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Back to Polyunsaturated fatty acids (PUFAs)

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Eicosapentaenoic acid (EPA) Reviews: 2006

Williams, C. M. and G. Burdge (2006). "Long-chain n-3 PUFA: plant v. marine sources." Proc Nutr Soc 65(1): 42-50.

            Increasing recognition of the importance of the long-chain n-3 PUFA, EPA and DHA, to cardiovascular health, and in the case of DHA to normal neurological development in the fetus and the newborn, has focused greater attention on the dietary supply of these fatty acids. The reason for low intakes of EPA and DHA in most developed countries (0.1-0.5 g/d) is the low consumption of oily fish, the richest dietary source of these fatty acids. An important question is whether dietary intake of the precursor n-3 fatty acid, alpha-linolenic acid (alphaLNA), can provide sufficient amounts of tissue EPA and DHA by conversion through the n-3 PUFA elongation-desaturation pathway. alphaLNA is present in marked amounts in plant sources, including green leafy vegetables and commonly-consumed oils such as rape-seed and soyabean oils, so that increased intake of this fatty acid would be easier to achieve than via increased fish consumption. However, alphaLNA-feeding studies and stable-isotope studies using alphaLNA, which have addressed the question of bioconversion of alphaLNA to EPA and DHA, have concluded that in adult men conversion to EPA is limited (approximately 8%) and conversion to DHA is extremely low (<0.1%). In women fractional conversion to DHA appears to be greater (9%), which may partly be a result of a lower rate of utilisation of alphaLNA for beta-oxidation in women. However, up-regulation of the conversion of EPA to DHA has also been suggested, as a result of the actions of oestrogen on Delta6-desaturase, and may be of particular importance in maintaining adequate provision of DHA in pregnancy. The effect of oestrogen on DHA concentration in pregnant and lactating women awaits confirmation.


Whelan, J. and C. Rust (2006). "Innovative dietary sources of n-3 fatty acids." Annu Rev Nutr 26: 75-103.

            It is now established that dietary n-3 polyunsaturated fatty acids (PUFAs) are involved in health promotion and disease prevention, particularly those traditionally derived from marine sources (e.g., eicosapentaenoic acid and docosahexaenoic acid). A number of organizations have made specific recommendations for the general population to increase their intakes of these nutrients. In response to and along with these recommendations, n-3 PUFAs are being incorporated into nontraditional food sources because of advances in the technology to safely enrich/fortify our food supply. Fatty acid compositions of traditional oils (e.g., canola and soybean) are being genetically modified to deliver more highly concentrated sources of n-3 PUFA. The advent of algal sources of docosahexaenoic acid provides one of the few terrestrial sources of this fatty acid in a concentrated form. All of this is possible because of newer technologies (microencapsulation) and improved processing techniques that ensure stability and preserve the integrity of these unstable fatty acids.


Wang, C., W. S. Harris, et al. (2006). "n-3 Fatty acids from fish or fish-oil supplements, but not alpha-linolenic acid, benefit cardiovascular disease outcomes in primary- and secondary-prevention studies: a systematic review." Am J Clin Nutr 84(1): 5-17.

            Studies on the relation between dietary n-3 fatty acids (FAs) and cardiovascular disease vary in quality, and the results are inconsistent. A systematic review of the literature on the effects of n-3 FAs (consumed as fish or fish oils rich in eicosapentaenoic acid and docosahexaenoic acid or as alpha-linolenic acid) on cardiovascular disease outcomes and adverse events was conducted. Studies from MEDLINE and other sources that were of > or =1 y in duration and that reported estimates of fish or n-3 FA intakes and cardiovascular disease outcomes were included. Secondary prevention was addressed in 14 randomized controlled trials (RCTs) of fish-oil supplements or of diets high in n-3 FAs and in 1 prospective cohort study. Most trials reported that fish oil significantly reduced all-cause mortality, myocardial infarction, cardiac and sudden death, or stroke. Primary prevention of cardiovascular disease was reported in 1 RCT, in 25 prospective cohort studies, and in 7 case-control studies. No significant effect on overall deaths was reported in 3 RCTs that evaluated the effects of fish oil in patients with implantable cardioverter defibrillators. Most cohort studies reported that fish consumption was associated with lower rates of all-cause mortality and adverse cardiac outcomes. The effects on stroke were inconsistent. Evidence suggests that increased consumption of n-3 FAs from fish or fish-oil supplements, but not of alpha-linolenic acid, reduces the rates of all-cause mortality, cardiac and sudden death, and possibly stroke. The evidence for the benefits of fish oil is stronger in secondary- than in primary-prevention settings. Adverse effects appear to be minor.


von Schacky, C. (2006). "A review of omega-3 ethyl esters for cardiovascular prevention and treatment of increased blood triglyceride levels." Vasc Health Risk Manag 2(3): 251-62.

            The two marine omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), prevalent in fish and fish oils, have been investigated as a strategy towards prophylaxis of atherosclerosis. While the results with fish and fish oils have been not as clear cut, the data generated with the purified ethyl ester forms of these two fatty acids are consistent. Although slight differences in biological activity exist between EPA and DHA, both exert a number of positive actions against atherosclerosis and its complications. EPA and DHA as ethyl esters inhibit platelet aggregability, and reduce serum triglycerides, while leaving other serum lipids essentially unaltered. Glucose metabolism has been studied extensively, and no adverse effects were seen. Pro-atherogenic cytokines are reduced, as are markers of endothelial activation. Endothelial function is improved, vascular occlusion is reduced, and the course of coronary atherosclerosis is mitigated. Heart rate is reduced, and heart rate variability is increased by EPA and DHA. An antiarrhythmic effect can be demonstrated on the supraventricular and the ventricular level. More importantly, two large studies showed reductions in clinical endpoints like sudden cardiac death or major adverse cardiac events. As a consequence, relevant cardiac societies recommend using 1 g/day of EPA and DHA for cardiovascular prevention, after a myocardial infarction and for prevention of sudden cardiac death.


Truksa, M., G. Wu, et al. (2006). "Metabolic engineering of plants to produce very long-chain polyunsaturated fatty acids." Transgenic Res 15(2): 131-7.

            Very long-chain polyunsaturated fatty acids (VLCPUFAs) are essential for human health and well-being. However, the current sources of these valuable compounds are limited and may not be sustainable in the long term. Recently, considerable progress has been made in identifying genes involved in the biosynthesis of VLCPUFAs. The co-expression of these genes in model systems such as plant embryos or yeast provided many valuable insights into the mechanisms of VLCPUFA synthesis. The recent successful reconstitution of pathways leading to the synthesis of arachidonic acid, eicosapentaenoic acid and finally docosahexaenoic acid in oil-seed plants indicates the feasibility of using transgenic crops as alternative sources of VLCPUFAs. The various approaches used to attain these results and the specific constraints associated with each approach are discussed.


Tisdale, M. J. (2006). "Clinical anticachexia treatments." Nutr Clin Pract 21(2): 168-74.

            Cachexia involves progressive loss of adipose tissue and skeletal muscle mass and is common in a number of end-stage diseases. Cachexia causes weakness and immobility, reduces the quality of life of the patient, and eventually results in death. We reviewed the medical literature concentrating upon agents that have undergone clinical evaluation for the treatment of patients with cachexia. These agents are discussed, together with their mechanisms of action. Megestrol acetate, corticosteroids, eicosapentaenoic acid, and thalidomide have shown some success in the treatment of cachexia. beta-hydroxy-beta-methylbutyrate, cyclooxygenase inhibitors, adenosine 5'-triphosphate, and growth hormone are undergoing clinical evaluation. Appetite stimulants such as cannabinoids and antiserotonic agents have been shown to be ineffective in preventing progressive weight loss in cachexia. Much of the success in the treatment of cachexia has come from agents capable of blocking protein degradation through the ubiquitin-proteasome proteolytic pathway. Muscle mass can be increased when such agents are combined with agents that stimulate protein synthesis. In order to develop new agents, more fundamental research is required on the cellular mechanisms governing protein synthesis and degradation in skeletal muscle in cachexia.


Thatcher, W. W., T. R. Bilby, et al. (2006). "Strategies for improving fertility in the modern dairy cow." Theriogenology 65(1): 30-44.

            The high producing dairy cow of the 21st century is subfertile during lactation. Our objectives are to characterize physiological periods limiting reproductive performance and to describe integrated management strategies to improve pregnancy rates. Ovarian recrudescence with normal re-occurring estrous cycles and restoration of fertility to first service are associated with a reduced occurrence of periparturient metabolic and reproductive disorders. Marked negative changes in energy balance and reduced immunocompetence influence gonadotropic and metabolic hormones. Induced ovarian inactivity was associated with enhanced uterine involution. Post-partum health and reproductive performance were improved when by-pass lipids enriched in polyunsaturated fatty acids were fed in the pre- and post-partum periods. Pharmaceutical control of follicle, CL, and uterine function with PGF, GnRH and intravaginal progesterone releasing inserts, has permitted development of more optimal timed-insemination programs for first service. Likewise, resynchronization of nonpregnant cows coupled with the use of ultrasound for early pregnancy diagnosis provides the opportunity for a second timed-insemination within 3 days of a nonpregnant diagnosis. Bovine somatotropin (bST) increases embryo development and embryo survival when coupled with a timed-insemination program or cows detected in estrus. Presence of a conceptus alters endometrial expression of genes and proteins in response to bST and nutraceuticals (i.e., unsaturated fatty acids such as eicosapentaenoic and docosahexaenoic acid in by-pass lipids) to improve pregnancy rates. Postovulatory increases in progesterone may enhance pregnancy rates in targeted populations of lactating dairy cows, but timing and magnitude of the progesterone increases are pharmaceutically dependent.


