Omega-3 (Mood)

Microalgae have gained attention in laying hen nutrition due to their richness in n-3 polyunsaturated fatty acids (PUFA), pigments, and antioxidants. However, their efficacy in poultry diets remains inconsistent. This meta-analysis quantitatively evaluated the effects of dietary microalgae supplementation on performance, egg quality, yolk fatty acid composition, and blood biochemistry in laying hens. Thirty-six peer-reviewed articles were retrieved from Scopus, ScienceDirect, PubMed, and Google Scholar following PRISMA guidelines, and effect sizes were calculated using weighted mean differences. Microalgae supplementation did not affect feed intake (p > 0.05) but significantly improved hen-day egg production, egg weight, egg mass, yolk weight, shell traits, and Haugh units (p < 0.05). Yolk pigmentation increased in color intensity and redness (p < 0.001) but decreased in lightness (p < 0.001). Microalgae enhanced yolk total n-3 PUFA, eicosapentaenoic acid, and docosahexaenoic acid (p < 0.001), while reducing n-6 PUFA and the n-6/n-3 ratio (p < 0.05). Blood total cholesterol, aspartate aminotransferase, and alanine aminotransferase concentrations decreased (p < 0.05). In conclusion, dietary microalgae supplementation augments laying performance, enhances egg quality and yolk pigmentation, fortifies yolk with beneficial n-3 fatty acids, and promotes liver health, highlighting its potential as a functional feed additive in layer diets. © 2025. The Author(s).

BACKGROUND: The existing evidence on the effect of dietary supplements for preventing migraines has generated conflicting results. METHODS: We assessed alterations in migraine clinical features corresponding to the intake of dietary supplements. Our main outcomes included the frequency (number of attacks), duration (in hours), the severity (intensity) and the monthly migraine days. Using a dose-response meta-analysis, we estimated the dose-dependent impact. The certainty of evidence was evaluated using the GRADE tool. RESULTS: Finally, twenty-two trials were included in the systematic review and meta-analysis. Magnesium supplementation reduced migraine attacks (mean difference (MD) = -2.51), severity (MD = -0.88), and the monthly migraine days (MD = -1.66) compared with the control group. CoQ10 decreased the frequency (MD = -1.73), severity (MD = -1.35), and duration of migraine (MD = -1.72). Riboflavin decreased attack frequency (MD = -1.34). Alpha-lipoic acid decreased attack frequency (MD = -1.24) and severity (MD = -0.38). Probiotics decreased the frequency (MD = -1.16), severity (MD = -1.07) and the monthly migraine days (MD = -3.02). Vitamin D reduced migraine frequency (MD = -1.69) and the monthly migraine days (MD = -2.41). In adults, compared with placebo, these supplements did not significantly affect other outcomes, and omega-3 supplementation did not yield a statistically significant reduction in any of these outcomes. CONCLUSION: The use of certain dietary supplements has resulted in a significant decrease in migraine prophylaxis. Further clinical trials of high quality appear to be beneficial. © 2024. Fondazione Società Italiana di Neurologia. Efficacy and safety of omega-3 fatty acids supplementation for anxiety symptoms: a systematic review and dose-response meta-analysis of randomized controlled trials. Bafkar N(1), Zeraattalab-Motlagh S(2), Jayedi A(3), Shab-Bidar S(4)(5). Author information: (1)Department of Community Nutrition, School of Nutritional Science and Dietetics, Tehran University of Medical Sciences, Tehran, Iran. (2)Department of Health and Human Performance, University of Houston, Houston, TX, USA. (3)Social Determinants of He

Update of Res Sq. 2024 Jan 12:rs.3.rs-3787917. doi: 10.21203/rs.3.rs-3787917/v1. Sub-optimal response in schizophrenia is frequent, warranting augmentation strategies over treatment-as-usual (TAU). We assessed nutraceuticals/phytoceutical augmentation strategies via network meta-analysis. Randomized controlled trials in schizophrenia/schizoaffective disorder were identified via the following databases: PubMed, MEDLINE, EMBASE, Scopus, PsycINFO, CENTRAL, and ClinicalTrials.gov. Change (Standardized Mean Difference = SMD) in total symptomatology and acceptability (Risk Ratio = RR) were co-primary outcomes. Secondary outcomes were positive, negative, cognitive, and depressive symptom changes, general psychopathology, tolerability, and response rates. We conducted subset analyses by disease phase and sensitivity analyses by risk of bias and assessed global/local inconsistency, publication bias, risk of bias, and confidence in the evidence. The systematic review included 49 records documenting 50 studies (n = 2384) documenting 22 interventions. Citicoline (SMD =-1.05,95%CI = -1.85; -0.24), L-lysine (SMD = -1.04,95%CI = -1.84; -0.25), N-acetylcysteine (SMD = -0.87, 95%CI = -1.27; -0.47) and sarcosine (SMD = -0.5,95%CI = -0.87-0.13) outperformed placebo for total symptomatology. High heterogeneity (tau2 = 0.10, I2 = 55.9%) and global inconsistency (Q = 40.79, df = 18, p = 0.002) emerged without publication bias (Egger's test, p = 0.42). Sarcosine improved negative symptoms (SMD = -0.65, 95%CI = -1.10; -0.19). N-acetylcysteine improved negative symptoms (SMD = -0.90, 95%CI = -1.42; -0.39)/general psychopathology (SMD = -0.76, 95%CI = -1.39; -0.13). No compound improved total symptomatology within acute phase studies (k = 7, n = 422). Sarcosine (SMD = -1.26,95%CI = -1.91; -0.60), citicoline (SMD = -1.05,95%CI = -1.65;-0.44), and N-acetylcysteine (SMD = -0.55,95%CI = -0.92,-0.19) outperformed placebo augmentation in clinically stable participants. Sensitivity analyses removing high-risk-of-bias studies confirmed overall findings in all phases and clinically stable samples. In contrast, the acute phase analysis restricted to low risk-of-bias studies showed a superior effe

4. BMC Psychiatry. 2024 Jun 18;24(1):455. doi: 10.1186/s12888-024-05881-2. Efficacy and safety of omega-3 fatty acids supplementation for anxiety symptoms: a systematic review and dose-response meta-analysis of randomized controlled trials. Bafkar N(1), Zeraattalab-Motlagh S(2), Jayedi A(3), Sha

