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Prenatal docosahexaenoic acid supplementation has long-term effects on childhood behavioral and brain responses during performance on an inhibitory task.
Gustafson, KM, Liao, K, Mathis, NB, Shaddy, DJ, Kerling, EH, Christifano, DN, Colombo, J, Carlson, SE
Nutritional neuroscience. 2022;(1):80-90
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Abstract
Introduction: Offsprings from a prenatal docosahexaenoic acid (DHA) supplementation trial, in which pregnant women were assigned to placebo or 600mg DHA/day, were followed to determine the effect of prenatal DHA supplementation on the behavior and brain function at 5.5 years (n=81 placebo, n=86 supplemented).Methods: Event-related potentials (ERP) were recorded during a visual task requiring a button press (Go) to frequent target stimuli and response inhibition to the rare stimuli (No-Go). Univariate ANOVAs were used to test differences between group and sex for behavioral measures. ERP differences were tested using a three-way mixed-design multivariate analysis of variance (MANOVA).Results: There was a significant sex × group interaction for hit rate and errors of omission; there was no difference between males and females in the placebo group, but DHA males outperformed DHA females. Males overall and the placebo group made more errors requiring response inhibition; DHA females were significantly better than placebo females and DHA males. ERP P2 amplitude was larger in the DHA group. A significant N2 amplitude condition effect was observed in females and DHA group males, but not in placebo group males.Discussion: Prenatal DHA supplementation improved inhibitory performance overall, especially for females in the DHA group, possibly accounting for their conservative behavior during Go trials. Development of brain regions responsible for visual processing may be sensitive to maternal DHA status, evidenced by greater P2 amplitude. Males may benefit more from maternal DHA supplementation, indicated by the N2 condition effect seen only in males in the DHA group.
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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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Aspirin and omega-3 fatty acid status interact in the prevention of cardiovascular diseases in Framingham Heart Study.
Block, RC, Shearer, GC, Holub, A, Tu, XM, Mousa, S, Brenna, JT, Harris, WS, Tintle, N
Prostaglandins, leukotrienes, and essential fatty acids. 2021;:102283
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Abstract
BACKGROUND The roles of omega-3 (n3) fatty acids [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] and low-dose aspirin in the primary prevention of ischemic cardiovascular disease (CVD) are controversial. Since omega-3 (n3) fatty acids and aspirin affect cyclooxygenase activity in platelets, there could be a clinically-relevant effect of aspirin combined with a particular n3 fatty acid level present in each individual. METHODS RBC EPA+DHA, arachidonic acid (AA) and docosapentaenoic acid (DPA) were measured in 2500 participants without known CVD in the Framingham Heart Study. We then tested for interactions with reported aspirin use (1004 reported use and 1494 did not) on CVD outcomes. The median follow-up was 7.2 years. RESULTS Having RBC EPA+DHA in the second quintile (4.2-4.9% of total fatty acids) was associated with significantly reduced risk for future CVD events (relative to the first quintile, <4.2%) in those who did not take aspirin (HR 0.54 (0.30, 0.98)), but in those reporting aspirin use, risk was significantly increased (HR 2.16 (1.19, 3.92)) in this quintile. This interaction remained significant when adjusting for confounders. Significant interactions were also present for coronary heart disease and stroke outcomes using the same quintiles. Similar findings were present for EPA and DHA alone but not for DPA and AA. CONCLUSIONS There is a complex interaction between aspirin use and RBC EPA+DHA levels on CVD outcomes. This suggests that aspirin use may be beneficial in one omega-3 environment but harmful in another, implying that a personalized approach to both aspirin use and omega-3 supplementation may be needed.
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The ALGOVUE Clinical Trial: Effects of the Daily Consumption of Eggs Enriched with Lutein and Docosahexaenoic Acid on Plasma Composition and Macular Pigment Optical Density.
Schnebelen-Berthier, C, Acar, N, Simon, E, Thabuis, C, Bourdillon, A, Mathiaud, A, Dauchet, L, Delcourt, C, Benlian, P, Crochet, M, et al
Nutrients. 2021;(10)
Abstract
BACKGROUND Carotenoids and docosahexaenoic acid (DHA) were identified as essential components for eye health and are both naturally present in eggs. OBJECTIVE We aimed to evaluate the effect of the daily consumption of two eggs enriched with lutein/zeaxanthin and DHA on macular pigment optical density (MPOD) and on circulating xanthophyll and fatty acid concentrations in healthy participants. METHODS Ninety-nine healthy volunteers consumed either two standard eggs or two enriched eggs per day for 4 months. MPOD was measured at baseline (V0) and at follow-up (V4) using a modified confocal scanning laser ophthalmoscope (primary outcome). Blood samples were collected to determine total plasma and lipoprotein fatty acids and lutein/zeaxanthin compositions at V0 and V4 (secondary outcomes). RESULTS A slight but significant increase in MPOD was observed for all study participants consuming two eggs per day for 4 months at all eccentricities (0.5°, 1°, 2°, and 4°). Plasma and lipoprotein lutein, zeaxanthin, and DHA concentrations significantly increased in both groups but were greater in the enriched group (for the enriched group (V0 vs. V4): lutein, 167 vs. 369 ng/mL; zeaxanthin, 17.7 vs. 29.2 ng/mL; DHA, 1.89 vs. 2.56% of total fatty acids). Interestingly, lutein from high-density lipoprotein (HDL) was strongly correlated with MPOD at 0.5 and 1° eccentricities (rho = 0.385, p = 0.008, and rho = 0.461, p = 0.001, respectively). CONCLUSIONS MPOD was slightly increased in both groups. Lutein, zeaxanthin, and DHA plasma concentrations were strongly enhanced in the enriched group compared with the standard group. A significant correlation was found between MPOD level and lutein concentration in HDL.
