Imperial College London

Michael A Crawford PhD, FRSB, FRCPath

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Visiting Professor
 
 
 
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Contact

 

+44 (0)7725 250 541michael.crawford Website CV

 
 
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Location

 

H 3.34Chelsea and Westminster HospitalChelsea and Westminster Campus

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Summary

 

Publications

Publication Type
Year
to

339 results found

Schmidt WF, Mookherji S, Crawford MA, 2009, Unit cell volume and liquid-phase immiscibility in oleate-stearate lipid mixtures., Chem Phys Lipids, Vol: 158, Pages: 10-15

The structural basis of immiscibility of stearic acid (SA) in two unsaturated lipids at room temperature was examined. A 5% SA mixture in octadec-9-enoic acid (OA) is cloudy; a 5% SA solution in the methyl ester of OA (MeOA) is fully miscible. At 10% SA in MeOA, a clear and immiscible phase formed. The composition of this immiscible phase however was not 10% SA, but 25% SA. Adding additional SA altered the amount of the second phase, not its stoichiometry. Molecular mechanics explains the molecular basis for the ratio of saturated and unsaturated lipids in the different phases. Packing order of lipids within a unit volume explains the discrete lipid composition ratio forming each of the observed miscible and immiscible phases. The smallest unit cell volume that explains the observed stoichiometry is a cube (not a sphere).

Journal article

Gow RV, Matsudaira T, Taylor E, Rubia K, Crawford M, Ghebremeskel K, Ibrahimovic A, Vallée-Tourangeau F, Williams LM, Sumich Aet al., 2009, Total red blood cell concentrations of omega-3 fatty acids are associated with emotion-elicited neural activity in adolescent boys with attention-deficit hyperactivity disorder., Prostaglandins Leukot Essent Fatty Acids, Vol: 80, Pages: 151-156, ISSN: 0952-3278

Affective impairment is observed in children and adolescents with attention-deficit hyperactivity disorder (ADHD). Low levels of long-chain polyunsaturated fatty acids (LC-PUFA), specifically omega-3 (omega-3) fatty acids in blood measures have been linked to a range of behavioural and mood disorders including ADHD. However, nothing is known about the relationship between omega-3 and brain function in children with ADHD. In the current study, 20 adolescent boys with ADHD were assessed for total lipid fractions in red blood cells and their event-related potential (ERP) response to the presentation of facial expressions of happiness, sadness and fearfulness. The results supported the hypothesis of a positive association between eicosapentaenoic acid (EPA) and a cognitive bias in orientation to overt expressions of happiness over both sad and fearful faces as indexed by midline frontal P300 amplitude. Additional exploratory analyses revealed a positive association between levels of docosahexaenoic acid (DHA) and the right temporal N170 amplitude in response to covert expressions of fear. The arachidonic (AA)/DHA ratio was negatively associated with the right temporal N170 amplitude also to covert expressions of fear. These findings indicate that EPA and DHA may be involved in distinct aspects of affect processing in ADHD and have implications for understanding currently inconsistent findings in the literature on EFA supplementation in ADHD and depression.

Journal article

Izzeldin SH, Crawford MA, Ghebremeskel K, 2009, Salt fortification with iodine: Sudan situation analysis., Nutr Health, Vol: 20, Pages: 21-30, ISSN: 0260-1060

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.

Journal article

Crawford MA, Bazinet RP, Sinclair AJ, 2009, Fat intake and CNS functioning: ageing and disease., Ann Nutr Metab, Vol: 55, Pages: 202-228

Journal article

Zhang J, Wang Y, Meng L, Wang C, Zhao W, Chen J, Ghebremeskel K, Crawford MAet al., 2009, Maternal and neonatal plasma n-3 and n-6 fatty acids of pregnant women and neonates from three regions of China with contrasting dietary patterns, ASIA PACIFIC JOURNAL OF CLINICAL NUTRITION, Vol: 18, Pages: 377-388, ISSN: 0964-7058

Journal article

Moodley T, Vella C, Djahanbakhch O, Branford-White CJ, Crawford MAet al., 2009, Arachidonic and docosahexaenoic acid deficits in preterm neonatal mononuclear cell membranes. Implications for the immune response at birth., Nutr Health, Vol: 20, Pages: 167-185, ISSN: 0260-1060

