This study explored the use of a milk thistle extract and isolated constituent, silibinin, as alternatives to orlistat, to support weight loss with reduced adverse events.
In this article, we discuss the Effect of silibinin on human pancreatic lipase inhibition and gut microbiota in healthy volunteers: A randomized controlled trial (1).
Plant name and species
The study used extracts of milk thistle (Silybum marianum) that included a general extract standardised to 50% silibinin, as well as a 100% silibinin extract.
Aim of study
To explore the safety and effectiveness of milk thistle extracts compared to a placebo and standard treatment on metabolic biomarkers, fat metabolism and gut microbiota composition in healthy volunteers.
Study method
This study was a double-blind, randomized, placebo-controlled, crossover pilot trial with five groups ingesting capsules comprising:
- Placebo
- Milk thistle extract
- Silibinin dose 1
- Silibinin dose 2
- Orlistat (a pancreatic lipase inhibitor used as a weight loss alternative to GLP1 analogues)
Participants attended an initial screening one week before the start of the trial where baseline measures were made, after which they participated in a three-day treatment phase and a follow-up visit with tests. After a month washout period, participants started their second treatment, and by the end participated in all five treatments in a cross-over design.
The outcome measures were:
- Anthropometric measures
- Faecal fat excretion
- Blood lipid biomarkers (cholesterol, high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), and triglycerides)
- Gut microbiota changes
- Perceptions of hunger and satiety
- Adverse events
Herbal preparation
- Thistle extract comprised silymarin (with a 50% silibinin content)
- Silibinin dose 1, 150 mg
- Silibinin dose 2, 300 mg
- Orlistat, 120 mg
Silymarin is an extract of milk thistle, and silibinin is the main active component. The treatments were given daily and compared to a placebo prepared in an identical capsule.
Sample size
Twelve healthy men and women volunteers (aged 18–45 years, body mass index < 25 kg/m2 received the treatments or placebo for three days whilst eating a standardised diet with 30% calories from fat. Volunteers were excluded if they had a history of hepatic dysfunction or recent bowel symptoms.
Results of study
Eleven participants completed the study. All four treatments significantly reduced waist circumference compared to the placebo, but there were no changes in body weight or fat mass.
Both orlistat and thistle extract resulted in a trend toward higher faecal fat excretion, although the statistical tests showed no significant difference from the placebo.
There were no significant changes to blood triglycerides although levels tended to be higher from the thistle extract. Orlistat was not significantly different from placebo suggesting this protocol was not sufficient to see changes expected from the lipase inhibitor drug.
For gut microbiota, there were no significant changes in alpha- or beta-diversity, which was presumably due to the low participant numbers and individual variation. For individual bacterial species, both doses of silibinin (150 mg and 300 mg) decreased Lachnospiracea incertae sedis species, and changes in other species were observed. Further statistical tests showed that higher levels of the Veillonellaceae and Flavobacteriaceae bacterial families were associated with higher levels of fat excretion.
There was no change in hunger or satiety sensations between treatment groups.
All interventions (placebo, 150 mg silibinin, 300 mg silibinin, thistle extract, and orlistat) were associated with adverse events, with the fewest from silibinin 300 mg (n = 9)and the most from orlistat (n = 23 events), and the most commonly experienced was constipation.
Discussion
This was a pilot study and the rationale was to explore herbal alternatives to the use of glucagon-like peptide 1 receptor agonists (GLP1Ra), which are effective in reducing weight but are associated with side effects.
Silibinin is a bioactive compound found in milk thistle (Silybum marianum) and is widely used to treat liver disorders, and the authors explored a silibinin-rich thistle extract alongside two doses of silibinin extract, and a lipase-inhibitory drug orlistat.
Overall the thistle extract showed the most promise with a reduction in waist circumference on par with orlistat, and both increased faecal fat excretion although this was not a statistically significant change. The number of adverse events was highest with orlistat and reasonably low with thistle extract and the other silibinin preparations, again suggesting an advantage to the herbal alternatives.
These actions suggest thistle extract and orlistat may be acting by reducing lipid absorption in the gut as well as reducing abdominal fat accumulation, both plausible mechanisms for contributing to weight loss. However, the reductions to weight were only small in this protocol.
An interesting feature of this pilot study was to begin an exploration of how the microbiota relates to lipid metabolism and excretion. Several species- and family-level changes were observed. Just taking one example, silibinin extracts caused a reduction in Lachnospiracea incertae sedis species, and these are associated with metabolic syndrome, obesity, diabetes, liver diseases, and inflammatory bowel conditions (2). The authors acknowledge that much more research is needed to understand the importance of the bacterial changes. Could they play a positive role in metabolic health, or are they bystanders of higher carbohydrate and lipid ingestion?
Conclusions
Milk thistle and silibinin preparations appear safe and may be supportive of weight loss and metabolic changes as observed in a healthy population.
The limitations of the study are clearly stated. This was a pilot study and small scale, and recruited healthy individuals whose weight fell within normal ranges. The study provides a useful foundation for further research into the use of milk thistle for metabolic disorders, and to explore the use of herbal alternatives to the popular GLP1 inhibitors. Future research will undoubtedly focus on diseased populations and look at treatments over longer periods of time.
References
- Ponce Martínez C, et al (2024). Effect of Silibinin on Human Pancreatic Lipase Inhibition and Gut Microbiota in Healthy Volunteers: A Randomized Controlled Trial. Int J Mol Sci. Nov 29;25(23):12853. doi: 10.3390/ijms252312853. PMID: 39684564; https://pmc.ncbi.nlm.nih.gov/articles/PMC11640983/
- Vacca M, Celano G, Calabrese FM, Portincasa P, Gobbetti M, De Angelis M. The Controversial Role of Human Gut Lachnospiraceae. Microorganisms. 2020 Apr 15;8(4):573. doi: 10.3390/microorganisms8040573. PMID: 32326636; https://pmc.ncbi.nlm.nih.gov/articles/PMC7232163/
