Omega-3 PUFA Research Articles

Omega-3 Supplementation in Coronary Artery Bypass Graft Patients: Impact on ICU Stay and Hospital Stay-A Systematic Review and Meta-Analysis.

Background/Objectives: Coronary artery bypass graft (CABG) is associated with inflammation and complications, potentially leading to prolonged ICU and hospital stays. Omega-3 PUFA has anti-inflammatory properties, thought to potentially reduce complications in CABG patients. This study aims to systematically review and meta-analyze the impact of perioperative omega-3 PUFA supplementation on total ICU and total hospital stays in CABG patients; Methods: Randomized controlled trials examining the effects of omega-3 PUFA supplementation (IV/oral) on ICU and hospital stays in CABG patients were included. Studies were searched for in PubMed, EMBASE, PsychINFO, CINAHL, and the Cochrane Central Register of Controlled Trial databases, along with hand searching of reference lists. The quality and risk of bias of the included studies were evaluated by two independent reviewers using the revised Cochrane risk-of-bias tool. Meta-analysis was performed using fixed or random effects models according to the level of heterogeneity by mean difference with their 95% confidence intervals; Results: Twelve studies were included in the qualitative analysis and seven in the meta-analysis. Omega-3 PUFA was associated with a significant reduction in days of hospital stay (-0.58 (95% CI -1.13, -0.04)). Subgroup analysis showed that only oral omega-3 PUFA supplementation resulted in a statistically significant reduction in length of hospitalization after subgroup analysis with MD -0.6 (95% CI -1.17, -0.04); Conclusions: This study suggests that perioperative omega-3 PUFA supplementation may reduce the length of hospitalization in CABG patients, especially when administered orally. However, the findings should be interpreted cautiously due to the high level of heterogeneity.

Omega-3 polyunsaturated fatty acids, especially DHA and EPA, remold gut microbiota to suppress inflammation in rabbits with atherosclerosis

Atherosclerosis (AS) caused by a high-fat diet becomes a critical cause of cardiovascular diseases, which has been regarded as an urgent public health problem. Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) have many beneficial effects on human health. However, in recent years, the critical role of gut microbiota in atherosclerosis has been gradually proposed, and the impact of omega-3 PUFAs on cardiovascular diseases via gut microbiota in rabbits remains unknown. Likewise, the role of omega-3 PUFAs in regulating endothelial lesions, visceral injury, and vascular inflammation caused by high-fat diet-induced trimethylamine-nitrogen oxide (TMAO) has not been reported. Here, we investigated the effects of omega-3 PUFAs administered orally on atherosclerosis via an atherosclerotic rabbit model induced by a high-fat diet. The results showed that omega-3 PUFAs obtained from deep-sea fish oil can alleviate high-fat diet-induced atherosclerosis by inhibiting the increase of plasma TMAO and the formation of liver foam cells, reducing inflammatory factors, fat deposition, and plasma lipid levels and suppressing organ damage. Furthermore, gut microbiota disrupted by a high-fat diet were remodeled in rabbits treated with omega-3 PUFAs. These results further confirm that omega-3 PUFAs are promising nutritional and medical health foods that can be supplemented daily to prevent cardiovascular diseases.

Omega-3 PUFAs counteracts high fructose diet-induced gonadal impairment via fortified antioxidant defense

Omega-3 PUFAs counteracts high fructose diet-induced gonadal impairment via fortified antioxidant defense

The role of supplementation in traumatic brain injury among athletes and non-athletes population

Introduction: Traumatic brain injury (TBI) is one of the most common causes of death and long-term disability. The consequences following TBI can be persistent and cause life-long implications for survivors. Treatment of TBI may be complex and involve large monetary costs. The frequent injury mechanisms are traffic-related, falls, violence or sport-related accidents. Higher risk of brain injury and its complications indicate that people affected by brain trauma may benefit from the prophylactic and post-traumatic use of certain supplements both in the context of physical performance and in the event of potential injury. Aim of the Study: This narrative review examines the current literature of the role of supplementation before and after TBI and its effects on the patient's outcome. Materials and Methods: A comprehensive search was performed using PubMed and Google Scholar focusing on the literature published up to April 2024. The review included randomized controlled trials, meta-analyses, systematic reviews that focused on the use of creatine monohydrate, omega-3 fatty acids, magnesium and zinc in TBI and among the general population. Data of pathophysiology and epidemiology of TBI and safety profile of supplements were involved. Results: The evidence indicates that the role of supplementation with creatine, omega-3 PUFAs and zinc is important in mitigating secondary damage after TBI, as well as in protecting against damage if administered before injury. Conclusion: Because of the complex and multifactorial nature of the TBI more studies are required to constitute an effective nutrition-based strategy for reducing the cognitive and behavioral deficits associated with this injury. The evidence supporting multiple dietary components to improve a patient's outcome seems strong and the cost of its implementation is low. A group of particular interest that may benefit additionally are athletes who use dietary supplementation in their daily routine.

