The effect of vitamin D3 and omega-3 combination, taken orally, on triglycerides, lining of intestine and the biodiversity of gut.

AIMS: The gut microbiota plays a key role in host health. An intake of omega-3 and vitamin D3 in a separate manner is vital for maintaining good health of gut microbiota and controlling some illness manifestations. The aim of this study is to investigate the potential change in biodiversity of the gut microbiome in healthy rats supplemented with vitamin D3, omega-3 alone and their combination and to reflect onto the triglyceride levels in serum and fecal samples. METHODS: Using the 16S rRNA gene Miseq Illumina NGS, and monitoring triglyceride levels in serum and fecal samples coupled with several clinical parameters, we examined the effect of orally taken combination of omega-3 and vitamin D3 alongside the separate intake of supplements on gut microbiota in 24 healthy white Wistar rats for six weeks. RESULTS: The study findings showed that combination treatment encouraged the growth of opportunistic Clostridia class during day 21 and 42 of treatment by 7.7 and 7.4 folds, respectively, exhibited incomplete absorption levels for both supplements when used concomitantly, demonstrated a damaging effect on the gut intestinal lining wall thickness (126um) when compared to control group (158um), increasing lumen diameter (400um) and showed higher triglyceride level in fecal samples. CONCLUSION: These findings indicate that omega-3 and vitamin D3 supplements as combination intake reveal unfavorable effects, thus, it is advised to conduct further in-depth studies to clarify the presence or absence of any chemical interaction between both supplements' molecules and to investigate based on human model to attain a superior perspective.

Modification in mitochondrial function is associated with the FADS1 variant and its interaction with alpha-linolenic acid-enriched diet - an exploratory study.

Fatty acid desaturase (FADS1) variant-rs174550 strongly regulates polyunsaturated fatty acid (PUFA) biosynthesis. Additionally, the FADS1 has been shown to be related to mitochondrial function. Thus, we investigated whether changes in mitochondrial function are associated with the genetic variation in FADS1 (rs174550) in human adipocytes isolated from individuals consuming diets enriched with either dietary alpha-linolenic (ALA) or linoleic acid (LA). Two cohorts of men homozygous for the genotype of FADS1 (rs174550) were studied: FADSDIET2 dietary intervention study with ALA- and LA-enriched diets and Kuopio Obesity Surgery study (KOBS), respectively. We could demonstrate that differentiated human adipose-derived stromal cells from subjects with the TT genotype had higher mitochondrial metabolism compared with subjects with the CC genotype of FADS1-rs174550 in the FADSDIET2. Responses to PUFA-enriched diets differed between the genotypes of FADS1-rs174550, showing that ALA, but not LA, -enriched diet stimulated mitochondrial metabolism more in subjects with the CC genotype when compared with subjects with the TT genotype. ALA, but not LA, proportion in plasma phospholipid fraction correlated positively with adipose tissue mitochondrial-DNA amount in subjects with the CC genotype of FADS1-rs174550 in the KOBS. These findings demonstrate that the FADS1-rs174550 is associated with modification in mitochondrial function in human adipocytes. Additionally, subjects with the CC genotype, when compared with the TT genotype, benefit more from the ALA-enriched diet, leading to enhanced energy metabolism in human adipocytes. Altogether, the FADS1-rs174550 could be a genetic marker to identify subjects who are most suitable to receive dietary PUFA supplementation, establishing also a personalized therapeutic strategy to improve mitochondrial function in metabolic diseases.

Testing maternal effects of vitamin-D and omega-3 levels on offspring neurodevelopmental traits in the Norwegian Mother, Father and Child Cohort Study.

BACKGROUND: Maternal vitamin-D and omega-3 fatty acid (DHA) deficiencies during pregnancy have previously been associated with offspring neurodevelopmental traits. However, observational study designs cannot distinguish causal effects from confounding. METHODS: First, we conducted Mendelian randomisation (MR) using genetic instruments for vitamin-D and DHA identified in independent genome-wide association studies (GWAS). Outcomes were (1) GWAS for traits related to autism and ADHD, generated in the Norwegian mother, father, and child cohort study (MoBa) from 3 to 8 years, (2) autism and ADHD diagnoses. Second, we used mother-father-child trio-MR in MoBa (1) to test causal effects through maternal nutrient levels, (2) to test effects of child nutrient levels, and (3) as a paternal negative control. RESULTS: Associations between higher maternal vitamin-D levels on lower ADHD related traits at age 5 did not remain after controlling for familial genetic predisposition using trio-MR. Furthermore, we did not find evidence for causal maternal effects of vitamin-D/DHA levels on other offspring traits or diagnoses. In the reverse direction, there was evidence for a causal effect of autism genetic predisposition on lower vitamin-D levels and of ADHD genetic predisposition on lower DHA levels. CONCLUSIONS: Triangulating across study designs, we did not find evidence for maternal effects. We add to a growing body of evidence that suggests that previous observational associations are likely biased by genetic confounding. Consequently, maternal supplementation is unlikely to influence these offspring neurodevelopmental traits. Notably, genetic predisposition to ADHD and autism was associated with lower DHA and vitamin-D levels respectively, suggesting previous associations might have been due to reverse causation.

