Cases in CAM: Milk Thistle for the Liver -- Any Evidence?

Commentary

Milk thistle (also known as Silybum marianum or silymarin) has been used medicinally for over 2000 years,^[1] primarily for the treatment of hepatic and biliary disorders.^[2,3,4,5]A flavonoid complex called silymarin is believed to be its active component.^[2,3] Silibinin (the most active component of silymarin) can inhibit the 5-lipoxygenase pathway (which is involved in the formation of free radicals), scavenge hydroxyl radicals, and inhibit tumor necrosis factor (TNF).^[6] Animal models have supported milk thistle’s role as an antioxidant that reduces free radical generation and affects cell growth and apoptosis, thereby reducing inflammation and supporting the liver’s tolerance of oxidative stress, including damage induced by toxins such as carbon tetrachloride.^{[7,8,9,10,11]} The German commission E approves milk thistle for use in the treatment of^[12,13,14]:

• Liver conditions including toxin-induced damage and hepatic cirrhosis; and

• Dyspepsia.

Milk thistle is one of the most frequently sold herbal products in the United States, with retail sales reaching $8.9 million in 2000, a 14% increase over sales in 1999.^[15] It is used in gastroenterology clinics to treat hepatitis and cirrhosis and in oncology settings as a hepatoprotectant to:

• Clear toxins;

• Assuage symptoms of cancer; and

• Improve tolerance to chemotherapy.

The intravenous form of silymarin has also been used as supportive treatment for Amanita phalloides mushroom poisoning.^[2,3] Preliminary studies suggest that milk thistle may be potentially beneficial in treating or preventing some cancers^[16] for example, it may prove to play a role in any one of the following cancers:

• Prostate;

• Skin;

• Squamous cell cancer of the tongue;

• Bladder;

• Breast;

• Cervical;

• Colon; and

• Leukemia.

Of note, a recent dermatologic review examined the use of topical milk thistle as a protectant against ultraviolet (UV) radiation and concluded that it may fall into the category of a botanical cosmeceutical with antioxidant properties that might offset the effects of skin aging and skin cancer.^[17]

Milk Thistle for Liver Disease: What Does the Data Support?

Four systematic reviews examined the efficacy of milk thistle for the treatment of liver diseases, in particular, alcoholic liver disease and hepatitis B and C.^{[18,19,20,21]} In one review, overall mortality for all chronic liver diseases studied in 14 trials was not reduced and there were no improvements in liver function by histology or biochemical testing that were of clinical significance.^[18] The investigators recommended more definitive trials to examine efficacy. In the other reviews, based on high-quality trials, milk thistle did not influence the course of alcoholic or hepatitis B or C disease by outcomes of mortality and histology, but it had the potential to affect liver injury, with improvements seen in liver function tests after acute injury.^[19,20,21]

A recent randomized, placebo-controlled clinical trial assessing the effects of silymarin on acute hepatitis (defined as alanine amino transferase levels higher than 2.5 times normal), mostly due to acute viral hepatitis, used 140 milligrams (mg) of silymarin 3 times daily and reported quicker resolution of symptoms of biliary retention and reduction in indirect bilirubin, but not other LFTs, over 4 weeks.^[22] Another recent study suggests that a mixture of Silybum marianum and Aloe vera was protective against carbon tetrachloride-induced acute hepatotoxicity and liver fibrosis.^[23]

What to tell your patients. The National Institutes of Health’s National Center for Complementary and Alternative Medicine (NCCAM) provides patient information on the use of milk thistle for hepatitis C.^[24] It emphasizes the lack of definitive evidence for its efficacy in treating hepatitis C and urges patients not to replace conventional medical therapy with milk thistle.

Preparations, Dosage, Side Effects, and Contraindications

Milk thistle capsules, tincture, and powder are standardized to contain 70% to 80% silymarin, but different preparations may vary in terms of bioavailability. Chromatographic methods have been used to identify its active ingredients to satisfy Good Manufacturing Practices.^[2] It is considered safe at doses up to 1500 mg daily and for treatment durations of up to 41 months.^[25] No significant interactions or contraindications have been reported for milk thistle use.^[26] Adverse effects are uncommon, with the most commonly reported being mild gastrointestinal disturbance, including a laxative effect.^[15]

There is insufficient data on its use in pregnancy and lactation; therefore, it is not recommended for women during these times.^[2,3]

Suggested doses in standardized preparations for cirrhosis and acute toxin-induced hepatotoxicity range from 160 to 800 mg daily by mouth. For chronic hepatitis, suggested doses range from 160 to 480 mg daily in silybin equivalents and 420 mg daily in 3 divided doses for silymarin.^[2] The preparations Legalon® (containing silymarin), Nature's Way® Thisilyn, and Standardized Milk Thistle Extract Maximum Absorption Formula 2X have been used in clinical trials. Silymarin is also found in some moisturizers for photoaging (for example, RosaCure+ and SkinCeuticals Antioxidant Lip Repair.^[17]

In summary, there is ample evidence from animal models for the antioxidant, anti-inflammatory, and antitoxin action of milk thistle, but limited up-to-date clinical evidence from high-quality randomized trials that milk thistle and its components offer significant benefit in the treatment of liver diseases including acute hepatitis and cirrhosis. The clinical benefits that have been demonstrated are of limited magnitude and significance. There are no studies documenting its efficacy in protecting against acute effects of alcohol intoxication or any evidence to suggest that it can reduce one’s appetite for alcohol. A recent review of an integrative medicine strategy for alcohol abuse advocates a balanced holistic approach that includes^[1]:

• Nutritional counseling;

• Healthy lifestyle;

• Relaxation;

• Judicious use of supplementation with B vitamins, probiotics, zinc, and carnitine, as well as botanical products such as milk thistle; and

• Acupuncture and mind-body therapy.

Abstinence from alcohol is the key to success in any case of chronic alcohol abuse.

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Cite this: Désirée Lie. Cases in CAM: Milk Thistle for the Liver -- Any Evidence? - Medscape - Mar 02, 2010.