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Prostaglandins, Leukotrienes, and... May 2023The omega-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic- (EPA), docosahexaenoic- (DHA) and docosapentaenoic acid (DPAn-3) are promising therapeutic options in... (Meta-Analysis)
Meta-Analysis Review
Effects of long-chain omega-3 polyunsaturated fatty acids on reducing anxiety and/or depression in adults; A systematic review and meta-analysis of randomised controlled trials.
The omega-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic- (EPA), docosahexaenoic- (DHA) and docosapentaenoic acid (DPAn-3) are promising therapeutic options in reducing the severity of anxious and depressive symptoms. However, meta-analyses of randomised controlled trials (RCTs) yield mixed findings. This systematic review and meta-analysis reviewed the evidence and assessed the efficacy of EPA, DHA and DPAn-3 in reducing the severity of anxiety and depression with specific consideration to methodological complications unique to the field e.g., dose and ratio of omega-3 PUFAs and placebo composition. Random-effects meta-analysis of ten RCTs comprising 1426 participants revealed statistically significant reduction in depression severity with EPA-enriched interventions at proportions ≥ 60% of total EPA + DHA (SMD: -0.36; 95% CI: -0.68, -0.05; p = 0.02) (I = 86%) and EPA doses between ≥ 1 g/day and < 2 g/day (SMD: -0.43; 95% CI: -0.79, -0.07; p = 0.02) (I = 88%); however, EPA doses ≥ 2 g/day were not associated with significant therapeutic effects (SMD: -0.20; 95% CI: -0.48, 0.07; p = 0.14). Only one study reported significant reduction in anxiety severity with 2.1 g/day EPA (85.6% of total EPA + DHA), therefore meta-analysis was not possible. No trials administering DPAn-3 were identified. Visual examination of the funnel plot revealed asymmetry, suggesting publication bias and heterogeneity amongst the trials. These results support the therapeutic potential of EPA in depression at proportions ≥ 60% of total EPA + DHA and doses ≥ 1 g/day and < 2 g/day. The observed publication bias and heterogeneity amongst the trials reflect the need for more high-quality trials in this area with consideration to the unique nature of omega-3 PUFAs research, to more fully elucidate the therapeutic potential of EPA, DHA and DPAn-3.
Topics: Adult; Humans; Eicosapentaenoic Acid; Docosahexaenoic Acids; Depression; Treatment Outcome; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Anxiety; Randomized Controlled Trials as Topic
PubMed: 37028202
DOI: 10.1016/j.plefa.2023.102572 -
Asia Pacific Journal of Clinical... 2019Docosahexaenoic acid (DHA) is a 22-carbon omega 3 PUFA highly enriched in the neuronal cell membranes and rod outer segment membranes. When DHA is depleted from these... (Review)
Review
Docosahexaenoic acid (DHA) is a 22-carbon omega 3 PUFA highly enriched in the neuronal cell membranes and rod outer segment membranes. When DHA is depleted from these cell membranes it is replaced nearly quantitatively by a 22-carbon omega 6 PUFA, docosapentaenoic acid, which has similar, but less potent, biophysical and physiological properties to DHA. It is speculated that omega 6-docosapentaenoic acid is a buffer to prevent the possible catastrophic effects of DHA depletion on brain and visual function. The primary insult from the loss of DHA from cell membrane glycerophospholipids, and replacement by omega 6-docosapentaenoic acid, is on the flexibility/compression of the membrane lipids which affects the optimal function of integral membrane proteins (receptors, voltage-gated ion channels and enzymes). This leads to effects on second messenger systems, and subsequently affects neurotransmitter concentrations due to 'weakened' signals from the initiating receptors. Remembering there are more than 80 billion neurones and many times more synaptic connections between neurons, a very small loss of "efficiency" in signal due to altered properties of membrane proteins would likely result in meaningful changes in brain and visual function. Additionally, impairment of neurotransmission could be due, in part, to sub-optimal brain energy metabolism (glucose entry into the brain), which is significantly reduced in omega 3 deficiency. Many studies report that dietary omega 3 deficiency results in changes in learning, coping with stress, behavioural changes, and responses in visual function. It is thus concluded that DHA is an essential fatty acid for optimal neuronal function.
