EPA (Eicosapentaenoic Acid)

OBJECT: Glioblastoma is a rapidly infiltrating tumor that consistently rematerializes despite various forms of aggressive treatment. Brain tumors are commonly treated with alkylating drugs, such as lomustine, which are chemotherapeutic agents. Use of these drugs, however, is associated with serious side effects. To reduce the side effects, one approach is to combine lower doses of chemotherapeutic drugs with other nontoxic anticancer agents. In this study, using glioblastoma cell lines, the authors investigated the anticancer effects of lomustine, alone and in combination with docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid normally abundant in the brain and known for its anticancer potential. METHODS: Cells were cultured from 3 human-derived tumor cell lines (U87-MG, DB029, and MHBT161) and supplemented with either DHA or lomustine to determine the growth inhibitory potential using WST-1, a mitochondrial functional indicator. Human-derived cerebral cortex microvascular endothelial cells served as a normal phenotypic control. Cellular incorporation of DHA was analyzed by gas chromatography. Using flow cytometric analysis, the DHA and/or lomustine effect on induction of apoptosis and/or necrosis was quantified; subsequently, the DHA and lomustine effect on cell cycle progression was also assessed. Western blot analysis confirmed the role of downstream cellular targets. RESULTS: U87-MG growth was inhibited with the supplementation of either DHA (ED50 68.3 μM) or lomustine (ED50 68.1 μM); however, growth inhibition was enhanced when U87-MG cells were administered equimolar doses of each compound, resulting in nearly total growth inhibition at 50 μM. Gas chromatography analysis of the fatty acid profile in DHA-supplemented U87-MG cells resulted in a linear dose-dependent increase in DHA incorporation (< 60 μM). The combination of DHA and lomustine potently induced U87-MG apoptosis and necrosis as indicated by flow cytometric analysis. Activation of caspase-3 and poly (ADP-ribose) polymerase (PARP) was evident in lomustine-treated U87-MG cells, although this activation did not appear to be dependent on DHA supplementation. Additionally, lomustine-tr

BACKGROUND & AIMS: In 2023, the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) issued new safety information on oral fish oil (FO) pharmacotherapy. This information indicated a dose-related increased risk of atrial fibrillation (AF) with FO in patients with established cardiovascular disease (CVD). The aim of this study is to analyse the existing evidence on this risk and establish whether it can be extrapolated to FO-enriched intravenous lipid emulsions (FO-ILEs) or to other patient groups, such as critically ill patients with organ dysfunction. METHODS: We searched for large (>50,000 participants) systematic reviews analysing the effect of long-term (>1 year) oral FO pharmacotherapy on the incidence of AF in non-critically ill patients with CVD. Reviews also had to include at least one large randomised study (>1,000 participants) on this topic. We examined these reviews with regard to specific limitations. We also estimated on a theoretical basis the extent to which short-term use of FO-ILEs in critically ill patients might alter plasmatic EPA (eicosapentaenoic acid)/DHA (docosahexaenoic acid) concentrations or myocardial EPA/DHA content, and investigated how these changes might affect the cardiac conduction system. We identified six meta-analyses, which consistently showed an increased risk of AF (primary, secondary, exploratory or safety outcome). In these analyses, however, significant bias may arise from including studies that ignored informative censoring or competing risks, or that used highly variable methods to search for AF. The results of these meta-analyses also conflicted with those of controlled trials in which AF was the primary endpoint, investigating the effect of long-term oral FO pharmacotherapy on the frequency of AF recurrence in patients with paroxysmal or persistent AF. Based on our theoretical considerations, it is unlikely that short-term (<4 weeks) use of FO-ILEs would increase EPA/DHA plasma concentrations or myocardial contents to levels that could induce AF in critically ill patients. RESULTS AND CONCLUSIONS: Short-term administration of FO-ILEs at the currently recommended dose (0.1-0.2 g/

Objectives: No pharmacologic treatment that targets the pathophysiologic alterations of acute respiratory distress syndrome (ARDS) has proven effective. Previous studies have revealed overactive oxidative stress as a potential therapeutic target. Thus we conducted this systematic review to assess the efficacyof antioxidant therapy on the clinical outcomes of ARDS patients.Methods: We retrieved clinical trials from electronic databases. Articles and conference abstracts about antioxidant therapies for patients with ARDS were identified in which the overall effect of each antioxidant therapy on the mortality of ARDS patients was summarized.Results: We identified 18 relevant studies that met the inclusion criteria, including 899 patients in the experimental group and 870 patients in the control group. The pooled results indicated that most antioxidant therapies could not improve all-cause mortality and might even be harmful in ARDS patients at low risk of death.Conclusion: Unclassified patients could not benefit from the antioxidant therapies, and thus discretion must be exercised when using these therapies.Abbreviations ARDS: Acute respiratory distress syndrome; ICU: Intensive care unit; NAC: N-acetylcysteine; ROS: Reactive oxygen species; RNS: Reactive nitrogen species; RR: Relative risk; CI: Confidence interval; OTC: L-2-oxothiazolidine-4-carboxylic acid; EPA: Eicosapentaenoic acid; DHA: Docosahexaenoic acid; GLA: Gamma-linolenic acid; NA: Not applicable; PaO2/FiO2 ratio: The ratio of partial pressure arterial oxygen and fraction of inspired oxygen; ALI: Acute lung injury.

