Role of Vitamin C As an Adjuvant Therapy with Different Iron Chelators in Young β-Thalassemia Major Patients: Safety and Efficacy in Relation to Tissue Iron Overload

Background: Treatment with antioxidants may neutralize the deleterious effects of oxidative damage by reactive oxygen species generated from labile plasma iron. Vitamin C has been known to increase the efficacy of desforaxamine (DFO). Few studies examined the influence of vitamin C supplementation in iron overloaded β-thalassemia major (β-TM) patients with oral chelators.

Aim: To determine the beneficial effects of Vitamin C as an adjuvant to iron chelators in children and adolescents with β-TM and its relation to tissue iron overload.

Methods: A randomized prospective study registered on ClinicalTrials.gov (NCT02083575) included 100 patients with β-TM recruited from the regular attendees of Thalassemia center. Inclusion criteria were β-TM patients 2-18 years with serum ferritin (SF) >1000-2500 ng/ml on regular transfusion-chelation therapy receiving the standard doses of Desferrioxamine (DFO), deferiprone (DFP), deferasirox (DFX) in a ratio1:1:1. All the enrolled patients had vitamin C deficiency. Exclusion criteria included patients suffered from insulin-dependent diabetes, clinical cardiac and/or advanced liver disease. The thalassemia patients received vitamin C in a dose of 100 mg daily. Patients were followed-up for 6 months with assessment of transfusion frequency and index, complete blood count, vitamin C levels, serum iron, total iron binding capacity (TIBC), SF and transferrin saturation (Tsat), liver iron content (LIC) and cardiac magnetic resonance imaging T2* before and after therapy were assessed.

Results: Laboratory variables at baseline were similarly distributed among patients receiving different iron chelating agents. Upon comparing baseline and post-therapy clinical and laboratory variables among the studied β-thalassemia patients; transfusion index was significantly decreased after 6 months of vitamin C therapy (p=0.03) and the number of transfused patients <3 weeks dropped from 66% to 57% although the difference did not reach a significant level. Hemoglobin level improved (p<0.01). SF, Tsat and LIC were significantly lower after treatment than baseline levels (p=0.048, p<0.01 and p=0.035, respectively). Cardiac MRI T2* and vitamin C levels increased 6 months after treatment (p=0.025 and p<0.001, respectively). Vitamin C supplementation to patients receiving DFO had significantly lowest transfusion index (p=0.035) with significant improvement in hemoglobin level and cardiac MRI T2* as well as decreased SF, Tsat and LIC (p<0.01). Patients on DFP or DFX showed non-significant improvement in hematological and radiological variables. Vitamin C level was negatively correlated to transfusion index, SF and LIC (p<0.01). Neither serious adverse reactions related to the chelators nor to Vitamin C administration have been reported.

Conclusions: Vitamin C in a dose of 100 mg, as an adjuvant therapeutic agent increased the efficacy of DFO in reducing iron burden in the moderately iron overloaded B-TM with vitamin C deficiency; it showed marginal improvement with DFP and DFX. Higher doses of vitamin C therapy might be tried with evaluation of possible additional adverse events.