Preterm neonates are more susceptible to infection than term neonates. Arachidonic acid (20:4n-6) and docosahexaenoic acid (22:6n-3) are biologically active components of cell membrane phospholipids. Arachidonic acid is a substrate for the synthesis of eicosanoids, potent regulators of immune function. Preterm babies may have a deficiency of arachidonic acid and docosahexaenoic acid, but the impact of this deficit on maturation of the immune system is unknown. To address this we explored links between placental provision of fatty acids to cord blood mononuclear cell (CBMC) membranes using gas chromatography (GC), and maturation of the immune response with gestational age by analysing lymphocyte subsets by flow cytometry. This is the first study to examine the lipid profile of the phosphatidylcholine (PC) and phosphatidylethanolamine (PE) fractions of CBMC membranes from preterm neonates. The long chain polyunsaturated fatty acid (LCPUFA) composition of CBMC membranes was dominated by arachidonic acid in both PE (34%) and PC (15%) fractions in healthy term neonates (> or =37 weeks, n=9), whilst in healthy preterm neonates (<37 weeks, n=10) the level of arachidonic acid was significantly lower at 28.8% and 12.5% respectively (p<0.05). Preterm neonates (<37 weeks, n=23) also had significantly lower absolute numbers of CD4+ (p<0.05) leukocytes and CD4+ (p<0.01) and CD8+ (p<0.05) naïve T-cells than term (> or =37 weeks, n=24) neonates that correlated with gestational age (p<0.01-0.05).

Journal article

Stark AH, Crawford MA, Reifen R, 2008, Update on alpha-linolenic acid., Nutr Rev, Vol: 66, Pages: 326-332, ISSN: 0029-6643

Consumption of omega 3 fatty acids is known to have health benefits. For many years, the importance of the only member of the omega 3 family considered to be essential, alpha-linolenic acid (ALA), has been overlooked. Current research indicates that ALA, along with its longer chain metabolites, may play an important role in many physiological functions. Potential benefits of ALA include cardioprotective effects, modulation of the inflammatory response, and a positive impact on both central nervous system function and behavior. Recommended levels for ALA intake have been set, yet the possible advantages of its consumption are just being revealed.

Journal article

Crawford MA, Sinclair AJ, 2008, Nutritional influences in the evolution of mammalian brain, Lipids, Malnutrition and the Developing Brain, Pages: 267-292, ISBN: 9789021940038

Book chapter

Ren H, Ghebremeskel K, Okpala I, Lee A, Ibegbulam O, Crawford Met al., 2008, Patients with sickle cell disease have reduced blood antioxidant protection., Int J Vitam Nutr Res, Vol: 78, Pages: 139-147, ISSN: 0300-9831

In previous studies, we found that homozygous sickle cell (HbSS) patients, compared with their healthy (HbAA) counterparts, had reduced levels of the omega-3 fatty acids, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, in red cells, platelets, and mononuclear cells. These differences were not due to lower intake of the two fatty acids. We have investigated whether reduced antioxidant status in the patients could help explain the observed phenomenon. Blood specimens previously obtained for fatty acid study from Nigerian (26 HbSS and 30 HbAA) and British (30 HbSS, 9 sickle cell-hemoglobin C/HbSC, and 15 HbAA) subjects were analyzed for antioxidant status. The Nigerian HbSS patients compared with the controls had lower plasma retinol, alpha-tocopherol, and beta-carotene concentrations (p < 0.005) and reduced activity of red cell Cu/Zn-superoxide dismutase (Cu/Zn-SOD) (p < 0.05). Similarly, the British HbSS group had reduced concentrations of plasma alpha-tocopherol (p < 0.005), and activities of red cell Cu/Zn-superoxide dismutase (p < 0.05) and Se-glutathione peroxidase (Se-GPx) (p < 0.005) than the controls. In addition, the British patients in comparison with those who had HbSC, a mild form of the disease, had lower alpha-tocopherol than that of the HbAA controls (p < 0.005). In the British sickle cell patients, there was a positive correlation between red cell ethanolamine phosphoglyceride (EPG) DHA and Cu/Zn-SOD activity (r = 0.700, p < 0.05), choline phosphoglyceride (CPG) DHA and Se-GPx activity (r = 0.605, p < 0.05), and CPG EPA and Se-GPx activity (r = 0.558, p > 0.05). Similarly, the percent DHA in red cell EPG was positively related with the activity of Se-GPx in the patients with HbSC (r = 0.674, p < 0.05). These findings suggest that the lower levels of membrane EPA and DHA in blood cells of the HbSS patients could be due to peroxidation resulting from a compromised antioxidant competence.

