daniele Rodrigues, Isadora Ferrari Teixeira, Pier Vitale Nuzzo, Hubert Pakula, David Nanus, Massimo Loda. Inhibition of de novo lipogenesis with PUFA supplementation induces ferroptosis in advanced prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 438.

A placebo-controlled, double-blind study evaluating the effect of orally administered polyunsaturated fatty acids on the oclacitinib dose for atopic dogs.

Supplementation of polyunsaturated fatty acids (PUFA) enables dose reduction of prednisolone and ciclosporin in canine atopic dermatitis (cAD). To determine if oral administration of PUFA reduces the dose of oclacitinib in cAD. Twenty-two client-owned dogs with cAD receiving oclacitinib. Dogs received a fish oil product (PUFA) or paraffin oil (placebo) for 16 weeks. Owners adjusted the oclacitinib dose according to daily pruritus assessments. On Day (D)0, D56 and D112, Canine Atopic Dermatitis Extent and Severity Index, fourth iteration (CADESI-04), pruritus Visual Analog Scale (PVAS), quality-of-life score (QoL), Global Assessment (GA), quality-of-coat (QoC) and adverse events were recorded. Mean daily oclacitinib dose was significantly reduced in the PUFA group from 0.51 ± 0.20 mg/kg/24 h (D0) to 0.19 ± 0.14 mg/kg/24 h (D85-112; p < 0.00001) and not in the placebo group (D0: 0.70 ± 0.33 mg/kg/24 h; D85-112: 0.53 ± 0.35 mg/kg/24 h, p = 0.5422). CADESI-04 did not change over time or differ between groups. PVAS was significantly lower in the PUFA group (2.8 ± 1.5) compared to placebo (4.2 ± 1.6) at D112 (p = 0.0375). QoL and QoC improved only in the PUFA group (QoL: D0: 20 ± 7, D112: 12 ± 5, p = 0.0057; QoC: D0: 0 ± 0.5, D112: 1 ± 0.5, p = 0.0410). GA on D112 was higher in the PUFA group (p = 0.008). No adverse events were observed. Oral supplementation of PUFA allowed dose reduction of oclacitinib and improved PVAS, QoL, QoC and GA. The use of PUFA is recommended and was safe in the atopic study dogs receiving oclacitinib.

Long chain n-3 polyunsaturated fatty acid intake across the life span for cardiovascular disease prevention in women.

Cardiovascular diseases (CVDs) are a major health concern for women. Historically there has been a misconception that men are at greater risk because CVD tends to occur earlier in life compared to women. Clinical guidelines for prevention of heart disease are currently the same for both sexes, but accumulating evidence demonstrates that risk profiles diverge. In fact, several CVD risk factors confer an even greater risk in women relative to men, including high blood pressure, obesity, diabetes and raised triglycerides. Furthermore, many female-specific CVD risk factors exist, including early menarche, pregnancy complications, polycystic ovary syndrome, reproductive hormonal treatments and menopause. Little is known about how diet interacts with CVD risk factors at various stages of a woman’s life. Long chain (LC) n-3 polyunsaturated fatty acid (PUFA) intakes are a key dietary factor that may impact risk of CVD throughout the life course differentially in men and women. Oestrogen enhances conversion of the plant n-3 PUFA, alpha-linolenic acid, to LCn-3 PUFA. Increasing the frequency of oily fish consumption or LCn-3 PUFA supplementation may be important for reducing coronary risk during the menopausal transition, during which time oestrogen levels decline and the increase in CVD risk factors is accelerated. Women are under-represented in the evidence base for CVD prevention following LC n-3 PUFA supplementation. Therefore it is not clear whether there are sex differences in response to treatment. Furthermore, there is a lack of evidence on optimal intakes of LC n-3 PUFA across the lifespan for CVD prevention in women.

Fish - a scoping review for Nordic Nutrition Recommendations 2023.

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.

