DHA supplementation for early preterm birth prevention: An application of Bayesian finite mixture models to adaptive clinical trial design optimization.

BACKGROUND: Early preterm birth (ePTB) - born before 34 weeks of gestation - poses a significant public health challenge. Two randomized trials indicated an ePTB reduction among pregnant women receiving high-dose docosahexaenoic acid (DHA) supplementation. One of them is Assessment of DHA on Reducing Early Preterm Birth (ADORE). A survey employed in its secondary analysis identified women with low DHA levels, revealing that they derived greater benefits from high-dose DHA supplementation. This survey's inclusion in future trials can provide critical insights for informing clinical practices. OBJECTIVE: To optimize a Phase III trial design, ADORE Precision, aiming at assessing DHA supplement (200 vs. 1000 mg/day) on reducing ePTB among pregnant women with a low baseline DHA. METHODS: We propose a Bayesian Hybrid Response Adaptive Randomization (RAR) Design utilizing a finite mixture model to characterize gestational age at birth. Subsequently, a dichotomized ePTB outcome is used to inform trial design using RAR. Simulation studies were conducted to compare a Fixed Design, an Adaptive Design with early stopping, an ADORE-like Adaptive RAR Design, and two new Hybrid Designs with different hyperpriors. DISCUSSION: Simulation reveals several advantages of the RAR designs, such as higher allocation to the more promising dose and a trial duration reduction. The proposed Hybrid RAR Designs addresses the statistical power drop observed in Adaptive RAR. The new design model shows robustness to hyperprior choices. We recommend Hybrid RAR Design 1 for ADORE Precision, anticipating that it will yield precise determinations, which is crucial for advancing our understanding in this field.

Association between fatty acid intake and age-related macular degeneration: a meta-analysis.

Objective: The association of age-related macular degeneration (AMD) with the intake of high and low fatty acids (FAs), respectively, remains controversial. To this end, we performed a comprehensive meta-analysis of all the existing studies on the association of various intake levels of FA subtypes with AMD to determine these associations. Methods: A systematic search of PubMed, Web of Science, Cochrane Library, and EMBASE databases was conducted from inception to September 2023. To compare the highest and lowest groups, odds ratio (OR) with 95% confidence intervals (CIs) was analyzed with a random-effects model/fixed-effects model. Results: A high intake of omega-3 LCPUFAs (OR:0.67; 95%CI:[0.51, 0.88]; p = 0.004), DHA (OR:0.80; 95%CI:[0.70, 0.90]; p < 0.001), EPA (OR:0.91; 95%CI:[0.86, 0.97]; p = 0.004), and simultaneous intake of DHA and EPA (OR:0.79; 95%CI:[0.67, 0.93]; p = 0.035) significantly reduced the risk of overall AMD. Conversely, a high intake of trans-FAs (OR: 2.05; 95%CI: [1.29, 3.25]; p = 0.002) was significantly related to an increased risk of advanced AMD compared to the low-intake group. The subgroup analysis results are shown in the articles. Conclusion: Increasing dietary intake of omega-3 LCPUFAs, specifically DHA, and EPA, or the simultaneous intake of DHA and EPA, is significantly associated with a reduced risk of overall AMD. Various subtypes of omega-3 also have a significant association with a reduced risk of different stages of AMD. The high intake of trans-fatty acids (TFAs) is significantly and positively correlated with the risk of advanced AMD. This could further support the idea that consuming foods rich in omega-3 LCPUFAs and reducing consumption of foods rich in TFAs may prevent AMD. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023467227.

How membrane phospholipids containing long chain polyunsaturated fatty acids and their oxidation products orchestrate lipid raft dynamics to control inflammation.