A novel method for non-destructive efficient green recovery of multiple high value products from microalgal cells with enzymatically enhanced permeability

A method is developed for simultaneous extraction of lipids, hydrocarbons and carotenoids from primary algal biomass without the need for cell sacrifice. Enzymatically predigested cells (from previous experiments) with enhanced permeability were used, for ‘milking’ with biocompatible solvent. The continuous non-destructive extraction of lipids and carotenoids from an improved permeabilized microalgal cell using crude enzyme concoctions and biocompatible solvents has not been reported so far. Oocystis sp. cells showed considerable viability following enzymatic pretreatment and extraction using dodecane which was verified through cell viability assays, and chlorophyll content. HPLC analysis confirmed the presence of lutein and zeaxanthin. GC-MS analysis showed the presence of omega-3 alpha linolenic acid, PUFAs, and phenolics, in enzymatically digested microalgal cells. The content of fatty acids and esters in enzyme treated samples was 57.18 %, and the enzyme with dodecane treated samples showed 31.4 % fatty acids and esters content. Omega-3 linolenic acid comprised 11.66 % in enzyme treated cells and showed a marginal increase of 12.5 % in enzyme with dodecane treated cells. The method enables recovery of multiple compounds from a single biomass. In the present study, a cultivation strategy of microalgal cells with enhanced permeability, grown in biocompatible solvent is proposed, whereby maximum yield of multiple valuable metabolites can be obtained from a single biomass. The method simplifies downstream processing operations by circumventing cell harvesting and drying. The use of green extraction solvents reduces the overall carbon footprint of the process.

Omega-3 PUFAs slow organ aging through promoting energy metabolism

Energy metabolism disorder, mainly exhibiting the inhibition of fatty acid degradation and lipid accumulation, is highly related with aging acceleration. However, the intervention measures are deficient. Here, we reported Omega-3 polyunsaturated fatty acids (Omega-3 PUFAs), especially EPA, exerted beneficial effects on maintaining energy metabolism and lipid homeostasis to slow organ aging. As the endogenous agonist of peroxisome proliferator–activated receptor α (PPARα), Omega-3 PUFAs significantly boosted fatty acid β-oxidation and ATP production in multiple aged organs. Consequently, Omega-3 PUFAs effectively inhibited age-related pathological changes, preserved organ function, and retarded aging process. The beneficial effects of Omega-3 PUFAs were also testified in mfat-1 transgenic mice, which spontaneously generate abundant endogenous Omega-3 PUFAs. In conclusion, our study innovatively demonstrated Omega-3 PUFAs administration in diet slow aging through promoting energy metabolism. The supplement of Omega-3 PUFAs or fat-1 transgene provides a promising therapeutic approach to promote healthy aging in the elderly.

Effectiveness of Omega-3 Polyunsaturated Fatty Acids in Non-alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis.

Non-alcoholic fatty liver disease (NAFLD) is a prevalent liver disorder characterized by excessive hepatic fat accumulation without alcohol intake. It can progress to non-alcoholic steatohepatitis, increasing the risk of cirrhosis and liver failure. This study aims to evaluate the efficacy of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in treating NAFLD. A systematic review and meta-analysis was conducted including studies published from January 2018 to June 2023. Databases searched included PubMed, Embase, Cochrane Library, and ClinicalTrials.gov. Inclusion criteria comprised randomized controlled trials and cohort studies involving human subjects or animal models with NAFLD. Data were extracted and analyzed to assess the impact of omega-3 PUFAs on liver fat, hepatic enzymes, and serum lipid profiles using RevMan 5.4. A total of 15 studies met the inclusion criteria. Omega-3 supplementation significantly decreased alanine aminotransferase (ALT) (mean difference = -2.12, 95% confidence interval (CI) = -3.36, -0.87) and aspartate aminotransferase (AST) (mean difference = -1.50, 95% CI = -2.59, -0.42). Gamma-glutamyl transferase levels showed a trend toward reduction (mean difference = -0.82, 95% CI = -1.66, 0.02). Serum lipid profiles improved significantly with reductions in triglycerides, low-density lipoprotein, and total cholesterol along with significant reductions in AST, ALT, and alkaline phosphatase in animal models. Omega-3 PUFAs appear to offer beneficial effects on liver enzymes, serum lipid profiles, and anthropometric indices in NAFLD patients. While their impact on liver fat content remains uncertain, omega-3 supplementation could serve as a valuable adjunct treatment for enhancing metabolic profiles and liver function in NAFLD patients.

