Biological Activities of Omega-3 Fatty Acids
Both of the omega-3 LC-PUFA, EPA and DHA, participate in diverse biologic activities that are thought to be beneficial to human health, most prominently in the regulation of immune function. These immune-modulating activities include eicosanoid metabolism, regulation of gene expression, cellular signaling and membrane organization. The omega-3 and omega-6 LC-PUFA are biologically active as precursors of eicosanoids (lipid mediators), including prostaglandins, leukotrienes, isoprostanes, lipoxins and thromboxanes.
Omega-3 fatty acids may act to decrease the inflammatory response by competitive inhibition of the proinflammatory effects of omega-6 dietary fats. Omega-3 fatty acid ingestion promotes synthesis of the prostaglandin E3 series, while ingestion of arachidonic acid and omega-6 fats promote the synthesis of the more potent prostaglandin E2 series, which, in turn, leads to increased synthesis of the proinflammatory cytokines. In particular, the ratio of omega-6 to omega-3 fatty acids may determine the degree of activation of the inflammatory response system and inflammatory cytokine production. Studies involving human dietary supplementation with linoleic acid (omega-6)-rich vegetable oil have demonstrated stimulation of IL-1 and TNF-α production, while studies involving supplementation with fish oil or omega-3-rich flaxseed oil have shown reduction in production of IL-1, IL-2 and TNF-α. In a study of the relationship of dietary supplementation with fish oil, flaxseed oil and sunflower oil, a dose–response relationship was demonstrated between mononuclear cell EPA and the degree of inhibition of cytokine production, particularly TNF-α and IL-1β. Similarly, in a review of five studies of dietary fish oil supplementation, James et al. identified reports of inhibition of TNF-α and IL-1β ranging from 40 to 90%.
In addition to DHA and EPA, recent research has found metabolites of omega-3 fatty acids to be biologically important as well. These mediators have potent anti-inflammatory effects and are named resolvins and protectins, with D- and E-series resolvins deriving from DHA and EPA, respectively. Protectins are derived from DHA.[6,11]
Dietary DHA is incorporated into neural and plasma cell membranes. In the brain, incorporation of DHA into cell membranes results in increased fluidity and permeability.[12,13] These alterations in membrane properties determine the binding or release of neurotransmitters, thus affecting cellular signaling. In situations of dietary deficiency of DHA, the omega-6 series LC-PUFA docosapentaenoic acid is incorporated into the membrane, altering its biochemical properties. In animal models, dietary omega-3 fatty acid deficiency has induced abnormalities in the dopaminergic and serotonergic neurotransmission systems. DHA may also quicken neurotransmission by enhancing glutamatergic synaptic activity. In a neonatal mouse model, treatment of cultured hippocampal neurons with DHA significantly increased spontaneous synaptic activity compared with neurons treated with arachidonic acid or controls.
Omega-3 fatty acids have both pro- and anti-apoptotic features, depending on the tissue and organ system. In human retinal pigment epithelial cells, neuroprotectin D1, a metabolite of DHA, exerts prominent antiapoptotic properties by upregulating the antiapoptotic proteins Bcl-2 and Bcl-xL and decreasing proapoptotic Bax and Bad expression.[17,18] Likewise, in a rat model of perinatal brain injury, dietary omega-3 fatty acid supplementation (max EPA) of pregnant rats prevented hypothyroidism-induced apoptosis in the developing rat cerebellum. Neuroprotectin D1 also counteracts leukocyte infiltration, NF-κB activation and proinflammatory gene expression in brain ischemia–reperfusion. By contrast, in several neoplastic disorders, including acute myeloid leukemia, as well as breast, ovarian, pancreatic, prostate, renal and colorectal cancer, DHA may exert antineoplastic properties by promoting tumor cell apoptosis.[21,22]
In addition, many nonobstetrical studies have focused on the antioxidant properties of omega-3 LC-PUFA. In a gynecologic population, Mehendale et al. studied elevated levels of malondialdehyde, an oxidative stress marker, in women with infertility. This study showed that plasma EPA and erythrocyte DHA levels were reduced in this population of infertile women with elevated oxidative markers. Likewise, in an animal model of coronary artery disease, Benson et al. demonstrated the protective role of omega-3 fatty acids against atherogenic index and lipid peroxidation, two indices of endogenous antioxidant properties in normal and stressed rodents. These studies demonstrated that both the quantity of omega-3 fatty acids in dietary oil and the type of fatty acid, omega-3-rich fats specifically, are important in integrating themselves into the oxidative stress process.
Box 1 summarizes the biologic activities of omega-3 fatty acids.
Expert Rev of Obstet Gynecol. 2010;5(1):125-138. © 2010
Cite this: Role of Omega-3 Fatty Acids in Maternal, Fetal, Infant and Child Wellbeing - Medscape - Jan 01, 2010.