The importance of the ratio of omega-6/omega-3 essential fatty acids.

Several sources of information suggest 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 15/1-16.7/1. Western diets are deficient in omega-3 fatty acids, and have excessive amounts of omega-6 fatty acids compared with the diet on which human beings evolved and their genetic patterns were established. Excessive amounts of omega-6 polyunsaturated fatty acids (PUFA) and a very high omega-6/omega-3 ratio, as is found in today's Western diets, promote the pathogenesis of many diseases, including cardiovascular disease, cancer, and inflammatory and autoimmune diseases, whereas increased levels of omega-3 PUFA (a lower omega-6/omega-3 ratio), exert suppressive effects. In the secondary prevention of cardiovascular disease, a ratio of 4/1 was associated with a 70% decrease in total mortality. A ratio of 2.5/1 reduced rectal cell proliferation in patients with colorectal cancer, whereas a ratio of 4/1 with the same amount of omega-3 PUFA had no effect. The lower omega-6/omega-3 ratio in women with breast cancer was associated with decreased risk. A ratio of 2-3/1 suppressed inflammation in patients with rheumatoid arthritis, and a ratio of 5/1 had a beneficial effect on patients with asthma, whereas a ratio of 10/1 had adverse consequences. These studies indicate that the optimal ratio may vary with the disease under consideration. This is consistent with the fact that chronic diseases are multigenic and multifactorial. Therefore, it is quite possible that the therapeutic dose of omega-3 fatty acids will depend on the degree of severity of disease resulting from the genetic predisposition. A lower ratio of omega-6/omega-3 fatty acids is more desirable in reducing the risk of many of the chronic diseases of high prevalence in Western societies, as well as in the developing countries.

/pdf/the-importance-of-the-omega-6-omega-3-fatty-acid-ratio-in-30qzf7e9ue.pdf

The Importance of the Omega-6/Omega-3 Fatty Acid Ratio in Cardiovascular Disease and Other Chronic Diseases

Among the fatty acids, it is the omega-3 polyunsaturated fatty acids (PUFA) which possess the most potent immunomodulatory activities, and among the omega-3 PUFA, those from fish oil— eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)—are more biologically potent than -linolenic acid (ALA). Some of the effects of omega-3 PUFA are brought about by modulation of the amount and types of eicosanoids made, and other effects are elicited by eicosanoid-independent mechanisms, including actions upon intracellular signaling pathways, transcription factor activity and gene expression. Animal experiments and clinical intervention studies indicate that omega-3 fatty acids have anti-inflammatory properties and, therefore, might be useful in the management of inflammatory and autoimmune diseases. Coronary heart disease, major depression, aging and cancer are characterized by an increased level of interleukin 1 (IL-1), a proinflammatory cytokine. Similarly, arthritis, Crohn’s disease, ulcerative colitis and lupus erythematosis are autoimmune diseases characterized by a high level of IL-1 and the proinflammatory leukotriene LTB4 produced by omega-6 fatty acids. There have been a number of clinical trials assessing the benefits of dietary supplementation with fish oils in several inflammatory and autoimmune diseases in humans, including rheumatoid arthritis, Crohn’s disease, ulcerative colitis, psoriasis, lupus erythematosus, multiple sclerosis and migraine headaches. Many of the placebocontrolled trials of fish oil in chronic inflammatory diseases reveal significant benefit, including decreased disease activity and a lowered use of anti-inflammatory drugs. Key teaching points:  In Western diets, omega-6 fatty acids are the predominant polyunsaturated fats. The omega-6 and omega-3 fatty acids are metabolically distinct and have opposing physiologic functions.  Eicosapentaenoic acid (EPA) is released to compete with arachidonic acid (AA) for enzymatic metabolism inducing the production of less inflammatory and chemotactic derivatives.  Animal and human studies support the hypothesis that omega-3 PUFA suppress cell mediated immune responses.  In experimental animals and humans, serum PUFA levels predict the response of proinflammatory cytokines to psychologic stress. Imbalance in the omega-6/omega-3 PUFA ratio in major depression may be related to the increased production of proinflammatory cytokines and eicosanoids in that illness.  The increased omega-6/omega-3 ratio in Western diets most likely contributes to an increased incidence of cardiovascular disease and inflammatory disorders.  Patients with autoimmune diseases, such as rheumatoid arthritis, inflammatory bowel disease and asthma, usually respond to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation by decreasing the elevated levels of cytokines.

