Aktuelle Ernährungsmedizin 2010; 35 - V7
DOI: 10.1055/s-0030-1254558

B-Vitamins and the risk for total mortality and cardiovascular disease in end-stage renal disease. A randomized controlled trial

J Dierkes 1, 2, J Heinz 2, 3, S Kropf 4, S Westphal 2, C Luley 2, U Domröse 5, KH Neumann 5
  • 1Institut für Agrar- und Ernährungswissenschaften, Halle (Saale), Germany
  • 2Institut für Klinische Chemie und Pathobiochemie, Med. Fakultät der Universität Magdeburg, Magdeburg, Germany
  • 3Institut für Med. Biometrie und Epidemiologie, Universitätskrankenhaus Hamburg-Eppendorf, hamburg, Germany
  • 4Institut für Biometrie und Med. Informatik, Med. Fakultät der. Universität Magdeburg, Magdeburg, Germany
  • 5Klinik für Nephrologie, Universitätsklinik Magdeburg, Magdeburg, Germany

Introduction: Observational studies have indicated a causal relationship between elevated plasma homocysteine concentrations and cardiovascular disease in patients with end-stage renal disease. Elevated homocysteine levels are very common in these patients and can be reduced by folic acid and vitamin B12. The objective of this trial was to determine whether treatment with high dose B vitamins reduces the risk for mortality and cardiovascular disease in patients treated with hemodialysis.

Methods: A total of 650 patients from 33 dialysis centres in Germany were included in this randomized, double-blinded, controlled study. Participants received either active treatment, which was a high dose vitamin preparation (2.5mg folic acid; 25µg vitamin B12 und 10mg vitamin B6) or placebo, which was a low dose vitamin preparation (0.1mg folic acid; 2µg vitamin B12 and 0.5mg vitamin B6) in order to prevent vitamin deficiencies. Time of follow up was between 2 and 6 years. The primary endpoint was total mortality. The secondary endpoint included fatal and nonfatal cardiovascular events (myocardial infarction, coronary vascularisation, unstable angina pectoris, sudden cardiac death, stroke, peripheral artery disease, pulmonary embolism, and thromboses).

Results: At baseline, 94% of the patients (271 female and 379 male with a mean age of 61±13 years) had homocysteine blood concentrations higher than 15µmol/L. Homocysteine was significantly lowered by the vitamin treatment (–10.4µmol/L), and remained unchanged in the control group (–1.8 mmol/L).

During follow up, 194 patients died, 102 (31%) in the active treatment group and 92 (28%) in the placebo group. Active treatment had no effect on total mortality (HR 1.13 [95% CI; 0.85–1.50]; p=0.51). The secondary outcome, a combination of fatal and nonfatal cardiovascular events occurred in 83 patients (25%) of the active treatment group and in 98 patients (30%) of the placebo group. The difference in the cardiovascular event rates between the treatment groups was not significant (HR 0.80 [95% CI; 0.60–1.07]; p=0.13).

Conclusion: Treatment with high dose B-vitamins did not improve survival or reduce the risk of cardiovascular events in patients with end-stage renal disease treated with hemodialysis.