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Effects of EPA and DHA on blood pressure and inflammatory factors: a meta-analysis of randomized controlled trials.
Guo, XF, Li, KL, Li, JM, Li, D
Critical reviews in food science and nutrition. 2019;(20):3380-3393
Abstract
The present study aimed to clarify whether eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have differential effects on blood pressure and inflammatory mediators. A systematic literature search was conducted in PubMed and Scopus updated to Apr. 2018. The mean changes in risk factors of chronic diseases were calculated as weighted mean difference (WMD) by using a random-effects model. Twenty randomized controlled trials (RCTs) were included. The summary estimate showed that EPA intervention significantly reduced systolic blood pressure (SBP) (-2.6 mmHg; 95%confident interval (CI): -4.6, -0.5 mmHg), especially in subjects with dyslipidemia (-3.8 mmHg; 95%CI: -6.7, -0.8 mmHg). The pooled effect indicated that supplemental DHA exerted a significant reduction in diastolic blood pressure (DBP) in subjects with dyslipidemia (-3.1 mmHg; 95%CI: -5.9, -0.2 mmHg). Both EPA (-0.56 mg/L; 95%CI: -1.13, 0.00) and DHA (-0.5 mg/L; 95%CI: -1.0, -0.03) significantly reduced the concentrations of C-reactive protein (CRP), respectively, especially in subjects with dyslipidemia and higher baseline CRP concentrations. Given that limited trials have focused on EPA or DHA intervention on concentrations of interleukin (IL)-6 and tumor necrosis factor (TNF)-α, further RCTs should be explored on these inflammatory factors. The present meta-analysis provides substantial evidence that EPA and DHA have independent (blood pressure) and shared (CRP concentration) effects on risk factors of chronic diseases, and high-quality RCTs with multi-center and large simple-size should be performed to confirm the present findings.
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2.
The Omega-6:Omega-3 ratio: A critical appraisal and possible successor.
Harris, WS
Prostaglandins, leukotrienes, and essential fatty acids. 2018;:34-40
Abstract
The well-known health effects of the long-chain, marine omega-3 (n-3) fatty acids (FAs) has led to a growing interest in the prognostic value that blood levels of these FAs might have vis-à-vis cardiovascular and neurocognitive diseases. The measurement and expression of n-3 FA levels is not straight-forward, however, and a wide variety of means of expression of n-3 FA status have been used in research and clinical medicine. This has led to considerable confusion as to what "optimal" n-3 FA status is. The n-6:n-3 ratio has enjoyed relatively widespread use, but this apparently simple metric has both theoretical and practical difficulties that have contributed to misunderstandings in this field. Just as the once-popular polyunsaturated:saturated FA ratio has largely disappeared from the nutritional and medical literature, it may be time to replace the n-6:n-3 ratio with a newer metric that focuses on the primary deficiency in Western diets - the lack of eicosapentaenoic and docosahexaenoic acids (EPA and DHA). The Omega-3 Index (red blood cell EPA+DHA) has much to recommend it in this regard.
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3.
The Differential Effects of Eicosapentaenoic Acid and Docosahexaenoic Acid on Cardiometabolic Risk Factors: A Systematic Review.
Innes, JK, Calder, PC
International journal of molecular sciences. 2018;(2)
Abstract
A large body of evidence supports the cardioprotective effects of the long-chain omega-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). There is increasing interest in the independent effects of EPA and DHA in the modulation of cardiometabolic risk factors. This systematic review aims to appraise the latest available evidence of the differential effects of EPA and DHA on such risk factors. A systematic literature review was conducted up to May 2017. Randomised controlled trials were included if they met strict eligibility criteria, including EPA or DHA > 2 g/day and purity ≥ 90%. Eighteen identified articles were included, corresponding to six unique studies involving 527 participants. Both EPA and DHA lowered triglyceride concentration, with DHA having a greater triglyceride-lowering effect. Whilst total cholesterol levels were largely unchanged by EPA and DHA, DHA increased high-density lipoprotein (HDL) cholesterol concentration, particularly HDL₂, and increased low-density lipoprotein (LDL) cholesterol concentration and LDL particle size. Both EPA and DHA inhibited platelet activity, whilst DHA improved vascular function and lowered heart rate and blood pressure to a greater extent than EPA. The effects of EPA and DHA on inflammatory markers and glycaemic control were inconclusive; however both lowered oxidative stress. Thus, EPA and DHA appear to have differential effects on cardiometabolic risk factors, but these need to be confirmed by larger clinical studies.
