DHA

BACKGROUND: Children who are securely attached to at least one parent are able to be comforted by that parent when they are distressed and explore the world confidently by using that parent as a 'secure base'. Research suggests that a secure attachment enables children to function better across all aspects of their development. Promoting secure attachment, therefore, is a goal of many early interventions. Attachment is mediated through parental sensitivity to signals of distress from the child. One means of improving parental sensitivity is through video feedback, which involves showing a parent brief moments of their interaction with their child, to strengthen their sensitivity and responsiveness to their child's signals. OBJECTIVES: To assess the effects of video feedback on parental sensitivity and attachment security in children aged under five years who are at risk for poor attachment outcomes. SEARCH METHODS: In November 2018 we searched CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, nine other databases and two trials registers. We also handsearched the reference lists of included studies, relevant systematic reviews, and several relevant websites SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs that assessed the effects of video feedback versus no treatment, inactive alternative intervention, or treatment as usual for parental sensitivity, parental reflective functioning, attachment security and adverse effects in children aged from birth to four years 11 months. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: This review includes 22 studies from seven countries in Europe and two countries in North America, with a total of 1889 randomised parent-child dyads or family units. Interventions targeted parents of children aged under five years, experiencing a wide range of difficulties (such as deafness or prematurity), or facing challenges that put them at risk of attachment issues (for example, parental depression). Nearly all studies reported some form of external funding, from a charitable organisation (n = 7) or public body, or both (n = 18). We considered most studies as bein

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

Preeclampsia (PE) remains a major cause of maternal and fetal morbidity and mortality worldwide, with placental dysfunction and angiogenic imbalance playing central roles in disease pathogenesis. Emerging evidence highlights epigenetic regulation and angiogenic biomarkers, including placental growth factor (PlGF), as key contributors to disease heterogeneity and risk stratification. A systematic review of studies published between 2022 and 2025 was conducted in accordance with PRISMA 2020 guidelines to synthesize current evidence on epigenetic mechanisms and biomarker potential in PE. In addition, a supplementary exploratory analysis was performed using laboratory-derived PlGF data to assess analytical variability and biological associations. Non-parametric methods were applied, including Mann-Whitney U testing to compare PlGF distributions by analytical sample classification and Kendall's tau correlation to evaluate associations with gestational age and the sFlt-1/PlGF ratio. The systematic review identified consistent epigenetic alterations involving DNA methylation, histone modifications, and non-coding RNAs across maternal and placental tissues. Supplementary analysis demonstrated significantly higher and more variable PlGF concentrations in analytically classified measured samples compared with accepted samples (P = 0.03), suggesting an influence of analytical factors on biomarker distribution. PlGF levels showed a positive association with gestational age (τ = 0.32, P = 0.04) and an inverse association with the sFlt-1/PlGF ratio (τ = -0.41, P = 0.02). These findings support PlGF as a biologically relevant marker of gestational progression and angiogenic balance while underscoring the importance of rigorous analytical quality control. Integrating epigenetic insights with robust biomarker analysis may enhance personalized risk stratification in preeclampsia. © 2026 The Author(s).

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.

