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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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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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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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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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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.
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Docosahexaenoic acid is a beneficial replacement treatment for spinocerebellar ataxia 38.
Manes, M, Alberici, A, Di Gregorio, E, Boccone, L, Premi, E, Mitro, N, Pasolini, MP, Pani, C, Paghera, B, Perani, D, et al
Annals of neurology. 2017;(4):615-621
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OBJECTIVE Spinocerebellar ataxia 38 (SCA38) is caused by mutations in the ELOVL5 gene, which encodes an elongase involved in the synthesis of polyunsaturated fatty acids, including docosahexaenoic acid (DHA). As a consequence, DHA is significantly reduced in the serum of SCA38 subjects. In the present study, we evaluated the safety of DHA supplementation, its efficacy for clinical symptoms, and changes of brain functional imaging in SCA38 patients. METHODS We enrolled 10 SCA38 patients, and carried out a double-blind randomized placebo-controlled study for 16 weeks, followed by an open-label study with overall 40-week DHA treatment. At baseline and at follow-up visit, patients underwent standardized clinical assessment, brain 18-fluorodeoxyglucose positron emission tomography, electroneurography, and ELOVL5 expression analysis. RESULTS After 16 weeks, we showed a significant pre-post clinical improvement in the DHA group versus placebo, using the Scale for the Assessment and Rating of Ataxia (SARA; mean difference [MD] = +2.70, 95% confidence interval [CI] = +0.13 to + 5.27, p = 0.042). At 40-week treatment, clinical improvement was found significant by both SARA (MD = +2.2, 95% CI = +0.93 to + 3.46, p = 0.008) and International Cooperative Ataxia Rating Scale (MD = +3.8, 95% CI = +1.39 to + 6.41, p = 0.02) scores; clinical data were corroborated by significant improvement of cerebellar hypometabolism (statistical parametric mapping analyses, false discovery rate corrected). We also showed a decreased expression of ELOVL5 in patients' blood at 40 weeks as compared to baseline. No side effect was recorded. INTERPRETATION DHA supplementation is a safe and effective treatment for SCA38, showing an improvement of clinical symptoms and cerebellar hypometabolism. Ann Neurol 2017;82:615-621.
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Modulation of Breast Cancer Risk Biomarkers by High-Dose Omega-3 Fatty Acids: Phase II Pilot Study in Postmenopausal Women.
Fabian, CJ, Kimler, BF, Phillips, TA, Nydegger, JL, Kreutzjans, AL, Carlson, SE, Hidaka, BH, Metheny, T, Zalles, CM, Mills, GB, et al
Cancer prevention research (Philadelphia, Pa.). 2015;(10):922-31
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Associational studies suggest higher intakes/blood levels of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) relative to the omega-6 arachidonic acid (AA) are associated with reduced breast cancer risk. We performed a pilot study of high-dose EPA + DHA in postmenopausal women to assess feasibility before initiating a phase IIB prevention trial. Postmenopausal women with cytologic evidence of hyperplasia in their baseline random periareolar fine needle aspiration (RPFNA) took 1,860 mg EPA +1500 mg DHA ethyl esters daily for 6 months. Blood and breast tissue were sampled at baseline and study conclusion for exploratory biomarker assessment, with P values uncorrected for multiple comparisons. Feasibility was predefined as 50% uptake, 80% completion, and 70% compliance. Trial uptake by 35 study entrants from 54 eligible women was 65%, with 97% completion and 97% compliance. Favorable modulation was suggested for serum adiponectin (P = 0.0027), TNFα (P = 0.016), HOMA 2B measure of pancreatic β cell function (P = 0.0048), and bioavailable estradiol (P = 0.039). Benign breast tissue Ki-67 (P = 0.036), macrophage chemoattractant protein-1 (P = 0.033), cytomorphology index score (P = 0.014), and percent mammographic density (P = 0.036) were decreased with favorable effects in a proteomics array for several proteins associated with mitogen signaling and cell-cycle arrest; but no obvious overall effect on proteins downstream of mTOR. Although favorable risk biomarker modulation will need to be confirmed in a placebo-controlled trial, we have demonstrated feasibility for development of high-dose EPA and DHA ethyl esters for primary prevention of breast cancer.
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Effects of omega-3 carboxylic acids on lipoprotein particles and other cardiovascular risk markers in high-risk statin-treated patients with residual hypertriglyceridemia: a randomized, controlled, double-blind trial.
Dunbar, RL, Nicholls, SJ, Maki, KC, Roth, EM, Orloff, DG, Curcio, D, Johnson, J, Kling, D, Davidson, MH
Lipids in health and disease. 2015;:98
Abstract
BACKGROUND This study examined the effects of a mixture of highly bioavailable omega-3 carboxylic acids (OM3-CA) on nuclear magnetic resonance spectroscopy-assessed lipoprotein particle concentrations and sizes and other cardiovascular risk markers in statin-treated patients with fasting triglycerides (TG) ≥ 2.3 mmol/L (200 mg/dL) and <5.6 mmol/L (500 mg/dL) and at high cardiovascular risk. METHODS After a diet lead-in and statin-stabilization period, 647 patients were randomly assigned to receive capsules of control (olive oil, OO) 4 g/d, OM3-CA 2 g/d (plus OO 2 g/d), or OM3-CA 4 g/d for 6 weeks. RESULTS Compared with OO, low-density lipoprotein (LDL) particle size was increased with OM3-CA 2 g/d (p < 0.01) and 4 g/d (p < 0.001), and very low-density lipoprotein (VLDL) and high-density lipoprotein (HDL) particle sizes were decreased with both OM3-CA dosages vs. OO (p < 0.001 and p < 0.05 for VLDL and HDL, respectively). Total VLDL/chylomicron remnant particle concentration was reduced by 8.5 and 16.0 % with OM3-CA 2 and 4 g/d, respectively, vs. a 6.9 % reduction with OO (p < 0.001 for OM3-CA 4 g/d vs. OO). Total HDL particle concentration was also reduced by 1.5 and 3.2 % with OM3-CA 2 and 4 g/d, respectively, vs. a 0.6 % increase with OO (at least p < 0.05 for both comparisons). Changes in total LDL particle concentration were not significantly different for OO vs. OM3-CA at either dosage. Apolipoprotein (Apo) CIII levels decreased by 7.6 and 13.1 % with OM3-CA 2 and 4 g/d, respectively, vs. 3.2 % with OO (p < 0.001 for OM3-CA 4 g/d vs. OO). Lipoprotein-associated phospholipase A2 (Lp-PLA2) mass was reduced by 6.2 and 10.7 % with OM3-CA 2 and 4 g/d, respectively, vs. a 0.1 % increase with OO (p < 0.001 for both vs. OO). There were no significant differences between treatments in high-sensitivity C-reactive protein responses. CONCLUSION OM3-CA were associated with shifts in lipoprotein particle sizes and concentrations, and reductions in Apo CIII and Lp-PLA2, in patients with hypertriglyceridemia while taking a statin. TRIAL REGISTRATION ClinicalTrials.gov Identifier NCT01408303.