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Omega-3
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Kompendium Omega-3: 6/2001
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Omega-3: Fakten - Therapie und Dosierung

Gehirn- und Sehleistung von Kleinkinder: 2,0g/Tag DHA & EPA spätestens ab 4. Monat der Schwangerschaft.
In Fachzeitschriften wurden folgende Artikel über Omega-3 publiziert. Die Liste dieser Publikationen wurde im April 2003 kompiliert und erhebt keinen Anspruch auf Vollständigkeit. Quelle: MEDLINE.
Die Daten dienen als Referenz für Ärzte und Therapeuten, damit ein mögliches Gesundheitsrisiko für Kleinkinder vermindert werden kann.

Long-chain polyunsaturated fatty acids in breast milk: are they essential?
Gibson RA: Child Nutrition Research Centre, Child Health Research Institute, Flinders Medical Centre, Adelaide, SA, Australia; Makrides M
Adv Exp Med Biol 2001  501:375-83

Abstract
The need for long-chain polyunsaturated fatty acids (LC-PUFA), such as docosahexaenoic acid (DHA, C22:6n3) and arachidonic acid (AA, C20:4n6), in the diet of infants in order to achieve full developmental potential is a matter of intense investigation by several research groups worldwide. It has been widely reported that breast-fed infants perform better on tests that assess neurodevelopmental outcomes than do formula-fed infants. Although human milk contains LC-PUFA that are absent from formula, it is necessary to demonstrate that any beneficial effects of human milk on infant development are purely attributed to the presence of LC-PUFA in human milk and their absence from formula to establish causality. The hypothesis that dietary DHA is associated with developmental outcome needs to be plausible; the effect must be consistent, specific, and independent of confounding factors. The hypothesis is certainly plausible. DHA is avidly incorporated and retained in brain cerebral phospholipids, and a most consistent finding has been the lower level of cerebral DHA in the brains of formula-fed infants (receiving no DHA) relative to those fed human milk (receiving DHA). The formula-fed infants in these studies were generally fed formulas with adequate alpha-linolenic acid levels, and this may indicate a nutritional requirement for preformed DHA. Several studies have compared the effects of breast- and formula-feeding on functional outcomes in preterm and term infants. While many of the outcomes have involved visual testing, others have attempted more global assessments. The results have shown differences in favor of breast-feeding but have been colored by the strong socioeconomic differences between mothers who choose to breast feed and those who choose formula-feeding. Randomized clinical trials involving preterm infants have shown a clear requirement for DHA for full visual and neural development. These results are consistent with primate studies. However, intervention studies with term infants that have attempted to improve the DHA supply of infant formula and hence infant development have not yielded consistent results. Some randomized studies have demonstrated improved visual and developmental indices in supplemented over unsupplemented infants, others have failed to demonstrate an effect. This disparity could be due to methodological and environmental differences. It is also notable that supplemental regimens have not specifically added DHA and have included other LC-PUFA, raising the question as to the specificity of the effect. However, only tissue DHA levels have consistently correlated with outcomes.

Neonatal polyunsaturated fatty acid metabolism.
Innis SM: Department of Paediatrics, University of British Columbia, Vancouver, Canada; Sprecher H, Hachey D, Edmond J, Anderson RE
Lipids 1999 Feb 34:139-49

Abstract
The importance of n-6 and n-3 polyunsaturated fatty acids (PUFA) in neonatal development, particularly with respect to the developing brain and retina, is well known. This review combines recent information from basic science and clinical studies to highlight recent advances in knowledge on PUFA metabolism and areas where research is still needed on infant n-6 and n-3 fatty acid requirements. Animal, cell culture, and infant studies are consistent in demonstrating that synthesis of 22:6n-3 involves C24 PUFA and that the amounts of 18:2n-6 and 18:3n-3 influence PUFA metabolism. Studies to show that addition of n-6 fatty acids beyond delta6-desaturase alters n-6 fatty acid metabolism with no marked increase in tissue 20:4n-6 illustrate the limitations of analyses of tissue fatty acid compositions as an approach to study the effects of diet on fatty acid metabolism. New information to show highly selective pathways for n-6 and n-3 fatty acid uptake in brain, and efficient pathways for conservation of 22:6n-3 in retina emphasizes the differences in PUFA metabolism among different tissues and the unique features which allow the brain and retina to accumulate and maintain high concentrations of n-3 fatty acids. Further elucidation of the delta6-desaturases involved in 24:5n-6 and 22:6n-3 synthesis; the regulation of fatty acid movement between the endoplasmic reticulum and peroxisomes; partitioning to acylation, desaturation and oxidation; and the effects of dietary and hormonal factors on these pathways is needed for greater understanding of neonatal PUFA metabolism.