BACKGROUND & AIMS: Colorectal cancer (CRC) is the third most common malignancy in developed countries. Therefore, omega-3 fatty acids (O3FAs) have been suggested as a beneficial complementary treatment due to their ability to regulate inflammatory responses and improve nutrition levels.This study aimed to evaluate the effects of O3FAs as a complementary treatment for inflammation, nutrition levels, post-operative infectious complications, and enhancement of recovery in CRC patients. METHODS: The literature search was carried out through three databases. The outcomes of interest were assessed by measuring pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and CRP levels, serum albumin levels for nutrition assessment, post-operative infectious complications, and length of stay for recovery evaluation. Quality appraisal and meta-analysis were performed using RoB 2.0 and RevMan 5.4, respectively. RESULTS: The result showed that O3FAs significantly reduced IL-6, CRP, and TNF-α, but did not affect IL-1β. Furthermore, the variable slightly increased serum albumin levels and the supplementation led to a decrease in post-operative infectious complications and shortened hospital stays. CONCLUSION: O3FAs as a complementary treatment provided advantages for CRC patients, Further clinical trials and experiments should also be made emphasizing the impact and clinical implementation of O3FA in the nutritional status of CRC patients.

Cognitive impairment and dementia are burgeoning public health concerns, especially given the increasing longevity of the global population. These conditions not only affect the quality of life of individuals and their families, but also pose significant economic burdens on healthcare systems. In this context, our comprehensive narrative review critically examines the role of nutritional supplements in mitigating cognitive decline. Amidst growing interest in non-pharmacological interventions for cognitive enhancement, this review delves into the efficacy of vitamins, minerals, antioxidants, and other dietary supplements. Through a systematic evaluation of randomized controlled trials, observational studies, and meta-analysis, this review focuses on outcomes such as memory enhancement, attention improvement, executive function support, and neuroprotection. The findings suggest a complex interplay between nutritional supplementation and cognitive health, with some supplements showing promising results and others displaying limited or context-dependent effectiveness. The review highlights the importance of dosage, bioavailability, and individual differences in response to supplementation. Additionally, it addresses safety concerns and potential interactions with conventional treatments. By providing a clear overview of current scientific knowledge, this review aims to guide healthcare professionals and researchers in making informed decisions about the use of nutritional supplements for cognitive health.

Literature is inconsistent regarding the effects of omega-3 polyunsaturated fatty acids (omega-3 PUFAs) supplementation on patients with metabolic syndrome (MetS) and related cardiovascular diseases (CVDs). Therefore, the aim of this systematic review and meta-analysis is to summarize data from available randomized controlled trials (RCTs) on the effect of omega-3 PUFAs on lipid profiles, blood pressure, and inflammatory markers. We systematically searched PubMed, Embase, and Cochrane Library databases to identify the relevant RCTs until 1 November 2022. Weighed mean difference (WMD) was combined using a random-effects model. Standard methods were applied to assess publication bias, sensitivity analysis, and heterogeneity among included studies. A total of 48 RCTs involving 8,489 subjects met the inclusion criteria. The meta-analysis demonstrated that omega-3 PUFAs supplementation significantly reduced triglyceride (TG) (WMD: -18.18 mg/dl; 95% CI: -25.41, -10.95; p < 0.001), total cholesterol (TC) (WMD: -3.38 mg/dl; 95% CI: -5.97, -0.79; p = 0.01), systolic blood pressure (SBP) (WMD: -3.52 mmHg; 95% CI: -5.69, -1.35; p = 0.001), diastolic blood pressure (DBP) (WMD: -1.70 mmHg; 95% CI: -2.88, -0.51; p = 0.005), interleukin-6 (IL-6) (WMD: -0.64 pg/ml; 95% CI: -1.04, -0.25; p = 0.001), tumor necrosis factor-α (TNF-α) (WMD: -0.58 pg/ml; 95% CI: -0.96, -0.19; p = 0.004), C-reactive protein (CRP) (WMD: -0.32 mg/l; 95% CI: -0.50, -0.14; p < 0.001), and interleukin-1 (IL-1) (WMD: -242.95 pg/ml; 95% CI: -299.40, -186.50; p < 0.001), and significantly increased in high-density lipoprotein (HDL) (WMD: 0.99 mg/dl; 95% CI: 0.18, 1.80; p = 0.02). However, low-density lipoprotein (LDL), monocyte chemoattractant protein-1 (MCP-1), intracellular adhesion molecule-1 (ICAM-1), and soluble endothelial selectin (sE-selectin) were not affected. In subgroup analyses, a more beneficial effect on overall health was observed when the dose was ≤ 2 g/day; Omega-3 PUFAs had a stronger anti-inflammatory effect in patients with CVDs, particularly heart failure; Supplementation with omega-3 PUFAs was more effective in improving blood pressure in MetS patients and blood lipids in CVDs patients,

IMPORTANCE: High-dose docosahexaenoic acid (DHA), a long-chain polyunsaturated fatty acid, may affect the risk of bronchopulmonary dysplasia (BPD). However, high-level summative evidence supporting such clinical association in very preterm infants is lacking. OBJECTIVE: To examine the association between enteral supplementation with high-dose DHA during the neonatal period and the risk of BPD in preterm infants born at less than 29 weeks' gestation. DATA SOURCES: PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, medRxiv, and ClinicalTrials.gov were searched from inception to August 1, 2022, for eligible articles with no language restrictions. STUDY SELECTION: Randomized clinical trials (RCTs) were eligible for inclusion (1) if their interventions involved direct administration of a minimum DHA supplementation of 40 mg/kg/d or breast milk or formula feeding of at least 0.4% of total fatty acids, and (2) if they reported data on either BPD, death, BPD severity, or a combined outcome of BPD and death. DATA EXTRACTION AND SYNTHESIS: Two investigators completed independent review of titles and abstracts, full text screening, data extraction, and quality assessment using the Cochrane Risk of Bias 2.0. Risk ratios (RRs) with 95% CIs were pooled using random-effect meta-analyses. MAIN OUTCOMES AND MEASURES: Primary outcome was BPD using trial-specific definitions, which was further stratified for RCTs that used a more stringent BPD definition based on systematic pulse oximetry assessment at 36 weeks' postmenstrual age. Other outcomes were BPD, death, BPD severity, or combined BPD and death. RESULTS: Among the 2760 studies screened, 4 RCTs were included, which involved 2304 infants (1223 boys [53.1%]; mean [SD] gestational age, 26.5 [1.6] weeks). Enteral supplementation with high-dose DHA was associated with neither BPD (4 studies [n = 2186 infants]; RR, 1.07 [95% CI, 0.86-1.34]; P = .53; I2 = 72%) nor BPD or death (4 studies [n = 2299 infants]; RR, 1.04 [95% CI, 0.91-1.18]; P = .59; I2 = 61%). However, an inverse association with BPD was found in RCTs that used a more stringent BPD definition (2 studies [n = 1686 infants]; RR, 1.20 [95% CI,

