Milk Thistle

What it is

Milk thistle is a plant, Silybum marianum. Its main active group of compounds is silymarin, a mixture of flavonolignans such as silybin [1]. It has been sold in Europe as a capsule of the plant extract since 1974 [2].

What the research says

The strongest finding is for liver enzymes in fatty liver. A review of 26 randomised trials with 2,375 people found that silymarin lowered ALT and AST [3]. A review of eight placebo-controlled trials found the same [4]. A 24-week trial of 83 people found lower liver stiffness, a scan measure of scarring [5]. In a 48-week trial of 99 people with NASH, the share who cut their disease score by 30% or more did not differ from placebo, but more people on silymarin had a one-point fibrosis improvement on biopsy (22.4% vs 6.0%) [6].

A 12-month trial of 179 people with fatty liver used a silybin complex with vitamin E and found better liver enzymes and biopsy scores than placebo [7]. Not all trials agree: in 154 people with hepatitis C, silymarin did not lower ALT more than placebo [8]. Five trials with 270 people with type 2 diabetes found lower fasting glucose and HbA1c [9], but a 12-week trial of 48 people found no change [10]. A 2007 Cochrane review of 18 trials found no significant effect on death in liver disease [11].

Doses used in studies

Study doses varied widely, from about 103 mg a day [5] to 2.1 g a day for seven days in a phase I study [12]. Examples: 700 mg three times a day for 48 weeks in NASH [6]; 420 or 700 mg three times a day for 24 weeks in hepatitis C [8]; three 140 mg capsules a day for 12 weeks in type 2 diabetes [10]. These are study doses, not recommendations.

Safety and interactions

Side effects in trials were mild. The NASH trial found no more adverse events than placebo [6], and a review lists nausea and diarrhoea [1]. We did not find an established upper intake limit. The highest dose tested in one study was 2.1 g a day for seven days, with no drug-related adverse events [12].

Warfarin: a 2020 case report describes a man whose INR rose from 2.64 to 4.12 while taking a supplement with 200 mg of milk thistle, which returned to normal after he stopped [13]. This is one case, not a controlled study. A review says silymarin may affect some drug-processing enzymes, but that clinical effects are unlikely [14], and another advises caution with narrow-safety-range drugs [1]. Our searches found no controlled trials of interactions with diabetes or blood-pressure medicines.

Pregnancy: one review notes a trial in pregnancy with no birth defects, but advises caution and more human studies [1]. We found no studies on breastfeeding. People with liver disease were the group studied in most trials [6][8]; ask a doctor first if you have liver disease or take blood thinners.

Caveats and open questions

Most trials are small and short, between 12 and 48 weeks [10][6]. Liver enzymes, liver stiffness and biopsy scores are markers, not clinical outcomes [5]. Silymarin is absorbed poorly at usual doses [12], so results depend on the product: standard silymarin and a silybin complex were tested in different trials [7]. One fatty liver trial had authors employed by BYHEALTH Institute of Nutrition and Health [5]. A paediatric fatty liver trial of 20 children is recruiting [NCT06477146].