Maternal supplementation with very-long-chain n-3 fatty acids during pregnancy and lactation augments children's IQ at 4 years of age.
Helland IB: Institute for Nutrition Research, University of Oslo, Oslo, Norway; Smith L, Saarem K, Saugstad OD, Drevon CA
Pediatrics 2003 Jan 111:e39-44
Abstract
OBJECTIVES: Docosahexaenoic acid (DHA; 22:6 n-3) and arachidonic acid (AA; 20:4 n-6) are important for development of the central nervous system in mammals. There is a growth spurt in the human brain during the last trimester of pregnancy and the first postnatal months, with a large increase in the cerebral content of AA and DHA. The fetus and the newborn infant depend on maternal supply of DHA and AA. Our hypothesis was that maternal intake of DHA during pregnancy and lactation is marginal and that high intake of this fatty acid would benefit the child. We examined the effect of supplementing pregnant and lactating women with very-long-chain n-3 polyunsaturated fatty acids (PUFAs; cod liver oil) on mental development of the children, compared with maternal supplementation with long-chain n-6 PUFAs (corn oil). METHODS: The study was randomized and double-blinded. Pregnant women were recruited in week 18 of pregnancy to take 10 mL of cod liver oil or corn oil until 3 months after delivery. The cod liver oil contained 1183 mg/10 mL DHA, 803 mg/10 mL eicosapentaenoic acid (20:5 n-3), and a total of 2494 mg/10 mL summation operator n-3 PUFAs. The corn oil contained 4747 mg/10 mL linoleic acid (18:2 n-6) and 92 mg/10 mL alpha-linolenic acid (18:3 n-3). The amount of fat-soluble vitamins was identical in the 2 oils (117 micro g/mL vitamin A, 1 micro g/mL vitamin D, and 1.4 mg/mL dl-alpha-tocopherol). A total of 590 pregnant women were recruited to the study, and 341 mothers took part in the study until giving birth. All infants of these women were scheduled for assessment of cognitive function at 6 and 9 months of age, and 262 complied with the request. As part of the protocol, 135 subjects from this population were invited for intelligence testing with the Kaufman Assessment Battery for Children (K-ABC) at 4 years of age. Of the 135 invited children, 90 came for assessment. Six children did not complete the examination. The K-ABC is a measure of intelligence and achievement designed for children aged 2.5 years through 12.5 years. This multisubtest battery comprises 4 scales: Sequential Processing, Simultaneous Processing, Achievement (not used in the present study), and Nonverbal Abilities. The Sequential Processing and Simultaneous Processing scales are hypothesized to reflect the child's style of problem solving and information processing. Scores from these 2 scales are combined to form a Mental Processing Composite, which serves as the measure of intelligence in the K-ABC. RESULTS: We received dietary information from 76 infants (41 in the cod liver oil group and 35 in the corn oil group), documenting that all of them were breastfed at 3 months of age. Children who were born to mothers who had taken cod liver oil (n = 48) during pregnancy and lactation scored higher on the Mental Processing Composite of the K-ABC at 4 years of age as compared with children whose mothers had taken corn oil (n = 36; 106.4 [7.4] vs 102.3 [11.3]). The Mental Processing Composite score correlated significantly with head circumference at birth (r = 0.23), but no relation was found with birth weight or gestational length. The children's mental processing scores at 4 years of age correlated significantly with maternal intake of DHA and eicosapentaenoic acid during pregnancy. In a multiple regression model, maternal intake of DHA during pregnancy was the only variable of statistical significance for the children's mental processing scores at 4 years of age. CONCLUSION: Maternal intake of very-long-chain n-3 PUFAs during pregnancy and lactation may be favorable for later mental development of children.