Deficiency of omega-3 polyunsaturated fatty acids (PUFAs) and an alteration between the ratio of omega-3 and omega-6 PUFAs may contribute to the pathogenesis of bipolar disorder and unipolar depression. Recent epidemiological studies have also demonstrated an association between the depletion of PUFAs and suicide. Our aim was to investigate the relationship between PUFAs and suicide; assess whether the depletion of PUFAs may be considered a risk factor for suicidal behavior; in addition to detailing the potential use of PUFAs in clinical practice. We performed a systematic review on PUFAs and suicide in mood disorders, searching MedLine, Excerpta Medica, PsycLit, PsycInfo, and Index Medicus for relevant epidemiological, post-mortem, and clinical studies from January 1997 to September 2016. A total of 20 articles from peer-reviewed journals were identified and selected for this review. The reviewed studies suggest that subjects with psychiatric conditions have a depletion of omega-3 PUFAs compared to control groups. This fatty acid depletion has also been found to contribute to suicidal thoughts and behavior in some cases. However, large epidemiological studies have generally not supported this finding, as the depletion of omega-3 PUFAs was not statistically different between controls and patients diagnosed with a mental illness and/or who engaged in suicidal behavior. Increasing PUFA intake may be relevant in the treatment of depression, however in respect to the prevention of suicide, the data is currently not supportive of this approach. Changes in levels of PUFAs may however be a risk factor to evaluate when assessing for suicide risk. Clinical studies should be conducted to prospectively assess whether prescriptive long-term use of PUFAs in PUFA-deficient people with depression, may have a preventative role in attenuating suicide.

OBJECTIVES: To update a prior systematic review on the effects of omega-3 fatty acids (n-3 FA) on maternal and child health and to assess the evidence for their effects on, and associations with, additional outcomes. DATA SOURCES: MEDLINE®, Embase®, the Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Centre for Agriculture and Biosciences (CAB) Abstracts from 2000 to August 2015; eligible studies from the original report; and relevant systematic reviews. REVIEW METHODS: We included randomized controlled trials (RCTs) of any defined dose of n-3 FA (or combination) compared to placebo, any other n-3 FA, or alternative dose with an outcome of interest conducted in pregnant or breastfeeding women or neonates (preterm or term). We also included prospective observational studies that analyzed the association between baseline n-3 FA intake or biomarker level and followup outcomes. Postnatal interventions began within a week of birth for term infants and within a week of beginning enteral or oral feeding for preterm infants. Standard methods were used for data abstraction and analysis, according to the Evidence-based Practice Center Methods Guide. RESULTS: We identified 4,275 potentially relevant titles from our searches, of which 95 RCTs and 48 observational studies met the inclusion criteria. Risk of bias was a concern with both RCTs and observational studies. Outcomes for which evidence was sufficient to draw a conclusion are summarized here with the Strength of Evidence (SoE). (Outcomes for which the evidence was insufficient to draw a conclusion are summarized in Appendix G of the report.). Maternal Exposures and Outcomes: Gestational length and risk for preterm birth: Prenatal algal docosahexaenoic acid (DHA) or DHA-enriched fish oil supplementation had a small positive effect on length of gestation (moderate SoE), but no effect on risk for preterm birth (low SoE). Prenatal EPA (eicosapentaenoic acid) plus DHA-containing fish oil supplementation has no effect on length of gestation (low SoE). Supplementation with DHA, or EPA plus DHA-, or DHA-enriched fish oil does not decreaserisk for preterm birth (low SoE). Birth wei

