Neonatal Docosahexaenoic Acid in Preterm Infants and Intelligence at 5 Years.

BACKGROUND: Docosahexaenoic acid (DHA) is a component of neural tissue. Because its accretion into the brain is greatest during the final trimester of pregnancy, infants born before 29 weeks' gestation do not receive the normal supply of DHA. The effect of this deficiency on subsequent cognitive development is not well understood. METHODS: We assessed general intelligence at 5 years in children who had been enrolled in a trial of neonatal DHA supplementation to prevent bronchopulmonary dysplasia. In the previous trial, infants born before 29 weeks' gestation had been randomly assigned in a 1:1 ratio to receive an enteral emulsion that provided 60 mg of DHA per kilogram of body weight per day or a control emulsion from the first 3 days of enteral feeds until 36 weeks of postmenstrual age or discharge home, whichever occurred first. Children from 5 of the 13 centers in the original trial were invited to undergo assessment with the Wechsler Preschool and Primary Scale of Intelligence (WPPSI) at 5 years of corrected age. The primary outcome was the full-scale intelligence quotient (FSIQ) score. Secondary outcomes included the components of WPPSI. RESULTS: A total of 1273 infants underwent randomization in the original trial; of the 656 surviving children who had undergone randomization at the centers included in this follow-up study, 480 (73%) had an FSIQ score available - 241 in the DHA group and 239 in the control group. After imputation of missing data, the mean (±SD) FSIQ scores were 95.4±17.3 in the DHA group and 91.9±19.1 in the control group (adjusted difference, 3.45; 95% confidence interval, 0.38 to 6.53; P = 0.03). The results for secondary outcomes generally did not support that obtained for the primary outcome. Adverse events were similar in the two groups. CONCLUSIONS: In infants born before 29 weeks' gestation who had been enrolled in a trial to assess the effect of DHA supplementation on bronchopulmonary dysplasia, the use of an enteral DHA emulsion until 36 weeks of postmenstrual age was associated with modestly higher FSIQ scores at 5 years of age than control feeding. (Funded by the Australian National Health and Medical Research Council and Nu-Mega Ingredients; N3RO Australian New Zealand Clinical Trials Registry number, ACTRN12612000503820.).

Early Enteral Administration of a Complex Lipid Emulsion Supplement Prevents Postnatal Deficits in Docosahexaenoic and Arachidonic Acids and Increases Tissue Accretion of Lipophilic Nutrients in Preterm Piglets.

BACKGROUND: Preterm delivery and current nutrition strategies result in deficiencies of critical long-chain fatty acids (FAs) and lipophilic nutrients, increasing the risk of preterm morbidities. We sought to determine the efficacy of preventing postnatal deficits in FAs and lipophilic nutrients using an enteral concentrated lipid supplement in preterm piglets. METHODS: Preterm piglets were fed a baseline diet devoid of arachidonic acid (AA) and docosahexaenoic acid (DHA) and randomized to enteral supplementation as follows: (1) Intralipid (IL), (2) complex lipid supplement 1 (CLS1) with an AA:DHA ratio of 0.25, or (3) CLS2 with an AA:DHA ratio of 1.2. On day 8, plasma and tissue levels of FAs and lipophilic nutrients were measured and ileum histology performed. RESULTS: Plasma DHA levels decreased in the IL group by day 2. In contrast, DHA increased by day 2 compared with birth levels in both CLS1 and CLS2 groups. The IL and CLS1 groups demonstrated a continued decline in AA levels during the 8-day protocol, whereas AA levels in the CLS2 group on day 8 were comparable to birth levels. Preserving AA levels in the CLS2 group was associated with greater ileal villus height and muscular layer thickness. Lipophilic nutrients were effectively absorbed in plasma and tissues. CONCLUSIONS: Enteral administration of CLS1 and CLS2 demonstrated similar increases in DHA levels compared with birth levels. Only CLS2 maintained AA birth levels. Providing a concentrated complex lipid emulsion with an AA:DHA ratio > 1 is important in preventing postnatal AA deficits.

Synergistic Effects of DHA and Sucrose on Body Weight Gain in PUFA-Deficient Elovl2 -/- Mice.

The omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) is implicated in theregulation of both lipid and carbohydrate metabolism. Thus, we questioned whether dietary DHAand low or high content of sucrose impact on metabolism in mice deficient for elongation of verylong-chain fatty acids 2 (ELOVL2), an enzyme involved in the endogenous DHA synthesis. Wefound that Elovl2 -/- mice fed a high-sucrose DHA-enriched diet followed by the high sucrose, highfat challenge significantly increased body weight. This diet affected the triglyceride rich lipoproteinfraction of plasma lipoproteins and changed the expression of several genes involved in lipidmetabolism in a white adipose tissue. Our findings suggest that lipogenesis in mammals issynergistically influenced by DHA dietary and sucrose content.

An Ω-3 fatty acid-deficient diet during gestation induces depressive-like behavior in rats: the role of the hypothalamo-pituitary-adrenal (HPA) system.

Low intake of omega-3 (Ω-3) polyunsaturated fatty acids (PUFAs) especially docosahexaenoic acid (DHA) is associated with postpartum depression. DHA deficiency is accompanied by impaired attention and cognition, and will precipitate psychiatric symptoms. However, the effects of dietary DHA on postpartum depression remain unclear. We established a normal pregnancy model to evaluate whether an Ω-3 PUFA-deficient diet during gestation could induce depressive-like behavior and aggravate dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in rats. A between-group design was used to assess the effects of Ω-3 PUFA content (deficiency, control and supplementary) and reproductive status (virgin or parous). We assessed depressive-like behavior and measured the fatty acid composition in the liver. The protein expressions of glucocorticoid receptor (GR) and mineralocorticoid receptor (MCR) were also measured to evaluate the HPA activity. Exposure to the Ω-3 PUFA-deficient diet resulted in an increased immobility time in a forced swimming test (FST). Additionally, our results firstly showed the decreased expression of GR in the hippocampus of parous rats that were exposed to Ω-3 PUFA-deficient diets, which may partly facilitate the hyperactivity of the HPA axis and exert detrimental effects. Moreover, the reduction of GR was ameliorated by Ω-3 PUFA supplementation, providing new evidence for Ω-3 PUFAs in the progression of postpartum depression.

Fetal DHA inadequacy and the impact on child neurodevelopment: a follow-up of a randomised trial of maternal DHA supplementation in pregnancy.

DHA is an important component of neural lipids accumulating in neural tissue during development. Inadequate DHA in gestation may compromise infant development, but it is unknown whether there are lasting effects. We sought to determine whether the observed effects of fetal DHA inadequacy on infant development persist into early childhood. This follow-up study assessed children (5-6 years) whose mothers received 400 mg/d DHA or a placebo during pregnancy. Child neurodevelopment was assessed with several age-appropriate tests including the Kaufman Assessment Battery for Children. A risk-reduction model was used whereby the odds that a child from the maternal placebo group would fail to achieve a test score in the top quartile was calculated. The association of maternal DHA intake and status in gestation with child test scores, as well as with child DHA intake and status, was also determined. No differences were detected in children (n 98) from the maternal placebo and DHA groups achieving a high neurodevelopment test score (P>0·05). However, maternal DHA status was positively related to child performance on some tests including language and short-term memory. Furthermore, child DHA intake and status were related to the mother's intake and status in gestation. The neurodevelopment effects of fetal DHA inadequacy may have been lost or masked by other variables in the children. Although we provide evidence that maternal DHA status is related to child cognitive performance, the association of maternal and child DHA intake and status limits the interpretation of whether DHA before or after birth is important.

Reduced blood-brain barrier expression of fatty acid-binding protein 5 is associated with increased vulnerability of APP/PS1 mice to cognitive deficits from low omega-3 fatty acid diets.

