Milk Thistle (Silybum marianum), Silymarin
  
Milk Thistle (Silybum marianum), Silymarin
Background
Milk thistle has been used medicinally for over 2000 years, most commonly for the treatment of liver and gallbladder disorders. A flavonoid complex called silymarin can be extracted from the seeds of milk thistle, and is believed to be the biologically active component. The terms "milk thistle" and "silymarin" are often used interchangeably.
Milk thistle products are popular in Europe and the United States for various types of liver disease. Although numerous human trials have been published, most studies have not been well designed or reported.
Synonyms
Bull thistle, cardo blanco, Cardui mariae fructus , Cardui mariae herba , Cardum marianum L., Carduus marianus L ., Chardon-Marie, Emetic root, Frauendistel, Fructus Silybi mariae , fruit de chardon Marie, heal thistle, Holy thistle, Isosilibinin, Kanger, Kocakavkas, Kuub, Lady's thistle, Marian thistle, mariana mariana, Mariendistel, Marienkrörner, Mary thistle, mild thistle, milk ipecac, pig leaves, royal thistle, shui fei ji, silidianin, Silybi mariae fructus , silybin, silybinin, silychristin, silymarin, snake milk, sow thistle, St. Mary's thistle, Venue thistle, variegated thistle, wild artichoke.
Evidence
These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.
Uses based on scientific evidenceGrade*Cirrhosis
Multiple studies from Europe suggest benefits of oral milk thistle for cirrhosis. In experiments up to 5 years long, milk thistle has improved liver function and decreased the number of deaths that occur in cirrhotic patients. Although these results are promising, most studies have been poorly designed. Better research is necessary before a strong recommendation can be made.
B
Chronic hepatitis (liver inflammation)
Several studies of oral milk thistle for hepatitis caused by viruses or alcohol report improvements in liver tests. However, most studies have been small and poorly designed. More research is needed before a recommendation can be made.
C
Acute viral hepatitis
Research on milk thistle for acute viral hepatitis has not provided clear results, and milk thistle cannot be recommended for this potentially life-threatening condition.
C
Amanita phalloides mushroom poisoning
Milk thistle has been used traditionally to treat Amanita phalloides mushroom poisoning, and several animal studies and isolated human cases have suggested possible benefits. However, there are not enough reliable studies in humans to support this use of milk thistle.
C
Cancer prevention
There are early reports from laboratory experiments that the chemicals silymarin and silibinin in milk thistle reduce the growth of human breast, cervical, and prostate cancer cells. There is also one report of a patient with liver cancer who improved following treatment with milk thistle. However, this research is too early to draw firm conclusions, and effects have not been shown in high-quality human trials.
C
Liver damage from drugs or toxins
Several studies suggest possible benefits of milk thistle to treat or prevent liver damage caused by drugs or toxic chemicals. Results of this research are not clear, and most studies have been poorly designed. Therefore, there is not enough scientific evidence to recommend milk thistle for this use.
C
High cholesterol
Although animal and laboratory research suggests cholesterol-lowering effects of milk thistle, human studies have provided unclear results. Further studies are necessary before a recommendation can be made.
C
Diabetes (in patients with cirrhosis)
A small number of studies suggest possible improvements of blood sugar control in cirrhotic patients with diabetes. However, there is not enough scientific evidence to recommend milk thistle for this use.
C
* Key to grades
A: Strong scientific evidence for this use;
B: Good scientific evidence for this use;
C: Unclear scientific evidence for this use;
D: Fair scientific evidence against this use (it may not work);
F: Strong scientific evidence against this use (it likely does not work).
Uses based on tradition or theory
The below uses are based on tradition or scientific theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.
Amiodarone toxicity reactions, asthma, bleeding, bronchitis, cough, diabetic nerve pain, dyspepsia, gallstones, hemorrhoids, liver "cleansing," liver cancer, malaria, menstrual problems, plague, prostate cancer, psoriasis, radiation sickness, skin cancer, snakebites, spleen disorders, sunscreen, varicose veins.
Dosing
The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.
Standardization
Standardization involves measuring the amount of certain chemicals in products to try to make different preparations similar to each other. It is not always known if the chemicals being measured are the "active" ingredients. Milk thistle is often standardized to contain 70-80% silymarin. Silymarin is a mixture of three flavonolignans: silybin, silidianin, and silychristin. Despite standardization, different preparations and brands may have different effects in the body. Silipide® (IdB 1016) is a special milk thistle product that is designed to be absorbed better into the body. Doses of Silipide® are measured by "silybin equivalents."
One study analyzing stability of milk thistle tincture found a shelf life of approximately 3 months.
Adults (18 years and older)
Cirrhosis : Silymarin (Legalon®) 280mg-420mg per day divided into 2-3 doses. Up to 450mg daily divided into three doses has been studied.
Hepatitis (chronic) : Silipide® (IdB 1016) 160-480mg per day in silybin equivalents, or silymarin (Legalon®) 420mg daily divided into three doses.
