Additive Efficacy of Intravenous Vitamin B12 on Hyperhomocysteinemia in Hemodialysis Patients on Maintenance Folic Acid Therapy

維生素B12對接受葉酸治療血液透析病人的高同胱胺酸血症有加成療效

蔡哲嘉(Jer-Chia Tsai) ； 郭弘典(Hong-Tien Kuo) ； 陳玲娜(Ling-Na Chen) ； 陳鴻鈞(Hung-Chun Chen) ； 顧進裕(Jinn-Yuh Guh) ； 黃尚志(Shang-Jyh Hwang) ； 張哲銘(Jer-Ming Chang) ； 賴永勳(Yung-Hsiung Lai)

《Acta Nephrologica》 14卷4期 (2000/10) Pp. 262-262

並列摘要

Hyperhomocysteinemia is an independent risk factor for cardiovascular diseases in both general population and uremic patients. The major causes of hyperhomocysteinemia include renal failure itself, deficiencies of folic acid, vitamin B6, or vitamin B12 and genetic mutations, such as methyleneterahydrofolate reductase (MTHFR) at C677T. Folic acid was effective to lower, but not to normalie plasma homocysteine levels in most uremic patients. The purposes of this study are to evaluate the efficacy of vitamin B12 on hyperhomocysteinemia in hemodialysis (HD) patients with or without maintenance folic therapy and the impact of MTHFR genotypes on the efficacy of vitamin B12 on hyperhomocysteinemia.
We enrolled 82 HD patients with elevate plasma total homocysteine levels (Hcy＞15 μmol/L). They were divided into 3 subgroups according to different regimens. FA+ B12 treatment group included 28 HD patients (M/F: 12/16, mean age: 55.3 ±10.8 years) with hyperhomocysteinemia despite of folic acid maintenance therapy (5 mg/day). They received vitamin B12 1000 μg intravenously thrice a week after each HD for 2 months. Their plasma Hcy levels decreased significantly (26.9±8.9 μmol/L vs. 16.8±5.8μmol/L, p＜0.0001, %decrement: 35.2±23.0%). Eleven of them (39.3%) could be reduced to normal (＜15 μmol/L). B12 treatment group included 28 HD patients (M/F: 12/16, mean age: 51.6±15.0 year) without folic acid supplementation. They received vitamin B12 1000 μg intravenously thrice a week after each HD for 2 months. Their plasma Hcy levels decreased significantly (24.3±6.2 μmol/L) vs. 19.4±6.8 μmol/L,p＜0.0001,%decrement: 19.8±18.7%). Five of them (17.6%) could be reduced to normal. Control group included 26 HD patients (M/F: 12/14, mean age: 49.9±15.5years).They did not receive either folic acid or vitamin B12 treatment. Plasma Hcy levels did not change significantly (24.3±5.4 vs. 26.3±5.4 μmol/L, p=NS) after 2 months. The homocysteine-lowering effect was better in FA+B12 treatment group than in B12 treatment group (%decrement: 35.2±vs.19.8±18.7%,P＜0.01). MTHFR genotypes did not affect the efficacy of vitamin B12 on hyperhomocysteinemia. However, plasma Hcy tended to increase in controls with MTHFR mutation at C677T after 2 months (24.9±6.6 vs. 32.0±12.5 μmol/L,p=0.059).
Vitamin B12 supplementation exerts an independent homocysteine-lowering effect in HD patients. Vitamin B12 further improves hyperhomocysteinemia in HD patients who are resistant to folic acid maintenance therapy. Folic acid plus vitamin B12 supplementation exert an additive effect on hyperhomocysteinemia. It implies that vitamin B12 supplementation is helpful to improve impaired homocysteine metabolism caused by defective remethylation pathway in HD patients.