Long chain polyunsaturated fatty acids (LC-PUFA) influence varying aspects of inflammation. One mechanism by which they regulate inflammation is by controlling the size and molecular composition of lipid rafts. Lipid rafts are sphingolipid/cholesterol-enriched plasma membrane microdomains that compartmentalize signaling proteins and thereby control downstream inflammatory gene expression and cytokine production. This review summarizes developments in our understanding of how LC-PUFA acyl chains of phospholipids, in addition to oxidized derivatives of LC-PUFAs such as oxidized 1-palmitoyl-2-arachidonyl-phosphatidylcholine (oxPAPC), manipulate formation of lipid rafts and thereby inflammation. We reviewed the literature, largely from the past two decades, on the impact of LC-PUFA acyl chains and oxidized products of LC-PUFAs on lipid raft biophysical organization of myeloid and lymphoid cells. The majority of the studies are based on rodent or cellular experiments with supporting mechanistic studies using biomimetic membranes and molecular dynamic simulations. These studies have focused largely on the LC-PUFA docosahexaenoic acid, with some studies addressing eicosapentaenoic acid. A few studies have investigated the role of oxidized phospholipids on rafts. The biophysical literature suggests a model in which n-3 LC-PUFAs, in addition to oxPAPC, localize predominately to non-raft regions and impart a disordering effect in this environment. Rafts become larger due to the ensuing increase in the difference in order between raft and non-rafts. Biochemical studies suggest some n-3 LC PUFAs can be found within rafts. This deviation from homeostasis is a potential trigger for controlling aspects of innate and adaptive immunity. Overall, select LC-PUFA acyl chains and oxidized acyl chains of phospholipids control lipid raft dynamics and downstream inflammation. Gaps in knowledge remain, particularly on underlying molecular mechanisms by which plasma membrane receptor organization is controlled in response to oxidized LC-PUFA acyl chains of membrane phospholipids. Validation in humans is also an area for future study.

Dietary supplementing South African indigenous rams with flaxseed oil and ascorbic acid improves cryopreserved semen quality and in vitro fertility.

The purpose of this study was to evaluate how ascorbic acid with dietary flaxseed oil affects the quality and fertility of cryopreserved ram sperm in South African indigenous rams. Treatment diets were supplemented 60 days before semen collection to afford proper spermatogenesis, adaptation to the feed formulated and fed throughout the study. Semen was collected with the use of artificial vagina following dietary supplementation with five treatment diets (neg. cont. - negative control, pos. cont. - positive control, FLO - 5% Flaxseed oil, ASA - 4% Ascorbic acid, and FLO + ASA). Semen was then extended using tris-based extender and cryopreserved using the programmable freezer (CBS Freezer 2100 series, Laboratory consumables & chemical suppliers, America). Ovaries were collected from a neighbouring slaughter house and conveyed to the lab in 0.9% saline at 37 °C. Data (sperm parameters and in vitro fertility) was then exposed to the GLM (General Linear Model) in Minitab 17. Pearson's correlation coefficient was utilized to investigate the relationship between cryopreserved sperm quality and in vitro fertility. The student Least Significant Difference Test was used to separate the treatment means, and differences were accepted when the p-value was less than 0.05. The FLO + ASA group had higher (p < 0.05) progressive (36.33 ± 1.87), total (88.24 ± 2.24), rapid motility (27.52 ± 1.74), intact plasma membrane (75.67 ± 2.08), total fertilization (65.98 ± 7.39), and total cleavage (66.19 ± 6.50) when compared to other treatment groups. Total fertilization rate had a medium significant (p < 0.001) medium correlation with the progressive motility (r2 = 0.435), total motility (r2 = 0.447) and rapid motility (r2 = 0.409). In conclusion, dietary flaxseed and ascorbic acid (FLO + ASA) improves cryopreserved semen quality, in vitro fertilization rate, and the total cleavage rate. Noteworthy, the progressive, total and rapid motility play a crucial in the in vitro fertilization rate.

Anti-Inflammatory Activity of the Combination of Nobiletin and Docosahexaenoic Acid in Lipopolysaccharide-Stimulated RAW 264.7 Cells: A Potential Synergistic Anti-Inflammatory Effect.

This study aimed to investigate a synergistic anti-inflammatory effect of a citrus flavonoid nobiletin and docosahexaenoic acid (DHA), one of n-3 long-chain polyunsaturated fatty acids, in combination. Simultaneous treatment with nobiletin and DHA synergistically inhibited nitric oxide production (combination index < 0.9) by mouse macrophage-like RAW 264.7 cells stimulated with lipopolysaccharide (LPS) without cytotoxicity. On the other hand, the inhibitory effect of nobiletin and DHA in combination on proinflammatory cytokine production was not synergistic. Neither nobiletin nor DHA affected the phagocytotic activity of RAW 264.7 cells stimulated with LPS. Immunoblot analysis revealed that the inhibition potency of DHA on the phosphorylation of ERK and p38 and nuclear translocation of NF-κB is markedly enhanced by simultaneously treating with nobiletin, which may lead to the synergistic anti-inflammatory effect. Overall, our findings show the potential of the synergistic anti-inflammatory effect of nobiletin and DHA in combination.

