(R)-Boc-2-amino-3-propargylsulfanyl-propionic acid DCHA

Life expectancy is increasing and so is the prevalence of age-related non-communicable diseases (NCDs). Consequently, older people and patients present with multi-morbidities and more complex needs, putting significant pressure on healthcare systems. Effective nutrition interventions could be an important tool to address patient needs, improve clinical outcomes and reduce healthcare costs. Inflammation plays a central role in NCDs, so targeting it is relevant to disease prevention and treatment. The long-chain omega-3 polyunsaturated fatty acids (omega-3 LCPUFAs) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are known to reduce inflammation and promote its resolution, suggesting a beneficial role in various therapeutic areas. An expert group reviewed the data on omega-3 LCPUFAs in specific patient populations and medical conditions. Evidence for benefits in cognitive health, age- and disease-related decline in muscle mass, cancer treatment, surgical patients and critical illness was identified. Use of DHA and EPA in some conditions is already included in some relevant guidelines. However, it is important to note that data on the effects of omega-3 LCPUFAs are still inconsistent in many areas (e.g., cognitive decline) due to a range of factors that vary amongst the trials performed to date; these factors include dose, timing and duration; baseline omega-3 LCPUFA status; and intake of other nutrients. Well-designed intervention studies are required to optimize the effects of DHA and EPA in specific patient populations and to develop more personalized strategies for their use.

Omega-3 fatty acids, particularly docosahexaenoic fatty acid (DHA), are widely recognized to impact fetal and infant neurodevelopment. The impact of DHA on brain development, and its inefficient synthesis from the essential alpha-linolenic acid (ALA), has led to recommended DHA intakes of 250-375 mg eicosapentaenoic acid + DHA/day for pregnant and lactating women by the Dietary Guidelines for Americans. Despite these recommendations, the intake of omega-3s in women of child-bearing age in the US remains very low. The low maternal status of DHA prior to pregnancy could impair fetal neurodevelopment. This review focuses on maternal omega-3 status in conditions of gestational diabetes mellitus (GDM) and preeclampsia, and the subsequent impact on placental transfer and cord blood concentration of omega-3s. Both GDM and preeclampsia are associated with altered maternal omega-3 status, altered placental omega-3 metabolism, reduced cord blood omega-3 levels and have an impact on neurodevelopment in the infant and on brain health later in life. These findings indicate lower DHA exposure of the developing baby may be driven by lower placental transfer in both conditions. Thus, determining approaches which facilitate increased delivery of DHA during pregnancy and early development might positively impact brain development in infants born to mothers with these diseases.

Dietary and supplemental intake of the ω-3 fatty acid docosahexaenoic acid (DHA) reduces risk of Alzheimer's disease (AD) and ameliorates symptoms. The apolipoprotein E ( APOE) 4 allele is the strongest risk factor for sporadic AD, exclusive of age. APOE4 carriers respond well to the DHA present in fish but do not respond as well to dietary supplements. The mechanisms behind this varied response remain unknown. I posit that the difference is that fish contain DHA in phospholipid form, whereas fish oil supplements do not. This influences whether DHA is metabolized to nonesterified DHA (free DHA) or a phospholipid form called lysophosphatidylcholine DHA (DHA-lysoPC). Free DHA is transported across the outer membrane leaflet of the blood-brain barrier (BBB) via passive diffusion, and DHA-lysoPC is transported across the inner membrane leaflet of the BBB via the major facilitator superfamily domain-containing protein 2A. I propose that APOE4 carriers have impaired brain transport of free DHA but not of DHA-lysoPC, as a consequence of a breakdown in the outer membrane leaflet of the BBB, putting them at increased risk for AD. Dietary sources of DHA in phospholipid form may provide a means to increase plasma levels of DHA-lysoPC, thereby decreasing the risk of AD.-Patrick, R. P. Role of phosphatidylcholine-DHA in preventing APOE4-associated Alzheimer's disease.