Stehr, S. N. and A. R. Heller (2006). "Omega-3 fatty acid effects on biochemical indices following cancer surgery." Clin Chim Acta 373(1-2): 1-8.

            Epidemiological studies have indicated that a high intake of saturated fat and/or animal fat increases the risk of colon and breast cancer. Laboratory and clinical investigations have shown a reduced risk of colon carcinogenesis after alimentation with omega-3 fatty acids, as found in fish oil. Mechanisms accounting for these anti-tumor effects are reduced levels of PGE(2) and inducible NO synthase as well as an increased lipid peroxidation, or translation inhibition with subsequent cell cycle arrest. Further, omega-3 eicosapentaenoic acid is capable of down-regulating the production and effect of a number of mediators of cachexia, such as IL-1, IL-6, TNF-alpha and proteolysis-inducing factor. In patients with advanced cancer, it is possible to increase energy and protein intake via an enteral or parenteral route, but this seems to have little impact on progressive weight loss. Fish oil administration improved patients' conditions in cancer cachexia and during radio- and chemotherapy. In patients undergoing tumor resection surgery we observed improvement of liver and pancreas biochemical indices when omega-3 fatty acids were administered. This paper is a review of recent developments in the field of nutrition in cancer patients with emphasis on the acute phase response following cancer surgery and the beneficial aspects of fish oil administration.


Sontrop, J. and M. K. Campbell (2006). "Omega-3 polyunsaturated fatty acids and depression: a review of the evidence and a methodological critique." Prev Med 42(1): 4-13.

            Several lines of evidence indicate an association between omega-3 polyunsaturated fatty acids (PUFAs) and depression. The purpose of this review was to evaluate the evidence to date within the context of the study design and methodology used. In case-control and cohort studies, concentrations of omega-3 PUFAs were lower in participants with unipolar and postpartum depression. Fish are the major dietary source of omega-3 PUFAs, and infrequent fish consumption is associated with depression in epidemiological studies. While these findings do not appear to be the result of confounding, in some studies failure to detect confounding may be due to a lack of power or incomplete control. In four of seven double-blind randomized controlled trials, depression was significantly improved upon treatment with at least 1 g/day of eicosapentaenoic acid, an omega-3 PUFA. While clinical significance was demonstrated, preservation of blinding may be a limitation in this area of research. It remains unclear whether omega-3 supplementation is effective independently of antidepressant treatment, for depressed patients in general or only those with abnormally low concentrations of these PUFAs. The relationship between omega-3 PUFAs and depression is biologically plausible and is consistent across study designs, study groups, and diverse populations, which increases the likelihood of a causal relationship.


Simopoulos, A. P. (2006). "Evolutionary aspects of diet, the omega-6/omega-3 ratio and genetic variation: nutritional implications for chronic diseases." Biomed Pharmacother 60(9): 502-7.

            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 approximately 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 1beta (IL-1beta), tumor necrosis factor-alpha (TNFalpha) 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.


Serhan, C. N. (2006). "Novel chemical mediators in the resolution of inflammation: resolvins and protectins." Anesthesiol Clin 24(2): 341-64.

            Resolvins and protectins are new families consisting of distinct chemical series of lipid-derived mediators, each with unique structures and apparent complementary anti-inflammatory actions. Both families of compounds, Rv and protectins, are also generated when aspirin is given in mammalian systems in their respective epimeric forms. The resolvins and protectins each dampen inflammation and PMN-mediated injury from within, which is a key culprit in many common human diseases. The results of these initial studies underscore the roles of resolvins and protectins in inflammation resolution as well as catabasis and spotlight the therapeutic potential for this new arena of immunomodulation and host protection. It is likely that the resolvins, protectins, and their AT-related forms may play roles in other tissues and organs. Moreover, it is noteworthy that fish (eg, trout) generate lipoxygenase products such as LXAs from endogenous EPA and also biosynthesize RvDs and protectins from endogenous DHA. Taken together, these findings suggest that these novel lipid mediators (eg, resolvins and protectins) are conserved in evolution as self-protective and host-protective chemical mediators. In view of the essential roles of DHA and EPA in human biology and medicine uncovered to date, the physiologic relevance of the resolvins and protectins is likely to extend beyond our current appreciation.


Schwab, J. M. and C. N. Serhan (2006). "Lipoxins and new lipid mediators in the resolution of inflammation." Curr Opin Pharmacol 6(4): 414-20.

            Lipoxins and aspirin-triggered lipoxins are lipid mediators generated from arachidonic acid that act to reduce inflammation and promote resolution. In addition, two new families of lipid mediators were uncovered, namely resolvins (resolution phase interaction products) and protectins, which derive from omega-3 polyunsaturated fatty acid. They possess potent anti-inflammatory, neuroprotective and pro-resolving properties. Eicosapentaenoic acid-derived mediators are denoted resolvins of the E series, and those biosynthesized from docosahexaenoic acid are resolvins of the D series (RvDs) and protectins. Aspirin impinges on these systems, triggering formation of the epimeric 17R-series RvDs--denoted as 'aspirin-triggered-RvDs'--which possess bioactivity in vivo equivalent to that evoked by their 17S-series counterparts (i.e. RvDs). These bioactive molecules open new avenues and approaches to therapeutic interventions via accelerated resolution of inflammation.


Robert, S. S. (2006). "Production of eicosapentaenoic and docosahexaenoic acid-containing oils in transgenic land plants for human and aquaculture nutrition." Mar Biotechnol (NY) 8(2): 103-9.

            A large body of evidence suggests that there is a significant underconsumption of omega-3, long-chain, polyunsaturated fatty acids (LC-PUFAs) and that this is the cause of multiple chronic diseases and developmental aberrations. The scope for increasing omega-3 LC-PUFA consumption from seafood is limited because global wild fisheries are unable to increase their harvests, and aquaculture fisheries currently rely on wild fisheries as a source of LC-PUFAs. Agricultural production of oils is highly efficient and has the potential to be sustainable. The transfer of genes from marine microalgae and other microorganisms into oilseed crops has shown that the production of terrestrial omega-3 LC-PUFA oils is indeed possible. The specifications of these oils or whole seeds for use in human and Atlantic salmon (Salmo salar) aquaculture nutrition are discussed.


Puri, B. K. (2006). "High-resolution magnetic resonance imaging sinc-interpolation-based subvoxel registration and semi-automated quantitative lateral ventricular morphology employing threshold computation and binary image creation in the study of fatty acid interventions in schizophrenia, depression, chronic fatigue syndrome and Huntington's disease." Int Rev Psychiatry 18(2): 149-54.

            Serial high-resolution structural magnetic resonance imaging scans of the brain can now be precisely aligned, with six degrees of freedom (three mutually orthogonal translational and three rotational degrees of freedom around three mutually orthogonal axes), using a rigid-body subvoxel registration technique. This is driven by the in-plane point spread function for images acquired in the Fourier domain with data obtained over a bounded region of k-space, namely the sinc interpolation function, where sinc z = (sin z)/z, with z being any complex number (including zero). Computational subtraction of the three-dimensional Cartesian spatial representation matrices of serially acquired scan data allows for the determination of structural cerebral changes with great precision, since voxel signals from unchanged structures are almost completely cancelled. Thus changes readily show up against a background of noise. Furthermore, lateral ventricular changes can now be accurately quantified using a semi-automated method involving contour production, threshold computation, binary image creation and ventricular extraction. These techniques have been applied to the investigation of the effects on cerebral structure of intervention with fatty acids, particularly the long-chain polyunsaturated n-3 fatty acid eicosapentaenoic acid (EPA), in disorders such as schizophrenia, treatment-resistant depression, chronic fatigue syndrome (myalgic encephalomyelitis or ME), and Huntington's disease.


Planas, M., C. Puiggros, et al. (2006). "[Contribution of nutritional support to fight cancer cachexia]." Nutr Hosp 21 Suppl 3: 27-36.

