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Administration of eicosapentaenoic acid may alter high-density lipoprotein heterogeneity in statin-treated patients with stable coronary artery disease: A 6-month randomized trial.
Tani, S, Matsuo, R, Yagi, T, Matsumoto, N
Journal of cardiology. 2020;(3):282-288
Abstract
BACKGROUND Combined statin plus eicosapentaenoic acid (EPA) therapy might be a potentially effective treatment option to prevent coronary artery disease (CAD). The serum EPA/arachidonic acid (AA) ratio has been identified as a potential new risk marker for CAD. Few data exist whether administration of EPA could affect high-density lipoprotein (HDL) particle size. We hypothesized that the addition of EPA to ongoing statin therapy may result in altered HDL heterogeneity. METHODS We conducted this 6-month, single-center, prospective, randomized open-label clinical trial to investigate the effect of the additional administration of EPA on the HDL heterogeneity (HDL2, HDL3, and HDL2/HDL3 ratio) in stable CAD patients receiving treatment with statins. We assigned stable CAD patients already receiving statin therapy to the EPA group (1800mg/day: n=50) or the control group (n=50). RESULTS A significant decrease in the serum HDL3 level (-4.7% vs. -0.5%, p=0.037), but not of the serum HDL2 level, and a significant increase in the HDL2/HDL3 ratio (5.5% vs. -5.1%, p=0.032) were observed in the EPA group as compared to the control group. Multiple regression analysis with adjustments for coronary risk factors identified the achieved EPA/ AA ratio as an independent and significant predictor of an increase of the HDL2/HDL3 ratio (β=0.295, p=0.001). Furthermore, the change in the serum cholesterol ester transfer protein mass was positively correlated with the change in the EPA/AA ratio in the EPA group (r=0.286, p=0.044), but not in the control group (r=0.121, p=0.401). CONCLUSION Administration of EPA might decrease the serum HDL3 level, resulting in an increase in the HDL2/HDL3 ratio. Furthermore, increased EPA/AA ratio by the addition of EPA to ongoing statin therapy might be an indicator of an increase in the HDL2/HDL3 ratio, thereby regulating HDL particle size. CLINICAL TRIAL REGISTRATION UMIN (http://www.umin.ac.jp/) Study ID: UMIN000010452.
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High Variability in Erythrocyte, Plasma and Whole Blood EPA and DHA Levels in Response to Supplementation.
Sparkes, C, Sinclair, AJ, Gibson, RA, Else, PL, Meyer, BJ
Nutrients. 2020;(4)
Abstract
(1) Aim: the aim of this secondary analysis was to report the variability in response to n-3 long chain polyunsaturated fatty acids (LCPUFA) supplementation in erythrocytes, plasma and whole blood of a previously published dose response study. (2) Methods: a randomized, double-blind, placebo-controlled trial of parallel design was conducted, whereby pre-menopausal women were randomly assigned to consume 0, 0.35, 0.7 or 1 g/day of supplemental eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA). Fasted blood samples were taken at baseline and after eight weeks intervention. Erythrocyte, plasma and whole blood fatty acids were extracted using the method of Lepage and Roy and analysed using gas chromatography. (3) Results: There were significant increases in EPA plus DHA levels in the 0.7 g and 1 g dose groups, with the highest increase with the 1 g dose notably: in erythrocytes (from 5.69% to 7.59%), plasma (from 2.94% to 5.48%) and in whole blood (from 3.81% to 6.03%). There was high variability in response to the supplement in erythrocytes, plasma and whole blood across the different doses. (4) Conclusion: there is high individual variability in n-3 LCPUFA levels in response to n-3 LCPUFA supplementation, which should be taken into account in clinical trials using n-3 LCPUFA supplements.
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Effect of APOE Genotype on Plasma Docosahexaenoic Acid (DHA), Eicosapentaenoic Acid, Arachidonic Acid, and Hippocampal Volume in the Alzheimer's Disease Cooperative Study-Sponsored DHA Clinical Trial.