Current Trends, Challenges for Research, and Therapeutic Perspectives in Nutritional Psychiatry

"Nutritional interventions in the field of psychiatry have been explored more intensively in the last two decades, but definitive conclusions based on the retrieved data in the literature about the efficacy of this therapeutic approach are difficult to formulate. This observation has multiple explanations, e.g., these therapeutic interventions are very heterogenous, cohort studies usually enroll different psychiatric populations or healthy subjects with minor psychiatric symptoms, nutritional supplements or special diets are commonly recommended as add-ons to the pharmacological interventions (thus making it difficult to differentiate the impact of each therapy on the outcomes), placebo-controlled randomized studies are still very few, etc. Therefore, a narrative review focused on the main challenges reported during the research in the field of nutritional psychiatry (NP) may be useful for clinicians interested in strategies to augment the efficacy of pharmacological treatments or to find new solutions with low risk of adverse events in patients with organic comorbidities or multiple concomitant medications. Data about the efficacy and tolerability of nutritional interventions explored for psychiatric disorders were searched in four electronic databases (PubMed, Cochrane, Clarivate/Web of Science, and EMBASE). Omega-3 polyunsaturated fatty acids supplementation, healthy diet interventions, folate and vitamin B12, S-adenosyl-L-methionine, N-acetyl cysteine, vitamin B1 and B6, vitamin D, minerals, psychobiotics, inositol, and herbal products were the main interventions identified, and their demonstrated efficacy was quite heterogenous, while their tolerability and safety were good. Therefore, NP is a domain of research that may benefit from more good-quality and longer-duration trials, in order to verify the effectiveness of such augmentation strategies to the already validated treatments."

Parenteral n–3 polyunsaturated fatty acids supplementation improves postoperative recovery for patients with Crohn’s disease after bowel resection: a randomized, unblinded controlled clinical trial

BackgroundThe postoperative inflammatory response is associated with postoperative recovery in surgery. n–3 (ω-3) polyunsaturated fatty acids have been reported to lower inflammation. The postoperative role of parenteral n–3 polyunsaturated fatty acids supplementation on outcomes in Crohn’s disease after bowel resection is unclear. ObjectivesWe aimed to investigate the effects of postoperative parenteral n–3 polyunsaturated fatty acids supplementation in Crohn’s disease. MethodsA prospective randomized, unblinded controlled clinical trial was conducted for patients with Crohn’s disease who underwent bowel resection between May 2019 and February 2022. Postoperative complications, complete blood count, serum biochemical values, and cytokine concentrations were compared in patients with and without parenteral n–3 polyunsaturated fatty acids supplementation for 5 d postoperatively. ResultsThere were 268 patients randomly assigned in the analysis, with 134 in the control group (a mix of long-chain and medium-chain fats at 1.0 g/kg/d) and 134 in the treatment group (long-chain, medium-chain, and n–3 polyunsaturated fats at 1.2 g/kg/d). Twenty-six did not complete the allocated treatment, and 8 patients were lost to follow-up. The intention–to-treat analysis and the per-protocol analysis showed that there were a significant reduction in overall complication rates (22.4% compared with 49.3%; P < 0.001 and 21.8% compared with 38.2%; P = 0.006) and postoperative stay (8.8 ± 4.5 d compared with 11.2 ± 6.8 d; P = 0.001 and 8.7 ± 4.0 d compared with 11.5 ± 7.3 d; P < 0.001) in patients with parenteral n–3 polyunsaturated fatty acids supplementation compared with patients in the control group. In the secondary outcomes, the mean ± standard deviation of interleukin (IL)-6 (17.11 ± 2.14 pg/mL compared with 30.50 ± 5.14 pg/mL; P = 0.014), IL-1β (2.01 ± 0.05 pg/mL compared with 2.24 ± 0.09 pg/mL; P = 0.019), tumor necrosis factor-α (2.09 ± 0.06 pg/mL compared with 2.29 ± 0.06 pg/mL; P = 0.029), and C-reactive protein concentrations (51.3 ± 4.2 mg/L compared with 64.4 ± 5.3 mg/L; P = 0.050) on postoperative day 5 in the treatment group were much lower than those in the control group. ConclusionsParenteral n–3 polyunsaturated fatty acids supplementation promotes postoperative recovery in patients with Crohn’s disease following bowel resection, with fewer complications and reduced inflammatory cytokines.This trial was registered at clinicaltrials.gov as NCT03901937 at https://classic.clinicaltrials.gov/ct2/show/NCT03901937?term=NCT03901937&cond=Crohn+Disease&draw=2&rank=1.

