Detectable Unmetabolized Folic Acid, and Sufficient Folate and Vitamin B12 Concentrations Are Evident in Canadian Children with Sickle Cell Disease

Abstract

Abstract Objectives Canadian children with sickle cell disease (SCD) are routinely supplemented with high-dose folic acid (1 mg/d), synthetic folate, due to increased erythrocyte production and turn-over in the disease. Folate also plays a vital role in one-carbon metabolism. Impairments in this folate-dependent mechanism can also occur due to secondary B-vitamin (vitamin B2, B6 and B12) deficiencies. The study objective was to determine B-vitamin status in Canadian children with SCD. Methods Serum and plasma samples from children diagnosed with SCD were obtained from BC Children's Hospital BioBank (Vancouver, Canada). Samples were analyzed for folate, vitamin B6, and related metabolites using electrospray ionization-liquid chromatography-tandem mass spectrometry. Vitamin B12 concentrations were analyzed using chemiluminescent immunoassay. World Health Organization cut-offs were used to determine deficiencies of folate (<10 nmol/L) and vitamin B12 (<150 pmol/L), and European Food Safety Authority Panel cut-offs were used for vitamin B6 (<30 nmol/L pyridoxal 5’-phosphate; PLP). Medians with interquartile ranges (IQR) are presented. Results Six individuals (50% male; SCD type: Hgb SS n = 3, Hgb SC n = 2, HbSβ,0-Thal n = 1) were included. Median age of participants was 15 (9, 18) years. Half (50%) of participants were prescribed hydroxyurea (median dose: 21(14, 30) mg/kg/d), and all participants were prescribed 1 mg/d folic acid (adherence data not available). Median serum folate was 55.4 (43.1, 71.9) nmol/L, with levels 3 to 15 times above the cut-off for deficiency. Unmetabolized folic acid (UMFA), unused folic acid in circulation, was detected in all six participants. All participants were vitamin B12 sufficient, with median plasma vitamin B12 of 325 (288, 411) nmol/L. The majority (n = 5; 83%) had sufficient B6 status, with median serum PLP of 39 (36.9, 44.2) nmol/L. Conclusions In this pilot project, there was limited evidence of B-vitamin deficiencies among Canadian children with SCD. Serum folate levels exceeded the cut-off for deficiency by 3 to 15 times, with all participants having detectable levels of UMFA. A randomized clinical trial re-assessing the routine practice of high-dose folic acid supplementation in children with SCD is warranted. Funding Sources Thrasher Research Fund and Rare Disease Foundation.