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1.
Higher-Dose DHA Supplementation Modulates Immune Responses in Pregnancy and Is Associated with Decreased Preterm Birth.
Valentine, CJ, Khan, AQ, Brown, AR, Sands, SA, Defranco, EA, Gajewski, BJ, Carlson, SE, Reber, KM, Rogers, LK
Nutrients. 2021;(12)
Abstract
Pregnancy and parturition involve extensive changes in the maternal immune system. In our randomized, multi-site, double-blind superiority trial using a Bayesian adaptive design, we demonstrated that 1000 mg/day of docosahexaenoic acid (DHA) was superior to 200 mg/day in preventing both early preterm birth (less than 34 weeks' gestation) and preterm birth (less than 37 weeks' gestation). The goal of this secondary study is to compare the effects of 1000 mg/day versus 200 mg/day on maternal inflammation, a possible mechanism by which DHA may prevent preterm birth. Maternal blood samples were collected at enrollment (12-20 weeks' gestation) and at delivery. Red blood cell DHA levels were measured by gas chromatography, and plasma concentrations of sRAGE, IL-6, IL-1β, TNFα, and INFγ were measured by ELISA. Data were analyzed for associations with the DHA dose, gestational age at birth, and preterm birth (<37 weeks). Higher baseline and lower delivery levels of maternal sRAGE were associated with a greater probability of longer gestation and delivery at term gestation. Higher-dose DHA supplementation increased the probability of a smaller decrease in delivery sRAGE levels. Higher IL-6 concentrations at delivery were associated with the probability of delivering after 37 weeks, and higher-dose DHA supplementation increased the probability of greater increases in IL-6 concentrations between enrollment and delivery. These data provide a proposed mechanistic explanation of how a higher dose of DHA during pregnancy provides immunomodulatory regulation in the initiation of parturition by influencing sRAGE and IL-6 levels, which may explain its ability to reduce the risk of preterm birth.
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2.
Docosahexaenoic acid nanoencapsulated with anti-PECAM-1 as co-therapy for atherosclerosis regression.
de Castro Leão, M, Raffin Pohlmann, A, de Cristo Soares Alves, A, Helena Poliselli Farsky, S, Klimuk Uchiyama, M, Araki, K, Sandri, S, Stanisçuaski Guterres, S, Alves Castro, I
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V. 2021;:99-107
Abstract
Atherosclerosis is a non-resolving inflammatory condition that underlies major cardiovascular diseases.Recent clinical trial using an anti-inflammatory drug has showna reduction of cardiovascular mortality, but increased the susceptibility to infections. For this reason, tissue target anti-inflammatory therapies can represent a better option to regress atherosclerotic plaques. Docosahexaenoic acid (DHA) is a natural omega 3 fatty acidcomponentof algae oil and acts asaprecursor of several anti-inflammatory compounds, such the specialized proresolving lipid mediators(SPMs). During the atherosclerosis process, the inflammatory condition of the endothelium leads to the higher expression of adhesion molecules, such as Endothelial Cell Adhesion Molecule Plate 1 (PECAM-1 or CD31), as part of the innate immune response. Thus, the objective of this study was to develop lipid-core nanocapsules with DHA constituting the nucleus and anti-PECAM-1 on their surface and drive this structure to the inflamed endothelium. Nanocapsules were prepared by interfacial deposition of pre-formed polymer method. Zinc-II was added to bind anti-PECAM-1 to the nanocapsule surface by forming an organometallic complex. Swelling experiment showed that the algae oil act as non-solvent for the polymer (weight constant weight for 60 days, p > 0.428) indicating an adequate material to produce kinetically stable lipid-core nanocapsules (LNC). Five formulations were synthesized: Lipid-core nanocapsules containing DHA (LNC-DHA) or containing Medium-chain triglycerides (LNC-MCT), multi-wall nanocapsules containing DHA (MLNC-DHA) or containing MCT (MLNC-MCT) and the surface-functionalized (anti-PECAM-1) metal-complex multi-wall nanocapsules containing DHA (MCMN-DHA-a1). All formulations showed homogeneous macroscopic aspects without aggregation. The mean size of the nanocapsules measured by laser diffraction did not show difference among the samples (p = 0.241). Multi-wall nanocapsules (MLNC) showed a slight increase in the mean diameter and polydispersity index (PDI) measured by DLS, lower pH and an inversion in the zeta-potential (ξP) compared to LNCs. Conjugation test for anti-PECAM-1 showed 94.80% of efficiency. The mean diameter of the formulation had slightly increased from 160 nm (LCN-DHA) and 162 nm (MLNC-DHA) to 164 nm (MCMN-DHA-a1) indicating that the surface functionalization did not induce aggregation of the nanocapsules. Biological assays showed that the MCMN-DHA-a1 were uptaken by the HUVEC cells and did not decrease their viability. The surface-functionalized (anti- PECAM-1) metal-complex multi-wall nanocapsules containing DHA (MCMN-DHA-a1) can be considered adequate for pharmaceutical approaches.