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Differential and shared effects of eicosapentaenoic acid and docosahexaenoic acid on serum metabolome in subjects with chronic inflammation.
Chang, WC, So, J, Lamon-Fava, S
Scientific reports. 2021;(1):16324
Abstract
The omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) affect cell function and metabolism, but the differential effects of EPA and DHA are not known. In a randomized, controlled, double-blind, crossover study, we assessed the effects of 10-week supplementation with EPA-only and DHA-only (3 g/d), relative to a 4-week lead-in phase of high oleic acid sunflower oil (3 g/day, defined as baseline), on fasting serum metabolites in 21 subjects (9 men and 12 post-menopausal women) with chronic inflammation and some characteristics of metabolic syndrome. Relative to baseline, EPA significantly lowered the tricarboxylic acid (TCA) cycle intermediates fumarate and α-ketoglutarate and increased glucuronate, UDP-glucuronate, and non-esterified DHA. DHA significantly lowered the TCA cycle intermediates pyruvate, citrate, isocitrate, fumarate, α-ketoglutarate, and malate, and increased succinate and glucuronate. Pathway analysis showed that both EPA and DHA significantly affected the TCA cycle, the interconversion of pentose and glucuronate, and alanine, and aspartate and glutamate pathways (FDR < 0.05) and that DHA had a significantly greater effect on the TCA cycle than EPA. Our results indicate that EPA and DHA exhibit both common and differential effects on cell metabolism in subjects with chronic inflammation and some key aspects of metabolic syndrome.
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Docosahexaenoic and Arachidonic Acids as Neuroprotective Nutrients throughout the Life Cycle.
Sambra, V, Echeverria, F, Valenzuela, A, Chouinard-Watkins, R, Valenzuela, R
Nutrients. 2021;(3)
Abstract
The role of docosahexaenoic acid (DHA) and arachidonic acid (AA) in neurogenesis and brain development throughout the life cycle is fundamental. DHA and AA are long-chain polyunsaturated fatty acids (LCPUFA) vital for many human physiological processes, such as signaling pathways, gene expression, structure and function of membranes, among others. DHA and AA are deposited into the lipids of cell membranes that form the gray matter representing approximately 25% of the total content of brain fatty acids. Both fatty acids have effects on neuronal growth and differentiation through the modulation of the physical properties of neuronal membranes, signal transduction associated with G proteins, and gene expression. DHA and AA have a relevant role in neuroprotection against neurodegenerative pathologies such as Alzheimer's disease and Parkinson's disease, which are associated with characteristic pathological expressions as mitochondrial dysfunction, neuroinflammation, and oxidative stress. The present review analyzes the neuroprotective role of DHA and AA in the extreme stages of life, emphasizing the importance of these LCPUFA during the first year of life and in the developing/prevention of neurodegenerative diseases associated with aging.
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Efficacy of Docosahexaenoic Acid for the Prevention of Necrotizing Enterocolitis in Preterm Infants: A Randomized Clinical Trial.
Bernabe-García, M, Calder, PC, Villegas-Silva, R, Rodríguez-Cruz, M, Chávez-Sánchez, L, Cruz-Reynoso, L, Mateos-Sánchez, L, Lara-Flores, G, Aguilera-Joaquín, AR, Sánchez-García, L
Nutrients. 2021;(2)
Abstract
Necrotizing enterocolitis (NEC) is an inflammatory bowel disease and a leading cause of morbidity and mortality in preterm infants. In this study, a randomized double-blind parallel-group (1:1) trial was carried out in two neonatal intensive care units of two tertiary hospitals. Two hundred and twenty-five preterm newborns with an expected functional gastrointestinal tract were recruited and received an enteral dose of 75 mg of docosahexaenoic acid (DHA)/kg body weight or high-oleic sunflower oil daily for 14 days from the first enteral feed after birth. Confirmed NEC was evaluated with Bell's scale from stage ≥ IIa. Two hundred and fourteen randomized infants were analyzed in terms of the intent-to-treat (DHA-group: n = 105; control-group: n = 109); data for two hundred infants were analysed per protocol. Confirmed NEC was lower in infants from the DHA-group compared with the control-group (0/100 vs. 7/100; p = 0.007), with RR = 0.93 (95% CI 0.881 to 0.981), risk difference = -7%, (95% CI -12.00 to -1.99), and number needed-to-treat = 15 (95% CI 8.3 to 50). Intent-to-treat analysis showed a lower level of treatment failure in the DHA-group compared with the control-group (6/105 (6%) vs. 16/109 (15%); p = 0.03, RR = 0.905, (95% CI 0.826 to 0.991)). The results after multivariate-regression analysis remained significant. Adverse events (apart from the incidence of NEC) were not different between groups. A daily dose of DHA for 14 days starting with the first enteral feed may prevent NEC in preterm infants.