Polyunsaturated fatty acids in human milk and their role in early infant development.
Koletzko B: Division Metabolic Diseases and Nutrition Kinderklinik and Kinderpoliklinik, Dr. von Haunersches Kinderspital, Ludwigs-Maximilians-University of Munich; Rodriguez-Palmero M
J Mammary Gland Biol Neoplasia 1999 Jul 4:269-84

Abstract
The lipid fraction of human milk represents the main source of energy for the newborn infant and supplies essential nutrients such as fat-soluble vitamins and polyunsaturated fatty acids (PUFA). The essential fatty acids linoleic and alpha-linolenic acids are precursors of long-chain polyunsaturated fatty acids (LC-PUFA), such as arachidonic (C20:4 n-6) and docosahexaenoic (C22:6 n-3) acids, present in human milk in considerable amounts. LC-PUFA are indispensable structural components of all cellular membranes, and they are incorporated in relatively large amounts during early growth of the brain and the retina. Moreover, some LC-PUFA are precursors of eicosanoids, molecules with potent biological activity that modulates various cellular and tissue processes. The supply of long-chain fatty acids has been associated with functional outcomes of the recipient infants such as visual acuity and development of cognitive functions during the first year of life. Here we discuss the PUFA composition of human milk, factors which determine and modulate milk PUFA content, and possible effects of milk LC-PUFA on infant growth and development.
Physiological aspects of human milk lipids.
Koletzko B: Department of Pediatrics, Kinderklinik and Kinderpoliklinik, Dr. von Haunersches Kinderspitel, Ludwig-Maximilians-University of Munich; Rodriguez-Palmero M, Demmelmair H, Fidler N, Jensen R, Sauerwald T
Early Hum Dev 2001 Nov 65 Suppl:S3-S18

Abstract
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.
Essential fatty acids in visual and brain development.
Uauy R: Institute of Nutrition and Food Technology (INTA), University of Chile, Santiago, Chile; Hoffman DR, Peirano P, Birch DG, Birch EE
Lipids 2001 Sep 36:885-95

Abstract
Essential fatty acids are structural components of all tissues and are indispensable for cell membrane synthesis; the brain, retina and other neural tissues are particularly rich in long-chain polyunsaturated fatty acids (LC-PUFA). These fatty acids serve as specific precursors for eicosanoids, which regulate numerous cell and organ functions. Recent human studies support the essential nature of n-3 fatty acids in addition to the well-established role of n-6 essential fatty acids in humans, particularly in early life. The main findings are that light sensitivity of retinal rod photoreceptors is significantly reduced in newborns with n-3 fatty acid deficiency, and that docosahexaenoic acid (DHA) significantly enhances visual acuity maturation and cognitive functions. DHA is a conditionally essential nutrient for adequate neurodevelopment in humans. Comprehensive clinical studies have shown that dietary supplementation with marine oil or single-cell oil sources of LC-PUFA results in increased blood levels of DHA and arachidonic acid, as well as an associated improvement in visual function in formula-fed infants matching that of human breast-fed infants. The effect is mediated not only by the known effects on membrane biophysical properties, neurotransmitter content, and the corresponding electrophysiological correlates but also by a modulating gene expression of the developing retina and brain. Intracellular fatty acids or their metabolites regulate transcriptional activation of gene expression during adipocyte differentiation and retinal and nervous system development. Regulation of gene expression by LC-PUFA occurs at the transcriptional level and may be mediated by nuclear transcription factors activated by fatty acids. These nuclear receptors are part of the family of steroid hormone receptors. DHA also has significant effects on photoreceptor membranes and neurotransmitters involved in the signal transduction process; rhodopsin activation, rod and cone development, neuronal dendritic connectivity, and functional maturation of the central nervous system.
Fatty acid composition of human brain phospholipids during normal development.
Martinez M: Center for Research in Biochemistry and Molecular Biology, Maternity-Children's Hospital Vall d'Hebron, Barcelona, Spain; Mougan I
J Neurochem 1998 Dec 71:2528-33