            To increase dietary intake and to fight anorexia several measures to treat symptoms and administer the most adequate diet according to composition, texture and flavour are proposed. However, in the anorexia-caquexia present in cancer patients not always these measures are effective. Now a day it seems more reasonable to approach this problem with different strategies directed to modulate the pathologic alterations associated. The analysis of specific nutritional support as part as the treatment of these patients from a systematic review conclude that no high methodological quality studies to analyze the impact of oral supplementation on a specific group of patients, neither the study of functional effects are done. However, an increase in the total energy intake, not maintained over the time, was observed. The effects on weight and corporal composition are variable, with small differences between groups with o without supplementation and confuse due to, mainly, the heterogeneity of the patients included in the different studies analyzed. The analysis of the effects of nutritional supplements administered by enteral feeding shown an increase in the energy intake with an increase in body weight or a lack of decrease it, and with some functional and clinical beneficial effects. Despite the results and conclusions obtained, a strong recommendation to conduct clinical trials in specific group of cancer patients with different antineoplasic treatment seems necessary. N-3 fatty acids, especially eicosapentaenoic acid may have anticachectic properties. Although further trials are necessary the limited results available suggests that nutritional supplements enriched with EPA may reverse cachexia in cancer patients.


Pins, J. J. and J. M. Keenan (2006). "Dietary and nutraceutical options for managing the hypertriglyceridemic patient." Prog Cardiovasc Nurs 21(2): 89-93.

            Scientific evidence continues to accumulate regarding fasting serum triglycerides as an independent risk factor for coronary heart disease. In response, the National Cholesterol Education Program has revised the acceptable level of fasting triglycerides from <200 mg/dL to <150 mg/dL. A significant percentage of Americans suffer from hypertriglyceridemia, and considering the expanding numbers of individuals who are physically inactive, overweight, and suffering from the metabolic syndrome, it is expected that these numbers will continue to rise over the next decade. Fortunately, nutraceutical and lifestyle options have been shown to substantially and consistently reduce this risk factor. This review will focus on management options for the hypertriglyceridemic patient with an emphasis on nicotinic acid, pantethine, fish oils (eicosapentaenoic and docosahexaenoic acids), and modified carbohydrate diets.


Parker, G., N. A. Gibson, et al. (2006). "Omega-3 fatty acids and mood disorders." Am J Psychiatry 163(6): 969-78.

            OBJECTIVE: This article is an overview of epidemiological and treatment studies suggesting that deficits in dietary-based omega-3 polyunsaturated fatty acids may make an etiological contribution to mood disorders and that supplementation with omega-3 fatty acids may provide a therapeutic strategy. METHOD: Relevant published studies are detailed and considered. RESULTS: Several epidemiological studies suggest covariation between seafood consumption and rates of mood disorders. Biological marker studies indicate deficits in omega-3 fatty acids in people with depressive disorders, while several treatment studies indicate therapeutic benefits from omega-3 supplementation. A similar contribution of omega-3 fatty acids to coronary artery disease may explain the well-described links between coronary artery disease and depression. CONCLUSIONS: Deficits in omega-3 fatty acids have been identified as a contributing factor to mood disorders and offer a potential rational treatment approach. This review identifies a number of hypotheses and studies for consideration. In particular, the authors argue for studies clarifying the efficacy of omega-3 supplementation for unipolar and bipolar depressive disorders, both as individual and augmentation treatment strategies, and for studies pursuing which omega-3 fatty acid, eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA), is likely to provide the greatest benefit.


Paillard, F. (2006). "[Nutritional aspects of hypertension]." Presse Med 35(6 Pt 2): 1077-80.

            Nutritional factors may explain 30-75% of cases of hypertension, depending on the population. Overweight alone can explain 11-25%. Nutritional measures are effective in reducing blood pressure or delaying the onset of hypertension. Globally, their impact is close to that of antihypertensive treatment with a single drug and they potentiate the drug's efficacy. The Dash diet, in particular, has been shown to be effective in lowering blood pressure. It is low in saturated fat and sodium, rich in fruit, vegetables and nonfat dairy products.


Osher, Y., R. H. Belmaker, et al. (2006). "Clinical trials of PUFAs in depression: State of the art." World J Biol Psychiatry 7(4): 223-30.

            Omega fatty acid treatment of depression is an unusual story in psychopharmacology in that the use and study of these compounds were advanced in cardiovascular disease before becoming of interest in psychiatry. Given the absence of an easily patentable derivative it is a tribute to the field that enough studies have accumulated for a reasonable review of omega-3 treatment of depression at this time. On the other hand, it is clearly not possible to compare the number of studies, variety of studies and the number of participants in each study with Federal Drug Administration style registration trials of patented antidepressant drugs. Most of the available studies of omega-3 in depression have been investigator initiated and use add-on design. This paper reviews 12 published and as yet unpublished clinical trials (all but one double-blind placebo-controlled) of polyunsaturated fatty acids in unipolar depression, bipolar disorder, and special populations with affective/depressive disorders. While overall results up to this point are encouraging, they are not unanimously positive. Outstanding issues that have not as yet been resolved include the dose of omega-3 necessary and the length of time required for significant response. Moreover, the complex issue of the relationship between two possible active ingredients, eicosapentaenoic acid and docosahexaenoic acid, remains unresolved.


Nannicini, F., F. Sofi, et al. (2006). "Alpha-linolenic acid and cardiovascular diseases omega-3 fatty acids beyond eicosapentaenoic acid and docosahexaenoic acid." Minerva Cardioangiol 54(4): 431-42.

            Over the last decades, an increasing body of evidence has been accumulated on the beneficial effect of polyunsaturated fatty acids both in primary and secondary prevention of cardiovascular diseases. However, the vast majority of the studies has been performed on long-chain polyunsaturated fatty acids, such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) and not on their biochemical precursor, alpha-linolenic acid (ALA). Actually, ALA has some other beneficial effects apart from the known antiarrhythmic effect. In fact, ALA has a strong inhibitory effect on omega-6 metabolic pathway. An adequate daily intake of ALA shifts metabolic pathway to EPA, so favoring the formation of products with a predominant antiaggregating and vasorelaxing action, with respect to eicosanoids with a predominant thrombotic effect. Some important evidences have been raised on the association between ALA and cardiovascular mortality. Indeed, dietary ALA has been associated with a lower rate of fatal and nonfatal coronary events. Hence, major scientific associations published nutritional guidelines including a specific recommendation for ALA.


Muskiet, F. A. and R. F. Kemperman (2006). "Folate and long-chain polyunsaturated fatty acids in psychiatric disease." J Nutr Biochem 17(11): 717-27.

            Schizophrenia, autism and depression do not inherit by Mendel's law, and the search for a genetic basis seems unsuccessful. Schizophrenia and autism relate to low birth weight and pregnancy complications, which are associated with developmental adaptations by "programming". Epigenetics might constitute the basis of programming and depend on folate status and one-carbon metabolism in general. Early folate status of patients with schizophrenia might be compromised as suggested by (i) coinciding incidences of schizophrenia and neural tube defects (NTDs) in the Dutch hunger winter, (ii) coinciding seasonal fluctuations in birth of patients with schizophrenia and NTDs, (iii) higher schizophrenia incidence in immigrants and (iv) higher incidence in methylene tetrahydrofolate reductase 677C-->T homozygotes. Recent studies in schizophrenia and autism point at epigenetic silencing of critical genes or chromosomal loci. The long-chain polyunsaturated fatty acids (LCPUFA), arachidonic acid (AA, from meat) and docosahexaenoic acid (fish) are components of brain phospholipids and modulators of signal transduction and gene expression. Patients with schizophrenia and, possibly, autism exhibit abnormal phospholipid metabolism that might cause local AA depletion and impaired eicosanoid-mediated signal transduction. National fish intakes relate inversely with major and postpartum depressions. Five out of six randomized controlled trials with eicosapentaenoic acid (fish) have shown positive effects in schizophrenia, and 4 of 6 were favorable in depression and bipolar disorders. We conclude that folate and LCPUFA might be important in both the etiology and severity of at least some psychiatric diseases.


Mozaffarian, D. and E. B. Rimm (2006). "Fish intake, contaminants, and human health: evaluating the risks and the benefits." Jama 296(15): 1885-99.

            CONTEXT: Fish (finfish or shellfish) may have health benefits and also contain contaminants, resulting in confusion over the role of fish consumption in a healthy diet. EVIDENCE ACQUISITION: We searched MEDLINE, governmental reports, and meta-analyses, supplemented by hand reviews of references and direct investigator contacts, to identify reports published through April 2006 evaluating (1) intake of fish or fish oil and cardiovascular risk, (2) effects of methylmercury and fish oil on early neurodevelopment, (3) risks of methylmercury for cardiovascular and neurologic outcomes in adults, and (4) health risks of dioxins and polychlorinated biphenyls in fish. We concentrated on studies evaluating risk in humans, focusing on evidence, when available, from randomized trials and large prospective studies. When possible, meta-analyses were performed to characterize benefits and risks most precisely. EVIDENCE SYNTHESIS: Modest consumption of fish (eg, 1-2 servings/wk), especially species higher in the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), reduces risk of coronary death by 36% (95% confidence interval, 20%-50%; P<.001) and total mortality by 17% (95% confidence interval, 0%-32%; P = .046) and may favorably affect other clinical outcomes. Intake of 250 mg/d of EPA and DHA appears sufficient for primary prevention. DHA appears beneficial for, and low-level methylmercury may adversely affect, early neurodevelopment. Women of childbearing age and nursing mothers should consume 2 seafood servings/wk, limiting intake of selected species. Health effects of low-level methylmercury in adults are not clearly established; methylmercury may modestly decrease the cardiovascular benefits of fish intake. A variety of seafood should be consumed; individuals with very high consumption (> or =5 servings/wk) should limit intake of species highest in mercury levels. Levels of dioxins and polychlorinated biphenyls in fish are low, and potential carcinogenic and other effects are outweighed by potential benefits of fish intake and should have little impact on choices or consumption of seafood (women of childbearing age should consult regional advisories for locally caught freshwater fish). CONCLUSIONS: For major health outcomes among adults, based on both the strength of the evidence and the potential magnitudes of effect, the benefits of fish intake exceed the potential risks. For women of childbearing age, benefits of modest fish intake, excepting a few selected species, also outweigh risks.


