ABSTRACT
We determined optimal folate, vitamin B12 and vitamin B6 dosages in 21 sickle cell disease (SCD) patients (11 HbSS, 10 HbSC; mean 7 years, range 7-16), using plasma homocysteine (Hcy) as functional marker. They received daily 400 g (0-3 weeks), 700 g (3-6) and 1000 g (6-70) folate; 1 (0-21), 3 (21-45 and 5 RDA (45-70) vitamin B12; and 1 RDA vitamin B6 (0-70). Blood was taken at baseline (P0) and after 3 (PI), 6 (P2), 9 (P3), 21 (P4), 33 (P5), 45 (P6), 57 (P7) and 70 (P8) weeks for measurement of erythrocyte (RBC), serum folate, plasma vitamin B12, whole blood vitamin B6 and plasma Hcy. Vitamin B6 increased from P0 to P1 and P1 to P2; vitamin B12 from P4 to P8; serum folate from P0 to P1 and P1 to P2; RBC folate from P0 to P1, P1 to P2 and P2 to P3. Hcy decreased from P1 to P2 and P4 to P6. Most pronounced Hcy decreases occurred from P0 to P1 (43 percent of patients), P1 to P2 (14 percent) and P4 to P5 (24 percent). Haematological indices did not change. Patients with HbSS had higher RBC folate at P1, P2 and P8. The entire group exhibited inverse relations between RBC folate and haemoglobin on P1, P2, P3, P6, P7 and P8. We conclude that RBC folate is less valuable for folate status assessment in SCD patients. The optimal daily supplement is 700 g folate (3.5-7 RDA vitamin B12 (4.2-6.0 g) and 1 RDA vitamin B6 (1.4-2.0 mg). This combination causes Hcy levels that do not decrease further upon higher dosages and may reduce by simple and relatively inexpensive means their inherently high risk of endothelial damage.(Au)
Subject(s)
Child , Humans , Anemia, Sickle Cell/blood , Vitamin B 12 Deficiency/diet therapy , Vitamin B 6 Deficiency/diet therapy , Pteroylpolyglutamic Acids/deficiency , Data CollectionABSTRACT
We investigated whether pediatric patients with sickle cell disease (SCD) (9 +/- 4 years; 27 homozygous SCD [HbSS]; 19 sickle-C disease [HbSC]) have different folate status compared with age-, sex-, and race-matched normal hemoglobin (HbAA) controls (n = 20), and whether their folate status can be improved by folate supplementation. The patients were supplemented with vitamins B6 and B12 during one week and with folate during the following week. Circulating folate, homocysteine, vitamin B6 and vitamin B12 levels were measured at baseline (patients and controls), after one week and after two weeks (patients). The patients had similar folate, vitamin B6, and vitamin B12, but higher homocysteine levels compared with HbAA controls (12.7 +/- 4.5 vs. 10.9 +/- 3.5 micromol/l; P = 0.04). Vitamin B6 and B12 supplementation did not change their homocysteine levels, but folate supplementation caused a 53% reduction (to 5.7 +/- 1.6). We conclude that patients with SCD have adequate vitamin B6 and B12 status, but suboptimal folate status, leading to elevated plasma homocysteine levels. They may therefore benefit from folate supplementation to reduce their high risk for endothelial damage.
Subject(s)
Anemia, Sickle Cell/blood , Folic Acid/physiology , Hemoglobin SC Disease/blood , Homocysteine/blood , Adolescent , Child , Child, Preschool , Dietary Supplements , Female , Folic Acid/administration & dosage , Humans , Infant , Male , Pyridoxine/administration & dosage , Pyridoxine/blood , Vitamin B 12/administration & dosage , Vitamin B 12/bloodABSTRACT
Vasoocclusion leads to pain, chronic organ damage, and a decreased life expectancy in patients with sickle cell disease. Therapeutic options for sickle cell disease have usually been evaluated according to their capacity for reducing the frequency of vasoocclusive crises requiring clinical attention. However, the frequency of vasoocclusive crises is not representative for the rate of accumulating organ damage in most sickle cell patients. This implies that the frequency of vasoocclusive crises needn't correlate with disease severity and, although being of importance, cannot solely serve as a parameter of treatment efficacy. Therefore, additional new objective parameters are needed to effectively study the vasoocclusive process in sickle cell disease. Several studies show that intricate adhesive interactions between (red) blood cells, plasma components, and endothelium play a crucial role in the pathophysiology of sickle cell vasoocclusion, offering new potential parameters to effectively assess disease severity as well as new therapeutical targets in the near future. Whether these adhesive mechanisms involve the causes or the effects of vasoocclusion will be determined if their inhibition, by interventive measures, results in therapeutic benefits.
