Essential Omega-3 Research Articles

Docosahexaenoic acid (DHA) blunts liver injury by conversion to protective lipid mediators: protectin D1 and 17S‐hydroxy‐DHA

Docosahexaenoic acid (DHA) is a omega-3 essential fatty acid that reduces the incidence and severity of a number of diseases. Recently, a novel series of DHA-derived lipid mediators with potent protective actions has been identified. In this study we demonstrate that dietary amplification of these DHA-derived products protects the liver from necroinflammatory injury. In vitro, supplementation of hepatocytes with DHA significantly reduced hydrogen peroxide-induced DNA damage, evaluated by the "comet assay," and oxidative stress, determined by measurement of malondialdehyde levels. In vivo, dietary supplementation of mice with DHA ameliorated carbon tetrachloride-induced necroinflammatory damage. In addition, hepatic cyclooxygenase-2 expression and PGE2 levels were significantly reduced in mice fed DHA-enriched diets. In these animals, increased hepatic formation of DHA-derived lipid mediators (i.e., 17S-hydroxy-DHA (17S-HDHA) and protectin D1) was detected by HPLC-gas chromatography/mass spectrometry analysis. Consistent with these findings, synthetic 17-HDHA abrogated genotoxic and oxidative damage in hepatocytes and decreased TNF-alpha release and 5-lipoxygenase expression in macrophages. In a transactivation assay, 17-HDHA acted in a concentration-dependent manner as a PPARgamma agonist. Taken together, these findings identify a potential role for DHA-derived products, specifically 17S-HDHA and protectin D1, in mediating the protective effects of dietary DHA in necroinflammatory liver injury.

Evolutionary aspects of diet, the omega-6/omega-3 ratio and genetic variation: nutritional implications for chronic diseases

Anthropological and epidemiological studies and studies at the molecular level indicate that human beings evolved on a diet with a ratio of omega-6 to omega-3 essential fatty acids (EFA) of ~1 whereas in Western diets the ratio is 15/1 to 16.7/1. A high omega-6/omega-3 ratio, as is found in today's Western diets, promotes the pathogenesis of many diseases, including cardiovascular disease, cancer, osteoporosis, and inflammatory and autoimmune diseases, whereas increased levels of omega-3 polyunsaturated fatty acids (PUFA) (a lower omega-6/omega-3 ratio), exert suppressive effects. Increased dietary intake of linoleic acid (LA) leads to oxidation of low-density lipoprotein (LDL), platelet aggregation, and interferes with the incorporation of EFA in cell membrane phospholipids. Both omega-6 and omega-3 fatty acids influence gene expression. Omega-3 fatty acids have anti-inflammatory effects, suppress interleukin 1β (IL-1β), tumor necrosis factor-α (TNFα) and interleukin-6 (IL-6), whereas omega-6 fatty acids do not. Because inflammation is at the base of many chronic diseases, dietary intake of omega-3 fatty acids plays an important role in the manifestation of disease, particularly in persons with genetic variation, as for example in individuals with genetic variants at the 5-lipoxygenase (5-LO). Carotid intima media thickness (IMT) taken as a marker of the atherosclerotic burden is significantly increased, by 80%, in the variant group compared to carriers with the common allele, suggesting increased 5-LO promoter activity associated with the (variant) allele. Dietary arachidonic acid (AA) and LA increase the risk for cardiovascular disease in those with the variants, whereas dietary intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) decrease the risk. A lower ratio of omega-6/omega-3 fatty acids is needed for the prevention and management of chronic diseases. Because of genetic variation, the optimal omega-6/omega-3 fatty acid ratio would vary with the disease under consideration.

Melanoma growth is reduced in fat-1 transgenic mice: impact of omega-6/omega-3 essential fatty acids.