Genetically Determined Circulating Saturated and Unsaturated Fatty Acids and the Occurrence and Exacerbation of Chronic Obstructive Pulmonary Disease-A Two-Sample Mendelian Randomization Study.

Research on dietary fatty acids (FAs) and lung health has reported skeptical findings. This study aims to examine the causal relationship between circulating FAs and Chronic Obstructive Pulmonary Disease (COPD) onset and exacerbation, using a two-sample Mendelian Randomization (MR) analysis. Strong and independent genetic variants of FAs were obtained from the UK Biobank of European ancestry. The exposure traits included saturated FA (SFA), poly- and mono-unsaturated FA (PUFA and MUFA), omega-3 and omega-6 PUFA, docosahexaenoic acid (DHA), and linoleic acid (LA), all expressed as total FA (TFA) percentages. Summary statistics for COPD outcomes were obtained from the FinnGen consortium including COPD, COPD hospitalization, COPD/asthma-related infections, COPD-related respiratory insufficiency, and COPD/asthma/interstitial lung disease (ILD)-related pneumonia. The inverse-variance weighted (IVW) was the primary MR approach. MR-Egger regression and MR-PRESSO were utilized to evaluate heterogeneity and pleiotropy. MR-PRESSO tests suggested no obvious horizontal pleiotropy. MR results by the IVW approach indicated that the genetically high SFA/TFA levels were associated with an increased risk of COPD/asthma/ILD-related pneumonia (OR: 1.275, 95%CI: 1.103-1.474, p for FDR = 0.002). No significant relationship was observed between other types of FAs and COPD outcomes. Our MR analysis suggests that there is weak evidence that the genetically predicted high SFA/TFA was associated with an increased risk of pneumonia.

The Effects of Diet on the Elimination and Prevention of Mental Health Illnesses

The study investigates the relationship between diet type and mental health, focusing on the impact of nutrient deficiencies on mental health illnesses and their treatment. We gathered results from 15 participants over ten years using self-administered questionnaires and biochemical assessments. The study discovered significant correlations between diets and mental health diseases, with Western diets increasing the incidence of major depressive disorder, anxiety disorder, and ADHD. Mediterranean and high-fiber diets showed protective effects, reducing the rates of these disorders by 40% and 30%, respectively. Some participants also showed deficiencies in omega-3 PUFAs and vitamin D. Pharmacological interventions, such as omega-3 supplementation and Mediterranean diets, improve mental health outcomes. The study emphasizes the importance of dietary change in preventing and treating psychiatric disorders and emphasizes the need for clinical and population-level dietary changes.

The Effects of Diet on the Elimination and Prevention of Mental Health Illnesses

The study investigates the relationship between diet type and mental health, focusing on the impact of nutrient deficiencies on mental health illnesses and their treatment. We gathered results from 15 participants over ten years using self-administered questionnaires and biochemical assessments. The study discovered significant correlations between diets and mental health diseases, with Western diets increasing the incidence of major depressive disorder, anxiety disorder, and ADHD. Mediterranean and high-fiber diets showed protective effects, reducing the rates of these disorders by 40% and 30%, respectively. Some participants also showed deficiencies in omega-3 PUFAs and vitamin D. Pharmacological interventions, such as omega-3 supplementation and Mediterranean diets, improve mental health outcomes. The study emphasizes the importance of dietary change in preventing and treating psychiatric disorders and emphasizes the need for clinical and population-level dietary changes.

Omega-3 PUFAs' efficacy in the therapy of coronary artery disease combined with anxiety or depression: a meta-analysis.

