How It Works
Bottom Line: Milk thistle can protect against alcohol-induced liver damage, and even reverse its effects in some cases. There is not enough evidence to say whether it can treat any other type of liver disease.
Laboratory studies support milk thistle's liver protectant effects. For example, when rats fed milk thistle are fed toxins and drugs that are known to be toxic to the liver, they are protected from liver damage compared to rats not given milk thistle. Scientists think that silymarin, a compound in milk thistle, alters and stabilizes the structure of the liver cells so that toxins cannot enter them as easily. In addition, it stimulates the synthesis of proteins, which is an important part of cell growth and regeneration after damage.
Recent laboratory studies have found that milk thistle has anti-cancer activity against colon and prostate cancer cells, but it is not known if this effect occurs in the human body.
Purported Uses
To prevent and treat alcohol-induced liver damage
Laboratory data and several clinical trials support this use.
As an antidote to poisonous mushrooms (such as Amanita phalloides)
No scientific evidence supports this use.
To prevent and treat drug-induced liver damage
Laboratory, animal, and clinical trials support this use, although the effect varies by drug.
To treat dyspepsia (gastrointestinal upset)
Some clinical trials support this use.
To treat cirrhosis of the liver
Clinical trials support this use, specifically for patients with alcohol-induced cirrhosis.
To treat hepatitis
Laboratory studies show that milk thistle protects and promotes regeneration of the liver, but there is no proof from clinical trials that milk thistle can treat hepatitis.
As supportive therapy for chronic inflammatory liver disease
Laboratory studies show that milk thistle protects and promotes regeneration of the liver, but there is no proof from clinical trials that milk thistle can treat inflammatory liver disease.
Research Evidence
Most clinical studies of milk thistle have been performed in Europe. They generally have used silymarin, the active compound in milk thistle, and have examined its effects on alcohol-induced liver damage.
Alcoholic liver disease and cirrhosis:
A study used silymarin to treat chronic alcoholic liver disease in 36 patients. For six months, 18 patients took silymarin, while 18 took a placebo. Liver function tests, usually elevated in patients with liver disease, were normalized in patients taking silymarin, while patients taking placebo showed no significant change. In addition, biopsies of liver tissue showed improvement in the group taking silymarin, compared to no change in the placebo group. These results suggest that silymarin exerts liver-protective activity and is able to improve liver function in alcoholic patients.
Ninety-seven patients with alcoholic liver disease and elevated liver function tests were studied in a clinical trial of silymarin. Patients were required to abstain from alcohol for at least one month before the beginning of the study. Forty-seven patients were randomly given silymarin, and 50 a placebo pill. After four months of treatment, key liver function tests were improved significantly in the silymarin group, while they worsened slightly in the placebo group. Liver biopsies also improved in the silymarin group. However, this study did not monitor abstinence from alcohol, which may have affected the results considerably.
A clinical trial studied 170 patients with cirrhosis of the liver to determine the effect of silymarin on their survival. For at least two years, 87 patients randomly received 140 mg of silymarin three times a day, while 83 patients received a similar regimen of placebo medication. Overall, patients taking silymarin had a higher four-year survival rate (58%) than those taking the placebo (39%). Further analysis showed that silymarin was most effective in patients with alcohol-induced cirrhosis.
Warnings
- This product is regulated by the FDA as a dietary supplement. Unlike approved drugs, supplements are not required to be manufactured under specific standardized conditions. This product may not contain the labeled amount or may be contaminated. In addition, it may not have been tested for safety or effectiveness.
Do Not Take If
You are taking medications that are metabolized by certain enzymes (cytochrome P-450 3A4) in the liver. Milk thistle inhibits this enzyme, which may inhibit the breakdown of certain medications (for example, ketoconazole, itraconazole, erythromycin, and triazolam), causing higher blood levels of these medications and in turn, possibly leading to increased adverse effects or toxicity. Ask your doctor if you are taking any medications metabolized by cytochrome P450 3A4.