Increasing the Survival of a Neuronal Model of Alzheimer's Disease Using Docosahexaenoic Acid, Restoring Endolysosomal Functioning by Modifying the Interactions between the Membrane Proteins C99 and Rab5.

Docosahexaenoic acid (DHA, C22:6 ω3) may be involved in various neuroprotective mechanisms that could prevent Alzheimer's disease (AD). Its influence has still been little explored regarding the dysfunction of the endolysosomal pathway, known as an early key event in the physiopathological continuum triggering AD. This dysfunction could result from the accumulation of degradation products of the precursor protein of AD, in particular the C99 fragment, capable of interacting with endosomal proteins and thus contributing to altering this pathway from the early stages of AD. This study aims to evaluate whether neuroprotection mediated by DHA can also preserve the endolysosomal function. AD-typical endolysosomal abnormalities were recorded in differentiated human SH-SY5Y neuroblastoma cells expressing the Swedish form of human amyloid precursor protein. This altered phenotype included endosome enlargement, the reduced secretion of exosomes, and a higher level of apoptosis, which confirmed the relevance of the cellular model chosen for studying the associated deleterious mechanisms. Second, neuroprotection mediated by DHA was associated with a reduced interaction of C99 with the Rab5 GTPase, lower endosome size, restored exosome production, and reduced neuronal apoptosis. Our data reveal that DHA may influence protein localization and interactions in the neuronal membrane environment, thereby correcting the dysfunction of endocytosis and vesicular trafficking associated with AD.

The benefits of flushing with Lemuru fish oil as a source of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on the performance of reproductive parameters in Garut ewes.

This study aimed to evaluate and analyze the effects of a flushing diet containing Docosahexaenoic acid (DHA) and Eicosapentaenoic acid (EPA) from Lemuru (Sardinella sp) fish oil on the reproductive performance parameters of Garut ewes. Forty (n = 40) primiparous Garut ewes aged 12-14 months with an average body weight of 28.92 ± 4.94 kg were assigned into four experimental treatment groups. The experimental diets contained roughage: concentrate (30:70%) designated as control concentrate (CNT), flushing concentrate with 6% palm oil (PO), flushing concentrate with 3% palm oil mixed with 3% lemuru oil as DHA and EPA sources (PFO), and flushing concentrate with the addition of 6% lemuru oil (FO). Treatment animals were fed two weeks before and after conception and parturition (8 weeks of total flushing treatment). The addition of fish oil at either 3% (PFO) or 6% (FO) resulted in significantly higher reproductive performance of ewes by increasing the litter size, as reflected by the birth of multiple kids (P < 0.05) compared to CNT and PO. Adding fish oil (PFO and FO) also maintains gestation, resulting in increased lamb yield, especially in the FO treatment, which yields the highest lamb yield (0% single lamb birth). The lamb male ratio was also higher with fish oil supplementation (PFO and PO) (P < 0.05). This research revealed a positive effect of 6% Lemuru oil on decreasing embryo loss and increasing the proportion of twin births. These findings thus support the hypothesis that ration flushing with double the required DHA and EPA from 6% Lemuru fish oil (FO) resulted in significantly higher reproductive performance in Garut sheep.

Cognitive Benefits of Folic Acid, Docosahexaenoic Acid, and a Combination of Both Nutrients in Mild Cognitive Impairment: Possible Alterations through Mitochondrial Function and DNA Damage.

INTRODUCTION: It is uncertain whether folic acid (FA) combined with docosahexaenoic acid (DHA) could improve cognitive performance. This study evaluated the effects of a 12-month FA and DHA supplementation, in combination or alone, on cognitive function, DNA oxidative damage, and mitochondrial function in participants with mild cognitive impairment (MCI). METHODS: This randomized, double-blind, placebo-controlled trial recruited MCI participants aged 60 years and older. Two hundred and eighty participants were randomly divided in equal proportion into four groups: FA + DHA (FA 800 µg/d + DHA 800 mg/d), FA (800 µg/d), DHA (800 mg/d), and placebo groups daily orally for 12 months. The primary outcome was cognitive function evaluated by the Wechsler Adult Intelligence Scale-Revised (WAIS-RC). Cognitive tests and blood mechanism-related biomarkers were determined at baseline and 12 months. RESULTS: During the 12-month follow-up, scores of full intelligence quotient (ßDHA: 1.302, 95% CI: 0.615, 1.990, p < 0.001; ßFA: 1.992, 95% CI: 1.304, 2.679, p < 0.001; ßFA+DHA: 2.777, 95% CI: 2.090, 3.465, p < 0.001), verbal intelligence quotient, and some subtests of the WAIS-RC were significantly improved in FA + DHA and single intervention groups compared to the placebo group. Moreover, the FA and DHA intervention combination was superior to either intervention alone (p < 0.001). Meanwhile, FA, DHA, and their combined use significantly decreased 8-OHdG level and increased mitochondrial DNA copy number compared to the placebo (p < 0.05). CONCLUSIONS: Supplementation of FA and DHA, alone or combined, for 12 months can improve cognitive function in MCI participants, possibly through mitigating DNA oxidative damage and enhancing mitochondrial function. Combined supplementation may provide more cognitive benefit than supplementation alone.

