Showing papers on "Docosahexaenoic acid published in 2021"
TL;DR: In this article, an association between moderate intake of the omega-6 PUFA linoleic acid and lower risk of cardiovascular diseases (CVDs), most likely as a result of lower blood cholesterol concentration.
Abstract: Oxidative stress and inflammation have been recognized as important contributors to the risk of chronic non-communicable diseases. Polyunsaturated fatty acids (PUFAs) may regulate the antioxidant signaling pathway and modulate inflammatory processes. They also influence hepatic lipid metabolism and physiological responses of other organs, including the heart. Longitudinal prospective cohort studies demonstrate that there is an association between moderate intake of the omega-6 PUFA linoleic acid and lower risk of cardiovascular diseases (CVDs), most likely as a result of lower blood cholesterol concentration. Current evidence suggests that increasing intake of arachidonic acid (up to 1500 mg/day) has no adverse effect on platelet aggregation and blood clotting, immune function and markers of inflammation, but may benefit muscle and cognitive performance. Many studies show that higher intakes of omega-3 PUFAs, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are associated with a lower incidence of chronic diseases characterized by elevated inflammation, including CVDs. This is because of the multiple molecular and cellular actions of EPA and DHA. Intervention trials using EPA + DHA indicate benefit on CVD mortality and a significant inverse linear dose–response relationship has been found between EPA + DHA intake and CVD outcomes. In addition to their antioxidant and anti-inflammatory roles, omega-3 fatty acids are considered to regulate platelet homeostasis and lower risk of thrombosis, which together indicate their potential use in COVID-19 therapy.
190 citations
TL;DR: The hypothesis was that daily addition of 1.8g n-3 PUFA to standard of care secondary prophylaxis in elderly patients who have survived an AMI would reduce the risk of subsequent cardiovascular events during 2 years follow-up.
Abstract: Background: High intake of marine n-3 polyunsaturated fatty acids (PUFA) has been associated with reduced risk of cardiovascular events; however, this has not been confirmed in patients with a rece...
147 citations
TL;DR: In this article, the authors examined whether excess uptake of specific fatty acid (FA) could lead to antitumor effects and found that n-3 but also remarkably n-6 polyunsaturated FA selectively induced ferroptosis in cancer cells under ambient acidosis.
126 citations
University of South Dakota1, Dordt College2, University of Cambridge3, Harvard University4, Brigham and Women's Hospital5, Johns Hopkins University6, The George Institute for Global Health7, Cancer Council Victoria8, Taipei Veterans General Hospital9, Kyushu University10, Wageningen University and Research Centre11, Karolinska Institutet12, University of Eastern Finland13, University of British Columbia14, University of Bordeaux15, Baylor College of Medicine16, Tufts University17, Public Health Research Institute18, National Taiwan University19, University of Melbourne20, RMIT University21, Ohio State University22, Imperial College London23, Laval University24, University of Ottawa25, University of Washington26, Uppsala University27, University of Iowa28, University of California, San Diego29, University of Tennessee Health Science Center30, University of Minnesota31, New York Academy of Medicine32
TL;DR: In this paper, the results of a de novo pooled analysis conducted with data from 17 prospective cohort studies examined the associations between blood omega-3 fatty acid levels and risk for all-cause mortality.
Abstract: The health effects of omega-3 fatty acids have been controversial. Here we report the results of a de novo pooled analysis conducted with data from 17 prospective cohort studies examining the associations between blood omega-3 fatty acid levels and risk for all-cause mortality. Over a median of 16 years of follow-up, 15,720 deaths occurred among 42,466 individuals. We found that, after multivariable adjustment for relevant risk factors, risk for death from all causes was significantly lower (by 15–18%, at least p < 0.003) in the highest vs the lowest quintile for circulating long chain (20–22 carbon) omega-3 fatty acids (eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids). Similar relationships were seen for death from cardiovascular disease, cancer and other causes. No associations were seen with the 18-carbon omega-3, alpha-linolenic acid. These findings suggest that higher circulating levels of marine n-3 PUFA are associated with a lower risk of premature death. Associations between of omega-3 fatty acids and mortality are not clear. Here the authors report that, based on a pooled analysis of 17 prospective cohort studies, higher blood omega-3 fatty acid levels correlate with lower risk of all-cause mortality.
96 citations
TL;DR: In this paper, the effects of omega-3 PUFAs on intestinal immunity and inflammation were described, and several pathways by which the microbiota modulates the gut immune system through Omega-3PUFAs were identified.
Abstract: Omega-3 polyunsaturated fatty acids (omega-3 PUFAs), which are essential fatty acids that humans should obtain from diet, have potential benefits for human health. In addition to altering the structure and function of cell membranes, omega-3 PUFAs (docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), alpha-linolenic acid (ALA), and docosapentaenoic acid (DPA)) exert different effects on intestinal immune tolerance and gut microbiota maintenance. Firstly, we review the effect of omega-3 PUFAs on gut microbiota. And the effects of omega-3 PUFAs on intestinal immunity and inflammation were described. Furthermore, the important roles of omega-3 PUFAs in maintaining the balance between gut immunity and the gut microbiota were discussed. Additional factors, such as obesity and diseases (NAFLD, gastrointestinal malignancies or cancer, bacterial and viral infections), which are associated with variability in omega-3 PUFA metabolism, can influence omega-3 PUFAs-microbiome-immune system interactions in the intestinal tract and also play roles in regulating gut immunity. This review identifies several pathways by which the microbiota modulates the gut immune system through omega-3 PUFAs. Omega-3 supplementation can be targeted to specific pathways to prevent and alleviate intestinal diseases, which may help researchers identify innovative diagnostic methods.