The evidence demonstrates that omega-3 polyunsaturated fatty acids (omega-3 PUFAs) protect the cardiovascular system and alleviate anxious or depressive situations. We conducted a meta-analysis to evaluate the effectiveness of omega-3 PUFAs in the treatment of anxiety or depressive states in patients with coronary artery disease. This meta-analysis analyzed data from randomized controlled trials to determine the efficacy of omega-3 PUFAs alone or in combination with conventional psychotropic medications in coronary artery disease patients suffering from anxiety or depression. Primary outcomes included changes in depression scores, the Beck Anxiety Inventory (BAI) scores, and the omega-3 index. Included were 6 trials involving 2,570 participants. Compared to controls,omega-3 PUFAs did not improve depression or anxiety {depression: [SMD=0.09 (95% CI: -0.07, 0.26)], anxiety [BAI: SMD=0.07 (95% CI: -0.17, 0.32)]}; For the results of the subgroup analyses, analyzed by different types of depression scales, four studies used the HAMD scale [SMD=0.19 (95% CI: -0.20, 0.58)]; 5 studies used the BDI-II scale [SMD=0.01 (95% CI: -0.07, 0.09)], all of which indicated no decrease in depression scale scores; analyzed by different types of intervention, 3 studies used the omega-3 PUFAs group [SMD=0.24 (95% CI: -0.26, 0.74)]; 2 studies used sertraline + omega-3 PUFAs [SMD=-0.08 (95% CI: -0.46, 0.31)], and the omega-3 index was elevated [SMD=1.33 (95% CI: 0.18, 2.49)], suggesting that the body's omega-3 content was indeed replenished but did not change the patient's depressive state; analyzed by different courses of therapy, a 10-week course of therapy [SMD=0.02 (95% CI: -0.23, 0.26)] and a 12-week course of therapy [SMD=0.40 (95% CI: -0.40, 1.20)] both resulted in a lack of improvement in depressive symptoms. According to the available evidence, omega-3 PUFAs do not alleviate anxiety or depression in coronary artery disease patients. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023391259.

Antioxidant, anti-amylase, anti-lipase, and efficiency of Satureja fatty acid on the anti-inflammatory parameters in lipopolysaccharide-stimulated macrophage through Nrf2/NF-kB/NADH oxidase pathway

Satureja is an aromatic plant that is used for flavoring, perfume, and food manufacturing due to its pleasant essential oil. Modern medicine research revealed several biological activities of Satureja essential oil, including antifungal, antibacterial, antiviral, antioxidant, anticancer, and anti-inflammatory. However, the functional properties of Satureja fatty acid have not been explored. This study examined the fatty acid profile, lipid nutritional quality, antioxidant, anti-amylase, and anti-lipase capacities of Satureja. The efficiency of Satureja fatty acid on the anti-oxidative and anti-inflammatory parameters in LPS-induced macrophage through the Nrf2/NF-kB/NADH oxidase pathway was examined. The whole lipid extract was prepared with chloroform/methanol/water solution. Fatty acids methyl ester from whole lipid extract were prepared with methanol/sulfuric acid reagent. The fatty acid profile was analyzed using gas chromatography-mass spectrometry. Total antioxidant was determined by ABTS decolorization. Lipase and amylase activities were determined by monitoring the decomposition of p-nitrophenyl butyrate and starch. The macrophage cell line was grown in DMEM media in the presence of fatty acid. The hydrogen peroxide production in treated cells was monitored using the FOX reagent. NADH oxidase activity was measured by monitoring NADH breakdown. The expression of NOX, NF-kB, and NRF2, were tested in the treated cells by real-time PCR. The main components of the Satureja fatty acid were linolenic acid (24.67–37.32%), palmitic acid (10.65–20.29%), linoleic acid (8.31–13.39%), oleic acid (4.42–14.35%), stearic acid (2.76–8.77%) and palmitoleic acid (1.77–4.95%). Given the nutritional quality, omega-3 PUFA (23.58–37.32%), SFA (21.53–26.70%), omega-6 PUFA (10.86–16.14%), omega-9 MUFA (4.42–14.35%), and omega-7 MUFA (1.77–4.95%) comprise the majority of fatty acids. Satureja fatty acid has a promising unsaturation index (120.77–164.27), PUFA/MUFA (2.07–6.41), hypocholesterolemic index (2.44–3.47), health-promoting index (2.03–2.42), PUFA/SFA (1.37–1.94), nutritive value index (0.53–1.71), MUFA/SFA (0.30–0.80) omega-6/omega-3 (0.34–0.65), atherogenicity index (0.41–0.49), and thrombogenicity index (0.17–0.27). Satureja fatty acid displayed strong antioxidant capacity (with IC50 ranging from 354 to 428 µg/mL), anti-lipase capacity (with IC50 ranging from 354 to 428 µg/mL), and anti-amylase capacity (with IC50 ranging from 370 to 390 µg/mL). LPS induced the expression of NOX, NRF2, and NF-kB and the synthesis of hydrogen peroxide in macrophage cells. In LPS-stimulated macrophages, Satureja fatty acid reduced NOX expression, hydrogen peroxide, and NF-kB expression and increased NRF2 at 0.04 mg/mL. In conclusion, Satureja fatty acids have potent antioxidant, anti-amylase, anti-lipase, and anti-inflammatory activities. The mechanisms in lowering oxidative stress markers depended on down-regulating superoxide-producing enzymes at gene and protein levels. Satureja polyunsaturated omega-3 fatty acids could be recommended for healthy products combined with dietary therapy to treat obesity, diabetes, and oxidative stress.

