Optimization of folic acid, vitamin B-12, and vitamin B-6 supplements in pediatric patients with sickle cell disease

Using homocysteine as a functional marker, we determined optimal folic acid, vitamin B-12, and vitamin B-6 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 mug), vitamin B-12 (1, 3, or 5 U.S. 1989 RDA), and vitamin B-6 (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 B-12, whole-blood vitamin B-6, and plasma homocysteine. Augmentation of folic acid from 700 to 1,000 mug and vitamin B-12 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 mug, vitamins B-12 and B-6 from 0 to 1 RDA), 14% (folic acid from 400 to 700 mug), 24% (vitamin B-12 from 1 to 3 RDA), and 18% (vitamin B-6 from 1 to 3 RDA). The lowest plasma homocysteine at 82 weeks was 5.9 +/- 2.2 mumol/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 mug folic acid (3.5-7 U.S. 1989 RDA), 3 U.S. 1989 RDA vitamin B-12 (4.2-6.0 mug), and 3 U.S. 1989 RDA vitamin B-6 (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 mug vitamin B-12 (2.5-5 U.S. 1998 RDA), and 6 mg vitamin B-6 (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.