93 citations
TL;DR: Omega-3 and Omega-6 PUFAs are competitively metabolized by the same set of desaturation, elongation, and oxygenase enzymes in the human body as mentioned in this paper.
Abstract: Polyunsaturated fatty acids (PUFAs) contain ≥2 double-bond desaturations within the acyl chain. Omega-3 (n-3) and Omega-6 (n-6) PUFAs are the two known important families in human health and nutrition. In both Omega families, many forms of PUFAs exist: α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) from the n-3 family and linoleic acid (LA), dihomo-γ-linolenic acid (DGLA), and arachidonic acid (AA) from the n-6 family are the important PUFAs for human health. Omega-3 and Omega-6 PUFAs are competitively metabolized by the same set of desaturation, elongation, and oxygenase enzymes. The lipid mediators produced from their oxidative metabolism perform opposing (antagonistic) functions in the human body. Except for DGLA, n-6 PUFA-derived lipid mediators enhance inflammation, platelet aggregation, and vasoconstriction, while those of n-3 inhibit inflammation and platelet aggregation and enhance vasodilation. Overconsumption of n-6 PUFAs with low intake of n-3 PUFAs is highly associated with the pathogenesis of many modern diet-related chronic diseases. The volume of n-6 PUFAs is largely exceeding the volume of n-3PUFAs. The current n-6/n-3 ratio is 20-50/1. Due to higher ratios of n-6/n-3 in modern diets, larger quantities of LA- and AA-derived lipid mediators are produced, becoming the main causes of the formation of thrombus and atheroma, the allergic and inflammatory disorders, and the proliferation of cells, as well as the hyperactive endocannabinoid system. Therefore, in order to reduce all of these risks which are due to overconsumption of n-6 PUFAs, individuals are required to take both PUFAs in the highly recommended n-6/n-3 ratio which is 4-5/1.
79 citations
TL;DR: In this paper, the long-chain polyunsaturated fatty acids (LCPUFAs) arachidonic acid (AA) and docosahexaenoic acid (DHA) are considered to be important components of breast milk.
Abstract: The immune system is complex: it involves many cell types and numerous chemical mediators. An immature immune response increases susceptibility to infection, whilst imbalances amongst immune components leading to loss of tolerance can result in immune-mediated diseases including food allergies. Babies are born with an immature immune response. The immune system develops in early life and breast feeding promotes immune maturation and protects against infections and may protect against allergies. The long-chain polyunsaturated fatty acids (LCPUFAs) arachidonic acid (AA) and docosahexaenoic acid (DHA) are considered to be important components of breast milk. AA, eicosapentaenoic acid (EPA) and DHA are also present in the membranes of cells of the immune system and act through multiple interacting mechanisms to influence immune function. The effects of AA and of mediators derived from AA are often different from the effects of the n-3 LCPUFAs (i.e., EPA and DHA) and of mediators derived from them. Studies of supplemental n-3 LCPUFAs in pregnant women show some effects on cord blood immune cells and their responses. These studies also demonstrate reduced sensitisation of infants to egg, reduced risk and severity of atopic dermatitis in the first year of life, and reduced persistent wheeze and asthma at ages 3 to 5 years, especially in children of mothers with low habitual intake of n-3 LCPUFAs. Immune markers in preterm and term infants fed formula with AA and DHA were similar to those in infants fed human milk, whereas those in infants fed formula without LCPUFAs were not. Infants who received formula plus LCPUFAs (both AA and DHA) showed a reduced risk of allergic disease and respiratory illness than infants who received standard formula. Studies in which infants received n-3 LCPUFAs report immune differences from controls that suggest better immune maturation and they show lower risk of allergic disease and respiratory illness over the first years of life. Taken together, these findings suggest that LCPUFAs play a role in immune development that is of clinical significance, particularly with regard to allergic sensitisation and allergic manifestations including wheeze and asthma.
54 citations
TL;DR: An overview of the pathogenesis of cardiovascular complications secondary to COVID-19 is provided and the mechanisms that may contribute to the likely benefits of n-3 PUFAs and their metabolites are focused on.
52 citations
TL;DR: In this paper, a review on the identified Fads and Elovl, as well as the regulatory mechanisms of LC-PUFA biosynthesis both at transcriptional and post-transcriptional levels in teleosts is presented.
50 citations
TL;DR: EPA and DHA had distinct effects on monocyte inflammatory response with a broader effect of DHA in attenuating pro-inflammatory cytokines, suggesting immunomodulatory activities of SPM and their intermediates.
49 citations
TL;DR: Botanical stearidonic acid (SDA, 18:4n-3) rich oils are emerging as a sustainable omega-3 source with efficient conversion rate to n-3 LC-PUFA especially to EPA, as it bypasses the Δ6-desaturase rate limiting step.
