Maternal nutrition has little or no effect on many nutrients in human milk; for others, human milk may not be designed as a primary nutritional source for the infant; and for a few, maternal ...nutrition can lead to substantial variations in human milk quality. Human milk fatty acids are among the nutrients that show extreme sensitivity to maternal nutrition and are implicated in neurological development. Extensive development occurs in the infant brain, with growth from ∼ 350 g at birth to 925 g at 1 y, with this growth including extensive dendritic and axonal arborization. Transfer of n-6 (omega-6) and n-3 (omega-3) fatty acids from the maternal diet into human milk occurs with little interconversion of 18:2n-6 to 20:4n-6 or 18:3n-3 to docosahexaenoic acid (DHA) and little evidence of mammary gland regulation to maintain individual fatty acids constant with varying maternal fatty acid nutrition. DHA has gained attention because of its high concentrations and roles in the brain and retina. Studies addressing DHA intakes by lactating women or human milk amounts of DHA at levels above those typical in the United States and Canada on infant outcomes are inconsistent. However, separating effects of the fatty acid supply in gestation or in the weaning diet from effects on neurodevelopment solely due to human milk fatty acids is complex, particularly when neurodevelopment is assessed after the period of exclusive human milk feeding. Information on infant fatty acid intakes, including milk volume consumed and energy density, will aid in understanding of the human milk fatty acids that best support neurological development.
Abstract The ω-3 fatty acids are essential dietary nutrients and one of their important roles is providing the fatty acid with 22 carbons and 6 double bonds known as docosahexaenoic acid (DHA) for ...nervous tissue growth and function. Inadequate intakes of ω-3 fatty acids decrease DHA and increase ω-6 fatty acids in the brain. Decreased DHA in the developing brain leads to deficits in neurogenesis, neurotransmitter metabolism, and altered learning and visual function in animals. Western diets are low in ω-3 fatty acids, including the 18 carbon ω-3 fatty acid alpha linolenic acid found mainly in plant oils, and DHA, which is found mainly in fish. The DHA status of the newborn and breast-fed infant depends on the maternal intake of DHA and varies widely. Epidemiological studies have linked low maternal DHA to increased risk of poor child neural development. Intervention studies have shown improving maternal DHA nutrition decreases the risk of poor infant and child visual and neural development. Thus, sufficient evidence is available to conclude that maternal fatty acid nutrition is important to DHA transfer to the infant before and after birth, with short and long-term implications for neural function. However, genetic variation in genes encoding fatty acid desaturases also influence essential fatty acid metabolism, and may increase requirements in some individuals. Consideration of ω-3 fatty acid to include brain development, optimizing ω-3 and ω-6 fatty acids in gestation and lactation, and in fatty acid nutrition support for intravenous and formula-fed neonates is important.
The (n-3) fatty acids are essential dietary nutrients, and one of their important roles is providing docosahexaenoic acid 22:6(n-3) (DHA) for growth and function of nervous tissue. Reduced DHA is ...associated with impairments in cognitive and behavioral performance, effects which are particularly important during brain development. Recent studies suggest that DHA functions in neurogenesis, neurotransmission, and protection against oxidative stress. These functions relate to the roles of DHA within the hydrophobic core of neural membranes and effects of unesterified DHA. Reviewed here are some of the recent studies that have begun to elucidate the role of DHA in brain development and function. A better understanding of development and age-specific changes in DHA transfer and function in the developing brain may provide important insight into the role of DHA in developmental disorders in infants and children, as well as at other stages of the lifespan.
Choline, an essential dietary nutrient for humans, is required for the synthesis of the neurotransmitter, acetylcholine, the methyl group donor, betaine, and phospholipids; and therefore, choline is ...involved in a broad range of critical physiological functions across all stages of the life cycle. The current dietary recommendations for choline have been established as Adequate Intakes (AIs) for total choline; however, dietary choline is present in multiple different forms that are both water-soluble (e.g., free choline, phosphocholine, and glycerophosphocholine) and lipid-soluble (e.g., phosphatidylcholine and sphingomyelin). Interestingly, the different dietary choline forms consumed during infancy differ from those in adulthood. This can be explained by the primary food source, where the majority of choline present in human milk is in the water-soluble form, versus lipid-soluble forms for foods consumed later on. This review summarizes the current knowledge on dietary recommendations and assessment methods, and dietary choline intake from food sources across the life cycle.
