Preformed Long-chain Polyunsaturated Fatty Acids Research Articles

Effect of long-chain polyunsaturated fatty acids in infant formula on long-term cognitive function in childhood: A systematic review and meta-analysis of randomised controlled trials.

PROSPERO registration numbers CRD42018105196 and CRD42018088868.

N-3 LC-PUFA supplementation: effects on infant and maternal outcomes

Long-chain polyunsaturated fatty acids (LC-PUFA), particularly docosahexaenoic acid (DHA) and arachidonic acid, are, respectively, n-3 and n-6 family members and play an important role in fetal and infant growth and development. Pregnancy and lactation impose special nutritional needs for the mother-fetus situation. Since the LC-PUFA required by the fetus is supplied by preferential placental transfer of preformed LC-PUFA rather than their precursor, it has been hypothesized that additional maternal supply of LC-PUFA, especially DHA, during pregnancy may improve maternal and infant outcomes. To summarize evidences of the effect of n-3 LC-PUFA intake during pregnancy and lactation on maternal and infant outcomes in order to offer a comprehensive view of this issue that should be useful for clinical practice. Maternal n-3 LC-PUFA supplementation may reduce risk for early preterm birth >34 weeks and seems very promising for primary allergy prevention during childhood. On the contrary, there are not sufficient data proving that the consumption of oils rich in n-3 LC-PUFA during pregnancy optimizes child's visual and neurodevelopment and reduces the risk for preeclampsia and perinatal depression; the implications of these findings remain to be elucidated. The implications of n-3 LC-PUFA supplementation on fetal development, maternal outcomes and later infant growth is worth being elucidated and is promising in its potential for a positive impact on fetal and maternal outcomes.

Biosynthesis of long-chain polyunsaturated fatty acids in marine fish: Characterization of an Elovl4-like elongase from cobia Rachycentron canadum and activation of the pathway during early life stages

Marine fish, unlike freshwater species, have been generally considered to have a limited ability to biosynthesize long-chain polyunsaturated fatty acids (LC-PUFA) from C 18 precursors due to apparent limited enzymatic activities involved in the pathway. Although LC-PUFA play important physiological roles throughout the entire life cycle, requirements for early life stages are especially high and provision of preformed LC-PUFA in egg lipids appears critical to support the formation of developing tissues where these compounds accumulate. No studies, however, have been conducted to explore the capability of marine fish embryos (here referring to life stages from zygote to the oesophagus opening) for de novo synthesis of the LC-PUFA required for normal growth and development. The present study aimed to investigate the activation of the LC-PUFA biosynthetic pathway during embryogenesis of the marine teleost cobia ( Rachycentron canadum). First, a fatty acyl elongase with sequence similarity to mammalian elongase of very long-chain fatty acids 4 (Elovl4) was isolated, and its biochemical function characterized showing that it catalyzed the production of very long-chain fatty acids (VLC-FA) including both saturated and polyunsaturated fatty acids with chain lenghts ≥ 24 carbons. Notably, cobia Elovl4 was able to elongate 22:5n−3 to 24:5n−3 and thus could play a key role in the biosynthesis of docosahexaenoic acid (22:6n−3), a critical fatty acid in neural tissues. Subsequently, the fatty acid dynamics of embryos at different developmental stages and the temporal expression patterns of target genes including elovl4, and the formerly characterized elovl5 elongase and ∆6 fatty acyl desaturase, were analyzed in order to elucidate the overall activation of the LC-PUFA biosynthetic pathway in cobia embryos. Our results indicated that expression of the LC-PUFA biosynthetic pathway in cobia embryos is initiated at 12–18 h post-fertilization.

The roles of long-chain polyunsaturated fatty acids in pregnancy, lactation and infancy: review of current knowledge and consensus recommendations

This paper reviews current knowledge on the role of the long-chain polyunsaturated fatty acids (LC-PUFA), docosahexaenoic acid (DHA, C22:6n-3) and arachidonic acid (AA, 20:4n-6), in maternal and term infant nutrition as well as infant development. Consensus recommendations and practice guidelines for health-care providers supported by the World Association of Perinatal Medicine, the Early Nutrition Academy, and the Child Health Foundation are provided. The fetus and neonate should receive LC-PUFA in amounts sufficient to support optimal visual and cognitive development. Moreover, the consumption of oils rich in n-3 LC-PUFA during pregnancy reduces the risk for early premature birth. Pregnant and lactating women should aim to achieve an average daily intake of at least 200 mg DHA. For healthy term infants, we recommend and fully endorse breastfeeding, which supplies preformed LC-PUFA, as the preferred method of feeding. When breastfeeding is not possible, we recommend use of an infant formula providing DHA at levels between 0.2 and 0.5 weight percent of total fat, and with the minimum amount of AA equivalent to the contents of DHA. Dietary LC-PUFA supply should continue after the first six months of life, but currently there is not sufficient information for quantitative recommendations.