Journal article

Crawford MA, 2008, The elimination of child poverty and the pivotal significance of the mother., Nutr Health, Vol: 19, Pages: 175-186, ISSN: 0260-1060

The child poverty not an independent condition: it is intimately related to the ecology of the family. It elimination will involve the elimination poor maternal nutrition, low birthweight and its life long consequences in chronic ill health and poor learning. Maternal nutrition and health is a prime determinant of the future of the child and also of her own health, mental state and ability to manage child care. Maternal nutrition and health is also relevant to the future employment opportunities, health, skills and literacy and social behaviour of the new born. Poor maternal nutrition and adverse outcomes conspire to maintain the state of poverty. Children need to be empowered by knowledge. Nutrition, health and home economics should be introduced from pre-school to advanced levels in the school curriculum. It makes little sense to educate children with everything they need to know except how to take charge of their own health, reproductive capacity, cognitive development and that of their own children that they are likely bear. Today non-communicable diseases account for more deaths than all the HIV-AIDS, Malaria, and Tuberculosis combined. The Global Forum for Health predicts that the top three burdens of ill health world-wide will by 2020 be heart disease, perinatal conditions (adverse pregnancy outcomes) and mental ill-health. Unfavourable nutritional conditions contribute substantially to the cause of these three conditions and other non-communicable diseases. Yet children today grow up in ignorance of the science of nutrition and health and become leaders in industry and government with little understanding of nutritional science which could, if taught properly, lead to large scale reductions in chronic disorders, substantial cost savings in the health services and especially in the enhancement of population skills and prosperity. It is also evident that education alone will not suffice. The priority in human development is vested in the brain. Nutrition and f

Journal article

Golfetto I, McGready R, Ghebremeskel K, Min Y, Dubowitz L, Nosten F, Drury P, Simpson JA, Arunjerdja R, Crawford MAet al., 2007, 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?, Pages: 319-332, ISSN: 0260-1060

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.

Conference paper

Cunnane SC, Plourde M, Stewart K, Crawford MAet al., 2007, Docosahexaenoic acid and shore-based diets in hominin encephalization: a rebuttal., Am J Hum Biol, Vol: 19, Pages: 578-581, ISSN: 1042-0533

Carlson and Kingston ([2007]: Am J Hum Biol 19:132-141) propose that preformed dietary docosahexaenoic acid (an omega-3 fatty acid in fish) did not have a significant role in hominin encephalization. Their position hinges on claiming that humans are able to make sufficient docosahexaenoic acid from the plant-based "parent" omega-3 fatty acid-alpha-linolenic acid. They also suggest that hominin fish consumption occurred too late to have materially influenced encephalization. The authors quantify here a summary of the published data showing that humans cannot make sufficient docosahexaenoic acid to maintain normal infant brain development. The authors also provide evidence that the fossil record shows that some of the earliest hominins were regularly consuming fish. Hence, we reject Carlson and Kingston's position and reiterate support for the concept that access to shore-based diets containing docosahexaenoic acid was necessary for hominin encephalization beyond the level seen in the great apes.

Journal article

Izzeldin HS, Crawford MA, Jooste PL, 2007, Population living in the Red Sea State of Sudan may need urgent intervention to correct the excess dietary iodine intake., Nutr Health, Vol: 18, Pages: 333-341, ISSN: 0260-1060

BACKGROUND: Both inadequate and high intakes of iodine are associated with thyroid disease and associated abnormalities. Consumption of foods deficient in iodine induces hypothyroidism. Conversely, excessive intake of the nutrient precipitates hyperthyroidism. Iodine deficiency causes impairment of thyroid hormonogenesis resulting in goiter (struma), cretinism which is associated with increased prenatal and infant mortality, deafness, motor disabilities and mental retardation due to damage during fetal and neonatal brain development. We have assessed the iodine status of school children from the locality of Port Sudan, Red Sea State of Eastern Sudan. The primary sources of iodine of the children are mainly iodized salt and rations supplied by local donors and various aid agencies operating in the Sudan. METHODS: Male and female children (n=141), aged 6 to 12 years (median age 9.8 years), were selected for the survey using a multistage random sampling technique, between May 22 and August 25, 2006. All the children were assessed for urinary iodine and visible goiter. In addition, the iodine content of twenty salt samples was determined using the lodometric titration method and spot test kits. The components of other foods that are routinely consumed by the children and households were noted using a questionnaire form. FINDINGS: Urinary iodine concentration exceeded 300 microg/l and 1000 microg/l in 65% and 9.9% of the children, respectively. The highest urinary iodine level was 1470 microg/l. The prevalence of visible goiter was 17%. All the salt samples collected from the schools had more than 150mg potassium iodate per kg of salt. CONCLUSIONS: The results of this pilot survey reveal that excessive intake of iodine in children exists in Port Sudan. Inappropriate and unregulated local fortification of salt and lack of monitoring of the imported and donated salt is the primary reason for the excessive intake. There is an urgent need for a regulatory mechanism during th

Journal article

Min Y, Nam J-H, Ghebremeskel K, Kim A, Crawford Met al., 2006, A distinctive fatty acid profile in circulating lipids of Korean gestational diabetics: a pilot study., Diabetes Res Clin Pract, Vol: 73, Pages: 178-183, ISSN: 0168-8227