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Effects of dietary eicosapentaenoic acid and docosahexaenoic acid supplementation on metabolic syndrome: A systematic review and meta-analysis of data from 33 randomized controlled trials.
Zhang, HJ, Gao, X, Guo, XF, Li, KL, Li, S, Sinclair, AJ, Li, D
Clinical nutrition (Edinburgh, Scotland). 2021;(7):4538-4550
Abstract
BACKGROUND & AIMS Previous randomized controlled trials (RCTs) have compared the effects of pure preparations of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in reducing metabolic syndrome (MetS) risk factors, but the results were inconsistent. The present study aimed to clarify whether EPA and DHA have differential effects on MetS features in humans. METHODS A systematic literature search was conducted in CNKI, PubMed, Embase and Scopus updated to February 2021. The mean changes in the characteristics of MetS were calculated as weighted mean differences by using a random-effects model. Thirty-three RCTs were included. RESULTS The results showed that both EPA and DHA were effective at lowering serum triglycerides (TG) levels. EPA supplementation decreased the serum levels of total cholesterol (TC) (WMD = -0.24 mmol/L; 95% CI, -0.43, -0.05 mmol/L), TG (WMD = -0.77 mmol/L; 95% CI, -1.54, -0.00 mmol/L) and low density lipoprotein-cholesterol (LDL-C) (WMD = -0.13 mmol/L; 95% CI, -0.25, -0.01 mmol/L), while DHA increased the serum levels of TC (WMD = 0.14 mmol/L; 95% CI, 0.03, 0.25 mmol/L), LDL-C (WMD = 0.26 mmol/L; 95% CI, 0.15, 0.38 mmol/L) and high density lipoprotein-cholesterol (HDL-C) (WMD = 0.07 mmol/L; 95% CI, 0.04, 0.09 mmol/L). Moreover, DHA increased the serum levels of insulin compared with EPA, especially in subgroups whose mean age was <60 years (0.43 mU/L; 95% CI: 0.04, 0.81 mU/L) and duration of DHA supplementation < 3 months (0.39 mU/L; 95% CI: 0.01, 0.77 mU/L). CONCLUSIONS The present meta-analysis provides evidence that EPA and DHA have different effects on risk factors of MetS.
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Dietary Reference Intakes based on chronic disease endpoints: outcomes from a case study workshop for omega 3's EPA and DHA.
Racey, M, MacFarlane, A, Carlson, SE, Stark, KD, Plourde, M, Field, CJ, Yates, AA, Wells, G, Grantham, A, Bazinet, RP, et al
Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme. 2021;(5):530-539
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Abstract
Given the focus on developing Dietary Reference Intakes (DRIs) based on chronic disease risk reduction and recent research for omega-3 long chain PUFA since the last DRI review, the Canadian Nutrition Society convened a panel of stakeholders for a 1-day workshop in late 2019. Attendees discussed the new NASEM guidelines for establishing DRI values based on chronic disease risk endpoints and the strength of current evidence for EPA and DHA as it relates to the new guidelines. Novelty: Summarizes evidence and expert opinions regarding the potential for reviewing DRI values for EPA and DHA and cardiovascular disease risk and early development.
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Secondary data analysis investigating effects of marine omega-3 fatty acids on circulating levels of leptin and adiponectin in older adults.
Rausch, JA, Gillespie, S, Orchard, T, Tan, A, McDaniel, JC
Prostaglandins, leukotrienes, and essential fatty acids. 2021;:102302
Abstract
BACKGROUND Higher leptin and lower adiponectin levels have been linked to progressing systemic inflammation and diseases of aging. Among older adults with obesity and an inflammatory conditions, we quantified effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation on leptin, adiponectin, and the leptin-to-adiponectin ratio (LAR). We also examined associations among adipokine and cytokine levels. METHODS Using a randomized, double-blind, placebo-controlled design, participants (mean age 61.3 ± 2.1) received 1.5 g EPA + 1.0 g DHA (n = 14) or mineral oil (n = 18) daily. Plasma adipokine and cytokine levels were quantified by electrochemiluminescence at all study intervals. RESULTS While no between-group differences were detected, there was a reduction in the LAR (by 23%, p=.065) between weeks 4 and 8 among the EPA+DHA group. Adiponectin levels were negatively associated with IL-1β levels at week 4 (p=.02) and TNF-α levels at week 8 (p=.03). CONCLUSION Potential benefits of EPA+DHA supplementation among aging populations warrant further study.