What is the Right Level of DHA in the Infant Diet?: Commentary on article by Hsieh et al. on page 537

Abstract

Docosahexaenoic acid (DHA,) is a most extraordinary molecule, containing six double bonds, about the most that you can fit onto a 22-carbon fatty acid in the methylene-interrupted structure commonly used in the biologic motif. What is even more extraordinary is that the brain and retina concentrate this fatty acid against a concentration gradient and incorporate it at high levels into their membrane phospholipids (1). Although these observations were made several decades ago, the curiosity of lipid biochemists has only recently begun to be assuaged with some appreciation of what the functions of this unusual fatty acid might be. It is now apparent that DHA-phospholipid species subserve a regulatory role for G protein coupled receptors (2) due to their ability to impart unique physical properties to biologic membranes or microenvironments thereof (3). Also of direct relevance to the issue of neurodevelopment is the demonstration that DHA can protect against apoptosis (4,5) and increase neuronal process outgrowth. DHA is also known to be a ligand for the RXR receptor and influence protein expression. It can be made into potent bioactive eicosanoid-like compounds termed neuroprotectins that may play a role in Alzheimer's disease (5). A wealth of animal work has indicated that when the nervous system is deficient in DHA, there are many adverse consequences for brain and retinal function as indicated by behavioral or physiologic endpoints (1,6). It should be no surprise then that leaving DHA out of infant formulas, as was done in the United States and much of the world in the 20 th century, could result in suboptimal neurodevelopment. There have now been many randomized, controlled trials of infant formula with or without DHA, or with DHA and arachidonic acid (ARA) as the key variable. Many of these studies, although not all, have shown a benefit for DHA in the range of from 0.12-0.36 wt% for nervous system function or development (7).These studies then lead to the question as to the level of DHA in human milk and the infant diet. A recent sampling of human milk DHA content in nine countries indicates a range of from a low of 0.17 wt% in both the United States and Canada to a high of 0.99 wt% in Japan (8). It was of interest that milk ARA content was more consistent with a value of around 0.4 wt% across these countries with their varied diets. The considerable variation in milk DHA content is a direct result of the varying levels of DHA intake in these populations and the milk content can be readily manipulated by increasing DHA intake (9). The low level of DHA observed in women in the Northern Hemisphere is due to their very low intake of preformed DHA.In the featured work in this issue of Pediatric Research, Hsieh and colleagues, working in Tom Brenna's laboratory, demonstrated that when DHA is added to formula fed to newborn baboons in a range similar to that found in some human infant formulas (0.33 wt% theoretical and 0.42 wt% actual), that brain DHA content was significantly increased in the plasma, erythrocyte...