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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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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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Body surface area-based omega-3 fatty acids supplementation strongly correlates to blood concentrations in children.
Ljungblad, L, Gleissman, H, Hedberg, G, Wickström, M, Eissler, N, Pickova, J, Johnsen, JI, Tedroff, K, Strandvik, B, Kogner, P
Prostaglandins, leukotrienes, and essential fatty acids. 2021;:102285
Abstract
Omega-3 fatty acids have been suggested as a complement in cancer treatment, but doses are not established. We performed a dose-finding study in 33 children in remission from cancer. Participants were allocated to a body surface area (BSA) adjusted dose (mg/m2) of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (40:60), ranging 233-3448 mg/m2 daily for 90 days. Fatty acid concentration in plasma phospholipids and red blood cells were determined by GC. Supplementation was well tolerated and correlated strongly with blood ω3-fatty acid concentrations and EPA showed the highest increase. Using the ω3-index disregards docosapentaenoic acid (DPA), which increased 30-43% in our study motivating an EDD-index (∑EPA,DPA,DHA). The ratio between arachidonic acid and EPA or DHA showed negative exponential trends. Dose per BSA enabled an individualized omega-3 supplementation decreasing the variation referred to interindividual differences. Based on our results, we suggest a dose of 1500 mg/m2 BSA for further studies.
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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 Association of Free Fatty Acids and Eicosanoids with the Severity of Depressive Symptoms in Stroke Patients.
Kotlega, D, Zembron-Lacny, A, Golab-Janowska, M, Nowacki, P, Szczuko, M
International journal of molecular sciences. 2020;(15)
Abstract
The study was designed to demonstrate the relationship of free fatty acids (FFAs) and eicosanoids levels with the severity of depressive symptoms in stroke. The ischemic stroke patients (n = 74) were included in the prospective study. The risk of depression was evaluated by the Beck Depression Inventory-II (BDI-II) 7 days and 6 months after the stroke onset. FFAs and inflammatory metabolites were determined by gas chromatography and liquid chromatography. In the acute phase of stroke, BDI-II and FFAs inversely correlated with C13:0 tridecanoic acid, C15:1 cis-10-pentadecanoid acid, C17:1 cis-10- heptadecanoid acid, C18:0 stearic acid, C20:3n6 eicosatrienoic acid, C22:1cis13 docosenoic acid and C22:6n3 docosahexaenoic acid (DHA). DHA level was significantly lower in patients with low vs. high BDI-II score. In the follow-up examination, BDI-II score directly correlated with C16:0 palmitic acid. The changes in BDI-II score during 6-month observation inversely correlated with lipoxin A4 and protectin D1, and directly correlated with 5-oxo-ETE. Importantly, the severity of depressive symptoms was associated with n3 PUFA level. Diet-derived FFAs were observed to potentially affect the inflammatory pathways in pathogenesis of depression in stroke and reduced DHA levels can attenuate depressive symptoms in stroke patients.
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In pregnancy, maternal HDL is specifically enriched in, and carries the highest proportion of, DHA in plasma.
Zamai, N, Cortie, CH, Jarvie, EM, Onyiaodike, CC, Alrehaili, A, Francois, M, Freeman, DJ, Meyer, BJ
Prostaglandins, leukotrienes, and essential fatty acids. 2020;:102209
Abstract
Arachidonic acid (AA) and docosahexaenoic acid (DHA) are important for neurological development. The aim was to determine the distribution and relative enrichment of AA and DHA among lipoprotein fractions prior to pregnancy, throughout gestation and in the post-partum period. Our hypothesis was that in pregnancy, in contrast to the non-pregnant state, AA and DHA are carried in highest concentration in the very low density lipoprotein (VLDL) fraction secondary to increased gestational liver triglyceride secretion. Two independent prospective, observational cohort studies carried out in Glasgow were combined; one early in pregnancy and one later in pregnancy with post-partum follow up. Across the pregnancy timeline plasma lipoproteins were isolated using sequential ultracentrifugation and lipoprotein fatty acids were extracted and analysed by gas chromatography. High density lipoprotein (HDL) had the highest concentration of AA and DHA compared to other lipoproteins. HDL became progressively enriched in the proportion of triglycerides at 16 weeks of gestation, which peaked at 35 weeks and returned to baseline at 13 weeks postpartum. HDL DHA per HDL-cholesterol and HDL DHA per apoA-I became progressively enriched at 16 weeks of gestation, peaked at 25 weeks and returned to baseline at 13 weeks postpartum, whereas HDL AA (per HDL-C or HDL-apoA-I) did not differ. DHA is carried primarily in HDL rather than VLDL. HDL has anti-oxidant properties that might afford DHA protection against oxidation.
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EPA and DHA as markers of nutraceutical treatment response in major depressive disorder.
van der Burg, KP, Cribb, L, Firth, J, Karmacoska, D, Mischoulon, D, Byrne, GJ, Bousman, C, Stough, C, Murphy, J, Oliver, G, et al
European journal of nutrition. 2020;(6):2439-2447
Abstract
PURPOSE Depression clinical trials are increasingly studying biomarkers to predict and monitor response to treatment. Assessment of biomarkers may reveal subsets of patients who are responsive to nutraceutical treatment, which may facilitate a personalized approach to treating depression. METHODS This is a post hoc analysis of an 8-week, double-blind, randomized, controlled trial (n = 158) investigating a combination nutraceutical comprising Omega-3 (EPA 1 g/DHA 656 mg), SAMe, zinc, 5-HTP, folinic acid, and co-factors versus placebo for the treatment of Major Depressive Disorder. The study explored levels of polyunsaturated fatty acids, folate, vitamin B12, zinc, homocysteine, and BDNF as possible predictors and correlates of response to nutraceutical supplementation. RESULTS Concentrations of EPA and DHA in red cell membranes increased in response to treatment and were significantly correlated with a decrease in depressive symptoms during active treatment (p = 0.003 and p = 0.029; respectively). Higher baseline levels of omega-6 fatty acid also correlated with depression reduction in the active treatment group ( p = 0.011). No other biomarkers were associated with a lessening of depressive symptoms. CONCLUSION Changes in fatty acid levels resulting from a nutraceutical combination containing EPA and DHA provide a response biomarker in treating depression.