Abstract: Dietary omega-3 long chain polyunsaturated fatty acids (n-3 LC-PUFA) like eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) are known to be potent biological regulators with therapeutic and preventive effects on human health. Many global health organizations have recommended consuming marine based omega-3 sources for neonatal brain development and reducing the risk of various chronic diseases. However, due to concerns regarding the origin, sustainable supply and safety of the marine sources, alternative n-3 PUFA sources are being explored. Recently, plant-based omega-3 sources are gaining much importance because of their sustainable supply and dietary acceptance. α-linolenic acid (ALA, 18:3n-3) rich seed oils are the major omega-3 fatty acid source available for human consumption. But, efficiency of conversion of ALA to n-3 LC-PUFAs in humans is limited due to a rate-limiting step in the n-3 pathway catalyzed by Δ6-desaturase. Botanical stearidonic acid (SDA, 18:4n-3) rich oils are emerging as a sustainable omega-3 source with efficient conversion rate to n-3 LC-PUFA especially to EPA, as it bypasses the Δ6-desaturase rate limiting step. Several recent studies have identified the major plant sources of SDA and explored its potential health benefits and preventive roles in inflammation, cardiovascular disease (CVD) and cancer. This systematic review summarizes the current state of knowledge on the sources, nutraceutical roles, food-based applications and the future perspectives of botanical SDA.
TL;DR: In this paper, Eicosapentaenoic acid (EPA) and docosahexaenoic acids (DHA) have been suggested to prevent the development of metabolic disorders.
Abstract: Background Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been suggested to prevent the development of metabolic disorders. However, their individual role in treating hyperglycemia and the mechanism of action regarding gut microbiome and metabolome in the context of diabetes remain unclear. Results Supplementation of DHA and EPA attenuated hyperglycemia and insulin resistance without changing body weight in db/db mice while the ameliorative effect appeared to be more pronounced for EPA. DHA/EPA supplementation reduced the abundance of the lipopolysaccharide-containing Enterobacteriaceae whereas elevated the family Coriobacteriaceae negatively correlated with glutamate level, genera Barnesiella and Clostridium XlVa associated with bile acids production, beneficial Bifidobacterium and Lactobacillus, and SCFA-producing species. The gut microbiome alterations co-occurred with the shifts in the metabolome, including glutamate, bile acids, propionic/butyric acid, and lipopolysaccharide, which subsequently relieved β cell apoptosis, suppressed hepatic gluconeogenesis, and promoted GLP-1 secretion, white adipose beiging, and insulin signaling. All these changes appeared to be more evident for EPA. Furthermore, transplantation with DHA/EPA-mediated gut microbiota mimicked the ameliorative effect of DHA/EPA on glucose homeostasis in db/db mice, together with similar changes in gut metabolites. In vitro, DHA/EPA treatment directly inhibited the growth of Escherichia coli (Family Enterobacteriaceae) while promoted Coriobacterium glomerans (Family Coriobacteriaceae), demonstrating a causal effect of DHA/EPA on featured gut microbiota. Conclusions DHA and EPA dramatically attenuated hyperglycemia and insulin resistance in db/db mice, which was mediated by alterations in gut microbiome and metabolites linking gut to adipose, liver and pancreas. These findings shed light into the gut-organs axis as a promising target for restoring glucose homeostasis and also suggest a better therapeutic effect of EPA for treating diabetes. Video abstract.
TL;DR: In this article, the first evidence for the relevance of LOX and CYP450-derived EPA/DHA bioactive lipid metabolites as neuroprotective molecular targets for human hippocampal neurogenesis and depression was detected using mass spectrometry lipidomics of the supernatant.
Abstract: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can exert antidepressant, anti-inflammatory and neuroprotective properties, but the exact molecular mechanism underlying their effects is still not fully understood. We conducted both in vitro and clinical investigations to test which EPA or DHA metabolites are involved in these anti-inflammatory, neuroprotective and antidepressant effects. In vitro, we used the human hippocampal progenitor cell line HPC0A07/03C, and pre-treated cells with either EPA or DHA, followed by interleukin 1beta (IL1β), IL6 and interferon-alpha (IFN-α). Both EPA and DHA prevented the reduction in neurogenesis and the increase in apoptosis induced by these cytokines; moreover, these effects were mediated by the lipoxygenase (LOX) and cytochrome P450 (CYP450) EPA/DHA metabolites, 5-hydroxyeicosapentaenoic acid (HEPE), 4-hydroxydocosahexaenoic acid (HDHA), 18-HEPE, 20-HDHA, 17(18)-epoxyeicosatetraenoic acid (EpETE) and 19(20)-epoxydocosapentaenoic acid (EpDPA), detected here for the first time in human hippocampal neurones using mass spectrometry lipidomics of the supernatant. In fact, like EPA/DHA, co-treatment with these metabolites prevented cytokines-induced reduction in neurogenesis and apoptosis. Moreover, co-treatment with 17(18)-EpETE and 19(20)-EpDPA and the soluble epoxide hydroxylase (sEH) inhibitor, TPPU (which prevents their conversion into dihydroxyeicosatetraenoic acid (DiHETE)/ dihydroxydocosapentaenoic acid (DiHDPA) metabolites) further enhanced their neurogenic and anti-apoptotic effects. Interestingly, these findings were replicated in a sample of n = 22 patients with a DSM-IV Major Depressive Disorder, randomly assigned to treatment with either EPA (3.0 g/day) or DHA (1.4 g/day) for 12 weeks, with exactly the same LOX and CYP450 lipid metabolites increased in the plasma of these patients following treatment with their precursor, EPA or DHA, and some evidence that higher levels of these metabolites were correlated with less severe depressive symptoms. Overall, our study provides the first evidence for the relevance of LOX- and CYP450-derived EPA/DHA bioactive lipid metabolites as neuroprotective molecular targets for human hippocampal neurogenesis and depression, and highlights the importance of sEH inhibitors as potential therapeutic strategy for patients suffering from depressive symptoms.