Erratum in Mol Psychiatry. 2016 Nov;21(11):1643. doi: 10.1038/mp.2016.128. The adult form of attention-deficit/hyperactivity disorder has a prevalence of up to 5% and is the most severe long-term outcome of this common disorder. Family studies in clinical samples as well as twin studies suggest a familial liability and consequently different genes were investigated in association studies. Pharmacotherapy with methylphenidate (MPH) seems to be the first-line treatment of choice in adults with attention-deficit hyperactive disorder (ADHD) and some studies were conducted on the genes influencing the response to this drug. Finally some peripheral biomarkers were identified in ADHD adult patients. We believe this work is the first systematic review and meta-analysis of candidate gene association studies, pharmacogenetic and biochemical (metabolomics) studies performed in adults with ADHD to identify potential genetic, predictive and peripheral markers linked specifically to ADHD in adults. After screening 5129 records, we selected 87 studies of which 61 were available for candidate gene association studies, 5 for pharmacogenetics and 21 for biochemical studies. Of these, 15 genetic, 2 pharmacogenetic and 6 biochemical studies were included in the meta-analyses. We obtained an association between adult ADHD and the gene BAIAP2 (brain-specific angiogenesis inhibitor 1-associated protein 2), even after Bonferroni correction, with any heterogeneity in effect size and no publication bias. If we did not apply the Bonferroni correction, a trend was found for the carriers allele 9R of dopamine transporter SLC6A3 40 bp variable tandem repeat polymorphism (VNTR) and for 6/6 homozygotes of SLC6A3 30 bp VNTR. Negative results were obtained for the 9-6 haplotype, the dopamine receptor DRD4 48 bp VNTR, and the enzyme COMT SNP rs4680. Concerning pharmacogenetic studies, no association was found for the SLC6A3 40 bp and response to MPH with only two studies selected. For the metabolomics studies, no differences between ADHD adults and controls were found for salivary cortisol, whereas lower serum docosahexaenoic acid (DHA) levels were found in ADHD adults. This last association was

BACKGROUND AND OBJECTIVE: Obesity rates continue to rise globally, highlighting the need for prevention and targeted treatment strategies. Chronic systemic low-grade inflammation and gut microbiota dysbiosis are key contributors to obesity-associated metabolic diseases. Anti-inflammatory dietary components, such as fish oil rich in omega-3 polyunsaturated fatty acids (n-3 PUFAs), reduce inflammation and improve metabolic outcomes. Similarly, physical activity improves metabolic health and attenuates chronic systemic inflammation, with varying benefits according to exercise intensity. While both interventions independently modulate inflammation and gut microbiota, their combined effects warrant further research. This study investigates the combined impact of n-3 PUFA supplementation and high-intensity interval training (HIIT) on obesity-related inflammation and gut microbiota dysbiosis, hypothesizing that improvements in gut microbiota composition driven by n-3 PUFAs may enhance the metabolic benefits of exercise. DESIGN AND METHODS: Adults with a body mass index (BMI) ≥ 25 kg/m2 are randomized to receive either 4 g/day n-3 PUFA or safflower oil (placebo) for 10 weeks. During weeks 0-4, participants take the assigned supplement. Beginning in week 4, one n-3 PUFA group and one placebo group will additionally complete 4-weeks of HIIT. Control groups perform low-intensity training (LIT) for 4 weeks. The last two weeks are a detraining phase with continued supplementation. DISCUSSION: This study explores the benefits of combining short-term HIIT and n-3 PUFA supplementation in individuals with overweight or obesity. The findings inform measurable, time-efficient interventions that target systemic inflammation, gut microbiota dysbiosis, and metabolic dysfunctions.

BACKGROUND: Structured triglycerides (STGs), in which eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are esterified with medium-chain triglycerides (MCTs), have demonstrated greater bioavailability and potential benefits in improving endurance and reducing post-exercise strength loss compared with physical mixtures (PMs) of EPA and MCTs. However, it remains unclear whether STGs have superior effects on blood EPA levels and muscular endurance and fatigue. This study compared the effects of 8-week STG and PM intake on blood EPA levels, muscular endurance, and fatigue following resistance exercise. METHODS: Twenty-eight healthy young men were randomly assigned to an STG group (n = 15) or a PM group (n = 13) in a double-blind, parallel-group, active comparator trial. Participants consumed 4,560 mg/day of the test oil (600 mg EPA, 260 mg DHA) for 8 weeks. After the intervention, the participants performed four sets of leg extensions to exhaustion at 40% of their body weight. Muscular endurance was assessed by the number of repetitions, and fatigue was evaluated by changes in maximal voluntary contraction, range of motion, thigh circumference, muscle thickness, echo intensity, and jump performance. RESULTS: The STG group showed a significantly greater increase in the serum EPA/arachidonic acid (AA) ratio compared with the PM group. However, no significant differences were found between groups in repetition counts or fatigue-related measures. CONCLUSION: Eight weeks of STG supplementation improved the blood EPA/AA ratio more than a PM, but did not yield superior effects on muscle endurance or fatigue.

