G. Sunder-plassmann et al., Effect of high dose folic acid therapy on hyperhomocysteinemia in hemodialysis patients: Results of the Vienna multicenter study, J AM S NEPH, 11(6), 2000, pp. 1106-1116
Homocysteine is associated with atherosclerosis and enhanced cardiovascular
risk. In previous studies, treatment with folic acid up to 15 mg/d failed
to correct hyperhomocysteinemia in the majority of end-stage renal disease
patients. A dose of 30 or 60 mg of folic acid per day was compared with 15
mg/d in an attempt to normalize hyperhomocysteinemia in 150 hemodialysis pa
tients. In a randomized, double-blind, multicenter study, 144 patients comp
leted the 4-wk treatment period and 121 patients completed the 6-mo follow-
up. Total homocysteine plasma levels were reduced by 32.1% (15 mg/d), 29.9%
(30 mg/d), or 37.8% (60 mg/d) with no significant differences found betwee
n the three treatment groups. Baseline total homocysteine plasma concentrat
ion was an independent predictor of the response to folic acid therapy (P =
0.0001). whereas the 5,10-methylenetetrahydrofolate reductase polymorphism
s (MTHFR 677C -->T and 1298A --> C) had no influence. Nevertheless, patient
s with the MTHFR 677TT genotype more frequently attained normal total homoc
ysteine plasma levels than patients with the CC or CT genotype (P = 0.025).
In response to 60 mg of folic acid per day, TT genotype patients had lower
folate plasma levels compared to CC or CT genotype patients (P = 0.016). A
fter completion of the 4-wk treatment period with 30 or 60 mg of folic acid
per day, there was a marked rebound of total homocysteine plasma levels at
the end of the follow-up in patients with the MTHFR 677TT genotype, which
even exceeded baseline values in several patients (P = 0.0001). This study
clearly demonstrates that doses of 30 or 60 mg of folic acid per day are no
t more effective than 15 mg/d in reducing hyperhomocysteinemia in regular h
emodialysis patients. Patients with the MTHFR 677TT genotype are more likel
y to realize normal total homocysteine plasma levels. Folic acid at 30 or 6
0 mg/d but not 15 mg/d results in a rebound of total homocysteine plasma co
ncentrations when treatment is stopped.