Morris, T., M. Stables, et al. (2006). "New perspectives on aspirin and the endogenous control of acute inflammatory resolution." ScientificWorldJournal 6: 1048-65.

            Aspirin is unique among the nonsteroidal anti-inflammatory drugs in that it has both anti-inflammatory as well as cardio-protective properties. The cardio-protective properties arise form its judicious inhibition of platelet-derived thromboxane A2 over prostacyclin, while its anti-inflammatory effects of aspirin stem from its well-established inhibition of prostaglandin (PG) synthesis within inflamed tissues. Thus aspirin and the other NSAIDs have popularised the notion of inhibiting PG biosynthesis as a common anti-inflammatory strategy based on the erroneous premise that all eicosanoids are generally detrimental to inflammation. However, our fascination with aspirin has shown a more affable side to lipid mediators based on our increasing interest in the endogenous control of acute inflammation and in factors that mediate its resolution. Epi-lipoxins (epi-LXs), for instance, are produced from aspirin's acetylation of inducible cyclooxygenase 2 (COX-2) and together with Resolvins represent an increasingly important family of immuno-regulatory and potentially cardio-protective lipid mediators. Aspirin is beginning to teach us what nature knew all along--that not all lipid mediators are bad. It seems that while some eicosanoids are pathogenic in a variety of diseases, others are unarguable protective. In this review we will re-count aspirin's colorful history, discuss its traditional mode of action and the controversies associated therewith, as well as highlight some of the new pathways in inflammation and the cardiovascular systems that aspirin has recently revealed.


Mori, T. A. and R. J. Woodman (2006). "The independent effects of eicosapentaenoic acid and docosahexaenoic acid on cardiovascular risk factors in humans." Curr Opin Clin Nutr Metab Care 9(2): 95-104.

            PURPOSE OF REVIEW: This review details the independent effects of purified eicosapentaenoic acid and docosahexaenoic acid on cardiovascular risk factors in humans. We report data from the recent literature and our own controlled clinical trials which compared the independent effects of these fatty acids in individuals at increased risk of cardiovascular disease, namely overweight hyperlipidaemic men and treated-hypertensive, type 2 diabetic men and women. We discuss the biological effects of these fatty acids and the potential mechanisms through which they may affect cardiovascular disease risk factors. RECENT FINDINGS: A cardioprotective effect for omega3 fatty acids is supported by prospective studies demonstrating an inverse association between fish intake and coronary heart disease mortality. Data from secondary prevention trials support a reduction in ventricular fibrillation as a primary mechanism for the decreased incidence of myocardial infarction. Clinical trials and experimental studies have shown that omega3 fatty acids have many other potentially important antiatherogenic and antithrombotic effects. Omega-3 fatty acids lower blood pressure and heart rate, improve dyslipidaemia, reduce inflammation, and improve vascular and platelet function. These favourable effects have until recently been primarily attributed to the omega3 fatty acid eicosapentaenoic acid, which is present in large amounts in fish oil. Controlled studies in humans now demonstrate that docosahexaenoic acid, although often present in lower quantities, has equally important anti-arrhythmic, anti-thrombotic and anti-atherogenic effects. SUMMARY: Available evidence strongly suggests that eicosapentaenoic acid and docosahexaenoic acid have differing haemodynamic and anti-atherogenic properties. The effects of the two fatty acids may also differ depending on the target population.


Mori, T. A. (2006). "Omega-3 fatty acids and hypertension in humans." Clin Exp Pharmacol Physiol 33(9): 842-6.

            1. Population studies and clinical trials provide compelling evidence that omega-3 (omega3) fatty acids have cardioprotective effects. The strongest evidence is from DART and GISSI-P, two secondary prevention trials in patients with previous myocardial infarctions. Data from these trials support a reduction in ventricular fibrillation as a primary mechanism for the decreased incidence of myocardial infarction. 2. Evidence suggests that w3 fatty acids may also provide protection against stroke, particularly ischaemic stroke. 3. The cardioprotective effects of omega3 fatty acids relate to improvements in blood pressure, cardiac function, arterial compliance and vascular function, as well as improved lipid metabolism, antiplatelet and anti-inflammatory effects. 4. Clinical trials in humans have shown that eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have different haemodynamic properties. Docosahexaenoic acid may be more favourable in lowering blood pressure and heart rate, as well as improving vascular function. However, the effects of EPA and DHA may also differ depending on the target population.


Mesa Garcia, M. D., C. M. Aguilera Garcia, et al. (2006). "Importance of lipids in the nutritional treatment of inflammatory diseases." Nutr Hosp 21 Suppl 2: 28-41, 30-43.

            Over the last decades, scientific advances in the knowledge of anti-inflammatory properties of lipids have lead to the development of new formulas for enteral and parenteral nutrition. These products have been utilised as a treatment for a variety of inflammatory diseases. In this review we expose the effects of lipids used in enteral nutriton on different inflammatory pathologies such as inflammatory bowel disease, atherosclerosis, lung fibrosis, rheumatoid arthritis, and others. During inflammatory diseases, eicosanoids are produced from polyunsaturated fatty acids present in cellular membranes. Inflammatory activity of these molecules depends on the nature of their precursors: when arachidonic acid (n-6) is present, pro-inflammatory molecules are released, whereas eicosapentaenoic acid (n-3)-derived eicosanoids are weakly inflammatory. In this way, fish oils, rich in n-3 polyunsaturated fatty acids, increase the content of eicosapentaenoic-eicosanoids and decrease arachidonic acid in immune and endothelial cells leading to a lower inflammatory activity. Likewise, oleic acid exhibits anti-inflammatory effects by preventing the release of particular chemotactic molecules. In summary, enteral diets supplemented with n-3 polyunsaturated fatty acids and oleic acid benefits the treatment of patients with inflammatory pathologies, leading to better outcomes, and decreasing the doses of anti-inflammatory drugs, which exhibit important secondary effects.


Lombardo, Y. B. and A. G. Chicco (2006). "Effects of dietary polyunsaturated n-3 fatty acids on dyslipidemia and insulin resistance in rodents and humans. A review." J Nutr Biochem 17(1): 1-13.

            For many years, clinical and animal studies on polyunsaturated n-3 fatty acids (PUFAs), especially those from marine oil, eicosapentaenoic acid (20:5,n-3) and docosahexaenoic acid (22:6,n-3), have reported the impact of their beneficial effects on both health and diseases. Among other things, they regulate lipid levels, cardiovascular and immune functions as well as insulin action. Polyunsaturated fatty acids are vital components of the phospholipids of membrane cells and serve as important mediators of the nuclear events governing the specific gene expression involved in lipid and glucose metabolism and adipogenesis. Besides, dietary n-3 PUFAs seem to play an important protecting role against the adverse symptoms of the Plurimetabolic syndrome. This review highlights some recent advances in the understanding of metabolic and molecular mechanisms concerning the effect of dietary PUFAs (fish oil) and focuses on the prevention and/or improvement of dyslipidemia, insulin resistance, impaired glucose homeostasis, diabetes and obesity in experimental animal models, with some extension to humans.


Kantarci, A., H. Hasturk, et al. (2006). "Host-mediated resolution of inflammation in periodontal diseases." Periodontol 2000 40: 144-63.


Jude, S., S. Roger, et al. (2006). "Dietary long-chain omega-3 fatty acids of marine origin: a comparison of their protective effects on coronary heart disease and breast cancers." Prog Biophys Mol Biol 90(1-3): 299-325.

