Omega-3 Highly Unsaturated Fatty Acids Research Articles

Polyunsaturated fatty acid biosynthesis pathway and genetics. implications for interindividual variability in prothrombotic, inflammatory conditions such as COVID-19✰,✰✰,★,★★

COVID-19 symptoms vary from silence to rapid death, the latter mediated by both a cytokine storm and a thrombotic storm. SARS-CoV (2003) induces Cox-2, catalyzing the synthesis, from highly unsaturated fatty acids (HUFA), of eicosanoids and docosanoids that mediate both inflammation and thrombosis. HUFA balance between arachidonic acid (AA) and other HUFA is a likely determinant of net signaling to induce a healthy or runaway physiological response. AA levels are determined by a non-protein coding regulatory polymorphisms that mostly affect the expression of FADS1, located in the FADS gene cluster on chromosome 11. Major and minor haplotypes in Europeans, and a specific functional insertion-deletion (Indel), rs66698963, consistently show major differences in circulating AA (>50%) and in the balance between AA and other HUFA (47–84%) in free living humans; the indel is evolutionarily selective, probably based on diet. The pattern of fatty acid responses is fully consistent with specific genetic modulation of desaturation at the FADS1-mediated 20:3→20:4 step. Well established principles of net tissue HUFA levels indicate that the high linoleic acid and low alpha-linoleic acid in populations drive the net balance of HUFA for any individual. We predict that fast desaturators (insertion allele at rs66698963; major haplotype in Europeans) are predisposed to higher risk and pathological responses to SARS-CoV-2 could be reduced with high dose omega-3 HUFA.

Design and methods for the Ranger Resilience and Improved Performance on Phospholipid bound Omega-3's (RRIPP-3 study)

Intake of nutrients fundamental for optimal neuronal function is of increasing interest. The potential importance of omega-3 highly unsaturated fatty acids (HUFAs) for optimizing emotional states, cognitive function, and mental health has been demonstrated in observational studies and randomized controlled trials. Omega-3 (HUFAs), specifically EPA (eicosapentaenoic acid) and docosahexaenoic acid (DHA), are concentrated in neural tissues and are essential for neural function, normative neurodevelopment, neurotransmitter, and neural immune functions. Omega-3 HUFAs must be obtained from the diet, predominantly from marine sources such as fish and other seafood. HUFAs also can be found in a variety of dietary supplements (omega-3 fatty acid esters, fish oil and krill oil). As dietary supplements, omega-3 HUFAs (fatty acid esters, fish and krill oils) differ substantially in their physicochemical properties and nutrient content. Here we present the design and methods for the Ranger Resilience and Improved Performance on Phospholipid bound Omega-3's (RRIPP-3) study. RRIPP-3 was a double blind, randomized, controlled trial among individuals in the United States (US) Army Infantry Basic Officer Leaders Course (IBOLC) and following US Ranger School training (RC) at Fort Benning, GA of omega-3 HUFA on krill oil versus placebo supplementation. The RRIPP-3 study sought to determine if krill oil supplementation with omega-3 HUFAs supports aspects of cognitive functioning critical to battlefield success when measured immediately after an intense combat simulation. Sub-analyses addressed basic improvements in IBOLC performance. We also describe additional outcome measures critical for interpretation of the study results, such as diet and other dietary supplement use.

Conversion efficiency of α-linolenic acid to omega-3 highly unsaturated fatty acids in aerial insectivore chicks.

Food availability and quality are both critical for growing young animals. In nature, swallows (Tachycineta bicolor) and other aerial insectivores feed on both aquatic insects, which are rich in omega-3 highly unsaturated fatty acids (HUFAs), and terrestrial insects, which contain considerably lower amounts of omega-3 HUFAs. Carnivorous mammals and fishes must obtain omega-3 HUFAs from their diet, as they have lost the capacity to convert the precursor omega-3 α-linolenic acid (ALA) into omega-3 HUFAs. Thus, the relative value of aquatic versus terrestrial insects depends not only on the fatty acid composition of the prey but also on the capacity of consumers to convert ALA into omega-3 HUFAs. We used a combination of stable-isotope-labeled fatty acid tracers to ask whether, and how efficiently, tree swallows can deposit newly synthesized omega-3 HUFAs into tissue. Our data show for the first time that tree swallows can convert ALA into omega-3 HUFAs deposited in liver and skeletal muscle. However, high tree swallow demand for omega-3 HUFAs combined with low ALA availability in natural terrestrial foods may strain their modest conversion ability. This suggests that while tree swallows can synthesize omega-3 HUFAs de novo, omega-3 HUFAs are ecologically essential nutrients in natural systems. Our findings thus provide mechanistic support for our previous findings and the importance of omega-3 HUFA-rich aquatic insects for tree swallows and most likely other aerial insectivores with similar niches.