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Effect of omega-3 fatty acids supplementation during pregnancy on lung function in preschoolers: a clinical trial.
Gutiérrez-Delgado, RI, Barraza-Villarreal, A, Escamilla-Núñez, C, Hernández-Cadena, L, Garcia-Feregrino, R, Shackleton, C, Ramakrishnan, U, Sly, PD, Romieu, I
The Journal of asthma : official journal of the Association for the Care of Asthma. 2019;(3):296-302
Abstract
RATIONALE Prenatal omega-3 fatty acids improve alveolarization, diminish inflammation, and improve pulmonary growth, but it is unclear whether these outcomes translate into improved postnatal lung function. OBJECTIVE We assessed the effect of prenatal supplementation with docosahexaenoic acid (DHA) on offspring lung function through 60 months of age. METHODS We included a cohort of 772 Mexican preschoolers whose mothers participated in a clinical trial (NCT00646360) of supplementation with DHA or a placebo from week 18-22 of gestation through delivery. MEASUREMENTS The children were followed after birth and anthropometric measurements and forced oscillation tests were performed at 36, 48, and 60 months of age. The effect of DHA was tested using a longitudinal mixed effect models. RESULTS Overall, mean (Standard Deviation) of the measurements of respiratory system resistance and respiratory system reactance at 6, 8, and 10 Hz during follow up period were 11.3 (2.4), 11.1 (2.4), 10.3 (2.2) and -5.2 (1.6), -4.8 (1.7), -4.6 (1.6), respectively. There were no significant differences in pulmonary function by treatment group. DHA did not affect the average lung function or the trajectories through 60 months. CONCLUSIONS Prenatal DHA supplementation did not influence pulmonary function in this cohort of Mexican preschoolers.
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Prenatal maternal docosahexaenoic acid intake and infant information processing at 4.5mo and 9mo: A longitudinal study.
Rees, A, Sirois, S, Wearden, A
PloS one. 2019;(2):e0210984
Abstract
Previous research suggesting an association between maternal prenatal docosahexaenoic acid (DHA) intake and infant cognition has yet to assess whether there is a critical trimester for the observed effects. We used a comprehensive Food Frequency Questionnaire to estimate DHA levels during both the second and third trimesters of pregnancy, in a sample of 125 pregnant women. Infants were assessed at 4.5 months and 9 months post-partum using specific tests of visual acuity, habituation, and visual attention. Based on maternal DHA levels during pregnancy, mothers were subdivided into high, medium, and low groups, and their infants compared for task performance using one-way ANOVAs with maternal DHA groups. On the 9 month visual acuity test, infants whose mothers were in the medium DHA group performed significantly better than those with mothers in the low or high DHA groups (p = 0.008). However, no significant finding was found for any of the other cognitive assessment measures. Despite a number of studies reporting a positive effect of higher DHA levels on cognitive development, this study fails to support those conclusions. We can, however, conclude that it appears to be DHA intake in the third trimester specifically, which is influencing the development of visual acuity towards the end of the first postnatal year.
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Dose-response relationship between docosahexaenoic acid (DHA) intake and lower rates of early preterm birth, low birth weight and very low birth weight.
Carlson, SE, Gajewski, BJ, Alhayek, S, Colombo, J, Kerling, EH, Gustafson, KM
Prostaglandins, leukotrienes, and essential fatty acids. 2018;:1-5
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Abstract
As previously reported, intention-to-treat findings from our phase III randomized clinical trial found that a supplement of 600 mg docosahexaenoic acid (DHA)/day during the last half of pregnancy reduced the incidence of early preterm birth (ePTB, <34 weeks gestation) and very low birth weight (VLBW < 1500 g) offspring. Given the potentially immense clinical significance of these findings, the goal of this secondary analysis was to (1) identify maternal characteristics related with capsule intake (i.e. DHA dose exposure) and (2) determine if DHA dose was associated with low (<2500 g) and very low birth weight after controlling for any relevant maternal characteristics. Three hundred forty-five pregnant mothers were recruited from hospitals in the Kansas City metropolitan area between 2006 and 2011. Most participants (n = 299) were from the phase III trial mentioned above, but we also included 46 participants from a second smaller, randomized trial that utilized an identical intervention design and was conducted concurrent to the larger trial. Both trials assigned participants to either 3 daily capsules of vegetable oil without DHA (n = 169) or 3 daily capsules of 200 mg DHA each (n = 176). Total capsules consumed was recorded by pharmacy supervised capsule count or participant self-report when needed. Maternal age, education, race and gestational age at delivery as well as infant birth weight were available for both trials. A Bayesian linear model indicated capsule intake increased with maternal age (p = 0.0100) and years of education (p = 0.0002). A Bayesian bivariate mixture-model associated capsule intake with simultaneous lower probability of ePTB, low birth weight (LBW, <2500 g) and VLBW (p = 0.0327). This, in conjunction with the positive findings in the clinical trial, support the need for future research to examine intervention methods to improve capsule compliance strategies in younger and less educated mothers.