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研究生:翁履珍
研究生(外文):Lu-Chen Weng
論文名稱:血漿同半胱胺酸及其代謝相關營養素:維生素B-6、B-12、葉酸之攝食與營養生化狀況對缺血型中風發生之預測性
論文名稱(外文):The Prediction of Plasma Homocysteine and Dietary and Biochemical Status of Vitamin B-6, B-12, and Folate on the Incidence of Ischemic Stroke.
指導教授:潘文涵潘文涵引用關係
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:微生物與生化學研究所
學門:生命科學學門
學類:微生物學類
論文種類:學術論文
論文出版年:2005
畢業學年度:93
語文別:中文
論文頁數:123
中文關鍵詞:缺血型中風葉酸維生素B-6維生素B-12同半胱胺酸竹東朴子心血管疾病研究
外文關鍵詞:Ischemic StrokeFolateVitamin B-6Vitamin B-12HomocysteineCardioVascular Disease risk FACtor Two-township Study
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摘要
前言
血液中的同半胱胺酸,是目前一個備受爭議的心血管疾病危險因子,而參與同半胱胺酸代謝的營養素葉酸、維生素B-6與B-12,被認為可以經由降低同半胱胺酸濃度,達到減少心血管疾病發生的風險。然而,目前的研究結果,仍無法定義葉酸、維生素B-6與B-12在缺血型中風發生中所扮演的角色,且其與缺血型中風的關連,是否真的是經由調控同半胱胺酸濃度達成。本研究以前瞻性的研究法,探討飲食與血漿中葉酸、維生素B-6及B-12的狀況,是否對缺血型中風發生危險,具有顯著的影響力;此外,其關連性是否與血漿同半胱胺酸有關,也是本研究探討的重點。

對象與方法
以竹東朴子地區心臟血管疾病長期追蹤研究之受試者為對象,選擇在基線40歲以上沒有重大疾病的中老年人進入研究。1991-1993年間收集受試者的基本資料與飲食頻率問卷。利用世代研究方式,進行血漿葉酸、維生素B-12 (N=2126)及飲食中葉酸、B-6、B-12的攝取量 (N=1779)與缺血型中風關連性探討。血漿維生素B-6與缺血型中風的關連性則利用重疊式病例對照研究(N=416),以病例組對控制組1:2的形式,進行探討。此外,利用因素分析評估21種營養素之攝取量,探討飲食型態與缺血型中風間的關連性。

結果
飲食與血漿中的葉酸、維生素B-6及B-12與同半胱胺酸的濃度具有顯著的負相關性存在。血漿中的葉酸或B-12的濃度較低,並不會造成缺血型中風的危險性增加,但較低的血漿維生素B-6,對於缺血型中風的發生危險有顯著的提升(HR=1.58; 95%CI: 1.09-2.31)。然而,當血漿中葉酸、B-6與B-12濃度皆低時,缺血型中風的危險性大幅度增加,且在校正血漿同半胱胺酸後,達到顯著差異(HR=3.20; 95%CI:1.17-8.78)。飲食葉酸的攝取量降低,會造成缺血型中風發生的危險性增加(HR=2.44; 95%CI:1.33-4.51),但B-6與B-12的攝取量則沒有顯著關連性。而在因素分析結果中,植物性營養素因子及營養素:鎂、鉀、膳食纖維,同樣也可看到與缺血型中風發生危險間的顯著線性趨勢。其中,以植物性營養素因子對於缺血型中風的保護性最強。

結論
由竹東朴子地區心臟血管疾病長期追蹤研究結果顯示,血漿中多重營養素瀕臨缺乏對於缺血型中風的發生危險性方呈現顯著之預測性,此效應獨立於同半胱胺酸。此外,植物性營養素因子較之單一營養素對缺血型中風發生有較高之預測性,顯示多重飲食營養因子攝取量之共同效應,是極其重要的。
Abstract
Introduction
Homocysteine is a controversial risk factor of cardiovascular disease. Nutrients participating in the pathway of homocysteine metabolism, vitamin B-6, B-12, and folate, were thought to decrease cardiovascular risk via reducing homocysteine concentration. Up to now, however, it has not been confirmed whether vitamin B-6, B-12, and folate play a significant role in the development of ischemic stroke by modulating homocysteine. The aim of this study is to investigate the effects of dietary and plasma folate, B-6, and B-12 on the risk of ischemic stroke. In addition, whether or not these effects relate to plasma homocysteine is another main focus.

