Effect of Silibinin on Human Pancreatic Lipase Inhibition and Gut Microbiota in Healthy Volunteers: A Randomized Controlled Trial

Thistle (Onopordum acanthium) has been traditionally employed for liver protection, however, we recently identified silibinin, the main bioactive compound of thistle extract, as an in vitro pancreatic lipase inhibitor, which suggested a potential role as anti-obesity agent. This study aimed to assess, in vivo, the efficacy, safety, and effects of silibinin on human lipase. As a secondary objective, we evaluated potential changes on gut microbiota after silibinina treatment. A randomized trial comparing 150mg/silibinin, 300mg/silibinin, and a thistle extract (equivalent to 150 mg/silibinin) with placebo and orlistat/120mg was conducted. Fecal fat excretion, clinical parameters, and microbiota changes were analyzed. Orlistat showed the highest fecal fat excretion, although thistle extract had similar results (p = 0.582). The 150 mg/silibinin group reported the fewest adverse effects. Both silibinin and orlistat reduced plasma triglycerides (p=0.016) and waist circumference (p=0.001). Specific microbiota changes, such as increases in Mycobacteriaceae and Veillonellaceae, were associated with higher fat excretion. Silibinin proved to be safe and effective for obesity, with minimal adverse effects and no significant changes in microbiota diversity. Further studies are needed to explore its microbiota-related benefits.