腎臓学と治療学ジャーナル

Biotin Deficiency as a Target for Treating Restless Legs Syndrome in Chronic Dialysis Patients

Abstract

Heidi Moretti*,Nell Matthews,John David Anthony Lakatua,Tammy Keeling-Hathaway,Donald M Mock

Restless Legs Syndrome is a neuropathic disorder seen in end stage renal disease. Since biotin is dialyzable, we examined the relationship between biotin status and Restless Legs Syndrome in end stage renal disease (Study 1) and determined the effect of biotin supplementation on Restless Legs Syndrome symptoms (Study 2). Comparison of prevalence of biotin deficiency in those with and without Restless Legs Syndrome (Study 1) and randomized assignment, double-blinded, placebo-controlled study of biotin supplementation (Study 2) were in a medical center’s outpatient dialysis unit. In Study 1, patients received chronic dialysis and routine biotin supplementation at ≈300 μg daily (10 times the recommended dietary allowance). In the intervention Study 2, biotin was supplemented at 10,000 μg daily for 8 weeks; the placebo group received ≈300 μg of biotin daily. Outcome was measured by Restless Legs Syndrome symptom score and biotin status as indicated by activation coefficient of the biotin-dependent enzyme propionyl-CoA carboxylase in peripheral blood lymphocytes. In Study 1, patients with (n=30) were more likely than those without (n=19) Restless Legs Syndrome to be biotin deficient as judged by increased activation coefficient of propionyl-CoA carboxylase; mean (± 1SD) was 1.17 ± 0.65 vs. 0.87 ± 0.39, respectively (P=0.007). In Study 2, Restless Legs Syndrome score of the biotin group (n=16), improved from 20 ± 6 to 13 ± 11 (P=0.001). However, in the placebo group (n=15), Restless Legs Syndrome score also improved from 17 ± 8 to 12 ± 10 (P=0.01). Consequently, this change was not different between biotin and placebo. Mean activation coefficient of propionyl-CoA carboxylase of the biotin group (n=8) improved from 1.38 ± 0.76 to 0.81 ± 0.25 (P=0.01) and did not change in the placebo group (0.98 ± 0.44 vs. 1.17 ± 0.32; P=0.17). The improvement of biotin status and of Restless Legs Syndrome score with the 10,000 μg supplement suggests that large biotin supplements might be necessary to optimize biotin status in dialysis patients.