Can Omega-3 prevent the accidence of stroke: a mendelian randomization study.

BACKGROUND: The lipid-lowering effects of Omega-3 fatty acids have been widely reported, yet their impact on ischemic stroke remains controversial. Reports on the protective effects of unsaturated fatty acids, such as Omega-6 and Omega-7, as well as saturated fatty acids in cardiovascular diseases, including hypertension and ischemic stroke, are less frequent. OBJECTIVES: This study aims to identify fatty acids associated with blood pressure and ischemic stroke through Mendelian randomization. Besides, it seeks to determine whether specific fatty acids can prevent ischemic stroke by managing blood pressure and revealing the specific mechanisms of this action. METHODS: This research involved downloading relevant data from websites and extracting SNPs that met the standard criteria as instrumental variables. Simultaneously, the 'MR-PRESSO' package and 'Mendelian Randomization' package were used to eliminate confounding SNPs that could bias the study results. Then, inverse variance weighting and the weighted median were employed as primary analysis methods, accompanied by sensitivity analysis to assess the validity of the causal relationships. Initially, multivariable Mendelian randomization was used to identify fatty acids linked to blood pressure and the incidence of ischemic stroke. The causal link between certain fatty acids and the initiation of ischemic stroke was then investigated using bidirectional and mediator Mendelian randomization techniques. Stepwise Regression and the Product of Coefficients Method in mediator Mendelian randomization were utilized to ascertain whether specific fatty acids reduce ischemic stroke risk by lowering blood pressure. RESULTS: Multivariable Mendelian randomization analysis indicated a potential inverse correlation between Omega-3 intake and both blood pressure and ischemic stroke. Consequently, Omega-3 was selected as the exposure, with blood pressure and ischemic stroke-related data as outcomes, for further bidirectional and mediation Mendelian Randomization analyses. Bidirectional Mendelian Randomization revealed that Omega-3 significantly influences DBP (P = 1.01e-04) and IS (P = 0.016). It also showed that DBP and SBP significantly affect LAS, SVS, CES, IS, and LS. Mediator Mendelian Randomization identified five established mediating pathways: Omega-3-Diastolic blood pressure-Small vessel stroke, Omega-3-Diastolic blood pressure-Cardioembolic stroke, Omega-3-Diastolic blood pressure-Lacunar stroke, Omega-3-Diastolic blood pressure-Large artery atherosclerosis stroke, and Omega-3-Diastolic blood pressure-Ischemic stroke. Of these, four pathways are complete mediation, and one pathway is partial mediation. CONCLUSIONS: The findings suggest that Omega-3 may indirectly reduce the incidence of ischemic stroke by lowering blood pressure. Thus, blood pressure modulation might be one of the mechanisms through which Omega-3 prevents ischemic stroke. In summary, incorporating an increased intake of Omega-3 in the diet can serve as one of the dietary intervention strategies for patients with hypertension. Additionally, it can act as an adjunctive therapy for the prevention of ischemic strokes and their complications.

The effects of ω-3 fatty acids on inflammatory and oxidative stress markers in patients with Type 2 diabetes mellitus: A systematic review and meta-analysis of controlled trials.