TL;DR: The aim of the present review is to summarize the recent biotechnological progress made regarding the production, purification, and concentration of ω-3 LC-PUFAs from marine microalgae.
Abstract: Recent advances in functional foods and nutraceuticals have emphasized the beneficial impact of bioactive molecules on human health and longevity. The omega-3 (ω-3) long-chain polyunsaturated fatty acids (LC-PUFAs), namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been shown to exert numerous positive effects on cardiovascular events, inflammatory disease, some cancers, and neurological disorders. The primary sources of ω-3 LC-PUFAs for human consumption are cold-water fish and seafood; however, these are harvested currently beyond a sustainable capacity. Therefore, new sources of ω-3 LC-PUFAs such as oleaginous microalgae are regarded as promising alternatives to fish and seafood. In this context, the aim of the present review is to summarize the recent biotechnological progress made regarding the production, purification, and concentration of ω-3 LC-PUFAs from marine microalgae.
Beth Israel Deaconess Medical Center1, Harvard University2, Brigham and Women's Hospital3, University of Cambridge4, Tufts University5, Uppsala University6, The George Institute for Global Health7, Dordt College8, University of Eastern Finland9, University of Minnesota10, Cancer Council Victoria11, Imperial College London12, Kyushu University13, National Taiwan University14, United States Department of Agriculture15, University of British Columbia16, University of Bordeaux17, Wageningen University and Research Centre18, University of South Dakota19, University of California, San Diego20, University of Iowa21, University of Melbourne22, Monash University, Clayton campus23, National Institute for Health and Welfare24, King Abdulaziz University25, New York Academy of Medicine26, University of Washington27, Tufts Medical Center28
TL;DR: In this paper, the prospective associations between n-3 fatty acid biomarkers and type 2 diabetes (T2D) risk are not consistent in individual studies through an individual participant-level pooled analysis.
Abstract: OBJECTIVE Prospective associations between n-3 fatty acid biomarkers and type 2 diabetes (T2D) risk are not consistent in individual studies. We aimed to summarize the prospective associations of biomarkers of α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with T2D risk through an individual participant-level pooled analysis. RESEARCH DESIGN AND METHODS For our analysis we incorporated data from a global consortium of 20 prospective studies from 14 countries. We included 65,147 participants who had blood measurements of ALA, EPA, DPA, or DHA and were free of diabetes at baseline. De novo harmonized analyses were performed in each cohort following a prespecified protocol, and cohort-specific associations were pooled using inverse variance–weighted meta-analysis. RESULTS A total of 16,693 incident T2D cases were identified during follow-up (median follow-up ranging from 2.5 to 21.2 years). In pooled multivariable analysis, per interquintile range (difference between the 90th and 10th percentiles for each fatty acid), EPA, DPA, DHA, and their sum were associated with lower T2D incidence, with hazard ratios (HRs) and 95% CIs of 0.92 (0.87, 0.96), 0.79 (0.73, 0.85), 0.82 (0.76, 0.89), and 0.81 (0.75, 0.88), respectively (all P CONCLUSIONS Higher circulating biomarkers of seafood-derived n-3 fatty acids, including EPA, DPA, DHA, and their sum, were associated with lower risk of T2D in a global consortium of prospective studies. The biomarker of plant-derived ALA was not significantly associated with T2D risk.
08 Feb 2021
TL;DR: In this article, it was shown that the deficiency of polyunsaturated fatty acids (PUFAs) may indicate malnutrition and deficiency of several minerals, trace elements and vitamins some of which are also much needed co-factors for the normal activity of desaturases.
Abstract: Lipids are an essential constituent of the cell membrane of which polyunsaturated fatty acids (PUFAs) are the most important component. Activation of phospholipase A2 (PLA2) induces the release of PUFAs from the cell membrane that form precursors to both pro- and ant-inflammatory bioactive lipids that participate in several cellular processes. PUFAs GLA (gamma-linolenic acid), DGLA (dihomo-GLA), AA (arachidonic acid), EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) are derived from dietary linoleic acid (LA) and alpha-linolenic acid (ALA) by the action of desaturases whose activity declines with age. Consequently, aged cells are deficient in GLA, DGLA, AA, AA, EPA and DHA and their metabolites. LA, ALA, AA, EPA and DHA can also be obtained direct from diet and their deficiency (fatty acids) may indicate malnutrition and deficiency of several minerals, trace elements and vitamins some of which are also much needed co-factors for the normal activity of desaturases. In many instances (patients) the plasma and tissue levels of GLA, DGLA, AA, EPA and DHA are low (as seen in patients with hypertension, type 2 diabetes mellitus) but they do not have deficiency of other nutrients. Hence, it is reasonable to consider that the deficiency of GLA, DGLA, AA, EPA and DHA noted in these conditions are due to the decreased activity of desaturases and elongases. PUFAs stimulate SIRT1 through protein kinase A-dependent activation of SIRT1-PGC1α complex and thus, increase rates of fatty acid oxidation and prevent lipid dysregulation associated with aging. SIRT1 activation prevents aging. Of all the SIRTs, SIRT6 is critical for intermediary metabolism and genomic stability. SIRT6-deficient mice show shortened lifespan, defects in DNA repair and have a high incidence of cancer due to oncogene activation. SIRT6 overexpression lowers LDL and triglyceride level, improves glucose tolerance, and increases lifespan of mice in addition to its anti-inflammatory effects at the transcriptional level. PUFAs and their anti-inflammatory metabolites influence the activity of SIRT6 and other SIRTs and thus, bring about their actions on metabolism, inflammation, and genome maintenance. GLA, DGLA, AA, EPA and DHA and prostaglandin E2 (PGE2), lipoxin A4 (LXA4) (pro- and anti-inflammatory metabolites of AA respectively) activate/suppress various SIRTs (SIRt1 SIRT2, SIRT3, SIRT4, SIRT5, SIRT6), PPAR-γ, PARP, p53, SREBP1, intracellular cAMP content, PKA activity and peroxisome proliferator-activated receptor γ coactivator 1-α (PGC1-α). This implies that changes in the metabolism of bioactive lipids as a result of altered activities of desaturases, COX-2 and 5-, 12-, 15-LOX (cyclo-oxygenase and lipoxygenases respectively) may have a critical role in determining cell age and development of several aging associated diseases and genomic stability and gene and oncogene activation. Thus, methods designed to maintain homeostasis of bioactive lipids (GLA, DGLA, AA, EPA, DHA, PGE2, LXA4) may arrest aging process and associated metabolic abnormalities.
