Kebreab Ghebremeskel

Are deficits of arachidonic and docosahexaenoic acids responsible for the neural and vascular complications of preterm babies

We review evidence suggesting that pre- or postnatal deficits of arachidonic acid (AA) and docosahexaenoic acid (DHA) together with underdeveloped antioxidant protection contribute to neurovisual developmental disorders and other complications of premature birth. These two synergistic deficits occur at a time when 70% of energy is focused on brain development and when the brain and blood vessels are growing at high speed. The types of essential fatty acids fed to preterm babies bear no relation to what the infant would have received had it remained a fetus. This failure to meet essential fatty acid requirements exacerbates the AA and DHA deficits seen at birth; furthermore, the immature superoxide defenses remain depressed until the expected date of delivery. Deficits of these systems, which are required for cell membranes, the endothelium, and neural tissue, could provide the biochemical prerequisite for the membrane disorders to which these babies are at high risk: intraventricular hemorrhage, periventricular leucomalacia, retinopathy of prematurity, and bronchopulmonary dysplasia. Although poor vascular development during fetal and neonatal life may be repaired, the structural and antioxidant deficits identified in preterm babies may impair blood vessel development with long-term consequences. The conclusion drawn from this review is that present parenteral and enteral lipid nutrition for preterm babies is flawed and could be pathogenic. Full-term milk composition is the basis for the design of preterm infant foods, but full-term milk is different from the placental product that is rich in AA and DHA. Preterm lipid nutrition should be revised to be more in line with placental lipid transfer to the fetus.

The potential role for arachidonic and docosahexaenoic acids in protection against some central nervous system injuries in preterm infants

The risk of central nervous, visual, and auditory damage increases from 2/1000 live births in the normal birthweight to >200/1000 as birthweight falls below 1500 g. Such babies are most likely to be born preterm. Advances in infant care have led to increasing numbers of very-low-birthweight, preterm infants surviving to school age with moderate to severe brain damage. Steroids are one of the current treatments, but they cause significant, long-term problems. The evidence reported here suggests an additional approach to protecting the very preterm infant by supporting neurovascular membrane integrity. The complications of preterm, very-low-birthweight babies include bronchopulmonary dysplasia, retinopathy of prematurity, intraventricular hemorrhage, periventricular leukomalacia, and necrotizing enterocolitis, all of which have a vascular component. Arachidonic acid (AA) and DHA are essential, structural, and functional constituents of cell membranes. They are especially required for the growth and function of the brain and vascular systems, which are the primary biofocus of human fetal growth. Molecular dynamics and experimental evidence suggest that DHA could be the ligand for the retinoid X receptor (RXR) in neural tissue. RXR activation is an obligatory step in signaling to the nucleus and in the regulation of gene expression. Very preterm babies are born with minimal fat stores and suboptimal circulating levels of these nutrients. Postanatally, they lose the biomagnification of the proportions of AA and DHA by the placenta for the fetus. No current nutritional management repairs these deficits. The placental biomagnification profile highlights AA rather than DHA. The resultant fetal FA profile closely resembles that of the vascular endothelium and not the brain. Without this nourishment, cell membrane abnormalities would be predicted. We present a scientific rationale for a common pathogenic process in the complications of prematurity.

Abnormal aortic fatty acid composition and small artery function in offspring of rats fed a high fat diet in pregnancy

1 Disturbances of the in utero environment are associated with an increased risk of cardiovascular disease in adulthood. In this study we have determined whether abnormal vascular function in the adult offspring of rats fed a high saturated fat diet in pregnancy is associated with altered plasma lipids or vascular fatty acid content. 2 Female Sprague‐Dawley rats were fed a breeding diet (4 % fat) or a diet high in saturated fat (20 % fat) for 10 days prior to and throughout pregnancy, and during weaning. Female offspring were then fed a maintenance diet (3 % fat) until 160 days of age. 3 Endothelium‐dependent relaxation induced by acetylcholine was blunted in isolated branches of the femoral artery from 160‐day‐old female offspring of dams fed the saturated fat diet when compared with female offspring of dams fed the breeding diet. These offspring exhibited elevated plasma triglyceride and reduced plasma high density lipoprotein cholesterol concentrations. 4 The fatty acid composition of the aortas was abnormal, with a marked reduction in the content of arachidonic and docosahexaenoic acids. 5 This study demonstrates that a high fat diet in pregnant rats produces abnormal vascular function, plasma lipid disturbances and altered vascular fatty acid content in their female offspring during adulthood.

Fatty Acid Ratios in Free-Living and Domestic Animals

• Human physiology during evolution would have been adapted to the nature of wild foods, yet there is a striking qualitative and quantitative difference between the fat in wild or extensive meat consumption compared to what we eat today.

Nutrition and neurodevelopmental disorders.