PURPOSE: Dyslipidemia is considered as a known risk factor for cardiovascular disease. Yet various trials with wide ranges of doses and durations have reported contradictory results. We undertook this meta-analysis of randomized controlled trials (RCTs) to determine whether omega-3 supplementation can affect lipid profile in children and adolescents. METHODS: Cochrane Library, Embase, PubMed, and Scopus databases were searched up to March 2021. Meta-analysis was performed using random-effect method. Effect size was expressed as weighted mean difference (WMD) and 95% confidence interval (CI). Heterogeneity was assessed using the I2 index. In order to identification of potential sources of heterogeneity, predefined subgroup and meta-regression analysis was conducted. RESULTS: A total of 14 RCTs with 15 data sets were included. Based on the combination of effect sizes, there was a significant reduction in TG levels (WMD: -15.71 mg/dl, 95% CI: -25.76 to -5.65, P=0.002), with remarkable heterogeneity (I2=88.3%, P<0.001). However, subgroup analysis revealed that omega-3 supplementation significantly decreased TG only in studies conducted on participants ≤13 years old (WMD=-25.09, 95% CI: -43.29 to -6.90, P=0.007), (I2=84.6%, P<0.001) and those with hypertriglyceridemia (WMD=-28.26, 95% CI: -39.12 to -17.41, P<0.001), (I2=0.0%, P=0.934). Omega-3 supplementation had no significant effect on total cholesterol, HDL, and LDL levels. Also, results of nonlinear analysis showed significant effect of treatment duration on HDL status (Pnon-linearity=0.047). CONCLUSION: Omega-3 supplementation may significantly reduce TG levels in younger children and those with hypertriglyceridemia. Also, based on the HDL-related results, clinical trials with longer duration of intervention are recommended in this population. © 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

PURPOSE: Menopause is associated with disturbances in the metabolism of lipids. Moreover, during the postmenopausal period, female subjects are more prone to develop dyslipidemia. Omega-3 fatty acids, which exert cardioprotective, anti-inflammatory, and lipid-lowering actions, are commonly recommended in postmenopausal women. However, their effect on serum lipids in this population remains unclear. This systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to clarify this research question. METHODS: We systematically searched the Web of Science, Scopus, PubMed/MEDLINE, and EMBASE databases from their inception until January 3, 2022. The DerSimonian and Laird random-effects model was used to combine effect sizes. FINDINGS: Omega-3 fatty acid supplementation resulted in a decrease in triglyceride concentrations (weighted mean difference [WMD], -17.8 mg/dL; 95% CI, -26 to -9.6; P < 0.001), particularly in the RCTs that lasted ≤16 weeks (WMD, -18.6 mg/dL), when the baseline triglyceride concentrations were ≥150 mg/dL (WMD, -22.8 mg/dL), in individuals with a body mass index ≥30 kg/m2 (WMD, -19.3 mg/dL), and when the dose of omega-3 fatty acids was ≥1 g/d (WMD, -21.10 mg/dL). LDL-C (WMD, 4.1 mg/dL; 95% CI, 1.80 to 6.36; P < 0.001) and HDL-C (WMD, 2.1 mg/dL; 95% CI, 0.97 to 3.2; P < 0.001) values increased. Total cholesterol levels (WMD, -0.15 mg/dL; 95% CI, -4 to 3.74; P = 0.94) remained unchanged after administration of omega-3 fatty acids. IMPLICATIONS: In postmenopausal women, supplementation with omega-3 fatty acids resulted in a significant reduction in triglyceride concentrations and a modest elevation in HDL-C and LDL-C levels, whereas this intervention did not affect total cholesterol values.

Objectives: The objective of this study was to evaluate the effect of 21-day dietary omega-3 fatty acid supplementation on the levels of postexercise inflammation response, oxidative stress, and selected exerkine secretion among physically active young men. Methods: In a randomized double-blind study, 24 physically active men were assigned to two groups: a supplementation group (n = 12), receiving 3250 mg of n-3 polyunsaturated fatty acids (PUFAs) daily, and a placebo group (n = 12). Blood samples were collected before and after twenty-one days of dietary supplementation to measure total fatty acids and inflammatory markers, including IL-1β, IL-6, IL-10, BDNF, and FGF23. Results: After 21 days of n-3 fatty acid supplementation, there were no significant changes in anaerobic performance parameters. However, significant interactions were found in the systemic immune-inflammation index (SII), FGF-23, IL-1β, IL-1Ra, IL-6, and IL-10 in response to exercise and supplementation. Conclusions: 21 days of n-3 fatty acid supplementation modified PUFA content and influenced inflammation status, but did not affect maximal anaerobic performance.

