Measures of cellular oxidative damage following vitamin E supplementation in young patients with transfusion-dependent thalassemia: a double-blind randomized controlled trial

Abstract

Background: Patients with thalassemia acquire cellular oxidative damage mainly from the degradation of excessive uncoupled hemoglobin (Hb) chains and iron overload. The oxidative damage of red blood cells (RBCs) and platelets potentially results in the worsening of ineffective erythropoiesis, hemolysis, and the occurrence of thromboembolic events. Vitamin E (VitE) is an antioxidant that inhibits membrane lipid peroxidation. It is widely used as a supplement in thalassemia; however, its benefits in improving cellular oxidative damage remain unclear. Methods: We conducted a double-blind, randomized, controlled trial registered in the Thai Clinical Trials Registry (TCTR20220801001) on 01/08/2022. We randomized transfusion-dependent (TD) β- and α-thalassemia (aged 10–25 years) to receive oral VitE 400 IU/day or placebo at a 1:1 ratio for 6 months. Cellular oxidative damage markers, including phosphatidyl serine (PS)-bearing RBCs, PS-bearing RBC vesicles, PS-bearing platelets, PS-bearing microparticles (MPs), PS-bearing RBC-MPs, PS-bearing platelet MPs (PMPs) and platelet activation, were measured before and after the intervention as the primary outcomes. Results: Seventy-four TD thalassemia patients were categorized into 63 β-thalassemia (10 splenectomy, β-Thal-S; and 53 non-splenectomy, β-Thal-NS) and 11 α-thalassemia (non-splenectomy, α-Thal-NS). Randomized from all patient groups, 36 received VitE and 38 received a placebo. A significant reduction in PS-bearing RBCs and PS-bearing RBC vesicles was observed in the β-Thal-NS receiving VitE. This occurred parallel with a substantial decrease in malondialdehyde levels, as a marker of lipid peroxidation, found only in the β-Thal-NS but not in β-Thal-S and α-Thal-NS groups. In the β-Thal-NS group, VitE had improved RBC pathology as demonstrated by the inverse correlation between post-treatment VitE levels and PS-bearing RBCs (p = 0.001) as well as reticulocyte count (p = 0.006), although Hb levels remained unchanged. The VitE treatment did not result in improving platelet pathology or reducing MPs. No adverse event was reported in both VitE and placebo groups. Conclusions: VitE 400 IU/day was well-tolerated and associated with improved oxidative damage of the RBCs in TD β-Thal-NS patients. Accordingly, advice for VitE supplementation in young TD β-Thal-NS patients can be beneficial.