An important nutritional question as to whether the ratio of omega-6 (n-6) to omega-3 (n-3) fatty acids plays a role in tumorigenesis remains to be clarified in well qualified experimental models. The recently engineered fat-1 mice, which can convert n-6 to n-3 fatty acids and have a balanced ratio of n-6 to n-3 fatty acids in their tissues and organs independent of diet, allow carefully controlled studies to be performed in the absence of potential confounding factors of diet and therefore are a useful model for elucidating the role of n-6/n-3 fatty acid ratio in tumorigenesis. We implanted mouse melanoma B16 cells into transgenic and WT littermates and examined the incidence of tumor formation and tumor growth rate. The results showed a dramatic reduction of melanoma formation and growth in fat-1 transgenic mice. The level of n-3 fatty acids and their metabolite prostaglandin E(3) (PGE(3)) were much higher (but the n-6/n-3 ratio is much lower) in the tumor and surrounding tissues of fat-1 mice than that of WT animals. The phosphatase and tensin homologue deleted on the chromosome 10 (PTEN) gene was significantly up-regulated in the fat-1 mice. In vitro experiments showed that addition of the n-3 fatty acid eicosapentaenoic acid or PGE(3) inhibited the growth of B16 cell line and increased the expression of PTEN, which could be partially attenuated by inhibition of PGE(3) production, suggesting that PGE(3) may act as an antitumor mediator. These data demonstrate an anticancer (antimelanoma) effect of n-3 fatty acids through, at least in part, activation of PTEN pathway mediated by PGE(3).

Wild berries: a good source of omega-3

It has been reported that some wild green vegetables are good sources of alpha-linolenic acid (ALA, an essential omega-3 fatty acid). Using available data from the Norwegian food composition table, the present study shows that three common Nordic berries (blueberry, cloudberry and cowberry) on average contain 0.7 g of fat (=21% of total energy) and 0.25 g ALA (=36% of total fat) per 100 g, which is quite similar to what has been reported for the ALA-rich wild green vegetables. In addition, this study shows that a hypothetical replacement of 5% of Norwegian 8th grade girls' diet, with a similar energy amount of wild berries, would significantly improve the diet - also improve intake of nutrients not commonly associated with berries.

Differential Effects of Omega-3 and Omega-6 fatty Acids on Gene Expression in Breast Cancer Cells

Essential fatty acids have long been identified as possible oncogenic factors. Existing reports suggest omega-6 (omega-6) essential fatty acids (EFA) as pro-oncogenic and omega-3 (omega-3) EFA as anti-oncogenic factors. The omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), inhibit the growth of human breast cancer cells while the omega-6 fatty acids induces growth of these cells in animal models and cell lines. In order to explore likely mechanisms for the modulation of breast cancer cell growth by omega-3 and omega-6 fatty acids, we examined the effects of arachidonic acid (AA), linoleic acid (LA), EPA and DHA on human breast cancer cell lines using cDNA microarrays and quantitative polymerase chain reaction. MDA-MB-231, MDA-MB-435s, MCF-7 and HCC2218 cell lines were treated with the selected fatty acids for 6 and 24 h. Microarray analysis of gene expression profiles in the breast cancer cells treated with both classes of fatty acids discerned essential differences among the two classes at the earlier time point. The differential effects of omega-3 and omega-6 fatty acids on the breast cancer cells were lessened at the late time point. Data mining and statistical analyses identified genes that were differentially expressed between breast cancer cells treated with omega-3 and omega-6 fatty acids. Ontological investigations have associated those genes to a broad spectrum of biological functions, including cellular nutrition, cell division, cell proliferation, metastasis and transcription factors etc., and thus presented an important pool of biomarkers for the differential effect of omega-3 and omega-6EFAs.