Efficacy of omega-3 highly unsaturated fatty acids in the treatment of depression.

Trials evaluating efficacy of omega-3 highly unsaturated fatty acids (HUFAs) in major depressive disorder report discrepant findings. To establish the reasons underlying inconsistent findings among randomised controlled trials (RCTs) of omega-3 HUFAs for depression and to assess implications for further trials. A systematic bibliographic search of double-blind RCTs was conducted between January 1980 and July 2014 and an exploratory hypothesis-testing meta-analysis performed in 35 RCTs including 6665 participants receiving omega-3 HUFAs and 4373 participants receiving placebo. Among participants with diagnosed depression, eicosapentaenoic acid (EPA)-predominant formulations (>50% EPA) demonstrated clinical benefits compared with placebo (Hedge's G = 0.61, P<0.001) whereas docosahexaenoic acid (DHA)-predominant formulations (>50% DHA) did not. EPA failed to prevent depressive symptoms among populations not diagnosed for depression. Further RCTs should be conducted on study populations with diagnosed or clinically significant depression of adequate duration using EPA-predominant omega-3 HUFA formulations.

Supplementation with Omega-3 Fatty Acids in Psychiatric Disorders: A Review of Literature Data.

A new application for omega-3 fatty acids has recently emerged, concerning the treatment of several mental disorders. This indication is supported by data of neurobiological research, as highly unsaturated fatty acids (HUFAs) are highly concentrated in neural phospholipids and are important components of the neuronal cell membrane. They modulate the mechanisms of brain cell signaling, including the dopaminergic and serotonergic pathways. The aim of this review is to provide a complete and updated account of the empirical evidence of the efficacy and safety that are currently available for omega-3 fatty acids in the treatment of psychiatric disorders. The main evidence for the effectiveness of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has been obtained in mood disorders, in particular in the treatment of depressive symptoms in unipolar and bipolar depression. There is some evidence to support the use of omega-3 fatty acids in the treatment of conditions characterized by a high level of impulsivity and aggression and borderline personality disorders. In patients with attention deficit hyperactivity disorder, small-to-modest effects of omega-3 HUFAs have been found. The most promising results have been reported by studies using high doses of EPA or the association of omega-3 and omega-6 fatty acids. In schizophrenia, current data are not conclusive and do not allow us either to refuse or support the indication of omega-3 fatty acids. For the remaining psychiatric disturbances, including autism spectrum disorders, anxiety disorders, obsessive-compulsive disorder, eating disorders and substance use disorder, the data are too scarce to draw any conclusion. Concerning tolerability, several studies concluded that omega-3 can be considered safe and well tolerated at doses up to 5 g/day.

Current evidence and future directions for research with omega-3 fatty acids and attention deficit hyperactivity disorder.

Nutritional insufficiencies of nutrients such as omega-3 highly unsaturated fatty acids (HUFAs), vitamins and minerals have been linked to suboptimal developmental outcomes including attention deficit hyperactivity disorder (ADHD). Although the predominant treatment is currently psychostimulant medications, randomized clinical trials with omega-3 HUFAs have reported small-to-modest effects in reducing symptoms of ADHD in children despite arguable individual methodological and design misgivings. This review presents, discusses and critically evaluates data and findings from meta-analytic and systematic reviews and clinical trials published within the last 12 months. Recent trajectories of this research are discussed, such as comparing eicosapentaenoic acid and docosahexaenoic acid and testing the efficacy of omega-3 HUFAs as an adjunct to methylphenidate. Discussion includes highlighting limitations and potential future directions such as addressing variable findings by accounting for other nutritional deficiencies and behavioural food intolerances. The authors conclude that given the current economic burden of ADHD, estimated in the region of $77 billion in the USA alone, in addition to the fact that a proportion of patients with ADHD are either treatment resistant, nonresponders or withdraw from medication because of adverse side-effects, the investigation of nonpharmacological interventions including omega-3 HUFAs in clinical practice warrants extrapolating.

