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.

Dietary fat intake, circulating and membrane fatty acid composition of healthy Norwegian men and women.

BACKGROUND: The present study aimed to assess the dietary fat intake and blood fatty acid status of healthy Norwegian men and women living in Bergen whose habitual diet is known to be high in long-chain omega-3 fat. METHODS: Healthy men (n = 41) and women (n = 40) aged 20-50 years who were regular blood donors completed 7-day food diaries and their nutrient intake was analysed by Norwegian food database software, kbs, version 4.9 (kostberegningssystem; University of Oslo, Oslo, Norway). Blood samples were obtained before blood donation and assessed for the fatty acid composition of plasma triglycerides and cholesterol esters, phosphatidylcholine, and red cell phosphatidylcholine and phosphatidylethanolamine. RESULTS: There was no difference in dietary fat intake between men and women. Total and saturated fat intakes exceeded the upper limits of the recommendations of the National Nutrition Council of Norway. Although polyunsaturated fat intake was close to the lower limit of the recommended level, the intake varied greatly among individuals, partly as a result of the use of supplementary fish oil. Moreover, the proportional fatty acid composition of plasma and red cell lipids was similar between men and women. Enrichment of docosahexaenoic acid in red cell phosphatidylethanolamine was found in fish oil users. CONCLUSIONS: The results of the present study provide a snapshot of the current nutritional status of healthy Norwegian adults. Moreover, the detailed blood fatty acid composition of men and women whose habitual diet constitutes high long-chain polyunsaturated omega-3 fat as well as saturated fat could be used as reference value for population studies.

Adverse Pregnancy Outcomes in Sickle Cell Trait: a Prospective Cohort Study Evaluating Clinical and Haematological Parameters in Postpartum Mothers and Newborns.

Background: Sickle cell trait (SCT) is a congenital condition caused by the inheritance of a single allele of the abnormal haemoglobin beta gene, HbS. Carriers of SCT are generally asymptomatic, and they do not manifest the clinical and haematological abnormalities of sickle cell anaemia (SCA). However, there is evidence that they display some symptoms in stressful situations. Pregnancy is a stressful physiological event, and it is not clear if SCT adversely affects pregnancy outcomes, particularly in those from developing countries where people regularly suffer from nutritional insufficiency. Objective: This study aims to investigate pregnancy outcomes in Sudanese women with SCT. Subjects and methods: Pregnant women with (HbAS, n=34) and without (HbAA, n=60) SCT were recruited during their first trimester at El Obeid Hospital, Kordofan, Western Sudan. Following appropriate ethical approval and informed consent from the participants, detailed anthropometric, clinical, haematological, obstetric, and birth outcome data were registered. In addition, blood samples were collected at enrolment and at delivery. Results: At enrolment in the first trimester, the SCT group did not manifest SCA symptoms, and there was no difference in the haematological parameters between the SCT and control groups. However, at delivery, the women with SCT, compared with the control group, had lower levels of hemoglobin (Hb, p=0.000), packed cell volume (PCV, p=0.000), mean corpuscular haemoglobin (MCH, p=0.002) and neutrophil counts (p=0.045) and higher mean corpuscular volume (MCV, p=0.000) and platelet counts (p=0.000). Similarly, at delivery, the babies of SCT women had lower birth weight (p=0.000), lower Hb (p=0.045), PCV (p=0.000), MCH (p=0.000), and higher neutrophil (p=0.004) and platelet counts (p=0.000) than the babies of the healthy control group. Additionally, there were more miscarriages, stillbirths, and admissions to the Special Care Baby Unit (SCBU) in the SCT group. Conclusions: The study revealed that SCT is associated with adverse pregnancy outcomes, including maternal and neonatal anaemia, low birth weight, and increased risk of stillbirth, miscarriage, and admission to SCBU. Therefore, pregnant women with SCT should be given appropriate pre-conceptual advice and multidisciplinary antenatal and postnatal care.

Dietary fat intake, body composition and blood lipids of university men and women.