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3.
Marine omega-3 fatty acid supplementation in non-alcoholic fatty liver disease: Plasma proteomics in the randomized WELCOME* trial.
Manousopoulou, A, Scorletti, E, Smith, DE, Teng, J, Fotopoulos, M, Roumeliotis, TI, Clough, GF, Calder, PC, Byrne, CD, Garbis, SD
Clinical nutrition (Edinburgh, Scotland). 2019;(4):1952-1955
Abstract
BACKGROUND & AIMS Non-alcoholic fatty liver disease (NAFLD) is a liver condition characterised by liver fat accumulation and often considered to be the liver manifestation of metabolic syndrome. The aim of this study was to examine in patients with NAFLD the system-wide effects of treatment with docosahexaenoic acid + eicosapentaenoic acid (DHA + EPA) versus placebo on the plasma proteome. METHODS Plasma from patients that participated in a 15-18 months randomised, double-blind placebo-controlled trial testing the effects of 4 g DHA + EPA daily was analysed using depletion-free quantitative proteomics. RESULTS Bioinformatics interpretation of the proteomic analysis showed that DHA + EPA treatment affected pathways involving blood coagulation, immune/inflammatory response and cholesterol metabolism (p < 0.05). Two key proteins of cardiovascular risk, prothrombin and apolipoprotein B-100, were shown to decrease as a result of DHA + EPA supplementation [Prothrombin: Males DHA + EPA Mean iTRAQ log2ratio (SD) = -0.13 (0.20) p = 0.05, Females DHA + EPA Mean iTRAQ log2ratio (SD) = -0.48 (0.35) p = 0.03; Apo B-100: Males DHA + EPA Mean iTRAQ log2ratio (SD) = -0.24 (0.16) p = 0.01, Females DHA + EPA Mean iTRAQ log2ratio (SD) = -0.15 (0.05) p = 0.02]. CONCLUSIONS Plasma proteomics applied in a randomised, placebo-controlled trial showed that high dose DHA + EPA treatment in patients with NAFLD affects multiple pathways involved in chronic non-communicable diseases.
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4.
DHA and ARA addition to infant formula: Current status and future research directions.
Lien, EL, Richard, C, Hoffman, DR
Prostaglandins, leukotrienes, and essential fatty acids. 2018;:26-40
Abstract
Docosahexaenoic acid (DHA) and arachidonic acid (ARA) are present in breast milk and play important roles in early infant development. A supply of these fatty acids in infant formula (typically following breast milk as a model with ARA > DHA) is thought to be important since endogenous synthesis is insufficient to maintain tissue levels equivalent to breast-fed infants. Intervention studies assessing the impact of DHA- and ARA-supplemented formulas have resulted in numerous positive developmental outcomes (closer to breast-fed infants) including measures of specific cognition functions, visual acuity, and immune responses. A critical analysis of outcome assessment tools reveals the essentiality of selecting appropriate, focused techniques in order to provide accurate evaluation of DHA- and ARA-supplemented formulas. Future research directions should encompass in-depth assessment of specific cognitive outcomes, immune function, and disease incidence, as well as sources of experimental variability such as the status of fatty acid desaturase polymorphisms.
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5.
Inflammatory gene expression in whole blood cells after EPA vs. DHA supplementation: Results from the ComparED study.