Neurodevelopment and Schizophrenia

Back to table of contents Previous article Next article Book ReviewsFull AccessNeurodevelopment and SchizophreniaFrederick J. Frese Ph.D.Frederick J. Frese Ph.D.Search for more papers by this authorPublished Online:1 Jun 2006https://doi.org/10.1176/ps.2006.57.6.887AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail Recently, considerable progress has been made in understanding how schizophrenia develops. The editors of Neurodevelopment and Schizophrenia have tapped the talents of some 56 authorities—including Francine Benes, Jeffrey Lieberman, and Anthony Grace—to produce one of the most richly rewarding reading experiences that I have had in some time. Some of the book's 24 chapters are particularly relevant for consumers and practicing clinicians. In Chapter 9, Sahebarao P. Mahadik covers recent findings concerning schizophrenia and nutrition. He makes very compelling arguments for including omega-3 essential polyunsaturated fatty acids and antioxidants, such as vitamins E and C, in the dietary intake of virtually all persons with schizophrenia.In Chapter 14, Chih-Ken Chen and Robin Murray reveal new, eye-opening evidence about how serious the consequences can be for people prone to schizophrenia who abuse such drugs as cannabis and amphetamines.The book's final three chapters focus on the clinical implications of recent research findings.Some chapters appear to be less immediately relevant for clinicians, and as Michael Rutter suggests in the well-written foreword, there are sections that are "not light bedtime reading."This caveat is probably most applicable to Chapters 1, 10, and 12, which deal with neurodevelopmental genetics, epigenetics, and transcriptomic DNA microarray analysis, respectively. Although these are among the heaviest of the offerings, they are also among the most interesting. Chapter 1 provides a review of evidence underpinning the status and functioning of some 33 schizophrenia susceptibility genes involved during brain development. This discussion is fascinating, partly because of the many colorful locutions employed. Terms such as "snip," "snap," and "snare"—shorthand for "single nucleotide polymorphism," "synaptosomal associated protein," and "soluble N-ethylmaleimide-sensitive attachment factor protein receptor"—lend a definite alliterative uplift to the information provided.Although most DNA sequences, particularly those for coding, are not thought to change during one's life, epigenetic modifications do occur. Such changes may have significant influence on regulation of gene expressions. Arturas Petronis presents evidence in Chapter 10 that developmental changes in schizophrenia can be affected by epigenetic factors.In Chapter 12, David A. Lewis and his associates provide an engaging description of the advent of the use of DNA microarrays as a method for determining and assessing transcriptomes, a technology yet in its infancy but with much promise for advancing our knowledge of brain function as it relates to schizophrenia.Other chapters address recent findings concerning such topics as magnetic resonance imaging, brain plasticity, cognitive development and long-term functioning after early cerebral insult, limbic and thalamocortical circuits, developmental dysregulation of dopamine neurotransmitting systems, and the role of sex chromosomes and steroids in brain development. Without exception, the contributors to this volume provide fresh, interesting, and valuable material from which all persons with a serious interest in schizophrenia can benefit. Finally, one cannot complete Neurodevelopment and Schizophrenia without suspecting that some of the material presented here may come to the attention of the folks in Stockholm who present the annual awards for progress in physiology or medicine. Dr. Frese is an assistant professor at the Northeastern Ohio Universities College of Medicine, Rootstown, and executive director of the Ohio Adult Recovery Network. FiguresReferencesCited byDetailsCited ByWhen does schizophrenia really begin? - A case report confirming the neurodevelopmental theory of schizophrenia22 October 2021 | Current Problems of Psychiatry, Vol. 22, No. 1 Volume 57Issue 6 June, 2006Pages 887-887PSYCHIATRIC SERVICES June 2006 Volume 57 Number 6 Metrics PDF download History Published online 1 June 2006 Published in print 1 June 2006

Time for an oil check: the role of essential omega-3 fatty acids in maternal and pediatric health

Deficiency of omega-3 fatty acids (omega3FAs) is an often unrecognized determinant of clinical disease; the adequate availability of these essential nutrients may prevent affliction or facilitate health restoration in some pregnant women and developing offspring. The human organism requires specific nutrients in order to carry out the molecular processes within cells and tissues and it is well established that omega3FAs are essential lipids necessary for various physiological functions. Accordingly, to achieve optimal health for patients, care givers should be familiar with clinical aspects of nutritional science, including the assessment of nutritional status and judicious use of nutrient supplementation. In view of the mounting evidence implicating omega3FA deficiency as a determinant of various maternal and pediatric afflictions, physicians should consider recommending purified fish oil supplementation during pregnancy and lactation. Furthermore, omega3FA supplementation may be indicated in selected pediatric situations to promote optimal health among children.