Omega-3 fatty acid supplementation affects tryptophan metabolism during a 12-week endurance training in amateur runners: a randomized controlled trial

The effects of long-term omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation during endurance training on tryptophan (Trp) metabolism and mental state of healthy individuals have not been evaluated so far. Concentrations of plasma Trp, its metabolites and IL-6 were assessed in 26 male runners before and after a 12-week training program combined with supplementation of n-3 PUFAs (O-3 + TRAIN group) or medium chain triglycerides (MCTs; TRAIN group). After the 12-week program participants' mood before and after stress induction was also assessed. The effects of the same supplementation protocol were evaluated also in 14 inactive subjects (O-3 + SEDEN group). Concentrations of 3-hydroxykynurenine (3-HK) and picolinic acid (PA) significantly increased only in the O-3 + TRAIN group (p = 0.01; ηp2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\\eta }_{p}^{2}$$\\end{document} = 0.22 and p = 0.01; ηp2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\\eta }_{p }^{2}$$\\end{document}= 0.26). Favorable, but not statistically significant changes in the concentrations of kynurenic acid (KYNA) (p = 0.06; ηp2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\\eta }_{p }^{2}$$\\end{document}= 0.14), xanthurenic acid (XA) (p = 0.07; ηp2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\\eta }_{p }^{2}$$\\end{document}= 0.13) and 3-hydroxyanthranilic acid (3-HAA) (p = 0.06; ηp2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\\eta }_{p }^{2}$$\\end{document}= 0.15) and in the ratio of neurotoxic to neuroprotective metabolites were seen also only in the O-3 + TRAIN group. No changes in mood and IL-6 concentrations were observed in either group. Supplementation with n-3 PUFAs during endurance training has beneficial effects on Trp's neuroprotective metabolites.Trial registry: This study was registered at ClinicalTrials.gov with identifier NCT05520437 (14/07/2021 first trial registration and 2018/31/N/NZ7/02962 second trial registration).

Enhancing cancer immunotherapy via inhibition of soluble epoxide hydrolase

Cancer therapy, including immunotherapy, is inherently limited by chronic inflammation-induced tumorigenesis and toxicity within the tumor microenvironment. Thus, stimulating the resolution of inflammation may enhance immunotherapy and improve the toxicity of immune checkpoint inhibition (ICI). As epoxy-fatty acids (EpFAs) are degraded by the enzyme soluble epoxide hydrolase (sEH), the inhibition of sEH increases endogenous EpFA levels to promote the resolution of cancer-associated inflammation. Here, we demonstrate that systemic treatment with ICI induces sEH expression in multiple murine cancer models. Dietary omega-3 polyunsaturated fatty acid supplementation and pharmacologic sEH inhibition, both alone and in combination, significantly enhance anti-tumor activity of ICI in these models. Notably, pharmacological abrogation of the sEH pathway alone or in combination with ICI counter-regulates an ICI-induced pro-inflammatory and pro-tumorigenic cytokine storm. Thus, modulating endogenous EpFA levels through dietary supplementation or sEH inhibition may represent a unique strategy to enhance the anti-tumor activity of paradigm cancer therapies.

Age-Dependent Changes in Nrf2/Keap1 and Target Antioxidant Protein Expression Correlate to Lipoxidative Adducts, and Are Modulated by Dietary N-3 LCPUFA in the Hippocampus of Mice.

The brain has a high metabolism rate that may generate reactive oxygen and nitrogen species. Consequently, nerve cells require highly efficient antioxidant defenses in order to prevent a condition of deleterious oxidative stress. This is particularly relevant in the hippocampus, a highly complex cerebral area involved in processing superior cognitive functions. Most current evidence points to hippocampal oxidative damage as a causal effect for neurodegenerative disorders, especially Alzheimer's disease. Nuclear factor erythroid-2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/Keap1) is a master key for the transcriptional regulation of antioxidant and detoxifying systems. It is ubiquitously expressed in brain areas, mainly supporting glial cells. In the present study, we have analyzed the relationships between Nrf2 and Keap1 isoforms in hippocampal tissue in response to aging and dietary long-chain polyunsaturated fatty acids (LCPUFA) supplementation. The possible involvement of lipoxidative and nitrosative by-products in the dynamics of the Nrf2/Keap1 complex was examined though determination of protein adducts, namely malondialdehyde (MDA), 4-hydroxynonenal (HNE), and 3-nitro-tyrosine (NTyr) under basal conditions. The results were correlated to the expression of target proteins heme-oxygenase-1 (HO-1) and glutathione peroxidase 4 (GPx4), whose expressions are known to be regulated by Nrf2/Keap1 signaling activation. All variables in this study were obtained simultaneously from the same preparations, allowing multivariate approaches. The results demonstrate a complex modification of the protein expression patterns together with the formation of adducts in response to aging and diet supplementation. Both parameters exhibited a strong interaction. Noticeably, LCPUFA supplementation to aged animals restored the Nrf2/Keap1/target protein patterns to the status observed in young animals, therefore driving a "rejuvenation" of hippocampal antioxidant defense.

