Effect of High Dose Folic Acid Therapy on Hyperhomocysteinemia in Hemodialysis Patients

Abstract

Abstract. 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 patients. In a randomized, double-blind, multicenter study, 144 patients completed 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 between the three treatment groups. Baseline total homocysteine plasma concentration was an independent predictor of the response to folic acid therapy (P= 0.0001), whereas the 5,10-methylenetetrahydrofolate reductase polymorphisms (MTHFR677C → T and 1298A → C) had no influence. Nevertheless, patients with theMTHFR677TT genotype more frequently attained normal total homocysteine 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). After 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 theMTHFR677TT 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 not more effective than 15 mg/d in reducing hyperhomocysteinemia in regular hemodialysis patients. Patients with theMTHFR677TT genotype are more likely to realize normal total homocysteine plasma levels. Folic acid at 30 or 60 mg/d but not 15 mg/d results in a rebound of total homocysteine plasma concentrations when treatment is stopped.

Food-Derived Uremic Toxins in Chronic Kidney Disease

“…Studies have also been performed to assess the effect of the supplementation of vitamin B6, B12, and folates on homocysteine levels in CKD patients. A study in hemodialysis patients found no improvement in homocysteine levels after a 4-week supplementation of different dosages of folic acid [ 161 ]. Similarly, Wrone et al noted no benefit of folates on cardiovascular event incidence in end-stage renal disease patients [ 162 ].…”

Homocysteine exchange across skeletal muscle in patients with chronic kidney disease

“…However, since Hcy muscle inflow is high (Fiona et al, 2009), a defective Hcy transport in muscle in uremia cannot be ruled out from our study. In most normal subjects, a folate dose of 400 to 600 μg produces a prompt fall of 20% to 30% in total plasma Hcy concentrations; in contrast, patients with ESRD are more resistant to this Hcy-lowering action of folic acid and even the use of pharmacological doses of folic acid or reduced folates does not normalize completely circulating Hcy levels (Ducloux et al, 2002;Massy, 2003;Sunder-Plassmann et al, 2000). More commonly occurring vitamin deficiencies in maintenance dialysis patients include those for vitamin C, folate and pyridoxine .…”

A Hypertrophic Spinal Pachymeningitis Patient With Factor V Leiden (G1691A), MTHFR C677T, MTHFR A1298C, PAI-1 4G-5G, Glycoprotein IIIa L33P Gene Mutations

“…It has been shown that the C677T homozygous polymorphism (TT) of the MTHFR enzyme slows down the enzyme activity, thus the activity of the remethylation cycle, and is associated with significantly higher homocysteine levels [ 8 ]. It has been shown that the A1298C polymorphism of the MTHFR enzyme also affects total homocysteine concentrations and is a risk factor for neural tube defects [ 9 ].…”