Retraction in J Affect Disord. 2026 Nov 15;413:122090. doi: 10.1016/j.jad.2026.122090. BACKGROUND/OBJECTIVES: Psychological stress, anxiety, depression, memory impairment, and poor sleep quality are prevalent issues that affect individuals' quality of life and overall health. Omega-3 polyunsaturated fatty acids (PUFAs) have been suggested to have mood-regulating effects. However, there is lack of data on the effect of omega-3 supplementation on depression, stress, anxiety, everyday memory, and sleep quality on Saudi population. Therefore, this study aimed to evaluate the impact of omega-3 supplementation on stress, anxiety, depression, everyday memory, and sleep quality in individuals with severe psychological distress. METHODS: A randomized, double-blind, placebo-controlled trial was conducted involving 64 participants with high levels of stress, anxiety, depression, memory issues and with poor quality of sleep with 32 allocated to the intervention group and 32 to the control group. The participants received either omega-3 supplementation (500 mg EPA + 250 mg DHA) or a placebo daily for three months. Pre- and post-intervention assessments were conducted using validated scales, including the Perceived Stress Scale (PSS), Generalized Anxiety Disorder-7 (GAD-7), the Patient Health Questionnaire-9 (PHQ-9), the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), and the Everyday Memory Questionnaire (EMQ). RESULTS: Significant improvements were observed in the intervention group regarding stress, anxiety, depression, sleep quality, and memory outcomes (p < 0.001 for PSS, GAD-7, PHQ-9, PSQI, and EMQ). Between-group comparisons showed statistically significant reductions in post-intervention scores for the intervention group versus the control group. Regression analysis revealed strong predictive relationships between pre- and post-scores, particularly for stress and depression. CONCLUSIONS: Omega-3 supplementation resulted in notable psychological and cognitive improvements, suggesting its potential as a safe and effective adjunct for managing stress, mood disorders, and sleep disturbances among participants with psychological distress. Furthe

Burn is accompanied by metabolic changes. The effects of fish oil on inflammatory pathways and glucose homeostasis have been reported in the previous studies. Various forms of omega-3 fatty acids affect differently the metabolic pathways. The present study was designed to investigate the effects of fish oil containing 500 mg eicosapentanoic acid (EPA) on inflammatory markers and glucose homeostasis in patients with non-severe burns. In this prospective double-blinded parallel-design randomized clinical trial, twenty-four patients with non-severe burns covering lower than 20% of total body surface area were divided into the fish oil (1.5 gr/d EPA and 600 mg/d DHA) or controls (1.5 gr/d corn oil and 600 mg/d DHA) for three weeks. C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fasting blood sugar (FBS), albumin, pre-albumin (PAB), transferrin, and insulin concentration were measured at baseline and end. The homeostatic model assessment for insulin resistance (HOMA-IR) was computed. The duration of hospital stay was assessed as the secondary outcome. The reduction in serum ESR and CRP levels was significantly higher in the fish oil group than the controls (p < 0.001). Moreover, serum fasting insulin significantly decreased in the fish oil group (p < 0.001). Insulin sensitivity significantly improved in the fish oil compared to the controls (p = 0.001). The duration of hospital stay showed no significant difference between the two groups. The most enormous clinically significant effect was observed on serum levels of FBS and insulin (Cohen's d = 2.7 and 1.4), respectively. Fish oil supplements containing 500 mg EPA improved glucose homeostasis and decreased inflammation in patients with non-severe burns. Results are not generalizable due to the small sample size. More clinical trials are needed to achieve conclusive. © 2025. The Author(s).

Prenatal supplementation with docosahexaenoic acid (DHA) has been reported to improve cognitive outcomes in infancy and early childhood in some studies. Existent studies have examined the effects of some dose of DHA against a true placebo; this report is the first to describe the effects of different doses of prenatal DHA on infant visual attention at 4 and 6 months of age. In a follow-up to a Phase III registered clinical trial (NCT02709239) designed to evaluate the effects of two prenatal doses of DHA supplementation (200 or 800 mg daily) on maternal physiology and fetal neurodevelopment, we assessed 215 infants delivered to these mothers at 4 and 6 months on a visual habituation task augmented with heart rate (HR) to assess visual stimulus processing, and a gap-overlap task to assess engagement and disengagement of attention. Infants of mothers supplemented with 800 mg/day of DHA had shorter look durations (indicative of more rapid visual learning) during habituation at both ages and a somewhat more mature pattern of HR-defined phases of attention. However, DHA dose did not affect infant HR, nor did it affect infant performance in the gap-overlap attention task. Results are consistent with positive effects of prenatal DHA supplementation on later outcomes, with higher benefit seen for a higher dose. © 2025 Wiley Periodicals LLC.

BACKGROUND: Human milk oligosaccharides (HMOs) are complex carbohydrates that act as prebiotics, supporting infants' gut microbial colonization and immune development. HMO levels are influenced by several maternal factors, including genetics, diet, and health status. In this study, we aim to investigate the effects of ω-3 PUFA (polyunsaturated fatty acids) and Limosilactobacillus (L.) reuteri supplementation on HMO levels in colostrum and mature milk. Another aim is to compare HMO levels between allergic and non-allergic mothers and to explore the correlation between HMOs and secretory immunoglobulin A (SIgA) in milk. METHODS: Milk samples (n = 136) were collected from mothers enrolled in a clinical trial (PROOM-3) designed to investigate the effect of pre- and postnatal supplementation with ω-3 PUFA and L. reuteri on allergy development in early childhood. HMOs were measured in colostrum and mature milk collected 3 months postpartum using high-performance anion exchange chromatography. SIgA was measured in colostrum, 1-, 2-, 3-, and 4-month milk using ELISA. RESULTS: The supplements did not affect HMO levels in colostrum or mature milk. However, maternal supplementation with ω-3 PUFA decreased the HMO diversity over time. Additionally, allergic mothers expressed significantly lower levels of several HMOs compared to non-allergic mothers. Additionally, SIgA correlated positively with fucosylated and negatively with sialylated HMOs. CONCLUSION: Supplementation with ω-3 PUFA could reduce the HMO diversity over the course of lactation. Also, maternal allergy seems to be associated with a reduction in levels of several HMOs. Furthermore, there is a possible dynamic interplay between HMOs and SIgA in milk. TRIAL REGISTRATION: ClinicalTrials.gov-ID: NCT01542970. © 2025 The Author(s). Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.

