Safety and toxicity of silymarin, the major constituent of milk thistle extract: An updated review

Abstract

Milk thistle (Silybum marianum) is a medicinal plant from the Asteraceae family. Silymarin is the major constituent of milk thistle extract and is a mixture of some flavonolignans such as silybin, which is the most active component of silymarin. It is most commonly known for its hepatoprotective effect. Also, studies have shown other therapeutic effects such as anticancer, anti‐Alzheimer, anti‐Parkinson, and anti‐diabetic, so its safety is very important. It has no major toxicity in animals. Silymarin was mutagen in Salmonella typhimurium strains in the presence of metabolic enzymes. Silybin, silydianin, and silychristin were not cytotoxic and genotoxic at concentration of 100 μM. Silymarin is safe in humans at therapeutic doses and is well tolerated even at a high dose of 700 mg three times a day for 24 weeks. Some gastrointestinal discomforts occurred like nausea and diarrhea. One clinical trial showed silymarin is safe in pregnancy, and there were no anomalies. Consequently, caution should be exercised during pregnancy, and more studies are needed especially in humans. Silymarin has low‐drug interactions, and it does not have major effects on cytochromes P‐450. Some studies demonstrated that the use of silymarin must be with caution when co‐administered with narrow therapeutic window drugs.

The Effects of a Fixed Combination of Berberis aristata and Silybum marianum on Dyslipidaemia – A Meta-analysis and Systematic Review

“…Including the most recent RCTs, no serious adverse events attributable to either plant were reported. In the included four trials, none of the patients reported side effects after given Berberol [22,23]. Changes in enzyme levels (ALT, AST, CK) were not significant in the trials, and our meta-analysis also confirmed that Berberol does not alter the level of these enzymes.…”

Therapeutic Potential of Flavonoids in Pain and Inflammation: Mechanisms of Action, Pre-Clinical and Clinical Data, and Pharmaceutical Development

“…Although there are a lot of patent requested to pharmaceutical compositions containing flavonoids and to use of flavonoids [257], to our knowledge, the Food and Drug Administration (FDA) has not yet endorsed any flavonoids as pharmaceutical drugs. Although antioxidant properties are commonly linked to flavonoid molecules, under specific conditions they can be prooxidant (hydroxyl radicals can be produced due to their iron and copper reducing activities [258]) and present side effects, as genotoxicity, nausea, and headache [259,260]. Supplementation of high doses may cause antithyroid and goitrogenic effects, in addition to lower bioavailability of vitamin C, trace elements, and vitamins such as folate [256].…”

Identification of a Potent Inhibitor Targeting the Spike Protein of Pandemic Human Coronavirus, SARS-CoV-2 by Computational Methods

“…Silymarin is a phytomedicine extracted from milk thistle seeds. Along with its hepatoprotective effects, it is also known for anti-oxidant, anti-viral, anti-inflammatory and anti-fibrotic activities (40,41). It exhibits interactions with both 'Site 1' and 'Site 2' residues thereby inhibiting His34 and Lys343 of ACE2 ( Figure 4G).…”