Treatment with different doses of folic acid in haemodialysis patients: effects on folate distribution and aminothiol concentrations

Background. Hyperhomocysteinaemia is highly prevalent among haemodialysis p atients and may contribute to their increased cardiovascular risk. Treatmen t with pharmacological doses of folic acid lowers the plasma homocysteine c oncentration in these patients. The purpose of the present study was to exp and the knowledge about such treatment by testing the effects of stepwise i ncreases in the dose of folic acid on the concentrations of plasma and red blood cell folate as well as the total plasma concentrations of homocystein e (tHcy), cvsteine (tCys), and glutathione (tGSH) in patients on chronic he modialysis. Methods. Fourteen stable haemodialysis patients completed the study which c onsisted of four consecutive periods, each of 6 weeks duration: (i) no trea tment with folic acid (control period); (ii) 5 mg of folic acid three times per week (15 mg/week); (iii) 5 mg of folic acid daily (35 mg/week); (iv) 1 0 mg of folic acid daily (70 mg/week). Results. Neither plasma or red cell folate nor plasma aminothiol concentrat ions changed significantly during the control period. The mean red cell fol ate concentration doubled during the administration of folic acid at the do se of 15 mg/week but at higher doses the further rise was only marginal. Th e mean folate concentration in plasma increased steeply especially at the h igher doses of folic acid. During treatment with 15 mg/week of folic acid, tHcy fell by a mean of 36%, tGSH increased by a mean of 34%, but tCys was u naffected. Increases in the dose of folic acid did not augment these respon ses. Conclusions. The maximal effect on tHcy seemed to be obtained already at th e lowest given dose of folic acid (15 mg/week). At that dose, the red blood cells approached folate saturation, which may reflect the situation in oth er cells that participate in homocysteine metabolism and explain why furthe r increases in the dose of folic acid are not effective from a tHcy-lowerin g point of view.