| 摘要: | 研究背景與目的：非酒精性脂肪肝疾病 (Non-alcoholic fatty liver disease, NAFLD) 為不過量飲酒者肝臟中脂肪大量堆積。全球盛行率為 25-30%，且日趨嚴重。疾病進展與肥胖、胰島素抗性、血脂異常、血壓異常及發炎反應有關。由於尚無臨床核准用藥，透過飲食與生活型態調整，改善 NAFLD 患者肝臟脂肪變性程度與代謝異常指標，為改善疾病的最有效途徑。咖啡是廣受歡迎的飲品，主要活性成分為咖啡因與綠原酸，具有抗氧化、抗發炎、調節脂質與葡萄糖代謝之益處，對肝臟脂肪變性程度與 NAFLD 相關代謝指標可能具有改善作用。先前統合分析多為探討綠原酸對健康人及各疾病患者之影響，或是分析咖啡攝取量與 NAFLD 盛行率之相關性，對於探討咖啡因與綠原酸對 NAFLD 患者之改善作用及有效劑量方面仍不夠全面。本研究以系統性回顧與統合分析方式，探討咖啡因與綠原酸對於 NAFLD 患者之脂肪變性程度與代謝指標的改善及影響。研究方法：以 PICOs 建立研究問題 (Participants: NAFLD patients; Intervention: coffee, caffeine, chlorogenic acid; Control: placebo; Outcomes: hepatic steatosis status, metabolic parameters; Study design: randomized controlled trials)。利用關鍵字於 PubMed、Embase、Cochrane Library、Scopus、Web of Science 中進行檢索，搜尋年份設定至 2024 年 6 月。將本研究內容於 International Prospective Register of Systematic Reviews (PROSPERO) 上登記註冊 (CRD42023481286)。萃取納入研究之資料，以 Cochrane risk of bias tool (RoB 2) 評估研究品質，以 Rstudio 4.2.3 版進行統合分析。結果：共納入 18 篇研究。結果顯示攝咖啡因與綠原酸顯著改善 NAFLD 患者的肝臟脂肪變性程度 (OR: 7.78; 95% CI: 1.04, 57.93)；血脂指標 triglycerides (TG) 顯著降低 23.91 mg/dL (95% CI: -33.89, -13.92)；血糖指標 fasting blood sugar (FBS) 顯著降低 4.23 mg/dL (95% CI：-7.46, -1.00)；血壓指標 systolic blood pressure (SBP) 顯著降低 2.47 mmHg (95% CI：-4.04, -0.90)、diastolic blood pressure (DBP) 顯著降低 1.04 mmHg (95% CI：-1.56, -0.52)。結?：對於不同疾病進展階段，涵蓋肝臟輕度至嚴重脂肪變性、NASH 及肝臟輕微纖維化之 NAFLD 患者，每日攝取單一成分的 200-500 mg 綠原酸補充劑，或含有 133 mg 綠原酸和 133 mg 咖啡因之雙成分補充劑，或是以混合物形式如苦橙花萃取物、薑黃萃取物、佛手柑萃取物、小檗、油棕萃取物、L-甲硫胺酸、L-谷胱甘?等混合含有 30-50 mg 綠原酸之補充劑，持續介入八週以上，能夠改善肝臟脂肪變性程度，並且顯著降低血清血脂指標 TG、血糖指標 FBS 及血壓指標 SBP 與 DBP 數值。顯示攝取咖啡因與綠原酸之補充劑能夠改善 NAFLD 患者的疾病進展與代謝指標。
Background & Objectives: Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide. It is closely associated with risk factors such as obesity, insulin resistance, dyslipidemia, hypertension, and inflammation. Improving hepatic steatosis status and metabolic abnormality parameters may be the most effective way to ameliorate the disease. Coffee containing caffeine and chlorogenic acid (CGA) has been shown to benefit NAFLD due to its antioxidant and anti-inflammatory abilities. Previous studies have only investigated the relationship between coffee and NAFLD, but the effective dosage of caffeine and CGA for improving NAFLD patients are still unclear. We conducted a comprehensive meta-analysis to evaluate the effectiveness of caffeine and CGA in alleviating hepatic steatosis status and NAFLD-related metabolic parameters, and to determine the effective dosage of the intervention. Methods: The PubMed, EMBASE, Cochrane Library, Scopus, and Web of Science were systematically searched from inception dates to June 2024. Included randomized controlled trials (RCTs) that treated NAFLD patients with caffeine or CGA. The meta-analysis was conducted using random effects models, analyzed the outcomes using mean difference (MD) and assessed study heterogeneity using Cochran's Q test and I2 statistics. Results: A total of 18 studies were included in the meta-analysis. Pooled effect sizes demonstrated that the intervention had significantly improved hepatic steatosis status (OR: 7.78; 95% CI: 1.04, 57.93), serum triglycerides (TG) (MD: -23.91 mg/dL; 95% CI: -33.89, -13.92), serum fasting blood sugar (FBS) (MD: -4.23 mg/dL; 95% CI: -7.46, -1.00), systolic blood pressure (SBP) (MD: -2.47 mmHg; 95% CI: -4.04, -0.90), diastolic blood pressure (DBP) (MD: -1.04 mmHg; 95% CI：-1.56, -0.52). Conclusions: For NAFLD patients at different stages of disease progression, covering mild to severe hepatic steatosis, NASH, and mild liver fibrosis, daily intake of supplements containing a single component of 200-500 mg CGA, or a supplement with 133 mg CGA and 133 mg caffeine, or in the form of a mixture such as C. aurantium flower extract, turmeric extract, bergamot extract, berberis extract, elaeis guineensis extract, L-methionine, L-glutathione, and mixed with 30-50 mg of CGA, for at least eight weeks, can improve hepatic steatosis and significantly reduce serum TG, FBS levels, SBP and DBP. This demonstrates that the intake of supplements containing caffeine and CGA can improve disease progression and metabolic parameters in NAFLD patients. |