Lower levels of the cognitively beneficial docosahexaenoic acid (DHA) are often observed in Alzheimer's disease (AD) brains. Brain DHA levels are regulated by the blood-brain barrier (BBB) transport of plasma-derived DHA, a process facilitated by fatty acid-binding protein 5 (FABP5). This study reports a 42.1 ± 12.6% decrease in the BBB transport of 14 C-DHA in 8-month-old AD transgenic mice (APPswe,PSEN1∆E9) relative to wild-type mice, associated with a 34.5 ± 6.7% reduction in FABP5 expression in isolated brain capillaries of AD mice. Furthermore, short-term spatial and recognition memory deficits were observed in AD mice on a 6-month n-3 fatty acid-depleted diet, but not in AD mice on control diet. This intervention led to a dramatic reduction (41.5 ± 11.9%) of brain DHA levels in AD mice. This study demonstrates FABP5 deficiency and impaired DHA transport at the BBB are associated with increased vulnerability to cognitive deficits in mice fed an n-3 fatty acid-depleted diet, in line with our previous studies demonstrating a crucial role of FABP5 in BBB transport of DHA and cognitive function.

Postnatal RBC arachidonic and docosahexaenoic acids deficiencies are associated with higher risk of neonatal morbidities and mortality in preterm infants.

Arachidonic (AA) and docosahexaenoic (DHA) acids are essential for the health and development of the neonate. Red blood cell (RBC) fatty acids were analyzed in 583 very low birth weight (VLBW) infants and 274 term infants using capillary gas chromatography. VLBW infants exhibited significantly lower RBC AA (13.0 ± 0.89 vs. 13.5 ± 0.98) and DHA (3.77 ± 0.60 vs. 3.80 ± 0.62), but higher n6:n3 ratio (3.97 ± 0.46 vs. 3.63 ± 0.37) than term infants. In VLBW infants, DHA was lower in those born with small for gestational age (3.69 ± 0.57 vs. 3.86 ± 0.58) and those who suffered from neonatal sepsis (3.73 ± 0.60 vs. 3.86 ± 0.55). Both AA and DHA were significantly lower in infants who developed respiratory distress syndrome or intraventricular hemorrhage, and those who died during the hospital stay. VLBW infants had lower postnatal RBC AA and DHA levels than term infants did. These deficits are associated with higher risk of neonatal morbidities and mortality.

Perinatal Brain Docosahexaenoic Acid Concentration Has a Lasting Impact on Cognition in Mice.

Background: Premature infants are deprived of prenatal accumulation of brain docosahexaenoic acid [DHA (22:6n-3)], an omega-3 fatty acid [ω-3 FA (n-3 FA)] important for proper development of cognitive function. The resulting brain DHA deficit can be reversed by ω-3 FA supplementation.Objective: The objective was to test whether there is a critical period for providing ω-3 FA to correct cognitive deficits caused by developmental ω-3 FA deprivation in mice.Methods: Twelve timed-pregnant mice [embryonic day 14 (E14), C57/BL6NCr] were fed an ω-3 FA-deficient diet containing 0.04% α-linolenic acid [ALA (18:3n-3)], and their offspring were fed the same deficient diet (Def group) or changed to an ω-3 FA-adequate diet containing 3.1% ALA at 3 wk, 2 mo, or 4 mo of age. In parallel, 3 E14 pregnant mice were fed the adequate diet and their offspring were fed the same diet (Adeq group) throughout the experiment. Brain FA composition, learning and memory, and hippocampal synaptic protein expression were evaluated at 6 mo by gas chromatography, the Morris water maze test, and western blot analysis, respectively.Results: Maternal dietary ω-3 FA deprivation decreased DHA by >50% in the brain of their offspring at 3 wk of age. The Def group showed significantly worse learning and memory at 6 mo than those groups fed the adequate diet. These pups also had decreased hippocampal expression of postsynaptic density protein 95 (43% of Adeq group), Homer protein homolog 1 (21% of Adeq group), and synaptosome-associated protein of 25 kDa (64% of Adeq group). Changing mice to the adequate diet at 3 wk, 2 mo, or 4 mo of age restored brain DHA to the age-matched adequate concentration. However, deficits in hippocampal synaptic protein expression and spatial learning and memory were normalized only when the diet was changed at 3 wk.Conclusion: Developmental deprivation of brain DHA by dietary ω-3 FA depletion in mice may have a lasting impact on cognitive function if not corrected at an early age.

Carriers of an apolipoprotein E epsilon 4 allele are more vulnerable to a dietary deficiency in omega-3 fatty acids and cognitive decline.