Palmitic acid (16:0) is a saturated fatty acid present in the diet and synthesized endogenously. Although often considered to have adverse effects on chronic disease in adults, 16:0 is an essential ...component of membrane, secretory, and transport lipids, with crucial roles in protein palmitoylation and signal molecules. At birth, the term infant is 13-15% body fat, with 45-50% 16:0, much of which is derived from endogenous synthesis in the fetus. After birth, the infant accumulates adipose tissue at high rates, reaching 25% body weight as fat by 4-5 months age. Over this time, human milk provides 10% dietary energy as 16:0, but in unusual triglycerides with 16:0 on the glycerol center carbon. This paper reviews the synthesis and oxidation of 16:0 and possible reasons why the infant is endowed with large amounts of fat and 16:0. The marked deviations in tissues with displacement of 16:0 that can occur in infants fed vegetable oil formulas is introduced. Assuming fetal fatty acid synthesis and the unusual delivery of 16:0 in human milk evolved to afford survival advantage to the neonate, it is timely to question if 16:0 is an essential component of tissue lipids whereby both deficiency and excess are detrimental.
Human milk TG are a remarkable example of stereo-specific positioning of fatty acids with structures that are highly conserved and unusual. Not only does human milk contain high amounts of fat and ...16:0, but ∼70% of the 16:0 is esterified at the TG stereo-specifically numbered (sn)-2 position, with preferential positioning of 18:1(n-9) and 18:2(n-6) at the TG sn-1,3 positions. The milk TG structures and digestive lipases combine to enable efficient digestion and absorption of 16:0 by conserving 16:0 in sn-2 monoacylglycerols, which are absorbed, reassembled, and secreted in plasma conserving the original milk TG configuration; these studies are reviewed in this article. The reason why the mammary gland invests in enzymes to provide the infant with 20–25% milk fatty acids as 16:0 rather than selecting against 16:0 is unknown, yet likely has a purpose given the mammary gland capacity for 10:0, 12:0, and 14:0 synthesis. Recent advances in the development-, tissue-, and species-specific activity of enzymes of TG synthesis and knowledge that dietary TG structures are maintained postabsorption suggest that the purpose of the milk TG structures is more sophisticated than simply avoiding 16:0 malabsorption. The overall aim is to expand consideration of fatty acids in the infant diet from a simple view of average fatty acid compositions to the complex lipids and molecular structures in which fatty acids are provided to tissues during early life and the biology through which the unique features of human milk enable the infant to grow and thrive on a high-fat, high-saturated-fat milk diet.
The enzymes encoded by fatty acid desaturase (FADS) 1 and FADS2 are rate-limiting enzymes in the desaturation of linoleic acid LA; 18:2(n-6) to arachidonic acid ARA; 20:4(n-6), and α-linolenic acid ...ALA; 18:3(n-3) to eicosapentaenoic acid EPA; 20:5(n-3) and docosahexaenoic acid DHA; 22:6(n-3). ARA, EPA, and DHA play central roles in infant growth, neural development, and immune function. The maternal ARA, EPA, and DHA status in gestation influences maternal-to-infant transfer and breast milk provides fatty acids for infants after birth. We determined if single nucleotide polymorphisms in FADS1 and FADS2 influence plasma phospholipid and erythrocyte ethanolamine phosphoglyceride (EPG) (n-6) and (n-3) fatty acids of women in pregnancy or their breast milk during lactation. We genotyped rs174553, rs99780, rs174575, and rs174583 in the FADS1 FADS2 gene cluster and analyzed plasma and erythrocyte fatty acids and dietary intake for 69 pregnant women and breast milk for a subset of 54 women exclusively breast-feeding at 1 mo postpartum. Minor allele homozygotes of rs174553(GG), rs99780(TT), and rs174583(TT) had lower ARA but higher LA in plasma phospholipids and erythrocyte EPG and decreased (n-6) and (n-3) fatty acid product:precursor ratios at 16 and 36 wk of gestation. Breast milk fatty acids were influenced by genotype, with significantly lower 14:0, ARA, and EPA but higher 20:2(n-6) in the minor allele homozygotes of rs174553(GG), rs99780(TT), and rs174583(TT) and lower ARA, EPA, 22:5(n-3), and DHA in the minor allele homozygotes G/G of rs174575. We showed that genetic variants of FADS1 and FADS2 influence blood lipid and breast milk essential fatty acids in pregnancy and lactation.
