臺灣博碩士論文加值系統

EPA (eicosapentaenoic acid) 和 DHA (docosahexaenoic acid) 屬ω−3脂肪酸，俗稱「魚油」，是頗受歡迎的保健食品。近年來國際間有多種藥品級魚油產品問市（prescription omega-3 fatty acid products, RxOME3FAs），分為兩大類：「EPA/DHA複方」及「EPA單方」。一般認為藥品級魚油十分安全，但其實目前尚缺乏關於安全性與耐受性的系統性科學驗證。本研究為系統性回顧（systematic review）加上統合分析（meta-analysis），包括以下步驟：搜尋六大醫學電子資料庫，找出所有採用RxOM3FAs的隨機對照臨床試驗（randomized controlled trials, RCTs）；篩選合適文獻，並做文獻品質評讀；抽取文獻中的副作用相關數據（資料不足者須與文獻的原作者聯繫）；執行統合分析、次群組分析(subgroup analysis)、統合回歸分析(meta-regression)。研究結果：總共有21篇RCTs被納入分析（共包括 24,460 位受試者），其中並沒有與RxOM3FAs直接相關的「嚴重副作用」報告。在「非嚴重副作用」方面，統合分析顯示RxOME3FAs治療組與對照組相比，在以下副作用項目，有達到統計顯著性差異：味覺改變(dysgeusia)、皮膚症狀(eruption, itching, exanthema, or eczema)、某些抽血檢驗值微幅惡化。次群組分析顯示「EPA/DHA複方」產品會引起較多腸胃道副作用，以及低密度脂蛋白膽固醇(LDL-C) 升高。 本研究顯示藥品級魚油十分安全，耐受性佳，但並非沒有副作用。至於藥品級魚油其他可能的長期或是罕見副作用，則仍需參考上市後監測調查(post-marketing surveillance)及更多觀察性研究來確認。

Omega-3 fatty acids [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] are widely recommended for health promotion. Over the last decade, the prescription omega-3 fatty acid products (RxOME3FAs) have been approved for medical indications and there are two subgroups of preparations available in the worldwide market (EPA/DHA combination and EPA-only products). RxOME3FAs appear to have favorable safety and tolerability profiles. However, there is no comprehensive analysis from any systematic investigation so far. A systematic review of randomized controlled trials (RCTs) was carried out based on searches in six electronic databases. The studies involving marketed RxOME3FAs were included, and adverse-effect data were extracted for meta-analysis. Subgroup analysis and meta-regression were conducted to explore the sources of potential heterogeneity. Among the 21 included RCTs (total 24,460 participants), there was no definite evidence of any RxOME3FA-emerging serious adverse event. Compared with the control group, RxOME3FAs were associated with more treatment-related dysgeusia (p= 0.011) and skin abnormalities (eruption, itching, exanthema, or eczema; p < 0.001). Besides, RxOME3FAs had mild adverse effects upon some non-lipid laboratory measurements [fasting blood sugar (p = 0.005); alanine transaminase (p = 0.022); blood urea nitrogen (p = 0.047); hemoglobin (p = 0.002); hematocrit (p = 0.009)]. Subgroup analysis revealed that EPA/DHA combinations were associated with more treatment-related gastrointestinal adverse events [eructation (p = 0.010); nausea (p = 0.044)] and low-density lipoprotein cholesterol elevation (p = 0.009). We concluded that RxOME3FAs are generally safe and well tolerated but not free of adverse effects. Post-marketing surveillance and observational studies are still necessary to identify long-term adverse effects and to confirm the safety and tolerability profiles of RxOME3FAs.

中文摘要 I
Abstract III
謝誌 V
目錄 VI
圖目錄 VIII
表目錄 IX
壹、研究之中文簡介 1
貳、論文本文 4
1. Introduction 4
2. Methods 8
2.1 Protocol 8
2.2 Literature search and screening 8
2.3 Study selection and quality appraisal 9
2.4 Data extraction and correspondence with the authors 9
2.5 Methods of meta-analysis 10
2.6 Heterogeneity, publication bias, and sensitivity test 11
2.7 Meta-regression and subgroup analysis 11
3. Results 12
3.1 Systematic review and the selection process 12
3.2 Description and quality assessment of the included studies 15
3.3 Methodological quality of the included studies 16
3.4 Review of the SAEs 16
3.5 Main results of the meta-analysis of the prevalence rates of AEs 16
3.6 Main results on laboratory adverse effects on lipid profiles 21
3.7 Main results on laboratory adverse effects on non-lipid profiles 26
4. Discussion 28
4.1 Treatment-related AEs 28
4.2 Treatment-related adverse effects on lipid profiles 34
4.3 Treatment-related adverse effects on non-lipid profiles 37
4.4 Limitations 37
5. Conclusion 39
6. References 40
參、附件 54
附件1.MBI國際研討會「研究海報」 54
附件2.MBI國際研討會「最佳海報獎」 55
附件3.SCI論文封面 56
肆、作者簡介 57 

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