BACKGROUND: Bipolar depression remains difficult to treat, and people often experience ongoing residual symptoms, decreased functioning and impaired quality of life. Adjunctive therapies targeting novel pathways can provide wider treatment options and improve clinical outcomes. Garcinia mangostana Linn. (mangosteen) pericarp has serotonogenic, antioxidant anti-inflammatory and neurogenic properties of relevance to the mechanisms of bipolar depression. AIMS: The current 28-week randomised, multisite, double-blind, placebo-controlled trial investigated mangosteen pericarp extract as an adjunct to treatment-as-usual for treatment of bipolar depression. METHOD: This trial was prospectively registered on the Australia New Zealand Clinical Trials Registry (no. ACTRN12616000028404). Participants aged 18 years and older with a diagnosis of bipolar I or II and with at least moderate depressive symptoms were eligible for the study. A total of 1016 participants were initially approached or volunteered for the study, of whom 712 did not progress to screening, with an additional 152 screened out. Seventy participants were randomly allocated to mangosteen and 82 to a placebo control. Fifty participants in the mangosteen and 64 participants in the placebo condition completed the treatment period and were analysed. RESULTS: Results indicated limited support for the primary hypothesis of superior depression symptom reduction following 24 weeks of treatment. Although overall changes in depressive symptoms did not substantially differ between conditions over the course of the trial, we observed significantly greater improvements for the mangosteen condition at 24 weeks, compared with baseline, for mood symptoms, clinical impressions of bipolar severity and social functioning compared with controls. These differences were attenuated at week 28 post-discontinuation assessment. CONCLUSIONS: Adjunctive mangosteen pericarp treatment appeared to have limited efficacy in mood and functional symptoms associated with bipolar disorder, but not with manic symptoms or quality of life, suggesting a novel therapeutic approach that should be verified by replication.

Supplementation of omega-3 (n-3) polyunsaturated fatty acids has been associated with reduced side effects and improved quality of life (QoL) in breast cancer patients receiving chemotherapy. The current study reports secondary outcomes from the DHA WIN randomized controlled trial which was designed to evaluate docosahexaenoic acid (DHA) supplementation (4.4 g/day) in conjunction with six cycles of neoadjuvant chemotherapy (NAC) (3 weeks/cycle) in women with non-metastatic breast cancer (n = 49). The objective of the current study was to assess the effects of DHA supplementation on QoL and exercise behaviour in women undergoing NAC for breast cancer. Self-administered questionnaires were used to measure QoL and exercise behaviour before starting chemotherapy (baseline), before each chemotherapy cycle (exercise), and after completing chemotherapy. DHA supplementation did not significantly affect QoL, aerobic exercise volume or resistance training frequency during treatment. However, mean aerobic exercise volume was significantly lower at week 12 (-53.5 minutes/week; 95% CI, -100.5 to -6.3; p = 0.02) and week 18 (-70.8 minutes/week; 95% CI, -123.0 to -18.6; p = 0.01) compared to baseline. Mean resistance training frequency was lower at week 12 (-0.57 times/week; 95% CI, -1.0 to -0.13; p = 0.02) compared to baseline. Meeting exercise guidelines during chemotherapy was not associated with better QoL. In the current exploratory study, QoL and exercise decreased during treatment regardless of DHA supplementation, highlighting the need for supportive care and potential therapies that may mitigate these declines in breast cancer patients receiving NAC. Adequately powered studies are needed to determine if DHA supplementation improves these two indices of health. The trial is registered at ClinicalTrials.gov (NCT03831178). Copyright: © 2025 Douglas et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

To explore whether prenatal conditions (i.e. chorioamnionitis, preeclampsia or small-for-gestational age (SGA)) affect the very preterm infant's response to docosahexaenoic acid (DHA) on bronchopulmonary dysplasia (BPD), according to mode of delivery, an independent factor shown to modulate this association. Secondary exploratory analysis of the MOBYDIck randomized controlled trial (NCT02371460) evaluating the effect of a neonatal high-dose DHA supplementation through maternal breastmilk compared to placebo. Population was preterm infants born before 29 weeks of gestation in sixteen Canadian neonatal intensive care units. Primary outcome was physiological BPD based on pulse oximetry assessment. Secondary outcomes included "death or BPD"; "moderate-or-severe" BPD; severe BPD; death from any causes. Heterogeneity in the effect of DHA on outcomes was assessed by prenatal conditions and mode of delivery using generalized estimating equation logistic regression models. The trial intended to enroll 800 mothers but was stopped early for safety, likely making subgroup analysis underpowered. 230 mothers (271 infants) were included in DHA group and 226 mothers (252 infants) in placebo group. The association between high-dose DHA and BPD differed by chorioamnionitis status (heterogeneity P=0.04). In infants exposed to chorioamnionitis and vaginal delivery, DHA supplementation was associated with a reduced risk of physiological BPD (adjusted odds ratio, 0.18 [95% CI, 0.05 to 0.62], P=0.007). No heterogeneity was found by maternal preeclampsia (heterogeneity P=0.44) nor SGA status (heterogeneity P=0.17). CONCLUSION: This secondary analysis generated hypotheses for a potential differential effect of neonatal enteral high-dose DHA supplementation on BPD in very preterm infants according to chorioamnionitis exposure. WHAT IS KNOWN: • The MOBYDIck trial reported a potential protective effect of docosahexaenoic acid (DHA) supplementation on bronchopulmonary dysplasia (BPD) in infants born vaginally, but not in those born via cesarean section. • Placenta pathologies are associated with inflammation in the infants and could affect the very preterm infant's response to a high-dose D

BACKGROUND: Medium-chain triglycerides (MCT) and docosahexaenoic acid (DHA) could affect cognitive function, but their combination effects remain unclear. This randomized, double-blind, placebo-controlled trial aimed to evaluate effects of MCT and DHA supplementation, alone or in combination, on mild cognitive impairment (MCI) patients. METHODS: A total of 280 MCI participants were randomly assigned to the placebo group, MCT group (14 g/d octanoic acid+10 g/d capric acid), DHA group (800 mg/d) and MCT + DHA (14 g/d octanoic acid, 10 g/d capric acid and 800 mg/d DHA) group, 70 individuals per group for 12 months. Cognitive function was assessed at baseline, 6 months and 12 months; blood indicators were analyzed at baseline and 12 months. This study is registered with Chinese Clinical Trial Registry (ChiCTR2200059641). RESULTS: After 12 months intervention, compared with the placebo group, MCT group, DHA group and MCT + DHA group had statistically significant improvements in full scale IQ (β: 0.107, 95 % CI: 0.006, 0.208; β: 0.135, 95 % CI: 0.034, 0.235; β: 0.136, 95 % CI: 0.035, 0.237), serum total ketone body levels (β: 10.540, 95 % CI: 9.550, 11.531; β: 5.884, 95 % CI: 4.894, 6.875; β: 13.186, 95 % CI: 12.196, 14.176), and decreases in mtDNA deletions (β: -0.370, 95 % CI: -0.648, -0.092; β: -0.335, 95 % CI: -0.613, -0.056; β: -0.427, 95 % CI: -0.705, -0.148) and plasma Aβ42 levels (β: -3.318, 95 % CI: -5.571, -1.064; β: -3.218, 95 % CI: -5.472, -0.965; β: -2.906, 95 % CI: -5.160, -0.653). CONCLUSIONS: Supplementation of MCT, DHA and their combination for 12 months can significantly improve cognitive function, mitochondria function and increase serum total ketone body levels in MCI individuals. Combined intervention was more beneficial than MCT or DHA alone.