Tomaszewski, N, He, X, Solomon, V, Lee, M, Mack, WJ, Quinn, JF, Braskie, MN, Yassine, HN
Journal of Alzheimer's disease : JAD. 2020;(3):975-990
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Abstract
BACKGROUND Docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (AA) play key roles in several metabolic processes relevant to Alzheimer's disease (AD) pathogenesis and neuroinflammation. Carrying the APOEɛ4 allele (APOE4) accelerates omega-3 polyunsaturated fatty acid (PUFA) oxidation. In a pre-planned subgroup analysis of the Alzheimer's Disease Cooperative Study-sponsored DHA clinical trial, APOE4 carriers with mild probable AD had no improvements in cognitive outcomes compared to placebo, while APOE 4 non-carriers showed a benefit from DHA supplementation. OBJECTIVE We sought to clarify the effect of APOEɛ4/ɛ4 on both the ratio of plasma DHA and EPA to AA, and on hippocampal volumes after DHA supplementation. METHODS Plasma fatty acids and APOE genotype were obtained in 275 participants randomized to 18 months of DHA supplementation or placebo. A subset of these participants completed brain MRI imaging (n = 86) and lumbar punctures (n = 53). RESULTS After the intervention, DHA-treated APOEɛ3/ɛ3 and APOEɛ2/ɛ3 carriers demonstrated significantly greater increase in plasma DHA/AA compared to ɛ4/ɛ4 carriers. APOEɛ2/ɛ3 had a greater increase in plasma EPA/AA and less decline in left and right hippocampal volumes compared to compared to ɛ4/ɛ4 carriers. The change in plasma and cerebrospinal fluid DHA/AA was strongly correlated. Greater baseline and increase in plasma EPA/AA was associated with a lower decrease in the right hippocampal volume, but only in APOE 4 non-carriers. CONCLUSION The lower increase in plasma DHA/AA and EPA/AA in APOEɛ4/ɛ4 carriers after DHA supplementation reduces brain delivery and affects the efficacy of DHA supplementation.
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Concomitant Use of Rosuvastatin and Eicosapentaenoic Acid Significantly Prevents Native Coronary Atherosclerotic Progression in Patients With In-Stent Neoatherosclerosis.
Sugizaki, Y, Otake, H, Kuroda, K, Kawamori, H, Toba, T, Nagasawa, A, Takeshige, R, Nakano, S, Matsuoka, Y, Tanimura, K, et al
Circulation journal : official journal of the Japanese Circulation Society. 2020;(10):1826-1836
Abstract
BACKGROUND In-stent neoatherosclerosis (NA) is a risk for future cardiovascular events through atherosclerotic progression in non-stented lesions. Using optical coherence tomography, this study assessed the efficacy of intensive therapy with 10 mg/day rosuvastatin plus 1,800 mg/day eicosapentaenoic acid (EPA) vs. standard 2.5 mg/day rosuvastatin therapy on native coronary plaques in patients with NA.Methods and Results:This was a subgroup analysis of the randomized LINK-IT trial, which was designed to compare changes in the lipid index in NA between intensive and standard therapy for 12 months. In all, 42 patients with native coronary plaques and NA were assessed. Compared with standard therapy, intensive therapy resulted in greater decreases in serum low-density lipoprotein cholesterol concentrations and greater increases in serum 18-hydroxyeicosapentaenoic acid concentrations, with significantly greater decreases in the lipid index and macrophage grade in both NA (-24 vs. 217 [P<0.001] and -15 vs. 24 [P<0.001], respectively) and native coronary plaques (-112 vs. 29 [P<0.001] and -17 vs. 1 [P<0.001], respectively) following intensive therapy. Although there was a greater increase in the macrophage grade in NA than in native coronary plaques in the standard therapy group, in the intensive therapy group there were comparable reductions in macrophage grade between NA and native coronary plaques. CONCLUSIONS Compared with standard therapy, intensive therapy prevented atherosclerotic progression more effectively in native coronary plaques in patients with NA.
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Effect of Omega-3 Long Chain Polyunsaturated Fatty Acids (n-3 LCPUFA) Supplementation on Cognition in Children and Adolescents: A Systematic Literature Review with a Focus on n-3 LCPUFA Blood Values and Dose of DHA and EPA.
van der Wurff, ISM, Meyer, BJ, de Groot, RHM
Nutrients. 2020;(10)
Abstract
Omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) supplementation in the cardiovascular field is effective if a certain Omega-3 index (O3I) is achieved or the daily n-3 LCPUFA dose is high enough. Whether this applies to studies on cognition in children and adolescents is unclear. The aims of the current review were to investigate whether: (1) a certain O3I level and (2) a minimum daily n-3 LCPUFA dose are required to improve cognition in 4-25 year olds. Web of Science and PubMed were searched. Inclusion criteria: placebo controlled randomized controlled trial; participants 4-25 years; supplementation with docosahexaenoic acid (DHA) and/or eicosapentaenoic acid (EPA); assessing cognition; in English and ≥10 participants per treatment arm. Thirty-three studies were included, 21 in typically developing participants, 12 in those with a disorder. A positive effect on cognitive measures was more likely in studies with an increase in O3I to >6%. Half of the studies in typically developing children with daily supplementation dose ≥450 mg DHA + EPA showed improved cognition. For children with a disorder no cut-off value was found. In conclusion, daily supplementation of ≥450 mg DHA + EPA per day and an increase in the O3I to >6% makes it more likely to show efficacy on cognition in children and adolescents.