BACKGROUND: Tools to measure omega-3 (n-3) polyunsaturated fatty acid (PUFA) half-lives and turnover deserve attention, as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) play vital roles in the body. Plants and marine life vary in fixed carbon-13 signatures (δ13C), allowing in vivo tracing. OBJECTIVES: To determine the half-lives and turnover of n-3 PUFAs using δ13C in this secondary analysis. METHODS: During a 28-d randomized crossover study (6-wk wash-in phase/washout phase), 12 participants (aged 19-34 y) were supplemented with 4.2 g/d α-linolenic acid (ALA) (flax oil) or 4.3 g/d DHA, 1.0 g/d EPA, and 0.2 g/d docosapentaenoic acid (n-3 DPA) (fish oil). Blood was collected on days 0, 1, 3, 7, 14, and 28. Plasma n-3 PUFA δ13C signatures were analyzed by gas chromatography-isotope ratio mass spectrometry (GC-IRMS) to calculate half-lives and turnover. RESULTS: δ13C signatures of flax oil ALA, fish oil EPA, n-3 DPA, and DHA were -33.2 ± 1.4, -26.3 ± 2.2, -26.2 ± 1.5, and -25.4 ± 1.3 mUr, respectively. Baseline signatures were not statistically different. Over time, δ13C of EPA, n-3 DPA, and DHA converged toward the isotopic signature of the fish oil supplement (P < 0.05). Using δ13C signatures, half-lives of EPA, n-3 DPA, and DHA (3.4 ± 2.7, 6.4 ± 5.3, and 6.3 ± 8.9 d, mean ± SD, respectively) and turnover rates (61.9 ± 53.1, 6.0 ± 2.9, and 78.0 ± 44.5 nmol/mL/d, respectively) were calculated. CONCLUSIONS: This is the first study to investigate n-3 PUFA half-lives and turnover in humans using GC-IRMS and the natural variance of 13C in commercial fish oils. These results were similar to preclinical model values and other clinically used methods but added the first estimate for n-3 DPA half-life and turnover rate. Compound-specific isotope analysis is a valuable tool in human studies for determining n-3 PUFA half-lives and turnover rate, as well as factors affecting them, including diet, exercise, sex, genetics, and disease.

Omega-3 polyunsaturated fatty acids (PUFAs) are known to modulate inflammatory signaling and enhance muscle recovery from exercise-induced stress. In this work, a meta-analysis was conducted that adhered to the PRISMA 2020 criteria, incorporating evidence from 41 randomized controlled trials on eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation, all of which had been conducted as evidence between 2011 and 2025 and evaluated the effects of EPA and DHA supplementation on the primary markers of the impact of exercise on inflammation and muscle injury, including the random-effects model with moderator dose, intervention duration, sex, and training status. The integrated findings showed that interleukin-6, tumor necrosis factor-α, creatine kinase, and delayed-onset muscle soreness (standardized mean difference = -0.4 to -0.7) were significantly and moderately reduced, indicating a uniform response to omega-3 supplementation's anti-inflammatory and recovery-promoting effects. C-reactive protein responses were more dispersed, suggesting that baseline inflammation differed and that the sampling protocols did as well. Subgroup analyses showed that doses of 2 g/day or more of mixed EPA + DHA, with a minimum duration of 6 weeks of administration, produced the strongest effects, especially among recreational athletes rather than elite athletes. Mechanistically, nuclear factor-kappa B activation and the ensuing synthesis of specialized pro-resolving mediators (resolvins, protectins, and maresins), as well as an increase in cellular antioxidant capacity, appear to be moderated by omega-3 supplementation and support efficient resolution of inflammation and tissue repair. These results form a body of evidence over more than 10 years, showing that omega-3 fatty acids are a strong, evidence-based nutritional tool for reducing the effects of post-exercise inflammation, supporting functional recovery, and sustaining long-term athletic performance. © 2026 Federation of American Societies for Experimental Biology.

Despite well-documented benefits of omega-3 for maternal and child health, evidence on high-docosahexaenoic acid (DHA) supplementation in low-risk pregnant women is limited. A randomized, double-blind, placebo-controlled trial was conducted among low-risk pregnant women aged 20-40 years at 22-24 weeks of gestation to evaluate the effects of high-DHA omega-3 supplementation on maternal and neonatal health outcomes. The control group (CG, n = 30) received oral olive oil supplementation, and the intervention group (IG, n = 30) received omega-3 [1700 mg, 260 mg of eicosapentaenoic acid (EPA), and 1440 mg of DHA] for ∼16 weeks or until delivery. Maternal and neonatal health outcomes were collected by telephone 15 days after delivery. Forty-five pregnant women completed the study (IG: 20; CG: 25). Adherence to supplementation was above 90% and did not differ between groups (P > .05). There were no differences between groups in mean gestational age (CG: 39.3 ± 1.6; IG: 39.2 ± 1.6; P = .877), adequate gestational weight gain (CG: 24.0%; IG: 50.0%; P = .088), adequate gestational BMI before delivery (CG: 33.3%; IG: 27.8%; P = .261), vaginal delivery (CG: 72.0%; IG: 60.0%; P = .396), full-term birth (CG: 92%; IG: 90%; P = .815), adequate weight (CG: 91.3%; IG: 94.7%; P = .237), and adequate length for gestational age (CG: 82.6%; IG: 100%; P = .056). Omega-3 supplementation with a higher concentration of DHA had no effect on the maternal and neonatal health outcomes investigated in a Brazilian sample of low-risk pregnant women. Further studies are needed to evaluate this effect in pregnant women at higher nutritional risk and with low dietary intake of omega-3. © The Author(s) [2026]. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact [email protected] for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact [email protected].

