Essential fatty acid supplementation of DHA and ARA and effects on neurodevelopment across animal species: a review of the literature

Abstract

Docosahexanoic acid (DHA) and arachidonic acid (ARA) are long chain essential fatty acids used as supplements in commercial infant formula. DHA/ARA deficient states are associated with adverse neurological outcomes in animals and humans. Preterm infants are at risk for DHA/ARA deficiency. A few clinical reports on the effects of fatty acid supplementation have shown benefit in preterm, low birth weight, and normal infants in the first year of life, whereas others did not. Studies in animals have reported shortened gestation, fetal growth retardation, reduced infant body mass, and increased fetal mortality with consumption of fatty acids during pregnancy. To understand the data that support fatty acid supplementation in infant formula, a review of the animal model literature was undertaken, to examine the effects of DHA/ARA on neurodevelopment, including the effects on visual acuity. Several points emerged from this review. (1) Animal studies indicate that requirements for DHA/ARA vary depending on developmental age. Alterations of the ratio of DHA/ARA can impact developmental outcome. (2) The available studies suggest that while supplementation of DHA/ARA in an appropriate ratio can increase tissue levels of these fatty acids in the brain and retina, tissues sensitive to depletion of fatty acids, the benefit of routine supplementation remains unclear. Few studies measure functional outcome relative to changes in physiologic pools of DHA/ARA after supplementation. (3) Animal literature does not support a clear long-term benefit of replenishing DHA/ARA tissue levels and administration of these fatty acids at concentrations above those in human milk suggests adverse effects on growth, survival, and neurodevelopment.

LPIAT1 regulates arachidonic acid content in phosphatidylinositol and is required for cortical lamination in mice

“…Human infants, as well as neonatal animals, have a reduced ability to elongate/desaturate fatty acids to an appropriate degree, and supplementation with linoleic acid and linolenic acid is not sufficient to overcome a PUFA-deficiency state (Abad-Jorge, 2008). AA is preferentially transferred across the placenta compared with other n-6 fatty acids (Davis-Bruno and Tassinari, 2011). Moreover, a neurological optimality score that quantifies the quality of neonatal neurological functioning is positively related with AA but not with other n-6 fatty acids (Dijck-Brouwer et al.…”

Physical activity level is impaired and diet dependent in preterm newborn pigs

“…Growth rate and nutrient intakes in early life may affect later neuromuscular and cognitive outcomes, but the mechanisms are largely unknown (10). Much focus has been devoted to the possible role of the lipid fraction of milk, but firm evidence for diet effects are lacking, not only in infants (11) but also in various animal models (12). In addition to the direct effects of nutrients and dietary factors on neurodevelopmental endpoints, indirect effects may arise from links between the early diet on gut growth, enteric nervous system, signaling molecules like serotonin (5-HT), and/ or gut microbiota.…”

Role and Progress of DHA Dietary Supply in Brain Development of Maternal and Golden Periods

“…To maintain homeostasis of DHA (5.2 mg/day) in the brain, over 200 mg/day of dietary DHA is needed (Fig.2), assuming that only 1.7% of performed dietary DHA reaches the brain [67][68][69] and the other source is provided from conversion of ALA to DHA 61 . Furthermore, earlier infant will need higher the level of DHA than maternal term, thus contributing the optimal neurodevelopment could be optimum [70][71][72][73] .…”