Omega 3
1: Curr Vasc Pharmacol. 2007 Apr;5(2):163-72.
Cardiovascular effects of omega-3 free Fatty acids.
Cardiologia-UTIC, Ospedale S. Giacomo, Roma, Italy. francesco.biscione@poste.it.
Omega-3 fatty acids are essential substances for the development and function of human organism. They cannot be synthesized in humans, and consequently have to be acquired from food, almost exclusively from fish. Omega-3 fatty acids exert potent anti-inflammatory and anti-atherosclerotic actions by interfering with the metabolism of arachidonic acid, modifying lipid composition (mainly lowering triglycerides), improving hemodynamics and reducing cardiac hypertrophy. Recently, clinical and experimental studies demonstrated an anti-arrhythmic effect and a significant impact on survival after myocardial infarction (MI). It follows that omega-3 fatty acids have been widely accepted for clinical use in patients with dyslipidemia or with atherosclerotic disease and in survivors of acute MI. This review briefly explores the metabolic mechanisms and the clinical effects of this class of substances and considers their use in patients with cardiovascular disease.
PMID: 17430221 [PubMed - in process]
1: J Nutr Health Aging. 2004;8(3):163-74.
Roles of unsaturated fatty acids (especially omega-3 fatty acids) in the brain at various ages and during ageing.
INSERM Research Director. Unit U26 Neuro-pharmaco-nutrition. Hopital Fernand Widal, 200 rue du Faubourg Saint Denis. 75745 Paris cedex 10. jean-marie.bourre@fwidal.inserm.fr
Among various organs, in the brain, the fatty acids most extensively studied are omega-3 fatty acids. Alpha-linolenic acid (18:3omega3) deficiency alters the structure and function of membranes and induces minor cerebral dysfunctions, as demonstrated in animal models and subsequently in human infants. Even though the brain is materially an organ like any other, that is to say elaborated from substances present in the diet (sometimes exclusively), for long it was not accepted that food can have an influence on brain structure, and thus on its function. Lipids, and especially omega-3 fatty acids, provided the first coherent experimental demonstration of the effect of diet (nutrients) on the structure and function of the brain. In fact the brain, after adipose tissue, is the organ richest in lipids, whose only role is to participate in membrane structure. First it was shown that the differentiation and functioning of cultured brain cells requires not only alpha-linolenic acid (the major component of the omega-3, omega3 family), but also the very long omega-3 and omega-6 carbon chains (1). It was then demonstrated that alpha-linolenic acid deficiency alters the course of brain development, perturbs the composition and physicochemical properties of brain cell membranes, neurones, oligodendrocytes, and astrocytes (2).This leads to physicochemical modifications, induces biochemical and physiological perturbations, and results in neurosensory and behavioural upset (3). Consequently, the nature of polyunsaturated fatty acids (in particular omega-3) present in formula milks for infants (premature and term) conditions the visual and cerebral abilities, including intellectual. Moreover, dietary omega-3 fatty acids are certainly involved in the prevention of some aspects of cardiovascular disease (including at the level of cerebral vascularization), and in some neuropsychiatric disorders, particularly depression, as well as in dementia, notably Alzheimer's disease. Recent results have shown that dietary alpha-linolenic acid deficiency induces more marked abnormalities in certain cerebral structures than in others, as the frontal cortex and pituitary gland are more severely affected. These selective lesions are accompanied by behavioural disorders more particularly affecting certain tests (habituation, adaptation to new situations). Biochemical and behavioural abnormalities are partially reversed by a dietary phospholipid supplement, especially omega-3-rich egg yolk extracts or pig brain. A dose-effect study showed that animal phospholipids are more effective than plant phospholipids to reverse the consequences of alpha-linolenic acid deficiency, partly because they provide very long preformed chains. Alpha-linolenic acid deficiency decreases the perception of pleasure, by slightly altering the efficacy of sensory organs and by affecting certain cerebral structures. Age-related impairment of hearing, vision and smell is due to both decreased efficacy of the parts of the brain concerned and disorders of sensory receptors, particularly of the inner ear or retina. For example, a given level of perception of a sweet taste requires a larger quantity of sugar in subjects with alpha-linolenic acid deficiency. In view of occidental eating habits, as omega-6 fatty acid deficiency has never been observed, its impact on the brain has not been studied. In contrast, omega-9 fatty acid deficiency, specifically oleic acid deficiency, induces a reduction of this fatty acid in many tissues, except the brain (but the sciatic nerve is affected). This fatty acid is therefore not synthesized in sufficient quantities, at least during pregnancy-lactation, implying a need for dietary intake. It must be remembered that organization of the neurons is almost complete several weeks before birth, and that these neurons remain for the subject's life time. Consequently, any disturbance of these neurons, an alteration of their connections, and impaired turnover of their constituents at any stage of life, will tend to accelerate ageing. The enzymatic activities of sytivities of synthesis of long-chain polyunsaturated fatty acids from linoleic and alpha-linolenic acids are very limited in the brain: this organ therefore depends on an exogenous supply. Consequently, fatty acids that are essential for the brain are arachidonic acid and cervonic acid, derived from the diet, unless they are synthesized by the liver from linoleic acid and alpha-linolenic acid. The age-related reduction of hepatic desaturase activities (which participate in the synthesis of long chains, together with elongases) can impair turnover of cerebral membranes. In many structures, especially in the frontal cortex, a reduction of cervonic and arachidonic acids is observed during ageing, predominantly associated with a reduction of phosphatidylethanolamines (mainly in the form of plasmalogens). Peroxisomal oxidation of polyunsaturated fatty acids decreases in the brain during ageing, participating in decreased turnover of membrane fatty acids, which are also less effectively protected against peroxidation by free radicals.