Gestational diabetes mellitus (GDM) is a transient metabolic disorder that is a strong predictor of type 2 diabetes and cardiovascular disease. Previously, GDM was associated with reduced red cell long-chain omega-6 and omega-3 fatty acids in population (British) with high intake of total and saturated fat. The aim of the study was to examine blood fatty acids status of GDM patients (n=12) and normoglycaemic women (control, n=12) from South Korea where typical diet retains high omega-3 fat with low total fat intake. Subjects were matched for BMI and gestation week. Blood obtained at delivery were analyzed for plasma triacylglycerols (TG), phosphatidylcholine (PC), sphingomyelin (SM), and red cell PC, phosphatidylethanolamine (PE) and SM fatty acids. GDM patients had lower total saturated fatty acids (SFA) in the plasma TG (p<0.05) and PC (p<0.0001), and higher omega-6 and omega-3 metabolites in the plasma PC (p<0.05) than the controls. Conversely, the red cell PC and PE of the GDM contained higher proportions of palmitic (p<0.05) and SFA (p<0.05) but lower arachidonic (p<0.05) and docosahexaenoic (p>0.05) acids compared with the controls. Interestingly, red cell PC arachidonic acid level was comparable between Korean and British women whereas docosahexaenoic acid level decreased in the order of Korean control (5.5+/-0.9)>Korean GDM (3.5+/-2.1)=British control (3.9+/-2.9)>British GDM (2.8+/-2.3) (p<0.05). The similarity in the plasma and red cell fatty acids profile between Korean and British cohort suggests that the reduced membrane arachidonic and docosahexaenoic acids in GDM might be attributed to the effect of the disease itself regardless of ethnicity, obesity, or diet.

Journal article

Bitsanis D, Ghebremeskel K, Moodley T, Crawford MA, Djahanbakhch Oet al., 2006, Gestational diabetes mellitus enhances arachidonic and docosahexaenoic acids in placental phospholipids., Lipids, Vol: 41, Pages: 341-346, ISSN: 0024-4201

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-gamma-linolenic (P < 0.05), docosatetraenoic (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.

Journal article

Hieu NT, Gainsborough M, Simpson JA, Thuy NT, Hang NN, Taylor AM, Ghebremeskel K, Crawford M, Golfetto I, Dubowitz L, Farrar Jet al., 2006, Neurological status of low-risk Vietnamese newborns: A comparison with a British newborn cohort, JOURNAL OF HEALTH POPULATION AND NUTRITION, Vol: 24, Pages: 57-63, ISSN: 1606-0997

Journal article

Zhou D, Ghebremeskel K, Crawford MA, Reifen Ret al., 2006, Vitamin A deficiency enhances docosahexaenoic and osbond acids in liver of rats fed an alpha linolenic acid-adequate diet., Lipids, Vol: 41, Pages: 213-219, ISSN: 0024-4201

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.

Journal article

Thomas B, Ghebremeskel K, Lowy C, Crawford M, Offley-Shore Bet al., 2006, Nutrient intake of women with and without gestational diabetes with a specific focus on fatty acids., Nutrition, Vol: 22, Pages: 230-236, ISSN: 0899-9007

OBJECTIVE: Diet therapy is the cornerstone for the management of gestational diabetes mellitus (GDM). Women with GDM are commonly given dietary advice that broadly focuses on a reduction of total energy and fat consumption. We compared nutrient intake and specifically fatty acids of women with GDM who had received individualized nutritional counseling with those of non-diabetic women who did not. METHOD: Women with GDM (n=44) and healthy pregnant women (n=44) with uncomplicated singleton pregnancies were recruited during the third trimester. Women with GDM were given consultation on diet, health, and macronutrient content of foods commonly consumed by the individual. The non-diabetic group did not receive any dietary advice. Both groups were asked to keep a detailed record of all of foods and fluid consumed over a 4-d period. RESULTS: After dietary counseling, the GDM group had lower intakes of energy (P<0.05), refined sugar (P<0.0001), total and saturated fats (P<0.0001), and monounsaturated (P<0.01) and trans (P<0.0001) fatty acids and higher levels of docosahexaenoic acid and fiber (P<0.05) compared with the non-diabetic group. CONCLUSIONS: Individualized dietary advice was associated with a lower consumption of the target nutrients in women with GDM. Another benefit of the advice was a slight increase in intake of eicosapentaenoic and docosahexaenoic acids, although consumption of omega-3 fatty acids by both groups was well below the recommendations for pregnancy. There is evidence that docosahexaenoic acid modulates insulin resistance and that it is vital for neurovisual development. We suggest that dietary management for women with GDM should foster the current recommendations for essential fatty acids in pregnancy.