Topics: Animals; Brain; Cell Membrane; Docosahexaenoic Acids; Humans; Neurons; Retinal Rod Photoreceptor Cells
PubMed: 31826363
DOI: 10.6133/apjcn.201912_28(4).0002 -
Biochemical Pharmacology Dec 2022Several lipoxygenase enzymes and cyclooxygenase-2 stereoselectively convert the polyunsaturated fatty acids arachidonic acid, eicosapentaenoic acid, docosahexaenoic... (Review)
Review
Several lipoxygenase enzymes and cyclooxygenase-2 stereoselectively convert the polyunsaturated fatty acids arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid, and n-3 docosapentaenoic acid into numerous oxygenated products. Biosynthetic pathway studies have shown, during the resolution phase of acute inflammation, that distinct families of endogenous products are formed. These products were named specialized pro-resolving mediators, given their specialized functions in the inflammation-resolution circuit, enhancing the return of inflamed and injured tissue to homeostasis. The lipoxins, resolvins, protectins and maresins, together with the sulfido-conjugates of the resolvins, protectins and maresins, constitute the four individual families of these local mediators. When administrated in vivo in a wide range of human disease models, the specialized pro-resolving mediators display potent bioactions. The detailed and individual biosynthetic steps constituting the biochemical pathways, the metabolism, recent reports on structure-function studies and pharmacodynamic data of the protectins, are presented herein. Emphasis is on the structure-function results on the recent members of the sulfido conjugated protectins and further metabolism of protectin D1. Moreover, the members of the individual families of specialized pro-resolving mediators and their biosynthetic precursor are presented. Today 43 specialized pro-resolving mediators possessing pro-resolution and anti-inflammatory bioactions are reported and confirmed, constituting a basis for resolution pharmacology. This emerging biomedical field provides a new approach for drug discovery, that is also discussed.
Topics: Humans; CD59 Antigens; Docosahexaenoic Acids; Inflammation; Eicosapentaenoic Acid; Inflammation Mediators; Anti-Inflammatory Agents
PubMed: 36341938
DOI: 10.1016/j.bcp.2022.115330 -
Nutrients Dec 2022Docosahexaenoic acid (DHA) is a major constituent of neural and visual membranes and is required for optimal neural and visual function. DHA is derived from food or by... (Review)
Review
Docosahexaenoic acid (DHA) is a major constituent of neural and visual membranes and is required for optimal neural and visual function. DHA is derived from food or by endogenous synthesis from α-linolenic acid (ALA), an essential fatty acid. Low blood levels of DHA in some westernised populations have led to speculations that child development disorders and various neurological conditions are associated with sub-optimal neural DHA levels, a proposition which has been supported by the supplement industry. This review searched for evidence of deficiency of DHA in human populations, based on elevated levels of the biochemical marker of -3 deficiency, docosapentaenoic acid (22:5-6). Three scenarios/situations were identified for the insufficient supply of DHA, namely in the brain of new-born infants fed with high-linoleic acid (LA), low-ALA formulas, in cord blood of women at birth who were vegetarians and in the milk of women from North Sudan. Twenty post-mortem brain studies from the developed world from adults with various neurological disorders revealed no evidence of raised levels of 22:5-6, even in the samples with reduced DHA levels compared with control subjects. Human populations most likely at risk of -3 deficiency are new-born and weanling infants, children and adolescents in areas of dryland agriculture, in famines, or are refugees, however, these populations have rarely been studied. This is an important topic for future research.
Topics: Infant, Newborn; Infant; Pregnancy; Adult; Child; Humans; Female; Adolescent; Animals; Docosahexaenoic Acids; Fatty Acids, Essential; Brain; Milk; Parturition; alpha-Linolenic Acid
PubMed: 36615819
DOI: 10.3390/nu15010161 -
Nutrients Oct 2022-3 polyunsaturated fatty acids (-3PUFA) are regarded as viable alternatives to aid the treatment of ulcerative colitis (UC). Most research focuses on eicosapentaenoic...
