Journal Article

Hyperhomocysteinaemia, folate and vitamin B12 in unsupplemented haemodialysis patients: effect of oral therapy with folic acid and vitamin B12

Stéphane Billion, Bruno Tribout, Estelle Cadet, Colette Queinnec, Jacques Rochette, Pascal Wheatley and Pierre Bataille

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 17, issue 3, pages 455-461
Published in print March 2002 | ISSN: 0931-0509
Published online March 2002 | e-ISSN: 1460-2385 | DOI:
Hyperhomocysteinaemia, folate and vitamin B12 in unsupplemented haemodialysis patients: effect of oral therapy with folic acid and vitamin B12

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Background. Hyperhomocysteinaemia, a risk factor for atherosclerosis, is common in dialysis patients and particularly in those homozygous for a common polymorphism in the 5,10‐methylenetetrahydrofolate reductase (MTHFR) gene (C677T transition). B‐complex vitamin supplements have been shown to lower plasma total homocysteine (tHcy) concentrations, but the respective effectiveness of folate and oral vitamin B12 is not yet known. Our objectives were: (i) to determine the status of folate and vitamin B12 in a cohort of unsupplemented dialysis patients (ii) to assess the homocysteine‐lowering effect of a folate supplement and then of a folate supplement with added vitamin B12. The responses were analysed for the C677T genotypes of MTHFR.

Methods. Plasma tHcy, folate and vitamin B12 were measured in 51 haemodialysis patients genotyped for the C677T MTHFR mutation (homozygotes, TT; heterozygotes, CT; without mutation, CC). All patients were then given daily supplements of 15 mg of folic acid for 2 months. They were given daily supplements of 1 mg of vitamin B12 in addition to the folate supplements for a further 2 months. Plasma tHcy, folate and vitamin B12 were monitored after each intervention.

Results. At baseline folate and vitamin B12 deficiencies were found in 10% and 6% of the patients. Initial plasma tHcy concentrations were high in all patients (mean 38.1±15 μmol/l). CC patients tended to have a lower tHcy concentration than pooled CT and TT patients. After 2 months of folate therapy, tHcy concentration decreased significantly to 20.2±7 μmol/l (P<0.001) and no significant differences were observed between the different genotype subgroups (19.4±6 for CC, 21.3±8 for CT, 18.5±4 for TT). A significant positive relationship was found between the reduction of tHcy and its initial value (ρ=0.615, P<0.0001). The impact of the added vitamin B12 was negligible since tHcy concentrations did not change for the patients as a whole (19.8±7 μmol/l, NS) or in any subgroup (19.1±5 for CC, 20.3±9 for CT and 20±7 μmol/l for TT).

Conclusions. (i) Folate and vitamin B12 deficiencies were observed in 10% and 6% respectively of our unsupplemented dialysis patients. (ii) After folate therapy, tHcy levels decreased significantly in all patients and were identical between the three C677T MTHFR genotype subgroups. (iii) Vitamin B12 supplements are useful in folate treated patients to prevent cobalamin deficiency and its neurological consequences but they did not lower tHcy plasma levels for the patients as a group or for any of the MTHFR subgroups.

Keywords: dialysis; folate; homocysteine; MTHFR genotypes; vitamin B12

Journal Article.  4666 words.  Illustrated.

Subjects: Nephrology

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