BACKGROUND: Cardiovascular disease rates are high in the U.K., particular in men, and are related to dietary fat intake. We conducted a pilot study to investigate relationships between saturated and unsaturated dietary fat intakes, body composition and blood lipid parameters in Caucasian men and women at university. METHODS: Volunteers (52 men and 52 women; age range 20-50 years) were recruited from staff and students of London Metropolitan University. Dietary intake, body composition, blood pressure and fasting blood glucose and lipids were assessed. Gender differences between the measured variables and their relationships were assessed by Mann-Whitney U-test, and by multi-linear (stepwise) regression, respectively. RESULTS: Men consumed more saturated fat (29.5 vs. 20.5 g/day, p < 0.001), and had elevated levels of glucose (5.34 + 0.74 vs. 4.85 + 0.49 mmol/l, p < 0.001), low-density lipoprotein (LDL) cholesterol (2.99 + 1.5 vs. 2.62+ 0.74 mmol/l, p < 0.05), systolic blood pressure (126.4 + 11.0 vs. 112.6 + 17.2 mm/Hg, p < 0.001), and lower high-density lipoprotein (HDL) cholesterol (1.41 ± 0.34 vs. 1.83 ± 0.43, p < 0.001). Saturated fat was positively associated with total body fat ( p < 0.05), trunk fat ( p < 0.001), HDL cholesterol ( p < 0.05) and systolic blood pressure ( p < 0.001) in women, while in men docosahexaenoic acid and total cholesterol ( p < 0.05), total omega-3 fatty acids and LDL cholesterol ( p < 0.001), total omega-3 fatty acids and triglycerides ( p < 0.01) were positively related. Similar n-3 fatty acid intakes were reported in nutritionally aware students and other university subjects. CONCLUSIONS: The data of this study indicate gender-related differences in response to dietary fat, and widespread low compliance with n-3 fatty acid recommendations. Although the men are highly health conscious and physically active, their blood lipid levels are indicative of a risk of cardiovascular disease. In addition to enhanced nutritional education to increase seafood intakes in this age group of men and women, customised dietary and lifestyle advice may be required in the men.

Dimethyl acetals, an indirect marker of the endogenous antioxidant plasmalogen level, are reduced in blood lipids of Sudanese pre-eclamptic subjects whose background diet is high in carbohydrate.

In Sudanese women with (n = 60) and without (n = 65) pre-eclampsia, circulating lipids, plasma and red cell saturated and monounsaturated fatty (MUFA) acids and dimethyl acetals (DMAs) were investigated. DMAs are an indirect marker of levels of plasmalogens, endogenous antioxidants, which play a critical role in oxidative protection, and cholesterol homeostasis. The pre-eclamptics had higher C18:1n-9 (p < 0.001) and ΣMUFA (p < 0.01) in plasma free fatty acids, C16:1n-7, C18:1n-9, ΣMUFA; 16:0/16:1n-7 (p < 0.01) in erythrocyte choline phosphoglycerides (ePC) and 16:1n-7, 18:1n-7 and 16:0/16:1n-7 (p < 0.01) in erythrocyte ethanolamine phosphoglycerides (ePE). In contrast, the DMAs 18:0, 18:1 and ΣDMAs in ePE, and 16:0, 18:0 and ΣDMAs in ePC were reduced (p < 0.001) in the pre-eclamptic women. This study of pregnant women with high carbohydrate and low fat background diet suggests pre-eclampsia is associated with oxidative stress and enhanced activity of the microsomal enzyme stearyl-CoA desaturase (delta 9 desaturase), as assessed by palmitic/palmitoleic (C16:0/C16:n-1) and stearic/oleic (C18/C18:1n-9) ratios.

Plasma fatty acid abnormality in Sudanese drug-resistant epileptic patients.