BACKGROUND: The seAFOod randomized controlled trial tested colorectal polyp prevention by the omega-3 (ω-3) highly unsaturated fatty acid (HUFA) eicosapentaenoic acid (EPA) and aspirin. Variable dietary intake of omega-3 HUFAs (also including docosahexaenoic acid [DHA]) and differential EPA capsule compliance could confound analysis of trial outcomes. OBJECTIVE: The objective of this study was to investigate the relationship between total (diet and capsule) daily omega-3 HUFA intake, red blood cell (RBC), and rectal mucosa omega-3 HUFA concentrations, and colorectal polyp outcomes in a secondary analysis of the seAFOod trial. METHODS: Individual-participant dietary omega-3 HUFA intake (mg/d) was derived from food frequency questionnaires using the European Prospective Investigation into Cancer and Nutrition-Norfolk fatty acid nutrient database. Capsule EPA intake (mg/d) was adjusted for compliance (capsule counting). Fatty acids were analyzed by liquid chromatography-tandem mass spectrometry (as % of total fatty acids). HUFA oxidation was measured using the HUFA/saturated fatty acid (SAT) ratio. The colorectal polyp detection rate (PDR; % with ≥1 polyps) and polyp number per participant were analyzed according to the change in RBC EPA concentrations during the trial (ΔEPA), irrespective of treatment allocation. RESULTS: There was a small degree of HUFA degradation over time in RBC samples stored at > -80oC at research sites (r = -0.36, P<0.001 for HUFA/SAT ratio over time), which did not affect analysis of omega-3 HUFA concentrations. Low baseline EPA concentration, as well as allocation to EPA and % compliance, were associated with a high ΔEPA. Individuals with a ΔEPA value >+0.5% points (ΔEPAhigh), irrespective of allocation to EPA or placebo, had a lower PDR than ΔEPAlow individuals (odds ratio: 0.63; 95% confidence interval [CI]: 0.40, 1.01) and reduced colorectal polyp number (incidence rate ratio: 0.74; 95% CI: 0.54, 1.02). CONCLUSIONS: Analysis of the seAFOod trial according to the change in EPA concentration, instead of treatment allocation, revealed a protective effect of EPA treatment on colorectal polyp recurrence (ISRCTN05926847).

Decreases in global cardiovascular disease (CVD) mortality and morbidity in recent decades can be partly attributed to cholesterol reduction through statin use. n-3 long chain polyunsaturated fatty acids are recommended by some authorities for primary and secondary CVD prevention, and for triglyceride reduction. The residual risk of CVD that remains after statin therapy may potentially be reduced by n-3 long chain polyunsaturated fatty acids. However, the effects of concomitant use of statins and n-3 long chain polyunsaturated fatty acids are not well understood. Pleiotropic effects of statins and n-3 long chain polyunsaturated fatty acids overlap. For example, cytochrome P450 enzymes that metabolize statins may affect n-3 long chain polyunsaturated fatty acid metabolism and vice versa. Clinical and mechanistic study results show both synergistic and antagonistic effects of statins and n-3 long chain polyunsaturated fatty acids when used in combination.

BACKGROUND: Omega-3 carboxylic acids (OM3-CA) can lower triglyceride levels. OM3-CA is often prescribed concomitantly with a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin). OBJECTIVE: The aim of the article was to assess the potential for pharmacokinetic interaction between OM3-CA and the statins rosuvastatin and simvastatin. METHODS: Data from 2 phase I studies (ECLIPSE III and OM-EPA-007 [NCT01486433]) were analyzed. In ECLIPSE III, 59 participants received OM3-CA 4 g once daily for 13 days, with rosuvastatin 40 mg (single dose) co-administered with the 11th dose. In OM-EPA-007, 52 participants received simvastatin 40 mg plus acetylsalicylic acid 81 mg daily for 14 days, with or without OM3-CA. Lack of a drug-drug interaction was declared if the 90% confidence interval (CI) of the geometric least-squares mean ratio of pharmacokinetic parameters was in the range 80% to 125%. RESULTS: For rosuvastatin, values for the geometric mean ratio (90% CI) with:without OM3-CA were 86.38% (80.68-92.48), 90.50% (85.99-95.25), and 89.01% (84.30-93.98), respectively, for maximum plasma concentration (Cmax), area under the concentration-time curve up to last measurable concentration (AUC0-t) and extrapolated to infinity (AUC0-inf). Co-administration with a single dose of rosuvastatin did not affect the multiple-dose pharmacokinetics of constituent OM3-CA fatty acids eicosapentaenoic acid and docosahexaenoic acid. For simvastatin, values for steady state geometric mean ratio (90% CI) with:without OM3-CA were 91.61% (82.82-101.33) and 87.47% (80.19-95.41), respectively, for Cmax and AUC0-t. No deaths or serious adverse events occurred in either trial. CONCLUSION: OM3-CA can be administered with either rosuvastatin or simvastatin without affecting the pharmacokinetics of these statins.

