The aim of our review was to evaluate the evidence for and against folic acid supplementation in sickle cell disease. Folic acid has been both widely prescribed and hotly debated for the last four decades. We undertook an extensive literature based review with the aim of evaluating the clinical benefits of this supplementation and its implications on future paediatric practice. Comprehensive scientific search engines were used to locate articles published up to June 2011. A wide range of search terms were used, and article references and citations were reviewed for further leads.
Studies in support of folic acid supplementation have cited low serum and erythrocyte folate levels in paediatric sickle cell patients, high incidence of megaloblastic anaemia, patient desire for folic acid and the positive effects of supplementation including; reversal of developmental delay, reduced dactylitis and reduction of homocysteine levels leading to reduced cardiovascular, stroke and venous thrombosis risk.
Studies against folic acid supplementation conversely found that folate is not deficient in patients, megaloblastic change is uncommon and both these parameters are not improved with supplementation. They have shown that folic acid does not lead to improvements in haemoglobin, growth characteristics, infections, splenic sequestration and dactylitis. Possible dangerous effects of supplementation are also referred to including increased priaprism, increased twin pregnancy rates and the risk of masking cobalamin deficiency with consequent neuropsychiatric manifestations. These studies also found that homocysteine levels are not lower in sickle cell patients and cardiovascular risk is not reduced with supplementation.
The conflicting results may be due to genetic polymorphisms in folic acid/homocysteine metabolism between patients, inconsistent supplementation doses and various ethnic group representations in the papers analysed. Drawing definitive conclusions is difficult due to the small number and heterogeneous nature of the studies and our review has emphasised the need for more prospective, sufficiently powered, research in this field. Till then, the safest clinical practice would be to individualise folic acid treatment for patients based on their needs and comorbidities whilst continuing to encourage compliance with more evidence based medications including Penicillin V and hydroxyurea.