Intervention studies have demonstrated that the n-3 fatty acids, docosahexaenoic and eicosapentaenoic acids, ameliorate seizure frequency in patients with drug-resistant epilepsy (DRE). There is a scarcity of fatty acid status of patients with epilepsy. We have investigated blood fatty acids of patients with DRE and assessed the indices of elongase and desaturase activities. DRE patients (n = 83) and healthy controls (n = 31) were recruited form Soba University Hospital Neurology Referral Clinic and Ibn-Auf paediatric Teaching Hospital Neurology Referral Clinic, Khartoum, Sudan. Fatty acid composition of plasma total lipids, phosphatidylcholine and neutral lipids were analysed. The patients compared with their healthy counterparts had higher levels of C14:0, C16:0, C18:0, C20:0, C22:0 (p<0.05) and C24:0, and total saturates (p<0.05). Similarly, the proportions of C16:1n-7, 18:1n-7, C18:1n-9, C20:1n-9, C24:1n-9 and total monounsaturated fatty acids; p<0.005) were higher in the drug-resistant patients. Conversely, the patients had lower levels of n-6 (C18:2n-6, C18:3n-6, C20:4n-6, n-6 metabolites and total n-6; p<0.005 and C20:2n-6 and C20:3n-6; p<0.05) and n-3 (C20:5n-3, C22:5n-3, C22:6n-3, ∑EPA and DHA, n-3 metabolites and total n-3; p<0.05) fatty acids. Indices of elongase and desaturase activities - The plasma total lipid ratios of C16:0/C14:0 (p = 0.001), C18:0/C16:0 (p = 0.001), C16:1n-7/C16:0 (p = 0.027), C18:1n-9/C18:0 (p = 0.022) and C22:4n-6/C20:4n-6 (p = 0.008) were higher and C18:3n-6/C18:2n-6 (p = 0.05), C20:4n-6/C20:3n-6 (p = 0.032) and C20:4n-6/C18:2n-6 (p>0.05) lower in the patients with drug-resistant epilepsy than in the healthy control subjects. DRE is associated with blood fatty acid perturbation and abnormal activities of long-chain fatty acid elongase (ELOVL-6), stearoyl-coenzyme A desaturase-1 (SCD-1), delta 6-fatty acid desaturase (D6D) and delta 5 fatty acid desaturase (D5D). N-3 fatty acids are known to ameliorate seizures frequency and dampen neuronal hyperexcitability. Therefore, patients with DRE should be regularly monitored and, if necessary, supplemented with n-3 fatty acids.

Milk of northern Sudanese mothers whose traditional diet is high in carbohydrate contains low docosahexaenoic acid.

AIM: The suckling neonates and infants are reliant primarily on the mother for optimal supply of docosahexaenoic acid (DHA). The richest source of preformed DHA is cold-water oily fish. Although there is paucity of data, existing evidence suggest women with restricted access to these foods have low or marginal DHA status. The aim of the study was to investigate milk fatty acids of Sudanese mothers whose traditional diet is high in carbohydrate and low in fat and gain some insight into the provision of DHA to the suckling offspring. METHODS: Colostrum (n =26), transitional (n=20) and mature (n=14) milk samples were obtained from Northern Sudanese women (NSW) recruited prior to delivery from Ibrahim Malik and Khartoum Teaching Hospitals. RESULTS: The arachidonic acid content of the colostrum (0.87±0.28%) and transitional (0.89± 0.29%) and mature (0.48±0.12%) milk of the NSW were broadly comparable with published international values. In contrast, the DHA level (colostrum 0.13±0.07%, transitional 0.13±0.06% and mature milk 0.06±0.05%) was very low. CONCLUSION: The study reveals breast milk of NSW, whose traditional diet is almost devoid of fish and fish products, is unlikely to provide sufficient DHA to support optimal postnatal neuro-visual development.

Erythrocyte antioxidant enzymes and plasma antioxidant vitamins in Sudanese women with pre-eclampsia.

This case-control study was conducted in Khartoum hospital, Sudan to investigate the levels of antioxidant enzymes (glutathione peroxidase, catalase and superoxide dismutase) in erythrocytes and plasma antioxidant vitamins (retinol and alpha-tocopherol) in Sudanese women with pre-eclampsia (37), in comparison with well-matched pregnant controls women with normal pregnancy (38). Enzymes were measured using ELISA and vitamins were measured using HPLC. There were no significant differences in the levels of these three antioxidant enzymes in pre-eclamptic women compared with the controls. Women with mild pre-eclampsia (diastolic blood pressure, DBP < 110) have slightly higher levels of erythrocyte glutathione peroxidase, and lower levels of catalase and superoxide dismutase compared with women with severe pre-eclampsia (DBP > or = 110). A significantly negative correlation was observed between the levels of glutathione peroxidase and DBP, r = -0.371, p = 0.02. There was no significant correlation between catalase (r = -0.033, p = 0.840) or superoxide dismutase levels (r = 0.067, p = 0.6) and DBP. While retinol levels were not different, levels of alpha-tocopherol were significantly higher in women with pre-eclampsia than the control group, p = 0.026. The plasma levels of both vitamins were not statistically significantly different when women with mild and severe pre-eclampsia were compared.

