Patrizia Colucci

Folate Supplementation in Peritoneal Dialysis Patients with Normal Erythrocyte Folate: Effect on Plasma Homocysteine

The possible role of folate supplementation in reducing hyperhomocysteinemia in dialysis patients has been reported in several recent papers. However, scant data are available for peritoneal dialysis patients; besides, none of these studies investigated either the role of intraerythrocyte folate concentration or the presence of side effects caused by folate administration. Sixty-six peritoneal dialysis patients with hyperhomocysteinemia (>15 µmol/l) and normal folate status (as assessed by erythrocyte folate level >600 nmol/l) were randomly allocated to receive either oral folate (5 mg/day) or no vitamin supplementation. After 2 months of therapy, patients were requested to answer a questionnaire investigating the occurrence of symptoms possibly related to folate supplementation. Twenty-nine treated patients and 30 untreated controls completed the study. In the treated patients, serum and erythrocyte folate increased significantly (p < 0.0001) (respectively from 10.6 ± 4.9 to 237 ± 231 nmol/l and from 1,201 ± 297 to 2,881 ± 294 nmol/l) to levels at the uppermost limit of detection by laboratory methods. Serum vitamin B12 levels did not change. Plasma homocysteine levels decreased from 54 ± 32 to 23 ± 14 µmol/l after folate supplementation and remained unchanged in the control group. After 4 months of folate therapy, homocysteine concentration was within the normal range in 5 patients (17%) and below 30 µmol/l in the other 21 (72%). Folate therapy resulted in a decrease in homocysteine of more than 50% in 45% of the patients and decrease of more than 20% in a further 38%. No significant symptoms were reported. Thus, serum and erythrocyte folate increase confirms that normal folate levels are inadequate in dialysis patients, even if serum and erythrocyte levels before folate supplementation cannot predict the effect on homocysteine plasma levels.

Effect of incremental doses of folate on homocysteine and metabolically related vitamin concentrations in nondiabetic patients on peritoneal dialysis

The role of folate supplementation in reducing hyperhomocystinemia in patients on dialysis has been reported, but the optimal dose of folate is still unknown. The aim of the present study was to investigate whether greater than 5 mg/day folate supplementation provides any additional effect on plasma homocysteine (HCY) levels. The study was prospective, open, and had no control group. Of the 64 eligible nondiabetic patients on peritoneal dialysis with hyperhomocystinemia (>20 &mgr;mol/L), 56 were given oral folate (5 mg/day) for 3 months. When Hcy did not fall below 20 &mgr;mol/L, folate doses were increased by 5 mg every 3 months to up to 15 mg/day. With 5 mg/day supplementation, serum folate concentrations increased above the upper confidence limit in 23 patients and erythrocyte folate concentrations in 27 patients. Hcy levels decreased to less than 15 &mgr;mol/L in 6 cases and by more than 50% in 12 cases. Nineteen of the remaining patients were given 10 mg/day folate. After increasing the dose, serum and erythrocyte folate levels rose above the upper detection limit. In one patient, plasma Hcy concentrations decreased to less than 15 &mgr;mol/L. Ten patients were given 15 mg/day oral folate for an additional 3 months with no effect on homocystinemia. This study confirms that oral folate supplementation may improve hyperhomocystinemia even in patients on dialysis with normal serum or erythrocyte folate concentrations. In fact, serum and erythrocyte levels cannot predict the effect of supplementation on plasma Hcy levels. However, 5 mg/day folate supplementation normalized Hcy in 10% of cases and reduced Hcy levels in another 21%. Increasing the folate dose to greater than 5 mg/day had a minimal (10 mg/day) or no (15 mg/day) additional effect on Hcy concentrations. Despite the minimal effect of increasing folate doses, given the low cost, the absence of side effects, and the high cardiovascular risk for patients on peritoneal dialysis, a careful attempt to increase the dose of oral folate up to 10 mg/day might be suggested.