BACKGROUND & AIMS: Taking into account the anti-inflammatory and antioxidant properties of omega-3 fatty acids and the evidence indicating the role of chronic inflammation and oxidative stress in the pathophysiology diabetes, this study aimed to determine the effect of ω-3 fatty acids on oxidative stress and inflammatory markers in Type 2 diabetes mellitus (T2DM) patients. METHODS: A systematic search up to July 30, 2023 was completed in Scopus, PubMed, Web of Science, and Embase databases, to identify eligible RCTs. Heterogeneity tests of the selected studies were performed using the I2. Random effects models were assessed and pooled data were determined as standardized mean differences (SMD) with a 95% CI. RESULTS: The meta-analysis of 23 trials, involving 1,523 patients, demonstrated a significant decrease in TNF-α (SMD: -1.62, 95% CI: -2.89 to -0.35, P= 0.013) and increase in TAC (SMD: 0.92, 95% CI: 0.33 to 1.52, P = 0.002) following ω-3 fatty acids administration. Meanwhile, supplementation did not have beneficial effects on malondialdehyde, C-reactive protein (CRP), superoxide dismutase (SOD), and interlukin-6 levels. The subgroup analysis revealed a significant decrease in CRP levels and an increase in SOD levels in studies with durations of less than 12 weeks. CONCLUSIONS: We found that ω-3 fatty acid intake can significantly decrease TNF-α and increase TAC levels, but this effect was not observed on other markers. Nevertheless, future well-designed with large sample size and long duration RCT studies with precise ω-3 fatty acids dose and ingredients are required to understand better the effects of these compounds and their constituents on oxidative stress and inflammatory markers in T2DM patients.

Omega-3 Polyunsaturated Fatty Acids as a Protective Factor for Myopia.

PURPOSE: Animal models suggest omega-3 polyunsaturated fatty acids (PUFAs) may protect against myopia by modulating choroidal blood perfusion, but clinical evidence is scarce and mixed. We aimed to determine the causality between omega-3 PUFAs and myopia using Mendelian randomization (MR) analysis. DESIGN: Two-sample MR analysis. METHODS: Exposures are genetically predicted 18 fatty acids (FAs) related traits. Spherical equivalent refraction (SER) and axial length were used as measurements of myopia. Genome-wide association study summary data on blood levels of 18 FAs related traits (n=115,006), refractive spherical equivalent (n=351,091), axial length (n=69,945) and choroidal thickness (n=44,823) were sourced from the UK Biobank, the Genetic Epidemiology Research on Adult Health and Aging cohort, and the Consortium for Refractive Error and Myopia Study. We used five MR models and considered results statistically significant if the Bonferroni-corrected P-value was ≤2.78 × 10-3 in at least 3 MR models. The beta represents the change in outcomes (SER in diopter; axial length in mm; choroidal thickness in standard deviation) per standard deviation unit increase in FAs levels. RESULTS: At a Bonferroni-corrected significance, higher levels of omega-3 (Beta, 0.32-0.34), omega-3/total FAs ratio (Beta, 0.31-0.44), docosahexaenoic acid (DHA) (Beta, 0.36-0.46), DHA/total FAs ratio (Beta, 0.37-0.53), PUFAs/total FAs ratio (Beta, 0.07-1.003), and degree of unsaturation (Beta, 0.28-0.44) were associated with a more positive SER, suggesting a lower risk of myopia. Similar trends were observed for axial length albeit with borderline significance (P≤0.035 in ≥2 models). Higher levels of omega-3, DHA, DHA/total FAs ratio, PUFAs/total FAs ratio, PUFAs/monounsaturated FAs ratio, and degree of unsaturation were nominally associated with thicker choroidal thickness (Beta, 0.05-0.13; P≤0.045 in ≥2 models). CONCLUSION: Our multiple MR models suggest a protective effect of omega-3 and DHA on myopia, potentially through modulation of choroidal blood perfusion. Further randomized clinical trials are needed to confirm the effectiveness and determine the optimal dose and duration.

Efficacy and Safety of Omega-3 Fatty Acids in Ameliorating Pruritus in Adult Patients With Chronic Kidney Disease: A Meta-Analysis of Randomized Controlled Trials.

Chronic kidney disease-associated pruritus (CKD-aP) represents a common distressing problem in patients with end-stage renal disease. This study aimed to assess the efficacy and safety of omega-3 supplementation in the treatment of CKD-aP. MEDLINE/PubMed, Cochrane Central Register of Controlled Trials, Web of Science, ProQuest, and Scopus databases were searched systematically for articles published from inception until May 21, 2024. Outcomes were pruritus severity at the end of the study or its change from baseline (primary) and intervention-related adverse effects (secondary). Results were pooled as standardized mean difference (SMD) and risk ratio (RR) for numeric and dichotomous outcomes, respectively, along with their 95% confidence intervals (CIs). Eight studies were included. Treatment with omega-3 fatty acids showed a significantly lower severity of CKD-aP at the end of treatment (pooled SMD (95% CI) = -1.03 (-1.85, -0.22), p = 0.024) and changed from baseline (pooled SMD (95% CI) = -0.93 (-1.57, -0.28), p = 0.014). Omega-3 supplementation reduced the risk of CKD-aP (pooled RR (95% CI) = 0.68 (0.12, 3.81), p = 0.661). Omega-3 fatty acid supplementation appears to be a promising effective and safe treatment for CKD-aP. However, the included studies had several limitations that warrant further high-quality studies to elucidate its effect and investigate the causes of non-response in patients who did not improve.