Erythrocyte omega-3 and omega-6 fatty acids profile in Sudanese women with pre-eclampsia.

A case-control study was conducted in Khartoum hospital, Sudan to compare omega-3 and omega-6 fatty acids profile in three phospholipid fractions (phosphatidylethanolamine, phosphatidylcholine and sphingomyelin) using gas chromatography in erythrocytes from 65 pre-eclamptic women and well-matched 60 healthy control pregnant women, both in the third trimester of pregnancy. While levels of arachidonic acid (omega-6 fatty acid) was significantly higher in women with pre-eclampsia in the sphingomyelin fraction only, the levels of eicosapentaenoic and docosahexaenoic acid (omega-3 fatty acid) in the three phospholipids fractions were significantly higher in women with pre-eclampsia than in the control group. Both omega-3 and omega-6 fatty acids profiles were not significantly different between patients with mild (diastolic blood pressure (DBP) <110 mmHg) and severe (DBP > or = 110 mmHg) pre-eclampsia.

Salt fortification with iodine: Sudan situation analysis.

Iodine deficiency disorders (IDD) constitute a severe public health problem in Sudan. IDD affects children and women throughout life. More than 2 out of 10 school age children have goiter. The prevalence reaches 40% in some regions of the country. Several interventional measures were introduced to control the IDD problem. While the situation with regard to production and supply of iodized salt was thus deteriorating, an Emergency Food Security and Nutrition Assessment Survey (EFSNA) revealed that the prevalence of IDD among adult women, as reflected in the presence of visible goiter, was as high as 25.5%. We have conducted a situation analysis survey in the Republic of Sudan to review the prevailing situation and suggest a benchmark that would help in developing effective control measures and in monitoring their implementations. SWOT analysis, questionnaire, focus groups discussion beside a combination of rapid assessment approach and qualitative method were used to critically evaluate the salt iodization situation in the country and assess the prevailing IDD situation in and propose a plan of action to overcome the bottlenecks. The survey concluded that Iodine deficiency affects children and women all through Sudan. The prevalence is even greater in some regions of the country and there is no supportive policy environment for successful universal salt iodization. To overcome this aggravated situation Sudan will need to conduct a baseline study to provide data on the prevalence of IDD, geographic distribution, knowledge, attitudes and practices relating to iodine deficiency. This will provide a benchmark that will help in developing effective control measures and in monitoring their implementation. The study recommended a set of actions to the government to overcome the prevailing situation and strengthening the current policy and implementation.

Fatty acid status in captive and free-ranging black rhinoceroses (Diceros bicornis).

The fatty acid (FA) patterns of plasma/serum triglycerides (TG), phospholipids (PL) and cholesteryl esters (CE) of captive and free-ranging black rhinoceroses (Diceros bicornis) were investigated. Free-ranging animals (n = 28) stemmed from four different regions. Captive animals sampled included specimens from North American (n = 11) and three different European facilities (n = 6). The European animals were tested on 1-4 different diets, resulting in a total of 15 blood samples. Regardless of differences between the free-ranging animals from different regions, differences between captive and free-ranging animals were relatively uniform: captive animals had higher overall proportions of polyunsaturated fatty acid (PUFA), due to levels of linoleic acid (LA, 18:2n6) that were drastically increased as compared to free-ranging animals. In contrast, levels of alpha-linolenic acid (ALA, 18:3n3) were consistently lower on conventional zoo diets. n6/n3 ratios for TG, PL and CE were 1.6, 10 and 8 in samples from free-ranging animals, respectively, as compared to 4.1-16.3, 16-148 and 40-277 in samples from captive animals. There was a distinct correlation between the proportion of grain-based products (commercial concentrates, plain grains and bread) in the diets of the European animals and the measured levels of n6 PUFA. An animal from a facility with a very low proportion of grain products in the diet nevertheless had high LA readings, most probably due to the use of sunflower oil as 2% (dry matter basis) of its diet. One animal that received a high proportion of grass meal pellets due to an oral disease had increased ALA contents after the diet change. These results allow conclusions on the suitability of diets fed in captivity: the black rhinoceros is prone to several uncommon diseases that have been suspected to be linked to oxidative damage, possibly due to the disposition of this species to excessive iron storage. An unnatural dietary loading with PUFAs would exacerbate this problem. Additionally, n6 FAs are known as precursors of pro-inflammatory mediators, and their overrepresentation could therefore exacerbate any inflammatory processes. Therefore, the current practice of using grain-based feeds as major ingredients in captive rhinoceros diets is discouraged. Diet items containing ALA (a precursor of anti-inflammatory mediators) such as, fresh grass, fresh browse, the respective silages should be included at higher levels in diets for captive black rhinoceroses. Grass meal pellets, although a good source of ALA and linked with high levels of ALA in an animal of this study, must be chosen with care for black rhinoceroses due to their particular proneness for high iron contents.

