The effects of dietary
n-3 fatty acids (n-3FAs) on the frequency of
pain episodes and ex vivo blood tests of
thrombosis have been evaluated in patients with
sickle cell disease (SCD) utilizing a double-blind,
olive oil-controlled clinical trial. Dietary n-3FA
therapy (0.1 g/kg/d) was provided as menhaden
fish oil (0.25 g/kg/d) containing 12%
eicosapentaenoic acid (EPA), and 18%
docosahexaenoic acid (DHA). Within 1 month dietary n-3FAs exchanged with n-6FAs in plasma and erythrocyte membrane
phospholipids (p <0.01 in all cases). Treatment with dietary n-3FAs for 1 year reduced the frequency of
pain episodes requiring presentation to the hospital from 7.8 events during the preceding year to 3.8 events/year (p <0.01; n = 5). By contrast, subjects receiving control dietary
olive oil (n = 5) experienced 7.1
pain events/year, compared to 7.6 during the previous year (p >0.4). The reduction in episodes in n-3FA-treated subjects was also significant when compared to control subjects (p <0.01). Dietary n-3FA
therapy was not associated with hemorrhagic, gastrointestinal or other adverse effects. Compared to 10 asymptomatic African-American controls, sickle cell subjects demonstrated significantly increased pretreatment: 1) flow cytometric expression 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 (PF4) and
beta-thromboglobulin (betaTG) (p <0.01 in both cases); 3) plasma products of
thrombin generation,
prothrombin fragment 1.2 (F1.2) and
thrombin:
antithrombin (TAT) complex (p <0.01 in both cases); and 4) plasma levels of thrombolytic products,
D-dimer and
plasmin:
antiplasmin (
PAP) complex (p <0.01 in both cases). Treatment with dietary n-3FAs concurrently decreased plasma levels of F1.2,
D-dimer, and PAP (p <0.05, compared to
olive oil controls), implying that the reduction in
pain events was related to n-3FA-dependent inhibition of
thrombosis. We conclude that dietary n-3FAs reduce the frequency of
pain episodes perhaps by reducing prothrombotic activity in
sickle cell disease.