TL;DR: It is suggested that arachidonic acid (AA) and similar bioactive lipids (BALs) inactivate SARS-CoV-2 and thus, may be of benefit in the prevention and treatment of COVID-19 and other enveloped viruses.
TL;DR: The role of docosahexaenoic acid (DHA) and arachidonic acid (AA) in neurogenesis and brain development throughout the life cycle is fundamental as discussed by the authors.
Abstract: The role of docosahexaenoic acid (DHA) and arachidonic acid (AA) in neurogenesis and brain development throughout the life cycle is fundamental. DHA and AA are long-chain polyunsaturated fatty acids (LCPUFA) vital for many human physiological processes, such as signaling pathways, gene expression, structure and function of membranes, among others. DHA and AA are deposited into the lipids of cell membranes that form the gray matter representing approximately 25% of the total content of brain fatty acids. Both fatty acids have effects on neuronal growth and differentiation through the modulation of the physical properties of neuronal membranes, signal transduction associated with G proteins, and gene expression. DHA and AA have a relevant role in neuroprotection against neurodegenerative pathologies such as Alzheimer's disease and Parkinson's disease, which are associated with characteristic pathological expressions as mitochondrial dysfunction, neuroinflammation, and oxidative stress. The present review analyzes the neuroprotective role of DHA and AA in the extreme stages of life, emphasizing the importance of these LCPUFA during the first year of life and in the developing/prevention of neurodegenerative diseases associated with aging.
TL;DR: For example, a lower Omega-3 Index was associated with increased risk for total mortality and ischemic stroke, reduced brain volume, impaired cognition, accelerated progression to dementia, psychiatric diseases, compromises of complex brain functions, and other brain issues in epidemiologic studies as mentioned in this paper.
Abstract: Brain structure and function depend on a constant and sufficient supply with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) by blood Blood levels of EPA and DHA reflect dietary intake and other variables and are preferably assessed as percentage in erythrocytes with a well-documented and standardized analytical method (HS-Omega-3 Index®) Every human being has an Omega-3 Index between 2 and 20%, with an optimum of 8–11% Compared to an optimal Omega-3 Index, a lower Omega-3 Index was associated with increased risk for total mortality and ischemic stroke, reduced brain volume, impaired cognition, accelerated progression to dementia, psychiatric diseases, compromises of complex brain functions, and other brain issues in epidemiologic studies Most intervention trials, and their meta-analyses considered EPA and DHA as drugs with good bioavailability, a design tending to produce meaningful results in populations characterized by low baseline blood levels (eg, in major depression), but otherwise responsible for many neutral results and substantial confusion When trial results were evaluated using blood levels of EPA and DHA measured, effects were larger than comparing EPA and DHA to placebo groups, and paralleled epidemiologic findings This indicates future trial design, and suggests a targeted use EPA and DHA, based on the Omega-3 Index
TL;DR: In this paper, a study was conducted to evaluate egg quality, egg yolk fatty acids, health-related indices and antioxidants from laying hens' eggs fed different combined vegetable byproducts, rich in fatty acids and antioxidants.
Abstract: The current study was conducted to evaluate egg quality, egg yolk fatty acids, health-related indices and antioxidants from laying hens' eggs fed different combined vegetable by-products, rich in fatty acids and antioxidants. One hundred twenty 50 weeks-old Tetra SL laying hens were divided into three groups. They were given daily a standard diet (Control, C), a diet containing 9% rapeseed meal with 3% grapeseed meal (T1 diet), or a diet containing 9% flaxseed meal and 3% sea buckthorn meal (T2 diet). Hen production performances, egg quality, egg yolk fatty acids total polyphenols content and antioxidant capacity were determined. The T1 diet significantly reduced the egg yolk content of palmitic acid from 76.615 mg (C) to 46.843 mg (T1) and that of oleic acid from 788.13 mg (C) to 682.83 mg (T1). Feeding flaxseed and sea buckthorn meals significantly increased the egg yolk content of α-linolenic acid in T2 yolks (35.297 mg) compared with C yolks (4.752 mg) and that of docosahexaenoic acid (DHA) from 16.282 mg (C) to 74.918 mg (T2). The atherogenicity indices (AI) were not significantly affected, whereas the thrombogenicity indices (TI) decreased significantly (p < 0.0007) from 0.72 (C) to 0.60 (T1) and 0.66 (T2), respectively. Adding this combination of meals to the hens' diets, increased the total polyphenol content and antioxidant capacity in T1 and T2 eggs compared to C eggs. The significant enrichment of eggs with n-3 fatty acids and antioxidant capacity, as well on the health-related indices especially from T2 eggs, represents a potential functional feed ingredient in poultry feeding, to obtain eggs as functional food.