Journal article

Ren H, Magulike N, Ghebremeskel K, Crawford Met al., 2006, Primary open-angle glaucoma patients have reduced levels of blood docosahexaenoic and eicosapentaenoic acids., Prostaglandins Leukot Essent Fatty Acids, Vol: 74, Pages: 157-163, ISSN: 0952-3278

The aetiology of primary open-angle glaucoma (POAG), which is the commonest cause of non-remediable blindness and visual impairment, is not well understood. Nevertheless, increased intraocular pressure, and vascular factors such as ocular blood flow deficits are thought to be risk factors. There is evidence of decreased optic nerve blood velocity and increased red blood cell aggregability in POAG. These factors are influenced by fatty acids. We have investigated if glaucoma patients have abnormal blood fatty acid composition. Patients with POAG (n=10) and their healthy siblings (n=8) were enrolled. Compared with their healthy siblings, the glaucoma patients had reduced eicosapentaenoic (EPA, P<0.01), and docosahexaenoic (DHA, P<0.05) fatty acids and total omega3 long-chain polyunsaturated fatty acids (LCPUFA) (P<0.05) in red cell choline phosphoglycerides (CPG); decreased EPA (P<0.05) in ethanolamine phosphoglycerides (EPG); lower EPA (P<0.05) and total omega3 LCPUFA (P<0.05) in serine phosphoglycerides (SPG). Similarly, they had reduced EPA, DHA and total omega3 LCPUFA in plasma CPG (P<0.005) and triglycerides (P<0.05). These findings may be significant, since EPA and DHA could modulate impaired systemic microcirculation and ocular blood flow and optic neuropathy, which are the main physiological changes associated with glaucoma.

Journal article

Ren H, Ghebremeskel K, Okpala I, Ugochukwu CC, Crawford M, Ibegbulam Oet al., 2006, Abnormality of erythrocyte membrane n-3 long chain polyunsaturated fatty acids in sickle cell haemoglobin C (HbSC) disease is not as remarkable as in sickle cell anaemia (HbSS)., Prostaglandins Leukot Essent Fatty Acids, Vol: 74, Pages: 1-6, ISSN: 0952-3278

Sickle cell disease (SCD) is a group of inherited blood disorders in which clinical illness results from the presence of erythrocytes with sickled haemoglobin (HbS). Blood vessel occlusion is a fundamental pathological process in SCD. Sickle cell haemoglobin C (HbSC) disease and sickle cell anaemia (HbSS) share some pathophysiology and clinical manifestations. However, the former is generally less severe. Erythrocytes of HbSC patients have longer life span, reduced haemolysis, and lower propensity to adhere to vascular endothelium than those of their HbSS counterparts. The structure and function of erythrocytes are strongly modulated by membrane long chain polyunsaturated fatty acids (LCPUFA). We have tested the possibility that HbSC and HbSS patients have different membrane fatty acid composition consistent with the difference in their clinical severity. Steady-state patients, 9 HbSC and 28 HbSS, and 15 HbAA were studied. The HbSC patients had a higher level of linoleic (LA, P<0.05) and docosahexaenoic (DHA, P<0.05) acids, and lower arachidonic acid (AA, P<0.01) and AA/eicosapentaenoic acid (EPA) ratio (P<0.05) in erythrocyte choline phosphoglycerides (CPG) compared with the HbSS group. Similarly, the level of EPA was higher and AA/EPA ratio (P<0.01) lower in serine phosphoglycerides of the HbSC patients. In contrast to the HbSC, the HbSS group had lower levels of EPA (P<0.001), DHA (P<0.05), total n-3 metabolites and total n-3 fatty acids (P<0.001) in erythrocyte CPG compared with the healthy HbAA controls. Moreover, the HbSS patients with disease complications compared with those without complications had reduced DHA and total n-3 fatty acids (P<0.005) in erythrocyte CPG. The abnormalities in erythrocyte in LCPUFA which is manifested by an increase in AA and a decrease in EPA and DHA in HbSS relative to HbSC disease observed in this study are consistent with the contrast in clinical severity between the two entities.

Journal article

Visioli F, Crawford MA, Cunnane S, Rise P, Galli Cet al., 2006, Lipid transport, dietary fats, and endogenous lipid synthesis: hypotheses on saturation and competition processes., Nutr Health, Vol: 18, Pages: 127-132, ISSN: 0260-1060

Plasma lipid concentrations are the net result of the balance between two opposite processes: the loading, i.e. the entry of new lipids into the plasma compartment through the ingestion (diet) and/or endogenous synthesis, and the unloading, i.e. energy utilization, incorporation into cell membranes, and storage. Even though many fatty acids are thought to be synthesized in the body, it appears as nearly all circulating fatty acids are, in fact, derived from the diet. In view of the wide dietary availabilty of such nutrients, the need to conserve energy likely minimizes endogenous synthesis. Consequently, the possibility exists to alter circulating the profile of fatty acids, including the "non essential" ones by dietary manipulations. In turn, a theory on the dietary vs endogenous contribution to circulating fatty acids, including those known as non-essential, is discussed based on critical interpretation of original data.

