葉酸及維生素B-12較維生素B-6對於降低冠狀動脈心臟病病人血漿同半胱胺酸濃度有顯著的效果

中文摘要 高同半胱胺酸血症已被證實為心血管疾病的獨立危險因子。在同半胱胺酸的代謝過程中，以維生素B-6、維生素B-12及葉酸的營養狀況最受到重視，並引起廣泛的討論與研究。目前許多研究已指出補充維生素B-12或葉酸有助於降低血漿同半胱胺酸的濃度，但維生素B-6與血漿同半胱胺酸濃度的相關性卻未獲得證實。本研究目的為探討給予冠狀動脈心臟病的病人，不同劑量的維生素B-6補充劑的介入是否能降低血漿同半胱胺酸濃度。本實驗的冠狀動脈心臟病病人為經心導管檢查結果至少有一條冠狀動脈狹窄程度大於70 %者，且必須為目前沒有服用任何B-維生素的補充劑。研究期間共篩選了50位患者，平均年齡為71.6 ± 9.7歲。以隨機的方式分為五組。最後完成本研究的人數分別為 (1) placebo (n=8)，(2) 維生素B-6, 5 mg/day (n=8)，(3)維生素B-6, 10 mg/day (n=8)，(4) 維生素B-6, 50 mg/day (n=9)，(5) 維生素B-12, 0.25 mg/day及葉酸, 5 mg/day (n=9)，共介入12週。受試者於第0週、第4週及第12週測量體位、血液生化值、血漿同半胱胺酸、磷酸比哆醛（PLP）、紅血球丙胺酸及天門冬胺酸轉胺酶活性係數（EAST-AC 及EALT-AC）、血清葉酸及維生素B-12濃度。另外，在第0週及第12週以二十四小時回憶法紀錄受試者營養素攝取量。研究結果顯示各組年齡、體位測量及在第0週與第12週的血液生化值檢驗和營養素攝取量方面，並無顯著的差異。在血漿同半胱胺酸濃度方面，無論是第4週或第12週，任一劑量維生素B-6補充劑的介入，對降低血漿同半胱胺酸的濃度並無作用（p>0.05）。值得注意的是，補充placebo、維生素B-6 10 mg/day及維生素B-6 50 mg/day的組別，雖未達統計上的差異，但其12週後的血漿同半胱胺酸濃度有增加25.5%、16.2%、18.3%的傾向。相反的，維生素B-12及葉酸補充劑的介入，可顯著地降低血漿同半胱胺酸的濃度約30.1%（p=0.002）。本研究結果顯示單獨使用維生素B-6補充劑的介入，對於降低冠狀動脈心臟病的病人的血漿同半胱胺酸濃度的效果顯著低於葉酸及維生素B-12的補充。 關鍵詞：維生素B-6、葉酸、維生素B-12、同半胱胺酸、補充劑、 冠狀動脈心臟病

Abstract Studies have shown that hyperhomocysteinemia is an independent risk factor for coronary artery disease (CAD). Many factors are associated with elevated homocysteine concentration; of particular interest are nutritional deficiencies in the vitamin cofactors that are required for homocysteine metabolism; namely folic acid, vitamin B-12 and vitamin B-6. Several studies have shown that vitamin B-12 and folic acid intake and/or biochemical status have a strong negative correlation with plasma homocysteine concentration. However, the correlation between vitamin B-6 and plasma homocysteine concentration remains uncertain. The purpose of this study was to investigate whether various doses of vitamin B-6 supplementation would have beneficial effects on lowering fasting plasma homocysteine concentrations in CAD patients. Subjects were identified by cardiac catheterization to have at least 70% stenosis of one major coronary artery. Subjects currently taking B-vitamin supplement were excluded. Fifty patients with the mean age of 71.6 ± 9.7 y enrolled after informed consent was obtained. A total of 42 CAD patients successfully completed the intervention study. Patients were randomly assigned to 1 of 5 groups and treated with a daily dose of placebo (n=8), 5 mg vitamin B-6 (n=8), 10 mg vitamin B-6 (n=8), 50 mg vitamin B-6 (n=9), or 5 mg folic acid combined with 0.25 mg vitamin B-12 (n=9) for 12 weeks. Hematological measurements, plasma homocysteine, pyridoxal-5''-phosphate (PLP), erythrocyte aspartate and alanine transaminase activity cofficients (EAST-AC and EALT-AC), serum folic acid and vitamin B-12 concentrations were measured at baseline (week 0), week 4 and week 12. Patients completed 24-h diet recalls when they returned to the cardiology clinic before the intervention (week 0) and at week 12. Result shows that there were no significant differences among groups with respect to age, anthropometric measurements, dietary intake and hematological measurements. Fasting plasma homocysteine concentration did not respond to high or low doses of vitamin B-6 compared with a placebo treatment after 12 weeks of supplementation (p>0.05). Further, within group, mean fasting plasma homocysteine concentration were no significantly increased by 25.5%, 16.2% and 18.3% in placebo, 10 mg/day and 50 mg/day vitamin B-6 suppltmented groups, respectively; whereas folic acid combined with vitamin B-12 supplementation significantly decreased plasma homocysteine concentration by 30.1% (p=0.002). Our results indicate that vitamin B-6 supplementation alone is less effective than folic acid combined with vitamin B-12 on lowering plasma homocysteine concentration in CAD patients. Key words : vitamin B-6, folic acid, vitamin B-12, homocysteine, supplementation, coronary artery disease.