TL;DR: In this article, the effects of n-3 polyunsaturated fatty acids (PUFA), particularly docosahexaenoic acid (DHA) and eicosapentaenoic acids (EPA), on the production of specialized pro-resolving mediators (SPMs) were evaluated.
Abstract: Fish oil supplementation is commonplace in human nutrition and is being used in both enteral and parenteral formulations during the treatment of patients with a large variety of diseases and immune status. The biological effects of fish oil are believed to result from their content of n-3 polyunsaturated fatty acids (PUFA), particularly docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). These fatty acids are known to have numerous effects upon immune functions and are described as immunomodulatory. However, immunomodulatory is a nondescript term that encompasses immunostimulation and immunosuppression. The primary goal of this review is to better describe the immune effects of n-3 PUFA as they relate to immunostimulatory vs. immunosuppressive effects. One mechanism proposed for the immune effects of n-3 PUFA relates to the production of specialized pro-resolving mediators (SPMs). A second goal of this review is to evaluate the effects of n-3 PUFA supplementation upon production of SPMs. Although n-3 PUFA are stated to possess anti-oxidative properties, these molecules are highly oxidizable due to multiple double bonds and may increase oxidative stress. Thus, the third goal of this review is to evaluate the effects of n-3 PUFA upon lipid oxidation. We conclude, based upon current scientific evidence, that n-3 PUFA suppress inflammatory responses and most cellular immune responses such as chemotaxis, transmigration, antigen presentation, and lymphocyte functions and should be considered immunosuppressive. n-3 PUFA induced production of resolution molecules is inconsistent with many resolution molecules failing to respond to n-3 PUFA supplementation. n-3 PUFA supplementation is associated with increased lipid peroxidation in most studies. Vitamin E co-administration is unreliable for prevention of the lipid peroxidation. These effects should be considered when administering n-3 PUFA to patients that may be immunosuppressed or under high oxidative stress due to illness or other treatments.
TL;DR: Animal studies show that DHA- and EPA-mediated vasodilation persists after endothelial removal, indicating a role for vascular smooth muscle cells (VSMCs), suggesting structural manipulation of ω-3 PUFA could generate novel, targeted, therapeutic leads.
Abstract: Hypertension is often characterised by impaired vasodilation involving dysfunction of multiple vasodilatory mechanisms. ω-3 polyunsaturated fatty acids (PUFAs), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) can reduce blood pressure and vasodilation. In the endothelium, DHA and EPA improve function including increased NO bioavailability. However, animal studies show that DHA- and EPA-mediated vasodilation persists after endothelial removal, indicating a role for vascular smooth muscle cells (VSMCs). The vasodilatory effects of ω-3 PUFAs on VSMCs are mediated via opening of large conductance calcium-activated potassium channels (BKCa ), ATP-sensitive potassium channels (KATP ) and possibly members of the Kv 7 family of voltage-activated potassium channels, resulting in hyperpolarisation and relaxation. ω-3 PUFA actions on BKCa and voltage-gated ion channels involve electrostatic interactions that are dependent on the polyunsaturated acyl tail, cis-geometry of these double bonds and negative charge of the carboxyl headgroup. This suggests structural manipulation of ω-3 PUFA could generate novel, targeted, therapeutic leads.
TL;DR: A review of the effect of Omega-3 polyunsaturated fatty acids (PUFAs) on epithelial cells is presented in this paper, where marine-derived ω-3 PUFAs, eicosapentaenoic acid and docosahexaenoic acids, as well as plant-derived alpha-linolenic acid, are incorporated into intestinal epithelial cell membranes.
Abstract: Epithelial cells (enterocytes) form part of the intestinal barrier, the largest human interface between the internal and external environments, and responsible for maintaining regulated intestinal absorption and immunological control. Under inflammatory conditions, the intestinal barrier and its component enterocytes become inflamed, leading to changes in barrier histology, permeability, and chemical mediator production. Omega-3 (ω-3) polyunsaturated fatty acids (PUFAs) can influence the inflammatory state of a range of cell types, including endothelial cells, monocytes, and macrophages. This review aims to assess the current literature detailing the effects of ω-3 PUFAs on epithelial cells. Marine-derived ω-3 PUFAs, eicosapentaenoic acid and docosahexaenoic acid, as well as plant-derived alpha-linolenic acid, are incorporated into intestinal epithelial cell membranes, prevent changes to epithelial permeability, inhibit the production of pro-inflammatory cytokines and eicosanoids and induce the production of anti-inflammatory eicosanoids and docosanoids. Altered inflammatory markers have been attributed to changes in activity and/or expression of proteins involved in inflammatory signalling including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), peroxisome proliferator activated receptor (PPAR) α and γ, G-protein coupled receptor (GPR) 120 and cyclooxygenase (COX)-2. Effective doses for each ω-3 PUFA are difficult to determine due to inconsistencies in dose and time of exposure between different in vitro models and between in vivo and in vitro models. Further research is needed to determine the anti-inflammatory potential of less-studied ω-3 PUFAs, including docosapentaenoic acid and stearidonic acid.