BACKGROUND: The first 1000 days of life, from conception to 2 years of age, represent a critical window during which nutrition can exert long-lasting effects on neurodevelopment, immune maturation, and susceptibility to prematurity-related morbidity. Docosahexaenoic acid (DHA) is a key structural n-3 long-chain polyunsaturated fatty acid of the brain and retina, characterized by rapid fetal accretion during the third trimester. METHODS: We conducted a narrative review of studies published from March 2015 up to December 2025, including randomized controlled trials, follow-up studies, and systematic reviews/meta-analyses about DHA supplementation during pregnancy, lactation, infancy and early childhood, and its role on development. RESULTS: Across the first 1000 days, DHA supplementation improves biochemical DHA status, particularly in populations with low baseline levels (moderate to high level of evidence), while clinical outcomes remain heterogeneous. During pregnancy, some benefits in specific cognitive and behavioral domains have been demonstrated, whereas effects on global cognition and long-term behavior are frequently null (moderate evidence). Visual outcomes appear favorable, with improvements in visual acuity (moderate evidence). In preterm infants, enteral DHA-often combined with arachidonic acid (ARA)-is feasible and well tolerated. DHA may reduce inflammatory markers and necrotizing enterocolitis risk when in equilibrium with ARA (low to moderate evidence), while no evidence supports the link between DHA and reduced risk of bronchopulmonary dysplasia and retinopathy of prematurity (moderate evidence). Neurodevelopmental outcomes are mixed: neuroimaging studies suggest enhanced white matter maturation with DHA + ARA, whereas most trials show no clear benefit regarding standardized developmental scores (moderate evidence). CONCLUSIONS: DHA is biologically essential during the first 1000 days, but its clinical impact depends on timing, dose, baseline status, and prematurity-related context. The balance between DHA and ARA, rather than DHA supplementation alone, emerges as a key determinant of clinical efficacy, supporting a shift toward precision-based n

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.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motor neuron loss, with limited effective therapies. Docosahexaenoic acid (DHA) exhibits neuroprotective effects, but its limited transport across the blood-brain barrier (BBB) restricts clinical utility. Major facilitator superfamily domain-containing protein 2A (MFSD2A) is the primary transporter of DHA into the central nervous system, yet its role in ALS remains unclear. This study investigated the therapeutic potential and mechanisms of MFSD2A overexpression combined with DHA supplementation in male SOD1^G93A ALS mice. We found that MFSD2A expression was markedly reduced in ALS mice and correlated with impaired motor function and neuronal damage. DHA supplementation or MFSD2A overexpression partially improved behavioral deficits, while their combination produced synergistic benefits. Histological analyses revealed attenuated neuronal degeneration and reduced muscle fibrosis following combined treatment. Furthermore, MFSD2A physically interacted with the E3 ubiquitin ligase TRIM21, regulating glycolytic metabolism by modulating key enzymes (GLUT1, HK2, LDHA, PDK1) and products (lactate/pyruvate and NADH/NADPH ratio). TRIM21 knockdown reversed MFSD2A-mediated neuroprotection and impaired glycolytic metabolism, indicating its critical role in this pathway. The combined intervention also suppressed systemic inflammation and oxidative stress by decreasing pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and restoring antioxidant enzyme activities (GSH-Px), while reducing lipid peroxidation (MDA). These findings suggest that MFSD2A facilitates DHA's neuroprotective effects by enhancing glycolytic metabolism and mitigating neuroinflammation. This study highlights MFSD2A and DHA as promising therapeutic targets in ALS and provides novel insights into overcoming BBB transport limitations for neurodegenerative disease treatment. © 2026. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

INTRODUCTION: Cow's milk allergy (CMA) is one of the most common food allergies in childhood frequently associated with body growth impairment and micronutrient deficiencies. Immunonutrition approach with selected bioactive compounds may have beneficial effects on nutritional status and immune tolerance mechanisms. We evaluated the effects of an immunonutrition approach, based on the use of a novel multicomponent food supplement containing prebiotics, postbiotics, vitamin D3, docosahexaenoic acid (DHA), Perilla frutescens extracts, and Quercetin in children with CMA. METHODS: Randomized, double-blind, placebo-controlled pilot trial, involving 30 pediatric CMA patients (both sexes, age 36-60 months) randomly assigned to receive the study product or placebo (maltodextrins) for 6 months. The active study product and placebo were provided as powder sachets with identical features. Primary outcomes were changes in body growth. Co-primary exploratory outcomes were serum 25-hydroxyvitamin D (25(OH)D) and DHA levels. Secondary endpoints included the evaluation of Th2 interleukins (ILs) and IL-10, regulatory T cells (Tregs), and growth factors and cytokines modulating ILs production (Tgfb1, Ifna2, Ptgs2, Csf2) in peripheral blood mononuclear cells (PBMCs) collected from CMA pediatric patients. RESULTS: All participants completed the study without adverse events and with >90% adherence to the allocated treatment. At 6-month follow-up, children in the study product group showed greater improvement in body weight, and height, compared with the patients in the placebo group. Serum 25(OH)D and DHA concentrations significantly improved only in the active study group. In PBMCs collected from the patients, the active study product, but not the placebo exposure, resulted in an inhibition of Th2 cytokines (IL- 4, IL-5, IL-13) response to the stimulation with antigenic peptide β-lactoglobulin and in an increase in IL-10 production and Treg activation rate. The expression of Tgfb1, Ifna2, Ptgs2, Csf2 resulted also upregulated, suggesting an overall modulation toward immune tolerance in these patients. CONCLUSIONS: This novel multicomponent food supplement improved growth parameters