PMID: 15129302 [PubMed - indexed for MEDLINE]
1: J Nutr Health Aging. 2005;9(1):31-8.
Dietary omega-3 Fatty acids and psychiatry: mood, behaviour, stress, depression, dementia and aging.
French Academy of Medicine, INSERM department of Neuro-pharmaco-nutrition, Hopital Fernand Widal, 75475 Paris cedex 10. jean-marie.bourre@fwidal.inserm.fr
In view of the high omega-3 poly unsaturated fatty acid content of the brain, it is evident that these fats are involved in brain biochemistry, physiology and functioning; and thus in some neuropsychiatric diseases and in the cognitive decline of ageing. Though omega-3 fatty acids (from fatty fish in the human diet) appear effective in the prevention of stress, their role as regulator of mood and of libido is a matter for discussion pending experimental proof in animal and human models. Dietary omega-3 fatty acids play a role in the prevention of some disorders including depression, as well as in dementia, particularly Alzheimer's disease. Their direct role in major depression, bipolar disorder (manic-depressive disease) and schizophrenia is not yet established. Their deficiency can prevent the renewal of membranes, and thus accelerate cerebral ageing; none the less, the respective roles of the vascular component on one hand (where the omega-3's are active) and the cerebral parenchyma itself on the other, have not yet been clearly resolved. The role of omega-3 in certain diseases such as dyslexia and autism is suggested. In fact, omega-3 fatty acids participated in the first coherent experimental demonstration of the effect of dietary substances (nutrients) on the structure and function of the brain. Experiments were first of all carried out one x-vivo cultured brain cells (1), then on in vivo brain cells(2), finally on physiochemical, biochemical, physiological, neurosensory, and behavioural parameters (3). These findings indicated that the nature of poly unsaturated fatty acids(in particular omega-3) present in formula milks for infants (both premature and term) determines the visual, cerebral,and intellectual abilities, as described in a recent review (4). Indeed,the insufficient dietary supply of omega-3 fatty acids in today's French and occidental diet raises the problem of how to correct dietary habits so that the consumer will select foods that are genuinely rich in omega-3/ the omega-3 family ; mainly rapeseed, (canola) and walnut oils on one hand and fatty fish on the other.
PMID: 15750663 [PubMed - indexed for MEDLINE]
1: Am J Cardiol. 2006 Aug 21;98(4A):61i-70i. Epub 2006 May 30.
Secondary prevention of coronary artery disease with omega-3 fatty acids.
Department of Medicine, Office of Health Promotion and Disease Prevention, Emory University School of Medicine, Atlanta, Georgia 30303, USA. tjaco02@emory.edu
Omega-3 fatty acid therapy is a promising intervention for the secondary prevention of coronary artery disease (CAD). Omega-3 fatty acids have properties that promote atherosclerotic plaque stability and decrease the incidence of ischemia-driven cardiac arrhythmias. A large number of clinical trials conducted in patients with CAD or prior myocardial infarction (MI) have examined hard cardiovascular end points, including total mortality, cardiovascular mortality, sudden death, and nonfatal MI. Several intermediate cardiovascular end-point studies have also examined whether ventricular arrhythmias can be suppressed in patients with implantable cardioverter defibrillators (ICDs). Significant reductions in total mortality and sudden death--20% to 50%--have been found in studies using doses of 0.85 to 4.0 g/day, with treatment durations from 12 to 42 months. Favorable trends toward reduction in the incidence of arrhythmic events have been demonstrated in some, but not all, ICD studies. Omega-3 fatty acid therapy shows a general positive trend toward benefit in reducing life-threatening events after MI and in patients with ICDs who have ischemic arrhythmias. Results of the recent Japan EPA Lipid Intervention Study (JELIS) in a large cohort (N = 18,645) of Japanese men and women suggest significant benefits in the reduction of unstable angina and nonfatal coronary events. The totality of evidence supports a strong role for omega-3 fatty acids derived from fish oil in secondary prevention through a presumptive role as an antiarrhythmic agent and through an ability to promote plaque stabilization.