The potential for military diets to reduce depression, suicide, and impulsive aggression: a review of current evidence for omega-3 and omega-6 fatty acids.

The current burden of psychological distress and illness poses as a significant barrier to optimal force efficacy. Here we assess nutrients in military diets, specifically highly unsaturated essential fatty acids, in the reduction of risk or treatment of psychiatric distress. Moderate to strong evidence from several meta-analyses of prospective cohort trials indicate that Mediterranean diet patterns reduce risk of clinical depressions. Specific nutrients and foods of biological interest in relation to mental health outcomes are then discussed and evaluated. Moderate evidence indicates that when fish consumption decreases and simultaneously omega-6 increases, the risk of clinical depressive symptoms are elevated. One meta-analysis examining tissue compositions provides moderate to strong evidence that higher levels of omega-3 highly unsaturated fatty acids (HUFAs) (eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) are associated with decreased risk of clinical depressions. Other meta-analytic reviews of randomized placebo-controlled trials provide moderate to strong evidence of significantly improving clinically depressive symptoms when the formulation given was >50% in eicosapentaenoic acid. Finally, a meta-analysis of omega-3 HUFAs provides modest evidence of clinical efficacy for attention-deficit hyperactivity disorder. This article recommends that a rebalancing of the essential fatty acid composition of U.S. military diets, achieve tissue compositions of HUFAs consistent with traditional Mediterranean diets, may help reduce military psychiatric distress and simultaneously increase force efficacy substantially.

Omega-3 fatty acid and nutrient deficits in adverse neurodevelopment and childhood behaviors.

Nutritional insufficiencies of omega-3 highly unsaturated fatty acids (HUFAs) may have adverse effects on brain development and neurodevelopmental outcomes. A recent meta-analysis reported a small to modest effect size for the efficacy of omega-3 in youth. Several controlled trials of omega-3 HUFAs combined with micronutrients show sizable reductions in aggressive, antisocial, and violent behavior in youth and young adult prisoners. Studies of HUFAs in youth, however, remain lacking. As the evidence base for omega-3 HUFAs as potential psychiatric treatment develops, dietary adjustments to increase omega-3 and reduce omega-6 HUFA consumption are sensible recommendations based on general health considerations.

Chemical Composition of Greek Avgotaracho Prepared from Mullet (Mugil cephalus): Nutritional and Health Benefits

Crude composition, lipid composition, and tocopherols, ascorbic acid, cholesterol, phytosterols, and squalene content together with fatty acids and antiplatelet activities of total, neutral, and polar lipids of avgotaracho (wax-covered, dried, and salted Mugil cephalus roe) were studied and compared with those of similar products. Wax and steryl esters accounted for 63.7% of roe lipids followed by phosphatidylcholine (PC), which comprised 20.3%. Wax esters were rich in saturated fatty alcohols, monounsaturated fatty acids, and long chain omega3 highly unsaturated fatty acids (HUFA). The fatty acid distribution in roe total and neutral lipids was similar to that of wax esters, while in polar lipids, the omega3 HUFA predominated. Avgotaracho provides significant amounts of protein, fat, alpha-tocopherol, ascorbic acid, and PC, certain amounts of squalene and phytosterols, and cholesterol at levels comparable to hens' eggs. Total, polar, and neutral lipids of avgotaracho exhibited a strong inhibition of platelet activating factors and thrombin, with polar lipids being more active. The results obtained indicate that avgotaracho is a food of high nutritive value, rich in protein and lipids with a healthy lipid profile in terms of omega3/omega6 ratio and major fatty acid classes, while the antiplatelet activity of its oil indicates a putative antithrombotic potential.

The importance of omega-3 fatty acids for behaviour, cognition and mood

There is mounting evidence that functional deficiencies or imbalances in certain highly unsaturated fatty acids (HUFA) of the omega-3 and omega-6 series may contribute to a wide range of developmental and psychiatric conditions, including dyslexia, dyspraxia, attention deficit hyperactivity disorder (ADHD), autism, depression, bipolar disorder and the schizophrenia spectrum. These nutrients are essential to the development and function of the brain, but the omega-3 HUFA in particular (eicosapentaenoic and docosahexaenoic acids) are often lacking from modern diets. The evidence implicating omega-3 fatty acids in these conditions is summarized here, with a focus on the results from randomized controlled treatment trials. These indicate that treatment with eicosapentaenoic acid can reduce symptoms in adults with mood disorders, schizophrenia and possibly Huntington’s disease. In children, preliminary evidence suggests that omega-3 HUFA could also reduce some of the behavioural and learning difficulties associated with ADHD, dyslexia and related conditions. The key features of most of these conditions can be found in milder form as part of normal individual differences in mood, behaviour and cognition. The evidence presented here therefore has implications for the general population, and indicates that an adequate dietary intake of omega-3 fatty acids in particular may be crucial for optimal mental health and functioning. Keywords: brain; development disorders; mental health; unsaturated fatty acids

