Reduction of pain episodes and prothrombotic activity in sickle cell disease by dietary n-3 fatty acids

The effects of dietary n-3 fatty acids (n-3FAs) on the frequency of pain ep isodes and ex vivo blood tests of thrombosis have been evaluated in patient s with sickle cell disease (SCD) utilizing a double-blind, olive oil-contro lled clinical trial. Dietary n-3FA therapy (0.1 g/kg/d) was provided as men haden fish oil (0.25 g/kg/d) containing 12% eicosapentaenoic acid (EPA). an d 18% docosahexaenoic acid (DHA). Within 1 month dietary n-3FAs exchanged w ith n-6FAs in plasma and erythrocyte membrane phospholipids (p < 0.01 in al l cases). Treatment with dietary n-3FAs for 1 year reduced the frequency of pain epis odes requiring presentation to the hospital from 7.8 events during the prec eding year to 3.8 events/year (p < 0.01: n = 5). By contrast, subjects: rec eiving control dietary olive oil(n = 5)experienced 7.1 pain events/year, co mpared to 7.6 during the previous year (p > 0.1). The reduction in episodes in n-3FA-treated subjects was also significant when compared to control su bjects (p < 0.01). Dietary n-3FA therapy was not associated with hemorrhagi c, gastrointestinal or other adverse effects. Compared to 10 asymptomatic African-American controls, sickle cell subjects demonstrated significantly increased pretreatment: flow cytometric express ion of platelet membrane P-selectin (CD62p; p < 0.01) and annexin V binding sites (p = 0.02); 2) plasma levels of platelet-specific secretory proteins platelet factor 4 (PW) and P-thromboglobulin (beta TG) (p < 0.01 in both c ases); 3) plasma products of thrombin generation, prothrombin fragment 1.2 (F1.2) and thrombin:antithrombin (TAT) complex (p < 0.01 in both cases): an d 4) plasma levels of thrombolytic products, D-dimer and plasmin:antiplasmi n (PAP) complex (p < 0.01 in both cases). Treatment with dietary n-3FAs con currently decreased plasma levels of F1.2. D-dimer, and PAP (p < 0.05, comp ared to olive oil controls), implying that the reduction in pain events was related to n-3FA-dependent inhibition of thrombosis. We conclude that diet ary n-3FAs reduce the frequency of pain episodes perhaps by reducing prothr ombotic activity in sickle cell disease.