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Effects of dietary eicosapentaenoic acid and docosahexaenoic acid supplementation on metabolic syndrome: A systematic review and meta-analysis of data from 33 randomized controlled trials.
Zhang, HJ, Gao, X, Guo, XF, Li, KL, Li, S, Sinclair, AJ, Li, D
Clinical nutrition (Edinburgh, Scotland). 2021;(7):4538-4550
Abstract
BACKGROUND & AIMS Previous randomized controlled trials (RCTs) have compared the effects of pure preparations of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in reducing metabolic syndrome (MetS) risk factors, but the results were inconsistent. The present study aimed to clarify whether EPA and DHA have differential effects on MetS features in humans. METHODS A systematic literature search was conducted in CNKI, PubMed, Embase and Scopus updated to February 2021. The mean changes in the characteristics of MetS were calculated as weighted mean differences by using a random-effects model. Thirty-three RCTs were included. RESULTS The results showed that both EPA and DHA were effective at lowering serum triglycerides (TG) levels. EPA supplementation decreased the serum levels of total cholesterol (TC) (WMD = -0.24 mmol/L; 95% CI, -0.43, -0.05 mmol/L), TG (WMD = -0.77 mmol/L; 95% CI, -1.54, -0.00 mmol/L) and low density lipoprotein-cholesterol (LDL-C) (WMD = -0.13 mmol/L; 95% CI, -0.25, -0.01 mmol/L), while DHA increased the serum levels of TC (WMD = 0.14 mmol/L; 95% CI, 0.03, 0.25 mmol/L), LDL-C (WMD = 0.26 mmol/L; 95% CI, 0.15, 0.38 mmol/L) and high density lipoprotein-cholesterol (HDL-C) (WMD = 0.07 mmol/L; 95% CI, 0.04, 0.09 mmol/L). Moreover, DHA increased the serum levels of insulin compared with EPA, especially in subgroups whose mean age was <60 years (0.43 mU/L; 95% CI: 0.04, 0.81 mU/L) and duration of DHA supplementation < 3 months (0.39 mU/L; 95% CI: 0.01, 0.77 mU/L). CONCLUSIONS The present meta-analysis provides evidence that EPA and DHA have different effects on risk factors of MetS.
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Effects of n-3 EPA and DHA supplementation on fat free mass and physical performance in elderly. A systematic review and meta-analysis of randomized clinical trial.
Rondanelli, M, Perna, S, Riva, A, Petrangolini, G, Di Paolo, E, Gasparri, C
Mechanisms of ageing and development. 2021;:111476
Abstract
The most studied n-3 polyunsaturated fatty acids (n-3 PUFAs) are eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3), and their intake seem to have a positive effect on skeletal muscle. This systematic review and meta-analysis aims to investigate the effect of n-3 EPA and DHA supplementation on fat free mass, and on different indexes of physical performance in the elderly. Eligible studies included RCT studies that investigated EPA and DHA intervention. Random-effects models have been used in order to estimate pooled effect sizes, the mean differences, and 95 % CIs. Findings from 14 studies (n = 2220 participants) lasting from 6 to 144 weeks have been summarized in this article. The meta-analyzed mean differences for random effects showed that daily n-3 EPA + DHA supplementation (from 0.7 g to 3.36 g) decreases the time of Time Up and Go (TUG) test of -0.28 s (CI 95 %-0.43, -0.13;). No statistically significant effects on physical performance indicators, such as 4-meter Walking Test, Chair Rise Test and Handgrip Strength, have been found. The fat free mass follows an improvement trend of +0.30 kg (CI 95 % -0.39, 0.99) but not statistically significant. N-3 EPA + DHA supplementation could be a promising strategy in order to enhance muscle quality and prevent or treat frailty.
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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.
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Docosahexaenoic acid supplementation in age-related cognitive decline: a systematic review and meta-analysis.