Cognitive protection and brain entropy changes from omega-3 polyunsaturated fatty acids supplement in late-life depression: A 52-week randomized controlled trial

BackgroundLate-life depression (LLD) is associated with risk of dementia, yet intervention of LLD provides an opportunity to attenuate subsequent cognitive decline. Omega-3 polyunsaturated fatty acids (PUFAs) supplement is a potential intervention due to their beneficial effect in depressive symptoms and cognitive function. To explore the underlying neural mechanism, we used resting-state functional MRI (rs-fMRI) before and after omega-3 PUFAs supplement in older adults with LLD. MethodsA 52-week double-blind randomized controlled trial was conducted. We used multi-scale sample entropy to analyze rs-fMRI data. Comprehensive cognitive tests and inflammatory markers were collected to correlate with brain entropy changes. ResultsA total of 20 patients completed the trial with 11 under omega-3 PUFAs and nine under placebo. While no significant global cognitive improvement was observed, a marginal enhancement in processing speed was noted in the omega-3 PUFAs group. Importantly, participants receiving omega-3 PUFAs exhibited decreased brain entropy in left posterior cingulate gyrus (PCG), multiple visual areas, the orbital part of the right middle frontal gyrus, and the left Rolandic operculum. The brain entropy changes of the PCG in the omega-3 PUFAs group correlated with improvement of language function and attenuation of interleukin-6 levels. LimitationsSample size is small with only marginal clinical effect. ConclusionThese findings suggest that omega-3 PUFAs supplement may mitigate cognitive decline in LLD through anti-inflammatory mechanisms and modulation of brain entropy. Larger clinical trials are warranted to validate the potential therapeutic implications of omega-3 PUFAs for deterring cognitive decline in patients with late-life depression.

Omega-3 polyunsaturated fatty acids supplementation improves memory in first-diagnosed, drug-naïve patients with depression: Secondary analysis of data from a randomized controlled trial

IntroductionCognitive impairments are found in most patients with major depressive disorder (MDD). It is believed that low Omega-3 polyunsaturated fatty acids (n-3 PUFAs) level raise the risk of anxiety, depressive symptoms and cognition dysfunction. Since our previous research has found n-3 PUFAs supplementation improves anxiety in MDD, this study was to further explore the effectiveness on cognitive impairment among depressed patients. MethodsA total of 72 venlafaxine treated outpatients with first-diagnosed, drug-naïve depression were enrolled. Daily n-3 PUFAs supplementation (2.4 g/d of fish oil, including 1440 mg eicosapentaenoic acid and 960 mg of docosahexaenoic acid) or placebo was used for 12 weeks. Cognitive function, measure by repeatable battery for the assessment of neuropsychological status ([RBANS]) scores, was compared over time. ResultsImmediate memory, delayed memory and RBANS total scores were significant higher in both groups at week 4 and week 12 compared with baseline. Both groups exhibited improvement on attention scores at week 12. No significant differences were observed comparing n-3 PUFAs with placebo groups in the improvement of total RBANS scores and other subscales except in the change of immediate memory at both week 4 and week 12 (p < 0.05). LimitationsSample size was relatively low. Moreover, multiple ethnic populations and the income of patients should be considered. Lastly, we used raw scores instead of the standardized scores of RBANS. ConclusionN-3 PUFAs supplementation yielded a small but statistically significant improvement on immediate memory in first-diagnosed, drug-naïve depressed patients. While, antidepressant treatment resulted in significant improvement of cognitive function.

N-3 polyunsaturated fatty acids alleviate the progression of obesity-related osteoarthritis and protect cartilage through inhibiting the HMGB1-RAGE/TLR4 signaling pathway