Maternal docosahexaenoic acid supplementation during lactation improves exercise performance, enhances intestinal glucose absorption and modulates gut microbiota in weaning offspring mice.

Introduction: Intestinal dysfunction induced by weaning stress is common during breastfeeding period. Docosahexaenoic acid (DHA) is well known for promoting visual and brain development, but its effects on early intestinal development remain unknown. This study investigated the impact of maternal DHA supplementation during lactation on intestinal glucose absorption and gut microbiota in weaning offspring mice. Materials and methods: Dams were supplemented with vehicle (control), 150 mg/(kg body weight · day) DHA (L-DHA), or 450 mg/(kg body weight · day) DHA (H-DHA) throughout lactation by oral administration. After weaning, pups were randomly divided into three groups for athletic analysis, microbial and proteomic analysis, biochemical analysis, 4-deoxy-4-fluoro-D-glucose (4-FDG) absorption test, and gene expression quantitation of glucose transport-associated proteins and mTOR signaling components. Results: The H-DHA group exhibited enhanced grip strength and prolonged swimming duration compared to the control group. Additionally, there were significant increases in jejunal and ileal villus height, and expanded surface area of jejunal villi in the H-DHA group. Microbial analyses revealed that maternal DHA intake increased the abundance of beneficial gut bacteria and promoted metabolic pathways linked to carbohydrate and energy metabolism. Proteomic studies indicated an increased abundance of nutrient transport proteins and enrichment of pathways involved in absorption and digestion in the H-DHA group. This group also showed higher concentrations of glucose in the jejunum and ileum, as well as elevated glycogen levels in the liver and muscles, in contrast to lower glucose levels in the intestinal contents and feces compared to the control group. The 4-FDG absorption test showed more efficient absorption after oral 4-FDG gavage in the H-DHA group. Moreover, the expressions of glucose transport-associated proteins, GLUT2 and SGLT1, and the activation of mTOR pathway were enhanced in the H-DHA group compared to the control group. The L-DHA group also showed similar but less pronounced improvements in these aspects relative to the H-DHA group. Conclusion: Our findings suggested that maternal DHA supplementation during lactation improves the exercise performance, enhances the intestinal glucose absorption by increasing the expressions of glucose transporters, and beneficially alters the structure of gut microbiome in weaning offspring mice.

Microfluidic-Derived Docosahexaenoic Acid Liposomes for Targeting Glioblastoma and Its Inflammatory Microenvironment.

Glioblastoma (GBM) is the most common malignant primary brain tumor, characterized by limited treatment options and a poor prognosis. Its aggressiveness is attributed not only to the uncontrolled proliferation and invasion of tumor cells but also to the complex interplay between these cells and the surrounding microenvironment. Within the tumor microenvironment, an intricate network of immune cells, stromal cells, and various signaling molecules creates a pro-inflammatory milieu that supports tumor growth and progression. Docosahexaenoic acid (DHA), an essential ω3 polyunsaturated fatty acid for brain function, is associated with anti-inflammatory and anticarcinogenic properties. Therefore, in this work, DHA liposomes were synthesized using a microfluidic platform to target and reduce the inflammatory environment of GBM. The liposomes were rapidly taken up by macrophages in a time-dependent manner without causing cytotoxicity. Moreover, DHA liposomes successfully downregulated the expression of inflammatory-associated genes (IL-6; IL-1ß; TNFα; NF-κB, and STAT-1) and the secretion of key cytokines (IL-6 and TNFα) in stimulated macrophages and GBM cells. Conversely, no significant differences were observed in the expression of IL-10, an anti-inflammatory gene expressed in alternatively activated macrophages. Additionally, DHA liposomes were found to be more efficient in regulating the inflammatory profile of these cells compared with a free formulation of DHA. The nanomedicine platform established in this work opens new opportunities for developing liposomes incorporating DHA to target GBM and its inflammatory milieu.

