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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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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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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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A combined effect of Cavacurcumin, Eicosapentaenoic acid (Omega-3s), Astaxanthin and Gamma -linoleic acid (Omega-6) (CEAG) in healthy volunteers- a randomized, double-blind, placebo-controlled study.
Birudaraju, D, Cherukuri, L, Kinninger, A, Chaganti, BT, Shaikh, K, Hamal, S, Flores, F, Roy, SK, Budoff, MJ
Clinical nutrition ESPEN. 2020;:174-179
Abstract
BACKGROUND Inflammation plays a key role and is one of the early steps in the pathogenesis of endothelial function, thereby increasing the risk of hypertension (HTN), coronary artery disease (CAD), stroke and several other risk factors of cardiovascular disease (CVD). We assessed the efficacy for improving cardiovascular health (blood pressure, inflammation and endothelial reactivity) over a 4-week intervention period in healthy individuals. METHODS We performed a randomized, double-blinded, placebo-controlled, randomized clinical trial to investigate Curcumin, Eicosapentaenoic acid (EPA), Astaxanthin and Gamma -linoleic acid (GLA) (CEAG) supplements with 80 individuals (30 men and 50 women). The mean age of participants was 48.8 ± 16.0 years. Participants were enrolled and randomized to active or placebo and followed for 4 weeks. Paired and Independent T-tests were used to analyze the mean differences between and within groups. RESULTS The primary endpoints of the study were the effect on inflammatory markers (IL-6, CRP), endothelial function and blood pressure at 4 weeks. There was a significant reduction in mean SBP at 4 weeks in the CEAG group compared to placebo [mean ± SD 4.7 ± 6.8 (p = 0.002)]. Relative to placebo, active group showed a significant decrease in High sensitivity C Reactive Protein (hsCRP) (-0.49 ± 1.9 vs + 0.51 ± 2.5, p = 0.059) and blunted increase in IL-6 (+0.2 vs + 0.4 in placebo, p = 0.60). CONCLUSION Inflammatory markers were reduced or blunted by CEAG, with a robust increase in both EPA levels and the fatty acid index. Furthermore, systolic BP was reduced over 4 weeks with concurrent improvement in endothelial function. CLINICALTRIALS. GOV ID NCT03906825.
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Administration of eicosapentaenoic acid may alter lipoprotein particle heterogeneity in statin-treated patients with stable coronary artery disease: A pilot 6-month randomized study.
Tani, S, Yagi, T, Matsuo, R, Kawauchi, K, Atsumi, W, Matsumoto, N, Okumura, Y
Journal of cardiology. 2020;(5):487-498
Abstract
BACKGROUND We hypothesized that the addition of eicosapentaenoic acid (EPA) to ongoing statin therapy could change the particle heterogeneity of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particles, even in stable coronary artery disease (CAD) patients. METHODS We assigned CAD patients already receiving statin therapy to one of two groups: an EPA group (1800 mg/day; n = 30) and a control group (n = 30). A gel permeation high-performance liquid chromatography method was used to measure the particle concentration and number of lipoprotein subclasses. RESULTS In the EPA group, significant decreases of both the concentration and number of medium LDL (p = 0.0002 and 0.0001), small LDL (p = 0.0004 and 0.0005) and very small LDL (p = 0.0005 and 0.002) particles were observed. Conversely, the concentration and number of large HDL particles increased significantly (p = 0.024 and 0.048). The concentration of very large HDL particles also increased significantly (p = 0.028). Furthermore, significant correlations between the variables that showed significant changes in the LDL and HDL particle subclasses, and the EPA/arachidonic acid (AA) ratio were found. No other significant associations of lipoprotein particle heterogeneity with the serum EPA/AA ratio were noted in either the control group or the EPA group. Interestingly, univariate and multivariate regression analyses revealed that increased serum lecithin-cholesterol acyltransferase activity, a key enzyme of HDL cholesterol efflux, was a predictor for increased above-mentioned HDL particles subclasses. CONCLUSIONS Administration of EPA might alter both LDL and HDL particle heterogeneity, causing decreased concentration and number of smaller LDL particles and increased concentration and number of larger HDL particles. Furthermore, addition of EPA to ongoing statin therapy appears to be capable of increasing the EPA/AA ratio, which might have an anti-atherosclerotic effect on lipoprotein particle heterogeneity, even in stable CAD patients with well-controlled serum lipid levels. CLINICAL TRIAL REGISTRATION UMIN (http://www.umin.ac.jp/) Study ID: UMIN000010452.
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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 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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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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Expert Opinion on Benefits of Long-Chain Omega-3 Fatty Acids (DHA and EPA) in Aging and Clinical Nutrition.
Troesch, B, Eggersdorfer, M, Laviano, A, Rolland, Y, Smith, AD, Warnke, I, Weimann, A, Calder, PC
Nutrients. 2020;(9)
Abstract
Life expectancy is increasing and so is the prevalence of age-related non-communicable diseases (NCDs). Consequently, older people and patients present with multi-morbidities and more complex needs, putting significant pressure on healthcare systems. Effective nutrition interventions could be an important tool to address patient needs, improve clinical outcomes and reduce healthcare costs. Inflammation plays a central role in NCDs, so targeting it is relevant to disease prevention and treatment. The long-chain omega-3 polyunsaturated fatty acids (omega-3 LCPUFAs) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are known to reduce inflammation and promote its resolution, suggesting a beneficial role in various therapeutic areas. An expert group reviewed the data on omega-3 LCPUFAs in specific patient populations and medical conditions. Evidence for benefits in cognitive health, age- and disease-related decline in muscle mass, cancer treatment, surgical patients and critical illness was identified. Use of DHA and EPA in some conditions is already included in some relevant guidelines. However, it is important to note that data on the effects of omega-3 LCPUFAs are still inconsistent in many areas (e.g., cognitive decline) due to a range of factors that vary amongst the trials performed to date; these factors include dose, timing and duration; baseline omega-3 LCPUFA status; and intake of other nutrients. Well-designed intervention studies are required to optimize the effects of DHA and EPA in specific patient populations and to develop more personalized strategies for their use.
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Omega-3 and its domain-specific effects on cognitive test performance in youths: A meta-analysis.
Emery, S, Häberling, I, Berger, G, Walitza, S, Schmeck, K, Albert, T, Baumgartner, N, Strumberger, M, Albermann, M, Drechsler, R
Neuroscience and biobehavioral reviews. 2020;:420-436
Abstract
Omega-3 fatty acids are vital for brain development. The aim of this meta-analysis was to broaden current knowledge of the effects of omega-3 supplementation on cognitive test performance in youths. Randomized controlled trials (RCTs) meeting selection criteria were identified through two independent literature searches on PubMed, Cochrane Library, PsycARTICLES and PsycINFO (last search June 2019). Twenty-nine out of 1126 studies assessing 4247 participants met all selection criteria. A meta-analysis using random-effects model was performed for eight different cognitive domains. This first analysis revealed no main effect of omega-3 fatty acid supplementation on domain-specific cognitive test performance in youths. Subgroup analyses identified beneficial effects of eicosapentaenoic acid (EPA)-rich but not docosahexaenoic acid (DHA)-rich formulations in the domains of long-term memory, working memory and problem solving and a tendency towards beneficial effects in clinical rather than non-clinical populations. Future research should investigate differential effects of EPA and DHA and consider their baseline levels, other nutritional components and interactions with gene variations as potential predictors of response.