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. 

University of Khartoum, Sudan

LNRC khartoum university

MAGNETOM Avanto 1.5T (Siemens)

LNRC siemen scaner

Magnetic Resonance Angiograph (MRA)

LNRC MRA image

Diffusion Tensor Imaging (DTI)

LNRC DTI image

Time of Flight Angiograph

LNRC tofmra scd

Arterial Spin Labeling Perfusion Imaging

LNRC asl scd

Published Papers

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 & 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.