            The relationship between high fish consumption and low mortality following coronary heart disease (CHD) and low incidence of breast cancer was first mentioned 3 decades ago. The fishes of interest are rich in omega-3 long-chain polyunsaturated fatty acids (omega-3 LC-PUFAs), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which could be the active nutrients. The current consensus about cardioprotection is that omega-3 LC-PUFAs would mainly exert antiarrhythmic effects. One of the proposed mechanisms is that circulating non-esterified LC-PUFAs partition into cardiac cells membrane phospholipids and exert a direct effect on ionic channels and/or modify intracellular calcium homeostasis. In another hypothesis, changes in the metabolism of phosphoinositides would be involved and lead to the differential activation of PKC isoforms. As compared to the mechanisms proposed for the cardioprotective effects of omega-3 LC-PUFAs, less is known about the molecular mechanisms involved in breast cancers prevention. Some proposed mechanisms such as the modulation of phosphoinositides metabolism and/or modulation of intracellular calcium homeostasis, are common to both pathologies. Other hypotheses involve the alteration of the cellular redox status induced by highly peroxidizable polyunsaturated fatty acids (FA), or the modulation of gene expression, both phenomena being tightly linked to apoptosis. In this review, we report and compare some proposed mechanisms for the involvement of omega-3 LC-PUFAs in both cardiac and breast cancer protection. Deliberately, we chose to discuss only the mechanisms, which are less described in other reviews such as ionic channels in cancer, calcium homeostasis, PKC activation or matrix metalloproteinases in both cancer and cardiac models. The leitmotiv along this review is that cardio- and cancero-protective effects use common pathways. Comparison of the cellular effects might therefore help to highlight the "protective" pathways.


Joy, C. B., R. Mumby-Croft, et al. (2006). "Polyunsaturated fatty acid supplementation for schizophrenia." Cochrane Database Syst Rev 3: CD001257.

            BACKGROUND: Limited evidence supports a hypothesis suggesting that schizophrenic symptoms may be the result of altered neuronal membrane structure and metabolism. The structure and metabolism is dependent on blood plasma levels of certain essential fatty acids and their metabolites. OBJECTIVES: To review the effects of polyunsaturated fatty acids for people with schizophrenia. SEARCH STRATEGY: We have updated the initial searches of 1998 and 2002 (Cochrane Schizophrenia Group's Register, July 2005), and where necessary, we contacted authors and relevant pharmaceutical companies. SELECTION CRITERIA: We included all randomised clinical trials of polyunsaturated fatty acid treatment for schizophrenia. DATA COLLECTION AND ANALYSIS: Working independently, we selected studies for quality assessment and extracted relevant data. We analysed on an intention-to-treat basis. Where possible and appropriate we calculated the Relative Risk (RR) and their 95% confidence intervals (CI) and estimated the number needed to treat (NNT). For continuous data we calculated weighted mean differences (WMD) and their 95% confidence intervals. We also inspected the data for heterogeneity. MAIN RESULTS: When any dose omega-3 (E-EPA or EPA) is compared with placebo, small short trials suggest that the need for neuroleptics appears to be reduced for people allocated omega-3 supplementation (n=30, 1 RCT, RR 0.73 CI 0.54 to 1.00) and mental state may improve (n=30, 1 RCT, RR not gaining 25% change in PANSS scores 0.54 CI 0.30 to 0.96, NNT3 CI 2-29). There are no differences in the number of people leaving the study early (n=271, 4 RCTs, RR 0.91 CI 0.36 to 2.33). There are few data on the comparison of any dose omega-6 (GLA) with placebo. For movement disorder outcomes, the only small study we found does not show any difference for average short-term endpoint AIMS score (n=16, 1 RCT, MD 1.30 CI -1.96 to 4.56). When any dose omega 3 (E-EPA or EPA) is compared with any dose omega-3 (DHA) there is no clear difference for mental state outcome of not gaining 25% change in PANSS scores (n=31, 1 RCT, RR 0.66 CI 0.39 to 1.11). When different doses of omega-3 (E-EPA) are compared with placebo there are no differences in measures of global and mental state between the studies. For the outcome of 'experiencing at least one adverse effect' no differences between groups are found for any dose (1g/day E-EPA vs placebo n=63 1 RCT, RR 0.97 CI 0.60 to 1.56; 2g/day E-EPA vs placebo n=63 1 RCT, RR 0.67 CI 0.37 to 1.20; 4g/day E-EPA vs placebo n=58, 1 RCT, RR 1.15 CI 0.72 to 1.82). AUTHORS' CONCLUSIONS: Two updates of this review have resulted in more included studies but relatively little useful additional data. The results remain inconclusive. The new trials all compare the omega-3 polyunsaturated fatty acids, in particular eicosapentaenoic acid and its ester, ethyl-eicosapentaenoic acid. The use of omega-3 polyunsaturated fatty acids for schizophrenia still remains experimental and this review highlights the need for large well designed, conducted and reported studies.


Jensen, C. L. (2006). "Effects of n-3 fatty acids during pregnancy and lactation." Am J Clin Nutr 83(6 Suppl): 1452S-1457S.

            n-3 Fatty acids exert important effects on eicosanoid metabolism, membrane properties, and gene expression and therefore are biologically important nutrients. One n-3 fatty acid, docosahexaenoic acid, is an important component of neural and retinal membranes and accumulates rapidly in the brain and retina during the later part of gestation and early postnatal life. It is reasonable to hypothesize that maternal n-3 fatty acid intakes might have significant effects on several pregnancy outcomes as well as on subsequent infant visual function and neurodevelopmental status. Studies, both observational and interventional, assessing the influence of n-3 fatty acids during pregnancy or the early postpartum period on duration of gestation and infant size at birth, preeclampsia, depression, and infant visual function and neurodevelopment have been reported. n-3 Fatty acid intakes (both in terms of absolute amounts of docosahexaenoic acid and eicosapentaenoic acid and the ratio of these 2 fatty acids) varied widely in these studies, however, and no clear consensus exists regarding the effects of n-3 fatty acids on any of these outcomes. The available data suggest a modest effect of these fatty acids on increasing gestational duration and possibly enhancing infant neurodevelopment. Although data from earlier observational studies suggested a potential role of these fatty acids in decreasing the incidence of preeclampsia, this has not been confirmed in randomized, prospective trials. Because of the paucity of data from randomized, prospective, double-blind trials, the effect of n-3 fatty acids on depression during pregnancy or the early postpartum period remains unresolved.


Hibbeln, J. R., T. A. Ferguson, et al. (2006). "Omega-3 fatty acid deficiencies in neurodevelopment, aggression and autonomic dysregulation: opportunities for intervention." Int Rev Psychiatry 18(2): 107-18.

            Mechanisms by which aggressive and depressive disorders may be exacerbated by nutritional deficiencies in omega-3 fatty acids are considered. Early developmental deficiencies in docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) may lower serotonin levels at critical periods of neurodevelopment and may result in a cascade of suboptimal development of neurotransmitter systems limiting regulation of the limbic system by the frontal cortex. Residual developmental deficits may be manifest as dysregulation of sympathetic responses to stress including decreased heart rate variability and hypertension, which in turn have been linked to behavioral dysregulation. Little direct data are available to disentangle residual neurodevelopmental effects from reversible adult pathologies. Ensuring optimal intakes of omega-3 fatty acids during early development and adulthood shows considerable promise in preventing aggression and hostility.


Harris, W. S., B. Assaad, et al. (2006). "Tissue omega-6/omega-3 fatty acid ratio and risk for coronary artery disease." Am J Cardiol 98(4A): 19i-26i.

            A ratio that estimates tissue proportions of omega-6 fatty acids (linoleic acid and/or arachidonic acid [AA]) and omega-3 fatty acids (eicosapentaenoic acid [EPA], docosahexaenoic acid [DHA], and/or alpha-linolenic acid) has been proposed as a biomarker of risk for coronary artery disease (CAD). Use of an omega-6/omega-3 fatty acid ratio instead of either fatty acid class alone is based on theoretical reasons and has not been validated. The relationship between risk for CAD events and tissue omega-3 and omega-6 fatty acid composition was evaluated by pooling data from case-control or prospective cohort studies that examined the risk for CAD end points as a function of tissue fatty acid composition. Thirteen studies were included, 11 case-control and 2 prospective cohort studies, and case-control differences in computed averages of several fatty acids and fatty acid ratios were compared. The largest and most consistent difference was for the sum of EPA + DHA (-11% in cases, p = 0.002). Proportions of EPA, DHA, and AA were about 8% lower in cases, but none of these differences was significant. Total omega-3 and omega-6 fatty acids were lower by 7% and 4%, respectively, in cases versus controls, but only the total omega-3 fatty acid difference was significant. The AA/EPA ratio was nonsignificantly lower by 10% in cases. Fatty acid ratios generally failed to distinguish cases from controls, and any discriminatory power they had derived from the omega-3 fatty acid component. Tissue EPA + DHA appears to be the best fatty acid metric for evaluating for CAD risk.


Gebauer, S. K., T. L. Psota, et al. (2006). "n-3 fatty acid dietary recommendations and food sources to achieve essentiality and cardiovascular benefits." Am J Clin Nutr 83(6 Suppl): 1526S-1535S.