Omega-3 Fatty Acids and Arrhythmias.

The pro- and antiarrhythmic effects of omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been extensively studied in preclinical and human trials. Despite early evidence of an antiarrhythmic role of n-3 PUFA in the prevention of sudden cardiac death and postoperative and persistent atrial fibrillation (AF), subsequent well-designed randomized trials have largely not shown an antiarrhythmic benefit. Two trials that tested moderate and high-dose n-3 PUFA demonstrated a reduction in sudden cardiac death, but these findings have not been widely replicated, and the potential of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) to reduce arrhythmic death in combination, or as monotherapy, remains uncertain. The accumulated clinical evidence does not support supplementation of n-3 PUFA for postoperative AF or secondary prevention of AF. Several large, contemporary, randomized controlled trials of high-dose n-3 PUFA for primary or secondary cardiovascular prevention have demonstrated a small, significant, dose-dependent increased risk of incident AF compared with mineral oil or corn oil comparator. These findings were reproduced with both icosapent ethyl monotherapy and a mixed EPA+DHA formulation. The proarrhythmic mechanism of increased AF in contemporary cohorts exposed to high-dose n-3 PUFA is unknown. EPA and DHA and their metabolites have pleiotropic cardiometabolic and pro- and antiarrhythmic effects, including modification of the lipid raft microenvironment; alteration of cell membrane structure and fluidity; modulation of sodium, potassium, and calcium currents; and regulation of gene transcription, cell proliferation, and inflammation. Further characterization of the complex association between EPA, EPA+DHA, and DHA and AF is needed. Which formulations, dose ranges, and patient subgroups are at highest risk, remain unclear.

A ketogenic diet, regardless of fish oil content, does not affect glucose homeostasis or muscle insulin response in male rats.

Ketogenic diets (KDs) are very high in fat and low in carbohydrates. Evidence supports that KDs improve glucose metabolism in humans and rodents that are obese and/or insulin resistant. Conversely, findings in healthy rodents suggest that KDs may impair glucose homeostasis. Additionally, most experimental KDs are composed of saturated and monounsaturated fatty acids, with almost no omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA). Evidence supports a beneficial role for n-3 LCPUFA on glucose homeostasis in the context of a metabolic challenge. To our knowledge, no study has examined whether the inclusion of n-3 LCPUFA affects the impact of a KD on glucose homeostasis. The objective of this study was to examine the impact of a KD on whole-body glucose tolerance and skeletal muscle insulin response in rats, and to determine if increasing the n-3 LCPUFA content in a KD with menhaden oil could improve metabolic outcomes. Male Sprague Dawley rats were pair-fed one of a low-fat diet, high-fat diet, KD, or a KD supplemented with menhaden oil (KDn-3) for 8 weeks. No significant differences in whole-body glucose tolerance, skeletal muscle insulin signaling, or skeletal muscle insulin-stimulated glucose uptake were detected between the dietary groups. Our findings suggest that KD feeding, with or without supplementation of n-3 LCPUFA, does not affect whole-body glucose homeostasis or skeletal muscle insulin response under pair-feeding conditions.

Understanding the Role of Polyunsaturated Fatty Acids in the Development and Prevention of Cancer.

Polyunsaturated fatty acids (PUFAs), notably omega-3 (n-3) and omega-6 (n-6), have received much attention owing to their multifaceted effects not only in the management of diverse pathological conditions but also in the maintenance of overall health of an individual. A disproportionately high n-6 to n-3 ratio contributes to the development of various disorders including cancer, which ranks as a leading cause of death worldwide with profound social and economic burden. Epidemiological studies and clinical trials combined with the animal and cell culture models have demonstrated the beneficial effects of n-3 PUFAs in reducing the risk of various cancer types including breast, prostate and colon cancer. The anti-cancer actions of n-3 PUFAs are mainly attributed to their role in the modulation of a wide array of cellular processes including membrane dynamics, apoptosis, inflammation, angiogenesis, oxidative stress, gene expression and signal transduction pathways. On the contrary, n-6 PUFAs have been shown to exert pro-tumor actions; however, the inconsistent findings and controversial data emphasize upon the need to further investigation. Nevertheless, one of the biggest challenges in future is to optimize the n-6 to n-3 ratio despite the genetic predisposition, age, gender and disease severity. Moreover, a better understanding of the potential risks and benefits as well as the cellular and molecular mechanisms of the basic actions of these PUFAs is required to explore their role as adjuvants in cancer therapy. All these aspects will be reviewed in this chapter.