Carriers of an epsilon 4 allele (E4) of apolipoprotein E (APOE) develop Alzheimer's disease (AD) earlier than carriers of other APOE alleles. The metabolism of plasma docosahexaenoic acid (DHA, 22:6n-3), an omega-3 fatty acid (n-3 FA), taken up by the brain and concentrated in neurons, is disrupted in E4 carriers, resulting in lower levels of brain DHA. Behavioural and cognitive impairments have been observed in animals with lower brain DHA levels, with emphasis on loss of spatial memory and increased anxiety. E4 mice provided a diet deficient in n-3 FA had a greater depletion of n-3 FA levels in organs and tissues than mice carrying other APOE alleles. However, providing n-3 FA can restore levels of brain DHA in E4 animals and in other models of n-3 FA deficiency. In E4 carriers, supplementation with DHA as early as possible might help to prevent the onset of AD and could halt the progression of, and reverse some of the neurological and behavioural consequences of their higher vulnerability to n-3 FA deficiency.

Vitamin E deficiency during embryogenesis in zebrafish causes lasting metabolic and cognitive impairments despite refeeding adequate diets.

Vitamin E (α-tocopherol; VitE) is a lipophilic antioxidant required for normal embryonic development in vertebrates, but the long-term effects of embryonic VitE deficiency, and whether they are ameliorated by feeding VitE-adequate diets, remain unknown. We addressed these questions using a zebrafish (Danio rerio) model of developmental VitE deficiency followed by dietary remediation. Adult zebrafish maintained on VitE-deficient (E-) or sufficient (E+) diets were spawned to obtained E- and E+ embryos, respectively, which we evaluated up to 12 days post-fertilization (dpf). The E- group suffered significantly increased morbidity and mortality as well as altered DNA methylation status through 5 dpf when compared to E+ larvae, but upon feeding with a VitE-adequate diet from 5 to 12 dpf both the E- and E+ groups survived and grew normally; the DNA methylation profile also was similar between groups by 12 dpf. However, 12 dpf E- larvae still had behavioral defects. These observations coincided with sustained VitE deficiency in the E- vs. E+ larvae (p < 0.0001), despite adequate dietary supplementation. We also found in E- vs. E+ larvae continued docosahexaenoic acid (DHA) depletion (p < 0.0001) and significantly increased lipid peroxidation. Further, targeted metabolomics analyses revealed persistent dysregulation of the cellular antioxidant network, the CDP-choline pathway, and glucose metabolism. While anaerobic processes were increased, aerobic metabolism was decreased in the E- vs. E+ larvae, indicating mitochondrial damage. Taken together, these outcomes suggest embryonic VitE deficiency causes lasting behavioral impairments due to persistent lipid peroxidation and metabolic perturbations that are not resolved via later dietary VitE supplementation.

Algal supplementation of vegetarian eating patterns improves plasma and serum docosahexaenoic acid concentrations and omega-3 indices: a systematic literature review.

BACKGROUND: Vegetarians are likely to have lower intakes of preformed docosahexaenoic acid (DHA) than omnivorous populations who consume fish and animal products. As such, vegetarian populations have omega-3 indices up to 60% lower than those who consume marine products. Algae, the primary producer of DHA in the marine food chain, offer an alternative source of DHA for those who do not consume marine or animal products. This systematic review aims to examine the evidence for the relationship between supplementation with algal forms of DHA and increased DHA concentrations in vegetarian populations. METHODS: The SCOPUS, Science Direct and Web of Science scientific databases were searched to identify relevant studies assessing the effect of algal DHA consumption by vegetarian (including vegan) populations. RESULTS: Four randomised controlled trials and two prospective cohort studies met the inclusion criteria. All included studies reported algal sources of DHA significantly improve DHA concentrations (including plasma, serum, platelet and red blood cell fractions), as well as omega-3 indices, in vegetarian populations. An evident time or dose response was not apparent given the small number of studies to date. CONCLUSIONS: Future studies should address long chain n-3 polyunsaturated fatty acid deficiencies in vegetarian populations using algal DHA and explore the potential physiological and health improvements in these individuals.