-3 polyunsaturated fatty acids (-3PUFA) are regarded as viable alternatives to aid the treatment of ulcerative colitis (UC). Most research focuses on eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA); little information is available about the effect of docosapentaenoic acid (DPA) on the gut microbiota and their metabolism in UC mice. In this study, the changes in gut microbiota and their metabolism in UC mice were studied through the 16S rRNA sequencing method and untargeted metabolomics. Moreover, the differential bacterial genus and differential metabolites in responding to DPA supplementation were screened through permutation test after orthogonal partial least squares discriminant analysis (OPLS-DA). The results indicated that DPA supplementation increased the diversity and altered the composition of the gut microbiota in UC mice; , , , and were selected as the differential bacterial genus. Supplementation of DPA also altered the fecal metabolite profile in the UC mice. Moreover, butyrate, -carbamylglutamate (NCG), and histamine were screened as the differential metabolites. In conclusion, the regulation effect of DPA on the gut microbiota and their metabolism might be involved in the intervention mechanism of DPA in UC. More research needs to be carried out to elucidate the mechanism systematically.
Topics: Animals; Bacteria; Butyrates; Colitis, Ulcerative; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids, Unsaturated; Gastrointestinal Microbiome; Histamine; Mice; RNA, Ribosomal, 16S
PubMed: 36235856
DOI: 10.3390/nu14194204 -
Nutrients Oct 2018Cardiovascular disease (CVD) is a major cause of mortality. The effects of several unsaturated fatty acids on cardiometabolic health, such as eicosapentaenoic acid (EPA)... (Review)
Review
Cardiovascular disease (CVD) is a major cause of mortality. The effects of several unsaturated fatty acids on cardiometabolic health, such as eicosapentaenoic acid (EPA) docosahexaenoic acid (DHA), α linolenic acid (ALA), linoleic acid (LA), and oleic acid (OA) have received much attention in past years. In addition, results from recent studies revealed that several other uncommon fatty acids (fatty acids present at a low content or else not contained in usual foods), such as furan fatty acids, -3 docosapentaenoic acid (DPA), and conjugated fatty acids, also have favorable effects on cardiometabolic health. In the present report, we searched the literature in PubMed, Embase, and the Cochrane Library to review the research progress on anti-CVD effect of these uncommon fatty acids. DPA has a favorable effect on cardiometabolic health in a different way to other long-chain -3 polyunsaturated fatty acids (LC -3 PUFAs), such as EPA and DHA. Furan fatty acids and conjugated linolenic acid (CLNA) may be potential bioactive fatty acids beneficial for cardiometabolic health, but evidence from intervention studies in humans is still limited, and well-designed clinical trials are required. The favorable effects of conjugated linoleic acid (CLA) on cardiometabolic health observed in animal or in vitro cannot be replicated in humans. However, most intervention studies in humans concerning CLA have only evaluated its effect on cardiometabolic risk factors but not its direct effect on risk of CVD, and randomized controlled trials (RCTs) will be required to clarify this point. However, several difficulties and limitations exist for conducting RCTs to evaluate the effect of these fatty acids on cardiometabolic health, especially the high costs for purifying the fatty acids from natural sources. This review provides a basis for better nutritional prevention and therapy of CVD.
Topics: Cardiovascular Diseases; Diet; Fatty Acids; Humans
PubMed: 30347833
DOI: 10.3390/nu10101559 -
Nutrients Dec 2020Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are n-3 polyunsaturated fatty acids (PUFAs) consumed in low abundance in the Western diet. Increased... (Review)
Review
Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are n-3 polyunsaturated fatty acids (PUFAs) consumed in low abundance in the Western diet. Increased consumption of n-3 PUFAs may have beneficial effects for a wide range of physiological outcomes including chronic inflammation. However, considerable mechanistic gaps in knowledge exist about EPA versus DHA, which are often studied as a mixture. We suggest the novel hypothesis that EPA and DHA may compete against each other through overlapping mechanisms. First, EPA and DHA may compete for residency in membrane phospholipids and thereby differentially displace n-6 PUFAs, which are highly prevalent in the Western diet. This would influence biosynthesis of downstream metabolites of inflammation initiation and resolution. Second, EPA and DHA exert different effects on plasma membrane biophysical structure, creating an additional layer of competition between the fatty acids in controlling signaling. Third, DHA regulates membrane EPA levels by lowering its rate of conversion to EPA's elongation product n-3 docosapentaenoic acid. Collectively, we propose the critical need to investigate molecular competition between EPA and DHA in health and disease, which would ultimately impact dietary recommendations and precision nutrition trials.