Perinatal long chain polyunsaturated fatty acid supply Are there long term consequences?

Long-chain polyunsaturated fatty acids (LC-PUFA), especially docosahexaenoic acid (DHA), are essential components of biological membranes or act as precursors for eicosanoid formation, in case of the 20 carbon atom fatty acids, arachidonic acid (AA), dihomo-c-linolenic acid and eicosapentaenoic acid. During pregnancy LC-PUFA are enriched in the fetal circulation relative to maternal plasma. The corresponding placental processes have not been fully elucidated so far, but there are good indications that the LC-PUFA enrichment during the materno-fetal transfer is mediated by differences in the incorporation into lipid classes within the placenta between fatty acids and that specific fatty acid binding and transfer proteins are of major importance. In vitro a plasma membrane fatty acid binding protein could be identified, which preferentially binds DHA and AA compared to linoleic and oleic acids; in addition the m-RNA expression of fatty acid transfer protein 4 (FATP-4) in placental tissue was found to correlate significantly with the DHA percentage in cord blood phospholipids. After birth the percentage of LC-PUFA in infantile blood rapidly declines to levels depending on the dietary LC-PUFA supply, although preterm and full-term babies can convert linoleic and _-linolenic acids into AA and DHA, respectively. Breast milk provides preformed LC-PUFA, and breastfed infants have higher LC-PUFA levels in plasma and tissue than infants fed formulas without LC-PUFA. The high percentage of DHA in brain and other nervous tissue and the fact that the perinatal period is a period of fast brain growth suggests the importance of placental DHA transfer and dietary DHA content for optimal infantile development. Most but not all randomized, double blind, controlled clinical trials in preterm and in healthy full term infants demonstrated benefits of formulas supplemented with DHA and AA for the neurological development compared to formulas without LC-PUFA. Furthermore, according to the concept of “metabolic programming” during the perinatal period a dietary factor, such as the availability of LC-PUFA, might have long term consequences. From the available data it has to be assumed that LC-PUFA are conditionally essential substrates during early life and a further investigation of the biological mechanisms related to their availability for the infant and of potential life long effects on cognitive function and potentially also risk factors for cardiovascular diseases and allergy are certainly warranted.

Dietary long‐chain polyunsaturated fatty acid supplementation in infants with phenylketonuria: a randomized controlled trial

Pre- and postnatal tissue accretion of long-chain polyunsaturated fatty acids (LCPUFA) has been related to visual and cognitive development in healthy children in several studies. Children with phenylketonuria (PKU) consume diets with very low contents of preformed LCPUFA. We studied prospectively the LCPUFA status in infants with PKU without or with LCPUFA supplementation during the first year of life. Infants with PKU were enrolled at diagnosis (<4 weeks of age) and randomized double blind to phenylalanine-free amino acid supplements without LCPUFA (n = 11) or with both arachidonic (AA, 0.46 wt%) and docosahexaenoic acids (DHA, 0.27 wt%) (n = 10). At enrolment and again at 1, 2, 3, 4, 6, 9 and 12 months, plasma phospholipid fatty acids were measured and dietary intakes were calculated from dietary protocols. Unsupplemented patients showed a marked LCPUFA depletion to levels clearly below those observed in healthy breast-fed infants. In contrast, supplemented infants had stable and higher LCPUFA levels than unsupplemented infants, reaching significant differences for AA values at 3, 4 and 6 months, and for DHA values at 1, 3, 4, 6, 9 and 12 months. Plasma phospholipid levels correlated closely with estimated dietary intakes of preformed LCPUFA. Low LCPUFA intakes with PKU diets induce marked depletion of AA and particularly of DHA in the first year of life. Thus endogenous synthesis of LCPUFA from precursors supplied by diet seems unable to compensate for low LCPUFA intakes. LCPUFA supplementation of PKU diets during the first year of life effectively enhances LCPUFA status to levels comparable to those of healthy breast-fed infants.