Omega-3 polyunsaturated fatty acids in the brain and visual system: Focus on invertebrates.

A critical role of omega-3 polyunsaturated fatty acids (PUFA), mainly docosahexaenoic acid 22:6ω3 (DHA), in the development and function of the brain and visual system is well established. DHA, the most abundant omega-3 PUFA in the vertebrate brain, contributes to neuro- and synaptogenesis, neuronal differentiation, synaptic transmission and plasticity, neuronal network formation, memory and behaviour formation. Based on these data, the unique importance of DHA and its irreplaceability in neural and retinal tissues has been postulated. In this review, we consider omega-3 PUFA composition in the brain and retina of various invertebrates, and show that DHA has only been found in marine mollusks and crustaceans. A gradual decrease in the DHA content until its disappearance can be observed in the brain lipids of the series marine-freshwater-terrestrial crustaceans and marine-terrestrial mollusks, suggesting that the transition to the land lifestyle in the evolution of invertebrates, but not vertebrates, was accompanied by a loss of DHA. As with terrestrial crustaceans and mollusks, DHA was not found in insects, either terrestrial or aquatic, or in nematodes. We show that the nervous and visual systems of various DHA-free invertebrates can be highly enriched in alpha-linolenic acid 18:3ω3 or eicosapentaenoic acid 20:5ω3, which affect neurological and visual function, stimulating synaptogenesis, synaptic transmission, visual processing, learning and even cognition. The review data show that, in animals at different levels of organization, omega-3 PUFA are required for the functioning of the nervous and visual systems and that their specific needs can be met by various omega-3 PUFA.

Flaxseed promotes productive performance through regulating gut microbiome in ducks.

BACKGROUND: Flaxseed has been widely used in animal diets to increase the omega-3 polyunsaturated fatty acid content in animal products and promote overall animal health, but little known about its effects on the productive performance and the mictobita of gut of laying duck. METHODS AND RESULTS: Jinding duck, a Chinese indigenous breed, was used in the study. The corn-soybean basal diet supplemented with 0, 2%, 3% 4% and 5% flaxseed were provided to Control, 2% Fla, 3% Fla, 4% Fla and 5% Fla groups for 53 days, respectively. Compared with Control group, groups fed with flaxseed diets showed higher egg production, egg mass, ovary weight and more preovulatory follicles. The Docosahexaenoic Acid content of egg was extremely significantly elevated by flaxseed diets (P < 0.01), and the albumen height and haugh unit were elevated, especially in 4% Fla and/or 5% Fla group (P < 0.05). Groups 4% Fla and 5% Fla had highest ileal villus height, jejunal and ileal crypt depth. Moreover, Flaxseed diets significantly increased the levels of IgG and IgM in all Fla groups (P < 0.01), while increased IgA levels except for in 3% Fla group (P < 0.05). The results of 16s rDNA sequencing showed that flaxseed diet altered the microbial composition of gut and reduced the diversity and evenness of gut microbial communities except for 5% Fla. The correlation analysis identified Blautia, Butyricicoccus and Subdoligranulum positively associated with egg production. Genera Fourinierella, Fusobacterium and Intestinimonas positively associated with ovary weight, haught unit and album height. And Mucispirillum positively associated with haugh unit and album height. CONCLUSION: This study has suggested that flaxseed play a positive role in productive performance, the overall or intestinal health of laying ducks.

Polyunsaturated fatty acids and diabetic microvascular complications: a Mendelian randomization study.

