Optimum dose of oral folic acid supplementation in transfusion-dependent thalassemia: a randomized controlled trial.

AIM AND OBJECTIVES:We compared the effect of different doses of oral folic acid (FA) supplementation (5 mg/day vs. 2.5 mg/day vs. 5 mg/week) on the proportion of children with folate excess (serum folate >20 ng/ml) and plasma homocysteine (Hcys) excess (>15 µmol/l) in transfusion-dependent thalassemia (TDT). MATERIALS AND METHODS:Children with TDT aged 5-18 years received oral FA in doses of 5 mg/day (Group 1), 2.5 mg/day (Group 2) and 5 mg/week (Group 3) for 9 months, after a wash-off period of 8 weeks. Folate levels (Serum and RBC) and plasma Hcys levels were measured after the therapy. RESULTS:Ninety children were randomized to receive one of the three interventions (30 per group). After wash-off period, the median serum folate levels were significantly lower and five children developed folate deficiency; the median [interquartile range (IQR)] serum folate levels (ng/dl) were comparable in the three groups [Group 1: 6.5 (3.3-14.2), Group 2: 5.1 (2.6-10.5) and Group 3: 4.8 (3.4-10.0)]. After 9 months of intervention, the median (IQR) serum folate levels (ng/ml) were comparable in all participants [Group 1: 18.0 (6.5-28), Group 2: 13.5 (6.4-24.5) and Group 3: 9.7 (5.3-22.5); p = 0.11]. Proportion of children with serum folate excess was 40%, 26.7% and 26.7% in Group 1, Group 2 and Group 3 (p = 0.48). Proportion of children with RBC folate excess was 92%, 86.7% and 86.7% in Group 1, Group 2 and Group 3 (p = 0.79). Hyperhomocysteinemia was seen in eight children with no significant difference between median Hcys levels in the groups (p = 0.75). CONCLUSION:Folic acid supplementation is recommended in TDT with 5 mg weekly dose being adequate.