Milk thistle

Scientific Name(s): Silybum marianum (L.) Gaertn. Family: Compositae; may be referred to in older texts as Carduus marianus .

Common Name(s): Holy thistle , lady's thistle , marian thistle , Mary thistle , milk thistle , St. Mary thistle , silybum

Clinical Overview

Uses of Milk thistle

Pharmacological studies for milk thistle fruit document antioxidant, anti-inflammatory, antifibrotic, and anticancer properties. Additional pharmacological studies include inhibition of lipid peroxidation and stimulation of protein biosynthesis. However, the majority of the literature concerns the hepatoprotective efficacy of silymarin and silibinin in particular against Amanita phalloides mushroom poisoning.

Milk thistle Dosing

Crude milk thistle seed has been administered at 12 to 15 g/day in clinical trials for hepatitis and other liver conditions. The most effective doses in clinical trials ranged from 420 to 600 mg/day of extracts, tablets, or capsules standardized to 70% silymarin.

Contraindications

There are no known contraindications.

Pregnancy/Lactation

There is no information on appropriate use in pregnancy or lactation.

Milk thistle Interactions

Care should be taken when using milk thistle. Silybin inhibits phase I and phase II enzymes and inactivates cytochromes P-450 3A4 and 2C9. Silybin is a potent selective inhibitor of the enzyme UGT1A1. The clinical relevance of these interactions is not well defined because of the absence of carefully controlled clinical studies. Milk thistle has been reported to reduce indinavir trough plasma concentrations.

Milk thistle Adverse Reactions

The most common reactions after oral ingestion of milk thistle include brief disturbances of GI function (eg, abdominal bloating, abdominal fullness or pain, anorexia, changes in bowel habits, diarrhea, dyspepsia, flatulence, nausea). Other reported adverse reactions include headache, skin reactions (eg, eczema, pruritus, rash, urticaria), neuropsychological events (eg, asthenia, insomnia, malaise), arthralgia, rhinoconjunctivitis, impotence, and anaphylaxis. For most clinical trials reporting adverse reactions, incidence was approximately equal in milk thistle and control groups.

Toxicology

There are no reports of milk thistle toxicities in humans.

Botany

Milk thistle is indigenous to Europe and Asia but has been naturalized in North and South America. It grows 1.5 to 3 m in height and has large, prickly leaves. When broken, the leaves and stems exude a milky sap. The reddish-purple flowers are ridged with sharp spines. The drug includes the shiny, mottled, black or grey-toned fruits that often are referred to as seeds. These make up the thistle portion, along with its silvery pappus, which readily falls away.

History

Milk thistle has been used medicinally since the fourth century BCE. Its use in treating hepatobiliary diseases dates back to the 1700s, and its use as a liver protectant can be traced back to Greek references. Pliny the Elder, a first century Roman writer, (AD 23 to 79) noted that the plant's juice was excellent for “carrying off bile.” Nicholas Culpepper, the 17th century English herbalist, noted milk thistle t o be useful against jaundice and for removing liver and spleen obstructions. The Eclectic medical system (19th to 20th century) used milk thistle for varicose veins, menstrual difficulty, and congestion in the liver, spleen, and kidneys. In homeopathy, a tincture of the seeds has been used to treat liver disorders, jaundice, gallstones, peritonitis, hemorrhage, bronchitis, and varicose veins. The fruit, stem, and seeds are all considered to have medicinal value.

Early colonists introduced milk thistle to North America. The plant was grown in Europe as a vegetable and the de-spined leaves were used in salads and as a green; the stalks and root parts also were consumed. The flower portion was eaten “artichoke-style.” The roasted seeds were used as a coffee substitute.

Chemistry

The ripe fruit or seed contains 4% to 6% silymarin, a mixture of 3 isomeric flavonolignans, first isolated in 1968. Silymarin has a molecular formula of C ₂₅ H ₂₂ O ₁₀ and a molecular weight of 482.45. The isomeric flavonolignans are silybin (silibinin), silychristin (silichristin), and silidianin (silidianin). These 3 stereoisomers differ only by the chemical link between the taxifolin moiety and coniferyl alcohol. A review of the isolation and structure of these components is available. Other flavonolignans include dehydrosilibinin, 3-desoxysilichristin, deoxysilydianin (silymonin), siliandrin, silybinome, silyhermin, and neosilyhermin.

Gel absorption and column chromatography methods have been employed to investigate flavones in milk thistle ; constituents from aerial parts and fruits have been analyzed. Betaine hydrochloride was isolated from milk thistle seeds and analyzed by chemical and spectroscopic methods. Spectrophotometric assay to determine flavone lignans from milk thistle and its preparations have been described. A near infrared (NIR) reflectance spectroscopic method was capable of identifying silybum samples from different geographical locations. Silymarin has been analyzed by extraction in small amounts using liquid carbon dioxide (supercritical conditions) in high-performance liquid chromatography (HPLC)-packed columns. The separation by this method may be useful for flavonolignan analysis  ; solubility and bioequivalence analyses of silymarin products has been performed.

Silybin is the most biologically active component with regard to milk thistle's antioxidant and hepatoprotective properties. A standardized milk thistle extract composed of silymarin and silybin was developed in Europe as Legalon . Silymarin is poorly soluble in water, so aqueous preparations such as teas are ineffective, except for use as supportive treatment in gallbladder disorders because of cholagogic and spasmolytic effects.  The drug is best administered parenterally because of poor silymarin absorption from the GI tract (23% to 47%). The drug must be concentrated for oral use.

The compound 5,7-dihydroxychromone has been isolated from S. marianum . Other seed components include apigenin; silybonol, a fixed oil (16% to 18%) consisting largely of linoleic and oleic acids, plus myristic, palmitic, and stearic acids; betaine hydrochloride; triamine; histamine and others.

From the roots of S. marianum Gaertn, 12 polyacetylenes and 1 polyene have been detected.