Abstract
The fatty acid composition of phosphatidylethanolamine (PE), ethanolamine plasmalogens (EPs), phosphatidylserine (PS), phosphatidylcholine (PC), and sphingomyelin was studied in 22 human forebrains, ranging in age from 26 prenatal weeks to 8 postnatal years. Phospholipids were separated by two-dimensional TLC, and the fatty acid methyl esters studied by capillary column GLC. Docosahexaenoic acid (22:6n-3) increased with age in PE and PC, whereas arachidonic acid (20:4n-6) remained quite constant. In EP, 22:6n-3 increased less markedly than 20:4n-6, adrenic (22:4n-6) and oleic (18:1n-9) acids being the predominant fatty acids during postnatal age. In PS, 18:1n-9 increased dramatically throughout development, and 20:4n-6 and 22:4n-6 increased only until approximately 6 months of age. Although 22:6n-3 kept quite constant during development in PS, its percentage decreased due to the accretion of other polyunsaturated fatty acids (PUFAs). As a characteristic myelin lipid, sphingomyelin was mainly constituted by very long chain saturated and monounsaturated fatty acids. Among them, nervonic acid (24:1n-9) was the major very long chain fatty acid in Sp, followed by 24:0, 26:1n-9, and 26:0, and its accretion after birth was dramatic. As myelination advanced, 18:1n-9 increased markedly in all four glycerophospholipids, predominating in EP, PS, and PC. In contrast, 22:6n-3 was the most important PUFA in PE in the mature forebrain.
Higher maternal plasma docosahexaenoic acid during pregnancy is associated with more mature neonatal sleep-state patterning.
Cheruku SR: Department of Nutritional Sciences, the University of Connecticut, Storrs, USA; Montgomery-Downs HE, Farkas SL, Thoman EB, Lammi-Keefe CJ
Am J Clin Nutr 2002 Sep 76:608-13

Abstract
BACKGROUND: The effect of docosahexaenoic acid (DHA) on the developing fetal central nervous system (CNS) and related functional outcomes in infancy remain unexplored. Sleep and wake states of newborns provide a tool for assessing the functional integrity of the CNS. OBJECTIVE: We investigated whether CNS integrity in newborns, measured with sleep recordings, was associated with maternal concentrations of long-chain polyunsaturated fatty acids, especially DHA. DESIGN: Plasma phospholipid fatty acid concentrations were measured in 17 women at parturition. On postpartum day 1 (P1) and day 2 (P2), a pressure-sensitive pad under the infants' bedding recorded body movements and respiratory patterns to measure sleep and wake states. RESULTS: Maternal plasma phospholipid DHA ranged from 1.91% to 4.5% by wt of total fatty acids. On the basis of previously published data and the median DHA concentration, the women were divided into 2 groups: high DHA (> 3.0% by wt of total fatty acids) and low DHA (</= 3.0% by wt of total fatty acids). Infants of high-DHA mothers had a significantly lower ratio of active sleep (AS) to quiet sleep (QS) and less AS than did infants of low-DHA mothers. Furthermore, the former infants had less sleep-wake transition and more wakefulness on P2. Correlations of maternal DHA status with infant sleep states were consistent with these data. Also, the ratio of maternal n-6 to n-3 fatty acids on P1 was inversely associated with QS and positively associated with arousals in QS. On P2, maternal n-6:n-3 was positively associated with AS, sleep-wake transition, and AS:QS. CONCLUSION: The sleep patterns of infants born to mothers with higher plasma phospholipid DHA suggest greater CNS maturity.
Role of essential fatty acids in the function of the developing nervous system.
Uauy R: Institute of Nutrition and Food Technology (INTA), University of Chile, Santiago, Chile; Peirano P, Hoffman D, Mena P, Birch D, Birch E
Lipids 1996 Mar 31 Suppl:S167-76

Abstract
The basis for n-3 fatty acid essentially in humans includes not only biochemical evidence but functional measures associated with n-3 deficiency in human and nonhuman primates. Functional development of the retina and the occipital cortex are affected by alpha-linolenic acid deficiency and by a lack of docosahexaenoic acid (DHA) in preterm infant formulas and, as reported more recently, in term diets. Functional effects of n-3 supply on sleep-wake cycles and heart rate rhythms support the need for dietary n-3 fatty acids during early development. Our results indicate that n-3 long-chain polyunsaturated fatty acids should be considered provisionally essential for infant nutrition. DHA may also be required by individuals with inherited metabolic defects in elongation and desaturation activity, such as patients with peroxisomal disorders and some forms of retinitis pigmentosa.
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