Background: Observational studies and clinical trials have implicated polyunsaturated fatty acids (PUFAs) in potentially safeguarding against diabetic microvascular complication. Nonetheless, the causal nature of these relationships remains ambiguous due to conflicting findings across studies. This research employs Mendelian randomization (MR) to assess the causal impact of PUFAs on diabetic microvascular complications. Methods: We identified instrumental variables for PUFAs, specifically omega-3 and omega-6 fatty acids, using the UK Biobank data. Outcome data regarding diabetic microvascular complications were sourced from the FinnGen Study. Our analysis covered microvascular outcomes in both type 1 and type 2 diabetes, namely diabetic neuropathy (DN), diabetic retinopathy (DR), and diabetic kidney disease (DKD). An inverse MR analysis was conducted to examine the effect of diabetic microvascular complications on PUFAs. Sensitivity analyses were performed to validate the robustness of the results. Finally, a multivariable MR (MVMR) analysis was conducted to determine whether PUFAs have a direct influence on diabetic microvascular complications. Results: The study indicates that elevated levels of genetically predicted omega-6 fatty acids substantially reduce the risk of DN in type 2 diabetes (odds ratio (OR): 0.62, 95% confidence interval (CI): 0.47-0.82, p = 0.001). A protective effect against DR in type 2 diabetes is also suggested (OR: 0.75, 95% CI: 0.62-0.92, p = 0.005). MVMR analysis confirmed the stability of these results after adjusting for potential confounding factors. No significant effects of omega-6 fatty acids were observed on DKD in type 2 diabetes or on any complications in type 1 diabetes. By contrast, omega-3 fatty acids showed no significant causal links with any of the diabetic microvascular complications assessed. Conclusions: Our MR analysis reveals a causal link between omega-6 fatty acids and certain diabetic microvascular complications in type 2 diabetes, potentially providing novel insights for further mechanistic and clinical investigations into diabetic microvascular complications.

Targeting maternal gut microbiome to improve mental health outcomes-a pilot feasibility trial.

Background: Perinatal depression and anxiety (PDA) is prevalent in new and expectant mothers, affecting millions of women worldwide. Those with a history of mood and anxiety disorders are at the greatest risk of experiencing PDA in a subsequent pregnancy. Current safety concerns with pharmacological treatments have led to a greater need for adjunctive treatment options for PDA. Changes in the composition of the microbiome have been associated with various diseases during pregnancy, and these changes are thought to play some role in perinatal mood disorders. While the relationship between PDA and the microbiome has not been explored, evidence suggests that nutritional interventions with fiber, fish oils, and probiotics may play a favorable role in neuropsychiatric outcomes during and after pregnancy. The primary objective of the present study is to assess the feasibility and acceptability of a combination of nonpharmacological interventions to maintain stability in pregnant women who have a history of depression and/or anxiety. This study will also aim to understand ease of recruitment and protocol adherence in this cohort. Methods: This is a single-centered, partially randomized, placebo-controlled, double-blind feasibility trial. One hundred pregnant women with a history of depression and/or anxiety/PDA will be recruited and randomized into one of four arms, which could include the following: receiving a daily dose of both investigational products and dietary counseling on increasing dietary fiber, receiving a daily dose of both investigational drugs only, receiving fish oil investigational product and placebo, and a control arm with no intervention. The study involves six study visits, all of which can be conducted virtually every 3 months from the time of enrollment. At all study visits, information on diet, mental health, physical activity, and sleep quality will be collected. Additionally, all participants will provide a stool sample at each visit. Discussion: It is anticipated that pregnant women with a history of depression and anxiety will be particularly interested in partaking in this trial, resulting in favorable recruitment rates. Given the positive findings of omega-3 fatty acids (O3FAs) and probiotic supplements on mental health symptoms in nonpregnant adults, we expect a similar trend in PDA symptoms, with a low likelihood of adverse events. This study will build the foundation for larger powered studies to further contribute evidence for the efficacy of this potential preventative treatment option. Trial registration: This trial was registered at ClinicalTrials/gov on October 6, 2023; NCT06074250. Trial Sponsor: The Canadian College of Naturopathic Medicine, 1255 Sheppard Ave E, Toronto, ON M2K 1E2, 416-498-1255.

Relationships of omega-3 and omega-6 polyunsaturated fatty acids with esophageal diseases: a two-sample Mendelian randomization analysis.