A importância dos ácidos graxos poliinsaturados de cadeia longa na gestação e lactação

Os ácidos graxos poliinsaturados de cadeia longa (AGPICL), ácido docosahexaenóico (DHA) e ácido araquidônico (AA) são componentes essenciais não só para o desenvolvimento neurológico quanto para a função visual da criança. O objetivo desta revisão foi buscar estudos recentes sobre a importância desses nutrientes no período gestacional e neonatal. A maior necessidade dos AGPICL ocorre durante a vida intra-uterina e nos primeiros meses de vida. A mãe é um fator determinante na oferta desses ácidos graxos para a criança. O leite materno contém todos os nutrientes necessários para o crescimento e desenvolvimento da criança. O bebê não tem capacidade de elongação e dessaturação dos ácidos graxos e dessa maneira as fórmulas infantis devem conter AGPICL pré-formados.

Perinatal supply and metabolism of long-chain polyunsaturated fatty acids: importance for the early development of the nervous system.

The long-chain polyunsaturated fatty acids, arachidonic (AA) and docosahexaenoic acid (DHA), are essential structural lipid components of biomembranes. During pregnancy, long-chain polyunsaturated fatty acids (LC-PUFA) are preferentially transferred from mother to fetus across the placenta. This placental transfer is mediated by specific fatty acid binding and transfer proteins. After birth, preterm and full-term babies are capable of converting linoleic and alpha-linolenic acids into AA and DHA, respectively, as demonstrated by studies using stable isotopes, but the activity of this endogenous LC-PUFA synthesis is very low. Breast milk provides preformed LC-PUFA, and breast-fed infants have higher LC-PUFA levels in plasma and tissue phospholipids than infants fed conventional formulas. Supplementation of formulas with different sources of LC-PUFA can normalize LC-PUFA status in the recipient infants relative to reference groups fed human milk. Some, but not all, randomized, double-masked placebo-controlled clinical trials in preterm and healthy full-term infants demonstrated benefits of formula supplementation with DHA and AA for development of visual acuity up to 1 year of age and of complex neural and cognitive functions. From the available data, we conclude that LC-PUFA are conditionally essential substrates during early life that are related to the quality of growth and development. Therefore, a dietary supply during pregnancy, lactation, and early childhood that avoids the occurrence of LC-PUFA depletion is desirable, as was recently recommended by an expert consensus workshop of the Child Health Foundation.

Physiological aspects of human milk lipids.

Human milk from healthy and well-nourished mothers is the preferred form of feeding for all healthy newborn infants. The nutrient supply with human milk supports normal growth and development of the infant. Here the general characteristics of human milk lipids and recent knowledge on lactational physiology, composition and functional aspects of human milk lipids are discussed. Lipids in human milk represent the main source of energy for the breastfed baby and supply essential nutrients such as fat-soluble vitamins and polyunsaturated fatty acids (PUFA). The essential fatty acids linoleic and alpha-linolenic acids (LA and ALA) are precursors of long-chain polyunsaturated fatty acids (LC-PUFA), including arachidonic (20:4n-6) and docosahexaenoic (22:6n-3) acids (AA and DHA). LC-PUFA serve as indispensable structural components of cellular membranes and are deposited to a considerable extent in the growing brain and the retina during perinatal development. The supply of preformed LC-PUFA with human milk lipids has been related to functional outcomes of the recipient infants such as visual acuity and development of cognitive functions during the first year of life. Recent stable isotope studies indicate that the major portion of milk PUFA is not derived directly from the maternal diet, but stems from endogenous body stores. Thus, not only the woman's current but also her long-term dietary intake is of marked relevance for milk fat composition.

Long chain polyunsaturated fatty acids (LC‐PUFA) and perinatal development

This paper reports on the conclusions of a workshop on the role of long chain polyunsaturated fatty acids (LC-PUFA) in maternal and child health. The attending investigators involved in the majority of randomized trials examining LC-PUFA status and functional outcomes summarize the current knowledge in the field and make recommendations for dietary practice. Only studies published in full or in abstract form were used as our working knowledge base. For healthy infants we recommend and strongly support breastfeeding as the preferred method of feeding, which supplies preformed LC-PUFA. Infant formulas for term infants should contain at least 0.2% of total fatty acids as docosahexaenoic acid (DHA) and 0.35% as arachidonic acid (AA). Since preterm infants are born with much less total body DHA and AA, we suggest that preterm infant formulas should include at least 0.35% DHA and 0.4% AA. Higher levels might confer additional benefits and should be further investigated because optimal dietary intakes for term and preterm infants remain to be defined. For pregnant and lactating women we consider it premature to recommend specific LC-PUFA intakes. However, it seems prudent for pregnant and lactating women to include some food sources of DHA in their diet in view of their assumed increase in LC-PUFA demand and the relationship between maternal and foetal DHA status.