The value of plasma omega-3 polyunsaturated fatty acids in predicting the response and prognosis of cervical squamous cell carcinoma patients to concurrent chemoradiotherapy.

Background: In recent years, abnormalities in plasma omega-3 polyunsaturated fatty acids (omega-3 PUFAs) have been proven to be related to the risk of cancer, but their prognostic value for cancer is unclear. The purpose of this study was to retrospectively evaluate the response and prognostic significance of plasma omega-3 PUFAs in patients with cervical squamous cell carcinoma (CSCC) treated with concurrent chemoradiotherapy (CCRT). Spearman rank correlation analysis was used to analyze the correlation between omega-3 PUFAs and squamous cell carcinoma antigen (SCC-Ag) levels. Methods: A total of 89 patients with CSCC who underwent CCRT were evaluated retrospectively. Binary logistic regression analysis was used to analyze the independent predictors related to complete response (CR) after CCRT. A Cox proportional hazard model and Kaplan-Meier analysis were utilized to perform survival analysis. Results: According to multivariate logistic regression analyses, a high level of plasma EPA was independently correlated with an increased incidence of CR after CCRT (odds ratio (OR), 0.980; 95% confidence interval (CI), 0.962-0.999, p = 0.038). With a median follow-up of 41.3months, the CSCC patients in the high EPA (≥46.0nmol/mL) group exhibited longer OS and PFS. According to our multivariate analysis, pretreatment plasma EPA level was an independent prognostic factor for PFS in patients with CSCC who underwent CCRT (hazard ratio (HR), 0.263; 95% CI, 0.089-0.782, p = 0.016). However, it was not an independent prognostic factor of OS. Spearman rank correlation analysis revealed was a negative correlation between pretreatment SCC-Ag (pre SCC-Ag) levels and EPA levels (r = -0.305, p = 0.004), and a weak negative correlation between posttreatment SCC-Ag (post SCC-Ag) levels and EPA levels (r = -0.251, p = 0.018). Conclusion: Plasma omega-3 PUFAs are related to the response and survival outcome of patients with CSCC who underwent CCRT. Pretreatment plasma EPA levels may be a promising biomarker for predicting the response and prognosis of patients with CSCC who undergo CCRT. In addition, the pretreatment plasma EPA levels presented a negative correlation with the SCC-Ag levels.

A novel hepatocyte ketone production assay to help the selection of nutrients for the ketogenic diet treatment of epilepsy

The classic ketogenic diet is an effective treatment option for drug-resistant epilepsy, but its high fat content challenges patient compliance. Optimizing liver ketone production guided by a method comparing substrates for their ketogenic potential may help to reduce the fat content of the diet without loss in ketosis induction. Here, we present a liver cell assay measuring the β-hydroxybutyrate (βHB) yield from fatty acid substrates. Even chain albumin-conjugated fatty acids comprising between 4 and 18 carbon atoms showed a sigmoidal concentration-βHB response curve (CRC) whereas acetate and omega-3 PUFAs produced no CRC. While CRCs were not distinguished by their half-maximal effective concentration (EC50), they differed by maximum response, which related inversely to the carbon chain length and was highest for butyrate. The assay also suitably assessed the βHB yield from fatty acid blends detecting shifts in maximum response from exchanging medium chain fatty acids for long chain fatty acids. The assay further detected a dual role for butyrate and hexanoic acid as ketogenic substrate at high concentration and ketogenic enhancer at low concentration, augmenting the βHB yield from oleic acid and a fatty acid blend. The assay also found propionate to inhibit ketogenesis from oleic acid and a fatty acid blend at low physiological concentration. Although the in vitro assay shows promise as a tool to optimize the ketogenic yield of a fat blend, its predictive value requires human validation.