Since the 1960s the structural requirements for the growth, development and function of the brain have become better understood due to the recognition of the prodigious energy needs for brain development and its structural requirements for lipids. The most vulnerable period of neural development is during embryonic and fetal growth. There is now both retrospective and prospective evidence that maternal nutrition prior to conception is most important to pregnancy outcome. Our studies on maternal nutrition in pregnancy again illustrate the relationship of maternal nutrition to birthweight and head circumference. In a study of 513 pregnancies we found that nutrient intakes in mothers of low birthweight babies were well below those of mothers whose babies were in the 3.5–4.5 Kg range at which morbidity is at its lowest. Nutrient intakes tracked with birthweight, independent of smoking and alcohol up to, but not above 3,270 g. The closest correlations were obtained with the diet of the mother at or about the time of conception rather than later in the pregnancy. Our studies also reveal that premature and intrauterine growth retarded babies were born with deficits of the types of essential fatty acids (arachidonic AA, docosahexaenoic DHA acids) known to be required for brain development. Deficits of brain DHA have been found experimentally to impair visual and cognitive development and also to cause haemorrhage, not unlike peri-ventricular haemorrhage in low birthweight babies, the above evidence is suggestive of a route to test the prevention and treatement of these types of membrane related disorders.

Effect of omega-3 (n−3) fatty acid supplementation in patients with sickle cell anemia: randomized, double-blind, placebo-controlled trial

BACKGROUND Blood cell aggregation and adherence to vascular endothelium and inflammation play a central role in vaso-occlusive crisis in sickle cell disease. The antiaggregatory, antiadhesive, antiinflammatory, and vasodilatory omega-3 (n-3) fatty acids (DHA and EPA) are significantly reduced in patients with the disease. OBJECTIVE The aim was to investigate the therapeutic potential of omega-3 fatty acids for patients with homozygous sickle cell disease in a randomized, placebo-controlled, double-blind trial. DESIGN One hundred forty patients recruited from a single center in Sudan were randomly assigned and received, daily, 1 (age 2-4 y), 2 (age 5-10 y), 3 (age 11-16 y), or 4 (age ≥17 y) omega-3 capsules containing 277.8 mg DHA and 39.0 mg EPA or placebo for 1 y. Of these patients, 128 were followed up and the data were obtained. The primary and secondary endpoints-rates of clinical vaso-occlusive crisis and hemolytic events, blood transfusion rate, school attendance, and blood count-were analyzed by intention-to-treat analysis (n = 140). RESULTS Omega-3 treatment reduced the median rate of clinical vaso-occlusive events (0 compared with 1.0 per year, P < 0.0001), severe anemia (3.2% compared with 16.4%; P < 0.05), blood transfusion (4.5% compared with 16.4%; P < 0.05), white blood cell count (14.4 ± 3.3 compared with 15.6 ± 4.0 ×10(3)/μL; P < 0.05), and the OR of the inability to attend school at least once during the study period because of illness related to the disease to 0.4 (95% CI: 0.2, 0.9; P < 0.05). CONCLUSION The findings of this trial, which need to be verified in a large multicenter study, suggest that omega-3 fatty acids can be an effective, safe, and affordable therapy for sickle cell anemia. This trial was registered with Current Controlled Trials as ISRCTN80844630.

Blood fatty acid composition of pregnant and nonpregnant Korean women: Red cells may act as a reservoir of arachidonic acid and docosahexaenoic acid for utilization by the developing fetus

Relative fatty acid composition of plasma and red blood cell (RBC) choline phosphoglycerides (CPG), and RBC ethanolamine phosphoglycerides (EPG) of pregnant (n=40) and nonpregnant, nonlactating (n=40), healthy Korean women was compared. The two groups were of the same ethnic origin and comparable in age and parity. Levels of arachidonic (AA) and docosahexaenoic (DHA) acids were lower (P<0.05) and palmitic and oleic acids higher (P<0.0001) in plasma CPG of the pregnant women. Similarly, the RBC CPG and EPG of the pregnant women had lower AA and DHA (P<0.05) and higher palmitic and oleic acids (P<0.01). The reduction in DHA and total n−3 fatty acids in plasma CPG of the pregnant women was paralleled by an increase in docosatetraenoic (DTA) and docosapentaenoic (DPA) acids of the n−6 series and in DPA/DTA ratio. In the RBC phospholipids (CPG and EPG) of the pregnant women, DTA and DPA acids of the n−6 series and DPA/DTA ratio did not increase with the decrease of the n−3 metabolites (eicosapentaenoic acid, DPA, and DHA) and total n−3. Since pregnancy was the main identifiable variable between the two groups, the lower levels of AA and DHA in RBC CPG and EPG of the pregnant women suggest that the mothers were mobilizing membrane AA and DHA to meet the high fetal requirement for these nutrients. It may also suggest that RBC play a role as a potential store of AA and DHA and as a vehicle for the transport of these fatty acids from maternal circulation to the placenta to be utilized by the developing fetus.

Gestational diabetes mellitus enhances arachidonic and docosahexaenoic acids in placental phospholipids.

