Animal study and clinical efficacy of fish oil (eicosapentaenoic acid) on dissolution of cholesterol gallstones.

药物（口服胆汁酸）治疗胆石症需要很长时间，而且往往无效。因此，期望开发更有效的药物治疗。我们以前发现，二十碳五烯酸（EPA），鱼油的主要成分，对胆固醇结石的形成发挥抑制作用。在本研究中，我们的目的是澄清实验和临床是否EPA可以溶解胆固醇结石。我们首先检查了EPA在胆结石动物模型中的作用。与单独的致石饮食相比，在患有胆固醇结石的仓鼠的致石饮食中添加EPA导致胆汁磷脂增加和总胆结石重量显著降低（部分溶解）。我们接下来检查了EPA在胆囊结石患者中的临床疗效。结果显示，与基线数据相比，口服EPA（1800 mg/天）6个月显著增加了胆汁磷脂水平，并改善了胆汁中的成石指数（胆固醇饱和指数和晶体观察时间）。此外，通过持续EPA给药超过一年，在两例病例中实现了结石完全溶解，在另一例病例中实现了部分溶解。总之，这项研究在实验和临床上证明了鱼油（EPA）对胆固醇结石的新溶解作用。

Medical (oral bile acid) therapy for gallstone disease requires long time and is often ineffective. Therefore, development of more effective pharmacologic therapy is expected. We have previously found that eicosapentaenoic acid (EPA), the major constituent of fish oil, exerts inhibitory effects on cholesterol gallstone formation. In the present study, we aimed to clarify both experimentally and clinically whether EPA can dissolve cholesterol gallstone. We firstly examined the effect of EPA in an animal model of gallstone. Addition of EPA to lithogenic diet in hamsters with cholesterol gallstones resulted in increases in biliary phospholipids and significant reduction in total gallstone weight (partial dissolution), compared with the lithogenic diet alone. We next examined the clinical efficacy, of EPA in patients with gallbladder stones. It was revealed that oral administration of EPA (1800 mg/day) for 6 months significantly increased the biliary phospholipid levels and improved the lithogenic indices (cholesterol saturation index and crystal observation time) in bile, compared with the baseline data. Furthermore, complete stone dissolution was achieved in two cases and partial dissolution in another 1 case by continuing the EPA administration for more, than a year. In summary, this study demonstrated both experimentally and clinically a novel dissolving effect of fish oil (EPA) on cholesterol gallstone.