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The Effects of Lipid-Lowering Therapy on Serum Eicosapentaenoic Acid to Arachidonic Acid Ratio: An HIJ-PROPER Sub-Analysis.
Arashi, H, Yamaguchi, J, Kawada-Watanabe, E, Otsuki, H, Sekiguchi, H, Ogawa, H, Hagiwara, N
Journal of cardiovascular pharmacology and therapeutics. 2020;(6):548-555
Abstract
BACKGROUND Controversy remains regarding the influence of lipid-lowering therapy on the eicosapentaenoic acid/arachidonic acid ratio. OBJECTIVE This study aimed to clarify the effects of lipid-lowering therapy on the eicosapentaenoic acid/arachidonic acid ratio in patients with acute coronary syndrome (ACS). METHODS This was a post hoc sub-analysis of the Heart Institute of Japan-PRoper level of lipid-lowering with pitavastatin and ezetimibe in ACS study. We compared the eicosapentaenoic acid/arachidonic acid ratio changes from baseline to the 3-month follow-up after contemporary lipid-lowering therapy with pitavastatin + ezetimibe therapy and pitavastatin mono-therapy. RESULTS Among patients with ACS and dyslipidemia, the eicosapentaenoic acid/arachidonic acid increased significantly in the pitavastatin mono-therapy group (0.40 ± 0.26 to 0.46 ± 0.34, P < .0001) but did not increase in the pitavastatin + ezetimibe group (0.37 ± 0.22 to 0.38 ± 0.27, P = .18). When the analysis was limited to patients who received 2 mg/day of pitavastatin during the follow-up period, these trends in changes of the eicosapentaenoic acid/arachidonic acid ratio remained unchanged. Multivariate analysis showed that ezetimibe use (P = .005; β = 0.09), ST-elevation myocardial infarction (P = .04; β = -0.01), and baseline low-density lipoprotein cholesterol (LDL-C) level (P = .0003; β = 0.12) were independent predictors of the percentage change in the eicosapentaenoic acid/arachidonic acid ratio. These trends were similar even when the analysis was limited to patients who did not take statins at enrollment. CONCLUSION Standard lipid-lowering therapy with pitavastatin mono-therapy improved the eicosapentaenoic acid/arachidonic acid ratio for patients with ACS. Intensive lipid-lowering therapy with pitavastatin + ezetimibe did not improve the eicosapentaenoic acid/arachidonic acid ratio, although LDL-C decreased significantly. Inhibition of the improvement in the eicosapentaenoic acid/arachidonic acid ratio by adding ezetimibe may affect cardiovascular disease prognosis.
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Very Long Chain Marine n-3 Polyunsaturated Fatty Acids in Atherothrombotic Heart Disease. A Brief Review, with a Focus on Metabolic Effects.
Arnesen, H, Myhre, PL, Seljeflot, I
Nutrients. 2020;(10)
Abstract
The global burden of atherothrombotic heart disease should be considered as a life-style disorder where differences in dietary habits and related risk factors like limited physical activity and adiposity together play important roles. Related metabolic changes have been scientifically elucidated in recent decades, and the role of the very-long-chain marine fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been much focused on, especially their possible effects on processes like inflammation and thrombosis. In the present brief review of related metabolic mechanisms, the effects of these fatty acids in a clinical setting have been referred to, including some of the authors' work on this topic. The main focus is the divergent results in the field and the important differences between the study population, the type of supplements and fresh marine sources, the proportion of EPA versus DHA dosages, and the duration of supplementation in clinical trials. We conclude that daily intake of at least 1 g of EPA + DHA may improve a dysmetabolic state in the population. The potential to reduce the risk and progression of atherothrombotic heart disease is still a matter of debate.
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Effect of High-Dose Omega-3 Fatty Acids vs Corn Oil on Major Adverse Cardiovascular Events in Patients at High Cardiovascular Risk: The STRENGTH Randomized Clinical Trial.