            Dietary recommendations have been made for n-3 fatty acids, including alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) to achieve nutrient adequacy and to prevent and treat cardiovascular disease. These recommendations are based on a large body of evidence from epidemiologic and controlled clinical studies. The n-3 fatty acid recommendation to achieve nutritional adequacy, defined as the amount necessary to prevent deficiency symptoms, is 0.6-1.2% of energy for ALA; up to 10% of this can be provided by EPA or DHA. To achieve recommended ALA intakes, food sources including flaxseed and flaxseed oil, walnuts and walnut oil, and canola oil are recommended. The evidence base supports a dietary recommendation of approximately 500 mg/d of EPA and DHA for cardiovascular disease risk reduction. For treatment of existing cardiovascular disease, 1 g/d is recommended. These recommendations have been embraced by many health agencies worldwide. A dietary strategy for achieving the 500-mg/d recommendation is to consume 2 fish meals per week (preferably fatty fish). Foods enriched with EPA and DHA or fish oil supplements are a suitable alternate to achieve recommended intakes and may be necessary to achieve intakes of 1 g/d.


Galli, C. and F. Marangoni (2006). "N-3 fatty acids in the Mediterranean diet." Prostaglandins Leukot Essent Fatty Acids 75(3): 129-33.

            Fats in the diet of countries in the Mediterranean basin are typically represented by olive oil, but the high consumptions of vegetables and to some extent also of fish result in appreciable intakes of n-3 fatty acids. In fact, various plant foods are relatively rich in the 18 carbon n-3 fatty acid, alpha linolenic acid, ALA, while the generally moderate consumption of fish, except for certain communities living close to the sea, contributes to the intake of the long-chain n-3. Although the amounts of fats in ALA-containing plant foods are low, the relatively high concentrations of this fatty acid and the large size of the portions consumed allow to reach appreciable doses of ALA, an n-3 fatty acid that has been shown to exert favourable effects on various relevant factors in cardiovascular protection. In addition, consumption of relatively small amounts of certain typical dry fruit components of the diet such as walnuts, provides a sizable supply of ALA that is also rather efficiently converted to the ALA derivative eicosapentaenoic acid (EPA). Additional rather typical wild food components of the diet in certain countries, i.e. snails and frogs, are also appreciable sources of ALA. It appears thus that the consumption of typical Mediterranean foods provides relevant intakes of n-3 fatty acids, especially ALA, that appears to be efficiently absorbed and also transformed at least to the long-chain derivative EPA.


Freemantle, E., M. Vandal, et al. (2006). "Omega-3 fatty acids, energy substrates, and brain function during aging." Prostaglandins Leukot Essent Fatty Acids 75(3): 213-20.

            The maintenance of optimal cognitive function is a central feature of healthy aging. Impairment in brain glucose uptake is common in aging associated cognitive deterioration, but little is known of how this problem arises or whether it can be corrected or bypassed. Several aspects of the challenge to providing the brain with an adequate supply of fuel during aging seem to relate to omega-3 fatty acids. For instance, low intake of omega-3 fatty acids, especially docosahexaenoic acid (DHA), is becoming increasingly associated with several forms of cognitive decline in the elderly, particularly Alzheimer's disease. Brain DHA level seems to be an important regulator of brain glucose uptake, possibly by affecting the activity of some but not all the glucose transporters. DHA synthesis from either alpha-linolenic acid (ALA) or eicosapentaenoic acid (EPA) is very low in humans begging the question of whether these DHA precursors are likely to be helpful in maintaining cognition during aging. We speculate that ALA and EPA may well have useful supporting roles in maintaining brain function during aging but not by their conversion to DHA. ALA is an efficient ketogenic fatty acid, while EPA promotes fatty acid oxidation. By helping to produce ketone bodies, the effects of ALA and EPA could well be useful in strategies intended to use ketones to bypass problems of impaired glucose access to the brain during aging. Hence, it may be time to consider whether the main omega-3 fatty acids have distinct but complementary roles in brain function.


Freeman, M. P. (2006). "Omega-3 fatty acids and perinatal depression: a review of the literature and recommendations for future research." Prostaglandins Leukot Essent Fatty Acids 75(4-5): 291-7.

            INTRODUCTION: Perinatal depression refers to major depression in the context of pregnancy and postpartum. In consideration of its prevalence and consequences, the treatment and prevention of perinatal depression should be important public health priorities. Omega-3 fatty acids are attractive for consideration in perinatal women, due to known health benefits for the mother and baby. Antidepressant medications may pose risks in utero and in breastfeeding. METHODS: MEDLINE and manual searches were conducted. RESULTS: Epidemiological and preclinical data support a role of omega-3 fatty acids in perinatal depression. Two studies failed to support a role of omega-3 fatty acids for postpartum depression prophylaxis, although one included a small sample, and the other utilized a low dosage. Two pilot studies suggest good tolerability and potential efficacy in the acute treatment of perinatal depression. CONCLUSIONS: Further research studies are warranted to determine the role of omega-3 fatty acids in the treatment of perinatal depression.


Freeman, M. P., J. R. Hibbeln, et al. (2006). "Omega-3 fatty acids: evidence basis for treatment and future research in psychiatry." J Clin Psychiatry 67(12): 1954-67.

            OBJECTIVE: To determine if the available data support the use of omega-3 essential fatty acids (EFA) for clinical use in the prevention and/or treatment of psychiatric disorders. PARTICIPANTS: The authors of this article were invited participants in the Omega-3 Fatty Acids Subcommittee, assembled by the Committee on Research on Psychiatric Treatments of the American Psychiatric Association (APA). EVIDENCE: Published literature and data presented at scientific meetings were reviewed. Specific disorders reviewed included major depressive disorder, bipolar disorder, schizophrenia, dementia, borderline personality disorder and impulsivity, and attention-deficit/hyperactivity disorder. Meta-analyses were conducted in major depressive and bipolar disorders and schizophrenia, as sufficient data were available to conduct such analyses in these areas of interest. CONSENSUS PROCESS: The subcommittee prepared the manuscript, which was reviewed and approved by the following APA committees: the Committee on Research on Psychiatric Treatments, the Council on Research, and the Joint Reference Committee. CONCLUSIONS: The preponderance of epidemiologic and tissue compositional studies supports a protective effect of omega-3 EFA intake, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in mood disorders. Meta-analyses of randomized controlled trials demonstrate a statistically significant benefit in unipolar and bipolar depression (p = .02). The results were highly heterogeneous, indicating that it is important to examine the characteristics of each individual study to note the differences in design and execution. There is less evidence of benefit in schizophrenia. EPA and DHA appear to have negligible risks and some potential benefit in major depressive disorder and bipolar disorder, but results remain inconclusive in most areas of interest in psychiatry. Treatment recommendations and directions for future research are described. Health benefits of omega-3 EFA may be especially important in patients with psychiatric disorders, due to high prevalence rates of smoking and obesity and the metabolic side effects of some psychotropic medications.


Elia, M., M. A. Van Bokhorst-de van der Schueren, et al. (2006). "Enteral (oral or tube administration) nutritional support and eicosapentaenoic acid in patients with cancer: a systematic review." Int J Oncol 28(1): 5-23.

            The aim of this systematic review was to determine the efficacy and potential benefits of enteral nutritional support [oral nutritional supplements (ONS) or enteral tube feeding (ETF)], and eicosapentaenoic acid (EPA, free acid, ethyl esters or fish oil; provided as capsules or enriched ONS or ETF) in patients with cancer. Clinical studies were identified using electronic databases, and studies were selected according to predetermined criteria. For each treatment modality (chemo/radiotherapy, surgery, and palliative care), the comparisons of interest were nutritional support vs. routine care (no nutritional support), EPA supplement (capsule or enriched ONS or ETF) vs. routine care (no supplement or standard supplement), ETF vs. parenteral nutrition (PN). The reviewed outcomes were dietary intake, anthropometry, clinical (mortality, length of hospital stay, complications, and quality of life) and haematological/biochemical (white blood cell count, serum transferrin and albumin, CD3-positive lymphocytes, and inflammatory markers). Meta-analyses were performed where possible. In patients undergoing radiotherapy, meta-analysis showed that ONS significantly increase dietary intake (381 kcal/day, 95% CI 193 to 569 in 3 RCTs) compared to routine care. In patients undergoing surgery, meta-analyses showed that ETF results in a significantly shorter length of hospital stay (1.72 fewer days, 95% CI 0.90 to 2.54 in 8 RCTs), lower incidence of any complications (OR 0.62, 95% CI 0.50 to 0.77 in 4 RCTs) and infectious complications (OR 0.67, 95% CI 0.55 to 0.82 in 11 RCTs) and lower sepsis scores (2.21 points, 95% CI 1.49 to 2.92 in 2 RCTs), but no difference in mortality (OR 0.72, 95% CI 0.40 to 1.29 in 7 RCTs) compared to PN. There was also no difference in mortality between ONS or ETF vs. routine care in patients undergoing chemotherapy/radiotherapy (OR 1.00, 95% CI 0.62-1.61 in 4 RCTs) or surgery (OR 2.44, 95% CI 0.75 to 7.95 in 4 RCTs). Individual studies of EPA supplementation as capsules showed improvements in survival, complications and inflammatory markers in patients undergoing bone marrow transplant (BMT). In palliative care patients receiving EPA-enriched ONS or capsules, there were inconsistent positive effects on survival and quality of life. In those undergoing surgery, EPA-enriched ETF had no effect. Further research is required to elucidate the clinical efficacy of enteral nutrition support, including the potential benefits of EPA supplementation, in patients with cancer.


