Vitamin C as an adjuvant therapy possibly potentiates the efficacy of DFO more than DFP and DFX in reducing iron burden in the moderately iron-overloaded vitamin C-deficient patients with β-TM, with no adverse events.
Objective: To evaluate the impact of iron chelating drugs and serum ferritin on the neurocognitive functions of patients with β thalassemia major (β-TM), using psychometric, neurophysiologic and radiologic tests. Methods: Eighty children with β-TM were enrolled into the study and were compared to 40 healthy controls. All participants were evaluated by measuring serum ferritin, neurocognitive assessment by Benton Visual Retention Test, Wechsler Intelligence Scale for Children, Wisconsin Card Sort Test, P300 and magnetic resonance spectroscopy (MRS). Results: WISC in our study showed that 40% of cases were borderline mental function as regards total IQ. Neurophysiologic tests were significantly impaired in patients compared to control group, with significant impairment in those receiving desferrioxamine (DFO). P300 amplitude was significantly lower in cases compared to controls (2.24 and 4.66 uv, respectively), recording the shortest amplitude in patients receiving DFO. Altered metabolic markers in the brain were detected by MRS in the form of reduced N-acetylaspartate to creatine ratio in 78.3% of our cases. There were significant correlations between psychometric tests and both neurophysiologic (P300) and radiologic (MRS) tests. Conclusion: β-TM is associated with neurocognitive impairment that can be assessed by psychometric, neurophysiologic and radiologic tests. The role of hemosiderosis and iron chelation therapy on cognitive functioning still need more research.
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.
Disclosures
No relevant conflicts of interest to declare.
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