A scarlet pimpernel for the resolution of inflammation? The role of supra-therapeutic doses of cobalamin, in the treatment of systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, and septic or traumatic shock

Cobalamin carrier proteins,the Transcobalamins (TCS), are elevated during trauma, infections and chronic inflammatory conditions. This remains un-explained. It is proposed that such TC elevations signal a need for cobalamin central to the resolution of inflammation. Thus Cobalamin may regulate the transcription factor, NFkappaB, activation or suppression of which determines the inflammatory response and its resolution. Such regulation may involve at least 5 separate mechanisms: (i) hormone-like regulation of TNFalpha, through reduction of excess NO by cobalamin, as well as through the selective inhibition, in tandem with glutathione, of inducible nitric oxide synthase; (ii) quenching of nitric oxide radicals and reactive oxygen species, enhanced by cobalamin's glutathione sparing effect; (iii) the promotion of acetylcholine synthesis, central to the neuro-immune cholinergic anti-inflammatory pathway; (iv) the promotion of oxidative phosphorylation; (v) and a bacteriostatic role of the TCS released by neutrophil secondary granules during phagocytosis, which also appears to modulate the inflammatory response. TC elevations are dependent on NFkappaB activation, through crosstalk between NFkappaB and Sp1, another member of the helix-loop-helix protein family, which directly mediates transcription of the TCII gene. Sp1 also has binding sites on the TNFalpha and EGF gene promoters. NFkappaB may thus ensure sufficient cobalamin to determine its own eventual suppression. Cobalamin's established regulation of EGF may additionally preserve normal function of macrophages and the coagulation cascade in wound healing. By regulating NFkappaB, Cobalamin may also be the as yet unidentified mediator needed to potentiate the anti-inflammatory action of eicosanoids derived from omega-3 essential fatty acids. Moreover, animal and human clinical data suggests that high dose cobalamin may prove a promising approach to SIRS/sepsis/septic and traumatic shock.

Protective effects of ω-3 essential fatty acids against formaldehyde-induced neuronal damage in prefrontal cortex of rats

The aim of this study was to examine the neurotoxicity of formaldehyde on prefrontal cortex and the protective effects of omega-3 essential fatty acids against these toxic effects. For this purpose, 21 male Wistar rats were divided into three groups. The rats in group I comprised the controls, while the rats in group II were injected every other day with formaldehyde (FA). The rats in group III received omega-3 fatty acids daily while exposed to formaldehyde. At the end of the 14-day experimental period, all rats were killed by decapitation. The brains of the rats were removed and the prefrontal cortex tissues were obtained from all brain specimens. Some of the prefrontal cortex tissue specimens were used for determination of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) levels. The remaining prefrontal cortex tissue specimens were used for light microscopic and immunohistochemical evaluation. The levels of SOD and GSH-Px were significantly decreased, and MDA levels were significantly increased in rats treated with formaldehyde compared with those of the controls. Furthermore, in the microscopic examination of this group, formation of apoptotic bodies, pycnotic cells, and apoptotic cells including nuclear fragmentation and membrane budding were observed. However, increased SOD and GSH-Px enzyme activities, and decreased MDA levels were detected in the rats administered omega-3 fatty acids while exposed to formaldehyde. Additionally, cellular damage caused by formaldehyde was decreased, and structural appearance was similar to that of the control rats in this group. The biochemical and histological findings observed in all groups were also confirmed by immunohistochemical evaluation. It was determined that formaldehyde-induced neuronal damage in prefrontal cortex was prevented by administration of omega-3 essential fatty acids.