Elamin, E. M., M. Glass, et al. (2006). "Pharmacological approaches to ameliorating catabolic conditions." Curr Opin Clin Nutr Metab Care 9(4): 449-54.

            PURPOSE OF REVIEW: Nutritional debilitation is among the most devastating and life-threatening aspect of various diseases. It arises from a complex interaction between the illness and the host. This process includes cytokine production, release of lipid-mobilizing and proteolysis-inducing factors, and alterations in intermediary metabolism. As a result, many patients develop cachexia with progressive body fat and muscle tissue wasting with associated worsening of their clinical status and a lower quality of life. In this review, up-to-date information about different approaches to pharmacologic management of cachexia will be addressed. RECENT FINDINGS: Until recently, the two major options for pharmacological therapy were either progestational agents or corticosteroids. Knowledge of the mechanisms of cachexia, however, has led to newer therapeutic interventions for treating several aspects of the syndrome. These include antiserotonergic agents, branched-chain amino acids, eicosapentaenoic acid, cannabinoids, melatonin, and thalidomide--all of which act on the feeding-regulatory circuitry to increase appetite and inhibit illness-derived catabolic factors. SUMMARY: Information from this review will guide health care providers in limiting weight loss and improving performance status of cachectic patients through pharmacological therapy, with the hope that such therapy will extend patients' survival and improve their qualities of life.


DeMichele, S. J., S. M. Wood, et al. (2006). "A nutritional strategy to improve oxygenation and decrease morbidity in patients who have acute respiratory distress syndrome." Respir Care Clin N Am 12(4): 547-66, vi.

            Enteral nutrition is increasingly becoming the standard of care for critically ill patients with the goal of providing nutritional support that prevents nutritional deficiencies and reduces morbidity. Furthermore, the development of nutritional strategies that dampen inflammation is an encouraging advance in the management of patients who have acute respiratory distress syndrome. This article discusses evidence from randomized, controlled studies that the use of a specialized nutritional formula containing eicosapentaenoic acid plus gamma-linolenic acid and elevated antioxidants offer physiologic and anti-inflammatory benefits over standard formulas.


Das, U. N. (2006). "Essential fatty acids: biochemistry, physiology and pathology." Biotechnol J 1(4): 420-39.

            Essential fatty acids (EFAs), linoleic acid (LA), and alpha-linolenic acid (ALA) are essential for humans, and are freely available in the diet. Hence, EFA deficiency is extremely rare in humans. To derive the full benefits of EFAs, they need to be metabolized to their respective long-chain metabolites, i.e., dihomo-gamma-linolenic acid (DGLA), and arachidonic acid (AA) from LA; and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from ALA. Some of these long-chain metabolites not only form precursors to respective prostaglandins (PGs), thromboxanes (TXs), and leukotrienes (LTs), but also give rise to lipoxins (LXs) and resolvins that have potent anti-inflammatory actions. Furthermore, EFAs and their metabolites may function as endogenous angiotensin-converting enzyme and 3-hdroxy-3-methylglutaryl coenzyme A reductase inhibitors, nitric oxide (NO) enhancers, anti-hypertensives, and anti-atherosclerotic molecules. Recent studies revealed that EFAs react with NO to yield respective nitroalkene derivatives that exert cell-signaling actions via ligation and activation of peroxisome proliferator-activated receptors. The metabolism of EFAs is altered in several diseases such as obesity, hypertension, diabetes mellitus, coronary heart disease, schizophrenia, Alzheimer's disease, atherosclerosis, and cancer. Thus, EFAs and their derivatives have varied biological actions and seem to be involved in several physiological and pathological processes.


Das, U. N. (2006). "Essential Fatty acids - a review." Curr Pharm Biotechnol 7(6): 467-82.

            Essential fatty acids (EFAs): cis-linoleic acid (LA) and alpha-linolenic acid (ALA) are essential for humans and their deficiency is rare in humans due to their easy availability in diet. EFAs are metabolized to their respective long-chain metabolites: dihomo-gamma-linolenic acid (DGLA), and arachidonic acid (AA) from LA; and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from ALA. Some of these long-chain metabolites form precursors to respective prostaglandins (PGs), thromboxanes (TXs), and leukotrienes (LTs), lipoxins (LXs) and resolvins. EFAs and their metabolites may function as endogenous angiotensin converting enzyme and HMG-CoA reductase inhibitors, nitric oxide enhancers, anti-hypertensives, and anti-atherosclerotic molecules. EFAs react with nitric oxide (NO) to yield respective nitroalkene derivatives that have cell-signaling actions via ligation and activation of peroxisome proliferator-activated receptors (PPARs). In several diseases such as obesity, hypertension, diabetes mellitus, coronary heart disease, alcoholism, schizophrenia, Alzheimer's disease, atherosclerosis, and cancer the metabolism of EFAs is altered. Thus, EFAs and their derivatives have significant clinical implications.


Chiang, N. and C. N. Serhan (2006). "Cell-cell interaction in the transcellular biosynthesis of novel omega-3-derived lipid mediators." Methods Mol Biol 341: 227-50.

            Omega-3 polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA) and docosa-hexaenoic acid (DHA) display beneficial actions in human diseases. The molecular basis for these actions remains of interest. We recently identified novel mediators generated from omega-3 PUFA during cell-cell interactions that displayed potent anti-inflammatory and proresolving actions. Compounds derived from EPA are designated resolvins of the E series (RvE1), and those biosynthesized from DHA are denoted resolvins of the D series (RvD) and docosatriene, such as protectin D1 (PD1), which belongs to the family of protectins. In addition, treatment using aspirin initiates a related epimeric series by triggering endogenous formation of the 17R-RvD series, denoted as aspirin-triggered (AT)-RvDs. These compounds possess potent anti-inflammatory actions in vivo that essentially are equivalent to their counterpart generated without aspirin, namely the 17S-RvDs. In this chapter, we provide an overview and detail protocols of the biosynthesis and bioactions of these newly uncovered pathways and products that include three distinct series: 18R-resolvins of the E series derived from EPA (i.e., RvE1); 17R-resolvins of the D series from DHA (AT-RvD1 through RvD4); and 17S-resolvins of the D series from DHA (RvD1 through RvD4).


Carpentier, Y. A., L. Portois, et al. (2006). "n-3 fatty acids and the metabolic syndrome." Am J Clin Nutr 83(6 Suppl): 1499S-1504S.

            The metabolic syndrome is defined as the coexistence of 3 or more components, some of which indicate alterations in glucose and lipid metabolism. The prevalence of the metabolic syndrome is rapidly increasing in relation to obesity, and it is considered to be an important predictor of cardiovascular disease. Increased intakes or supplements of n-3 marine fatty acids may improve defects in insulin signaling and prevent alterations in glucose homeostasis and the further development of type 2 diabetes. This is largely mediated through a reduction in fatty acid accumulation in muscle and liver. n-3 Polyunsaturated fatty acids (n-3 PUFAs) reduce plasma triacylglycerols and improve the lipoprotein profile by decreasing the fraction of atherogenic small, dense LDL. However, n-3 PUFAs do not lower LDL cholesterol. These effects are likely mediated through the activity of transcription factors relating to expression of genes involved in lipid oxidation and synthesis. Other pleiotrophic effects of n-3 PUFAs may contribute to decreasing the burden of the metabolic syndrome, such as modulating inflammation, platelet activation, endothelial function, and blood pressure. Although studies comparing the effect of both major n-3 PUFAs are limited, docosahexaenoic acid appears at least as efficient as eicosapentaenoic acid in correcting several risk factors. The use of n-3 PUFAs should be considered in more global strategies including changes in lifestyle, such as adhering to a healthy Mediterranean type of diet and practicing regular physical exercise.


Burdge, G. C. (2006). "Metabolism of alpha-linolenic acid in humans." Prostaglandins Leukot Essent Fatty Acids 75(3): 161-8.

            Alpha-linolenic acid (18:3n-3) is essential in the human diet, probably because it is the substrate for the synthesis of longer-chain, more unsaturated n-3 fatty acids eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3) which are required for tissue function. This article reviews the recent literature on 18:3n-3 metabolism in humans, including fatty acid beta-oxidation, recycling of carbon by fatty acid synthesis de novo and conversion to longer-chain polyunsaturated fatty acids (PUFA). In men, stable isotope tracer studies and studies in which volunteers increased their consumption of 18:3n-3 show conversion to 20:5n-3 and 22:5n-3, but limited conversion to 22:6n-3. However, conversion to 18:3n-3 to 20:5n-3 and 22:6n-3 is greater in women compared to men, due possibly to a regulatory effect of oestrogen, while partitioning of 18:3n-3 towards beta-oxidation and carbon recycling was lower than in men. These gender differences may be an important consideration in making dietary recommendations for n-3 PUFA intake.


