High-dose folic acid supplementation in children with sickle cell disease: Friend or foe?
BACKGROUND: Children with sickle cell disease are considered to have high requirements for folate (a B-vitamin required for DNA synthesis and erythropoiesis), owing to chronic hemolytic anemia, and higher erythropoiesis and RBC turnover. As such, high-dose supplementation with 1-5 mg/d folic acid, the synthetic form of folate, has been a long-standing recommendation for children with SCD.
GAP: There is scant evidence that high-dose folic acid supplementation improves hematological or clinical outcomes in individuals with sickle cell disease, and some evidence of potential harm.
HYPOTHESIS: There will be no difference in mean RBC folate concentrations across the high-dose folic acid and control groups after 12-wk, and none of the children will have folate deficiency. Compared to children taking placebo, children taking high-dose folic acid for 12-wk will show no difference in clinical outcomes, but higher plasma UMFA concentrations.
METHODS: We propose a double-blind randomized controlled cross-over trial among children with sickle cell disease (n=40, aged 2-19 y) recruited from BC Children’s Hospital (Vancouver, Canada) and randomized to 1 mg/d folic acid or a placebo for 12-wk (after a 12-wk washout period, treatments will be reversed). Children with sickle cell disease aged 2-19 y attending BC Children’s Hospital who have not had a blood transfusion in the prior 12-wk.
IMPACT: The findings of this clinical trial will contribute to the evidence base to inform policy and the clinical practice of high-dose folic acid supplementation in children with sickle cell disease.