TL;DR: The roles of DHA through human lifespan, the sources, and its recommended daily intake in different countries are discussed to provide a better understanding of the importance of this review.
Abstract: Docosahexaenoic acid (DHA) is the predominant omega-3 long-chain polyunsaturated fatty acid found in human brain and eyes. There are a number of studies in the literature showing the health benefits of DHA. It is critical throughout all life stages from the need for fetal development, the prevention of preterm birth, and the prevention of cardiovascular disease to the improvements in the cognitive function and the eye health of adults and elderly. These benefits might be related to the modulation of gut microbiota by DHA. In addition, there are some discrepancies in the literature regarding certain health benefits of DHA, and this review is intended to explore and understand these discrepancies. Besides the variations in the DHA contents of different supplement sources, bioavailability is crucial for the efficacy of DHA supplements, which depends on several factors. For example, DHA in phospholipid and triglyceride forms are more readily to be absorbed by the body than that in ethyl ester form. In addition, dietary lipids in meals and emulsification of DHA oil can increase the bioavailability of DHA. Estrogens stimulated the biosynthesis of DHA, whereas testosterone stimulus induced a decrease in DHA. The roles of DHA through human lifespan, the sources, and its recommended daily intake in different countries are also discussed to provide a better understanding of the importance of this review.
TL;DR: Thraustochytrids, non-photosynthetic marine microorganisms often mislabeled as ‘algae’, represent a promising commercial source of omega-3 fatty acids due to their high content of PUFAs.
Abstract: Backgrounds Omega-3 and omega-6 fatty acids are examples of polyunsaturated fatty acids (PUFAs). The omega-3 α-linolenic acid and omega-6 linoleic acid cannot be generated by humans and, therefore, are considered essential fatty acids. Long-chain PUFAs, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), can be produced from α-linolenic acid in the human body, but at a level too low to meet daily requirements and must be supplemented through the diet. Daily intake of EPA and DHA reduces the risk of heart disease, Alzheimer's, bipolar disorder, schizophrenia, and type 2 diabetes; moreover, DHA is essential for proper visual and neurological postnatal development. Scope and approach Fish oil and seafood are widely used as sources of omega fatty acids, which represents a two-fold problem. First, it depletes fish stocks and impacts negatively on the aquatic environment through excessive aquaculture. Second, the growing popularity of veganism and vegetarianism puts these consumers at risk of omega-3 fatty acid deficiency. Hence, alternative sources of long-chain PUFAs for human consumption should be found. Plants produce only a handful of PUFAs, such as linoleic acid, α-linolenic acid, γ-linolenic acid, and octadecatetraenoic acid. Key findings and conclusions Thraustochytrids, non-photosynthetic marine microorganisms often mislabeled as ‘algae’, represent a promising commercial source of omega-3 fatty acids due to their high content of PUFAs. In this review, we describe lipid synthesis in thraustochytrids and distinguish it from that of other microorganisms, including proper microalgae. Furthermore, we detail the advances in omega-3 fatty acids production from thraustochytrids at laboratory and industrial scale.
TL;DR: The H3-L6 and H3 interventions altered bioactive mediators implicated in headache pathogenesis and decreased frequency and severity of headaches, but did not significantly improve quality of life.
Abstract: Objective To determine whether dietary interventions that increase n-3 fatty acids with and without reduction in n-6 linoleic acid can alter circulating lipid mediators implicated in headache pathogenesis, and decrease headache in adults with migraine. Design Three arm, parallel group, randomized, modified double blind, controlled trial. Setting Ambulatory, academic medical center in the United States over 16 weeks. Participants 182 participants (88% women, mean age 38 years) with migraines on 5-20 days per month (67% met criteria for chronic migraine). Interventions Three diets designed with eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and linoleic acid altered as controlled variables: H3 diet (n=61)—increase EPA+DHA to 1.5 g/day and maintain linoleic acid at around 7% of energy; H3-L6 diet (n=61)—increase n-3 EPA+DHA to 1.5 g/day and decrease linoleic acid to ≤1.8% of energy; control diet (n=60)—maintain EPA+DHA at Main outcome measures The primary endpoints (week 16) were the antinociceptive mediator 17-hydroxydocosahexaenoic acid (17-HDHA) in blood and the headache impact test (HIT-6), a six item questionnaire assessing headache impact on quality of life. Headache frequency was assessed daily with an electronic diary. Results In intention-to-treat analyses (n=182), the H3-L6 and H3 diets increased circulating 17-HDHA (log ng/mL) compared with the control diet (baseline-adjusted mean difference 0.6, 95% confidence interval 0.2 to 0.9; 0.7, 0.4 to 1.1, respectively). The observed improvement in HIT-6 scores in the H3-L6 and H3 groups was not statistically significant (−1.6, −4.2 to 1.0, and −1.5, −4.2 to 1.2, respectively). Compared with the control diet, the H3-L6 and H3 diets decreased total headache hours per day (−1.7, −2.5 to −0.9, and −1.3, −2.1 to −0.5, respectively), moderate to severe headache hours per day (−0.8, −1.2 to −0.4, and −0.7, −1.1 to −0.3, respectively), and headache days per month (−4.0, −5.2 to −2.7, and −2.0, −3.3 to −0.7, respectively). The H3-L6 diet decreased headache days per month more than the H3 diet (−2.0, −3.2 to −0.8), suggesting additional benefit from lowering dietary linoleic acid. The H3-L6 and H3 diets altered n-3 and n-6 fatty acids and several of their nociceptive oxylipin derivatives in plasma, serum, erythrocytes or immune cells, but did not alter classic headache mediators calcitonin gene related peptide and prostaglandin E2. Conclusions The H3-L6 and H3 interventions altered bioactive mediators implicated in headache pathogenesis and decreased frequency and severity of headaches, but did not significantly improve quality of life. Trial registration ClinicalTrials.gov NCT02012790
TL;DR: In this paper, the role of free fatty acid (FFA) receptors on immune cells has been investigated, showing their role as anti-inflammatory or pro-inflammatory molecules and elucidating their intracellular mechanisms.