Atopy, eczema and breast milk fatty acids in a high‐risk cohort of children followed from birth to 5 yr

The incidence of atopic diseases such as eczema is increasing in westernized societies. The suggestion that there is a "protective" association between the unique fatty acid composition of breast milk, particularly the omega-3 (n-3) and omega-6 (n-6) essential polyunsaturated fatty acid content, and the development of atopic disease in children was investigated in a cohort study of 263 infants born into families with a history of allergy (one or both parents had asthma, hayfever, eczema). The objectives of this study were to determine the lipid profile [specifically in relation to long-chain polyunsaturated fatty acid (LC-PUFA) composition] in maternal breast milk samples collected at 6 wk and at 6 months following birth, and to investigate the potential role of these fatty acids in modulating the phenotype of children at high genetic risk of developing atopic disease. Breast milk samples were available from 91 atopic mothers at their child's ages of 6 wk and 6 months. These samples were analysed for the fatty acid spectrum. Analysis of variance was used to detect differences between groups of outcomes (no atopy or eczema, non-atopic eczema, atopy, atopic eczema) at ages 6 months and 5 yr, and a multiple comparisons procedure was conducted to isolate the parameters producing the different results (F-test, LSD test). For the exposure variables, n-3 and n-6 fatty acids are expressed as weight percentage and as a ratio (at both time-points). The fatty acid profiles of maternal breast milk at 6 wk and 6 months were similar. An increased ratio of n-6: n-3 fatty acids in both 6 wk and 6 month milk samples was associated with non-atopic eczema (p < 0.005) but not atopy alone or atopic eczema. We found milk fatty acids were a significant modulator of non-atopic eczema but not atopy or atopic eczema in infants at 6 months. In mothers with a history of asthma, hayfever or eczema, their 6-month-old infants were more likely to develop non-atopic eczema if their milk had a higher ratio of n-6: n-3 LC-PUFA.

Systemic Omega-6 Essential Fatty Acid Treatment and PGE1Tear Content in Sjögren’s Syndrome Patients

To determine the effect of oral omega-6 essential fatty acids on PGE(1) tear content and signs and symptoms of ocular discomfort in patients with Sjögren's syndrome (SS). This randomized, double-masked, controlled, clinical trial involved 40 patients with primary SS, divided into two groups: group 1: 20 patients (18 women, 2 men; mean age, 36.9 +/- 7.9 years [SD]) treated for 1 month with linoleic acid (LA; 112 mg), and gamma-linolenic acid (GLA; 15 mg) administered twice daily; group 2: 20 patients (19 women, 1 man; mean age, 36.3 +/- 5.5 years) treated twice daily with placebo. Patients underwent three examinations: at baseline (T0), after 1 month of treatment (T1), and 15 days after suspension of treatment (T2). At each examination, the following tests were performed: tear sampling (2 microL) from the inferior meniscus, tear break-up time (BUT), fluorescein stain of the ocular surface, and tear basal secretion. A symptom score was also obtained at each examination. PGE1 was evaluated by enzyme immunoassay. The primary efficacy variable was PGE1 content of tears. The tear PGE1 levels were significantly increased in group 1 at T1 versus T0 (PGE1 level: T0, 44 +/- 5.4 ng/mL; T1, 58.3 +/- 5.5 ng/mL; P < 0.01 versus T0 and group 2 at T1). At examination T2, a statistically significant reduction of PGE1 levels toward baseline was observed (45.7 +/- 5.2 ng/mL; P < 0.01 versus T1). A statistically significant reduction of symptom score was observed in group 1 at examination T1 (P < 0.01 versus T0 and group 2 score). At examination T2, the symptom score was significantly higher than T1 but remained lower than T0. The corneal fluorescein stain in group 1 showed a statistically significant improvement at examination T1 versus T0 and group 2 (P < 0.01). This improvement was also present at T2 (P < 0.02). No statistically significant differences were found for the other tests. No statistically significant changes were observed in the patients in group 2 at all examination time points. Omega-6 administration increases the PGE1 levels in tears of patients with SS and improves ocular surface signs and symptoms of ocular discomfort.