Introduction: Omega-3 polyunsaturated fatty acids (PUFAs) have been widely studied and used as nutritional supplements because of their anti-inflammatory effects. Previous studies have shown an association between polyunsaturated fatty acids such as omega-3 and omega-6 PUFAs with the development of malignant tumors. However, the relationships of omega-3 and omega-6 PUFAs with esophageal diseases have not been characterized. Methods: Mendelian randomization (MR) is a statistical method for identifying instrumental variables (IVs) from genome-wide association study (GWAS) data, and is associated with little confounding by environmental or other disease-related factors. We used genome-wide association study (GWAS) data from previously published studies on circulating concentrations of omega-3, omega-6, docosahexaenoic acid (DHA) and linoleic acid (LA), as well as esophageal cancer and other esophageal diseases, which were downloaded from the IEU OpenGwas database (https://gwas.mrcieu.ac.uk/) and the GWAS Catalog database (https://www.ebi.ac.uk/). The inverse variance-weighted approach was used as the principal analysis, and the MR-Egger and weighted median methods were used alongside. A series of sensitivity analyses were used to ensure the robustness of the causality estimates. Results: We found that the circulating omega-3 PUFAs concentration was positively associated with esophageal cancer (p = 8 × 10-4), and circulating DHA concentration (the main component of omega-3 in food), was also positively associated with esophageal cancer (p = 2 × 10-2), but no significant association was found between circulating omega-6 PUFAs and esophageal cancer (p = 0.17), and circulating LA concentration (the main component of omega-6 in food), was also no significant associated with esophageal cancer (p = 0.32). We found no significant relationships of circulating omega-3 and omega-6 PUFAs concentration with four other esophageal diseases. Conclusion: This study indicates that higher levels of circulating omega-3 PUFAs and DHA concentrations may be a risk factor for the development of esophageal cancer. Conversely, an increased omega-6/omega-3 ratio may serve as a protective factor against esophageal cancer. These findings have significant implications for the clinical application of omega-3 PUFAs and the prevention and treatment of esophageal cancer.

Long-chain polyunsaturated fatty acids and brain functions - literature review.

Long-chain ω-3 PUFAs such as DHA and EPA are often present in high amounts in algae and fish. DHA in particular is crucial for the proper development and functioning of the brain because it is the main structural component of ω-3 PUFA in the brain. This makes it an indispensable element of the phospholipids of the nervous membrane. The purpose of this article is to present the benefits of Omega-3 acids in the functioning of the nervous system. The text discusses a literature review focusing on the impact of omega-3 fatty acids. Polyunsaturated fatty acids (PUFAs) are essential for overall health and have been extensively studied for their contributions to human well-being and disease management. Recent research indicates their effectiveness in preventing and treating various diseases. Omega-3 PUFAs have been identified as therapeutic agents, particularly in combating inflammatory conditions like cardiovascular and neurodegenerative diseases. The aim of this article is to present the benefits of omega-3 fatty acids supplementation. Publications outlining properties of polyunsaturated fatty acids on the brain and articles presenting the effects of polyunsaturated fatty acids were reviewed using the Pubmed platform. The review included the keywords "Omega-3 fatty acids" "DHA" "EPA" "PUFA.

A plasma lipid signature in acute human traumatic brain injury: Link with neuronal injury and inflammation markers.

Traumatic brain injury (TBI) leads to major membrane lipid breakdown. We investigated plasma lipids over 3 days post-TBI, to identify a signature of acute human TBI and assess its correlation with neuronal injury and inflammation. Plasma from patients with TBI (Abbreviated Injury Scale (AIS)3 - serious injury, n = 5; AIS4 - severe injury, n = 8), and controls (n = 13) was analysed for lipidomic profile, neurofilament light (NFL) and cytokines, and the omega-3 index was measured in red blood cells. A lipid signature separated TBI from controls, at 24 and 72 h. Major species driving the separation were: lysophosphatidylcholine (LPC), phosphatidylcholine (PC) and hexosylceramide (HexCer). Docosahexaenoic acid (DHA, 22:6) and LPC (0:0/22:6) decreased post-injury. NFL levels were increased at 24 and 72 h post-injury in AIS4 TBI vs. controls. Interleukin (IL-)6, IL-2 and IL-13 were elevated at 24 h in AIS4 patients vs. controls. NFL and IL-6 were negatively correlated with several lipids. The omega-3 index at admission was low in all patients (controls: 4.3 ± 1.1% and TBI: 4.0 ± 1.1%) and did not change significantly over 3 days post-injury. We have identified specific lipid changes, correlated with markers of injury and inflammation in acute TBI. These observations could inform future lipid-based therapeutic approaches.

The Impact of Dietary Unsaturated Fat or the Mediterranean Diet on Women Diagnosed With Breast Cancer: A Systematic Review.