Side Effects
Diarrhea
Uterine and menstrual stimulation
In one case report, a patient experienced episodes of sweating, nausea, vomiting, diarrhea, abdominal pain, weakness, and collapse after taking milk thistle. These symptoms resolved after the patient discontinued use of milk thistle.
Scientific Name
Silybum marianum, Carduus marianum
Common Name
Holy thistle, lady's thistle, Mary thistle, Marian thistle
Clinical Summary
Derived from the seed, pod, or fruit of the plant. Silymarin, a flavolignan from milk thistle, is used primarily to manage various liver diseases. Placebo-controlled clinical studies show its efficacy in reducing aminotransferases in alcoholic liver disease (9) and conclusions from a systematic review also suggest usefulness of silymarin for liver cirrhosis (19). Studies for other types of hepatic disease are flawed (10) (11). Data from a randomized controlled study indicate benefits of milk thistle supplementation in improving glycemic profile in type II diabetic patients (18). In vitro and animal studies suggest that flavonoids in milk thistle have antioxidant and anticancer effects (7) (8) (12) (16) (17), but there are no clinical data on survival or quality of life.
One case of toxicity (sweating, nausea, vomiting, and weakness) has been reported from use of milk thistle (5). Milk thistle inhibits cytochrome p450 3A4 (4). This may result in increased levels of medications that are metabolized via this pathway.
Purported uses
Alcoholism
Cancer prevention
Cirrhosis
Drug-induced hepatotoxicity
Food poisoning
Hepatitis
Indigestion
Liver disease
Constituents
Flavolignan: 1.5% silymarin; a mixture of three compounds silybinin, silidyanin, and silychristin. Also dehydrosilybin, siliandrin, silybinome, and silyhermin
Tocopherol sterols: Cholesterol, capesterol, stigmasterol, and sitosterol
Other constituents: Taxifolin, quercetin, dihydrokaempferol, kaempferol, apigenin, naringin, eriodyctiol, chrysoeriol, linoleic acid, palmitic acid
(1)
Mechanism of Action
Milk thistle provides hepatocellular protection by stabilizing hepatic cell membranes. It alters the structure of the outer cell membrane of the hepatocytes in such a way as to prevent the penetration of the liver toxins into the interior of the cell. The stimulation effect on nucleolar polymerase A results in an increase in ribosomal protein synthesis, and thus increases the regenerative ability of the liver and the formation of new hepatocytes. Other actions include interruption of enterohepatic recirculation of toxins and regeneration of damaged hepatocytes
(2). An animal study performed in rats demonstrated a reduction in kidney damage following administration of cisplatin without diminished anti-tumor activity
(7). Other studies indicate the flavonoids in milk thistle have anticancer effects by inducing G1 and S phase arrest in cells
(8). Anecdotal data suggests that milk thistle may prevent liver damage from hepatotoxic medications including butyrophenones, phenothiazines, and phenytoin
(6).
Pharmacokinetics
Following oral administration, milk thistle is poorly absorbed from the gastrointestinal tract with a bioavailability of approximately 23-47%. Peak plasma concentrations occur within 2-4 hours
(3). Milk thistle inhibits cytochrome p450 isoenzyme 3A4 and has an elimination half-life of approximately 4 hours. 30-40% of administered dose is recoverable from the bile as both glucuronide or sulfate conjugates and 2-5% is excreted in the urine
(4).
Adverse Reactions
Common: Diarrhea caused by mild laxative effect, uterine and menstrual stimulation.
Case report: One report of a patient who experienced intermittent episodes of sweating, nausea, vomiting, diarrhea, abdominal pain, weakness and collapse that resolved after discontinuation of supplement.
(5)
Herb-Drug Interactions
Cytochrome P-450 3A4: Milk thistle has been shown to inhibit cytochrome P-450 3A4
(4). However, conflicting data indicate no such effects
(13) (14).