Polyunsaturated fatty acid synthesis and release by brain-derived cells in vitro.

The brain is more highly enriched than most other tissues in long-chain polyunsaturated fatty acids (PUFA), particularly docosahexaenoic acid (DHA). In vitro studies of PUFA synthesis and release utilizing cell cultures of astrocytes, neurons, and cerebral microvascular endothelium have contributed significantly to our understanding of mechanisms potentially involved in the accretion of PUFA in brain. Both cerebral endothelium and astrocytes avidly elongate and desaturate precursors of the long-chain PUFAs when grown individually or in various co-culture combinations. The products, such as arachidonic acid (AA) and DHA, are released from the cells. In contrast, neurons appear unable to carry out fatty acid desaturation and thus are dependent upon preformed long-chain PUFA. Indeed, neurons co-cultured with astrocytes accumlate docosahexaenoate synthesized by the glial cells. Cerebral endothelial cultures are additionally capable of enriching the basolateral compartment (analogous to the brain extracellular space) with n-3 PUFA when grown in a membrane/chamber apparatus. The enrichment of this compartment with DHA is increased when cerebral endothelium is co-cultured with astrocytes. These data suggest that endothelial cells and astrocytes cooperate in the local synthesis and release of PUFA, collectively maintaining a brain environment enriched in long-chain PUFA.

Long-chain polyunsaturated fatty acids in diets for infants: choices for recommending and regulating bodies and for manufacturers of dietary products.

While the scientific evaluation of the physiologic effects, potential benefits, and risks of dietary preformed long-chain polyunsaturated fatty acids (LCPUFA) for infants have been discussed elsewhere, this manuscript addresses some of the resulting consequences and challenges of interpreting the available knowledge from the perspective of recommending and regulating bodies, and of manufacturers of dietary products and their ingredient materials. Traditionally human milk composition has served as a reference point for infant formula design. With respect to the use of LCPUFA in infant formula, much more emphasis than ever before invested for any other group of micronutrients has been put on clinical studies investigating the potential advantages and disadvantages of LCPUFA in infant foods, including growth, safety aspects, and a variety of other outcome measures.

Effects of Dietary Long-Chain Polyunsaturated Fatty Acids on Plasma Amino Acids and Indices of Protein Metabolism in Infants: Results from a Randomized Clinical Trial

Background/Aim: Previous studies in vitro and in animals in vivo found that α-linolenic acid (C18:3ω3) may enhance oxidative damage of essential amino acids. We investigated whether the addition of the long-chain polyunsaturated fatty acids (LCPUFA) arachidonate (C20:4ω-6; AA) and docosahexaenoate (C22:6-ω3; DHA) in the form of egg phospholipids to infant formula affects plasma amino acid concentrations and indices of protein metabolism in term infants. Methods: In a double-blind, randomized clinical trial, healthy infants were fed from day 5 of life formula with or without preformed LCPUFA (n = 10 and 12, respectively). At the age of 5 days and 1, 2, 3 and 4 months, blood samples were obtained and analyzed for plasma amino acids by high-performance liquid chromatography and for plasma phospholipid fatty acid composition by gas chromatography. Results: At the age of 3 months, plasma threonine concentrations were significantly lower in infants receiving dietary LCPUFA than in controls (124 ± 16 vs. 216 ± 28 µmol/l, p < 0.05). Values of other plasma essential amino acids, total protein, albumin, creatinine and urea nitrogen did not differ between the two feeding groups throughout the study. At the age of 5 days, plasma phospholipid AA and DHA concentrations were inversely correlated with histidine concentrations (AA: r = –0.60, p = 0.01; DHA: r = –0.53, p < 0.05). At the age of 3 months, DHA concentrations were inversely related to plasma histidine, methionine and threonine concentrations (r = –0.66, –0.62, and –0.64, respectively, p < 0.05). Conclusions: The dietary LCPUFA supplementation of infant formula used in this study has no adverse effects on infant plasma amino acid concentrations and indicators of protein metabolism. Nonetheless, the apparent interaction of LCPUFA with some amino acids in formula-fed infants warrants further investigation.