Omega-3 Fatty Acids in Inflammation and Autoimmune Diseases

Bias and causal associations in observational research

The Canadian Network for Mood and Anxiety Treatments (CANMAT) previously published treatment guidelines for bipolar disorder in 2005, along with international commentaries and subsequent updates in 2007, 2009, and 2013. The last two updates were published in collaboration with the International Society for Bipolar Disorders (ISBD). These 2018 CANMAT and ISBD Bipolar Treatment Guidelines represent the significant advances in the field since the last full edition was published in 2005, including updates to diagnosis and management as well as new research into pharmacological and psychological treatments. These advances have been translated into clear and easy to use recommendations for first, second, and third- line treatments, with consideration given to levels of evidence for efficacy, clinical support based on experience, and consensus ratings of safety, tolerability, and treatment-emergent switch risk. New to these guidelines, hierarchical rankings were created for first and second- line treatments recommended for acute mania, acute depression, and maintenance treatment in bipolar I disorder. Created by considering the impact of each treatment across all phases of illness, this hierarchy will further assist clinicians in making evidence-based treatment decisions. Lithium, quetiapine, divalproex, asenapine, aripiprazole, paliperidone, risperidone, and cariprazine alone or in combination are recommended as first-line treatments for acute mania. First-line options for bipolar I depression include quetiapine, lurasidone plus lithium or divalproex, lithium, lamotrigine, lurasidone, or adjunctive lamotrigine. While medications that have been shown to be effective for the acute phase should generally be continued for the maintenance phase in bipolar I disorder, there are some exceptions (such as with antidepressants); and available data suggest that lithium, quetiapine, divalproex, lamotrigine, asenapine, and aripiprazole monotherapy or combination treatments should be considered first-line for those initiating or switching treatment during the maintenance phase. In addition to addressing issues in bipolar I disorder, these guidelines also provide an overview of, and recommendations for, clinical management of bipolar II disorder, as well as advice on specific populations, such as women at various stages of the reproductive cycle, children and adolescents, and older adults. There are also discussions on the impact of specific psychiatric and medical comorbidities such as substance use, anxiety, and metabolic disorders. Finally, an overview of issues related to safety and monitoring is provided. The CANMAT and ISBD groups hope that these guidelines become a valuable tool for practitioners across the globe.

/pdf/canadian-network-for-mood-and-anxiety-treatments-canmat-and-3lm5mpt404.pdf

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder

Background ω3 Fatty acids may inhibit neuronal signal transduction pathways in a manner similar to that of lithium carbonate and valproate, 2 effective treatments for bipolar disorder. The present study was performed to examine whether ω3 fatty acids also exhibit mood-stabilizing properties in bipolar disorder. Methods A 4-month, double-blind, placebo-controlled study, comparing ω3 fatty acids (9.6 g/d) vs placebo (olive oil), in addition to usual treatment, in 30 patients with bipolar disorder. Results A Kaplan-Meier survival analysis of the cohort found that the ω3 fatty acid patient group had a significantly longer period of remission than the placebo group ( P =.002; Mantel-Cox). In addition, for nearly every other outcome measure, the ω3 fatty acid group performed better than the placebo group. Conclusion ω3 Fatty acids were well tolerated and improved the short-term course of illness in this preliminary study of patients with bipolar disorder.

https://jamanetwork.com/journals/jamapsychiatry/articlepdf/204999/yoa8185.pdf

Omega 3 Fatty Acids in Bipolar Disorder: A Preliminary Double-blind, Placebo-Controlled Trial

Several distinct classes of agents have demonstrated efficacy as mood stabilizers in patients with bipolar disorder. It may be reasonable to assume that these agents share one or more common mechan...

W. Emanuel Severus

Papers

Omega 3 Fatty Acids in Bipolar Disorder: A Preliminary Double-blind, Placebo-Controlled Trial

Mood Stabilizers: Shared Mechanisms of Action at Postsynaptic Signal-Transduction and Kindling Processes