Extremely low. Toxicity studies in rats and mice have shown that silymarin, even at daily doses as high as 2500-5000 mg/kg, produced no adverse toxic effects (Anon 1998). In a 12-month study in rats and dogs given up to 2500 mg/day, no signs of toxicity were seen.
A review of studies involving more than 7000 participants identified three cases of serious adverse reactions (two anaphylaxis and one gastroenteritis symptoms).
Overall, adverse effect frequency was the same as for placebo and had a low frequency, ranging from 2% to 10% in controlled trials. In practice, loose bowels have been reported, although the reaction is considered rare.
Controlled studies are not available; therefore, interactions are based on evidence of activity and are largely theoretical and speculative. Preliminary evidence of CYP3A4 inhibition suggests it could theoretically increase levels of drugs metabolised, although a 2003 crossover study found no evidence of significant effect.
Elevation of serum warfarin levels is theoretically possible owing to CYP inhibition seen in vitro — use this combination with caution.
Preliminary research has shown this combination may reduce toxic effects, yet enhance antitumour activity — beneficial interaction.
Contraindications and Precautions
Contraindicated in people with known allergy to the Asteraceae (Compositae) family of plants.
Insufficient reliable information is available to determine safety in pregnancy.