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Omega-3 fatty acids and non-alcoholic fatty liver disease: Evidence of efficacy and mechanism of action.
Scorletti, E, Byrne, CD
Molecular aspects of medicine. 2018;:135-146
Abstract
For many years it has been known that high doses of long chain omega-3 fatty acids are beneficial in the treatment of hypertriglyceridaemia. Over the last three decades, there has also been a wealth of in vitro and in vivo data that has accumulated to suggest that long chain omega-3 fatty acid treatment might be beneficial to decrease liver triacylglycerol. Several biological mechanisms have been identified that support this hypothesis; notably, it has been shown that long chain omega-3 fatty acids have a beneficial effect: a) on bioactive metabolites involved in inflammatory pathways, and b) on alteration of nuclear transcription factor activities such as peroxisome proliferator-activated receptors (PPARs), sterol regulatory element-binding protein 1c (SREBP-1c) and carbohydrate-responsive element-binding protein (ChREBP), involved in inflammatory pathways and liver lipid metabolism. Since the pathogenesis of non alcoholic fatty liver disease (NAFLD) begins with the accumulation of liver lipid and progresses with inflammation and then several years later with development of fibrosis; it has been thought in patients with NAFLD omega-3 fatty acid treatment would be beneficial in treating liver lipid and possibly also in ameliorating inflammation. Meta-analyses (of predominantly dietary studies and small trials) have tended to support the assertion that omega-3 fatty acids are beneficial in decreasing liver lipid, but recent randomised controlled trials have produced conflicting data. These trials have suggested that omega-3 fatty acid might be beneficial in decreasing liver triglyceride (docosahexanoic acid also possibly being more effective than eicosapentanoic acid) but not in decreasing other features of steatohepatitis (or liver fibrosis). The purpose of this review is to discuss recent evidence regarding biological mechanisms by which long chain omega-3 fatty acids might act to ameliorate liver disease in NAFLD; to consider the recent evidence from randomised trials in both adults and children with NAFLD; and finally to discuss key 'known unknowns' that need to be considered, before planning future studies that are focussed on testing the effects of omega-3 fatty acid treatment in patients with NAFLD.
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History and future of omega-3 fatty acids in cardiovascular disease.
Sperling, LS, Nelson, JR
Current medical research and opinion. 2016;(2):301-11
Abstract
BACKGROUND/OBJECTIVES Epidemiological, diet-based, and some interventional outcomes studies suggest that polyunsaturated omega-3 fatty acids (OM3FAs), specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), confer cardiovascular protection in some patient populations. This review examines the historical context of OM3FAs in cardiovascular disease and future perspectives on the place of OM3FA products in reducing cardiovascular risk. METHODS Relevant articles were identified via PubMed/Medline and Google Scholar searches through 2015 and through reference lists of selected publications. Articles determined by the authors to be relevant to the topic of this review were included. RESULTS Review of the identified articles indicated that inconsistent results among interventional outcomes studies have been attributed to use of low doses of OM3FAs, patient cohorts with non-elevated triglyceride (TG) levels, differential use of concomitant statin therapy, and study designs with insufficient statistical power. Several prescription OM3FA products are now approved as an adjunct to diet to reduce TG levels in adults with severe (≥500 mg/dL) hypertriglyceridemia. Most formulations contain both EPA and DHA; one formulation contains purified EPA. In randomized controlled trials, these products significantly reduced TG levels in patients with very high TG levels (≥500 mg/dL [≥13.0 mmol/L]) and in statin-treated patients with high TG levels (200-499 mg/dL [5.2-12.9 mmol/L]). The DHA-containing products raised LDL-C levels in these studies, whereas the EPA-only product had no effect on LDL-C, suggesting that all OM3FA prescription products are not therapeutically equivalent. Besides lowering TG levels, OM3FAs (particularly EPA) exert anti-inflammatory effects and may slow multiple atherogenic processes. Two well designed interventional outcomes studies (REDUCE-IT and STRENGTH) are evaluating prescription-strength, high-dose OM3FAs (4 g/day) in statin-treated patients with persistently high TG levels. CONCLUSIONS The results of the ongoing prescription-strength, high-dose OM3FA interventional trials will help define the potential role of OM3FAs in addressing residual cardiovascular risk despite statin therapy.