In previous studies, we reported that neonates of women with gestational diabetes mellitus (GDM) have reduced blood levels of arachidonic acid (AA) and docosahexaenoic acid (DHA) that were unrelated to maternal status. Since both AA and DHA are selectively transferred from maternal to fetal circulation by the placenta, we have investigated whether the FA composition of the placenta is altered by GDM. Thirty-six women, 11 with and 25 without GDM, were recruited from Newham General Hospital, London. The women with GDM had higher levels of di-homo-γ-linolenic (P<0.05), docosate-traenoic (n-6 DTA; P<0.0001), docosapentaenoic n-6 (P<0.005), total n-6 (P<0.005), docosapentaenoic (n-3 DPA; P<0.005), and total n-3 (P<0.01) FA, as well as higher levels of AA (P<0.05) and DHA (P<0.01), in placental choline phosphoglycerides (CPG) compared with the healthy women who served as controls. Similarly, the women with GDM had elevated n-6 DTA (P<0.005), AA, total n-6 metabolites (P<0.05), DHA, total n-3 metabolites, and total n-3 FA (P<0.005) in ethanolamine phosphoglycerides (EPG). In contrast to CPG and EPG, the placental TG of the women with GDM had higher linoleic acid (P<0.05) and lower AA, n-6 metabolites, and n-3 DPA (P<0.01). The placenta is devoid of desaturase activity, and it is thought to be reliant on maternal circulation for both AA and DHA. Hence, the enhanced levels of the two FA in the placenta of the GDM group suggests that these FA are taken up from the maternal circulation and retained after esterification into phosphoglycerides instead of being transferred to the fetus. Further study is needed to elucidate the mechanism involved and the effect of the phenomenon on postnatal growth and development of the offspring.

Adverse effect of obesity on red cell membrane arachidonic and docosahexaenoic acids in gestational diabetes

Aims/hypothesisGestational diabetes is a metabolic disorder affecting 2–5% of women and is a predictor of obesity, Type 2 diabetes mellitus and cardiovascular disease. Insulin resistance, a characteristic of gestational diabetes and obesity, is correlated with the fatty acids profile of the red cell and skeletal muscle membranes. We investigated the plasma and red cell fatty acid status of gestational diabetes. The effect of obesity on membrane fatty acids was also examined.MethodsFasting blood obtained at diagnosis was analysed for the fatty acids in plasma choline phosphoglycerides and red cell choline and ethanolamine phosphoglycerides.ResultsThere were reductions in arachidonic acid (controls 10.74±2.35 vs gestational diabetes 8.35±3.49, p<0.01) and docosahexaenoic acid (controls 6.31±2.67 vs gestational diabetes 3.25±2.00, p<0.0001) in the red cell choline phosphoglycerides in gestational diabetes. A similar pattern was found in the ethanolamine phosphoglycerides. Moreover, the arachidonic and docosahexaenoic acids depletion in the red cell choline phosphoglycerides was much greater in overweight/obese gestational diabetes (arachidonic acid=7.49±3.37, docosahexaenoic acid=2.98±2.18, p<0.01) compared with lean gestational diabetes (arachidonic acid=10.03±2.74, docosahexaenoic acid=4.18±1.42).Conclusion/interpretationApparently normal plasma choline phosphoglycerides fatty acids profile in the gestational diabetic women suggested that membrane lipid abnormality is associated specifically with perturbation in the membrane. The fact that the lipid abnormality is more pronounced in the outer leaflet of the membrane where most of receptor binding and enzyme activities take place might provide an explanation for the increased insulin resistance in gestational diabetes and obesity.

Modern organic and broiler chickens sold for human consumption provide more energy from fat than protein.

OBJECTIVE In 1976, the Royal College of Physicians and the British Cardiac Society recommended eating less fatty red meat and more poultry instead because it was lean. However, the situation has changed since that time, with a striking increase in fat content of the standard broiler chicken. The aim of the present study was to report a snapshot of data on fat in chickens now sold to the public. DESIGN Samples were obtained randomly between 2004 and 2008 from UK supermarkets, farm shops and a football club. The amount of chicken fat was estimated by emulsification and chloroform/methanol extraction. SETTING Food sold in supermarkets and farms in England. SUBJECTS Chicken samples. RESULTS The fat energy exceeded that of protein. There has been a loss of n-3 fatty acids. The n-6:n-3 ratio was found to be as high as 9:1, as opposed to the recommendation of about 2:1. Moreover, the TAG level in the meat and whole bird mostly exceeded the proportion of phospholipids, which should be the higher for muscle function. The n-3 fatty acid docosapentaenoic acid (DPA, 22 : 5n-3) was in excess of DHA (22 : 6n-3). Previous analyses had, as usual for birds, more DHA than DPA. CONCLUSIONS Traditional poultry and eggs were one of the few land-based sources of long-chain n-3 fatty acids, especially DHA, which is synthesized from its parent precursor in the green food chain. In view of the obesity epidemic, chickens that provide several times the fat energy compared with protein seem illogical. This type of chicken husbandry needs to be reviewed with regard to its implications for animal welfare and human nutrition.