Osteoarthritis (OA) is a common joint degenerative disease. There is currently no cure for OA. Dietary fatty acids have potential value in the prevention and treatment of OA. n-3 polyunsaturated fatty acids (PUFAs) have anti-inflammatory effects, but their anti-OA mechanism remains unclear. High-mobility group box 1 (HMGB1) promotes inflammation and participates the pathogenesis of OA. The purpose of this study was to investigate the protective effect of n-3 PUFAs on cartilage and whether n-3 PUFAs could exert an anti-OA effect through inhibiting HMGB1-RAGE/TLR4 signaling pathway. We established an obesity-related post-traumatic OA mice model and an in vitro study was conducted to explore the regulatory mechanism of n-3 PUFAs on HMGB1 and its signal pathway against OA. We found that diet rich in n-3 PUFAs alleviated OA-like lesions of articular cartilage with the decrease of HMGB1-RAGE/TLR4 signaling protein in mice. In SW1353 cells, DHA significantly reduced the expression of HMGB1-RAGE/TLR4 signaling protein which was up-regulated by IL-1β stimulation. HMGB1 overexpression reversed the inhibitory effect of DHA on HMGB1-RAGE/TLR4 signaling pathway. The activation of SIRT1 may participate the inhibitory effect of DHA on HMGB1-RAGE/TLR4 signaling pathway. In conclusion, n-3 PUFAs could attenuate the progression of obesity-related OA and exert protective effect on cartilage by inhibiting HMGB1-RAGE/TLR4 signaling pathway, which may be associated with the activation of SIRT1. Dietary n-3 PUFAs supplements can be considered as a potential therapeutic substance for OA.

Fatty acid synthesis suppresses dietary polyunsaturated fatty acid use

Dietary polyunsaturated fatty acids (PUFA) are increasingly recognized for their health benefits, whereas a high production of endogenous fatty acids – a process called de novo lipogenesis (DNL) - is closely linked to metabolic diseases. Determinants of PUFA incorporation into complex lipids are insufficiently understood and may influence the onset and progression of metabolic diseases. Here we show that fatty acid synthase (FASN), the key enzyme of DNL, critically determines the use of dietary PUFA in mice and humans. Moreover, the combination of FASN inhibition and PUFA-supplementation decreases liver triacylglycerols (TAG) in mice fed with high-fat diet. Mechanistically, FASN inhibition causes higher PUFA uptake via the lysophosphatidylcholine transporter MFSD2A, and a diacylglycerol O-acyltransferase 2 (DGAT2)-dependent incorporation of PUFA into TAG. Overall, the outcome of PUFA supplementation may depend on the degree of endogenous DNL and combining PUFA supplementation and FASN inhibition might be a promising approach to target metabolic disease.

Effects of polyunsaturated fatty acids on interleukin-6 and brain-derived neurotrophic factor in monosodium glutamate-induced depression male rats

Background: Depression is the most common psychiatric disorder affecting around 5% of the population worldwide. It leads to morbidity and affects quality of life. Monosodium glutamate (MSG) popularly called a tastemaker is used as a food additive in fast food and other processed foods. MSG has been implicated in causing depression. Since many adolescents and children are being habituated to fast foods, the current study is to evaluate the effects of polyunsaturated fatty acids (PUFAs) supplementation on plasma concentration of brain-derived neurotrophic factor (BDNF) and IL-6 which are important biochemical and immunological markers found in depression. Aims and Objectives: The aim of the current study was to assess the effect of supplementation of PUFA on MSG-induced depression in Wistar albino rats. Materials and Methods: The present prospective interventional study was conducted on 3-month-old, 24 male Wistar albino rats (weighing 200–300 g) for 21 days. The study group was divided into four equal groups among which 1st group that is control received distilled water with carboxymethylcellulose (CMC), the 2nd group positive control group received 500 mg of MSG along with CMC, the 3rd group normal control with PUFA received PUFA dissolved in CMC and the 4th group was positive control with PUFA received MSG dissolved in CMC and PUFA intervention was introduced from the 7th day. The study period was for 21 days and the 22nd day was an acclimatization day. The parameters in the blood samples of the rats were tested on the 23rd day using an ELISA kit and results were analyzed using Tukey’s post hoc test among the various groups and it was taken as statistically significant when the P &lt; 0.05. Results: Among the groups, IL-6 levels raised and BDNF levels dropped in plasma of MSG-induced depressed rats. In PUFA-treated MSG-induced depressed rats, the plasma level of IL-6 was reduced and there was a significant rise in BDNF levels. Conclusion: PUFA supplementation is effective in treating MSG-induced depression in rats.

The association between polyunsaturated fatty acids and chronic obstructive pulmonary disease: a meta-analysis.

