Trial reportThe American journal of clinical nutrition2025
Folic acid supplementation in children with sickle cell disease: a randomized double-blind noninferiority cross-over trial.
Trial report in The American journal of clinical nutrition, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04011345 (Folic Acid Supplementation in Children With Sickle-Cell Disease), which is not on this map. Not yet cited in PubMed.
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The trial behind it
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Folic Acid Supplementation in Children With Sickle-Cell Disease: A Randomized Double-Blind Cross-Over Trial
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Authors and funding
8 authors.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundChildren with sickle cell disease (SCD) in Canada are routinely supplemented with folic acid to provide sufficient folate for the increased demands of erythropoiesis. However, with the mandatory folic acid fortification of refined grains and pharmacotherapies that extend the lifespan of sickled red blood cells (RBC), this clinical practice is in question.
objectivesThis study aims to determine the efficacy of folic acid supplementation by measuring the effect of 12 ± 1 wk of 1 mg/d folic acid, compared with placebo, on concentrations of RBC folate (primary outcome), serum folate, and 1-carbon-related metabolites, and clinical outcomes in children with SCD.
methodsIn this double-blind randomized controlled noninferiority cross-over trial, 31 children with SCD, aged 2-19 y, were enrolled and randomly assigned (1:1 with blocks of 4) to 1 mg/d folic acid, the current standard of care, or a placebo for 12 ± 1 wk. After a 12 ± 1 wk washout period, treatments were reversed.
resultsThe mean [95% confidence interval (CI)] difference in endline RBC folate concentrations across treatments was -179 (-260, -99) nmol/L, with the lower boundary of the CI exceeding noninferiority but the upper boundary not (P = 0.0001; modified intention-to-treat). There was no significant difference in the number of participants who had RBC folate deficiency after each treatment (P = 0.059). No participants presented with serum folate deficiency (<7 nmol/L). There were no significant differences observed in 1-carbon metabolite concentrations (total homocysteine, S-adenosylhomocysteine, S-adenosylmethionine, vitamin B
conclusionsDespite mandatory food fortification and advances in the medical treatment of SCD, it appears that some children with this condition may still benefit from daily folic acid supplementation. Whether this translates to improved clinical outcomes remains uncertain. This trial was registered at clinicaltrials.gov as NCT04011345 (https://clinicaltrials.gov/study/NCT04011345).
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