Effect of dietary docosahexaenoic acid (DHA) in phospholipids or triglycerides on brain DHA uptake and accretion.

Tracer studies suggest that phospholipid DHA (PL-DHA) more effectively targets the brain than triglyceride DHA (TAG-DHA), although the mechanism and whether this translates into higher brain DHA concentrations are not clear. Rats were gavaged with [U-(3)H]PL-DHA and [U-(3)H]TAG-DHA and blood sampled over 6h prior to collection of brain regions and other tissues. In another experiment, rats were supplemented for 4weeks with TAG-DHA (fish oil), PL-DHA (roe PL) or a mixture of both for comparison to a low-omega-3 diet. Brain regions and other tissues were collected, and blood was sampled weekly. DHA accretion rates were estimated using the balance method. [U-(3)H]PL-DHA rats had higher radioactivity in cerebellum, hippocampus and remainder of brain, with no differences in other tissues despite higher serum lipid radioactivity in [U-(3)H]TAG-DHA rats. TAG-DHA, PL-DHA or a mixture were equally effective at increasing brain DHA. There were no differences between DHA-supplemented groups in brain region, whole-body, or tissue DHA accretion rates except heart and serum TAG where the PL-DHA/TAG-DHA blend was higher than TAG-DHA. Apparent DHA ß-oxidation was not different between DHA-supplemented groups. This indicates that more labeled DHA enters the brain when consumed as PL; however, this may not translate into higher brain DHA concentrations.

A role for 12/15-lipoxygenase-derived proresolving mediators in postoperative ileus: protectin DX-regulated neutrophil extravasation.

Resolution of inflammation is an active counter-regulatory mechanism involving polyunsaturated fatty acid-derived proresolving lipid mediators. Postoperative intestinal motility disturbances, clinically known as postoperative ileus, occur frequently after abdominal surgery and are mediated by a complex inflammation of the intestinal muscularis externa. Herein, we tested the hypothesis that proresolving lipid mediators are involved in the resolution of postoperative ileus. In a standardized experimental model of postoperative ileus, we detected strong expression of 12/15-lipoxygenase within the postoperative muscularis externa of C57BL/6 mice, predominately located within CX3CR1(+)/Ly6C(+) infiltrating monocytes rather than Ly6G(+) neutrophils. Mass spectrometry analyses demonstrated that a 12/15-lipoxygenase increase was accompanied by production of docosahexaenoic acid-derived lipid mediators, particularly protectin DX and resolvin D2, and their common precursor 17-hydroxy docosahexaenoic acid. Perioperative administration of protectin DX, but not resolvin D2 diminished blood-derived leukocyte infiltration into the surgically manipulated muscularis externa and improved the gastrointestinal motility. Flow cytometry analyses showed impaired Ly6G(+)/Ly6C(+) neutrophil extravasation after protectin DX treatment, whereas Ly6G(-)/Ly6C(+) monocyte numbers were not affected. 12/15-lipoxygenase-deficient mice, lacking endogenous protectin DX synthesis, demonstrated increased postoperative leukocyte levels. Preoperative intravenous administration of a docosahexaenoic acid-rich lipid emulsion reduced postoperative leukocyte infiltration in wild-type mice but failed in 12/15-lipoxygenase-deficient mice mice. Protectin DX application reduced leukocyte influx and rescued 12/15-lipoxygenase-deficient mice mice from postoperative ileus. In conclusion, our results show that 12/15-lipoxygenase mediates postoperative ileus resolution via production of proresolving docosahexaenoic acid-derived protectin DX. Perioperative, parenteral protectin DX or docosahexaenoic acid supplementation, as well as modulation of the 12/15-lipoxygenase pathway, may be instrumental in prevention of postoperative ileus.

Association between very long chain fatty acids in the meibomian gland and dry eye resulting from n-3 fatty acid deficiency.