DHA-enriched re-esterified triacylglycerol fish oil supplementation and oily fish consumption enhance red blood n-3 fatty acid index in Omani pre-adolescent schoolchildren.

Dietary habits of Omani population particularly of children and young adults have changed significantly. Consumption of imported calorie-dense foods, vegetable oils, milled and polished grains and carbonated beverages have become the norm. Concomitantly, there has been an exponential increase in the prevalence of non-communicable diseases. The impact of the westernisation of eating habits on children has not been evaluated. We have investigated blood fatty acid profile of male (n = 125) and female (n = 160) children aged 9 and 10 (9.8 ±â€¯0.4) years enrolled from three state-funded schools. The schools, which are homogenous with respect to socio-economic background of their pupils, were randomised into fish oil (n = 98), oily fish (n = 82) or control (n = 105) group. Subsequently, the children were given during morning tea break for 12 weeks: 1. DHA-enriched re-esterified triacylglycerol fish oil capsule with cheese/salad sandwich (fish oil group), 2. Lightly grilled oily fish with salad (fish group) or 3. Cheese/salad sandwich (control group). At baseline, the males had higher myristic, palmitic and oleic and lower adrenic acids than the females (p < 0.05). There was no difference in n-3 fatty acid index (4.86 ±â€¯1.95 vs. 5.12 ±â€¯1.67, p > 0.05) or AA (14.6 ±â€¯1.9 vs. 14.9 ±â€¯1.8, p > 0.05) between the genders. There was no difference in any of the fatty acids between the three groups at baseline. Post-intervention, the oily fish group had lower n-3 fatty acid index (EPA + DHA, 6.03 ±â€¯1.39 vs. 6.60 ±â€¯1.63, p < 0.05) and higher AA (15.2 ±â€¯1.8 vs. 13.7 ±â€¯2.0, p = 0.0001) and n-3 DPA (1.40 ±â€¯0.27 vs. 1.07 ±â€¯0.22, p = 0.0001) compared with those who received fish oil capsules. In both the fish oil and oily fish groups, fatty acid index correlated positively with AA (r = 0.394, p = 0.0001; r = 0.231, p = 0.038) and negatively with total saturated (r = - 0.816, p = 0.0001; r = - 0.439, p = 0.0001) and total mono-unsaturated (r = - 0.431, p = 0.0001; r = - 0.231, p = 0.037) fatty acids. Although seafood is an integral part of traditional Omani cuisine the children had a low level of n-3 fatty acids index. There is a need to address this nutritional insufficiency through school feeding programme, targeted intervention with n-3 fatty acid enriched food products and/or family education programme.

Fatty acid composition of milk of refugee Karen and urban Korean mothers. Is the level of DHA in breast milk of Western women compromised by high intake of saturated fat and linoleic acid?

BACKGROUND: Lower proportions of docosahexaenoic acid (DHA) and total n-3 metabolites have been reported in breast milk of European, Australian and North American women compared with milk of mothers from non-Western countries. This difference is not always explained by intakes of marine products. OBJECTIVE: We investigated the possibility that the relative composition of DHA and total n-3 metabolites in breast milk of non-Western mothers with low fat intakes is higher than the levels commonly reported in their Western counterparts. SUBJECTS: Mature milk of refugee Karen women from two different camps in Thailand (n=26 and n=53), and transition milk from urban Korean mothers (n=12) in Seoul was collected. In common with their respective community, the mothers have low fat intake, which is predominately of plant origin. RESULTS: The percentage levels of DHA and n-3 metabolites in the milk of the Karen mothers were 0.52 +/- 0.14 and 0.85 +/- 0.24 (camp 1) and 0.54 +/- 0.22 and 0.92 +/- 0.42 (camp 2). In the Korean milk, DHA was 0.96 +/- 0.21 and total n-3 metabolites 1.51 +/- 0.3. CONCLUSION: We postulate that the levels of DHA and total n-3 metabolites may be compromised in breast milk of mothers on the Western high fat diet. This calls into question the use of DHA composition of such milk as a reference for the formulation of milk designed, for infant feed or, to test the function of DHA in neuro-visual development.

