UDCA vs Silymarin: what to choose and for whom

When a person sees elevated liver tests or simply wants to «support the liver», UDCA and milk thistle often end up in the pharmacy basket. The editorial team examined in which situations the choice between them makes any sense at all, when the decision should be made only by a doctor, and why sometimes the right answer is neither of the two.

Where the choice begins

The question «what is better for the liver» is meaningless without an answer to another: what exactly is happening with the liver. A rise in the transaminases ALT and AST, an increase in alkaline phosphatase and GGT, gallstones, fatty infiltration on ultrasound - these are different conditions with different causes, and each has its own approach.

Broadly, all situations can be divided into two groups. The first is conditions linked to impaired formation or outflow of bile (cholestasis). The second is damage to the liver cells themselves through toxins, alcohol, fat, viruses or medication. UDCA has its strongest evidence base precisely in the first group.

So the basic algorithm looks like this: blood tests (ALT, AST, GGT, alkaline phosphatase, bilirubin), an ultrasound of the abdominal organs and, if needed, testing for viral hepatitis and other causes. Only after this does it make sense to talk about choosing an agent, and often that choice is made by a gastroenterologist or hepatologist.

Self-treatment without a diagnosis has one more drawback: it can delay a visit to the doctor. A person «cleanses the liver» for several months while the real cause - from gallstone disease to viral hepatitis - remains unaddressed.

When UDCA comes first

The most clear-cut situation is primary biliary cholangitis. The EASL guidelines regard UDCA as the first-line standard; in this indication the dose is calculated per body weight and treatment lasts for years. Silymarin is not an alternative here, and replacing the drug with a «natural» agent may be harmful.

The second group is gallstone disease, but only in some patients. According to the EASL guidelines on gallstones, dissolution with UDCA is possible for small radiolucent cholesterol stones and a functioning gallbladder. The process is lengthy, and after discontinuation the stones may form again, so the decision is always individual.

The third scenario is prevention of stone formation during rapid weight loss, for example after bariatric surgery. A sharp drop in body weight increases the lithogenicity of bile, and in certain clinical situations doctors prescribe UDCA for this period. This is also an indication for which separate recommendations have been developed.

Finally, UDCA is used in some forms of cholestasis of other origin - in particular in cholestasis of pregnancy and certain drug-induced cholestatic injuries. In all these cases we are talking about a medicinal product prescribed by a doctor after examination, taking into account contraindications, above all obstruction of the bile ducts.

For whom silymarin may be suitable

It makes sense to consider silymarin as an auxiliary agent in people without a serious diagnosis who want to use a well-tolerated plant product and understand the limits of its effectiveness. The Cochrane review did not confirm an effect on hard outcomes in alcoholic and viral injury, so expectations should be modest.

In non-alcoholic fatty liver disease some small studies described an improvement in enzymes, but according to the EASL-EASD-EASO guidelines the basis of treatment remains weight loss, physical activity and dietary correction. If a person takes milk thistle, it should not replace these steps.

For those who do choose silymarin, product quality matters. It is worth looking for a standardised extract with a stated content of silymarin or silibinin, and also paying attention to a form with improved bioavailability. Studies most often used standardised extracts with a silymarin content of about 70-80%, split across several intakes a day.

Silymarin should not be chosen by people allergic to plants of the Asteraceae family (ragweed, chamomile, chrysanthemums), nor - without a consultation - by those taking drugs with a narrow therapeutic window. Pregnant and breastfeeding women should also take plant extracts only after speaking with a doctor.

People who train: a separate case

In strength-sport circles both agents are often bought «for a cycle» as protection against oral anabolic steroids. The editorial team stresses: neither UDCA nor silymarin has evidence that it prevents steroid-induced liver injury. The LiverTox database describes cholestasis, hepatic peliosis and adenomas linked to androgens, and a prophylactic agent does not cancel these risks.

Intense strength training in itself raises ALT and AST because of the release of enzymes from muscle. So a person who has had tests done after a hard workout may mistakenly decide they have «liver problems». Before drawing conclusions it is worth checking GGT and creatine kinase and repeating the test after a few days of rest.

But if, while taking any drugs, itching of the skin, darkening of the urine, yellowing of the sclerae or a rise in bilirubin appear, these are signs of cholestasis that require a doctor. In such a situation the decision about UDCA or other agents is made by a specialist, and the first and main step is to stop taking the substance that caused the injury.

For an athlete who does not use hepatotoxic substances and has no abnormalities in tests, there is usually no need for either of the two agents. A balanced diet, moderate alcohol consumption and weight control do more for the liver than any capsule.

Typical mistakes and when neither is needed

The most common mistakes in choosing relate not to the agents themselves but to the logic of their use. The editorial team has gathered the ones readers encounter most often:

• taking UDCA «to cleanse the liver» without an ultrasound, when there may be large or calcified stones in the gallbladder;
• expecting silymarin to «restore» the liver after alcohol while alcohol consumption continues;
• taking several hepatoprotectors at once on the idea that «more is better»;
• interpreting elevated ALT after a workout as liver injury;
• using an agent as «insurance» for hepatotoxic substances.

A note on the combination. Taking UDCA and silymarin together is theoretically possible, since the mechanisms differ, but there is no evidence of additional benefit from such a combination. If a doctor has already prescribed UDCA on indication, adding plant agents should be agreed with them.

Finally, quality is worth remembering. UDCA as a medicinal product undergoes control, whereas the market for milk thistle supplements is heterogeneous. The review by Navarro and co-authors reminds us of cases where the composition of plant supplements did not match what was declared, so the reliability of the manufacturer matters.

Editorial conclusions

If there is a diagnosis linked to bile stasis, primary biliary cholangitis or small cholesterol stones, UDCA will be first on the list - but only as prescribed by a doctor. Silymarin is not a substitute for it in these conditions.

Silymarin may be an acceptable auxiliary agent for people without serious diseases who understand that its benefit is not convincingly proven and that the foundation of liver health is weight, diet, alcohol and avoiding toxic substances.

For more on the differences in mechanisms of action, read the article «UDCA vs Silymarin: what is the difference». We also recommend the editorial pieces on NAC and silymarin, on interpreting liver tests in athletes and on TUDCA.

References

1. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of cholestatic liver diseases. J Hepatol. 2009;51(2):237–267.
2. European Association for the Study of the Liver. EASL Clinical Practice Guidelines on the prevention, diagnosis and treatment of gallstones. J Hepatol. 2016;65(1):146–181.
3. European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), European Association for the Study of Obesity (EASO). EASL–EASD–EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016;64(6):1388–1402.
4. Rambaldi A, Jacobs BP, Gluud C. Milk thistle for alcoholic and/or hepatitis B or C virus liver diseases. Cochrane Database Syst Rev. 2007;(4):CD003620.
5. Navarro VJ, Khan I, Björnsson E, et al. Liver injury from herbal and dietary supplements. Hepatology. 2017;65(1):363–373.
6. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Androgenic steroids. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012–.
7. Pettersson J, Hindorf U, Persson P, et al. Muscular exercise can cause highly pathological liver function tests in healthy men. Br J Clin Pharmacol. 2008;65(2):253–259.