In our previously study, we reported lower tear volume in with an n-3 fatty acid deficient mice and that the docosahexaenoic acid and total n-3 fatty acid levels in these mice are significantly reduced in the meibomian gland, which secretes an oily tear product. Furthermore, we noted very long chain fatty acids (≥25 carbons) in the meibomian gland. To verify the detailed mechanism of the low tear volume in the n-3 fatty acid-deficient mice, we identified the very long chain fatty acids in the meibomian gland, measured the fatty acid composition in the tear product. Very long chain fatty acids were found to exist as monoesters. In particular, very long chain fatty acids with 25-29 carbons existed for the most part as iso or anteiso branched-chain fatty acids. n-3 fatty acid deficiency was decreased the amount of meibum secretion from meibomian gland without change of fatty acid composition. These results suggest that the n-3 fatty acid deficiency causes the enhancement of evaporation of tear film by reducing oily tear secretion along with the decrease of meibomian gland function.

Beyond building better brains: bridging the docosahexaenoic acid (DHA) gap of prematurity.

Long-chain polyunsaturated fatty acids (LCPUFA) including docosahexaenoic acid (DHA) are essential for normal vision and neurodevelopment. DHA accretion in utero occurs primarily in the last trimester of pregnancy to support rapid growth and brain development. Premature infants, born before this process is complete, are relatively deficient in this essential fatty acid. Very low birth weight (VLBW) infants remain deficient for a long period of time due to ineffective conversion from precursor fatty acids, lower fat stores and a limited nutritional provision of DHA after birth. In addition to long-term visual and neurodevelopmental risks, VLBW infants have significant morbidity and mortality from diseases specific to premature birth, including bronchopulmonary dysplasia, necrotizing enterocolitis, and retinopathy of prematurity. There is increasing evidence that DHA has protective benefits against these disease states. The aim of this article is to identify the unique needs of premature infants, review the current recommendations for LCPUFA provision in infants and discuss the caveats and innovative new ways to overcome the DHA deficiency through postnatal supplementation, with the long-term goal of improving morbidity and mortality in this at-risk population.

Effect of docosahexaenoic acid-enriched fish oil supplementation in pregnant women with Type 2 diabetes on membrane fatty acids and fetal body composition--double-blinded randomized placebo-controlled trial.

AIMS: To test if docosahexaenoic acid-enriched fish oil supplementation rectifies red cell membrane lipid anomaly in pregnant women with Type 2 diabetes and their neonates, and alters fetal body composition. METHODS: Women with Type 2 diabetes (n = 88; 41 fish oil, 47 placebo) and healthy women (n = 85; 45 fish oil, 40 placebo) were supplemented from the first trimester until delivery. Blood fatty acid composition, fetal biometric and neonatal anthropometric measurements were assessed. RESULTS: A total of 117 women completed the trial. The women with Type 2 diabetes who took fish oil compared with those who received placebo had higher percentage of docosahexaenoic acid in red cell phosphatidylethanolamine in the third trimester (12.0% vs. 8.9%, P = 0.000) and at delivery (10.7% vs. 7.4%, P = 0.001). Similarly, the neonates of the women with Type 2 diabetes supplemented with the fish oil had increased docosahexaenoic acid in the red cell phosphatidylethanolamine (9.2% vs. 7.7%, P = 0.027) and plasma phosphatidylcholine (6.1% vs. 4.7%, P = 0.020). Docosahexaenoic acid-rich fish oil had no effect on the body composition of the fetus and neonates of the women with Type 2 diabetes. CONCLUSIONS: A daily dose of 600 mg of docosahexaenoic acid was effective in ameliorating red cell membrane docosahexaenoic acid anomaly in pregnant women with Type 2 diabetes and neonates, and in preventing the decline of maternal docosahexaenoic acid during pregnancy. We suggest that the provision of docosahexaenoic acid supplement should be integrated in the antenatal care of pregnant women with Type 2 diabetes.

Depletion of brain docosahexaenoic acid impairs recovery from traumatic brain injury.