The relationship between folate and docosahexaenoic acid in men

Docosahexaenoic acid (DHA, 22:6n-3), an essential omega 3 fatty acid, may protect against disorders of emotional regulation as well as cardiovascular disease. Animal studies demonstrate that dietary folate can increase tissue concentrations of DHA, although the literature, to date, includes no human studies examining the possibility that folate status may affect plasma DHA concentrations. The objective of this study is to determine if the blood concentrations of folate and DHA are correlated in humans. Retrospective study. An American research hospital. A total of 15 normal and 22 hostile and aggressive subjects, with a mean age of 38 years. Concentrations of plasma polyunsaturated essential fatty acids and red blood cell folate (RBC folate) were obtained prior to 1996, before American flour was enriched with folate. RBC folate was significantly correlated with plasma DHA, r=0.57, P=0.005 in the aggressive group. Age, smoking and alcohol consumption did not alter the results. No other essential fatty acids were significantly associated with RBC folate in either group. The positive relationship between plasma DHA and RBC folate concentrations suggests that these two nutrients should be examined together in order to make the most accurate inferences about their relative contributions to disease pathogenesis. Our findings present one explanation why some conditions associated with hostility and low DHA status, such as cardiovascular disease and emotional disorders, are also associated with low folate status. National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism.

Rethinking lipid mediators

One of the characteristics of the modern western diet is the imbalance of the two essential fatty acids, the omega-6 and the omega-3 fatty acids (figure). The most important omega-6 fatty acid is arachidonic acid (20:4n 6); the important omega-3 fatty acids are eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3). Today's western diet has a ratio of omega-6 to omega-3 fatty acids of 15:1, when data suggest that human beings evolved, and lived for most of their existence, on a ratio close to 1:1. Changes in eating habits and in agriculture within the past 100–200 years are the main cause of this changed ratio. 1 Simopoulos AP The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomed Pharmacother. 2002; 56: 365-379 Crossref PubMed Scopus (2561) Google Scholar This shift might be important because these fatty acids are the precursors of the eicosanoid lipid mediators: the prostaglandins (PGs) and leukotrienes, lipoxins, epoxyprostanoids and isoprostanes. COX=cyclo-oxygenases, LO=lipoxygenases. Prostaglandins (PG), thromboxanes (TX), leukotrienes (LT), lipoxins (LX), resolvins (Rv), docosatrienes (DT), and aspirin-triggered lipoxins (ATLs) are shown with their respective abbreviations. Underlined are those mediators for which specific receptors have been identified.

Mechanisms of omega-3 fatty acid-induced growth inhibition in MDA-MB-231 human breast cancer cells

The omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), inhibit the growth of human breast cancer cells in animal models and cell lines, but the mechanism by which this occurs is not well understood. In order to explore possible mechanisms for the modulation of breast cancer cell growth by omega-3 fatty acids, we examined the effects of EPA and DHA on the human breast cancer cell line MDA-MB-231. Omega-3 fatty acids (a combination of EPA and DHA) inhibited the growth of MDA-MB-231 cells by 30-40% (p<0.05) in both the presence and absence of linoleic acid, an essential omega-6 fatty acid. When provided individually, DHA was more potent than EPA in inhibiting the growth of MDA-MB-231 cells (p<0.05). EPA and DHA treatment decreased tumor cell proliferation (p<0.05), as estimated by decreased [methyl-(3)H]-thymidine uptake and expression of proliferation-associated proteins (proliferating cell nuclear antigen, PCNA, and proliferation-related kinase, PRK). In addition, EPA and DHA induced apoptosis, as indicated by a loss of mitochondrial membrane potential, increased caspase activity and increased DNA fragmentation (p<0.05). Cells incubated with omega-3 fatty acids demonstrated decreased Akt phosphorylation, as well as NFkappaB DNA binding activity (p<0.05). The results of this study indicate that omega-3 fatty acids decrease cell proliferation and induce apoptotic cell death in human breast cancer cells, possibly by decreasing signal transduction through the Akt/NFkappaB cell survival pathway.