Abstract: Long-chain fatty acids are molecules that act as metabolic intermediates and constituents of membranes; however, their novel role as signaling molecules in immune function has also been demonstrated. The presence of free fatty acid (FFA) receptors on immune cells has contributed to the understanding of this new role of long-chain fatty acids (LCFAs) in immune function, showing their role as anti-inflammatory or pro-inflammatory molecules and elucidating their intracellular mechanisms. The FFA1 and FFA4 receptors, also known as GPR40 and GPR120, respectively, have been described in macrophages and neutrophils, two key cells mediating innate immune response. Ligands of the FFA1 and FFA4 receptors induce the release of a myriad of cytokines through well-defined intracellular signaling pathways. In this review, we discuss the cellular responses and intracellular mechanisms activated by LCFAs, such as oleic acid, linoleic acid, palmitic acid, docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA), in T-cells, macrophages, and neutrophils, as well as the role of the FFA1 and FFA4 receptors in immune cells.
TL;DR: The optimal dietary DHA/EPA ratios of mud crab S. paramamosa were estimated to be 2.2 and 1.2 when supplied with optimal n-3 LC-PUFA at 7% and 12% lipid, respectively.
TL;DR: In this paper, the two main omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoive acid (DHA), are associated with coronary plaque progression.
Abstract: Inflammation in arterial walls leads to coronary artery disease (CAD). We previously reported that a high omega-3 fatty index was associated with prevention of progression of coronary atherosclerosis, a disease of chronic inflammation in the arterial wall. However, the mechanism of such benefit is unclear. The two main omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are precursors of specialized pro-resolving lipid mediators (SPMs)-resolvins and maresins-which actively resolve chronic inflammation. To explore whether SPMs are associated with coronary plaque progression, levels of SPMs and proinflammatory mediators (leukotriene B4 [LTB4 ] and prostaglandins) were measured using liquid chromatography-tandem mass spectrometry in 31 statin-treated patients with stable CAD randomized to either EPA and DHA, 3.36 g daily, or no EPA/DHA (control). Coronary plaque volume was measured by coronary computed tomographic angiography at baseline and at 30-month follow-up. Higher plasma levels of EPA+DHA were associated with significantly increased levels of two SPMs-resolvin E1 and maresin 1-and 18-hydroxy-eicosapentaenoic acid (HEPE), the precursor of resolvin E1. Those with low plasma EPA+DHA levels had a low (18-HEPE+resolvin E1)/LTB4 ratio and significant plaque progression. Those with high plasma EPA+DHA levels had either low (18-HEPE+resolvin E1)/LTB4 ratios with significant plaque progression or high (18-HEPE+resolvin E1)/LTB4 ratios with significant plaque regression. These findings suggest that an imbalance between pro-resolving and proinflammatory lipid mediators is associated with plaque progression and potentially mediates the beneficial effects of EPA and DHA in CAD patients.
TL;DR: In this article, the effects of different omega-3 fatty acid (eicosapentaenoic acid, DHA, and arachidonic acid (AA) on the bioavailability of nitric oxide (NO) and fatty acid composition in human umbilical vein endothelial cells (HUVECs) were compared.
Abstract: Treatment with high dose icosapent ethyl (IPE), an ethyl ester of the omega-3 fatty acid eicosapentaenoic acid (EPA), significantly reduced ischemic events in patients with either cardiovascular disease (CV) or diabetes plus other risk factors (REDUCE-IT) but the mechanism is not well understood. We compared the effects of EPA, docosahexaenoic acid (DHA), and the omega-6 fatty acid arachidonic acid (AA) on bioavailability of nitric oxide (NO) and fatty acid composition. Human umbilical vein endothelial cells (HUVECs) were pretreated with EPA, DHA, or AA (10 µM). Cells were stimulated with calcium ionophore and NO and peroxynitrite (ONOO-) were measured using porphyrinic nanosensors. Levels of EPA, DHA, AA and other fatty acids were measured by gas chromatography (GC). EPA treatment caused the greatest NO release (18%, p < 0.001) and reduction in ONOO- (13%, p < 0.05) compared to control; the [NO]/[ ONOO-] ratio increased by 35% (p < 0.001). DHA treatment increased NO levels by 12% (p < 0.01) but had no effect on ONOO- release. AA did not affect either NO or ONOO- release. Fatty acid treatments increased their respective levels in endothelial cells. EPA levels increased 10-fold to 4.59 mg/g protein (p < 0.001) with EPA treatment and the EPA/AA ratio increased by 10-fold (p < 0.001) compared to vehicle. Only EPA increased docosapentaenoic acid (DPA, omega-3) levels by 2-fold (p < 0.001). AA alone decreased the EPA/AA ratio 4-fold (p<0.001). These findings support a preferential benefit of EPA on endothelial function and omega-3 fatty acid content.