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 Abnaof Paediatric Hospital, Khartum, 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 Maarie 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 the study protocol can be downloaded SCD & Omega 3-Study Protocol.pdf .

University of Khartoum, Sudan

MAGNETOM Avanto 1.5T (Siemens)

Magnetic Resonance Angiograph (MRA)

Diffusion Tensor Imaging (DTI)

Time of Flight Angiograph

Arterial Spin Labeling Perfusion Imaging

Published Papers

Daak AA, Ghebremeskel K, Elbashir MI, Bakhita A, Hassan Z, Crawford MA (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.