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
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339 results found

Rees GA, Doyle W, Srivastava A, Brooke ZM, Crawford MA, Costeloe KLet al., 2005, The nutrient intakes of mothers of low birth weight babies - a comparison of ethnic groups in East London, UK., Matern Child Nutr, Vol: 1, Pages: 91-99, ISSN: 1740-8695

The objective of this paper was to compare the nutrient intakes of mothers of different ethnic origins after they had given birth to a low birth weight (LBW) baby (< 2.5 kg). A total of 165 participants from East London, UK completed a prospective 7-day diet diary using household measures, between 8 and 12 weeks post-partum. The data were originally collected as baseline data prior to two separate nutrition intervention studies and were combined and re-interrogated for the purpose of this paper. Folate and iron intakes were low in all ethnic groups compared to the Reference Nutrient Intakes (RNI). Half did not meet the RNI for folate and 88% did not meet the RNI for iron. Nearly a quarter of the group did not achieve the Lower Reference Nutrient Intake (LRNI) for iron. The mean vitamin D and calcium intakes were significantly different between the ethnic groups (P = 0.007, P = 0.001, respectively). African women had the highest vitamin D intakes (4.72 microg d(-1)) and Caucasians and Asians the lowest (2.4 microg d(-1)). Caucasians had the highest calcium intakes (780 mg d(-1)) and Africans the lowest (565 mg d(-1)). Over two-thirds of African, Asian and African-Caribbean women did not meet the RNI for calcium. Thirty-one per cent of Africans did not meet the LRNI for calcium. Our data show a high prevalence of inadequate nutrition among women who deliver LBW babies with differences in nutrient intake between ethnic groups. This information can be used to target specific appropriate dietary advice to ethnic minorities for the prevention or repetition of LBW.

Journal article

Zhou D, Zaiger G, Ghebremeskel K, Crawford MA, Reifen Ret al., 2004, Vitamin A deficiency reduces liver and colon docosahexaenoic acid levels in rats fed high linoleic and low alpha-linolenic acid diet., Prostaglandins Leukot Essent Fatty Acids, Vol: 71, Pages: 383-389, ISSN: 0952-3278

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 t

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Thomas B, Ghebremeskel K, Lowy C, Min Y, Crawford MAet al., 2004, Plasma AA and DHA levels are not compromised in newly diagnosed gestational diabetic women., Eur J Clin Nutr, Vol: 58, Pages: 1492-1497, ISSN: 0954-3007

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.

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Broadhurst CL, Schmidt WF, Crawford MA, Wang YQ, Li Ret al., 2004, <SUP>13</SUP>C nuclear magnetic resonance spectra of natural undiluted lipids:: Docosahexaenoic-rich phospholipid and triacylglycerol from fish, JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, Vol: 52, Pages: 4250-4255, ISSN: 0021-8561

Journal article

Ghebremeskel K, Thomas B, Lowy C, Min Y, Crawford MAet al., 2004, Type 1 diabetes compromises plasma arachidonic and docosahexaenoic acids in newborn babies., Lipids, Vol: 39, Pages: 335-342, ISSN: 0024-4201

The activity of delta6- and delta5-desaturase, enzymes required for the synthesis of AA and DHA, are impaired in human and experimental diabetes. We have investigated whether neonates of type 1 diabetic women have compromised plasma AA and DHA at birth. Cord blood was obtained from healthy babies born to mothers with (n = 31) and without (n = 59) type 1 diabetes. FA composition of plasma choline phosphoglycerides (CPG), TG, and cholesterol esters (CE) was assayed. The neonates of the diabetics had lower levels of AA (20:4n-6, P< 0.0001), adrenic acid (22:4n-6, P < 0.01), sigman-6 metabolites (P < 0.0001), docosapentaenoic acid (22:5n-3, P < 0.0001), DHA (22:6n-3, P < 0.0001), sigman-3 (P < 0.0001), and sigman-3 metabolites (P< 0.0001) in CPG compared with the corresponding babies of the nondiabetic mothers. Similarly, they had lower levels of AA (P< 0.05), sigman-6 metabolites (P < 0.05), DHA (P< 0.0001), and sigman-3 metabolites (P< 0.01) in plasma CE. There was also a nonsignificant reduction of AA and DHA in TG in the babies of the diabetic group. The current investigation indicates that healthy neonates born to mothers with type 1 diabetes have highly compromised levels of AA and DHA. These nutrients are of critical importance for neurovisual and vascular system development. In poorly controlled maternal diabetes, it is conceivable that the relative "insufficiency" of AA and DHA may exacerbate speech and reading impairments, behavioral disorders, suboptimal performance on developmental tests, and lower IQ, which have been reported in some children born to mothers with type 1 diabetes mellitus. Further studies are needed to understand the underlying mechanism for this biochemical abnormality and its implications for fetal and infant development.

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Crawford MA, Bloom M, Broadhurst CL, Schmidt WF, Cunnane SC, Galli C, Gehbremeskel K, Linseisen F, Lloyd-Smith J, Parkington Jet al., 2004, Evidence for the unique function of DHA during the evolution of the modern hominid brain, OCL - Oleagineux Corps Gras Lipides, Vol: 11, Pages: 30-37, ISSN: 1258-8210

The African savanna ecosystem of the large mammals and primates was associated with a dramatic decline in relative brain capacity. This reduction happened to be associated with a decline in docosahexaenoic acid (DHA) from the food chain. DHA is required for brain structures and growth. The biochemistry implies that the expansion of the human brain required a plentiful source of preformed DHA. The richest source of DHA is the marine food chain while the savannah environment offers very little of it. Consequently H. sapiens could not have evolved on the savannahs. Recent fossil evidence indicates that the lacustrine and marine food chain was being extensively exploited at the time cerebral expansion took place and suggests the alternative that the transition from the archaic to modern humans took place at the land/water interface. Contemporary data on tropical lake shore dwellers reaffirms the above view. Lacustrine habitats provide nutritional support for the vascular system, the development of which would have been a prerequisite for cerebral expansion. Both arachidonic acid (AA) and DHA would have been freely available from such habitats providing the double stimulus of preformed acyl components for the developing blood vessels and brain. The w3 docosapentaenoic acid precursor (w3DPA) was the major w3 metabolite in the savanna mammals. Despite this abundance, neither it or the corresponding w6DPA were used for the photoreceptor nor the synapse. A substantial difference between DHA and other fatty acids is required to explain this high specificity. Studies on fluidity and other mechanical features of cell membranes have not revealed a difference of such magnitude between even a-linolenic acid (LNA) and DHA sufficient to explain the exclusive use of DHA. We suggest that the evolution of the large human brain depended on a rich source of DHA from the land/water interface. We review a number of proposals for the possible influence of DHA on physical properties of the b

Journal article

Muskiet FAJ, Fokkema MR, Schaafsma A, Boersma ER, Crawford MAet al., 2004, Is docosahexaenoic acid (DHA) essential? Lessons from DHA status regulation, our ancient diet, epidemiology and randomized controlled trials., J Nutr, Vol: 134, Pages: 183-186, ISSN: 0022-3166

Journal article

Min Y, Ghebremeskel K, Lowy C, Thomas B, Crawford MAet al., 2004, Adverse effect of obesity on red cell membrane arachidonic and docosahexaenoic acids in gestational diabetes., Diabetologia, Vol: 47, Pages: 75-81, ISSN: 0012-186X

AIMS/HYPOTHESIS: Gestational 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. METHODS: Fasting blood obtained at diagnosis was analysed for the fatty acids in plasma choline phosphoglycerides and red cell choline and ethanolamine phosphoglycerides. RESULTS: There 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/INTERPRETATION: Apparently 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.

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Wang YQ, Crawford MA, Chen JS, Li JY, Ghebremeskel K, Campbell TC, Fan WX, Parker R, Leyton Jet al., 2003, Fish consumption, blood docosahexaenoic acid and chronic diseases in Chinese rural populations, COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR & INTEGRATIVE PHYSIOLOGY, Vol: 136, Pages: 127-140, ISSN: 1095-6433

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McGready R, Simpson JA, Arunjerdja R, Golfetto I, Ghebremeskel K, Taylor A, Siemieniuk A, Mercuri E, Harper G, Dubowitz L, Crawford M, Nosten Fet al., 2003, Delayed visual maturation in Karen refugee infants, ANNALS OF TROPICAL PAEDIATRICS, Vol: 23, Pages: 193-204, ISSN: 0272-4936

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Cunnane SC, Crawford MA, 2003, Survival of the fattest: fat babies were the key to evolution of the large human brain., Comp Biochem Physiol A Mol Integr Physiol, Vol: 136, Pages: 17-26, ISSN: 1095-6433

In the past 2 million years, the hominid lineage leading to modern humans evolved significantly larger and more sophisticated brains than other primates. We propose that the modern human brain was a product of having first evolved fat babies. Hence, the fattest (infants) became, mentally, the fittest adults. Human babies have brains and body fat each contributing to 11-14% of body weight, a situation which appears to be unique amongst terrestrial animals. Body fat in human babies provides three forms of insurance for brain development that are not available to other land-based species: (1) a large fuel store in the form of fatty acids in triglycerides; (2) the fatty acid precursors to ketone bodies which are key substrates for brain lipid synthesis; and (3) a store of long chain polyunsaturated fatty acids, particularly docosahexaenoic acid, needed for normal brain development. The triple combination of high fuel demands, inability to import cholesterol or saturated fatty acids, and dependence on docosahexaenoic acid puts the mammalian brain in a uniquely difficult situation compared with other organs and makes its expansion in early humans all the more remarkable. We believe that fresh- and salt-water shorelines provided a uniquely rich, abundant and accessible food supply, and the only viable environment for evolving both body fat and larger brains in human infants.

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Crawford MA, Golfetto I, Ghebremeskel K, Min Y, Moodley T, Poston L, Phylactos A, Cunnane S, Schmidt Wet al., 2003, The potential role for arachidonic and docosahexaenoic acids in protection against some central nervous system injuries in preterm infants, LIPIDS, Vol: 38, Pages: 303-315, ISSN: 0024-4201

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Ghebremeskel K, Bitsanis D, Koukkou E, Lowy C, Poston L, Crawford MAet al., 2002, Liver triacylglycerols and free fatty acids in streptozotocin-induced diabetic rats have atypical n-6 and n-3 pattern., Comp Biochem Physiol C Toxicol Pharmacol, Vol: 132, Pages: 349-354, ISSN: 1532-0456

In diabetes there is a decrease in membrane arachidonic (AA) and docosahexaenoic (DHA) acids and a concomitant increase in linoleic (LA) and alpha-linolenic (ALA) acids. This metabolic perturbation is thought to be due to impaired activity of Delta(6)- and Delta(5)-desaturases. Triacylglycerols are the major lipid pool in plasma and liver tissue and have a significant influence on fatty acid composition of membrane and circulating phospholipids. Data on the distribution of n-6 and n-3 polyunsaturated fatty acids of triacylglycerols in diabetes are sparse. We investigated whether streptozotocin-induced diabetes in Sprague-Dawley rats alters fatty acid composition of triacylglycerols and free fatty acids of liver tissue. The animals were fed a breeding diet prior to mating, during pregnancy and lactation. On days 1-2 of pregnancy, diabetes was induced in 10 of the 25 rats. Liver was obtained at post partum day 16 for analysis. Relative levels of LA (P=0.03), dihomo-gamma-linolenic acid (DHGLA) (P=0.02), AA (P=0.049), total n-6 (P=0.02), ALA (P=0.013), eicosapentaenoic acid (EPA) (P=0.004), docosapentaenoic acid (22:5n-3, DPA) (P=0.013), DHA (P=0.033), n-3 metabolites (P=0.015) and total n-3 (P=0.011) were significantly higher in the triacylglycerols of the diabetics compared with the controls. Similarly, liver free fatty acids of the diabetics had higher levels of LA (P=0.0001), DHGLA (P=0.001), AA (P=0.001), n-6 metabolites (P=0.002), total n-6 (P=0.0001), ALA (P=0.003), EPA (P=0.015), docosapentaenoic (22:5n-3, P=0.003), DHA (P=0.002), n-3 metabolites (P=0.005) and total n-3 (P=0.001). We conclude that impaired activity of desaturases and/or long chain acyl-CoA synthetase could not explain the higher levels of AA, DHA and n-6 and n-3 metabolites in the diabetics. This seems to be consistent with an alteration in the regulatory mechanism, which directs incorporation of polyunsaturated fatty acids either into triacylglycerols or phospholipids.

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Broadhurst CL, Wang YQ, Crawford MA, Cunnane SC, Parkington JE, Schmidt WFet al., 2002, Brain-specific lipids from marine, lacustrine, or terrestrial food resources:: potential impact on early African <i>Homo sapiens</i>, COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY, Vol: 131, Pages: 653-673, ISSN: 1096-4959

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Crawford M, Galli C, Simopoulos A, Reifen Ret al., 2002, Inequality of international public health., Lancet, Vol: 359, Pages: 258-259, ISSN: 0140-6736

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Crawford MA, 2002, Cerebral evolution., Nutr Health, Vol: 16, Pages: 29-34, ISSN: 0260-1060

We suggest that the evolution of the large human brain could not have occurred on the savannahs of Africa. It depended on avoiding the trap of universal loss of brain capacity amongst all land species as they evolved larger bodies. The nutrition at the water's front would have given evolving humans the edge over other hominid species. They would have had access to a rich, plentiful and easily harvested food resource, rich in DHA, trace elements and anti-oxidants, for little energy expenditure. This does not deny the possibility that the men hunted for meat. However, a reliable and consistent nutrient dense food resource, rich in DHA would have been especially important for women during pregnancy and lactation and of course the children during the period of fetal and neonatal brain development and reproductive maturation.

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Crawford MA, 2002, Introduction: The Saugstad Prize for Elaine Morgan. The conditions of human evolution., Nutr Health, Vol: 16, Pages: 3-6, ISSN: 0260-1060

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Min Y, Ghebremeskel K, Crawford MA, Nam JH, Kim A, Lee IS, Suzuki Het al., 2001, Maternal-fetal n-6 and n-3 polyunsaturated fatty acids gradient in plasma and red cell phospholipids., Int J Vitam Nutr Res, Vol: 71, Pages: 286-292, ISSN: 0300-9831

Fatty acid distribution was investigated in ethnically and economically homogenous Korean mothers (n = 40) and neonates. Venous blood, maternal before delivery and cord, was obtained. Choline (CPG) and ethanolamine (EPG) phosphoglycerides and sphingomyelin (SM) were assayed. Mean arachidonic acid (AA) level was higher in plasma CPG and SM (p < 0.0001), and red cell CPG (p < 0.0001), EPG (p < 0.0001) and SM (p = 0.005) of the neonates. Similarly, the neonates had higher proportions of docosahexaenoic acid (DHA) in plasma CPG (p < 0.0001) and red cell CPG (p = 0.001) and EPG (p = 0.036). In contrast, linoleic and alpha-linolenic acids were significantly higher in maternal blood. Mead acid was elevated in plasma CPG (p < 0.0001) and red cell CPG and EPG (p < 0.0001) of the neonates. Consistent with data from high-fat-intake populations, our subjects, whose traditional diet is low in fat, exhibited maternal-fetal gradient in AA and DHA in plasma and red cell phospholipids. This may be due to an imbalance between supply and maternal and fetal requirements, and/or a physiological response to pregnancy. Prenatal nutritional constraint is associated with impaired development and a risk of chronic diseases in adults. AA and DHA are vital nutrients. Hence, there is a need to investigate whether the discrepancy between maternal and neonatal AA and DHA is a manifestation of nutritional insufficiency.

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Golfetto I, Min YJ, Wang YQ, Ghebremeskel K, Crawford MAet al., 2001, Serum cholesterol and haemorrhagic stroke, LANCET, Vol: 358, Pages: 508-508, ISSN: 0140-6736

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Doyle W, Srivastava A, Crawford MA, Bhatti R, Brooke Z, Costeloe KLet al., 2001, Inter-pregnancy folate and iron status of women in an inner-city population., Br J Nutr, Vol: 86, Pages: 81-87, ISSN: 0007-1145

The purpose of the present study was to evaluate whether micronutrient supplementation improved the nutritional status of women with poor diets during the inter-pregnancy interval. Fifty-five women who had given birth to a low birth weight baby (<2.5 kg), and who planned to have a further pregnancy, were recruited to a prospective randomised study in East London, UK. Of the fifty-five mothers recruited, forty-four (78 %) met fewer than four of sixteen dietary reference values according to the information provided in a 7 d diet diary, and were categorised as having an 'inadequate' diet. Half of the mothers in the 'inadequate'-diet group were randomly assigned to receive a micronutrient and a single cell oil supplement containing docosahexaenoic acid. All participants received dietary advice based on analysis of their diet diaries, and general lifestyle advice on preparing for pregnancy. Mothers had a blood sample taken at 3 and 9 months post-partum to measure their folate, Fe stores and fatty acid status. Mean serum and erythrocyte folate levels increased significantly between 3 and 9 months post-partum in both the adequate-diet group and the supplemented group. At 9 months post-partum, over half of the unsupplemented, inadequate-diet group remained severely deficient in folate (serum folate <230 nmol/l) and had low serum ferritin levels (<15 microg/l). The high prevalence of inadequate diets in this inner-city population and the low motivation of women to participate in a nutrition programme suggests that consideration should be given to the provision of free folate and Fe supplements to all women in this and similar populations, or at least to women who have delivered a low birth weight baby, who plan further pregnancies.

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Ghosh P, Bitsanis D, Ghebremeskel K, Crawford MA, Poston Let al., 2001, Abnormal aortic fatty acid composition and small artery function in offspring of rats fed a high fat diet in pregnancy., J Physiol, Vol: 533, Pages: 815-822, ISSN: 0022-3751

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.

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Visioli F, Crawford M, Galli C, 2001, Neonatal salt intake and blood pressure., Lancet, Vol: 357, ISSN: 0140-6736

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Crawford MA, Bloom M, Cunnane S, Holmsen H, Ghebremeskel K, Parkington J, Schmidt W, Sinclair AJ, Broadhurst CLet al., 2001, Docosahexaenoic acid and cerebral evolution., World Rev Nutr Diet, Vol: 88, Pages: 6-17, ISSN: 0084-2230

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Golfetto I, Crawford, Campo R, 2001, Treatment of hemorrhagic stroke with arachidonic acid., Nutr Neurosci, Vol: 4, Pages: 75-79, ISSN: 1028-415X

Eighty-seven year old man, previously healthy, active and independent, was admitted to a hospital unconscious with hemorrhagic stroke. Treatment with arachidonic acid was initiated two weeks after his admission. After one year, despite his age, large hemorrhagic area and a history of ischemic heart disease, he had no physical disability or mental impairment and scored 95 points on the Barthel Scale.

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Crawford MA, 2000, Commentary on the workshop statement. Essentiality of and recommended dietary intakes for Omega-6 and Omega-3 fatty acids., Prostaglandins Leukot Essent Fatty Acids, Vol: 63, Pages: 131-134, ISSN: 0952-3278

The Workshop document is welcome and important in its content and objectives. My comments deal with three topics, and are intended to set the historical perspective and take the discussion further as regards attitudes to infant nutrition. 1. ADVERSE ARACHIDONIC EFFECTS. I have some difficulty with the statement on the need to reduce LA (linoleic acid) content of the diet because 'This is necessary to reduce adverse effects of excesses of arachidonic acid and its eicosanoid products.'I have no problem with suggesting a reduction in the present level of LA in the USA but consider the expression 'adverse effects of arachidonic acid ...' to be misleading. Linking LA and AA in this way also implies a direct conversion of LA to AA, which is not the case. In fact, a very high dietary LA will reduce membrane AA. 2. EFA RATIOS. I suspect that their choice of omega 3/omega 6 ratio of 5.7 for early life may be high. Their recommendation for adults gives the much lower ratio of about 1.4. In view of the high requirement for DHA during neural development, I would have thought the ratios would have been the other way round or the same for infants as adults but with AA included in the omega 6. Also, I have some difficulty with the concept of a unitary ratio when there is clear disunity in the biological activities of the different parent and LCP EFAs. Hence the concept of omega 6/omega 3 ratio based on activity equality does not reflect the biological reality. 3. FDA RECOMMENDATIONS ON INFANT FORMULA. The Workshop essentially disagrees with the recent FDA recommendations on inclusion of LCPs in infant formula. There is, in addition, a need to re-think the requirements of the preterm infant beyond their recommendation.

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Ghebremeskel K, Min Y, Crawford MA, Nam JH, Kim A, Koo JN, Suzuki Het al., 2000, 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., Lipids, Vol: 35, Pages: 567-574, ISSN: 0024-4201

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.

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Doyle W, Crawford M, Costeloe K, 2000, Maternal nutrition and birth weight. These factors are related., BMJ, Vol: 320, Pages: 941-942, ISSN: 0959-8138

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Doyle W, Crawford M, Costeloe K, Mathews F, Yudkin P, Neil Aet al., 2000, Maternal nutrition and birth weight, BMJ, Vol: 320, ISSN: 0959-8138

Journal article

Min Y, Ghebremeskel K, Crawford MA, Nam JH, Kim A, Koo JN, Suzuki Het al., 2000, Pregnancy reduces arachidonic and docosahexaenoic in plasma triacylglycerols of Korean women., Int J Vitam Nutr Res, Vol: 70, Pages: 70-75, ISSN: 0300-9831

Plasma triacylglycerol (TG) fatty acid composition of healthy non-pregnant and non-lactating women, expectant mothers and their term neonates from Seoul, South Korea was investigated. They were ethnically homogeneous and the women had comparable age and parity. Blood samples were obtained at recruitment, third trimester and birth from the non-pregnant women, expectant mothers and neonates respectively. Percent levels of linoleic and arachidonic acids and n-6 metabolites and total n-6 were significantly lower in the pregnant women than in the non-pregnant (p < 0.0001). Similarly, there were lower levels of alpha-linolenic (p = 0.033), eicosapentaenoic and docosahexaenoic acids and n-3 metabolites and total n-3 (p < 0.0001) in the expectant mothers. Compared with their mothers, the neonates had higher proportions of dihomo-gamma-linolenic, arachidonic, docosatetraenoic and docosapentaenoic acids and n-6 metabolites (p < 0.0001) and lower linoleic acid (p < 0.0001). Of the n-3 series, alpha-linolenic acid was lower (p < 0.0001) and eicosapentaenoic, docosapentaenoic and docosahexaenoic acids and n-3 metabolites and total n-3 higher (p < 0.0001) in the neonates compared with their mothers. The study reveals that pregnancy is associated with a reduction in the relative levels of plasma triacylglycerol arachidonic and docosahexaenoic acids. Moreover, it indicates that the decline is a manifestation of selective transfer of these fatty acids to the developing fetus.

Journal article

Cunnane SC, Francescutti V, Brenna JT, Crawford MAet al., 2000, Breast-fed infants achieve a higher rate of brain and whole body docosahexaenoate accumulation than formula-fed infants not consuming dietary docosahexaenoate., Lipids, Vol: 35, Pages: 105-111, ISSN: 0024-4201

Docosahexaenoate (DHA) has been increasingly recognized as an important fatty acid for neural and visual development during the first 6 mon of life. One important point of controversy that remains is the degree to which adequate levels of DHA can be acquired from endogenous synthesis in infants vs. what should be provided as dietary DHA. We have approached this problem by a retrospective analysis of published body composition data to estimate the actual accumulation of DHA in the human infant brain, liver, adipose tissue, remaining lean tissue, and whole body. Estimating whether infants can synthesize sufficient DHA required comparison to and extrapolation from animal data. Over the first 6 mon of life, DHA accumulates at about 10 mg/d in the whole body of breast-fed infants, with 48% of that amount appearing in the brain. To achieve that rate of accumulation, breast-fed infants need to consume a minimum of 20 mg DHA/d. Virtually all breast milk provides a DHA intake of at least 60 mg/d. Despite a store of about 1,050 mg of DHA in body fat at term birth and an intake of about 390 mg/d alpha-linolenate (alpha-LnA), the brain of formula-fed infants not consuming DHA accumulates half the DHA of the brain of breast-fed infants while the rest of the body actually loses DHA over the first 6 mon of life. No experimental data indicate that formula-fed infants not consuming DHA are able to convert the necessary 5.2% of alpha-LnA intake to DHA to match the DHA accumulation of breast-fed infants. We conclude that dietary DHA should likely be provided during at least the first 6 mon of life.

Journal article

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