Balachandar, R, Soundararajan, S, Bagepally, BS
European journal of clinical pharmacology. 2020;(5):639-648
Abstract
PURPOSE To investigate the role of DHA supplementation in preventing age-related cognitive decline (ARCD) in individual cognitive domains by conducting systematic review and meta-analysis. METHODS Relevant clinical trials were systematically searched at Medline, PubMed, Scopus, Cochrane, ProQuest, and Embase databases since inception to June 2018. The PRISMA guidelines were adhered for data abstraction, quality assessment, and validation of included studies. Study details such as participant characteristics, DHA supplementation, and cognitive function outcome measures, i.e., memory, attention, working memory, and executive function, were extracted to perform meta-analysis according to the Cochrane guidelines. Additional meta-regression and subgroup analyses were performed to detect confounding variables and sensitivity of results, respectively. RESULTS Ten studies including 2327 elderly individuals were part of the final results. Study exhibited minimal or no pooled incremental effects on memory (0.22, 95%CI = - 0.17 to 0.61, I2 = 94.36%), attention (0.1, 95%CI = - 0.04 to 0.25, I2 = 32.25%), working memory (0.01, 95%CI = - 0.10 to 0.12, I2 = 0%), and executive function (0.03, 95%CI = - 0.05 to 0.11, I2 = 78.48%) among the DHA-supplemented group. The results from standard mean difference between the groups, on memory (0.08, 95%CI = - 0.12 to 0.28, I2 = 76.82%), attention (0.04, 95%CI = - 0.09 to 0.23, I2 = 42.63%), working memory (- 0.08, 95%CI = - 0.26 to 0.10, I2 = 37.57%), and executive function (0.17, 95%CI = - 0.01 to 0.36, I2 = 78.48%) were similar to the results of pooled incremental analysis. Lastly, results remained unaffected by sensitivity and sub-group analyses. CONCLUSIONS Current pieces of evidence do not support the role of DHA supplementation, in preventing/retarding ARCD of memory, executive function, attention, and working memory. Protocol registered at PROSPERO (ID: PROSPERO 2018 CRD42018099401).
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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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International Society for Nutritional Psychiatry Research Practice Guidelines for Omega-3 Fatty Acids in the Treatment of Major Depressive Disorder.
Guu, TW, Mischoulon, D, Sarris, J, Hibbeln, J, McNamara, RK, Hamazaki, K, Freeman, MP, Maes, M, Matsuoka, YJ, Belmaker, RH, et al
Psychotherapy and psychosomatics. 2019;(5):263-273
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Abstract
Major depressive disorder (MDD) is a complex mental illness with unmet therapeutic needs. The antidepressant effects of ω-3 polyunsaturated fatty acids (n-3 PUFAs) have been widely reported. The subcommittee of the International Society for Nutritional Psychiatry Research organized an expert panel and conducted a literature review and a Delphi process to develop a consensus-based practice guideline for clinical use of n-3 PUFAs in MDD. The guideline focuses on 5 thematic areas: general concepts, acute treatment strategy, depression recurrence monitoring and prevention, use in special populations, and potential safety issues. The key practice guidelines contend that: (1) clinicians and other practitioners are advised to conduct a clinical interview to validate clinical diagnoses, physical conditions, and measurement-based psychopathological assessments in the therapeutic settings when recommending n-3 PUFAs in depression treatment; (2) with respect to formulation and dosage, both pure eicosapentaenoic acid (EPA) or an EPA/docosahexaenoic acid (DHA) combination of a ratio higher than 2 (EPA/DHA >2) are considered effective, and the recommended dosages should be 1-2 g of net EPA daily, from either pure EPA or an EPA/DHA (>2:1) formula; (3) the quality of n-3 PUFAs may affect therapeutic activity; and (4) potential adverse effects, such as gastrointestinal and dermatological conditions, should be monitored, as well as obtaining comprehensive metabolic panels. The expert consensus panel has agreed on using n-3 PUFAs in MDD treatment for pregnant women, children, and the elderly, and prevention in high-risk populations. Personalizing the clinical application of n-3 PUFAs in subgroups of MDD with a low Omega-3 Index or high levels of inflammatory markers might be regarded as areas that deserve future research.
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Meta-analysis and meta-regression of omega-3 polyunsaturated fatty acid supplementation for major depressive disorder.