Essential Fats in Walnuts Are Good for the Heart and Diabetes

A cardio-protective dietary fat profile is recommended for the treatment of type 2 diabetes ( 1 Franz M.J. Bantle J.P. Beebe C.A. Brunzell J.D. Chiasson J.L. Garg A. Holzmeister L.A. Hoogwerf B. Mayer-Davis E. Mooradian A.D. Purnell J.Q. Wheeler M. American Diabetes AssociationEvidence-based nutrition principles and recommendations for the treatment and prevention of diabetes and related complications. Diabetes Care. 2002; 25: 148-198 Google Scholar ). There have been major changes in the American diet in the past few decades as people have increased their use of processed foods containing saturated and trans-fats. This has led to an unhealthful balance of essential fatty acids ( 2 Simopoulos A.P. The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomed Pharmacother. 2002; 56: 365-379 Google Scholar , 3 Simopoulos A.P. Leaf A. Salem N. Workshop on the essentiality of and recommended dietary intakes for omega-6 and omega-3 fatty acids. 1999 Google Scholar ). Ideally, the two families of essential fatty acids (n-6 and n-3) should be balanced in a ratio of no more than 4:1 for optimum health ( 2 Simopoulos A.P. The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomed Pharmacother. 2002; 56: 365-379 Google Scholar , 3 Simopoulos A.P. Leaf A. Salem N. Workshop on the essentiality of and recommended dietary intakes for omega-6 and omega-3 fatty acids. 1999 Google Scholar ). The average American’s dietary ratio can be in excess of 20:1, or more ( 2 Simopoulos A.P. The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomed Pharmacother. 2002; 56: 365-379 Google Scholar ). According to Simopoulos, “Walnuts are unique because they have a perfect balance of n-6 and n-3 polyunsaturated fatty acids, a ratio of 4:1, which has been shown to decrease the risk of sudden death in the Lyon Heart Study” ( 2 Simopoulos A.P. The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomed Pharmacother. 2002; 56: 365-379 Google Scholar ). n-3s are heart healthy because they reduce the bloodstream levels of low-density lipoprotein cholesterol and maintain or raise high-density lipoprotein cholesterol ( 2 Simopoulos A.P. The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomed Pharmacother. 2002; 56: 365-379 Google Scholar , 3 Simopoulos A.P. Leaf A. Salem N. Workshop on the essentiality of and recommended dietary intakes for omega-6 and omega-3 fatty acids. 1999 Google Scholar ).

Lipid-lowering drugs and essential omega-6 and omega-3 fatty acids in patients with coronary heart disease

There are only little data about the effects of lipid-lowering drugs (LLDs) on the metabolism of essential n-6 and n-3 fatty acids in patients with established coronary heart disease (CHD). Male patients with CHD and high cholesterol levels (>6.2 mmol/L) were randomized (double-blind protocol) to receive either simvastatin 20mg (S) or fenofibrate 200mg daily (F) for 3 months. Dietary habits and plasma fatty acids were not different in the two groups at baseline. After treatment, there were significant changes in both the groups for the main n-6 fatty acids, with an increase in arachidonate (from 6.5+/-1.7% of total fatty acids to 7.5+/-2.1, p<0.001 in S and from 6.2+/-1.4 to 6.8+/-1.4, p<0.005 in F) and a decrease in linoleate (from 26.9+/-3.9 to 24.2+/-3.6, p<0.001, and from 27.8+/-3.4 to 26.1+/-4.2, p<0.05, in S and F, respectively). In addition, there was a decrease in two major n-3 fatty acids (alpha-linolenate and docosahexanoate, both p<0.05), but only in F. For the first time in a double-blind randomized study in CHD patients, we report that LLDs significantly alter the metabolism of essential fatty acids that are critically important for the pathogenesis and prevention of CHD. Further studies are urgently needed to examine the effects of higher dosages of statins (as currently proposed to reduce more cholesterol) on these essential fatty acids in the clinical setting and the crucial questions of whether specific dietary intervention (combining low intake of n-6 fatty acids and high intake of n-3 fatty acids) may improve the effectiveness of these drugs.

