Milk thistle

Milk thistle (Silybum marianum (L.) Gaertn.; Asteraceae) is an herbaceous flowering plant belonging to the daisy and sunflower family. The plant is native to North Africa, Southern Europe, and the Mediterranean region through to central Asia and India. Milk thistle has been introduced to and has naturalised across Europe, North and South America, and Australasia, both as a cultivated plant and noxious weed. The flower heads are a reddish-purple colour, and the shiny green leaves have distinct white vein markings. When broken, the leaves excrete a ‘milky-white’ sap, giving the plant its name. Like other thistle plants, the leaves, stems and flowers of milk thistle have stiff, sharp spines. The seed (sometimes referred to as the ‘fruit’) is primarily the part used medicinally.

Milk thistle has a long history of traditional use for treating various ailments, including liver and kidney disorders, rheumatism, gastrointestinal disturbances, cardiac disorders and fever. More recent interest has focused on the hepatoprotective, cardiometabolic and anticancer properties of milk thistle.¹

Common names

Lady’s thistle, holy thistle, blessed milk thistle, St Mary’s thistle [English] and many others. [NB: the common name ‘milk thistle’ is also used to refer to several other (unrelated) plants.]

Preparations

Traditional preparations of milk thistle include (depending on the intended use) powdered seeds, and decoctions and infusions made with water for oral consumption. Additionally, milk thistle decoctions have been applied externally for haemorrhoids and injuries.¹ Contemporary preparations are available in oral (capsules, teas, tonics, liquid extracts) and topical dose forms (eg creams). Preparations are formulated as single- and multi-ingredient products with other herbal and non-herbal ingredients. In New Zealand, milk thistle products are sold as ‘dietary supplements’ and are available as capsules, powders, liquid extracts and teas.

Manufacturers’ claims

Milk thistle products are mostly marketed for supporting liver health, including for liver detoxification and ‘cleansing’, protection of the liver from harmful exposures (eg alcohol), as well as for specific liver-related disorders, such as jaundice, hepatitis and cirrhosis. Some products are promoted to aid digestion, reduce bloating, and to support an anti-inflammatory response, among other claims.

Active constituents

The most pharmacologically important component of milk thistle seed is silymarin, a complex mixture of several flavonolignans, including silybin (silibinin), silydianin, isosilybin, silychristin and others; the flavonoid taxifolin is also present in the seed, along with lipids (eg linoleic acid), and sterols (eg cholesterol, stigmasterol). Silybin is the main bioactive component of silymarin. Research has primarily focused on silymarin and silybin, which are often used interchangeably in the literature.

Evidence for efficacy

Preclinical studies provide some evidence supporting the effects of milk thistle, particularly its hepatoprotective, anti-inflammatory and anti-tumour properties.^1,2

Clinical research with preparations containing milk thistle has concentrated on the hepatoprotective and anti-cancer effects. However, there is currently no definitive evidence demonstrating efficacy in patients with liver disorders or types of cancer.^1,2

Systematic reviews have explored the efficacy of milk thistle or its constituents (namely, silymarin) in liver disease, including its potential benefits in chronic hepatitis B and C virus (HCV) infection, and in non-alcoholic fatty liver disease (NAFLD).^3,4 Some systematic reviews suggest that silymarin may reduce liver enzyme concentrations and improve liver function in specific contexts – such as NAFLD – but the evidence overall remains inconclusive.⁵

A Cochrane systematic review of clinical trials assessing the efficacy of milk thistle, or milk thistle constituents, in liver disease related to alcoholism and/or HBV or HCV infection included 13 RCTs involving a total of 915 participants. The review found no statistically significant effects for milk thistle or its constituents on all-cause mortality, complications of liver disease, or liver histology, compared with placebo, or no intervention, over a median duration of 6 months’ treatment. Liver-related mortality was significantly reduced in all trials (RR = 0.50), but not in high-quality trials only (RR = 0.57). The authors concluded that higher-quality trials indicate milk thistle does not significantly impact the progression of liver disease caused by alcohol, HBV, or HCV.⁶ Overall, while milk thistle appears to have some protective effects, particularly in specific liver conditions, the evidence for its efficacy is limited and inconsistent.

Clinical studies on milk thistle used in oncology have focused primarily on its potential to manage cancer treatment-related adverse effects.^1,2 However, current evidence is limited due to the low methodological quality of studies, many of which involve small sample sizes.

In general, larger methodologically robust trials of milk thistle are required; studies should report comprehensive descriptions of milk thistle preparations used, including whether the product meets accepted standards for pharmaceutical quality.

Adverse effects

The available evidence indicates that preparations of milk thistle are generally regarded as safe when used at recommended doses for short-term periods. However, clinical safety and toxicity data for milk thistle are limited and comprehensive investigation of the clinical safety profile of milk thistle and its important constituents when used in a pharmaceutical/medicinal context, including long-term use, is required.

Common adverse effects include mild, transient gastrointestinal symptoms, such as nausea, vomiting, diarrhoea, and abdominal pain/discomfort. There are isolated reports of allergic reactions, including anaphylaxis, associated with preparations containing milk thistle.^1,2 Causality has not necessarily been established in these cases. Milk thistle should be used with caution by individuals who have known hypersensitivities to other species in the Asteraceae family.

Due to insufficient safety data, use of milk thistle in children and by pregnant or breastfeeding women should be avoided.

Interactions

In vitro studies have shown that constituents of milk thistle may interact with certain pharmaceutical medicines by inhibiting the activity of some cytochrome P450 enzymes (CYP2D6, CYP2E1 and CYP3A4), thus affecting drugs metabolised by these enzymes. In most cases, this inhibition is unlikely to be clinically relevant, although the impact of the decrease in metabolism of losartan to its active metabolite in the presence of milk thistle requires clarifying.⁷ Silymarin reduces metronidazole concentrations in healthy individuals and, in a preclinical study, milk thistle increased concentrations of a hepatotoxic metabolite of pyrazinamide, although the clinical relevance of this is not clear.⁸ Milk thistle has been shown to lower blood glucose concentrations and, therefore, may have an additive effect when used with other hypoglycaemic agents.

The potential for interactions between preparations of milk thistle and other medicines, particularly those with similar or opposing pharmacological effects, should be considered.