According to another study, consumption of milk thistle did not reduce levels of indinavir, an AIDS drug
(15).
Lab Interactions
Liver function tests may be altered. Reduced aminotransferases.
References
- Bissett N, et al. Herbal Drugs and Phytopharmaceuticals. New York: Medpharm, CRC Press; 1994.
- Blumenthal M. Herbal Medicine, Expanded Commission E Monographs, 1st ed. Austin: American Botanical Council; 2000.
- Schandalik R, Perucca E. Pharmacokinetics of silybin following oral administration of silipide in patients with extrahepatic biliary obstruction. Drugs Exp Clin Res 1994;20:37-42.
- Venkataramanan R, et al. Milk thistle, a herbal supplement, decreases the activity of CYP3A4 and uridine diphosphoglucoronosyl transferase in human hepatocyte cultures. Drug Metab Dispos 2000;28:1270-3.
- Adverse Drug Reactions Advisory Committee. An adverse reaction to the herbal medication milk thistle (Silybum marianum). Med J Aust 1999;170:218-9.
- Brinker F. Herb Contraindications and Drug Interactions, 2nd ed. Sandy (OR): Eclectic Med; 1998.
- Kohno H, et al. Silymarin, a naturally occurring polyphenolic antioxidant flavonoid, inhibits azoxymethane-induced colon carcinogenesis in male F344 rats. Int J Cancer 2002;101:461-8.
- Tyagi A, et al. Antiproliferative and apoptotic effects of silibinin in rat prostate cancer cells. Prostate 2002 ;53:211-217.
- Feher J, et al. Liver-protective action of silymarin therapy in chronic alcoholic liver diseases. Orv Hetil 1989;130:2723-7.
- Salmi HA, et al.Effect of Silymarin on chemical, functional, and morphological alterations of the liver: a double blind study. Scand J Gastroenterol 1982;17:517-21.
- Ferenci P, et al. Randomized controlled trial of silymarin treatment in patients with cirrhosis of the liver. J Hepatol 1989;1:105-13.
- Thelen P, Wuttke W, Jarry H, Grzmil M, Ringert RH. Inhibition of telomerase activity and secretion of prostate specific antigen by silibinin in prostate cancer cells. J Urol. 2004 May;171(5):1934-8.
- Gurley B, Hubbard MA, Williams KD, et al. Assessing the clinical significance of botanical supplementation on human cytochrome P450 3A activity: comparison of a milk thistle and black cohosh product to rifampin and clarithromycin. J Clin Pharmacol. 2006 ;46(2):201-13.
- Fuhr U, Beckmann-Knopp S, Jetter A, et al. The effect of silymarin on oral nifedipine pharmacokinetics. Planta Med 2007;73(14):1429-35.
- Mills E, Wilson K, Clarke M, et al. Milk thistle and indinavir: a randomized controlled pharmacokinetics study and meta-analysis. Eur J Clin Pharmacol. 2005;61(1):1-7.
- Ramasamy K and Agarwal R. Multitargeted therapy of cancer by silymarin. Cancer Lett 2008 May 8.
- Verschoyle RD, Greaves P, Patel K, et al. Evaluation of the cancer chemopreventive efficacy of silibinin in genetic mouse models of prostate and intestinal carcinogenesis: relationship with silibinin levels. Eur J Cancer 2008 ;44(6):898-906.
- Huseini HF, Larijani B, Heshmat R, et al. The efficacy of Silybum marianum (L.) Gaertn. (silymarin) in the treatment of type II diabetes: a randomized, double-blind, placebo-controlled, clinical trial. Phytother Res 2006;20(12):1036-9.
- Saller R, Brignoli R, Melzer J, Meier R. An updated systematic review with meta-analysis for the clinical evidence of silymarin.Forsch Komplementmed 2008;15(1):9-20.