PMID: 16919518 [PubMed - indexed for MEDLINE]
1: Psychosom Med. 2007 Mar 30; [Epub ahead of print]
Depressive Symptoms, omega-6:omega-3 Fatty Acids, and Inflammation in Older Adults.
Departments of Psychiatry (J.K.K.-G.), Human Nutrition (M.A.B.), Ohio State University Center for Biostatistics (K.P., S.L.), Neurology (D.Q.B.), Ohio State University School of Public Health (S.L.), Molecular Virology, Immunology, and Medical Genetics (R.G.), Ohio State Institute for Behavioral Medicine Research (J.K.K.-G., S.L., R.G.); Ohio State University, Columbus, Ohio.
Objective: To address how interactions between polyunsaturated fatty acid (PUFA) levels and depressive symptoms were related to proinflammatory cytokine synthesis. Depression and stress promote proinflammatory cytokine production. Dietary intakes of omega-3 (n-3) and omega-6 (n-6) PUFAs also influence inflammation; high n-6:n-3 ratios enhance proinflammatory cytokine production, although n-3 has anti-inflammatory properties. Methods: Blood samples from 43 older adults (mean age = 66.67 years, SD = 10.09) provided data on PUFAs and tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-6 soluble receptor (sIL-6r). Depressive symptoms were assessed by the Center for Epidemiological Studies Depression Scale. Results: Depressive symptoms and n-6:n-3 ratios worked together to enhance proinflammatory cytokines beyond the contribution provided by either variable alone, with substantial variance explained by their interaction: 13% for IL-6 and 31% for TNF-alpha, whereas full models accounted for 18% and 40%, respectively. Although predicted cytokine levels were consistent across n-6:n-3 ratios with low depressive symptoms, higher n-6:n-3 ratios were associated with progressively elevated TNF-alpha and IL-6 levels as depressive symptoms increased. Higher levels of sIL-6r were associated with higher n-6:n-3 ratios. Six individuals who met the criteria for major depressive disorder had higher n-6:n-3 ratios and TNF-alpha, IL-6, and sIL-6r levels than those who did not meet the criteria; excluding these six individuals reduced the variance explained by the depressive symptoms and n-6:n-3 ratio interaction. Conclusions: Diets with high n-6:n-3 PUFA ratios may enhance the risk for both depression and inflammatory diseases.
PMID: 17401057 [PubMed - as supplied by publisher]
1: Hepatology. 2007 Apr;45(4):864-9.
Omega-3 fatty acids alleviate chemically induced acute hepatitis by suppression of cytokines.
Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
Cytokines such as tumor necrosis factor alpha (TNF-alpha) are key factors in liver inflammation. Supplementation with essential omega-3 polyunsaturated fatty acids (n-3 PUFA) has been demonstrated to lower TNF-alpha and IL-1 production in mononuclear cells. An inflammation-dampening effect has been observed with increased omega-3 fatty acid supplementation in several inflammatory diseases. In this study, we used the transgenic fat-1 mouse, expressing a Caenorhabditis elegans desaturase endogenously forming n-3 PUFA from n-6 PUFA, to analyze the effect of an increased n-3 PUFA tissue status in the macrophage-dependent acute D-galactosamine/lipopolysaccaride (D-GalN/LPS) hepatitis model. We show less severe inflammatory liver injury in fat-1 mice with a balanced n-6/n-3 PUFA ratio as evidenced by reduced serum alanine aminotransferase levels and less severe histological liver damage. This decreased inflammatory response was associated with decreased plasma TNF-alpha levels and with reduced hepatic gene expression of TNF-alpha, IL-1beta, IFN-gamma and IL-6 in fat-1 mice, leading to a decreased rate of apoptosis in livers from fat-1 animals, as measured by DAPI-staining. Conclusion: The results of this study offer evidence for an inflammation dampening effect of omega-3 polyunsaturated fatty acids in the context of liver inflammation. (HEPATOLOGY 2007;45:864-869.).
PMID: 17393517 [PubMed - in process]