Understanding of the importance of dietary fatty acids has grown beyond a simple source of energy to complex roles in regulating gene expression and cell and intracellular communication. This is ...important because the metabolic and neuroendocrine environment of the fetus and infant plays a key role in guiding the set point of neural receptors that regulate energy homeostasis and expression of genes that control energy storage and oxidation. Early deviations in these pathways have the potential to lead to lasting adaptations, termed metabolic programming, which may combine to increase the risk of metabolic syndrome in later life. The quality of fatty acids in human diets has undergone major changes in the last 50 years, characterized by an increase in ω‐6 and decrease in ω‐3 fatty acids. Evidence is accumulating to support the concept that the maternal intake of ω‐6 and ω‐3 fatty acids in gestation and lactation, possibly involving both excess ω‐6 and inadequate ω‐3 fatty acids, can impact the developing infant tissue lipids and neuroendocrine and metabolic pathways relevant to metabolic programming. Further work is needed to understand the needs for different ω‐6 and ω‐3 fatty acids during fetal and infant life, and their roles with respect to development of energy homeostasis and metabolism.
Abstract Fatty acids play central roles in growth and development through their roles in membrane lipids, as ligands for receptors and transcription factors that regulate gene expression, precursor ...for eicosanoids, in cellular communication, and through direct interactions with proteins. Adverse fatty acid supplies during fetal and child development alter the fatty acid composition of membrane phospholipids and storage triglycerides with the potential to disrupt cellular environments, and program structure and function. Maternal fatty acid nutrition during pregnancy and lactation determines the transfer of essential n-6 and n-3, and non-essential trans fatty acids via the placenta and through human milk. Poor maternal docosahexaenoic acid (DHA) status increases risk of inadequate DHA to support brain and retinal development, delaying or limiting neural and visual system development. The implications of recent changes in the dietary fatty acids on maternal to infant fatty acid transfer, including the composition of human milk has been insufficiently studied.
Docosahexaenoic acid (DHA) and arachidonic acid (ARA) are important structural components of the central nervous system. These fatty acids are transferred across the placenta, are present in human ...milk, and are accumulated in the brain and retina during fetal and infant development. The high concentrations of DHA in the retina and of DHA and ARA in brain gray matter suggests that these fatty acids have important roles in retinal and neural function. Animal studies have shown that depletion of DHA from the retina and brain results in reduced visual function and learning deficits. The latter effects may be explained by changes in the membrane bilayer that alter membrane-associated receptors and signal transduction systems, ion channel activity, or direct effects on gene expression. DHA can be formed in the liver from alpha linolenic acid, but it is unclear if the rate of DHA synthesis in humans is sufficient to support optimal brain and retinal development. Although there is no evidence that the ability to form ARA from linoleic acid is limiting, supplementation with DHA reduces tissue ARA, possibly creating a conditional need for ARA in infants with a dietary intake of DHA. The amount of DHA in human milk varies widely and is positively correlated with visual and language development in breast-fed infants. Advances in understanding essential fatty acid requirements will benefit from intervention studies that use functionally relevant tests to probe the deficiency or adequacy of physiologically important pools of DHA and ARA in developing infants.
PDF