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Global survey of the omega-3 fatty acids, docosahexaenoic acid and eicosapentaenoic acid in the blood stream of healthy adults.
Stark, KD, Van Elswyk, ME, Higgins, MR, Weatherford, CA, Salem, N
Progress in lipid research. 2016;:132-52
Abstract
Studies reporting blood levels of the omega-3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), were systematically identified in order to create a global map identifying countries and regions with different blood levels. Included studies were those of healthy adults, published in 1980 or later. A total of 298 studies met all inclusion criteria. Studies reported fatty acids in various blood fractions including plasma total lipids (33%), plasma phospholipid (32%), erythrocytes (32%) and whole blood (3.0%). Fatty acid data from each blood fraction were converted to relative weight percentages (wt.%) and then assigned to one of four discrete ranges (high, moderate, low, very low) corresponding to wt.% EPA+DHA in erythrocyte equivalents. Regions with high EPA+DHA blood levels (>8%) included the Sea of Japan, Scandinavia, and areas with indigenous populations or populations not fully adapted to Westernized food habits. Very low blood levels (≤4%) were observed in North America, Central and South America, Europe, the Middle East, Southeast Asia, and Africa. The present review reveals considerable variability in blood levels of EPA+DHA and the very low to low range of blood EPA+DHA for most of the world may increase global risk for chronic disease.
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Omega-3 supplements for patients in chemotherapy and/or radiotherapy: A systematic review.
de Aguiar Pastore Silva, J, Emilia de Souza Fabre, M, Waitzberg, DL
Clinical nutrition (Edinburgh, Scotland). 2015;(3):359-66
Abstract
BACKGROUND & AIMS Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in vitro and in vivo, used along with anticancer drugs, have improved cancer treatment outcome. Clinical studies have reported positive results with omega-3 supplements in oncologic patients. We summarized only randomized controlled clinical trials involving the administration of DHA and/or EPA during chemotherapy and/or radiotherapy to assess the effects on treatment outcomes. METHODS We conducted a systematic literature search using specific terms. Of 157 publications, 10 were selected on the basis of their methodological quality, according to the Oxford Quality Scale and the Cochrane Concealment Assessment. Outcome included body weight and composition, peripheral neuropathy, immune, inflammatory and oxidative status, quality of life, and membrane omega-3 fatty acids incorporation. RESULTS Treatment regimens included radiotherapy (1), chemotherapy (8), and chemoradiotherapy (1). The number of patients ranged from 11 to 92 and the daily dose of EPA and/or DHA from 600 mg to 3.6 g. For high quality methodology studies only, the combination of omega-3 fatty acids supplements with conventional chemotherapy was beneficial. None of the studies reported a worse outcome for the supplement patients. CONCLUSIONS There are beneficial effects of omega-3 fatty acids supplements in patients undergoing chemotherapy and/or radiotherapy on different outcomes, being the preservation of body composition the most evident. Some important outcome like decrease tumor size and prolonging patient survival, are not observed.