Vors, C, Allaire, J, Marin, J, Lépine, MC, Charest, A, Tchernof, A, Couture, P, Lamarche, B
Atherosclerosis. 2017;:116-122
Abstract
BACKGROUND AND AIMS Whether EPA and DHA exert similar anti-inflammatory effects through modulation of gene expression in immune cells remains unclear. The aim of the study was to compare the impact of EPA and DHA supplementation on inflammatory gene expression in subjects at risk for cardiometabolic diseases. METHODS In this randomized double-blind crossover trial, 154 men and women with abdominal obesity and low-grade inflammation were subjected to three 10-wk supplementation phases: 1) EPA (2.7 g/d); 2) DHA (2.7 g/d); 3) corn oil (3 g/d), separated by a 9-wk washout. Pro- and anti-inflammatory gene expression was assessed in whole blood cells by RT-qPCR after each treatment in a representative sample of 44 participants. RESULTS No significant difference was observed between EPA and DHA in the expression of any of the genes investigated. Compared with control, EPA enhanced TRAF3 and PPARA expression and lowered CD14 expression (p < 0.01) whereas DHA increased expression of PPARA and TNFA and decreased CD14 expression (p < 0.05). Variations in gene expression after EPA and after DHA were strongly correlated for PPARA (r = 0.73, p < 0.0001) and TRAF3 (r = 0.66, p < 0.0001) and less for TNFA (r = 0.46, p < 0.005) and CD14 (r = 0.16, p = 0.30). CONCLUSIONS High-dose supplementation with either EPA or DHA has similar effects on the expression of many inflammation-related genes in immune cells of men and women at risk for cardiometabolic diseases. The effects of EPA and of DHA on anti-inflammatory gene expression may be more consistent than their effects on expression of pro-inflammatory genes in whole blood cells.
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6.
The importance of dietary DHA and ARA in early life: a public health perspective.
Forsyth, S, Gautier, S, Salem, N
The Proceedings of the Nutrition Society. 2017;(4):568-573
Abstract
Although the literature on the contribution of DHA and arachidonic acid (ARA) to fundamental metabolic functions in brain, immune and cardiovascular systems is extensive, there is a lack of consensus on the need for explicit recommendations on dietary intake for both DHA and ARA during the early years of life. This review takes a public health perspective with the objective of ensuring that recommendations protect the most vulnerable children worldwide. Most studies on the effects of DHA and ARA in early life have been undertaken in high-income countries and this is reflected in policy recommendations. Although breast milk is considered the gold standard and always contains DHA and ARA, there are proposals that infant formulas, especially follow-on formulas, do not need to be supplemented with these fatty acids. Complementary foods frequently have low concentrations of ARA and DHA and this is most significant in low-income countries where availability is also limited. Recent evidence shows that in developing countries, intakes of DHA and ARA during the age period 6-36 months are low and this relates to low national income. It is concluded that a continuum of DHA and ARA intake needs to be maintained during early life, a critical period of infant growth and development. For both infant and follow-on formulas, DHA and ARA should be mandatory at levels that are equivalent to breast milk. An optional recommendation may be limited to countries that can demonstrate evidence of adequate intakes of DHA and ARA during early life.
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7.
Long-Chain Polyunsaturated Fatty Acids and Clinical Outcomes of Preterm Infants.
Lapillonne, A, Moltu, SJ
Annals of nutrition & metabolism. 2016;:35-44
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Abstract
Long-chain polyunsaturated fatty acids (LCPUFAs) play specific roles during the perinatal period and are very important nutrients to consider. The possible effects of LCPUFAs, particularly docosahexaenoic acid (DHA), on various clinical outcomes of preterm infants are discussed in this paper. Since DHA accumulates in the central nervous system during development, a lot of attention has focused on the effects of DHA on neurodevelopment. Experimental studies as well as recent clinical trials show that providing larger amounts of DHA than currently and routinely provided is associated with better neurological outcomes at 18 months to 2 years. This early advantage, however, does not seem to translate into detectable change in visual and neurodevelopmental outcomes or behavior when assessed in childhood. There is growing evidence that, in addition to effects on development, omega-3 LCPUFAs may reduce the incidence or severity of neonatal morbidities by affecting different steps of the immune and anti-inflammatory response. Studies in preterm infants suggest that the omega-3 LCPUFAs may play a significant role by reducing the risk of bronchopulmonary dysplasia, necrotizing enterocolitis and possibly retinopathy of prematurity and sepsis. Overall, evidence is increasing to support the benefits of high-dose DHA for various health outcomes of preterm infants. These findings are of major clinical relevance mainly because infants born preterm are at particularly high risk for a nutritional deficit in omega-3 fatty acids, predisposing to adverse neonatal outcomes. Further studies are warranted to address these issues as well as to more precisely determine the LCPUFA requirement in order to favor the best possible outcomes of preterm infants.
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Low immune cell ARA and high plasma 12-HETE and 17-HDHA in iron-deficient South African school children with allergy.