Iron Reduces the Trafficking of Fatty Acids from Human Immortalised Brain Microvascular Endothelial Cells Through Modulation of Fatty Acid Transport Protein 1 (FATP1/SLC27A1).

PURPOSE: Alzheimer's disease (AD) is associated with brain accumulation of amyloid-beta (Aß) and neurofibrillary tangle formation, in addition to reduced brain docosahexaenoic acid (DHA) and increased brain iron levels. DHA requires access across the blood-brain barrier (BBB) to enter the brain, and iron has been shown to affect the expression and function of a number of BBB transporters. Therefore, this study aimed to assess the effect of iron on the expression and function of fatty acid binding protein 5 (FABP5) and fatty acid transport protein 1 (FATP1), both which mediate brain endothelial cell trafficking of DHA. METHODS: The mRNA and protein levels of FABP5 and FATP1 in human cerebral microvascular endothelial (hCMEC/D3) cells was assessed by RT-qPCR and Western blot, respectively following ferric ammonium citrate (FAC) treatment (up to 750 µM, 72 h). The function of FABP5 and FATP1 was assessed via uptake and efflux of radiolabelled 3H-oleic acid and 14C-DHA. RESULTS: FAC (500 µM, 72 h) had no impact on the expression of FABP5 at the protein and mRNA level in hCMEC/D3 cells, which was associated with a lack of effect on the uptake of 14C-DHA. FAC led to a 19.7% reduction in FATP1 protein abundance in hCMEC/D3 cells with no impact on mRNA levels, and this was associated with up to a 32.6% reduction in efflux of 14C-DHA. CONCLUSIONS: These studies demonstrate a role of iron in down-regulating FATP1 protein abundance and function at the BBB, which may have implications on fatty acid access to the brain.

Medium-chain triglycerides combined with DHA improve cognitive function by inhibiting neurocyte apoptosis of the brain in SAMP8 mice.

Medium-chain triglycerides (MCTs) and docosahexaenoic acid (DHA, Cn-3, 22:6) are essential in improving cognitive function and protecting neurocytes. This study explored the effects of the combined intervention of MCTs and DHA on inhibiting neurocyte apoptosis of the brain and improving cognitive function in senescence-accelerated mouse-prone 8 (SAMP8). Four-month-old male SAMP8 mice were randomly divided into four treatment groups (12 mice/group): DHA, MCT, DHA + MCT, and control groups, which intervened for seven months. Twelve age-matched male senescence-accelerated mouse resistant 1 (SAMR1) was used as the natural aging group. TUNEL assay and HE staining were used to assess neurocyte apoptosis and damage in the brain of mice. Moreover, the cognitive function was analyzed using the Morris water maze (MWM) and open field (OF) tests. The results showed that the cognitive function of 11-month-old SAMP8 mice decreased with age, and further pathological examination revealed the damaged neurocyte structure, karyopyknosis, cell atrophy, and even apoptosis. MCTs combined with DHA supplementation could increase octanoic acid (C8:0), decanoic acid (C10:0), and DHA levels in the serum, inhibit neurocyte apoptosis, improve neurocyte damage, moreover delay age-related cognitive decline after seven-month treatment. Furthermore, combining MCTs and DHA was significantly more beneficial than MCTs or DHA alone. In conclusion, MCTs combined with DHA could delay cognitive decline by inhibiting neurocyte apoptosis of the brain in SAMP8 mice.

Fish Oil, Plasma n-3 PUFAs, and Risk of Macro- and Microvascular Complications among Individuals with Type 2 Diabetes.

