Detectable Unmetabolized Folic Acid and Elevated Folate Concentrations in Folic Acid-Supplemented Canadian Children With Sickle Cell Disease

Brock A Williams; Cara Mayer; Heather McCartney; Angela M Devlin; Yvonne Lamers; Suzanne M Vercauteren; John K Wu; Crystal D Karakochuk

doi:10.3389/fnut.2021.642306

Detectable Unmetabolized Folic Acid and Elevated Folate Concentrations in Folic Acid-Supplemented Canadian Children With Sickle Cell Disease

Front Nutr. 2021 Apr 21:8:642306. doi: 10.3389/fnut.2021.642306. eCollection 2021.

Authors

Brock A Williams^{1

2}, Cara Mayer^{1

2}, Heather McCartney³, Angela M Devlin^{2

3}, Yvonne Lamers^{1

2}, Suzanne M Vercauteren^{2

4}, John K Wu^{2

3}, Crystal D Karakochuk^{1

2}

Affiliations

¹ Food, Nutrition, and Health, The University of British Columbia, Vancouver, BC, Canada.
² BC Children's Hospital Research Institute, Vancouver, BC, Canada.
³ Department of Pediatrics, Faculty of Medicine, The University of British Columbia, Vancouver, BC, Canada.
⁴ Division of Hematopathology, Department of Pathology and Laboratory Medicine, BC Children's Hospital, Vancouver, BC, Canada.

Abstract

Sickle cell disease (SCD) is an inherited hemoglobinopathy caused by a variant (rs344) in the HBB gene encoding the β-globin subunit of hemoglobin. Chronic hemolytic anemia and increased erythropoiesis and RBC turnover in individuals with SCD can result in increased needs for folate and other B-vitamins. We assessed B-vitamin status, and the distribution of folate forms, including unmetabolized folic acid (UMFA), in Canadian children with SCD supplemented with 1 mg/d folic acid (current routine practice). Non-fasted serum and plasma samples were analyzed for concentrations of folate, and vitamins B-2, B-6, and B-12. Eleven individuals (45% male; SCD type: HbSS n = 8, HbSC n = 2, HbSβ⁰-Thal n = 1), with a median (IQR) age of 14 (7, 18) years, were included. Total folate concentrations were 3-27 times above the deficiency cut-off (10 nmol/L), and 64% of children had elevated folate levels (>45.3 nmol/L). UMFA (>0.23 nmol/L) was detected in all children, and 36% of participants had elevated levels of UMFA (>5.4 nmol/L). All children were vitamin B-12 sufficient (>150 pmol/L), and the majority (55%) had sufficient B-6 status (>30 nmol/L). Among this sample of Canadian children with SCD, there was limited evidence of B-vitamin deficiencies, but UMFA was detectable in all children.

Keywords: B-vitamins; folate; nutrition; pediatrics; sickle cell disease; unmetabolized folic acid.