BACKGROUND: Omega-3 carboxylic acids (OM3-CA) can lower triglyceride levels. OBJECTIVE: Our objective was to assess the effects of OM3-CA on warfarin pharmacokinetics and pharmacodynamics and on acetylsalicylic acid (ASA)-dependent and independent platelet activation when co-administered with ASA in two phase I studies. METHODS: In ECLIPSE II (NCT01431690), 26 participants received warfarin 25 mg on days 1 and 22 and OM3-CA 4 g once daily from day 8 to day 28. In OM-EPA-007 (NCT01486433), 52 participants received simvastatin 40 mg plus ASA 81 mg once daily for 14 days, with or without OM3-CA 4 g. Lack of a drug-drug interaction was indicated when 90% confidence intervals (CIs) fell entirely within the range 80-125% for least-squares mean (LSM) ratios of area under the concentration-time curve (AUC), maximum observed plasma concentration (C max), international normalized ratio (INR) AUC to 168 h and maximum INR. RESULTS: In ECLIPSE II, 90% CIs for LSM ratios of with:without OM3-CA fell within 80-125% for AUC and C max of S- and R-warfarin enantiomers. The 90% CIs for LSM ratios of with:without OM3-CA fell within 80-125% for INR AUC to 168 h after dosing and for maximum INR of warfarin. In OM-EPA-007, no significant effect of OM3-CA was observed on ASA-dependent or ASA-independent platelet activation. No deaths or serious adverse events occurred in either study. CONCLUSION: OM3-CA did not affect the pharmacokinetics or pharmacodynamics of warfarin or the pharmacodynamic effects of ASA. OM3-CA did not affect platelet function when co-administered with ASA.

Crude lecithin, a mixture of mainly phospholipids, potentially helps to increase the systemic availability of dietary omega-3 polyunsaturated fatty acids (n-3 PUFA), such as docosahexaenoic acid (DHA). Nevertheless, no clear data exist on the effects of prolonged combined dietary supplementation of DHA and lecithin on RBC and plasma PUFA levels. In the current experiments, levels of DHA and choline, two dietary ingredients that enhance neuronal membrane formation and function, were determined in plasma and red blood cells (RBC) from rats after dietary supplementation of DHA-containing oils with and without concomitant dietary supplementation of crude lecithin for 2-3 weeks. The aim was to provide experimental evidence for the hypothesized additive effects of dietary lecithin (not containing any DHA) on top of dietary DHA on PUFA levels in plasma and RBC. Dietary supplementation of DHA-containing oils, either as vegetable algae oil or as fish oil, increased DHA, eicosapentaenoic acid (EPA), and total n-3 PUFA, and decreased total omega-6 PUFA levels in plasma and RBC, while dietary lecithin supplementation alone did not affect these levels. However, combined dietary supplementation of DHA and lecithin increased the changes induced by DHA supplementation alone. Animals receiving a lecithin-containing diet also had a higher plasma free choline concentration as compared to controls. In conclusion, dietary DHA-containing oils and crude lecithin have synergistic effects on increasing plasma and RBC n-3 PUFA levels, including DHA and EPA. By increasing the systemic availability of dietary DHA, dietary lecithin may increase the efficacy of DHA supplementation when their intake is combined.

The risk of upper gastrointestinal complications (UGIC) due to low-dose aspirin (LDA) can be further increased by the concurrent exposure to other antithrombotic agents. Little is known on the combined therapy with LDA and medications containing omega-3 (OM3) fatty acids, which also exert antiplatelet activity. The aim of this study was to investigate the risk of UGIC in patients exposed to LDA-OM3 combination. The Italian Health Search IMS Health Longitudinal Patients Database was used to perform a population-based cohort study. Patients aged ≥18 years with cardio- or cerebrovascular ischaemic disease recorded between 2002 and 2012 (cohort entry) were selected. All UGIC cases (index date) observed up to December 2013 were identified. According to a nested case-control analysis, up to 10 controls were matched to each case on age, sex and calendar period. The risk of UGIC was investigated among current (up to 30 days preceding index date), recent (31-60 days) and past users (61-365 days) of the LDA-OM3 combination. Exposure assessment was lagged by 30 days to minimize reverse causation. Additionally, a duration-response analysis was performed. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression. Non-users of the LDA-OM3 combination were the reference category. Current (OR = 0.66; 95% CI: 0.44-1.00), recent (OR = 0.83; 95% CI: 0.52-1.33) and past users (OR = 0.81; 95% CI: 0.57-1.15) did not statistically significantly increase the risk of UGIC. No duration-response relationship was found. Our results suggest that LDA-OM3 combination therapy does not affect the UGIC risk in patients with cardio- or cerebrovascular ischaemic diseases. Given the novelty of these findings, further studies are needed. © 2015 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Lymphoma is the most common hematopoietic tumor in dogs and humans, with similar pathogenesis and therapeutic responses. Anticancer drugs like vincristine (VCR) and doxorubicin (DOX) are often used in treating lymphoma. However, the cure rate is generally poor due to chemoresistance. Here, we sought to determine whether stearidonic acid (SDA), a plant-based dietary fatty acid, sensitizes chemoresistant canine lymphoid-tumor cells. GL-1 B-cell lymphoid-tumor cells were found to be highly sensitive to the antitumor-activity of VCR and DOX, while OSW T-cell and 17-71 B-cell lymphoid-tumor cells were moderately and fully resistant, respectively. SDA, at its non-toxic concentrations, significantly promoted the antitumor action of VCR and DOX in both OSW and 17-71 cells. SDA-mediated chemosensitization was associated with SDA inhibition of P-glycoprotein (P-gp) function. This was confirmed in HEK293 cells stably expressing P-gp as well as by increased binding-affinity of SDA to P-gp in P-gp docking analysis. SDA at its chemosensitizing concentrations did not affect the viability of healthy dog peripheral blood mononuclear cells, suggesting that SDA is non-toxic to normal dog peripheral blood leucocytes at its chemosensitizing concentrations. Our study identifies a novel dietary fatty acid that may be used as a dietary supplement in combination with chemotherapy to promote the antitumor efficacy of the chemotherapy drugs in dogs and possibly in humans with chemoresistant lymphoma.

