Optimization of folic acid, vitamin B12, and vitamin B6 supplements in pediatric patients with sickle cell disease

Abstract

Using homocysteine as a functional marker, we determined optimal folic acid, vitamin B12, and vitamin B6 dosages in 21 pediatric sickle cell disease (SCD) patients (11 HbSS, 10 HbSC; 7-16 years). Daily supplements of folic acid (400, 700, or 1,000 μg), vitamin B12 (1, 3, or 5 U.S. 1989 RDA), and vitamin B6 (1 or 3 U.S. 1989 RDA) were gradually increased in an 82-week dose-escalation study. Blood was taken at 9 occasions for measurements of erythrocyte (RBC) and serum folate, plasma vitamin B12, whole-blood vitamin B6, and plasma homocysteine. Augmentation of folic acid from 700 to 1,000 μg and vitamin B12 from 3 to 5 RDA did not further decrease homocysteine. Percentages of patients exhibiting significant individual homocysteine decreases amounted to 43% (folic acid from 0 to 400 μg, vitamins B12 and B6 from 0 to 1 RDA), 14% (folic acid from 400 to 700 μg), 24% (vitamin B12 from 1 to 3 RDA), and 18% (vitamin B6 from 1 to 3 RDA). The lowest plasma homocysteine at 82 weeks was 5.9 ± 2.2 μmol/L. Patients with HbSS had higher RBC folate than HbSC. The entire group exhibited an inverse relation between RBC folate and hemoglobin. We conclude that RBC folate is less valuable for folate status assessment in SCD patients. Optimal dosages are as follows: 700 μg folic acid (3.5-7 U.S. 1989 RDA), 3 U.S. 1989 RDA vitamin B12 (4.2-6.0 μg), and 3 U.S. 1989 RDA vitamin B6 (4.2-6.0 mg). A practical daily combination is 1 mg folic acid (4.3-8.5 U.S. 1998 RDA when taken with meals), 6 μg vitamin B12 (2.5-5 U.S. 1998 RDA), and 6 mg vitamin B6 (4.6-10 U.S. 1998 RDA). This combination may by simple and relatively inexpensive means reduce these patients' inherently high risk of endothelial damage. © 2002 Wiley-Liss, Inc.