Journal article

Crawford MA, 2006, Docosahexaenoic acid in neural signaling systems., Nutr Health, Vol: 18, Pages: 263-276, ISSN: 0260-1060

Docosahexaenoic acid has been conserved in neural signalling systems in the cephalopods, fish, amphibian, reptiles, birds, mammals, primates and humans. This extreme conservation, despite wide genomic changes over 500 million years, testifies to a uniqueness of this molecule in the brain. The brain selectively incorporates docosahexaenoic acid and its rate of incorporation into the developing brain has been shown to be greater than ten times more efficient than its synthesis from the omega 3 fatty acids of land plant origin. Data has now been published demonstrating a significant influence of dietary omega 3 fatty acids on neural gene expression. As docosahexaenoic acid is the only omega 3 fatty acid in the brain, it is likely that it is the ligand involved. The selective uptake, requirement for function and stimulation of gene expression would have conferred an advantage to a primate which separated from the chimpanzees in the forests and woodlands and sought a different ecological niche. In view of the paucity of docosahexaenoic acid in the land food chain it is likely that the advantage would have been gained from a lacustrine or marine coastal habitat with access to food rich in docosahexaenoic acid and the accessory micronutrients, such as iodine, zinc, copper, manganese and selenium, of importance in brain development and protection against peroxidation. Land agricultural development has, in recent time, come to dominate the human food chain. The decline in use and availability of aquatic resources is not considered important by Langdon (2006) as he considers the resource was not needed for human evolution and can be replaced from the terrestrial food chain. This notion is not supported by the biochemistry nor the molecular biology. He misses the point that the shoreline hypothesis is not just dependent on docosahexaenoic acid but also on the other accessory nutrients specifically required by the brain. Moreover he neglects the basic principle of Darwinian evo

Journal article

Min Y, Lowy C, Ghebremeskel K, Thomas B, Offley-Shore B, Crawford Met al., 2005, Unfavorable effect of type 1 and type 2 diabetes on maternal and fetal essential fatty acid status: a potential marker of fetal insulin resistance., Am J Clin Nutr, Vol: 82, Pages: 1162-1168, ISSN: 0002-9165

BACKGROUND: Pregestational maternal diabetes increases obesity and diabetes risks in the offspring. Both conditions are characterized by insulin resistance, and diabetes is associated with low membrane arachidonic (AA) and docosahexaenoic (DHA) acids. OBJECTIVE: We investigated whether type 1 and type 2 diabetes in pregnancy compromise maternal and fetal membrane essential fatty acids (FAs). DESIGN: We studied 39 nondiabetic (control subjects), 32 type 1 diabetic, and 17 type 2 diabetic pregnant women and the infants they delivered. Maternal and cord blood samples were obtained at midgestation and at delivery, respectively. Plasma triacylglycerols and choline phosphoglycerides and red blood cell (RBC) choline and ethanolamine phosphoglyceride FAs were assessed. RESULTS: The difference in maternal plasma triacylglycerol FAs between groups was not significant. However, the type 1 diabetes group had lower plasma choline phosphoglyceride DHA (3.7 +/- 0.9%; P < 0.01) than did the control group (5.2 +/- 1.6%). Likewise, RBC DHA was lower in the type 1 [choline: 3.4 +/- 1.5% (P < 0.01); ethanolamine: 5.9 +/- 2.5% (P < 0.05)] and type 2 [choline: 3.5 +/- 1.6% (P < 0.05)] diabetes groups than in the control group (choline: 5.5 +/- 2.2%; ethanolamine: 7.5 +/- 2.5%). Cord AA and DHA were lower in the plasma (type 1: P < 0.01) and RBC (type 2: P < 0.05) choline phosphoglycerides of the diabetics than of the control subjects, and cord RBC ethanolamine phosphoglycerides were lower in DHA (P < 0.05) in both diabetes groups than in the control group. CONCLUSIONS: Diabetes (either type) compromises maternal RBC DHA and cord plasma and RBC AA and DHA. The association of these 2 FAs with insulin sensitivity may mean that the current finding explains the higher incidence of insulin resistance and diabetes in the offspring of diabetic women.