INTRODUCTION: Sarcopenia imposes a substantial burden on society, while omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation holds the potential for preventing and treating this condition. This study aims to investigate the efficacy of three different n-3 PUFA supplementation regimens compared with each other and to corn oil placebo intervention on muscle health in community-dwelling older adults at high risk of sarcopenia. METHODS AND ANALYSIS: A total of 400 community-dwelling older adults aged 60 years or older, with handgrip strength <28 kg (men) or <18 kg (women), will be recruited for this multicentre, randomised, double-blind, placebo-controlled trial. Participants will be randomly allocated (1:1:1:1) to one of four groups for 6 months: (1) the high eicosapentaenoic acid (EPA) group, (2) the high docosahexaenoic acid (DHA) group, (3) the high sn2-DHA group, (4) the corn oil control group. All intervention products will be packaged as capsules and administered at a daily dose of 2.5 g. The primary outcome is the change in handgrip strength. Secondary outcomes include changes in skeletal muscle mass, physical function, inflammation- and metabolism-related blood biomarkers and gut microbiota diversity. A ETHICS AND DISSEMINATION: This study was approved by the Ruijin Hospital Ethics Committee. Trial findings will be disseminated via publications in international peer-reviewed journals and presentations at relevant academic conferences. Study results will be made available to participants and the public on study completion. TRIAL REGISTRATION NUMBER: ChiCTR2500110506. © Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.

Background: Structured lipids, composed of re-esterified triacylglycerols containing eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and medium-chain fatty acids, may influence metabolism and endurance performance. This trial aimed to evaluate the effects of eight weeks of structured lipid supplementation on substrate utilization, erythrocyte fatty acid content, and endurance performance in healthy untrained men. Methods: In a double-blind, placebo-controlled, randomized design, 36 participants (18 per group) received either structured lipids or placebo supplementation for eight weeks. Pre- and post-supplementation assessments included maximal oxygen uptake, time to exhaustion, substrate oxidation during exercise at 65% VO2max, and erythrocyte membrane fatty acid content. Non-parametric statistical methods were used to analyze within- and between-group differences. Results: After supplementation, the structured lipids group showed statistically significant within-group changes in substrate utilization, including lower respiratory exchange ratio and higher percentage fat oxidation, total fat oxidation, and mean fat oxidation rate. Statistically significant increases were also observed in erythrocyte EPA + DHA content and time to exhaustion. Compared with the placebo group, the structured lipids group showed statistically significant post-intervention differences in substrate oxidation, erythrocyte EPA + DHA levels, and time to exhaustion. Conclusions: Eight weeks of structured lipid supplementation increased erythrocyte membrane EPA and DHA and enhanced fat oxidation during moderate-intensity exercise in untrained men. Although endurance performance improved, the change was within natural variability and showed substantial interindividual differences. Further rigorously controlled studies are needed to determine whether these metabolic adaptations yield meaningful functional benefits.

BACKGROUND AND AIM: Hypertension is an unparalleled risk factor among cardiovascular diseases (CVD) and has been reported to target over 1.4 billion people globally. The Omega-3 polyunsaturated fatty acids (PUFAs), especially the eicosapentaenoic acid (EPA) and the docosahexaenoic acid (DHA) have been put forward as possible non-pharmacological interventions to control blood pressure because they are known to be vasoactive. The purpose of the systematic review was to summarize available evidence on the vasoactive properties of omega-3 PUFAs, and how these properties apply in managing hypertension and reduction of cardiovascular risk. METHODS: Systematic review was done in compliance with the PRISMA guidelines. The search in PubMed, Scopus, and Web of Science was conducted to identify the publications published between 2010 and 2025. Inclusion criteria were randomized controlled trials, cohort studies, and other related meta-analyses on the effect of EPA and/or DHA on blood pressure, and endothelial function, inflammation, lipid metabolism, and cardiovascular outcomes. Synthesis of data was done in the form of systematic narrative without quantitative pooling. RESULTS: Randomized controlled trial evidence has shown that omega-3 PUFA supplementation is linked with slight systolic and diastolic blood pressure decreases especially in hypertensive or those with high cardiometabolic risk persons. These effects have been shown to mediate via enhancement of endothelial nitric oxide bioavailability, reduction of vascular inflammation and positive remodeling of lipid profiles. Diversity of the outcomes of the studies was noticed and probably it is the difference in dosage, ratios of EPA:DHA, duration of the intervention, and the population specifics at the baseline. CONCLUSION: Omega-3 PUFAs have shown promise as supplemental agents in the process of controlling hypertension and prevention of cardiovascular disease by a variety of complementary vasoactive pathways. Nonetheless, the heterogeneity of the studies does not allow conclusive findings on the best dosing strategies. Standardized hypertension-oriented large-scale randomized controlled trials conducted in the futur