Nicholls, SJ, Lincoff, AM, Garcia, M, Bash, D, Ballantyne, CM, Barter, PJ, Davidson, MH, Kastelein, JJP, Koenig, W, McGuire, DK, et al
JAMA. 2020;(22):2268-2280
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Abstract
IMPORTANCE It remains uncertain whether the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) reduce cardiovascular risk. OBJECTIVE To determine the effects on cardiovascular outcomes of a carboxylic acid formulation of EPA and DHA (omega-3 CA) with documented favorable effects on lipid and inflammatory markers in patients with atherogenic dyslipidemia and high cardiovascular risk. DESIGN, SETTING, AND PARTICIPANTS A double-blind, randomized, multicenter trial (enrollment October 30, 2014, to June 14, 2017; study termination January 8, 2020; last patient visit May 14, 2020) comparing omega-3 CA with corn oil in statin-treated participants with high cardiovascular risk, hypertriglyceridemia, and low levels of high-density lipoprotein cholesterol (HDL-C). A total of 13 078 patients were randomized at 675 academic and community hospitals in 22 countries in North America, Europe, South America, Asia, Australia, New Zealand, and South Africa. INTERVENTIONS Participants were randomized to receive 4 g/d of omega-3 CA (n = 6539) or corn oil, which was intended to serve as an inert comparator (n = 6539), in addition to usual background therapies, including statins. MAIN OUTCOMES AND MEASURES The primary efficacy measure was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina requiring hospitalization. RESULTS When 1384 patients had experienced a primary end point event (of a planned 1600 events), the trial was prematurely halted based on an interim analysis that indicated a low probability of clinical benefit of omega-3 CA vs the corn oil comparator. Among the 13 078 treated patients (mean [SD] age, 62.5 [9.0] years; 35% women; 70% with diabetes; median low-density lipoprotein [LDL] cholesterol level, 75.0 mg/dL; median triglycerides level, 240 mg/dL; median HDL-C level, 36 mg/dL; and median high-sensitivity C-reactive protein level, 2.1 mg/L), 12 633 (96.6%) completed the trial with ascertainment of primary end point status. The primary end point occurred in 785 patients (12.0%) treated with omega-3 CA vs 795 (12.2%) treated with corn oil (hazard ratio, 0.99 [95% CI, 0.90-1.09]; P = .84). A greater rate of gastrointestinal adverse events was observed in the omega-3 CA group (24.7%) compared with corn oil-treated patients (14.7%). CONCLUSIONS AND RELEVANCE Among statin-treated patients at high cardiovascular risk, the addition of omega-3 CA, compared with corn oil, to usual background therapies resulted in no significant difference in a composite outcome of major adverse cardiovascular events. These findings do not support use of this omega-3 fatty acid formulation to reduce major adverse cardiovascular events in high-risk patients. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02104817.
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Effects of a plant-based fatty acid supplement and a powdered fruit, vegetable and berry juice concentrate on omega-3-indices and serum micronutrient concentrations in healthy subjects.
Dams, S, Holasek, S, Tsiountsioura, M, Edelsbrunner, M, Dietz, P, Koefeler, H, Malliga, DE, Gürbüz, A, Meier-Allard, N, Poncza, B, et al
International journal of food sciences and nutrition. 2020;(6):769-780
Abstract
The major aim of this controlled, randomised, open-labelled, parallel-grouped, clinical trial was to investigate whether supplementation with different dosages of omega-3 fatty acids (0.5 g/d and 1 g/d) from a plant-based fatty acid supplement affected omega-3-indices (O3I) in well-nourished, healthy people. In addition, the combined ingestion of the plant-based fatty acid supplement, together with an encapsulated fruit, vegetable and berry (FVB) juice powder concentrate, was applied in order to observe the absorption of certain micronutrients and to examine some aspects related to the safe consumption of the products. The data demonstrate that the intake of only 0.5 g/day of omega-3 fatty acids from of a vegan supplement was able to increase the O3I significantly after 8 and 16 weeks. The combined ingestion with the FVB supplement concurrently increased serum concentrations of specific vitamins and carotenoids without effects on hepatic, kidney and thyroid function or changes in blood lipids.
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Sports-related concussions and subconcussive impacts in athletes: incidence, diagnosis, and the emerging role of EPA and DHA.
Lust, CAC, Mountjoy, M, Robinson, LE, Oliver, JM, Ma, DWL
Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme. 2020;(8):886-892
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Abstract
Sports-related concussions (SRC) are traumatic brain injuries induced as the result of a biomechanical force to the body that temporarily impair neurological functions. Not all traumatic impacts reach the threshold necessary to produce concussive symptoms; however, the culmination of these events is known as a subconcussive impact (SCI). Athletes who have been diagnosed with a SRC or those who accumulate multiple SCI have exhibited structural damage to the brain, impairments to learning and memory, and an increase in depressive symptoms. This area is rapidly evolving, and current clinical definitions of injury, diagnosis, and treatment of SRC and SCI are reviewed. In tandem, there is also growing research examining the role of nutrition in brain injuries, focusing primarily on n-3 polyunsaturated fatty acids (PUFA). The potential role of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in reducing inflammation and promoting recovery following brain injury are also reviewed. Overall, advancements in the evaluation of SRC and SCI coupled with n-3 PUFA supplementation show promise in the management of brain injuries, leading to better long-term health outcomes for athletes. Novelty SRC have garnered widespread attention due to the growing body of reported prevalence in youth and professional sports. Current definitions and protocol(s) for diagnosing SRC and SCI have improved, but still require further evaluation. n-3, EPA and DHA, reduce inflammation and promote recovery following brain injuries in experimental models.