Association between omega-3 polyunsaturated fatty acids and osteoarthritis: results from the NHANES 2003–2016 and Mendelian randomization study

BackgroundOmega-3 polyunsaturated fatty acids (omega-3 PUFAs) exhibit potential as therapeutics for a variety of diseases. This observational and Mendelian randomization (MR) study aims to explore the relationship between omega-3 PUFAs and osteoarthritis (OA).MethodsExcluding individuals under 20 years old and those with missing data on relevant variables in the National Health and Nutrition Examination Survey (NHANES) spanning from 2003 to 2016, a total of 22 834 participants were included in this cross-sectional study. Weighted multivariable-adjusted logistic regression was used to estimate the association between omega-3 PUFAs and OA in adults. Moreover, restricted cubic splines were utilized to examine the dose-response relationship between omega-3 PUFAs and OA. To further investigate the potential causal relationship between omega-3 PUFAs and OA risk, a two-sample MR study was conducted. Furthermore, the robustness of the findings was assessed using various methods.ResultsOmega-3 PUFAs intake were inversely associated with OA in adults aged 40 ∼ 59 after multivariable adjustment \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$[\ ext{OR} (95\\% \ ext{CI): }0.85 (0.73, 0.98), P = 0.027]$$\\end{document}, with a nonlinear relationship observed between omega-3 PUFAs intake and OA \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\left(P \ ext{ for non-linearity}\ ext{ = 0.034}\\right)$$\\end{document}. The IVW results showed there was no evidence to suggest a causal relationship between omega-3 PUFAs and OA risk \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ ext{[OR} (95\\% \ ext{CI): }0.967 (0.863, 1.084), P = 0.568]$$\\end{document}.ConclusionsOmega-3 PUFAs were inversely associated with OA in adults aged 40 ∼ 59. However, MR studies did not confirm a causal relationship between the two.

Harnessing Oxylipins and Inflammation Modulation for Prevention and Treatment of Colorectal Cancer.

Colorectal cancer (CRC) is one of the most prevalent cancers worldwide, ranking as the third most malignant. The incidence of CRC has been increasing with time, and it is reported that Westernized diet and lifestyle play a significant role in its higher incidence and rapid progression. The intake of high amounts of omega-6 (n - 6) PUFAs and low levels of omega-3 (n - 3) PUFAs has an important role in chronic inflammation and cancer progression, which could be associated with the increase in CRC prevalence. Oxylipins generated from PUFAs are bioactive lipid mediators and have various functions, especially in inflammation and proliferation. Carcinogenesis is often a consequence of chronic inflammation, and evidence has shown the particular involvement of n - 6 PUFA arachidonic acid-derived oxylipins in CRC, which is further described in this review. A deeper understanding of the role and metabolism of PUFAs by their modifying enzymes, their pathways, and the corresponding oxylipins may allow us to identify new approaches to employ oxylipin-associated immunomodulation to enhance immunotherapy in cancer. This paper summarizes oxylipins identified in the context of the initiation, development, and metastasis of CRC. We further explore CRC chemo-prevention strategies that involve oxylipins as potential therapeutics.

Abstract PO5-23-11: Elevated linoleic acid levels in red blood cells membrane predicts response to neoadjuvant chemotherapy in breast cancer patients