Vitamin A deficiency enhances docosahexaenoic and osbond acids in liver of rats fed an alpha linolenic acid-adequate diet.

The synthesis of docosahexaenoic (DHA, 22:6n-3) and Osbond acid (OA, 22:5n-6) is regulated by the heterodimer of peroxisome proliferator-activated receptor and retinoid X receptor (RXR). 9-Cis retinoic acid, a metabolite of vitamin A, is the most potent ligand of RXR. We tested whether vitamin A deficiency impairs DHA and OA synthesis in rats fed a vitamin A- and alpha-linolenic acid (ALA)-sufficient (VASALAS), vitamin A-sufficient and ALA-deficient (VASALAD), vitamin A-deficient and ALA-sufficient (VADALAS), or vitamin A- and ALA-deficient (VADALAD) diet. After 7 wk of feeding, liver and colon choline (CPG) and ethanolamine (EPG) phosphoglyceride FA were analyzed. The VADALAS compared with the VASALAS rats had elevated levels of both DHA (P< 0.05) and OA (P < 0.005) in liver CPG and EPG. In contrast, the VADALAD group had a lower DHA (P < 0.01) and higher OA (P < 0.005) level in CPG and EPG of both tissues than their VASALAD counterparts. ALA deficiency reduced DHA and enhariced OA levels in liver and colon CPG and EPG in both the vitamin A-sufficient (VASALAS vs. VASALAD) and -deficient (VADALAS vs. VADALAD) rats (P < 0.005). The study demonstrates that ALA deficiency reduced DHA and enhanced OA levels in tissue membranes, and dietary vitamin A deficiency has a profound effect on membrane DHA and OA in rat tissues. Both vitamin A and DHA are involved in a myriad of vital physiological functions pertaining to growth and development and health. Hence, there is a need for a further study to unravel the mechanism by which vitamin A influences membrane DHA and OA.

Deleterious effects of lard-enriched diet on tissues fatty acids composition and hypothalamic insulin actions.

Altered tissue fatty acid (FA) composition may affect mechanisms involved in the control of energy homeostasis, including central insulin actions. In rats fed either standard chow or a lard-enriched chow (high in saturated/low in polyunsaturated FA, HS-LP) for eight weeks, we examined the FA composition of blood, hypothalamus, liver, and retroperitoneal, epididymal and mesenteric adipose tissues. Insulin-induced hypophagia and hypothalamic signaling were evaluated after intracerebroventricular insulin injection. HS-LP feeding increased saturated FA content in adipose tissues and serum while it decreased polyunsaturated FA content of adipose tissues, serum, and liver. Hypothalamic C20:5n-3 and C20:3n-6 contents increased while monounsaturated FA content decreased. HS-LP rats showed hyperglycemia, impaired insulin-induced hypophagia and hypothalamic insulin signaling. The results showed that, upon HS-LP feeding, peripheral tissues underwent potentially deleterious alterations in their FA composition, whist the hypothalamus was relatively preserved. However, hypothalamic insulin signaling and hypophagia were drastically impaired. These findings suggest that impairment of hypothalamic insulin actions by HS-LP feeding was not related to tissue FA composition.

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.

Vitamin A deficiency reduces liver and colon docosahexaenoic acid levels in rats fed high linoleic and low alpha-linolenic acid diet.

