Role of Omega-3 Fatty Acids in Maternal, Fetal, Infant and Child Wellbeing

Ellen Mozurkewich; Deborah R Berman; Julie Chilimigras


Expert Rev of Obstet Gynecol. 2010;5(1):125-138. 

In This Article

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.[4] The omega-3 and omega-6 LC-PUFA are biologically active as precursors of eicosanoids (lipid mediators), including prostaglandins, leukotrienes, isoprostanes, lipoxins and thromboxanes.[6]

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.[7] 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.[8] 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.[9] 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%.[10]

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.[14] In situations of dietary deficiency of DHA, the omega-6 series LC-PUFA docosapentaenoic acid is incorporated into the membrane, altering its biochemical properties.[15] In animal models, dietary omega-3 fatty acid deficiency has induced abnormalities in the dopaminergic and serotonergic neurotransmission systems.[14] 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.[16]

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.[19] Neuroprotectin D1 also counteracts leukocyte infiltration, NF-κB activation and proinflammatory gene expression in brain ischemia–reperfusion.[20] 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.[23] This study showed that plasma EPA and erythrocyte DHA levels were reduced in this population of infertile women with elevated oxidative markers.[23] 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.[24] 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.[24]

Box 1 summarizes the biologic activities of omega-3 fatty acids.


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