Subjects and methods
The study population consisted of subjects over 40 years old with data collected at the baseline of the CardioVascular Disease risk FACtor Two-township Study. Both the approaches of cohort and nested case-control studies were employed, with the utilization of the baseline data and dietary information collected in 1991 to 1993. In the cohort study design, the plasma homocysteine, vitamin B-12, and folate (N=2126), and the dietary B-6, B-12 and folate (N=1779) were prospectively studied for their relationships with the incidence of ischemic stroke. In the nested case-control design, the association between plasma B-6 (N=416) and incidence of ischemic stroke was examined with a case-to-control ratio of 1 to 2. In addition, we used factor analysis to extract dietary factors from 21 nutrients in order to evaluate the association between dietary patterns and ischemic stroke.

Results
The significant inverse correlations were found between dietary or plasma levels of folate, vitamin B-6, and B-12 and homocysteine concentration. Decreased plasma folate or vitamin B-12 concentration did not increase the risk of ischemic stroke, while decreased plasma B-6 concentration increased its risk (HR=1.58; 95%CI: 1.09-2.31). When plasma B-6, B-12, and folate were below the level of marginal deficiency, the risk of ischemic stroke elevated substantially but not significantly. The risk became statistically significant after having plasma homocysteine adjusted (HR=3.20; 95%CI:1.17-8.78). Decreased dietary folate intake was shown to increase the risk of ischemic stroke (HR=2.44; 95%CI:1.33-4.51), but such an effect was not found for dietary vitamin B-6 or B-12 intake. Other nutrients or dietary patterns correlated with folate intake also had negatively linear association with the risk of ischemic stroke. In the results of factor analysis, plant-source nutrient factor, magnesium, potassium, dietary fiber had significant dose-response associations with risk of ischemic stroke. Among them, plant-source nutrient factor had the strongest protective effect to ischemic stroke.

Conclusion
The study showed that plasma multi-nutrients marginal deficiency had significant prediction on the risk of ischemic stroke. The effect was independent of homocysteine. In addition, compared with single nutrient, plant-source nutrient factor was more predictive to the incidence of ischemic stroke. The joint effects of muti-nutrients intakes on the risk of ischemic stroke has great etiologic implications.
目 錄

致謝…………………………………………………………………………………I
中文摘要…………………………………..……………………………..………..IV
英文摘要……………………………………………………………..….…………V
目錄……………………………………….……………………………..………..VII
序言…………………………………………………………………….…………..1
第一章 文獻探討
第一節 中風……………………………………………….…………..3
第二節 同半胱胺酸及其代謝相關之葉酸、維生素B-6
及維生素B-12…………………………………….….………9
第二章 對象與方法
第一節 研究族群…………………………………….….……………22
第二節 基本問卷…………………………………….….……………22
第三節 飲食評估…………………………………….……….………22
第四節 血液生化值測量……………………………….…….………26
第五節 中風病例的確認……………………………….…….………27
第六節 可能之干擾因子……………………………….…….………28
第七節 統計及分析方法……………………………….…….………29
第三章 飲食中之維生素B-6、B-12與葉酸,及其血漿生化值之
相關性評估
第一節 材料與方法……………..………………….…….…………..32
第二節 結果……………………..………….…………….……….….33
第三節 討論……………………..………….…………….……….….35
第四章 維生素B-6、B-12與葉酸飲食攝取及營養生化狀況與
血漿同半胱胺酸濃度之關係
第一節 材料與方法……………..………………….……….…….….46
第二節 結果……………………..………….………….………….….48
第三節 討論……………………..………….………………….….….50
第五章 維生素B-6、B-12、葉酸之攝食及營養生化狀況與血漿同半胱胺酸
對缺血型中風發生之預測性
第一節 材料與方法……………...………………….…………….….59
第二節 結果………………………...……….…………………….….62
第三節 討論…………………………...…….…………………….….70
第六章 結論與建議
第一節 結論………………………………….…………………….…95
第二節 未來展望………………………………….……………….…95
參考文獻……………………………….………………………………………….97
附錄……………………………….………………………………………...……102
附錄一……………………………….………………………………………...…103
附錄二……………………………….………………………………………...…106
附錄三……………………………….………………………………………...…117
附錄四……………………………….………………………………………...…120
附錄五……………………………….…………………………………….…..…121
附錄六……………………………….…………………………………….…..…122
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