OBJECTIVE: To evaluate associations of fish oil supplementation and plasma omega 3 polyunsaturated fatty acids (n-3 PUFAs) with risks of macrovascular and microvascular complications among people with type 2 diabetes, and to further explore the potential mediating role of metabolism-related biomarkers. RESEARCH DESIGN AND METHODS: This study included 20,338 participants with type 2 diabetes from UK Biobank. Diabetic complications were identified through hospital inpatient records. RESULTS: During 13.2 years of follow-up, 5,396 people developed macrovascular complications, and 4,868 people developed microvascular complications. After multivariable adjustment, hazard ratios (HRs) and 95% confidence intervals (CIs) for patients with fish oil were 0.90 (0.85, 0.97) for composite macrovascular complications, 0.91 (0.84, 0.98) for coronary heart disease (CHD), 0.72 (0.61, 0.83) for peripheral artery disease; and 0.89 (0.83, 0.95) for composite microvascular complications, 0.87 (0.79, 0.95) for diabetic kidney disease, and 0.88 (0.80, 0.97) for diabetic retinopathy. In addition, higher n-3 PUFA levels, especially docosahexaenoic acid (DHA), were associated with lower risks of macrovascular and microvascular complications. Comparing extreme quartiles of plasma DHA, the HRs (95% CIs) were 0.68 (0.57, 0.81) for composite macrovascular complications, 0.63 (0.51, 0.77) for CHD; and 0.59 (0.38, 0.91) for diabetic neuropathy. Moreover, biomarkers including lipid profile and inflammation collectively explained 54.4% and 63.1% of associations of plasma DHA with risks of composite macrovascular complications and CHD. CONCLUSIONS: Habitual use of fish oil supplementation and higher plasma n-3 PUFA levels, especially DHA, were associated with lower risks of macrovascular and microvascular complications among individuals with type 2 diabetes, and the favorable associations were partially mediated through improving biomarkers of lipid profile and inflammation.

Docosahexaenoic acid supplementation during porcine oocyte in vitro maturation improves oocyte quality and embryonic development by enhancing the homeostasis of energy metabolism.

Although supplementation with docosahexaenoic acid (DHA) during porcine oocyte IVM is well-established, the available data are limited due to the lack of consistency. Moreover, to our knowledge, the anti-oxidant effects of DHA on porcine oocytes have not been reported. Hence, this study aimed to examine the effects of DHA supplementation on the regulation of energy metabolism during porcine oocyte maturation to improve oocyte maturation and embryonic development. By supplementing the IVM medium with various DHA concentrations, 25 µM DHA was identified as the optimal concentration which improved intraoocyte glutathione content and enhanced embryonic development after parthenogenesis. Compared to embryos derived from the control group, those derived from SCNT or IVF showed significantly improved blastocyst formation upon DHA supplementation during IVM. In addition, various transcription factors associated with oocyte development and apoptosis in mature oocytes were beneficially regulated in the DHA-treated oocytes. Moreover, DHA improved the AMP-activated protein kinase (AMPK)-regulatory ability of porcine oocytes and ameliorated nuclear maturation and embryonic development, which were decreased by artificially downregulating AMPK. To our knowledge, this is the first study to examine the effects of DHA as an AMPK regulator on oocyte maturation and embryo development in pigs. Furthermore, DHA addition to the IVM medium upregulated the relative expression of genes associated with mitochondrial potential and lipid metabolism. Therefore, the membrane potential of mitochondria (evaluated based on the JC-1 aggregate/JC-1 monomer ratio) and the levels of fatty acids and lipid droplets in matured oocytes increased, resulting in increased ATP synthesis. In conclusion, the DHA treatment of porcine oocytes with 25 µM DHA during IVM enhances the homeostasis of energy metabolism by improving mitochondrial function and lipid metabolism, leading to improved quality of matured oocytes and enhanced embryonic developmental potential of in vitro produced (IVP) embryos. Thus, 25 µM DHA supplementation could serve as a tool for improving the quality of IVP embryos. The study findings provide a basis for further research on improving the production efficiency of cloned animals by securing high-quality matured oocytes and enhancing energy metabolism in mammalian oocytes, including those of pigs.

Insight into low methoxyl pectin enhancing thermal stability and intestinal delivery efficiency of algal oil nanoemulsions.

BACKGROUND: Algae oil has garnered widespread acclaim due as a result of its high purity of docosahexaenoic acid (DHA) and excellent safety profile. The present study aimed to develop stable nanoemulsions (NEs) systems containing DHA from algae oil through thermal sterilization by combining modified whey protein concentrate (WPC) with low methoxyl pectin (LMP), as well as to investigate the impact of LMP concentration on the thermal stability and the gastrointestinal delivery efficiency of DHA NEs. RESULTS: The addition of LMP enhanced the stability of the emulsion after sterilization, at the same time as improving the protective and sustained release effects of DHA in the gastrointestinal tract. Optimal effect was achieved at a LMP concentration of 1% (10 g kg-1 sample), the stability of the emulsion after centrifugation increased by 17.21 ± 5.65% compared to the group without LMP, and the loss of DHA after sterilization decreased by only 0.92 ± 0.09%. Furthermore, the addition of 1% LMP resulted in a substantial reduction in the release of fatty acids from the NEs after gastrointestinal digestion simulation, achieving the desired sustained-release effect. However, excessive addition of 2% (20 g kg-1 sample) LMP negatively impacted all aspects of the NEs system, primarily because of the occurrence of depletion effects. CONCLUSION: The construction of the LMP/WPC-NEs system is conducive to the protection of DHA in algae oil and its sustained-release in the gastrointestinal tract. The results of the present study can provide reference guidance for the application of algae oil NEs in the food field. © 2024 Society of Chemical Industry.