Journal article

Bitsanis D, Crawford MA, Moodley T, Holmsen H, Ghebremeskel K, Djahanbakhch Oet al., 2005, Arachidonic acid predominates in the membrane phosphoglycerides of the early and term human placenta., J Nutr, Vol: 135, Pages: 2566-2571, ISSN: 0022-3166

The aim of this study was to determine whether the high concentration of arachidonic acid (AA) in term placentae accumulates during pregnancy or is an inherent characteristic of placental lipids. We investigated the lipid content and fatty acid composition of the human placental phospholipids at 2 gestational periods, early in pregnancy (8-14 wk, n = 48) and at term (38-41 wk of gestation, n = 19). The subjects were healthy, normotensive, and free of medical and obstetric complications. The lipid concentration of placentae increased from 0.8% in early gestation to 1.4% at term (P < 0.0001). The mean proportions of AA were lower in the choline (P < 0.05), inositol (P < 0.0001), and ethanolamine (P < 0.0001) phosphoglycerides of the term compared with the early placenta. In contrast, the proportions of the immediate precursor of AA, dihomo-gamma-linolenic acid (DGLA), were higher in the term placenta, particularly in the inositol and serine phosphoglycerides (P < 0.0001). In sphingomyelin, the percentage of lignoceric acid was increased and that of nervonic acid was reduced at term (P < 0.01). The dominance of AA, particularly in the early placenta, suggests that it has an important role for placental development, i.e., organogenesis and vascularization. There was no evidence of an accumulation of AA in the placenta toward term, which might be a trigger for parturition. In contrast, the increased proportion of DGLA (precursor of the vasorelaxant and anticoagulant prostaglandin E(1)) at term is more consistent with a profile favoring optimal blood flow to nourish the fetal growth spurt.

Journal article

Ren H, Okpala I, Ghebremeskel K, Ugochukwu CC, Ibegbulam O, Crawford Met al., 2005, Blood mononuclear cells and platelets have abnormal fatty acid composition in homozygous sickle cell disease., Ann Hematol, Vol: 84, Pages: 578-583, ISSN: 0939-5555

Leukocyte adhesion to vascular endothelium contributes to vaso-occlusion and widespread organ damage in sickle cell disease (SCD). Previously, we found high expression of the adhesion molecules alphaMbeta2 integrin and L-selectin in HbSS individuals with severe disease. Since membrane n-6 and n-3 polyunsaturated fatty acids modulate cell adhesion, inflammation, aggregation and vascular tone, we investigated the fatty acid composition of mononuclear cells (MNC) and platelets of HbSS patients in steady state (n=28) and racially matched, healthy HbAA controls with similar age and sex distribution living in the same environment (n=13). MNC phospholipids of the patients had lower levels of docosahexaenoic acid (DHA, p<0.01) and increased arachidonic acid (AA, p<0.005) relative to HbAA controls. Similarly, platelets from HbSS patients had less eicosapentaenoic acid (EPA, p<0.05) and more AA (p<0.05) in choline phosphoglycerides (CPG), with reduced DHA (p<0.05) in ethanolamine phosphoglycerides. Platelet CPG had lower DHA levels in SCD patients with complications compared to those without (p<0.05). Reduced cell content of EPA and DHA relative to AA favours the production of aggregatory and proinflammatory eicosanoids that activate leukocytes and platelets. This facilitates inflammation, leukocyte adhesion, platelet aggregation and vaso-occlusion in SCD.

Journal article

Crawford MA, Ghebremeskel K, Hibbeln JR, House S, Hunter D, Morley DC, Nicholson P, Stuart Ket al., 2005, The Lancet and the Royal Society are both right and wrong., Lancet, Vol: 366, Pages: 714-715

Journal article

Goodwin SR, Haberkern C, Crawford M, Lerman J, Mancuso T, Yaster Met al., 2005, Sickle cell and anesthesia: do not abandon well-established practices without evidence., Anesthesiology, Vol: 103, ISSN: 0003-3022

Journal article

Min Y, Lowy C, Ghebremeskel K, Thomas B, Bitsanis D, Crawford MAet al., 2005, Fetal erythrocyte membrane lipids modification: preliminary observation of an early sign of compromised insulin sensitivity in offspring of gestational diabetic women., Diabet Med, Vol: 22, Pages: 914-920, ISSN: 0742-3071

AIMS: Intrauterine exposure to diabetes is a significant determinant of the development of obesity and early onset of Type 2 diabetes mellitus in the offspring. Both conditions are characterized by insulin resistance and the latter is associated with reduced membrane arachidonic and docosahexaenoic acids. Hence, we investigated if the membrane arachidonic and docosahexaenoic acids are depressed in the cord blood of babies born to women with gestational diabetes. METHODS: Cord (fetal) and maternal blood were obtained at delivery from control subjects (n = 33) and women with gestational diabetes (n = 40) and analysed for plasma triglycerides and cholinephosphoglycerides, and erythrocyte choline- and ethanolaminephosphoglycerides fatty acids. RESULTS: Babies of gestational diabetic mothers had reduced docosahexaenoic acid in the plasma (5.9 +/- 1.4 vs. 7.1 +/- 2.0, P < 0.01) and erythrocyte (4.0 +/- 2.2 vs. 5.4 +/- 2.9, P < 0.05) cholinephosphoglycerides. Moreover, the total omega-6 and omega-3 fatty acids of the erythrocyte cholinephosphoglycerides were significantly lower (P < 0.05) in these babies. A similar trend was observed in plasma triglycerides and erythrocyte ethanolaminephosphoglycerides. The maternal plasma triglycerides and erythrocyte ethanolaminephosphoglycerides fatty acids profile were not different between the two groups. However, there was a reduction in arachidonic acid and total omega-6 fatty acids in the erythrocyte cholinephosphoglycerides of the gestational diabetic women. CONCLUSION: The altered plasma and erythrocyte fatty acids in the cord blood of babies born to women with gestational diabetes suggests a perturbation in the maternal-fetal nutrient transport and/or fetal lipid metabolism.

Journal article

Ren H, Obike I, Okpala I, Ghebremeskel K, Ugochukwu C, Crawford Met al., 2005, Steady-state haemoglobin level in sickle cell anaemia increases with an increase in erythrocyte membrane n-3 fatty acids., Prostaglandins Leukot Essent Fatty Acids, Vol: 72, Pages: 415-421, ISSN: 0952-3278

The aim of the study was to investigate, whether (a) patients with homozygous sickle cell disease (SCD, HbSS) have abnormal blood fatty acids; (b) the abnormality, if it exists, affects all the plasma and erythrocyte lipids or it is restricted to a particular lipid moiety; (c) there is an association between levels of membrane n-3 or n-6 long-chain polyunsaturated fatty acids (LCPUFA) and the degree of anaemia. Fatty acids of erythrocyte choline (CPG), serine (SPG) and ethanolamine (EPG) phosphoglycerides and sphingomyelin (SPM); and plasma CPG, triglycerides and cholesterol esters of 43 steady-state HbSS patients and 43 ethnically matched, healthy, HbAA controls were analysed. The levels of the n-6 LCPUFA, arachidonic (AA), adrenic and docosapentaenoic acids in erythrocyte CPG (P<0.001) and EPG (P<0.01) were higher in the patients compared with the controls. In contrast, the proportions of eicosapentaenoic acid (EPA) in CPG and EPG (P<0.001) and docosahexaenoic acid (DHA) and total n-3 metabolites in CPG (P<0.001) were lower in the patients. The steady-state haemoglobin level of the patients correlated with erythrocyte DHA (r=0.55, P<0.01), EPA (r=0.38, P<0.05) and total n-3 metabolites (r=0.51, P<0.001) in CPG. Also, it correlated with erythrocyte EPA (r=0.64, P<0.01) and total n-3 metabolites (r=0.42, P<0.01) in EPG. The study revealed an imbalance between n-3 and n-6 LCPUFA in erythrocyte and plasma lipid moieties of the HbSS group. Furthermore, it suggested that correction of the imbalance by supplementation with EPA and DHA could ameliorate anaemia in the patients. This observation is consistent with the results of pilot studies, which demonstrated that treatment with n-3 fatty acids confers clinical benefit to sickle cell patients.

Journal article

Thomas BA, Ghebremeskel K, Lowy C, Offley-Shore B, Crawford MAet al., 2005, Plasma fatty acids of neonates born to mothers with and without gestational diabetes., Prostaglandins Leukot Essent Fatty Acids, Vol: 72, Pages: 335-341, ISSN: 0952-3278

Women with gestational diabetes mellitus (GDM) and their neonates have lower levels of arachidonic (AA) and docosahexaenoic (DHA) acids in red cell membranes. It is not clear if this abnormality is restricted to red cells or is a generalised problem. We have investigated plasma fatty acids of neonates (venous cord) of GDM (n=37), and non-diabetic (n=31) women. The GDMs had lower levels of dihomogamma-linolenic (20:3n-6, DHGLA) acid, summation operator n-6 metabolites, DHA and summation operator n-3 metabolites (p<0.05) in choline phosphoglycerides (CPG). They also had lower levels of AA (-4.5%), adrenic acid (22:4n-6, -13%), osbond acid (22:5n-6, -7%) and summation operator n-6 (-2.5%). There was a similar pattern in triglycerides (TG) and cholesterol esters (CE). Mead acid, a marker of generalised shortage of derived and parent essential fatty acids, was higher in CPG and TG of the GDM group by 73% and 76%. The adrenic/osbond acid (22:4n-6/22:5n-6) ratio, a biochemical marker of DHA insufficiency, was reduced in CPG (-4.5%), TG (-63%) and CE (-75%) of the GDM group. These findings, which are consistent with the previous red cell data, suggest that the neuro-visual and vascular development and function of the offspring of GDM women may be adversely affected if the levels of AA and DHA are compromised further by other factors, pre- or post-natally. Studies are required to elucidate the underlying mechanism for the reduction of the two fatty acids and to evaluate the developmental and health implications.

Journal article

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