Although preclinical studies suggest that omega-3 fatty acids may benefit skeletal health, there are few randomized controlled trials investigating effects of supplemental omega-3 on bone outcomes. This VITamin D and OmegA-3 TriaL (VITAL) ancillary study investigated effects of marine omega-3 (1 g/d; EPA+DHA in a 1.2:1 ratio) vs placebo supplements on fracture risk and bone density/structure. VITAL is a 2 × 2 factorial randomized placebo-controlled trial that studied effects of supplemental marine omega-3 fatty acids and/or vitamin D3 vs placebo on cancer and cardiovascular events. The intervention took place from November 2011 through December 2017; median follow-up was 5.3 yr. The study included 25 871 U.S. men (aged ≥50) and women (aged ≥55) without baseline cancer or cardiovascular disease, not selected for low bone density or fracture history. Primary outcomes were adjudicated incident total, nonvertebral, and hip fractures in the overall cohort. In a subcohort of 771 individuals, we measured 2-yr changes in areal BMD (aBMD) by DXA, and volumetric BMD (vBMD), cortical thickness, and bone strength indices at the radius and tibia by peripheral QCT. Supplemental omega-3 vs placebo had no effect on total (HR, 1.02; 95% CI, 0.92-1.13; p = .73), nonvertebral (HR, 1.01; 95% CI, 0.91-1.12; p = .80), or hip fractures (HR, 0.89; 95% CI, 0.61-1.30; p = .55). In the subcohort, omega-3 supplementation resulted in a small increase in whole body aBMD (+0.03% vs -0.41%, p = .006) and no effect on aBMD at the spine or hip, or vBMD or bone strength indices at the radius or tibia. No serious adverse effects were observed. Supplementation with marine omega-3 fatty acids did not reduce incident fracture risk. It led to a small increase in whole body aBMD but had no other effects on BMD or bone strength measures compared to placebo in generally healthy midlife and older adults. Plain Language Summary: Animal studies suggest that omega-3 fatty acid supplements may help bone health. However, there are few human clinical trials assessing the impact of supplemental omega-3 on bone density and fracture risk. This ancillary study to the VITamin D and OmegA-3 TriaL investigated if sup

Objective: This trial evaluated marine-derived omega-3 supplementation for primary cardiovascular prevention in middle-aged and elderly adults, focusing on endothelial activation markers and vasodilation. Methods: 240 participants were randomized to four groups receiving 0 g, 1 g, 2 g, or 4 g daily of fish oil (containing 129 mg DHA and 182 mg EPA per gram) for 12 weeks. Fasting blood samples were analyzed for fatty acids and endothelial function biomarkers (NO, ET-1, ICAM-1, MCP-1, Ox-LDL) at baseline and post-intervention. Results: Baseline characteristics and dietary intake did not differ significantly among groups (P > 0.05). Post-intervention analysis revealed a significant increase (P < 0.05) in serum EPA and DHA in all fish oil groups except the control group. The key between-group result was a significantly greater reduction in ICAM-1 (-24.21% vs. -10.90%; P = 0.026) and MCP-1 (-27.38% vs. -14.92%; P = 0.024) in the 1 g d-1 group compared to control, with higher doses (2 g d-1 and 4 g d-1) not showing incremental benefit. No other biomarkers (NO, ET-1, Ox-LDL) showed significant between-group differences. Notably, within-group changes included increased NO in the 2 g d-1 group and decreased ET-1 in the 1 g d-1 and 4 g d-1 groups from baseline. Conclusions: This study found that low-dose fish oil significantly reduced endothelial inflammatory markers (ICAM-1, MCP-1) with a U-shaped dose-response in a community-based middle-aged/elderly population, suggesting optimal anti-inflammatory effects at modest intake. No effects were seen on vasodilatory or oxidative lipid markers.