This review explores the multifaceted relationship between dietary factors and breast cancer outcomes, focusing on unsaturated fats, the Mediterranean diet (MD), and other nutritional components. Breast cancer remains a significant global health concern, with lifestyle factors like diet playing a pivotal role in prevention and management. The review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Articles written in English and released between 2019 and 2024 were acceptable. We used pertinent search terms such as "unsaturated fats", "Mediterranean diet", "breast cancer", and "nutrition" to perform searches in PubMed, PubMed Central (PMC), EBSCOhost, and grey literature such as Google Scholar. After screening, 11 of the 479 original papers were chosen and included in the final review. These include cross-sectional analysis and systematic review, cohort study, narrative review, systematic review and meta-analysis, case-control study, randomized controlled trials (RCTs), and cross-sectional study. Key findings suggest that adherence to the MD correlates with improved quality of life measures and reduced mortality rates among women with breast cancer, particularly in older age groups. The diet's emphasis on antioxidant-rich foods, anti-inflammatory compounds, and healthy fats contributes to these observed benefits. Specific unsaturated fats, notably omega-3 polyunsaturated fatty acids (PUFAs) like docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), demonstrate anti-cancer properties by modulating cancer cell behavior and enhancing treatment responses. Biomarkers associated with the MD, such as ß-carotene and lycopene, serve as indicators of dietary compliance and potential risk reduction. Furthermore, components found in olive oil, including polyphenols and monounsaturated fatty acids, exhibit promising effects in preventing breast cancer by exerting antioxidant and anti-proliferative actions. Other dietary factors like calcium, legumes, fruits, and vegetables also play a role in reducing breast cancer risk and improving survival rates. This review underscores the importance of dietary interventions in optimizing outcomes for breast cancer patients and highlights the need for further research to elucidate underlying mechanisms and refine dietary recommendations.

Lipid-Lowering Medications for Managing Dyslipidemia: A Narrative Review.

Dyslipidemia refers to the change in the normal levels of one or more lipid components in the bloodstream, which include triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). Dyslipidemia represents a substantial source of danger for cardiovascular disease (CVD). Effectively managing dyslipidemia involves a thorough strategy that includes changing one's lifestyle and using medications that are specifically designed to target the complex processes involved in lipid metabolism. Lipid-lowering treatments play a crucial role in this approach, providing a wide range of medications that are developed to specifically target different components of dyslipidemia. Statins are the main drug among these medications. Other drugs that are used with statin or as monotherapy include fibrates, omega-3 fatty acids (OM3FAs), ezetimibe, bile acid sequestrants, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, and bempedoic acid. Using the PubMed database, we reviewed the literature about dyslipidemia, drugs used for treating dyslipidemia, their efficacy parameters, and common adverse events. We also reviewed the international guidelines for treating dyslipidemia and discussed the future of lipid-lowering medications. More trials and experiments are still required to verify the effectiveness of many lipid-lowering drugs and to know their common adverse events to be able to manage them properly.

The efficacy and acceptability of anti-inflammatory omega-3 polyunsaturated fatty acid supplements in sepsis management: a network meta-analysis of randomized controlled trials.

Sepsis is a critical medical condition associated with high mortality for patients. Current pharmacological strategies for sepsis management or prevention had not achieved satisfactory results. The omega-3 fatty acids, with anti-inflammatory benefits, are considered to be promising agents for sepsis management/prevention. The aim of this network meta-analysis (NMA) is to compare the efficacy of various dosages and formulations of fish oil supplements for sepsis management and sepsis prevention. The current NMA consisted of two parts: (1) sepsis management and (2) sepsis prevention. The PubMed, ClinicalKey, Embase, ProQuest, Cochrane CENTRAL, ScienceDirect, Web of Science, and ClinicalTrials.gov databases were systematically searched to date of February 22nd, 2024 for relevant randomized controlled trials (RCTs). RCTs were eligible for inclusion if they enrolled participants with a diagnosis of sepsis or who with high risk for sepsis. All NMA procedures were conducted under the frequentist model. The primary outcomes assessed are (1) mortality rate in sepsis treatment or (2) incidence of sepsis in sepsis prevention. Our NMA, based on 28 RCTs and 1718 participants (mean age=51.6 years, mean female proportion=35.6 %), showed that (1) high dose parenteral fish oil supplement yield the lowest mortality rate in sepsis management in adult patients, and (2) high dose enteral fish oil supplement yield the lowest incidence of sepsis in pediatric patients. This study provides compelling evidence that high-dose fish oil supplements provide beneficial effects for both sepsis management and sepsis prevention. Our findings provide a preliminary rationale for future large-scale RCTs to investigate the role of fish oil supplementation in sepsis management or prevention.