Impact on Cognitive Development and Inflammation

T he n-3 or 5-3 polyunsaturated fatty acids (n-3 PUFAs) and particularly the long-chain, highly unsaturated ones (LC PUFAs), that is, eicosapentaenoic and docosahexaenoic acid (EPA and DHA), together with LC PUFAs of the n-6 or 5-6 series (ie, arachidonic acid [AA]), are found in appreciable concentrations in the structural membranes of highly specialized organs and systems. Cell membranes with well-developed functional activities (eg excitable and contractile cells) are rich in n-3 PUFA compounds, especially DHA, primarily present in an esterified form in complex glycerophospholipids. Through coordinated and sometimes antagonistic interactions with AA, n-3 PUFAs modulate several key cellular functions (eg, receptor activators, lipid mediators, ion channels, and gene expression). Unlike 5-6, 5-3 and especially EPA and DHA are present in very low concentrations in our diets, being almost exclusively provided by fish and aquatic organisms, whereas their metabolic precursor ! -linolenic acid (LNA) is present only in selected oils and plant food and is not even effectively converted in the body to the LC n-3 PUFAs. This is in contrast to the efficient conversion of the very abundant linoleic acid (LA) to AA in the 5-6 series. Figures 1 and 2 summarize the sources and synthesis of the 5-6 and 5-3 series, respectively. The 5-3 series has been found to provide benefits in multiple diseases. In heart disease, 5-3 series appears to lower (i) blood platelet clotting function, (ii) circulating harmful fats, and (iii) blood pressure and cardiac arrhythmias after modifying membrane fluidity and vessel dilation. There is also evidence of better outcomes in terms of survival, reduced length of hospitalization, and lower rates of infections in cancer patients, in liver diseases, and in critical care patients. The list of other pediatric and adult diseases, which may benefit from the assumption of 5-3 FA, is growing continuously and includes cystic fibrosis, some inborn errors of metabolism, Crohn’s disease, metabolic syndrome and obesity, diabetes, arthritis, osteoporosis, and cognitive impairments such as attention-deficit disorders, mood disorders, and senile dementia. Finally, supplementations during pregnancy and especially during the perinatal period are 2 times in life in which much intensive research is being devoted as a result of a well-defined positive correlation between an adequate preventive supplementation of 5-3 FA and an appropriate mental, neurological, and visual development of the offspring. Overall, the beneficial role of 5-3 FA is exerted through a direct incorporation into cell membranes and the production of metabolites (prostaglandins and leukotrienes), which reduce the negative effects of stress-induced inflammatory responses. The inflammatory response is modulated by both proinflammatory and anti-inflammatory reactions, depending on which type of LC PUFAs is supplemented. In particular, the 5-6 FA series preferentially reinforces inflammation, whereas the 5-3 FA series inhibits it. Thus, this article strives to review the role of 5-3 during prenatal and postnatal periods and its effects on inflammatory conditions.