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EFFECT OF EICOSAPENTAENOIC ACID AND DOCOSAHEXAENOIC ACID SUPPLEMENTATIONS TO CONTROL COGNITIVE DECLINE IN DEMENTIA AND ALZHEIMER'S DISEASE: A SYSTEMATIC REVIEW.
de Souza Fernandes, DP, Canaan Rezende, FA, Pereira Rocha, G, De Santis Filgueiras, M, Silva Moreira, PR, Gonçalves Alfenas, Rde C
Nutricion hospitalaria. 2015;(2):528-33
Abstract
INTRODUCTION there is a lack of consensus on the benefits of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementations on cognition in dementia and/or Alzheimer's disease (AD) elderly. OBJECTIVE this study presents a systematic review of the results of randomized clinical trials about this topic. The adopted search criteria were randomized clinical trials involving elderly over 65 years of age with no limit to the year of publication of the study. RESULTS we identified 139 articles, and from the eligible ones a reverse search was conducted. The quality of the trials was assessed using the Jadad scale. Of the four selected studies, three were related to mild to moderate AD elderly, of both genders. Mini Mental State Examination, Alzheimer's Disease Assessment Scale Cognitive, and Clinical Dementia Rate were the main tests used to assess cognitive performance. CONCLUSION EPA and/or DHA supplementations did not affect scores obtained on the cognitive tests. However, supplementation with EPA and/or DHA improved verbal fluency and attention in patients who had only very mild dementia or AD or presented APOEε4 negative genotype. In case of advanced AD elderly patients, EPA and/or DHA supplementations did not reduce cognitive decline rates.
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Dietary manipulation of platelet function.
Bachmair, EM, Ostertag, LM, Zhang, X, de Roos, B
Pharmacology & therapeutics. 2014;(2):97-113
Abstract
Activated platelets contribute to plaque formation within blood vessels in the early and late stages of atherogenesis, and therefore they have been proposed as risk factor for cardiovascular disease. Anti-platelet drugs, such as aspirin, are now the most prescribed pharmacological treatment in Europe. Certain dietary bioactives also beneficially affect platelet function, and with less side effects, albeit that effects are generally more subtle. Therefore, consumption of dietary bioactives could play a role in the prevention of atherothrombotic vascular disease. Here we review the efficacy of dietary treatment strategies, especially those involving certain dietary fatty acids and polyphenols, to modulate platelet function in healthy subjects or in patients with cardiovascular disease. Variation in study populations, small study sizes and lack of comparability between methods to assess platelet function currently limit robust evidence on the efficacy of dietary bioactives in healthy subjects or specific patient groups. Also, limited knowledge of the metabolism of dietary bioactives, and therefore of the bioavailability of bioactive ingredients, restricts our ability to identify the most effective dietary regimes to improve platelet function. Implementation of uniform point-of-care tests to assess platelet function, and enhanced knowledge of the efficacy by which specific dietary compounds and their metabolites affect platelet function, may enable the identification of functional anti-platelet ingredients that are eligible for a health claim, or combined treatment strategies, including both pharmacological anti-platelet treatment as well as dietary intervention, to tackle atherothrombotic vascular disease.
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The evidence for α-linolenic acid and cardiovascular disease benefits: Comparisons with eicosapentaenoic acid and docosahexaenoic acid.
Fleming, JA, Kris-Etherton, PM
Advances in nutrition (Bethesda, Md.). 2014;(6):863S-76S
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Abstract
Our understanding of the cardiovascular disease (CVD) benefits of α-linolenic acid (ALA, 18:3n-3) has advanced markedly during the past decade. It is now evident that ALA benefits CVD risk. The expansion of the ALA evidence base has occurred in parallel with ongoing research on eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) and CVD. The available evidence enables comparisons to be made for ALA vs. EPA + DHA for CVD risk reduction. The epidemiologic evidence suggests comparable benefits of plant-based and marine-derived n-3 (omega-3) PUFAs. The clinical trial evidence for ALA is not as extensive; however, there have been CVD event benefits reported. Those that have been reported for EPA + DHA are stronger because only EPA + DHA differed between the treatment and control groups, whereas in the ALA studies there were diet differences beyond ALA between the treatment and control groups. Despite this, the evidence suggests many comparable CVD benefits of ALA vs. EPA + DHA. Thus, we believe that it is time to revisit what the contemporary dietary recommendation should be for ALA to decrease the risk of CVD. Our perspective is that increasing dietary ALA will decrease CVD risk; however, randomized controlled clinical trials are necessary to confirm this and to determine what the recommendation should be. With a stronger evidence base, the nutrition community will be better positioned to revise the dietary recommendation for ALA for CVD risk reduction.