Omega-3 Fatty Acid Deficiency in Sickle Cell Disease Correlates with Clinical Severity and Has Therapeutic Implications.

Background: Clinical illness in SCD results not only from the β-globin gene mutation, but also from other genetic and environmental factors acting in concert. The biological basis of individual variation in the severity of SCD is not fully understood. Our previous study revealed that WBCs from people with severe SCD express high levels of the adhesion molecules L-selectin (CD62L) and αMβ2 integrin (CD11a/18) in steady state. These cell membrane proteins mediate leukocyte adherence to vascular endothelium and facilitate vaso-occlusion: a fundamental pathological process in SCD. The lipid composition of cell membranes affects the level of expression of adhesion molecules on the membrane, its structural integrity and function. Abnormalities of plasma and erythrocyte lipids in SCD had been recognised. However, there is little information on lipid composition of leukocyte and platelet membranes in SCD, and its relationship with clinical severity.

Objectives: To analyse the membrane fatty acid (FA) composition of blood mononuclear cells and platelets in SCD, find out if the degree of lipid abnormalities in RBCs affects the Hb level, and whether differences in FA composition of blood cells relate to clinical severity.

Study Design & Methods: The fatty acid (FA) composition of blood cells and plasma in 71 HbSS and 9 HbSC steady-state patients were compared with those of 58 healthy, racially-matched, HbAA controls with similar age and sex distribution. To minimise the confounding effects of differences in dietary patterns, patients were compared with controls living in the same environment. We excluded cigarette smokers, SCD patients with other diseases, HbF levels ≥ 10%, and blood transfusion or pregnancy in the previous 3 months. Hb genotype was determined by electrophoresis or High Performance Liquid Chromatography. The manifestations of SCD were ascertained in each patient by clinical assessment. FA composition of cell membranes and plasma was analysed as described by Folch et al. The statistical package SPSS for Windows (SPSS Ltd, Woking, UK) was used for data analyses.

Results: Mononuclear leukocytes, platelets, plasma and erythrocytes of SCD patients showed deficiency of omega-3 FA relative to matched HbAA controls (p< 0.05). Steady-state Hb level in SCD patients showed strong direct correlation with the proportion of omega-3 FA in RBCs (p< 0.01). HbSS patients had significantly lower amounts of omega-3 FA compared with HbSC individuals in erythrocytes (p< 0.001) and plasma (p< 0.05). The deficiency of omega-3 FA was significantly greater in patients with complications of SCD in comparison to those who had none (p< 0.005).

Therapeutic Implications: The findings suggest that steady-state Hb level in SCD patients might be improved by administration of omega-3 FA. That HbSC patients are also deficient in omega-3 FA suggests that they might derive clinical benefit from therapy with these naturally occurring substances; as previously demonstrated in a pilot clinical trial involving HbSS individuals. Considering that omega-3 fatty acids are generally consumed as food across the world, more widely available and affordable, safer and have less side-effects compared to hydroxyurea or blood transfusion, it is appropriate to assess their efficacy in SCD in a large clinical trial.