Background: Chronic obstructive pulmonary disease (COPD) is a common respiratory disease, and its development and prognosis are influenced by many nutrients. However, the relationship between polyunsaturated fatty acids (PUFAs) and COPD remains unclear. Methods: This study searched all literature reports on PUFAs and COPD based on electronic databases from their inception up to October 2023. Meta-analysis was conducted to evaluate the differences in PUFAs between COPD patients and controls, the risk of COPD in subjects with different levels of PUFA concentrations, and the effect of PUFA supplementation on COPD. Results: A total of nineteen studies met our inclusion criteria, which included 155 636 subjects. Our meta-analysis results showed that the daily dietary intake of PUFAs was lower in COPD patients than in controls (SMD = -0.80 g, 95% CI: -1.28, -0.31 g, I2 = 98.6%, P < 0.001). Meanwhile, the lower n-3 PUFA levels and higher n-6 PUFA levels were associated with an increased risk of COPD (effect size n-3 = 0.87, 95% CI: 0.77, 0.98, I2 = 52.2%, P = 0.018; effect size n-6 = 1.23, 95% CI: 1.05, 1.43, I2 = 75.2%, P < 0.001). Furthermore, the content of low-density lipoprotein cholesterol in the PUFA supplementation group was higher than that in the control group (SMD = 0.63 mg dL-1, 95% CI: 0.15, 1.12 mg dL-1, I2 = 0.0%, P = 0.697). Conclusions: Our meta-analysis indicated a potential relationship between PUFAs and COPD. More large-scale prospective cohort studies and clinical trials are necessary to validate this relationship.

Effects of omega-3, omega-6, and total dietary polyunsaturated fatty acid supplementation in patients with atherosclerotic cardiovascular disease: a systematic review and meta-analysis.

Background: Uncertainty exists about the link between omega-3 fatty acid, omega-6 fatty acid, and total polyunsaturated fatty acid (PUFA) intake and mortality in atherosclerotic cardiovascular disease (ASCVD) patients, and no meta-analyses summarize the relationship between these various types of PUFAs and ASCVD. Methods: Web of Science, PubMed, EBSCO and Cochrane Library up to November 30, 2022 were searched for prospective randomized controlled studies investigating the relationships among omega-3, omega-6, and PUFA intake and mortality and cardiovascular events in ASCVD patients. This study has been registered at PROSPERO (No. CRD42023407566). Results: This meta-analysis included 21 publications from 17 studies involving 40 861 participants published between 1965 and 2022. In ASCVD patients, omega-3 may lower all-cause mortality (RR: 0.90, 95% CI [0.83, 0.98], I2 = 8%), CVD mortality (RR: 0.82, 95% CI [0.73, 0.91], I2 = 34%) and CVD events (RR: 0.90, 95% CI [0.86, 0.93], I2 = 79%). Subgroup analyses showed that EPA or EPA ethyl ester supplementation reduced CVD events, while the mixture of EPA and DHA had no significant impact. Long-chain omega-3 consumption of 1.0-4.0 g per d reduced death risk by 3.5% for each 1 g per d increase. Omega-6 and PUFA had no significant effect on mortality or CVD events, with low-quality evidence and significant heterogeneity. Conclusions: omega-3 intake is associated with a reduced risk of all-cause mortality, CVD mortality, and CVD events in ASCVD patients, while omega-6 or total PUFA intake showed no significant association. Increasing the omega-3 intake by 1 g per d resulted in a 3.5% decrease in the risk of death. These findings support the recommendation of supplements with omega-3 fatty acids for the secondary prevention of ASCVD.

Assessing and mitigating foodborne acetochlor exposure induced ileum toxicity in broiler chicks: The role of omega-3 polyunsaturated fatty acids supplementation and molecular pathways analysis

Excessive acetochlor residues present ecological and food safety challenges. Here, broiler chicks were exposed to varied acetochlor doses to first assess its effects on the gut. Subsequent dietary supplementation with omega-3 was used to assess its anti-contamination effects. Pathologically, acetochlor induced notable ileal lesions including inflammation, barrier disruption, tight junction loss, and cellular anomalies. Mechanistically, acetochlor stimulated the TNFα/TNFR1 and TLR4/NF-κB/NLRP3 pathways, promoting RIPK1/RIPK3 complex formation, MLKL phosphorylation, NLRP3 inflammasome activation, Caspase-1 activation, and GSDMD shearing with inflammatory factor release. These mechanisms elucidate ileal cell death patterns essential for understanding chicken enteritis. Omega-3 supplementation showed promise in mitigating inflammation, though its precise counteractive role remains unclear. Our findings suggest early omega-3 intervention offered protective benefits against acetochlor's adverse intestinal effects, emphasizing its potential poultry health management role. Harnessing dietary interventions' therapeutic potential will be pivotal in ensuring sustainable poultry production and food safety despite persistent environmental contaminants.