Abstract Introduction: Fatty acids (FA) consumed in the diet have been implicated in increasing the risk of breast cancer (BC). Humans have a wide variety of FAs, including saturated (SFA), monounsaturated (MUFA), and polyunsaturated (PUFA) FAs. PUFAs can be further classified into omega-3 (n-3) and omega-6 (n-6) PUFAs. While n-3 has been associated with reducing inflammation and promoting apoptosis in BC cells, n-6 has been linked to increased inflammation, oxidative stress, and the promotion of BC cell proliferation and treatment resistance. In healthy women, the n-3 content in mammary tissue correlates with n-3 content in red blood cells (RBCs). The FA profile of the RBC membrane provides an unbiased option to assess lipid intake and composition, reflecting long-term FA intake and providing an objective and sensitive measure of lipid intake and body fat deposits. Notably, BC patients have been found to display a high n-6:n-3 ratio in RBCs, which is associated with inflammatory and oxidative stress biomarkers. The neoadjuvant chemotherapy treatment (NACT) model presents a unique opportunity to study resistance mechanisms in non-metastatic BC patients. In this approach, the absence of tumor (pathologic complete response: pCR, or Residual Cancer Burden (RCB) = 0) after NACT indicates treatment sensitivity and better overall survival (OS). Objective: The objective of this study is to determine whether differences in FA profiles determined in the RBC membrane and plasma are associated with the response to NACT in non-metastatic BC patients. Methods: A prospective study was conducted, including non-metastatic BC patients scheduled to receive NACT. Blood samples were collected before the first cycle of NACT to measure plasma and RBC FA derivatives, SFAs, MUFAs, and PUFAs. The pathological complete response (pCR) and residual cancer burden (RCB) were assessed. Results: A total of twenty-eight BC patients were included in the study. When comparing pCR vs. no-pCR using total SFA, MUFA, and PUFA plasma samples, no significant differences were observed. However, in RBC, an increase in PUFA was associated with a higher rate of no-pCR (**p< 0.01). Furthermore, comparing omega-6 and omega-3 (both PUFA) levels, an increase in omega-6 was associated with no-pCR (**p< 0.01), while no significant differences were observed with omega-3. No differences were obtained in plasma samples for either omega-6 and omega-3. To determine which specific omega-6 PUFAs were responsible for the association with no-pCR, elevated levels of linoleic acid (LA) in RBC were found to be associated with no-pCR (**p< 0.01). Other omega-6 PUFAs, including gamma-linolenic acid (GLA), eicosadienoic acid (EDA), dihomo-gamma linolenic acid (DGLA), and arachidonic acid (ARA), showed no significant associations. Multivariate and regression analysis confirmed LA (C18:2 n-6, LA) as the most relevant FA when assessing RCB (0-1 vs. 2-3) in RBC membranes, but not in plasma. The receiver operating characteristic (ROC) curve analyzing LA levels in RBC showed an area under the curve (AUC) of 0.855 for RCB (sensitivity: 76.9%, specificity: 92.3%). Conclusions: To the best of our knowledge, this is the first study demonstrating a clear connection between RBC membrane FA composition, specifically LA concentration, and the pathological response in BC patients after NACT. The measurements taken in plasma did not show significant associations, suggesting that RBC membrane FA profile of could serve as a relevant prognostic biomarker for studying resistance mechanisms to NACT in early BC patients Table. Measured FAs in RBC membrane and plasma by pathologic complete response *Indicates p<0.05; abbreviations: pCR: pathological complete response; SD: standard deviation; yr: years; BMI: body mass index; HR: hormone receptor; HER2: human epidermal growth factor receptor type-2; NLR: neutrophil to lymphocyte ratio; HG: histological grade; RCB: residual cancer burden; NA: not applicable Citation Format: Benjamin Walbaum, César Sánchez, Francisco Acevedo. Elevated linoleic acid levels in red blood cells membrane predicts response to neoadjuvant chemotherapy in breast cancer patients [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-23-11.

Omega-3 fatty acids and health of auditory and vestibular systems: a comprehensive review.

The purpose of this study was to comprehensively review animal and human studies that explore the role of omega-3 PUFAs in maintaining the health of the auditory organ across all life stages. This narrative review involved searching Scopus, PubMed, Google Scholar, and Cochrane Library databases for relevant articles from December 1980 to July 2023. some animal and human studies suggest that both deficiency and excessive intake of long-chain omega-3 PUFAs, particularly docosahexaenoic acid (DHA), can lead to auditory neural conduction impairment and reduced hearing acuity from fetal development to old age (presbycusis). These effects are likely to be dependent on the dosage. Some research indicates that an excessive intake of omega-3, rather than a deficiency, can result in nutritional toxicity and hearing impairments. Animal studies highlight the positive impact of omega-3 supplements with high DHA content in addressing hearing damage, but human research on this subject is limited. Furthermore, certain studies propose that omega-3 PUFAs may prevent or delay age-related hearing loss, with high plasma omega-3 concentration, particularly long-chain omega-3 PUFA, linked to reduced hearing loss. Additionally, consuming fish more than twice a week may be associated with a lower risk of hearing loss in adulthood, with these effects potentially influenced by age and gender. However, the majority of studies have been conducted on animals, and clinical trials are scarce. Research on the influence of omega-3 PUFAs on the peripheral and central vestibular systems remains limited. This article delves into the impact of omega-3 on the auditory-vestibular system, exploring its influence on neurodevelopment, protection, and treatment. It not only highlights specific research gaps but also offers valuable insights for potential future studies.

Abstract PO5-14-01: Weight loss and omega-3 polyunsaturated fatty acid intervention in overweight and obese peri- and postmenopausal women with increased breast cancer risk modifies the gut microbiome and is associated with circulating biomarkers