Topics: Animals; Arachidonic Acid; Diet; Diet, Western; Dietary Supplements; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Humans; Inflammation; Phospholipids
PubMed: 33276463
DOI: 10.3390/nu12123718 -
F1000Research 2013Fish oil contains a complex mixture of omega-3 fatty acids, of which eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) are the... (Review)
Review
Fish oil contains a complex mixture of omega-3 fatty acids, of which eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) are the three predominant forms. There has been a plethora of previous research on the effects and associations of fish oil supplementation with various clinical manifestations. While the majority of this work was focused on EPA and DHA as the active compounds, emerging research has begun to elucidate the specific role that DPA plays in these physiological processes and its differences with the other omega-3 fatty acids. The purpose of this review is to focus on the new studies undertaken with DPA. This review summarizes the biochemical mechanisms involved in the biosynthesis and metabolism of DPA before focusing on its effects in cardiovascular disease, immune function, and psychiatric and cognitive health. The limited studies point toward a positive role that DPA supplementation can play in these processes and that is separate and distinct from traditional supplementation with DHA and EPA.
PubMed: 25232466
DOI: 10.12688/f1000research.2-256.v2 -
Journal of Nutritional Science and... 2015Metabolic syndrome is a cluster of metabolic disorders that contribute to increased cardiovascular morbidity and mortality. Although the pathogenesis of metabolic... (Review)
Review
Metabolic syndrome is a cluster of metabolic disorders that contribute to increased cardiovascular morbidity and mortality. Although the pathogenesis of metabolic syndrome is complicated, dietary lipids have been recognized as contributory factors in the development and the prevention of cardiovascular risk clustering. We investigated the physiological functions and molecular actions of functional lipids, especially omega3-polyunsaturated fatty acid (PUFA)-containing lipids, in the development of metabolic syndrome using obese model animals. Feeding of omega3-PUFA-containing lipids, such as eicosapentaenoic acid, docosapentaenoic acid, docosahexaenoic acid, tetracosahexaenoic acid, and omega3-phosphatidylcholine, alleviated hepatic lipid accumulation through the suppression of lipogenic gene expression in the liver. Additionally, dietary omega3-PUFA-containing lipids increased serum adiponectin levels in obese animal models. Their molecular actions in the prevention and alleviation of metabolic syndrome could be attributed to the regulation of the activity or abundance of several transcriptional factors in the liver and adipose tissue. Dietary functional lipids would be useful to prevent or alleviate metabolic syndrome in obese animals. In particular, the function of omega3-containing lipids as dietary adiponectin inducers deserves attention with respect to alleviation of metabolic syndrome by dietary manipulation.
Topics: Adiponectin; Adipose Tissue; Animals; Diet; Fatty Acids, Omega-3; Functional Food; Humans; Liver; Metabolic Syndrome; Obesity; Transcription Factors
PubMed: 26598838
DOI: 10.3177/jnsv.61.S159 -
Cancer Medicine Apr 2019Observational studies have shown that excessive dietary fat may be associated with lung carcinogenesis. However, findings from previous studies are inconsistent and it...
BACKGROUND
Observational studies have shown that excessive dietary fat may be associated with lung carcinogenesis. However, findings from previous studies are inconsistent and it remains unclear whether docosapentaenoic acid (DPA), a kind of polyunsaturated fatty acid, is linked to the risk of lung cancer. The aim of this study is to investigate the causal effect of DPA on lung cancer with Mendelian randomization (MR) method.
METHODS
With a two-sample MR approach, we analyzed the summary data from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE, 8866 individuals of European ancestry) Consortium and International Lung Cancer Consortium (ILCCO, 11 348 lung cancer cases and 15 861 controls; European ancestry) to assess the possible causal relationship of DPA on the risk of lung cancer.
RESULTS
Our results indicated that genetically predicted higher DPA level has a positive association with lung cancer, where 1% higher DPA was associated with a 2.01-fold risk of lung cancer (odds ratio [OR]: 2.01, 95% CI = 1.34-3.01; P = 7.40 × 10 ). Additionally, lung cancer was not a causal factor for DPA. The results of MR-Egger regression analysis showed that there was no evidence for the presence of directional horizontal pleiotropy.
CONCLUSIONS
Genetically elevated DPA is positively associated with risk of lung cancer, and more work is needed to investigate the potential mechanisms.
Topics: Adenocarcinoma of Lung; Carcinoma, Squamous Cell; Case-Control Studies; Fatty Acids, Unsaturated; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Lung Neoplasms; Mendelian Randomization Analysis; Polymorphism, Single Nucleotide; Risk Assessment
PubMed: 30741477
DOI: 10.1002/cam4.2018