Background: Alzheimer's disease (AD) remains a major public health challenge. Observational associations between dietary patterns and reduced dementia risk have prompted investigations of dietary bioactives (DBs) as cognitive nutraceuticals. Methods: This critical narrative review examines interventional trials for nine prominent DBs relevant to AD: docosahexaenoic acid (DHA), curcumin, resveratrol, epigallocatechin gallate (EGCG), nicotinamide riboside (NR), tricaprilin, vitamin E (α-tocopherol), cannabinoids, and NIC5-15 (D-pinitol). Trials were identified through ClinicalTrials.gov (search date: December 2024) and supplemented by PubMed searches for published results. Data were extracted on trial phase, design, cognitive/functional endpoints, biomarker outcomes, and development status. Findings are synthesized qualitatively; no formal meta-analysis or risk of bias assessment was conducted. Results: None of the nine bioactives demonstrated consistent cognitive efficacy in AD. Phase III trials of DHA, curcumin, and tricaprilin did not meet primary cognitive endpoints. Resveratrol reduced CSF Aβ40 without cognitive benefit. Cannabinoids improved behavioral symptoms but showed no measurable cognitive effects. High-dose vitamin E slowed functional decline, while cognition remained unchanged. In contrast, trials in preclinical or at-risk populations reported preliminary cognitive signals for EGCG and biomarker engagement for NR, suggesting potential for early intervention. Conclusions: Current clinical evidence does not support high-dose DBs supplementation as an effective treatment for AD. Predominantly negative late-phase findings highlight limitations, with potential contributors including limited bioavailability, late intervention, insufficient target engagement, and biological heterogeneity. Future research may benefit from early biomarker-defined populations, optimized formulations, multi-nutrient or dietary approaches, and precision nutrition strategies considering genetic risk and baseline nutrient status. DBs may be better positioned for prevention or early-stage intervention rather than late-stage therapy.

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

This study aimed to investigate the effects of maternal supplementation with fish oil, flaxseed oil, and walnut oil rich in omega-3 fatty acids during lactation on mammary tissue structure and milk quality. Rats were randomly assigned to negative control, control, fish oil, walnut oil, and flaxseed oil groups. The supplements were administered by oral gavage from parturition (Day 0) to the end of lactation (Day 21). Mammary tissues were evaluated immunohistochemically, and blood samples were analyzed biochemically. The docosahexaenoic acid (DHA) level in the fish oil group was significantly higher than in other groups (p < 0.05). Fatty Acid Desaturase-2 (FADS2) levels also differed significantly between the negative control and all other groups (p < 0.05), while no significant change was observed in the walnut oil group (p > 0.05). Immunostaining intensities for insulin-like growth factor 1 (IGF-1), transforming growth factor beta 1 (TGF-β1), and vascular endothelial growth factor (VEGF) varied significantly among all groups (p < 0.05). These findings suggest that maternal fish oil supplementation during lactation more effectively enhances milk quality and mammary tissue function than flaxseed or walnut oil, indicating its potential as a dietary strategy to improve milk composition and support offspring nutrition. Trial Registration: Registered on the Clinical Trial Registry (www.clinicaltrials.gov; Clinical Trials identifier: NCT06111378 (26/10/2023). © 2026 Wiley‐VCH GmbH.

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.