Abstract Background: Obesity-associated gut microbiome dysbiosis is thought to increase risk for postmenopausal breast cancer through alteration of estrogen metabolism and an increase in pro-inflammatory microbe abundance. Many studies have reported an increase in the Firmicutes/Bacteroidetes phyla ratio as a biomarker of obesity and is associated with adverse metabolic outcomes. Marine omega-3 eicosapentaenoic (EPA) and docosahexaenoic (DHA) fatty acids are thought to have favorable metabolic and inflammation resolving properties resulting in reduced risk for several epithelial cancers. One possible mechanism is the effect of EPA and DHA on the gut microbiome. We assessed the effect of weight loss and/or omega-3 supplementation on the gut microbiome and circulating molecular breast cancer risk factors. Methods: 46 peri/postmenopausal overweight and obese women at increased risk for breast cancer were enrolled into a weight-loss intervention and after 2 weeks randomized to 3.25 g/day combined EPA and DHA or placebo (PMC8416797). Fecal samples were collected at 0, 2-weeks and 6-months, with matched fecal samples for all timepoints available for 26 patients. Fecal samples at 6-months were available for 34 patients. 12M read depth metagenomic sequencing was performed on DNA isolated from feces to determine shifts in the gut microbiome. Fasting and non-fasting blood was also collected for circulating biomarker analysis. Body composition by DXA scan were also performed at baseline and 6-month time points. Results: Mean baseline BMI was 32 kg/m2. There was no significant difference between arms in age, baseline BMI, % body fat, or baseline Firmicutes/Bacteroidetes ratio. We identified gut microbiota species (A. hadrus and P. faecium) that correlated with metabolic parameters (% body fat, adiponectin/leptin ratio, and fasting insulin), species (P. dorei and B. ovatus) that correlated with estradiol levels, and mucin-degrading species (D. formicigenerans and R. gnavus) whose abundance correlated with inflammation (as measured by circulating monocyte-chemoattractant protein 1 (MCP-1)). Median 6-month weight change for all randomized subjects was -10% from baseline. Favorable change in the Firmicutes/Bacteroidetes ratio was associated both with the degree of weight loss and with omega-3 supplementation, although significant species modification differed between weight loss and omega-3 PUFA groups. Women with both >10% weight loss and omega-3 supplementation had a significantly reduced Firmicutes abundance and lower Firmicute/Bacteroidetes ratio than other groups. Species abundance shifts appear to differ between weight loss and omega-3 supplementation with 3 species modified by weight loss and 12 species shifted by omega-3 PUFA administration. Omega-3 PUFA supplementation significantly reduced proportional abundance of Dorea formicigenerans, which was a microbe associated with inflammation. Conclusions: Omega-3 supplementation at 3.25 g/day compared to placebo had a greater net effect on changing the gut microbiome in overweight and obese women at increased risk for breast cancer undergoing a weight loss intervention. Change in the gut microbiome may serve as a useful response biomarker in Phase II prevention trials of omega-3 fatty acid and weight loss. Citation Format: Katherine L. Cook, Erin Giles, Amy Kreutzjans, Shahid Umar, Christie Befort, Bruce Kimler, Stephen Hursting, Carol Fabian. Weight loss and omega-3 polyunsaturated fatty acid intervention in overweight and obese peri- and postmenopausal women with increased breast cancer risk modifies the gut microbiome and is associated with circulating biomarkers [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-14-01.

The disparate effects of omega-3 PUFAs on intestinal microbial homeostasis in experimental rodents under physiological condition

The health benefits of omega-3 polyunsaturated fatty acids (omega-3 PUFAs), primarily eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are linked to their regulatory effects on the composition of the gut microbiota. However, there is a lack of direct evidence on whether omega-3 PUFAs regulate the gut microbial homeostasis under physiological conditions. This study investigated the impact of equivalent doses of EPA, DHA, and fish oil (FO) with a DHA to EPA ratio of approximately 1:1 on the bacterial and fungal composition of normal young mice. This study also analyzed changes in key components of the gut microenvironment, including the colonic mucus barrier and short-chain fatty acids, to address the prebiotic potential of omega-3 PUFAs. The results showed that all three omega-3 PUFAs interventions induced significant fluctuations in the gut bacteria and fungi, leading to an increase in the abundance of some probiotics. Notably, DHA, EPA, and FO interventions significantly increased the abundance of the probiotic Lactobacillus, Bifidobacterium, and Akkermansia, respectively. Both DHA and fish oil interventions also significantly reduced the abundance of potentially pathogenic fungi, such as Aspergillus and Penicillium. Association analysis of the top 19 differential fungal and bacterial genera in abundance revealed a much more bacteria-bacteria and bacteria-fungi connections, but fewer fungi-fungi connections. This highlights the importance of bacteria in the gut microecological network. Furthermore, the levels of butyric acid and valeric acid in the colonic contents of DHA intervention group were significantly increased, and the colonic mucus layer thickness was increased in three treatment groups. In summary, DHA, EPA and FO interventions showed targeted enhancement of different probiotics and enhanced colon defense barrier (mucus barrier), showing potential prebiotic effects.