Simple-by-design approach for production of stabilizer-free cubosomes from phosphatidylglycerol and docosahexaenoic acid monoacylglycerol.

Docosahexaenoic acid monoacylglycerol represents a promising lipid constituent in the development of drug nanocarriers owing to its amphiphilicity and the beneficial health effects of this docosahexaenoic acid precursor in various disorders including cancer and inflammatory diseases. Here, we describe the formation and characterization of simple-by-design and stabilizer-free lamellar and non-lamellar crystalline nanoparticles (vesicles and cubosomes, respectively) from binary mixtures of docosahexaenoic acid monoacylglycerol and phosphatidylglycerol, which is a ubiquitous amphiphilic component present in biological systems. At the physiological temperature of 37 °C, these single amphiphilic components tend to exhibit inverse hexagonal and lamellar liquid crystalline phases, respectively, on exposure to excess water. They can also be combined and dispersed in excess water by employing a high-energy emulsification method (by means of ultrasonication) to produce through an electrostatic stabilization mechanism colloidally stable nanodispersions. A colloidal transformation from vesicles to cubosomes was detected with increasing MAG-DHA content. Through use of synchrotron small-angle X-ray scattering, cryo-transmission electron microscopy, and nanoparticle tracking analysis, we report on the structural and morphological features, and size characteristics of these nanodispersions. Depending on the lipid composition, their internal liquid crystalline architectures were spanning from a lamellar (Lα) phase to biphasic features of coexisting inverse bicontinuous (Q2) cubic Pn3m and Im3m phases. Thus, a direct colloidal vesicle-cubosome transformation was detected by augmenting the concentration of docosahexaenoic acid monoacylglycerol. The produced cubosomes were thermally stable within the investigated temperature range of 5-60 °C. Collectively, our findings contribute to understanding of the imperative steps for production of stabilizer-free cubosomes from biocompatible lipids through a simple-by-design approach. We also discuss the potential therapeutic use and future implications for development of next-generation of multifunctional vesicles and cubosomes for co-delivery of docosahexaenoic acid and drugs in treatment of diseases.

Impact of fish oil supplementation on plasma levels of highly unsaturated fatty acid-containing lipid classes and molecular species in American football athletes.

BACKGROUND: Previous studies have linked sports-related concussions and repeated subconcussive head impacts in contact sport athletes to elevated brain injury biomarkers. Docosahexaenoic acid (DHA), the primary omega-3 (n-3) highly unsaturated fatty acid (HUFA) in the brain, has shown neuroprotective effects in animal models after brain injury, but clinical research has shown mixed results. METHODS: We conducted a randomized, double-blind, placebo-controlled study on 29 Division 1 collegiate American football players, exploring the impact of DHA (2.5 g) and eicosapentaenoic acid (EPA) (1.0 g) supplied as ethyl esters, on levels of plasma lipids shown to cross the blood-brain barrier. Dietary intake data was collected using food frequency questionnaires (FFQ). Complex lipids and unesterified fatty acids were isolated from plasma, separated via reversed-phase liquid chromatography and analyzed by targeted lipidomics analysis. RESULTS: FFQ results indicated that participants had low dietary n-3 HUFA intake and high omega-6 (n-6):n-3 polyunsaturated fatty acids (PUFA) and HUFA ratios at baseline. After DHA + EPA supplementation, plasma lysophosphatidylcholine (LPC) containing DHA and EPA significantly increased at all timepoints (weeks 17, 21, and 26; p < 0.0001), surpassing placebo at Weeks 17 (p < 0.05) and 21 (p < 0.05). Phosphatidylcholine (PC) molecular species containing DHA or EPA, PC38:6 PC36:6, PC38:7, PC40:6, and PC40:8, increased significantly in the DHA + EPA treatment group at Weeks 17 (and 21. Plasma concentrations of non-esterified DHA and EPA rose post-supplementation in Weeks 17 and 21. CONCLUSIONS: This study demonstrates that n-3 HUFA supplementation, in the form of ethyl esters, increased the DHA and EPA containing plasma lipid pools the have the capacity to enrich brain lipids and the potential to mitigate the effects of sports-related concussions and repeated subconcussive head impacts. TRIAL REGISTRATION: All deidentified data are available at ClinicalTrials.gov #NCT0479207.