Studies indicate that the transcription factor peroxisome proliferator-activated receptors (PPARs) regulate the activity of delta-6 and -5 desaturases and several key enzymes of peroxisomal beta-oxidation, including acyl-CoA oxidase. These enzymes are vital for the synthesis of docosahexaenoic (22:6 omega 3; DHA) and osbond (22:5 omega 6, OA) acids. An activated PPAR must form a hetrodimer with the obligate cofactor retinoid X receptor (RXR) to interact with a peroxisome proliferator responsive element (PPRE) of a target gene and to regulate transcriptional expression. The vitamin A metabolite, 9-cis retinoic acid, is the most potent ligand of RXR. We have tested the possibility that deficiency of vitamin A would compromise tissue levels of both DHA and OA in rats. Two groups of male Wistar rats were randomly distributed to receive vitamin A deficient (VAD) or sufficient (VAS) diet. After seven weeks of feeding, the rats were killed and colon and liver tissues removed for the analysis of fatty acids and antioxidant status. The VAD compared to the VAS rats had elevated levels of arachidonic (AA, P<0.001), adrenic acid (22:4 omega 6, P<0.005) and OA (P<0.0001) and reduced proportions of eicosapentaenoic (EPA, docosapentaenoic (DPA), DHA and total omega 3 fatty (P<0.0001) in colon choline phosphoglycerides (CPG). Similarly, liver CPG of the VAD rats had higher AA and adrenic acid and OA (P<0.0001), and lower EPA, DPA and DHA (P<0.0001) than the VAS rats. There was a similar fatty acid pattern in ethanolamine phosphoglycerides of the colon and liver tissues. These differences could not be explained by the conventional microsomal-peroxisomal pathway of the synthesis of the long-chain omega 6 and omega 3 polyunsaturated fatty acids. We postulate that deficiency of dietary vitamin A and the consequential depletion of retinoids inhibits DHA, and enhances OA, synthesis by differential effects on the independent synthetic pathways of the two fatty acids in the mitochondria. Various studies have documented that both DHA and vitamin A are vital for optimal visual and neural development and function. There is a need for further investigations to elucidate how vitamin A deficiency reduces membrane DHA level, and to delineate the synergistic effect of the two nutrients on vision, learning and memory.

Electron transfer processes in the reactivity of nonsteroidal anti-inflammatory drugs in the ground and excited states.

The nonsteroidal anti-inflammatory drugs (NSAID), naproxen, sulindac and indomethacin, were shown to donate electrons to nitro blue tetrazolium (NBT) when irradiated with UV light in deoxygenated aqueous buffer solution (pH 7.4, 30 degrees C). The reaction was monitored spectrophotometrically by the appearance of the diformazan reduction product from NBT. The electron transfer process facilitates the decomposition of the drugs. Naproxen in the presence of NBT is photodegraded principally to the alcohol (2-[1-hydroxyethyl]-6-methoxynaphthalene) at a rate approximately 20-fold faster than when irradiated alone in deoxygenated conditions. The photoproduct from naproxen also participates in the electron transfer to NBT but at a much slower rate than naproxen. Irradiation of sulindac or indomethacin in the presence of NBT caused the slow photoreduction of NBT to diformazan. In the absence of NBT, indomethacin and sulindac are essentially unreactive when irradiated in aqueous solution. The ability of a number of NSAID to act as electron donors in their ground state was studied by observing their oxidation by potassium peroxodisulfate in pH 7.0 phosphate buffer at 50 degrees C. The HPLC analysis of the drug remaining showed that the 2-arylpropionic acid NSAID (naproxen, ibuprofen, ketoprofen and suprofen) reacted at a rate equivalent to the thermal decomposition of peroxodisulfate. The major products were the same as detected in the photooxidation of these drugs, resulting from decarboxylation and oxygen addition but also included a dimeric compound. On the other hand, the NSAID that do not contain the propionic acid substituent all reacted more slowly with peroxodisulfate, enabling specific reaction rate constants to be evaluated.

Plasma AA and DHA levels are not compromised in newly diagnosed gestational diabetic women.