BACKGROUND: Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have unique properties that are advantageous for female. However, no study has explored the effects of omega-3 PUFA supplementation on serum ferritin levels. Thus, the objective of this study was to investigate the effects of omega-3 PUFA supplementation on serum ferritin levels in university female students. METHODS: Thirty-nine iron-deficient university female students aged 18-29 years randomly assigned in a 1:1 ratio to either the intervention group (receiving 525 mg eicosapentaenoic acid [EPA] and 175 mg docosahexaenoic acid [DHA] daily for 8 weeks) or the control group. Hemoglobin and serum ferritin levels, dietary intake, and lipidomics were assessed at baseline and after the 8-week intervention period. Analyses were performed by an independent, blinded statistician. RESULTS: The adherence rate in the study was 94.9 %. n-3 PUFA supplementation increased the omega-3 index (1.8 ± 1.7 vs. 0.4 ± 1.1; p = 0.007), while it decreased the omega-6/3 ratio (-2.6 ± 2.5 vs. -0.9 ± 1.5; p = 0.016) and arachidonic acid/EPA ratio (-9.1 ± 11.6 vs. 1.4 ± 8.5; p = 0.004) compared to those in the control group. These supplementation increased serum ferritin levels (7.8 ± 9.1 vs. 1.8 ± 8.0 ng/mL; p = 0.041); however, it did not change hemoglobin and hepcidin levels compared to those in the control group. No adverse events were observed. CONCLUSION: In this pilot study, omega-3 PUFA supplementation was associated with modest changes in iron status markers in young healthy females. These findings are exploratory, and further placebo-controlled trials are needed to confirm the effects. NAME OF TRIAL REGISTRY: The effect of omega-3 fatty acids intake on hepcidin and anemia Identifying number: UMIN000050570. DATE OF REGISTRATION: 2023/03/14.

BACKGROUND: Although several studies have examined the relationship between omega-3 (ω-3) fatty acids and pulmonary function and clinical outcomes in critically ill patients, their findings remain mixed and inconclusive, and additional research is warranted. OBJECTIVES: This study aimed to evaluate the effects of ω-3 fatty acids on pulmonary function and clinical outcomes in critically ill patients. METHODS: We searched 5 databases (PubMed, Web of Science, Embase, EBSCO, and Cochrane Central Register of Controlled Trials) to identify randomized controlled trials involving critically ill adults who received ω-3 fatty acids. Both enteral and parenteral routes of administration were included. Effect estimates were pooled using fixed- or random-effects models, and heterogeneity among studies was assessed using the I2 statistic. RESULTS: The analysis included 29 studies involving 2551 critically ill patients. The ω-3 fatty acids intervention significantly increased EPA and DHA levels. For inflammatory and immune markers, it increased CD4+ T lymphocytes, the CD4+/CD8+ ratio, and decreased C-reactive protein (CRP) levels. For pulmonary function, it increased PaO2, SaO2, and PaO2/FiO2, and decreased airway resistance, positive end expiratory pressure, and lactate levels. For clinical outcomes, it significantly shortened mechanical ventilation days [mean difference: -1.31; 95% confidence interval (CI): -2.54, -0.09; P = 0.04] and length of hospitalization (mean difference: -3.96; 95% CI: -7.83, -0.09; P = 0.04). Both enteral and parenteral supplementation with ω-3 could reduce CRP levels, shorten hospital stay, and improve the oxygenation index. Besides, ω-3 via enteral nutrition also increases PaO2 and shortens mechanical ventilation days. CONCLUSIONS: In critically ill patients, ω-3 fatty acids may improve fatty acid concentrations, modulate immune regulation, enhance pulmonary function, and be associated with improved clinical outcomes.

IMPORTANCE: Meta-analyses of ω-3 fatty acids for depression have reported inconsistent results, and pediatric evidence is sparse. Promotion of unproven supplements may delay evidence-based care. OBJECTIVE: To evaluate whether adjunctive ω-3 fatty acid supplementation improves outcomes in moderate-to-severe pediatric major depressive disorder (MDD). DESIGN, SETTING, AND PARTICIPANTS: In a multicenter, double-blind, placebo-controlled randomized clinical trial at 5 Swiss child and adolescent psychiatry centers, 257 youths with MDD were enrolled and randomized between April 28, 2017, and March 24, 2022, and followed up for 36 weeks, with final analysis from July 1, 2022, to January 26, 2023. Analysis was based on intention to treat. INTERVENTIONS: Participants received ω-3 fatty acids, 1.5 g/d (1 g of eicosapentaenoic acid [EPA] and 0.5 g of docosahexaenoic acid [DHA], 2:1 ratio), or medium-chain triglyceride placebo in combination with standardized psychotherapy. Antidepressant use was permitted per national guidelines. MAIN OUTCOMES AND MEASURES: The primary outcome was the trajectory of Children's Depression Rating Scale-Revised (CDRS-R) scores analyzed with a joint mixed-effects and time-to-event model accounting for dropout or initiation of off-trial antidepressant therapy. Secondary outcomes included response (≥30% reduction in CDRS-R scores), remission (CDRS-R score ≤28), self-rated depression, quality of life, suicidality, and safety. RESULTS: Of 257 randomized participants (mean [SD] age, 15.7 [1.7] years; 188 [73.2%] female; mean [SD] CDRS-R score, 58.5 [8.8]), 129 received ω-3 supplements and 128 received placebo. The mean (SD) CDRS-R scores decreased similarly in both groups: at 12 weeks, 45.93 (11.98) vs 46.08 (12.99); at 36 weeks, 36.50 (13.12) vs 36.83 (15.46). The adjusted mean difference in CDRS-R scores was 0.77 (95% CI, -1.39 to 2.93; P = .49) points. The hazard ratio for time to dropout was 1.22 (95% CI, 0.83-1.79; P = .32). Response occurred in 34 of 109 (31.2%) ω-3 recipients vs 43 of 110 (39.1%) placebo recipients at 12 weeks; remission occurred at 36 weeks in 30 of 94 ω-3 recipients (31.9%) vs 37 of 90 (41.1%) placebo recipients (all differe