Mocking, RJ, Harmsen, I, Assies, J, Koeter, MW, Ruhé, HG, Schene, AH
Translational psychiatry. 2016;(3):e756
Abstract
Omega-3 polyunsaturated fatty acid (PUFA) supplementation has been proposed as (adjuvant) treatment for major depressive disorder (MDD). In the present meta-analysis, we pooled randomized placebo-controlled trials assessing the effects of omega-3 PUFA supplementation on depressive symptoms in MDD. Moreover, we performed meta-regression to test whether supplementation effects depended on eicosapentaenoic acid (EPA) or docosahexaenoic acid dose, their ratio, study duration, participants' age, percentage antidepressant users, baseline MDD symptom severity, publication year and study quality. To limit heterogeneity, we only included studies in adult patients with MDD assessed using standardized clinical interviews, and excluded studies that specifically studied perinatal/perimenopausal or comorbid MDD. Our PubMED/EMBASE search resulted in 1955 articles, from which we included 13 studies providing 1233 participants. After taking potential publication bias into account, meta-analysis showed an overall beneficial effect of omega-3 PUFAs on depressive symptoms in MDD (standardized mean difference=0.398 (0.114-0.682), P=0.006, random-effects model). As an explanation for significant heterogeneity (I(2)=73.36, P<0.001), meta-regression showed that higher EPA dose (β=0.00037 (0.00009-0.00065), P=0.009), higher percentage antidepressant users (β=0.0058 (0.00017-0.01144), P=0.044) and earlier publication year (β=-0.0735 (-0.143 to 0.004), P=0.04) were significantly associated with better outcome for PUFA supplementation. Additional sensitivity analyses were performed. In conclusion, present meta-analysis suggested a beneficial overall effect of omega-3 PUFA supplementation in MDD patients, especially for higher doses of EPA and in participants taking antidepressants. Future precision medicine trials should establish whether possible interactions between EPA and antidepressants could provide targets to improve antidepressant response and its prediction. Furthermore, potential long-term biochemical side effects of high-dosed add-on EPA supplementation should be carefully monitored.
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Docosahexaenoic acid and adult memory: a systematic review and meta-analysis.
Yurko-Mauro, K, Alexander, DD, Van Elswyk, ME
PloS one. 2015;(3):e0120391
Abstract
INTRODUCTION Subjective memory complaints are common with aging. Docosahexaenoic acid (DHA; 22:6 n-3) is a long-chain polyunsaturated fatty acid (LCPUFA) and an integral part of neural membrane phospholipids that impacts brain structure and function. Past research demonstrates a positive association between DHA plasma status/dietary intake and cognitive function. OBJECTIVES The current meta-analysis was designed to determine the effect of DHA intake, alone or combined with eicosapentaenoic acid (EPA; 20:5 n-3), on specific memory domains: episodic, working, and semantic in healthy adults aged 18 years and older. A secondary objective was to systematically review/summarize the related observational epidemiologic literature. METHODS A systematic literature search of clinical trials and observational studies that examined the relationship between n-3 LCPUFA on memory outcomes in healthy adults was conducted in Ovid MEDLINE and EMBASE databases. Studies of subjects free of neurologic disease at baseline, with or without mild memory complaints (MMC), were included. Random effects meta-analyses were conducted to generate weighted group mean differences, standardized weighted group mean differences (Hedge's g), z-scores, and p-values for heterogeneity comparing DHA/EPA to a placebo. A priori sub-group analyses were conducted to evaluate the effect of age at enrollment, dose level, and memory type tested. RESULTS Episodic memory outcomes of adults with MMC were significantly (P<.004) improved with DHA/EPA supplementation. Regardless of cognitive status at baseline, > 1 g/day DHA/EPA improved episodic memory (P<.04). Semantic and working memory changes from baseline were significant with DHA but no between group differences were detected. Observational studies support a beneficial association between intake/blood levels of DHA/EPA and memory function in older adults. CONCLUSION DHA, alone or combined with EPA, contributes to improved memory function in older adults with mild memory complaints.
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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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Gender differences in the long-chain polyunsaturated fatty acid status: systematic review of 51 publications.
Lohner, S, Fekete, K, Marosvölgyi, T, Decsi, T
Annals of nutrition & metabolism. 2013;(2):98-112
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Abstract
BACKGROUND/AIMS: Sex hormones may influence the activity of enzymes which are involved in the synthesis of long-chain polyunsaturated fatty acids. The objective of this review was to assess the role of gender in determining the fatty acid composition of human samples, like plasma and erythrocyte membrane lipids, and adipose tissue. METHODS The method included a structured search strategy on MEDLINE, Scopus and the Cochrane databases, with formal inclusion/exclusion criteria, data extraction procedure and meta-analysis. RESULTS We evaluated 51 publications, dated from 1975 to 2011. Meta-analysis showed significantly lower values of both arachidonic acid (AA) and docosahexaenoic acid (DHA) in total plasma lipids (32 and 33 studies) and in plasma phospholipids (PL; 21 and 23 studies) in men than in women. Primary analysis of the phospholipid fraction showed the mean difference in AA to be 0.42% weight/weight (95% CI: 0.18-0.65, n = 7,769) and in DHA 0.37% weight/weight (95% CI: 0.24-0.51, n = 8,541), while there was no gender difference in the values of linoleic acid and α-linolenic acid. CONCLUSIONS This systematic review based on 51 publications showed significantly lower contribution of AA and DHA to plasma total lipids and plasma PL in men than in women. Gender distribution should be regarded as a significant potential confounding factor in every study assessing data on fatty acid composition.