Omega-3 fatty acids are crucial for proper development and function of the brain where docosahexaenoic acid (DHA), the primary omega-3 fatty acid in the brain, is retained avidly by the neuronal membranes. We investigated the effect of DHA depletion in the brain on the outcome of traumatic brain injury (TBI). Pregnant mice were put on an omega-3 fatty acid adequate or deficient diet from gestation day 14 and the pups were raised on the respective diets. Continuation of this dietary regime for three generations resulted in approximately 70% loss of DHA in the brain. Controlled cortical impact was delivered to both groups of mice to produce severe TBI and the functional recovery was compared. Compared to the omega-3 adequate mice, the DHA depleted mice exhibited significantly slower recovery from motor deficits evaluated by the rotarod and the beam walk tests. Furthermore, the DHA deficient mice showed greater anxiety-like behavior tested in the open field test as well as cognitive deficits evaluated by the novel object recognition test. The level of alpha spectrin II breakdown products, the markers of TBI, was significantly elevated in the deficient mouse cortices, indicating that the injury is greater in the deficient brains. This observation was further supported by the reduction of NeuN positive cells around the site of injury in the deficient mice, indicating exacerbated neuronal death after injury. These results suggest an important influence of the brain DHA status on TBI outcome.

Fatty-acid composition of maternal and umbilical cord plasma and early childhood atopic eczema in a Spanish cohort.

BACKGROUND/OBJECTIVES: Fatty-acid status during in-utero development might influence the risk of atopic diseases in early childhood. The aim of this work was to identify the relationship between maternal plasma and cord blood fatty acid (FA) composition and the risk of atopic eczema in the offspring at 14 months of age. SUBJECTS/METHODS: Two hundred and eleven non-atopic mothers and their children were studied. Mothers were recruited in their first trimester of gestation and children were monitored until 14 months of age. Samples of maternal plasma and cord blood plasma were analyzed to determine the FA profile of total lipids. Presence of atopic eczema in the infants was documented through questionnaires at 6 and 14 months of age. RESULTS: Higher concentrations of total long-chain polyunsaturated FA (LC-PUFA) were found in maternal plasma of non-atopic children in relation to atopic group. Moreover, this maternal plasma LC-PUFA content was negatively correlated with the atopic eczema (odds ratios (OR)=0.83, P=0.04) in infants. Regarding cord blood samples, docosahexaenoic acid (DHA C22:6n3) and the sum of total n-3 and of LC-PUFA n-3 showed a negative correlation with the prevalence of the disease (OR=0.50, 0.49 and 0.49, respectively). CONCLUSIONS: Our results show that the fatty-acid status of the fetus during pregnancy has an important role in the development of atopic eczema in early childhood. The prevalence of this atopic disorder is related to lower cord blood plasma levels of FA belonging to n-3 series, especially DHA.

Omega-3 fatty acids and brain resistance to ageing and stress: body of evidence and possible mechanisms.

The increasing life expectancy in the populations of rich countries raises the pressing question of how the elderly can maintain their cognitive function. Cognitive decline is characterised by the loss of short-term memory due to a progressive impairment of the underlying brain cell processes. Age-related brain damage has many causes, some of which may be influenced by diet. An optimal diet may therefore be a practical way of delaying the onset of age-related cognitive decline. Nutritional investigations indicate that the ω-3 poyunsaturated fatty acid (PUFA) content of western diets is too low to provide the brain with an optimal supply of docosahexaenoic acid (DHA), the main ω-3 PUFA in cell membranes. Insufficient brain DHA has been associated with memory impairment, emotional disturbances and altered brain processes in rodents. Human studies suggest that an adequate dietary intake of ω-3 PUFA can slow the age-related cognitive decline and may also protect against the risk of senile dementia. However, despite the many studies in this domain, the beneficial impact of ω-3 PUFA on brain function has only recently been linked to specific mechanisms. This review examines the hypothesis that an optimal brain DHA status, conferred by an adequate ω-3 PUFA intake, limits age-related brain damage by optimizing endogenous brain repair mechanisms. Our analysis of the abundant literature indicates that an adequate amount of DHA in the brain may limit the impact of stress, an important age-aggravating factor, and influences the neuronal and astroglial functions that govern and protect synaptic transmission. This transmission, particularly glutamatergic neurotransmission in the hippocampus, underlies memory formation. The brain DHA status also influences neurogenesis, nested in the hippocampus, which helps maintain cognitive function throughout life. Although there are still gaps in our knowledge of the way ω-3 PUFA act, the mechanistic studies reviewed here indicate that ω-3 PUFA may be a promising tool for preventing age-related brain deterioration.