BACKGROUND: Considering the role of a healthy diet in preventing atherogenesis, the use of beetroot as a functional food with anti-inflammatory, antioxidant, and anti-dyslipidemic effects due to its high nitrate content and bioactive compounds is one of the interesting approaches in coronary artery disease (CAD), a common worldwide chronic disease. METHODS: This is a secondary analysis of a randomized, double-blind, placebo-controlled clinical trial that was conducted on 90 male (67.8%) and female (32.2%) chronic patients with CAD for 4 weeks. This secondary analysis investigated the effect of beetroot capsules within three groups on fatty acid profile, total antioxidant capacity, total oxidant status, malondialdehyde, and myeloperoxidase. RESULTS: In subjects with 4 weeks of beetroot consumption, significant changes in the level of SFAs/PUFAs (-130 μg/mL, p = 0.04), PA/OA (-250 μg/mL, p = 0.02), and MPO (-9.60 U/L, p < 0.01) were established. In beetroot-vitamin C group, docosahexaenoic acid (9.3 μg/mL, p < 0.01), omega 3 (31 μg/mL, p < 0.001), EPA + DHA (10 μg/mL, p < 0.01), SFAs/PUFAs (-370 μg/mL, p < 0.001), PA/OA (-360 μg/mL, p < 0.001), TOS (-1.42 μM, p < 0.01), and MPO (-12.42 U/L, p < 0.001) had notable changes. CONCLUSION: Beetroot capsule consumption had favorable effects on serum omega 3 fatty acids as well as TOS and MPO, the oxidant and atherogenesis factors.

BACKGROUND: Infants born extremely preterm (EP; < 28 weeks of gestation) or term born infants with hypoxic-ischemic encephalopathy (HIE) have increased risk of long-term cognitive and learning deficits. Early supplementation with long chain polyunsaturated fatty acids (LCPUFAs) docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (ARA), choline, uridine-5'-monophosphate (UMP), and cytidine-5'-monophosphate (CMP), zinc, iodine, and vitamin B12 may improve cognitive and language outcomes in these populations. METHODS: This multicentre, blinded, stratified, randomised controlled trial, including an economic evaluation, will investigate the impact of nutritional supplementation on cognitive development in infants born EP or term born infants with HIE. The planned sample size is 1010 (538 EP, and 472 HIE) infants from up to 40 National Health Service neonatal units in the UK. The trial patient populations are infants born EP (preterm stratum) and term infants (born at or more than 35 weeks of gestation) with HIE who received therapeutic hypothermia (HIE stratum). Patient strata were chosen to include infants at high risk of adverse neurodevelopmental outcomes by virtue of EP birth, or HIE requiring therapeutic hypothermia. Infants are randomly assigned, in a 1:1 allocation ratio, to receive either the active supplement or a matched control, in addition to standard care. Families, clinical teams, investigators, and Clinical Trials Unit staff are blinded to allocation. Only the Senior Trials Programmer and Trial Statisticians have access to allocation information. The active supplement is a nutrient powder formulated to be mixed with breast milk, infant formula, or food, containing LCPUFAs (including DHA, EPA, and ARA), choline, UMP, CMP, zinc, iodine, and vitamin B12. Supplementation commences once infants achieve full milk feeds and continues until 12 months post-estimated date of delivery (EDD), with a daily dosage of 1 g per kilogram of body weight. The primary outcome is the Parent Report of Children's Abilities-Revised non-verbal cognitive scale at 24 months post-EDD. EP and HIE patient population comparisons have been appropriately power