2026-11-092026-11-09https://scholars.csmu.edu.tw/handle/123456789/38644Colorectal cancer is now the third leading cause of cancer mortality among men and women in Taiwan. Colorectal adenomas are considered precursors of colorectal cancer, prevention of colorectal adenomas may decrease the occurrence of colorectal cancer. Vitamin B6 and folate may play a critical role in the colorectal polyps progression. The specific aims of this proposal are: 1) to compare folate and vitamin B6 status (dietary intakes and biochemical indicators) between colorectal hyperplastic polyps adenomatous polyps; 2) to compare the prevalence the methylenetetrahydrofolate reductase 677C→T genetic polymorphism between colorectal hyperplastic polyps adenomatous polyps; 3) to compare and evaluate folate and vitamin B6 status in relation to oxidative stress, antioxidant activities and DNAmethylation; 4) to compare folate and vitamin B6 status (dietary intakes and biochemical indicators) between colorectal polyps subjects and age-, sex-matched healthy subjects; 5) to evaluate the effect of vitamin B6 and folate status on the risk of colorectal polyps; 6) to evaluate whether folic acid and/or pyridoxine supplementation had a beneficial effect on reducing oxidative stress, increasing antioxidant function and DNAmethylation in patients with colorectal adenomas. This protocol is designed as a hospital-based cross-sectional, case-control and double-blinded randomized placebo-controlled intervention trial. One hundred and fifty colorectal adenomatous polyps subjects, 150 colorectal hyperplastic polyps and 150 age-, sex-matched controls who meet the inclusion criteria will be recruited from the Chung Shan Medical University Hospital. If colorectal adenomatous polyps subjects’ plasma PLP level under the 50th percentile will be asked to participate the intervention study. Sixty subjects will be blinded and randomly assigned to either the 1) placebo; 2) 100 mg vitamin B6; 3) 5 mg folic acid folate group; or 4) vitamin B6 (100 mg/d) plus folate (5 mg/d) for 16 weeks. Data on demography, anthropometry, medical history, food frequency questionnaire and 24-h diet recall will be collected. Subjects in the case-control study will have fasting blood drawn. Fasting blood samples of the intervention study at week 0, 4, 8 and week 16 will be drawn to measure hematological and biochemical measurements [plasma and erythrocyte pyridoxal 5’phosphate, plasma pyridoxal and 4-pyridoxic acid, serum and erythrocyte folate, serum vitamin B12, homocysteine, SAM, SAH, oxidative stress, antioxidant enzymatic activities, TBARS and oxidized low density lipoprotein] levels and MTHFR 677C®T polymorphism. DNA will be extracted for the genotype determination and methylation assay. Tissue samples will be analyzed for folate and vitamin B6 concentrations and DNAmethylation. Hopefully, the results of this study could provide more information to what has been known in colorectal polyps subjects; and let physicians, nurses or dietetics consider using vitamin B6 and/or folate supplementation to prevent the colorectal adenomas recurrence and further cut down the medical expenses.大腸直腸癌目前已為台灣十大癌症死亡的第三名。腺瘤性息肉已被認為是發生大腸 直腸癌的前身。葉酸與維生素B6 被認為在大腸直腸息肉形成中扮演重要角色。本計劃 的主要目的為：1) 觀察及比較大腸直腸增殖性息肉及腺瘤性息肉受試者的維生素B6 及 葉酸的營養狀況、氧化壓力程度、抗氧化酵素活性及DNA 甲基化程度的差異性；2) 觀 察及比較大腸直腸增殖性息肉及腺瘤性息肉受試者的甲基四氫葉酸還原酶677C→T基 因多型的分布狀況；3) 探討維生素B6 及葉酸的營養狀況與大腸直腸息肉受試者的氧化 壓力程度、抗氧化酵素活性及DNA 甲基化程度的關係；4) 觀察及比較大腸直腸腺瘤性 息肉受試者與年齡、性別配對後的健康受試者的維生素B6 及葉酸的營養狀況、氧化壓 力程度、抗氧化酵素活性及DNA 甲基化程度的差異性；5) 探討維生素B6 及葉酸的營 養狀況與罹患大腸直腸息肉的危險對比值；6) 評估及比較給予大腸直腸腺瘤性息肉受 試者維生素B6 及葉酸單獨補充或合併補充後對養化壓力程度、抗氧化功能及DNA 甲基 化程度的差異及影響。 本研究設計方法是以醫院為基礎的橫斷面、病例-對照及隨機雙盲的補充劑介入試 驗。本研究將於中山醫學大學附設醫院肝膽胃腸科募集150 位大腸直腸息肉受試者與體 檢科募集150 位年齡、性別配對後的健康受試者。若參加此研究的腺瘤性息肉受試者的 血漿PLP 濃度經分析後位於全部腺瘤性息肉受試者的50 百分位以下，將詢問是否參加 介入研究。介入研究將於受試者接受息肉切除後且經臨床醫師評估同意後進行。介入研 究60 位受試者將被隨機分成以下四組，以雙盲試驗進行16 週：1) 安慰劑；2) 100 mg 維 生素B6；3) 5 mg 葉酸及4)維生素B6 (100 mg/d) 合併葉酸(5 mg/d)。所有受試者的體 位測量紀錄，藥物疾病史，飲食頻率問卷及24 小時飲食回憶問卷將被收集。大腸直腸 息肉受試者的血液採集將於接受息肉切除前採集，健康受試者的組織取樣及血液採集將 於進行體檢時進行。參加介入研究的受試者的空腹血液採集將於第0、4、8、16 週進行， 血液樣本將進行臨床血液生化值(紅血球、血紅素、白蛋白、肌酸酐、鹼性磷酸酶和高 敏感度C-反應蛋白) 及生化檢驗值(血漿與紅血球磷酸比哆醛、血漿比哆醛、血清與紅 血球葉酸、血清維生素B12、同半胱胺酸、半胱胺酸、腺核苷甲硫酸及腺核苷同半胱胺 酸)的分析，萃取DNA 分析甲基四氫葉酸還原酶677CC®T 基因型及DNA 甲基化作用， 及測定氧化壓力程度、脂質過氧化及抗氧化酵素活性。另外大腸直腸息肉組織樣本將進 行磷酸比哆醛及葉酸濃度及甲基化作用的測定。 本研究以大腸直腸息肉為研究模式，透過給予患者單獨或合併維生素B6 及葉酸補 充劑觀察是否能降低氧化壓力程度、增加抗氧化功能及改善DNA 甲基化作用來釐清相 關問題。進行完這一系列的研究將可以提供更多有關大腸直腸息肉的資訊，而使醫師、 護士及營養師在大腸直腸息肉病人的治療及照護上可利用給予維生素B6 或葉酸的補充 劑達到預防息肉再發，進而減少醫療費用的支出。大腸直腸息肉維生素B6葉酸基因多型性抗氧化活性甲基化colorectal polypsvitamin B6folategenetic polymorphismantioxidant activitiesmethylationProject