Poly unsaturated oils / fatty acids

Two families of polyunsaturated fatty acids are distinguished depending on the location of the first double bond counted from the methyl end. The essential fatty acid linoleic acid (C18:2n-6) belongs to the n-6 family. It is found in seeds, e.g. sunflower seeds, and can be converted to the more unsaturated derivative, Arachidonic acid (AA) (C20:4n-6). Food sources of AA are only animal-derived foods such as meat and egg yolk. The fatty acids α-linolenic acid (C18:3n-3), eicosapentaenoic acid (EPA; C20:5n-3) and docosahexaenoic acid (DHA; C22:6n-3) are the most abundant n-3 fatty acids in food. α-Linolenic acid is found in linseed and walnut oil, whereas EPA and DHA are typical fish oil fatty acids, which are contained in oily fishes In addition to their roles in membrane phospholipids, polyunsaturated fatty acids are required for the formation of eicosanoids which are metabolic regulators, for example in immune, cardiovascular and regulatory systems. Eicosanoid members include prostaglandins (PGs), thromboxanes, LTs, hydroxyl acids and lipoxins. For example, AA can be converted to PGE2 and to LTB4, whereas eicosanoids derived from EPA are PGE3 and LTB5. The EPA-derived eicosanoids, PGE3 and LTB5, possess less inflammatory action than do PGE2 or LTB4, both formed from AA. This is why eicosanoids derived from AA can exacerbate inflammatory processes and those derived from EPA exhibit anti-inflammatory properties.

The balance between proinflammatory and anti-inflammatory eicosanoids is influenced in large part by the type of dietary fatty acids consumed. An anti inflammatory diet consists basically of an emphasis on “good fats” (cold water fish, seeds, olive oil, other high quality oils), whole grains, legumes, vegetables, and fruits and the avoidance of “bad fats” (saturated animal fats, trans fats, fried and processed foods, poor quality oils) and refined carbohydrates. In addition, an excessive amount of omega-6 fatty acids in the diet can contribute to inflammatory response.

The primary sources of dietary omega-6 oils are vegetable oils such as corn soy, safflower, and sunflower, while the primary sources of arachidonic acid are meat, eggs, and dairy. Prostaglandin E2 (PGE2) is a prominent eicosanoid derived from the omega-6 fatty acid arachidonic acid. A dominant action of PGE2 as messenger molecules is to enhance sensitivity in pain neurons, increase swelling, and constrict blood vessels. Over-consumption of omega-6 oils provides excess substrate for the synthesis of PGE2, which drives an aggressive and sustained inflammatory response.

Prostaglandin E3 (PGE3) is derived from the omega-3 fatty acid, eicosapentaenoic acid (EPA). Higher levels of PGE3 reduce sensitivity to pain, relax blood vessels, increase blood flow, and support the body’s natural anti-inflammatory response, while both PGE2 and PGE3 are necessary for proper homeostasis, the relative amounts of these competing messenger molecules either contribute to or mitigate chronic inflammatory syndromes. EPA is thought to act by competing with arachidonic acid for binding sites on cyclooxygenase-2 (COX-2), producing a less potent inflammatory mediator, therefore reducing inflammation.

The standard American diet supplies an average omega-6: omega-3 ratio of approximately 11:1. A vegetarian-based diet may put an individual at risk for eating high amounts of vegetable oils and soy products and low amounts of fish, which can tip the balance toward a pro-inflammatory state. Reducing dietary vegetable oils and increasing the omega-3 fats EPA and docosahexaenoic acid (DHA) by consuming fatty fish such as cod and salmon can benefit individuals experiencing chronic inflammatory conditions.

Several herbs used as seasonings, including turmeric, red pepper, cloves, ginger, cumin, anise, fennel basil, rosemary, garlic, and pomegranate, can block nuclear factor-kappaB (NFkB) activation of inflammatory cytokines. Dietary approaches that modify fatty acid intake can influence the eicosanoid profile in such a way that inflammatory processes such as arachidonic acid production and T-cell activation are dampened, while cytokines such as interleukin-4 (the primary cytokine responsible for stimulating a Th2 immune response) are up regulated. Essential fatty acids (EFAs) influence the pathophysiology of psoriasis in three ways: first, EFAs impact the kinetics of cell membranes; second, EFAs impact dermal and epidermal blood flow via improved endothelial function; and third, EFAs act as an immune modulating agent through their impact on eicosanoids. EFAs are used as basic substrates in the development of the phospholipids bi-layer in virtually every cell in the human body, including the dermis and epidermis.

They create structural integrity that regulates fluidity which impacts cell transport, messenger binding, and cell communication. Omega-3 fatty acids can act both directly and indirectly on endothelial function by reducing mononuclear cell cytokines such as IL-1 and TNF- α, decreasing formation of chemo-attractant protein platelet-derived growth factor (PDGF), increasing bioavailability of nitric oxide, and reducing expression of adhesion molecules. The cumulative effect modulating these bioactive mediators is to prevent vascularization, or new blood vessel growth within the psoriatic plaque while simultaneously allowing improved perfusion of dermal tissue. Components of both natural and acquired immunity including the production of key immune modulators can be affected by omega-3 and -6 fatty acid intake, as discussed above.

Immunomodulatory effects of omega-3 fatty acids include suppression of lymphoproliferation CD4+ cells, antigen presentation, adhesion molecule presentation, Th1 and Th2 responses, and pro-inflammatory cytokine production, Several studies have demonstrated the benefit of intravenous or oral supplementation of fish oil for psoriasis. In a study by Mayser et al, intravenous infusion of omega-3 fatty acids led to an increase in the anti-inflammatory leukotriene B5 (LTB5) within 4-7 days of starting treatment, when compared to control patients. In this trial, patients received either an omega3 or omega-6 preparation twice daily for 10 days. No side effects were noted. EPA competes with arachidonic acid (AA) for 5-lipoxygenase and produces LTB5, which is only one-tenth as potent as the inflammatory mediator leukotriene B4 (LTB4). Levels of LTB4 have been shown to be elevated in psoriatic plaques and demonstrate chemotactic properties necessary for infiltration of leukocyte and keratinocyte proliferation.

Also it’s reported that PGE1, PGE2 and PGE3 similarly affect cytokine production in human PBMC. This may implicate that the immunomodulatory effects of PUFAs, with respect to cytokine production, are not caused by a shift in the subtype of PGE. Consequently, other mechanisms may be responsible for selective modulations by PUFAs, including synthesis of specific oxygenated metabolites from the different fatty acids. For example, it was found that DGLA is not converted to a leukotriene product but is converted to a 15-hydroxyl derivative that can block transformation of AA to (proinflammatory) leukotrienes. Individual PUFAs may also differ in their ability to modulate intracellular signalling,such as binding to peroxisome proliferator-activated receptor- γ or changing nuclear factor-kβ activity. Overall, further studies with focus on signaling pathways are necessary to clarify the mechanism of the immunomodulatory effects of PUFAs and the interactions of cytokines and prostaglandins during an inflammatory response .
  
What to Know About Omega-3s and Fish

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"Psoriasis – Pathophysiology, Conventional, and Alternative Approaches to Treatment", Michael Traub, ND, and Keri Marshall MS, ND, Alternative Medicine Review Volume 12, Number 4 2007

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