Molecular cloning and functional analysis of a plastidial ω3 desaturase from Emiliania huxleyi.

Emiliania huxleyi is a marine microalga playing a significant ecological and biogeochemical role in oceans. It can produce several polyunsaturated fatty acids (PUFAs), such as docosahexaenoic acid (DHA, 22:6-4,7,10,13,16,19) and octadecapentaenoic acid (OPA, 18:5-3,6,9,12,15), providing a primary source for nutritionally important ω3 PUFAs in the marine food chain. However, the biosynthesis of these PUFAs in this organism is not well understood. In this study, a full length plastidial ω3 desaturase cDNA (EhN3) was cloned from this alga. Heterologous expression of EhN3 with and without the chloroplast targeting peptide (cTP) in cyanobacterium Synechococcus elongatus showed that it possessed high desaturation activity toward C18-ω6 PUFAs, linoleic acid (LA, 18:2-9,12), γ-linolenic acid (GLA, 18:3-6,9,12), and C20-ω6 PUFAs, dihomo-γ-linolenic acid (DGLA, 20:3-8,11,14) and arachidonic acid (ARA, 20:4-5,8,11,14) that were exogenously supplied. Desaturation efficiency could reach almost 100% in a time course. On the other hand, when expressed in Saccharomyces cerevisiae, EhN3 with and without cTP did not exhibit any activity. Lipid analysis of Synechococcus transformants expressing EhN3 showed that it utilized galactolipids as substrates. Transcriptional expression analysis revealed that the expression of the gene increased while the growth temperature decreased, which was correlated with the increased production of ω3-PUFAs, particularly OPA. This is the first report of a plastidial ω3 desaturase from microalgae that can effectively introduce an ω3 double bond into both C18-ω6 and C20-ω6 PUFAs. EhN3 might also be one of the key enzymes involved in the biosynthesis of OPA in E. huxleyi through the plastidial aerobic pathway.

Docosahexaenoic acid-enriched diet improves the flesh quality of freshwater fish (Megalobrama amblycephala): Evaluation based on nutritional value, texture and flavor.

Docosahexaenoic acid (DHA) is a potential regulatory substance for flesh quality of fish, while the related evaluation is still barely. In this study, the effects of DHA-enriched diets on the flesh quality of freshwater fish (Megalobrama amblycephala) were investigated systematically. The sub-adult M. amblycephala were randomly fed with control diet (CON), 0.2% DHA diet (DL) or 0.8% DHA diet (DH). After 12-week feeding trial, the DH group flesh had higher concentrations of essential amino acids and polyunsaturated fatty acids compared to the CON group. Meanwhile, the hardness, springiness, shear force and moisture-holding capacity, as well as the values of umami, richness and sweetness were also improved by DH. The non-targeted metabolomics analysis revealed the key metabolites that may have significantly positive influence on flavor. Collectively, the diet supplementation with 0.8% DHA could achieve the improvement of the flesh quality in terms of nutritional value, texture and flavor in freshwater fish.

Unsaturated fatty acids, omega-3 index and hospitalization in MISC.

The growing interest in Omega-3 fatty acids as diagnostic markers or new therapeutic approaches also for COVID-19 disease, led us to investigate the presence of potential correlations between Omega-3 fatty acids' levels in whole blood and days of hospitalization or admission to the paediatric intensive care unit (PICU) in 51 children with MIS-C diagnosis following SARS-CoV-2 infection. A statistically significant negative correlation was observed between days of hospitalization and docosapentaenoic acid (22:5n-3,DPA), docosahexaenoic acid (DHA) and total Omega-3 FA levels. Dividing the study group into quartiles according to Omega-3-Index (O3I), no statistically significant difference was observed with respect to the PICU admission rate. In contrast, the number of days of hospitalization in Q4 (O3I ≥ 2.51 %) was different from the number observed in groups Q1-3 (O3I < 2.51 %), with subjects showing higher O3I needing shorter hospitalizations than the subjects with lower O3I. According to previous study investigating O3I in adults affected by Sars-cov-2 we explored the levels of this nutrients in children with MIS-C. Our exploratory study shows that high DPA, DHA and O3I levels could be effective in reducing the length of hospitalization.