Malan, L, Baumgartner, J, Calder, PC, Smuts, CM
Prostaglandins, leukotrienes, and essential fatty acids. 2016;:35-41
Abstract
Allergy has been associated with altered fatty acid and inflammatory status. In this cross-sectional study of 321 rural iron deficient (ID) South African children (aged 6-11 years), a subsample (n=111) of children with parent-reported allergy data were divided into an allergic (n=30) and non-allergic (n=81) group and compared. PBMC arachidonic acid (ARA; P=0.010) and the PBMC ARA to dihomo-gamma-linolenic acid (DGLA) ratio (P=0.035) were lower in the allergic children. Plasma 12-hydroxyeicosatetraenoic acid and 17-hydroxydocosahexaenoic acid (17-HDHA) were higher (P=0.040 and 0.020, respectively) in the allergic group. Thus, a fatty acid composition and lipid mediator levels indicative of increased release of ARA from PBMC membranes, increased inflammation as well as the resolving thereof, were associated with parent-reported allergy symptoms. This study used baseline data of an intervention study which was registered at clinicaltrials.gov as NCT01092377.
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Training Enhances Immune Cells Mitochondrial Biosynthesis, Fission, Fusion, and Their Antioxidant Capabilities Synergistically with Dietary Docosahexaenoic Supplementation.
Busquets-Cortés, C, Capó, X, Martorell, M, Tur, JA, Sureda, A, Pons, A
Oxidative medicine and cellular longevity. 2016;:8950384
Abstract
Exercise training induces adaptations in mitochondrial metabolism, dynamics, and oxidative protection. Omega-3 fatty acids change membrane lipid composition and modulate mitochondrial function. The aim was to investigate the effect of 8-week training and docosahexaenoic acid (DHA) supplementation (1.14 g/day) on the mitochondria dynamics and antioxidant status in peripheral blood mononuclear cells (PBMCs) from sportsmen. Subjects were assigned to an intervention (N = 9) or placebo groups (N = 7) in a randomized double-blind trial. Nutritional intervention significantly increased the DHA content in erythrocyte membranes from the experimental group. No significant differences were reported in terms of circulating PBMCs, Mn-superoxide dismutase protein levels, and their capability to produce reactive oxygen species. The proteins related to mitochondrial dynamics were, in general, increased after an 8-week training and this increase was enhanced by DHA supplementation. The content in mitofusins Mtf-1 and Mtf-2, optic atrophy protein-1 (Opa-1), and mitochondrial transcription factor A (Tfam) were significantly higher in the DHA-supplemented group after intervention. Cytochrome c oxidase (COX-IV) activity and uncoupling proteins UCP-2 and UCP-3 protein levels were increased after training, with higher UCP-3 levels in the supplemented group. In conclusion, training induced mitochondrial adaptations which may contribute to improved mitochondrial function. This mitochondrial response was modulated by DHA supplementation.
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Omega-3 supplements for patients in chemotherapy and/or radiotherapy: A systematic review.
de Aguiar Pastore Silva, J, Emilia de Souza Fabre, M, Waitzberg, DL
Clinical nutrition (Edinburgh, Scotland). 2015;(3):359-66
Abstract
BACKGROUND & AIMS Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in vitro and in vivo, used along with anticancer drugs, have improved cancer treatment outcome. Clinical studies have reported positive results with omega-3 supplements in oncologic patients. We summarized only randomized controlled clinical trials involving the administration of DHA and/or EPA during chemotherapy and/or radiotherapy to assess the effects on treatment outcomes. METHODS We conducted a systematic literature search using specific terms. Of 157 publications, 10 were selected on the basis of their methodological quality, according to the Oxford Quality Scale and the Cochrane Concealment Assessment. Outcome included body weight and composition, peripheral neuropathy, immune, inflammatory and oxidative status, quality of life, and membrane omega-3 fatty acids incorporation. RESULTS Treatment regimens included radiotherapy (1), chemotherapy (8), and chemoradiotherapy (1). The number of patients ranged from 11 to 92 and the daily dose of EPA and/or DHA from 600 mg to 3.6 g. For high quality methodology studies only, the combination of omega-3 fatty acids supplements with conventional chemotherapy was beneficial. None of the studies reported a worse outcome for the supplement patients. CONCLUSIONS There are beneficial effects of omega-3 fatty acids supplements in patients undergoing chemotherapy and/or radiotherapy on different outcomes, being the preservation of body composition the most evident. Some important outcome like decrease tumor size and prolonging patient survival, are not observed.