Burdan, F., A. Chalas, et al. (2006). "[Cyclooxygenase and prostanoids--biological implications]." Postepy Hig Med Dosw (Online) 60: 129-41.

            Arachidonic acid is the main precursor of eikosanoids, which regulate the function of various organs and systems. It is released from cellular membrane phospholipids by phospholipase A2 or indirectly by phospholipases C and D. Prostaglandins, prostacyclin (PGI2), and thromboxane A2 (TAX2) are synthesized from arachidonic acid on a metabolic pathway dependent on prostaglandin H2 synthase activity, also known as cyclooxygenase (COX). Of the 12 prostaglandins, the most potent are PGD2, PGE2, and PGF2. The others are synthesized in a primary step of arachidonic acid transformation (PGG2, PGH2), by degradation of the above-mentioned prostaglandins, or are not presented physiologically and may be chemically generated (PGK2, PGL2). Similar compounds could originate from dihomo-gamma-linolenic, alpha-linoleic, and eicosapentaenoic acids. Three primary COX isoenzymes are distinguished: COX-1 (constitutive), COX-2 (inducible), and COX-3, which is detected mainly in the central nervous system. A number of partial forms of COX-1 and COX-2 are also known, but their biological functions have not been well evaluated. Although they differ in genes, transcription factors, primary protein structure, reactivity to substrates, and drugs which inhibit enzyme activity, the crystal structure is similar for all the izoenzymes. In contrast to the COX-1 gene, whose expression is typical for most of the cells, constant COX-2 expression was detected in the placenta and fetal tissue in late pregnancy. In the postnatal period, COX-2 expression decreases rapidly physiologically, and is observed in kidney, forebrain, spinal cord, as well as some other organs, but to a minor degree. It increases in inflammatory, degenerative, and neoplastic processes.


Breslow, J. L. (2006). "n-3 fatty acids and cardiovascular disease." Am J Clin Nutr 83(6 Suppl): 1477S-1482S.

            The results of prospective cohort studies indicate that consuming fish or fish oil containing the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is associated with decreased cardiovascular death, whereas consumption of the vegetable oil-derived n-3 fatty acid a-linolenic acid is not as effective. Randomized control trials (RCTs) in the context of secondary prevention also indicate that the consumption of EPA plus DHA is protective at doses <1 g/d. The therapeutic effect appears to be due to suppression of fatal arrhythmias rather than stabilization of atherosclerotic plaques. At doses >3 g/d, EPA plus DHA can improve cardiovascular disease risk factors, including decreasing plasma triacylglycerols, blood pressure, platelet aggregation, and inflammation, while improving vascular reactivity. Mainly on the basis of the results of RCTs, the American Heart Association recommends that everyone eat oily fish twice per week and that those with coronary heart disease eat 1 g/d of EPA plus DHA from oily fish or supplements. Directions for future research include (1) RCTs to confirm the initial trials showing that EPA plus DHA decreases cardiovascular death and additional studies to determine whether this effect is due to EPA, DHA, or the combination; the dosage of the effective components; and whether the mechanism of action in humans is prevention of fatal arrhythmias. (2) Clinical studies to determine whether the reduction in cardiovascular disease risk factors is due to EPA, DHA, or the combination and the dosage of the effective components. (3) Clinical studies to determine whether vegetable oil-derived alpha-linolenic acid added to a diet enriched in n-6 fatty acids can effectively substitute for fish oil-derived EPA plus DHA.


Berger, G. E., S. Smesny, et al. (2006). "Bioactive lipids in schizophrenia." Int Rev Psychiatry 18(2): 85-98.

            Bioactive lipids, in particular arachidonic acid (AA), are vital for monoaminergic neurotransmission, brain development and synaptic plasticity. Phospholipases A2 (PLA2) are key-enzymes in AA metabolism and are activated during monoaminergic neurotransmission. Reduced membrane AA levels, and an altered activity of PLA2 have been found in peripheral membranes of drug-naive patients with schizophrenia with some conflicting results in more chronic patient populations. Furthermore, in vivo brain phosphorus-31 magnetic resonance spectroscopy suggests reduced lipid membrane precursors (phosphomonoesters) and increased membrane breakdown products (phosphodiesters) in drug-naive or early treated first-episode schizophrenia patients compared to age-matched controls or chronic populations and these changes were correlated with peripheral red blood cell membrane AA levels. We postulate that processes modulating membrane lipid metabolism are associated with psychotic illnesses and might partially explain the mechanism of action of antipsychotic agents, as well as experimental agents such as purified ethyl-eicosapentaenoic acid (E-EPA). Recent supplementation trials suggest that E-EPA is a modestly effective augmentation treatment resulting in reduced doses of antipsychotic medication in acutely ill patients with schizophrenia (but not in residual-type schizophrenia). This review investigates the role of bioactive lipids in schizophrenia and its treatment, as well as its potential use in prevention.


Bays, H. (2006). "Clinical overview of Omacor: a concentrated formulation of omega-3 polyunsaturated fatty acids." Am J Cardiol 98(4A): 71i-76i.

            Omacor (omega-3-acid ethyl esters; Reliant Pharmaceuticals, Inc., Liberty Corner, NJ) is a highly purified, prescription omega-3 fatty acid formulation with high concentrations of eicosapentaenoic acid (EPA) (465 mg) and docosahexaenoic acid (DHA) (375 mg) in each 1-g capsule, along with 4 mg (6 IU) of vitamin E. At a typical dose of 4 capsules/day, Omacor significantly lowers plasma triglyceride levels either as monotherapy or in combination with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) or fibrates. Omacor also modestly increases plasma levels of low-density lipoprotein cholesterol, increases high-density lipoprotein cholesterol levels, and has favorable effects on lipoprotein particle size and subclass distribution. Omacor is well tolerated, with few side effects other than mild gastrointestinal symptoms. Hyperglycemia, abnormal bleeding, elevations in muscle or liver enzymes, and/or abnormalities in kidney or nerve function have not been reported. Through its intensive purification process, Omacor has minimal "fishy" smell and taste, and it has not been reported to cause hypervitaminosis or illness due to exposure to environmental toxins. Omacor provides a safe, effective, well-tolerated approach to management of hypertriglyceridemia.


Arterburn, L. M., E. B. Hall, et al. (2006). "Distribution, interconversion, and dose response of n-3 fatty acids in humans." Am J Clin Nutr 83(6 Suppl): 1467S-1476S.

            n-3 Fatty acids have important visual, mental, and cardiovascular health benefits throughout the life cycle. Biodistribution, interconversion, and dose response data are reviewed herein to provide a basis for more rational n-3 dose selections. Docosahexaenoic acid (DHA) is the principal n-3 fatty acid in tissues and is particularly abundant in neural and retinal tissue. Limited storage of the n-3 fatty acids in adipose tissue suggests that a continued dietary supply is needed. A large proportion of dietary alpha-linolenic acid (ALA) is oxidized, and because of limited interconversion of n-3 fatty acids in humans, ALA supplementation does not result in appreciable accumulation of long-chain n-3 fatty acids in plasma. Eicosapentaenoic acid (EPA) but not DHA concentrations in plasma increase in response to dietary EPA. Dietary DHA results in a dose-dependent, saturable increase in plasma DHA concentrations and modest increases in EPA concentrations. Plasma DHA concentrations equilibrate in approximately 1 mo and then remain at steady state throughout supplementation. DHA doses of approximately 2 g/d result in a near maximal plasma response. Both dietary DHA and EPA reduce plasma arachidonic acid concentrations. Tissue contents of DHA and EPA also increase in response to supplementation with these fatty acids. Human milk contents of DHA are dependent on diet, and infant DHA concentrations are determined by their dietary intake of this fatty acid. We conclude that the most predictable way to increase a specific long-chain n-3 fatty acid in plasma, tissues, or human milk is to supplement with the fatty acid of interest.


Arends, J., G. Bodoky, et al. (2006). "ESPEN Guidelines on Enteral Nutrition: Non-surgical oncology." Clin Nutr 25(2): 245-59.

            Enteral nutrition (EN) by means of oral nutritional supplements (ONS) and tube feeding (TF) offers the possibility of increasing or ensuring nutrient intake in cases where normal food intake is inadequate. These guidelines are intended to give evidence-based recommendations for the use of ONS and TF in cancer patients. They were developed by an interdisciplinary expert group in accordance with officially accepted standards, are based on all relevant publications since 1985 and were discussed and accepted in a consensus conference. Undernutrition and cachexia occur frequently in cancer patients and are indicators of poor prognosis. EN should be started if undernutrition already exists or if food intake is markedly reduced for more than 7-10 days. Standard formulae are recommended for EN. Nutritional needs generally are comparable to non-cancer subjects. In cachectic patients metabolic modulators such as progestins, steroids and possibly eicosapentaenoic acid may help to improve nutritional status. EN is indicated preoperatively for 5-7 days in cancer patients undergoing major abdominal surgery. During radiotherapy of head/neck and gastrointestinal regions dietary counselling and ONS prevent weight loss and interruption of radiotherapy. Routine EN is not indicated during (high-dose) chemotherapy.

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