Omega-6 Essential Fatty Acids and Tear PGE

Omega-6 Essential Fatty Acids and Tear PGE

Supplementation of ewe diets with algal biomass rich in Docosahexaenoic acid for different time periods before lambing affects measures of lamb viability

The improvement of neonatal viability by maternal nutrition during gestation has been widely studied in numerous species. Recent investigations have explored the role of long chain omega-3 essential fatty acids (EFAs) in maternal diets during pregnancy. These are the major fatty acids, docosahexaenoic acid (DHA) in particular, in brain and nervous tissue, with specific roles in neural development and cognitive function. Studies in monogastric species have shown that supplementing maternal gestation diets with EFAs positively influences neonatal survival and growth (Rookeet al., 2001), but work in ruminant species is scarce. Previous investigations have predominantly used fish oil as the source of omega-3 EFAs but alternative, more sustainable, sources are desirable. To date, the effect of period of inclusion of EFAs in gestation diets has not been thoroughly explored. The period of rapid brain growth in the ovine foetus occurs between 10 and 6 weeks prior to birth (Turleyet al., 1996). This study explored the effects of feeding an algal source of EFAs, with a high content of DHA, during different time periods on measures of lamb viability.

Resolvins, docosatrienes, and neuroprotectins, novel omega‐3‐derived mediators, and their endogenous aspirin‐triggered epimers

The molecular basis for the beneficial impact of essential omega-3 (n-3) FA remains of interest. Recently, we identified novel mediators generated from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) that displayed potent bioactions identified first in resolving inflammatory exudates and in tissues enriched with DHA. The trivial names resolvin (resolution phase interaction products) and docosatrienes were introduced for the bioactive compounds from these novel series since they possess potent anti-inflammatory and immunoregulatory actions. Compounds derived from EPA carrying potent biological actions (i.e., 1-10 nM range) are designated E series and denoted resolvins of the E series (resolvin E1 or RvE1), and those biosynthesized from the precursor DHA are denoted resolvins of the D series (resolvin D1 or RvD1). The number 1 designates the bioactive compounds in this family (#1-4). Bioactive members from DHA-containing conjugated triene structures or docosatrienes (DT) that possess immunoregulatory and neuroprotective actions were termed neuroprotectins. Aspirin treatment initiates a related epimeric series by triggering endogenous formation of the 17R-D series resolvins and docosatrienes. These epimers are denoted as aspirin-triggered (AT)-RvD and DT, and possess potent anti-inflammatory actions in vivo essentially equivalent to their 17S series pathway products. These include five distinct series: (i) 18R resolvins from EPA (i.e., RvE1); (ii) 17R series (AT) resolvins from DHA (RvD1 through RvD4); (iii) 17S series resolvins from DHA (RvD1 through RvD4), (iv) DT from DHA; and (v) their AT form 17R series DT. In this article, we provide an overview of the formation and actions of these newly uncovered pathways and products.

Food for ThoughtEssential Fatty Acid Protects against Neuronal Deficits in Transgenic Mouse Model of AD

Interactions between environmental and genetic factors may contribute to neurodegenerative disease. In this issue of Neuron, Calon et al. report that a diet low in an essential omega-3 polyunsaturated fatty acid (docosahexaenoic acid) depletes postsynaptic proteins and exacerbates behavioral alterations in a transgenic mouse model of Alzheimer's disease.