We previously reported that combined fluoxetine administration at antidepressant doses renders additive antidepressant effects, whereas non-antidepressant doses potentiate the omega-3 fatty acid antidepressant effect. In the present study, we aimed to evaluate putative pharmacokinetic and brain omega-3 fatty acid-related aspects for fluoxetine potentiation of omega-3 fatty acid antidepressant effect in rats. Coadministration of omega-3 fatty acids with a non-antidepressant dose of fluoxetine (1 mg/kg day) failed to affect both brain fluoxetine concentration and norfluoxetine plasma concentration profile. Fluoxetine plasma concentrations remained below the sensitivity limit of the detection method. Either antidepressant (10 mg/kg day) or non-antidepressant (1 mg/kg day) doses of fluoxetine in combination with omega-3 fatty acids increased hippocampal docosapentaenoic acid (DPA, 22:5 omega-3) levels. Although individual treatments had no effects on DPA concentration, DPA increase was higher when omega-3 were combined with the non-antidepressant dose of fluoxetine. Chronic DPA administration exerted antidepressant-like effects in the forced swimming test while increasing hippocampal docosahexaenoic (22:6 omega-3) and DPA levels. Our results suggest no pharmacokinetic interaction and reveal specific hippocampal DPA changes after fluoxetine and omega-3 combined treatments in our experimental conditions. The DPA role in the synergistic effect of fluoxetine and omega-3 combined treatments will be for sure the focus of future studies. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:3316-3325, 2014. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Breast cancer patients often develop bone metastasis evidenced by osteolytic lesions, leading to severe pain and bone fracture. Attenuation of breast cancer metastasis to bone and associated osteolysis by fish oil, rich in EPA and DHA, has been demonstrated previously. However, it was not known whether EPA and DHA differentially or similarly affect breast cancer bone metastasis and associated osteolysis. In vitro culture of parental and luciferase gene encoded MDA-MB-231 human breast cancer cell lines treated with EPA and DHA revealed that DHA inhibits proliferation and invasion of breast cancer cells more potently than EPA. Intra-cardiac injection of parental and luciferase gene encoded MDA-MB-231 cells to athymic NCr nu/nu mice demonstrated that DHA-treated mice had significantly less breast cancer cell burden in bone, and also significantly less osteolytic lesions than EPA-treated mice. In vivo cell migration assay as measured by luciferase intensity revealed that DHA attenuated cell migration specifically to the bone. Moreover, the DHA-treated group showed reduced levels of CD44 and TRAP positive area in bone compared to EPA-treated group. Breast cancer cell burden and osteolytic lesions were also examined in intra-tibially breast cancer cell injected mice and found less breast cancer cell growth and associated osteolysis in DHA-treated mice as compared to EPA-treated mice. Finally, doxorubicin-resistant MCF-7 (MCF-7dox) human breast cancer cell line was used to examine if DHA can improve sensitization of MCF-7dox cells to doxorubicin. DHA improved the inhibitory effect of doxorubicin on proliferation and invasion of MCF-7dox cells. Interestingly, drug resistance gene P-gp was also down-regulated in DHA plus doxorubicin-treated cells. In conclusion, DHA attenuates breast cancer bone metastasis and associated osteolysis more potently than EPA, possibly by inhibiting migration of breast cancer cell to the bone as well as by inhibiting osteoclastic bone resorption.

Considerable research supports cardiovascular benefits of consuming omega-3 PUFA, also known as (n-3) PUFA, from fish or fish oil. Whether individual long-chain (n-3) PUFA have shared or complementary effects is not well established. We reviewed evidence for dietary and endogenous sources and cardiovascular effects on biologic pathways, physiologic risk factors, and clinical endpoints of EPA [20:5(n-3)], docosapentaenoic acid [DPA, 22:5(n-3)], and DHA [22:6(n-3)]. DHA requires direct dietary consumption, with little synthesis from or retroconversion to DPA or EPA. Whereas EPA is also largely derived from direct consumption, EPA can also be synthesized in small amounts from plant (n-3) precursors, especially stearidonic acid. In contrast, DPA appears principally derived from endogenous elongation from EPA, and DPA can also undergo retroconversion back to EPA. In experimental and animal models, both EPA and DHA modulate several relevant biologic pathways, with evidence for some differential benefits. In humans, both fatty acids lower TG levels and, based on more limited studies, favorably affect cardiac diastolic filling, arterial compliance, and some metrics of inflammation and oxidative stress. All three (n-3) PUFA reduce ex vivo platelet aggregation and DHA also modestly increases LDL and HDL particle size; the clinical relevance of such findings is uncertain. Combined EPA+DHA or DPA+DHA levels are associated with lower risk of fatal cardiac events and DHA with lower risk of atrial fibrillation, suggesting direct or indirect benefits of DHA for cardiac arrhythmias (although not excluding similar benefits of EPA or DPA). Conversely, EPA and DPA, but not DHA, are associated with lower risk of nonfatal cardiovascular endpoints in some studies, and purified EPA reduced risk of nonfatal coronary syndromes in one large clinical trial. Overall, for many cardiovascular pathways and outcomes, identified studies of individual (n-3) PUFA were relatively limited, especially for DPA. Nonetheless, the present evidence suggests that EPA and DHA have both shared and complementary benefits. Based on current evidence, increasing consumption of either would be advantageous compar

This study describes the effects of long-chain fatty acids on inflammatory signaling in cultured astrocytes. Data show that the saturated fatty acid palmitic acid, as well as lauric acid and stearic acid, trigger the release of TNFα and IL-6 from astrocytes. Unsaturated fatty acids were unable to induce cytokine release from cultured astrocytes. Furthermore, the effects of palmitic acid on cytokine release require Toll-like receptor 4 rather than CD36 or Toll-like receptor 2, and do not depend on palmitic acid metabolism to palmitoyl-CoA. Inhibitor studies revealed that pharmacologic inhibition of p38 or p42/44 MAPK pathways prevents the pro-inflammatory effects of palmitic acid, whereas JNK and PI3K inhibition does not affect cytokine release. Depletion of microglia from primary astrocyte cultures using the lysosomotropic agent l-leucine methyl ester revealed that the ability of palmitic acid to trigger cytokine release is not dependent on the presence of microglia. Finally, data show that the essential ω-3 fatty acid docosahexaenoic acid acts in a dose-dependent manner to prevent the actions of palmitic acid on inflammatory signaling in astrocytes. Collectively, these data demonstrate the ability of saturated fatty acids to induce astrocyte inflammation in vitro. These data thus raise the possibility that high levels of circulating saturated fatty acids could cause reactive gliosis and brain inflammation in vivo, and could potentially participate in the reported adverse neurologic consequences of obesity and metabolic syndrome. © 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry.