Partners and projects

Charities and organisations that have supported our research endeavours

EU and UK government EU Research Promotion FoundationEuropean Commission – FP6 Marie Curie Actions (Contract No. 29914); Food Standards AgencyMinistry of Agriculture, Food and FisheriesNATO
Charities Diabetes UKDown's Syndrome Research FoundationKitchener FundLaing TrustMarch of Dimes Birth Defect FoundationNutriciaPrisoners of ConscienceSir Halley Stewart TrustThe Christopher H. R. Reeves Charitable TrustThe Foyle FoundationThe Henry Lester Trust LimitedThe Henry Smith TrustThe Letten FoundationThe Mother and Child FoundationWolfson FoundationYews Trust
Independent charitable organisations The Royal SocietyThe Wellcome Trust
Professional organisations St Bartholomew's & The Royal London School of Medicine Research BoardThe Foundation of American Oil Chemists SocietyThe Worshipful Company of Innholders
Industries Efamol Ltd/Wassen InternationalEquazen Ltd.; Kellogg's Co.; Martek Biosciences; Milupa Plc.; Roche UKScientific Hospital SuppliesShida Kanzume Co.; Vifor Pharma
Overseas Ministry of Agriculture and Fisheries Wealth (Sultanate of Oman)

Funding

Applied to:

  • African Association of Medical Sciences (DELTAS AFRICA II Research/Training Funding Opportunity) in collaboration with Professor Iheany Okpala (University of Nigeria, Medical School) and Professor Betty Pace (Augusta University, Medical School). (Ghebremeskel K and Min Y).
  • The BMA Foundation for Medical Research (TP Gunton Research Grant) in collaboration with Professor Alexander Sumich and colleagues (Nottingham Trent University) – Prostate Cancer, Depression and Blood Lipid (Ghebremeskel K and Harbige L).

Planned applications:

  • Autistic Spectrum Disorder/Cognitive Function to Aurora Medicine Europe and Bayer HealthCare with Dr Ben Marlowe (Colchester Hospital) and Dr Mike Leach (University of Greenwich) (Harbige L and Ghebremeskel K).
  • Multiple Sclerosis/Epilepsy to Multiple Sclerosis Society and Hertie Foundation with Dr Mohammad Sharief (Colchester Hospital) and Dr Refik Pul (University Hospital Essen) (Harbige L, Ghebremskel K and Min Y).
  • Sickle disease and omega-3 fatty acid therapy to Oman Research Council with Professor Salam Al Kindi (School of Medicine, Sultan Qaboos University) (Ghebremeskel K and Min Y).

Major grant applications

Waterloo Foundation and the Leverhulme Trust (Epilepsy); Diabetes UK and Sir Halley Stewart Trust (Diabetes); Medical Research Council, Henry Smith Foundation, British Council, Mother and Child Foundation (Sickle Cell Disease); Vifor International, Switzerland (Autism Spectrum Disorder); The BMA Foundation for Medical Research (Prostate Cancer); African Association of Medical Sciences (Research and Training).

Research projects

DHA supplementation to improve maternal, foetal and infant outcomes: is the current recommendation appropriate for women with very low intake and status?

It is widely acknowledged that there is an enhanced demand for docosahexaenoic acid (DHA) in pregnancy and lactation. Moreover, DHA is one of the most important limiting nutrients. The conversion of alpha-linolenic acid (ALA), which is a minor constituent of most vegetable oils except linseed, soybean and rapeseed, to DHA is very low and variable, although women of child-bearing age are thought to have enhanced synthetic ability.

Preformed DHA is found in seafood in significant amounts. However, except in countries where fish and seafood intake remains high (ie Japan and Korea), the consumption of these foods by most individuals is sub-optimal, even in wealthy nations. Consequently, it has been recommended by working groups that expectant and nursing mothers need to consume 300 milligrams per day (mg/d) and at least 200 mg/d of DHA. These recommended values (which are based on breast milk and maternal, neonatal and infant blood DHA data from supplemented and unsupplemented women mainly from developed countries) are essentially guesstimates. In our study of a cohort of unsupplemented pregnant British women, the level of DHA in maternal and cord plasma choline phosphoglycerides and mature milk total lipid were 5.2, 6.6 and 0.4%. The corresponding values in our Sudanese study were 2.3, 3.34 and 0.06%. The data clearly show that the level of DHA in plasma of the Sudanese mothers and neonates was lower by about 50% and in breast milk by 85%. The question is whether supplementation of the Sudanese mothers with 200 or even 300 mg/d would increase maternal and neonate plasma and breast milk DHA more than two-fold to broadly match the levels of the unsupplemented British women.

The aims are to:

  • Determine the amount of docosahexaenoic acid (DHA) required to increase the status of the nutrient in healthy Sudanese expectant and nursing mothers to levels commonly observed in supplemented and unsupplemented British women.
  • Investigate whether antenatal supplementation with DHA is sufficient to raise breast milk concentration to levels of women who received the supplement during antenatal and postnatal periods.
  • Assess the effect of DHA supplementation of Sudanese pregnant women on foetal growth, premature delivery, gestation week at delivery, birth weight, head circumference and length.

The study is being carried out in collaboration with the University of Khartoum Hospital, Khartoum, Sudan (Professor Mustafa Idrin Elbashir). 

The study is registered with Current Controlled Trials (registration number ISRCTN03848493).

Omega-3 fatty acid supplementation to prevent seizure in patients with refractory epilepsy

The omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) play a pivotal role in physiological processes that govern normal and optimal neuronal, and cardio-and cerebro-vascular functions. In addition, they have been shown to ameliorate certain neurological and cardiological abnormalities. Moreover, there are indications that lipids could help reduce drug-induced toxicity and improve the efficacy of an active compound (ingredient) if given as an adjunct to drug therapy. Consequently, it has been postulated that omega-3 fatty acids will benefit patients with epilepsy by reducing seizures (frequency and severity) and seizure-associated cardiac arrhythmia and sudden unexpected death and by modulating psychological/psychiatric manifestations of the disorder. As there are indications of a link between seizures and the expression of pro-inflammatory cytokines, epileptic patients may also benefit from the anti-inflammatory function of omega-3 fatty acids.

The aim of the study is to investigate the therapeutic potential of omega-3 fatty acids for prevention of seizures and morbidities in patients with refractory (intractable) epilepsy.

The study is being carried out in collaboration with the University of Khartoum Hospital, Khartoum, Sudan (Professor Mustafa Idrin Elbashir, Professor Ammar Eltahit M Ahmed).

The study is registered with Current Controlled Trials (registration number ISRCTN57643242).

Published papers

  • Ibrahim FAS, Ghebremeskel K, Abdel-Rahman ME, Ahmed AAM, Mohmed IM, Osman G,  Elseed M, Hamed A, Rabinowicz AL, Salih MAM, Elbashir MI, Daak AA (2018), The differential effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on seizure frequency in patients with drug-resistant epilepsy – A randomized, double-blind, placebo-controlled trial. Epilepsy Behav. 28;87:32-38. doi: 10.1016/j.yebeh.2018.08.016.

Sickle cell disease – alternative dietary lipid therapy

In Britain, there are over 5,000 sickle cell sufferers and more than 150 are born every year. Sickle cell disease is associated with appreciable morbidity in children, adolescents and adults. We have investigated the fatty acid composition of red blood cells and the effect of treatment with n-3 fatty acids on blood parameters.

The results indicate that red cells of sickle cell patients have an abnormal long chain polyunsaturated (n-6 and n-3) fatty acid profile. It also shows that supplementation with n-3 fatty acids exerts a positive benefit on blood viscosity, platelet count, fibrinogen and fatty acid composition of red blood cells and platelets.

Defining fatty acid composition of plasma, red blood cells and platelets of sickle cell patients will identify whether metabolism of fatty acids, or their incorporation into the cells, is the primary defect. Clinical trials with linoleic acid and n-3 fatty acids supplementation is in progress in collaboration with Professor Mustafa Idrin Elbashir at the Faculty of Medicine, University of Khartum, and Sickle Cell Disease Clinic Abna of Paediatric Hospital, Khartoum, Sudan.

Various magnetic resonance imaging techniques such as Magnetic Resonance Angiography (MRA), Diffusion Tensor Imaging (DTI), Arterial Spin Labeling (ASL) perfusion, T2 weighted Fast Spin Echo (FSE), Axial T1 weighted Spin Echo, and Time of Flight Angiography (TOF-MRA) are being used to assess the effect of the supplement on haemolysis and vaso-occulusion of the blood vessel in the brain using MAGNETOM Avanto 1.5T (Simens).

The outcome will help to develop a novel therapy to reduce haemolysis, vaso-occulusive events and associated pathogenic complications, incidence of premature birth, maternal and neonatal morbidity and mortality.

This work is funded by the FP6 Marie Curie Actions Transfer of Knowledge (MTKD-CT-2005-029914), Efamol Wesson International, and Kitchener Fund.

This trial is registered with Current Controlled Trials (registration number ISRCTN80844630) and you can also download the SCD and omega-3 study protocol . 

Published Papers

  • Daak A, Rabinowicz A, Ghebremeskel K (2018) Omega-3 fatty acids are a potential therapy for patients with sickle cell disease. Nat Rev Dis Primers. 9;4(1):15. doi: 10.1038/s41572-018-0012-9.
  • Awoda S, Daak AA, Husain NE, Ghebremeskel K, Elbashir MI (2017) Coagulation profile of Sudanese children with homozygous sickle cell disease and the effect of treatment with omega-3 fatty acid on the coagulation parameters. BMC Hematol17:18.
  • Daak AA, Elsamani E, Ali EH, Mohamed FA, Abdel-Rahman ME, Elderdery AY, Talbot O, Kraft P, Ghebremeskel K, Elbashir MI, Fawzi W (2016) Sickle cell disease in western Sudan: genetic epidemiology and predictors of knowledge attitude and practices. Trop Med Int Health. 21(5):642-53.  
  • Daak A, Elderdery AY, Elbashir LM, Mariniello K, Mills J, Scarlett G, Elabshir MI, Ghebremeskel K (2015) Omega 3 (n-3) fatty acids down-regulate nuclear factor-kappa B (NF-kB) genen and blood cell adhesion molecule expression in patients with homozygous sickle cell disease. Blood cells Mol Dis 55(1): 45-55
  • Daak AA, Ghebremeskel K (2013) Omega-3 fatty acids and sickle cell disease: Intriguing association and promising therapeutic effect. Lipid Technology 25(12): 275-277
  • Daak A, Ghebremeskel K, Mariniello K, Hassan Z, Attallah B, Clough P, Elbashir MI (2013) Oxidative stress and intravascular haemolysis in homozygous sickle cell patients supplemented with omega 3 fatty acids. Prostaglandins Leukot Essent Fatty Acids 89(5):305-311
  • Daak AA, Ghebremeskel K, Hassan Z, Attallah B, Azan HH, Elbashir MI (2012) Effect of omega-3 fatty acid supplementation in patients with sickle cell anemia: randomized, double-blind, placebo-controlled trial. Am J Clini Nutr 97(1):37-44
  • Daak AA, Ghebremeskel K, Elbashir MI, Bakhita A, Hassan Z (2011) Hydroxyurea therapy mobilises arachidonic acid from inner cell membrane aminophospholipids in patients with homozygous sickle cell disease. J Lipids 2011:718014
  • Ren H, Ghebremeskel K, Okpala I, Ugochukwu CC, Crawford A, Ibegbulam O (2008) Patients with sickle cell disease have reduced blood antioxidant protection. Int J Vit Nutr Res 78(3):139-147.
  • Ren H, Ghebremeskel K, Okpala I, Ugochukwu CC, Crawford, Ibegbulam O. Abnormality of erythrocyte membrane n-3 long-chain polyunsaturated fatty acids in sickle cell hemoglobin (HbSC) disease is not as remarkable as in sickle cell anaemia (HbSS). Prostaglandins Leuko Essent Fatty Acids 2006; 74: 1-6
  • Ren H, Okpala I, Ghebremeskel K, Ugochukwu CC,Ibegbulam O, Crawford M. Blood mononuclear cells and platelets have abnormal fatty acid composition in homozygous sickle cell disease. Ann Hematol 2005 84(9);578-583.
  • Ren H, Ibegbulam O, Okpala I, Ghebremeskel K, Ugochukwu CC, Crawford M. Steady state haemoglobin level in sickle cell anaemia increases with an increase in erythrocyte membrane n-3 fatty acids. Prostaglandins Leuko Essent Fatty Acids 2005; 72(6):415-421.

Abstracts

  • Elbashir L, Daak AA, Elbashir M, Eltahir H, Hassan Z and Ghebremeskel K (2012) C-reactive protein concentration and total blood cell count in homozygous sickle cell patients are not influenced by omega 3 fatty acid supplementation. 10th International Meeting y for the Study of Fatty Acids and Lipids, Vancouver, Canada.
  • Suliman F, Daak AA, Elbashir M, Ali E, Hassan Z and Ghebremeskel K (2012) Homozygous sickle cell patients supplemented with DHA and EPA have reduced urinary albumin. 10th International Meeting for the Study of Fatty Acids and Lipids, Vancouver, Canada.
  • Daak A, Mariniello K, Elbashir M, Crawford M, Clough P and Ghebremeskel K (2012) Oxidative stress in homozygous sickle cell patients is not aggravated by supplementation with docosahxaenoic and eicosapentaenoic acids. 10th International Meeting for the Study of Fatty Acids and Lipids, Vancouver, Canada.
  • Daak A, Ghebremeskel K, Clough P, Elbashir M, Attalla B, Hassan Z and Crawford MA (2010) The effect of omega 3 fatty acids on prevention of vaso-occlusive crisis in homozygous sickle cell disease. 9th International Meeting for the Study of Fatty acids and Lipids, Maastricht, The Netherlands.
  • Ren H, Ghebremeskel K, Lee A, Okpala I, Ibegbulam O, Ugochukwu C, Crawford M (2006) Compromised antioxidants status may partly explain the low levels of eicosapentaenoic and docosahexaenoic acids in patients with sickle cell disease. 97th AOCS Annual Meeting and Expo, America's Center, St. Louis, Missouri, USA.
  • Okpala I, Ren H, Ghebremeskel K, Ibegbulam O, Cynthia C Ugochukwu CC and Crawford M (2005) Blood Lipid Abnormalities In Sickle Cell Disease Are Pancellular And Clinically Important. American Society of Hematology, 47th annual meeting, Atlanta, USA.
  • Ren H, Ghebremeskel K, Ibegbulam O, Okpala I, Ugochukwu CC and Crawford MA (2005) Fatty acid abnormality in homozygous sickle cell patients (HbSS) is a universal phenomenon that affects plasma, erythrocytes, mononuclear cells and platelets. 96th American Oil Chemists’ Society Annual Meeting and Exhibition, Salt Lake City, USA.
  • Okpala I, Ren H, Ibegbulam O, Ghebremeskel K, Ugochukwu CC, Crawford M. (2004) Steady state haemoglobin level in sickle cell anaemia increases with an increase in erythrocyte membrane n-3 fatty acids. 46th Annual Meeting and Exposition of the American Society of Hematology. San Diego, California, USA.
  • Ren Hongmei, Okpala I, Ghebremeskel K and Crawford MA (2004) Blood mononuclear cells and platelets have abnormal fatty acid composition in homozygous (HbSS) sickle cell disease (SCD). 6th International Meeting for the Study of Fatty Acids and Lipids, Brighton, UK.
  • Ren H, Ibegbulam O, Okpala I, Ghebremeskel K and   Crawford MA (2004) Homozygous (HbSS) sickle cell disease (SCD) enhances the accretion of arachidonic, adrenic and docosapentaenoic acids in red cell phospholipids. 6th International Meeting for the Study of Fatty Acids and Lipids, Brighton, UK.

 

Intervention study of long-chain omega-3 fatty acids in school children with attention deficit hyperactive disorder (ADHD)

Published papers

Matsudaira T, Gow RV, Kelly J, Murphy C, Potts L, Sumich A, Ghebremeskel K, Crawford MA, Taylor E (2015) Biochemical and Psychological Effects of Omega-3/6 Supplements in Male Adolescents with attention-Deficit/Hyperactivity Disorder: A Randomized, Placebo-Controlled, Clinical Trial. J Child Adolesc Psychopharmacol. 25(10):775-782. 

Gow RV, Vallee-Tourangeau F, Sumich A, Crawford MA, Ghebremeskel K,  Bueno AA, Hibbeln JR, Taylor E and Rubia K (2013) Omega-3 Fatty Acids Are Related to Abnormal Emotion Processing in Adolescent Boys with Attention Deficit Hyperactivity Disorder. Prostaglandins, Leukotrienes and Essential Fatty Acids 88(6):419-429.

Sumich A, Matsudaira T, Gow RV, Ibrahimovic A, Ghebremeskel K, Crawford MA, Taylor E (2013) Fatty acid correlates of temperament in adolescent boys with attention deficit hyperactivity disorder. Prostaglandins, Leukotrienes and Essential Fatty Acids 88(6):431-436.

Gow RV, Vallee-Tourangeau F, Crawford MA, Bueno AA, Ghebremeskel K, Hibbeln JR, Taylor E and Rubia K (2013) Omega-3 Fatty Acids Are Inversely Related to Callous and Unemotional Traits in Adolescent Boys with Attention Deficit Hyperactivity Disorder. Prostaglandins, Leukotrienes and Essential Fatty Acids 88(6):411-418.

Sumich AL, Matsudaira T, Gow R, Ibrahimovic A, Ghebremeskel K, Crawford MA, Taylor E (2009) Resting state electroencephalographic correlates with red cell long chain fatty acids, memory performance and age in adolescent boys with attention and hyperactivity disorder. Neuropharmacology 57(7-8):708-14

Gow RV, Matsudaira T, Taylor E, Rubia K, Crawford M, Ghebremeskel K, Ibrahimovic A, Vallée-Tourangeau F, Williams LM, Sumich A (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. 80(2-3): 151-156

Abstracts

Gow R, Rubia K, Sumich A, Vallee-Tourangeau F, Ghebremeskel K, Amador-Bueno A, Taylor E and Crawford MA (2012), An investigation into polyunsaturated essential fatty acids, event related potential assessments of brain function and behaviour measures in children and adolescents with and without attention deficit hyperactivity disorder. 10th International Society for the Study of Fatty Acids and Lipids, Vancouver, Canada.

Gow RV, Sumich A, Rubia K, Vakkee_Tourangeau F, Crawford MA, Ghebremeskel K, Amador-Beuno A and Taylor E (2010), The relationship between measures of depression, anxiety and anger/disruptive behaviour and omega 3/6 fatty acids in adolescents with and without ADHD. 9th Congress of the International Society for the Study of Fatty acids and Lipids, Maastricht, The Netherlands

Matsudaira T, Ibrahimovic A, Gow R, Sumich A, Ghebremeskel K, Crawford M, Taylor E (2008). Omega-3 fatty acid supplementation of adolescent boys with symptoms of attention deficit hyperactivity disorder, a double-blind, randomized controlled trial. 8th International Scientific Meeting for the study of fatty acids and Lipids, Kansas City, Missouri (USA).

 

The impact of fish and fish oil capsule intake on omega-3 fatty acid status, health and cognitive function of Omani school children (Fish Feeding study)

Epidemiological studies have suggested that incidence of ischemic heart disease is significantly lower in populations consuming a diet rich in marine products (ie fish, seafood, etc). Fish and seafood are primary sources of long-chain omega-3 fatty acids, namely eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3). Studies have also suggested that increased consumption of EPA and/or DHA might help children with behavioural problems such as attention deficit hyperactivity disorder (ADHD).

This joint project, which is funded by the Ministry of Agriculture and Fisheries Wealth – Sultanate of Oman, will investigate if feeding schoolchildren of nine to ten years old fish meal or one capsule of omega-3 oil four days a week for four months will modulate blood lipid profile and cognitive function.

The ethical approval has been obtained from the Research, Ethical Review and Approve Committee of Ministry of Health, Sultanate of Oman (Ref. MH/DGP/R&S/PROPOSAL_APPROVED/8/2012), and NRES Committee North West – Haydock (Ref.12/NW/0760).

This project is carried out in collaboration with Ministry of Agriculture and Fisheries Wealth, Ministry of Health, Ministry of Education, and Sultan Qaboos University, Sultanate of Oman.

This trial is registered with Current Controlled Trials (registration number: ISRCTN93233285).

Publications

  • Al-Ghannami SS, Sedlak E, Hussein IS, Min Y, Al-Shmmkhi SM, Al-Oufi HS, Al-Mazroui A, Clough P, Ghebremeskel K (2018) 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. Prostaglandins Leukot Essent Fatty acids doi.org/10.1016/j.plefa.2018.07.005
  • Al-Ghannami SS, Al-Adawi S, Ghebremeskel K, Cramer MT, Hussein I, Min Y, Jeyaseelan L, Al-Sibani N, Al-Shammakhi S, Al-Mamary F, Dorvlo ASS (2018) Attention deficit hyperactivity disorder and parental factors in school children aged nine to ten years in urban regions of Oman. Oman Med J 33(3):193-199.
  • Al-Ghannami SS, Al-Adawi S, Ghebremeskel K, Hussein IS, Min Y, Jeyaseelan L, Al-Shammakhi SM, Mabry RM, Al-Oufi HS (2018) Randomised open-label trial of docosahexaenoic acid -enriched fish oil and fish meal on cognitive and behavioural functioning in Omani children. Nutrition doi: 10.1016/j.nutr.2018.04.008.
  • Delextrat A, Hayes LD, Al-Ghannami SS, Min Y, Hussein I, Al Oufi H, Cohen DD, Ghebremeskel K (2018) Physical fitness characteristics of Omani primary school children according to body mass index. J Sports Med Phys Fitness. doi: 10.23736/S0022-4707.18.08136-7.
  • Al-Ghannami AA, Sedlak E, Hussein IS, Min Y, Al-Shmmkhi SM, Al-Oufi HS, Al-Mazroui A, Ghebremeskel K (2016), Lipid-soluble nutrient status of healthy Omani school children before and after intervention with oily fish meal or re-esterified triglyceride fish oil. Nutrition 32(1): 73-78

Abstracts

  • Ghebremeskel K, Al-Ghannami SS, Hussein IS, Min Y, Delextrat A, Hayes L, Al-Adawi S, Al-Mazroui A, Al-Oufi HS (2014) The effect of fish consumption, fish oil supplementation and physical exercise on body composition, blood biochemistry, cognitive function and fitness of Omani school children. (Invited Opening Lecture) International Conference on Seafood Safety, Quality and Traceability Systems, 03-05 March 2014. Muscat, Sultanate of Oman.
  • Al-Ghannami SS, Sedlak E, Hussein IS, Min Y, Al-Shmmkhi SM, Al-Oufi HS, Al-Mazroui A, Ghebremeskel K (2014) Low dose omega 3 fatty acids reduce fat mass and systolic blood pressure in school children. Abstr. No. 334. 11th Biennial ISSFAL Congress 2014, 28.06 – 02.07.2014, Stockholm, Sweden.
  • Al-Ghannami SS, Al-Adawi S, Sedlak E, Hussein IS, Min Y, Al-Shmmkhi SM, Al-Oufi HS, Al-Mazroui A, Ghebremeskel K (2014) Fish consumption for a short period of time improves cognitive ability of healthy Omani school children. Abstr. No. 338. 11th Biennial ISSFAL Congress 2014, 28.06 – 02.07.2014, Stockholm, Sweden.
  • Al-Ghannami SS, Sedlak E, Hussein IS, Min Y, Al-Shmmkhi SM, Al-Oufi HS, Al-Mazroui A, Ghebremeskel K (2014) The effect of omega 3 fatty acid supplementation on plasma vitamin D status of school children. Abstr. No. 345. 11th Biennial ISSFAL Congress 2014, 28.06 – 02.07.2014, Stockholm, Sweden.
  • Al-Ghannami SS, Sedlak E, Hussein IS, Min Y, Al-Shmmkhi SM, Al-Oufi HS, Al-Mazroui A, Ghebremeskel K (2014) Erythrocyte palmitoleic acid correlates positively with fat mass and plasma triglycerides in normal weight school children. Abstr. No. 410. 11th Biennial ISSFAL Congress 2014, 28.06 – 02.07.2014, Stockholm, Sweden.

Omega 3 fatty acid supplementation in diabetic pregnancy

Implications for the genesis of diabetogenic factors in the offspring

In diabetic pregnancies, there is an increased risk of birth defects and we have discovered a membrane defect in diabetic pregnant women, the consequences of which are passed on to the fetus.

Our previous work on diabetes in pregnancy at St Thomas' Hospital funded by the Mother and Child Foundation and Diabetes UK has uncovered a disturbing metabolic deficiency of omega-3 fatty acids in blood cell membranes in the mother that also appears in the blood of the newborn child. We have evidence that this deficiency during fetal life retards brain development and harms the development of the arteries. Moreover, we have evidence that gives reason to believe this deficit is causative of prenatal programming of vascular disorder and neurological deficits in the fetus that will affect health in adult life. Therefore we consider it of vital importance to establish if supplementation can correct the deficits in the mother and therefore help protect both her and the fetus.

This trial has been carried out at London's Newham University Hospital in collaboration with Professor Ovrang Djahanbakhch, Mr Manickam Raveendran and research midwives Joanne Hutchinson and Irene Namuquer. The recruitment and follow-up of women was completed on 1 June 2012.

This work is funded by The Foyle Foundation, The Letten Foundation, Vifor Pharma, FP6 Marie Curie Actions-Transfer of Knowledge (MTKD-CT-2005-029914), Sir Halley Stewart Trust, Newham University Hospital NHS Trust and Diabetes Research Network (North East London Diabetes Local Research Network).

This trial is registered with Current Controlled Trials (registration number ISRCTN68997518). The DM and Omega 3-Study Protocol is also available to download.

Published papers

  • Mariniello K, Min Y, Ghebremeskel K (2018) Phosphorylation of protein kinase B, the key enzyme in insulin signalling cascade, is enhanced in linoleic and arachidonic acid treated HT29 and HepG2 cells. Nutrition (In press)
  • Min Y, Djahanbakhch O, Hutchinson J, Eram S, Bhullar AS, Namugere I, Ghebremeskel K. Efficacy of docosahexaenoic acid-enriched formula to enhance maternal and fetal blood docosahexaenoic acid levels: randomized double-blinded placebo-controlled trial of pregnant women with gestational diabetes mellitus. Clin Nutr 2016;35(3): 608-614
  • Min Y, Djahanbakhch O, Hutchinson J, Bhullar AS, Raveendran M, Hallot A, Eram S, Namugere I, Nateghian S, Ghebremeskel K. 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. Diabet Med. 2014; 31(11): 1331-1340
  • Min Y, Nam JH, Ghebremeskel K, Kim A, Crawford M. A distinctive fatty acid profile in circulating lipids of Korean gestational diabetics: A pilot study. Diab Res Clin Pract 2006; 73:178-183
  • Thomas B, Ghebremeskel K, Lowy C, Offley-Shore B, Crawford MA. Nutrient intake of women with and without gestational diabetes with a specific focus on fatty acids. Nutrition 2006; 22:230-236
  • Min Y, Lowy C, Ghebremeskel K, Thomas B, Offley-Shore B, Crawford M. Unfavourable 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 2005; 82: 1162-1168
  • Thomas B, Ghebremeskel K, Lowy C, Min Y, Crawford MA. Plasma fatty acids of neonates born to mothers with and without gestational diabetes. Prostaglandins Leuko Essent Fatty Acids 2005; 72(5):335-341
  • Min Y, Lowy C, Ghebremeskel K, Thomas B, Bitsanis D, Crawford MA. Fetal erythrocyte membrane lipids modification: Preliminary observation of en early sign of compromised insulin sensitivity in the offspring of gestational diabetics. Diab Med 2005; 22:914-920
  • Ghebremeskel K, Thomas B, Lowy C, Min Y, Crawford MA. Type 1 diabetes compromises plasma arachidonic and docosahexaenoic acids in newborn babies. Lipids 2004; 39(4):335-342
  • Min Y, Ghebremeskel K, Lowy C, Thomas B, Crawford MA. Adverse effect of obesity on red cell membrane arachidonic and docosahexaenoic acids in gestational diabetes. Diabetologia 2004; 47(1): 75-81
  • Thomas B, Ghebremeskel K, Lowy C, Min Y, Crawford MA. Plasma AA and DHA levels are not compromised in newly diagnosed gestational diabetic women. Eur J Clin Nutr 2004; 58:1492-1497
  • Ghebremeskel K, Bitsanis D, Koukkou E, Lowy C, Poston L and Crawford M. 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 2002; 132(3):349-354
  • Ghosh P, Bitsanis D, Ghebremeskel K, Crawford MA and Poston L. Abnormal aortic fatty acid composition and small artery function in offspring of rats fed a high fat diet in pregnancy. J Physiol 2001; 533.3:815-822
  • Ghebremeskel K, Bitsanis D, Koukkou E, Lowy C, Poston L and Crawford MA. Post natal modulation of heart and liver phosphoglyceride fatty acids in pups. Ann Nutr Metab 1999; 43: 365-373
  • Ghebremeskel K, Bitsanis D, Koukkou E, Lowy C, Poston L and Crawford MA. Maternal diet high in fat reduces docosahexaenoic acid in liver lipids of newborn and sucking rat pups. Br J Nutr 1999; 81: 395-404
  • Crawford MA, Lowy C, Koukkou E, Poston L, Ghebremeskel K. Sex ratio of offspring of diabetics. Lancet 1998; 351(9114):1515-1516
  • Ghebremeskel K, Thomas B, Min Y, Stacey F, Koukkou E, Lowy C, Erskine K, Crawford M and Offley-Shore B. Fatty acids in pregnant diabetic women and neonates: Implications for growth and development. In: Essential Fatty Acids and Eicosanoids, Invited Papers from the Fourth International Congress. Riemersma RA et al. (eds), Champaign, Illinois, 1998, p104-107

Abstracts

  • Min Y, Bhullar A, Hutchinson J, Namugere I, Djahanbakhch O, Ghebremeskel K Platelet fatty acid composition of pregnant women with type 2 diabetes in early gestation.  International Society for the Study of Fatty Acids and Lipids (ISSFAL), 5 - 9 September 2016, Stellenbosch, South Africa
  • Cabello-Moruno R, Min Y, Hallot A, Hutchinson J, Mariniello K, Djahanbakhch O, Ghebremeskel K. Erythrocyte membrane phospholipid molecular species in pregnant women with gestational and type 2 diabetes. International Society for the Study of Fatty Acids and Lipids (ISSFAL), 29 May - 2 June 2010, Maastricht, The Netherlands
  • Min Y, Lowy C, Geppert J, Islam S, Tait S, Alexandre V, Khan FS, Swaminathan R, Ghebremeskel K (2008). Membrane fatty acids and adipocytokine of individuals with varying degrees of insulin sensitivity. Eighth Biennial International Scientific Meeting of ISSFAL, Kansas City, Missouri, USA
  • Lowy C, Min Y (2008). Maternal nutrition, obesity, diabetes and adverse pregnancy outcome. International Conference on the Economic Importance of Fisheries and their Impact on Public Health. Muscat, Sultanate of Oman.
  • Khan FS, Islam S, Min Y, Swaminathan R, Tait S, Lowy C (2006) Relationship between insulin resistance and adipokines with body composition and glucose tolerance. 197th Meeting of the Society for Endocrinology, Endocrine Abstracts 12, page 38
  • Aurora R, Gothard P, Thomas B, Lowy C, Min Y, Ghebremeskel K (2005). High dose of MaxEPA treatment reduces fat mass of diet-treated type 2 diabetic patients. 23rd International Symposium on Diabetes and Nutrition Diabetes and Nutrition Study Group of the European Association for the Study of Diabetes, Ebeltoft, Denmark
  • Min Y, Lowy C, Thomas B, Ghebremeskel K (2004). Altered long-chain n-3 and n-6 fatty acids in cord plasma and red cell phospholipids born to Type 1 and Type 2 diabetic women. 35th Annual Meeting of Diabetic Pregnancy Study Group, Luso Village, Portugal
  • Min Y, Ghebremeskel K, Nam JH, Kim A, Crawford MA (2004). Membrane lipid imbalance in lean women with gestational diabetes from South Korea. Sixth Congress of the International Society for the Study of Fatty Acids and Lipids, Brighton, UK
  • Min Y, Lowy C, Ghebremeskel K, Crawford MA, Thomas B, Offley-Shore B (2003). Red cell choline phosphoglycerides fatty acid profiles in mothers and their newborns in control and gestational diabetes. Science and Medicine Conference, Medical Research Society, London, UK
  • Min Y, Lowy C, Thomas B, Ghebremeskel K, Crawford MA, Offley-Shore B (2002). Changes in red cell choline phosphoglyceride fatty acid in control and diabetic pregnancies. pp924, 38th Annual Meeting of the European Association for the Study of Diabetes, Budapest, Hungary
  • Min Y, Lowy C, Thomas B, Ghebremeskel K, Crawford MA, Offley-Shore B (2002). Red cell choline phosphoglycerides fatty acid profiles in mothers and their newborns in control and gestational diabetes. OP-12, 34th Annual Meeting of the Diabetic Pregnancy Study Group of the European Association for the Study of Diabetes, Lake Balaton, Hungary
  • Min Y, Thomas B, Ghebremeskel K, Crawford MA, Offley-Shore B, Lowy C (2000). Do gestational diabetics have abnormal membrane fatty acid composition?, p87, 4th International Congress for the Study of Fatty Acids and Lipids, Tsukuba, Japan
  • Min Y, Thomas B, Ghebremsekel K, Offley-Shore B, Lowy C, Crawford MA (1999). Pregestational diabetes reduces maternal red cell membrane docosahexaenoic acid in mother. A248-935, 35th European Association for the Study of Diabetes, Brussels, Belgium

Effect of vitamin A and fish oil on inflammatory bowel disease

Vitamin A is an antioxidant and activator of peroxisome proliferator-activated nuclear receptors (PPARs). The target genes of PPARs are known to participate in fatty acid uptake, binding, oxidation and transport.

In collaboration with Dr Ram Reifen at the Hebrew University of Jerusalem, Israel, we have investigated the effect of vitamin A deprivation on membrane DHA levels in experimental animals. The study demonstrates that membrane DHA is reduced by vitamin A deficiency. DHA is vital for the structure and function of visual and neural systems. Our finding will be relevant to nutritional management of vitamin A-deficient communities.

Published papers

Zhou D, Ghebremeskel K, Crawford MA, Reifen R (2008) Chapter 11. The effect of vitamin A deficiency and inflammation on long chain polyunsaturated fatty acids in rat colon and liver membranes. In: Malnutrition Research Advances, Editor: Vesler LW. Nova Science Publishers, Inc., p183-212

Zhou D, Ghebremeskel K, Crawford MA, Reifen R (2006), Vitamin A deficiency enhances liver and colon membrane docosahexaenoic and docosapentaenoic acids in rats fed alpha-linolenic acid adequate diet. Lipids 41(3):213-219.

Zhou D, Zaiger G, Ghebremeskel K, Crawford MA, Reifen R (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 71:383-389.

Uritski R, Barshack I, Bilkis I, Ghebremeskel K, Reifen R (2004), Dietary iron affects the inflammatory status of colitis. J Nutr 2004; 134(9): 2251-2255.

Reifen R, Nur T, Ghebremeskel K, Zaiger G, Urizky R and Pines M (2002), Vitamin A deficiency exacerbates inflammation in a rat model of colitis through activation of nuclear factor-kB and collagen formation. J Nutr 132: 2743-2747.

Comparative study of essential fatty acid status of Chinese pregnant women and their neonates

Published papers

Zhang J, Wang Y, Meng L, Wang C, Zhao W, Chen J, Ghebremeskel K, Crawford MA (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 18(3):377-88.

Meng LP, Zhang J, Wang YQ, Wang CR, Ghebremeskel K, Zhao WH (2008) Dietary fatty acids intake and their food sources in pregnant women from different aquatic-product intake regions in China. Acta Nutrimenta Sinica, 30(3): 249-252.

Nutritional status of internally displaced pregnant, lactating and non-pregnant Sudanese women

This project investigated the nutritional status of displaced pregnant and lactating women women living in Khartoum, Sudan. Habitual dietary intake and fatty acids composition of maternal and cord plasma and breast milk, and vitamins and trace elements were assessed.

Published papers

Nyuar KB, Min Y, Dawood M, Abukashawa S, Daal A, Ghebremeskek (2013), Regular consumption of Nile river fish could ameliorate the low milk DHA of Southern Sudanese women living in Khartoum City area. Prostaglandins Leukot Essent Fatty Acids 89(2-3):65-69.

Nyuar KB, Ghebremeskel, Crawford MA (2012), Sudanese women's and neonates' vitamin A status. Nutr Health 21(1):45-55.

Nyuar KB, Khalil AK, Crawford MA (2012), Dietary intake of Sudanese women: a comparative assessment of nutrient intake of displaced and non-displaced women. Nutr Health 21(2):131-144.

Nyuar KB, Min Y, Ghebremeskel K, Khalil AKH, Elbashir MI, Crawford MA (2010), Milk of northern Sudanese mothers whose traditional diet is high in carbohydrate contains low docosahexaenoic acid. Acta Paediatrica 2010 99(12):1824-7.

Essential fatty acid and antioxidant status in patients with pre-eclampsia

Published Papers

Bakheit KH, Ghebremeskel K, Pol K, Elbashir MI, Adam I (2010) Erythrocyte omega-3 and omega-6 fatty acids profile in Sudanese women with pre-eclampsia. J Obstet Gynaecol 30(2):151-154

Bakheit KH, Ghebremeskel K, Zaiger G, Elbashir MI, Adam I (2010) Erythrocyte antioxidant enzymes and plasma antioxidant vitamins in Sudanese women with pre-eclampsia. J Obstet Gynaecol 30(2):147-150