OBJECTIVE: The polyunsaturated fatty acids, arachidonic (AA) and docosahexaenoic (DHA), are vital structural and functional components of the neural, vascular and visual systems. There is increased demand for these fatty acids during pregnancy. Diabetes impairs the synthesis of both AA and DHA. We have investigated the possibility that pregnancy-induced diabetes compromises the levels of plasma AA and DHA in newly diagnosed expectant mothers. DESIGN: Cross-sectional study. SETTING: London, UK. SUBJECTS AND METHODS: Venous blood was obtained from 44 women with gestational diabetes mellitus (GDM) and from the same number of nondiabetics, during the third trimester. Fatty acid composition of plasma choline phosphoglycerides (CPG), triglycerides (TG) and cholesterol esters (CE) was analysed. RESULTS: The GDM women had higher levels of AA (20:4n-6; P<0.0001) and AA/linoleic acid ratio (20:4n-6/18:2n-6; P<0.01) in the CPG, and linoleic acid (LA; P<0.0001), total n-6 (P<0.01), DHA (P<0.05) and n-3 metabolites (P<0.05) in TG compared to their nondiabetic counterparts. Similarly, AA (P<0.0001), osbond acid (22:5n-6; P<0.05), total n-6 metabolites (P<0.0001), AA/LA (P<0.0001) and n-6 metabolites/LA (P<0.01) were higher in the CE of the GDM women. There was no difference in the levels of DHA in CPG and CE between the two groups (P>0.05). CONCLUSIONS: The results of this study do not provide evidence that the activity of delta-6 or delta-5 desaturases, which are vital for the synthesis of AA and DHA, is compromised by pregnancy-induced diabetes. However, since the samples were taken at diagnosis, it is conceivable that the duration of the diabetes was too short to have a discernable adverse effect on the levels of AA and DHA in plasma lipids.

Arachidonic and docosahexaenoic acids are strongly associated in maternal and neonatal blood.

BACKGROUND: The red cell membrane fatty acid composition has frequently been used as an index of essential fatty acid (EFA) nutrition. After birth there is a decline in plasma arachidonic acid (AA) and docosahexaenoic (DHA) acids in babies fed on conventional formula which contains only the parent linoleic and alpha-linolenic acids. In human studies, the red cell phosphoglyceride composition appears to be more constant than that of plasma. In infants fed fish oil without AA, the AA proportions fall in the plasma but much less so in the red cells. This result might be considered to mean that there is no need for preformed AA. On the other hand, in a study where the levels of AA fell there was reduction of infant growth. Indeed, where cell membrane composition does change there is often an associated alteration in physiological functions of membranes. We therefore felt it worth investigating the balance between AA and DHA in a physiological situation where plasma levels are known to change, namely in pregnancy. PURPOSE: The aim of the study was to investigate a relationship between blood phosphoglyceride AA and DHA in pregnant women and neonates. SUBJECTS: Health pregnant women from London, England (n=193) and their term babies (n=45); healthy pregnant women from Seoul, South Korea (n=40) and their term babies (n=40); and preterm neonates (n=72) from London. METHOD: Blood samples were taken from British and Korean pregnant women during the third trimester, and from term and preterm babies at birth. These samples were taken for routine monitoring purposes in Korea and were a part of a study on pregnancy outcome for which ethical permission was granted from the East London and The City Health Authority and Lambeth, Southwark and Lewisham Health Authority. Approval was also obtained from the Ethical Committee of the Asan Medical Centre, Seoul, South Korea. RESULTS: AA and DHA correlated in plasma choline phosphoglycerides (CPG) of the British mothers (r=0.52 P<0.0001). The correlation coefficients and significance were much stronger in the red cell CPG and even more so in the term and preterm infant red cell CPGs ( r=0.75, 0.80 and 0.88, respectively). Similarly, AA and DHA correlated in red cell CPGs of the Korean women and their term babies. There was also a significant relationship between the two fatty acids in red cell ethanolamine phosphoglycerides in the mothers and their babies. Both linoleic (LA) and alpha-linolenic acids (ALA) were inversely associated with AA and DHA in some of the phosphoglyceride fractions of the mothers and babies. CONCLUSIONS: Although AA and DHA have different primary dietary origins, there were significant relationships between AA and DHA in the phosphoglycerides of the red cell membrane. This finding seems surprising if the red cell composition is determined by diet. These results suggest a physiological mechanism which attempts to maintain an appropriate balance between AA and DHA. It is plausible that there is an optimum balance between AA and DHA for membrane stability, deformability, enzyme and receptor function. SPONSORSHIP: The British Diabetic Association, March of Dimes Birth Defects Foundation and The Christopher H.R. Reeves Charitable Trust. European Journal of Clinical Nutrition (2000) 54, 50-56