The importance of omega-3 fatty acids for behaviour, cognition and mood

There is mounting evidence that functional deficiencies or imbalances in certain highly unsaturated fatty acids (HUFA) of the omega-3 and omega-6 series may contribute to a wide range of developmental and psychiatric conditions, including dyslexia, dyspraxia, attention deficit hyperactivity disorder (ADHD), autism, depression, bipolar disorder and the schizophrenia spectrum. These nutrients are essential to the development and function of the brain, but the omega-3 HUFA in particular (eicosapentaenoic and docosahexaenoic acids) are often lacking from modern diets. The evidence implicating omega-3 fatty acids in these conditions is summarized here, with a focus on the results from randomized controlled treatment trials. These indicate that treatment with eicosapentaenoic acid can reduce symptoms in adults with mood disorders, schizophrenia and possibly Huntington’s disease. In children, preliminary evidence suggests that omega-3 HUFA could also reduce some of the behavioural and learning difficulties associated with ADHD, dyslexia and related conditions. The key features of most of these conditions can be found in milder form as part of normal individual differences in mood, behaviour and cognition. The evidence presented here therefore has implications for the general population, and indicates that an adequate dietary intake of omega-3 fatty acids in particular may be crucial for optimal mental health and functioning. Keywords: brain; development disorders; mental health; unsaturated fatty acids

Biochemistry and physiology of eicosanoid precursors in cell membranes

Excessive action of omega-6 eicosanoids formed from the body’s omega-6 essential fats occurs in many health disorders, and it can be diminished with dietary omega-3 fats. The current abundance of omega-6 (n-6) eicosanoidmediated disorders (e.g. thrombotic heart attack and stroke, cardiac arrhythmia, atherogenesis, arthritis, asthma, osteoporosis, tumour metastases, etc.) accompanies n-6 acid intakes that are more than ten times than the adequate level of 0·5% of energy. The n-3 and n-6 highly unsaturated fatty acids (HUFAs) are maintained in tissue phospholipids in a competitive, hyperbolic relationship to the dietary abundance of their 18-carbon polyunsaturated fatty acid (PUFA) precursors. In contrast, 18:2n-6 and 18:3n-3 acids are maintained in tissue triacylglycerols in a linear proportion to their dietary abundance expressed as percentage of daily caloric energy. The near absence of 20:3n-9 acid in plasma phospholipids in the U.S.A. population reflects very high intakes of polyunsaturated fats that compete with oleate for conversion to tissue HUFAs. The ethnic food combinations for Greenland, Japanese, Mediterranean, and American populations give proportions of omega-6 isomers in the body long-chain acids near 30%, 50% 60% and 80%, respectively. It is of interest that these values mimic clinical outcomes associated with cardiovascular mortalities ranging from 20 to 50 to 90 to 200 per 100 000, respectively. Therapeutic treatment to cut excessive omega-6 eicosanoid signalling has involved billions of dollars being spent to develop and market new pharmaceutical agents while a preventive nutrition approach to cut excessive omega-6 eicosanoid signalling has yet to be applied systematically in dietetics, clinical nutrition and public health. Voluntary choices of food combinations can produce proportions of omega-6 HUFAs and of omega-3 plus omega-6 HUFAs in the total body ranging from 30% to 90%, respectively. Adverse eects of excessive omega-6 eicosanoid signalling can be lowered by two interdependent dietary changes: first, reduce the daily intake of foods overly rich in the precursors of 20:4n-6 acid; and second, simultaneously increase the omega-3 PUFAs in the diet to competitively inhibit the conversion of LA into tissue omega-6 HUFAs. An inter active computer software application has been developed to combine the complex biomedical information on competitive interactions among essential fats and eicosanoids, and to interpret and display the finding in terms of multiple daily food choices understandable by the general public.