Hepatitis (acute, viral) : Silymarin 420mg daily divided into three doses.
Drug/toxin-induced hepatotoxicity : Silymarin (Legalon®) 280-420mg daily divided into three doses. Up to 800mg daily has been studied.
High cholesterol : Silymarin 420mg per day has been studied.
Diabetes (insulin-dependent) associated with cirrhosis : Silymarin (Legalon®) 230-600mg per day has been studied. Effectiveness and safety have not been proven.
Children (younger than 18 years)
There is not enough scientific data to recommend milk thistle for use in children.
Safety
The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.
Allergies
People with allergies to plants in the aster family ( Compositea, Asteraceae ) or to daisies, artichokes, common thistle, kiwi, or to any of milk thistle's constituents (silibinin, silychistin, silydianin, silymonin, siliandrin) may have allergic reactions to milk thistle. Anaphylactic shock (a severe allergic reaction) from milk thistle tea or tablets has been reported in several patients.
Side Effects and Warnings
Milk thistle appears to be well tolerated in recommended doses for up to 6 years. Some patients in studies have experienced stomach upset, headache, and itching. There are rare reports of appetite loss, gas, heartburn, diarrhea, joint pain, and impotence with milk thistle use. One person experienced sweating, nausea, stomach pain, diarrhea, vomiting, weakness and collapse after taking milk thistle. This reaction may have been due to an allergic reaction, and improved after 24 hours. High liver enzyme levels in one person taking milk thistle returned to normal after the person stopped taking the herb.
In theory, milk thistle may lower blood sugar levels. Caution is advised in patients with diabetes or hypoglycemia, and in those taking drugs, herbs, or supplements that affect blood sugars. Serum glucose levels may need to be monitored by a healthcare provider, and medication adjustments may be necessary.
Pregnancy and Breastfeeding
Milk thistle has been used historically to improve breast milk flow, and two brief studies of milk thistle in pregnant women reported no side effects. However, there is not enough scientific evidence to support the safe use of milk thistle during pregnancy or breastfeeding at this time.
References
1. Agoston M, Orsi F, Feher E, Hagymasi K, Orosz Z, Blazovics A, Feher J, Vereckei A. Silymarin and vitamin E reduce amiodarone-induced lysosomal phospholipidosis in rats. Toxicology 2003;190(3):231-241.
2. Allain H, Schuck S, Lebreton S, et al. Aminotransferase levels and silymarin in de novo tacrine-treated patients with Alzheimer's disease. Dement Geriatr Cogn Disord 1999;10(3):181-185.
3. Bettini R, Gorini M. [Use of ursodeoxycholic acid combined with silymarin in the treatment of chronic ethyl-toxic hepatopathy] Clin Ter. 2002 Sep-Oct;153(5):305-307
4. Bilia AR, Bergonzi MC, Gallori S, Mazzi G, Vincieri FF. Stability of the constituents of Calendula, milk-thistle and passionflower tinctures by LC-DAD and LC-MS. J Pharm Biomed Anal 2002;30(3):613-24.
5. Breschi MC, Martinotti E, Apostoliti F, Nieri P. Protective effect of silymarin in antigen challenge- and histamine-induced bronchoconstriction in in vivo guinea-pigs.
6. Buzzelli G, Moscarella S, Giusti A, et al. A pilot study on the liver protective effect of silybinphosphatidylcholine complex (IdB1016) in chronic active hepatitis. Int J Clin Pharmacol Ther Toxicol 1993;31(9):456-460.
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8. DiCenzo R, Shelton M, Jordan K, Koval C, Forrest A, Reichman R, Morse G. Coadministration of milk thistle and indinavir in healthy subjects. Pharmacotherapy. 2003 Jul;23(7):866-70.
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11. Lawrence V, Jacobs B, Dennehy C, et al. Report on milk thistle: effects on liver disease and cirrhosis and clinical adverse effects. Evidence Report/Technology Assessment No. 21 (Contract 290-97-0012 to the San Antonio Evidence-based Practice Center, based at the University of Texas Health Science Center at San Antonio, and The Veterans Evidence-based Research, Dissemination, and Implementation Center, a Veterans Affairs Services Research and Development Center of Excellence). AHRQ Publication No. 01-E025. Rockville, MD: Agency for Healthcare Research and Quality. October 2000.
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13. Lucena MI, Andrade RJ, de la Cruz JP, et al. Effects of silymarin MZ-80 on oxidative stress in patients with alcoholic cirrhosis. Results of a randomized, double-blind, placebo- controlled clinical study. Int J Clin Pharmacol Ther 2002;40(1):2-8.
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15. Marcelli R, Bizzoni P, Conte D, et al. Randomized controlled study of the efficacy and tolerability of a short course of IdB 1016 in the treatment of chronic persistent hepatitis. Eur Bull Drug Res 1992;1(3):131-135.
16. Palasciano G, Portincasa P, Palmieri V, et al. The effect of silymarin on plasma levels of malon-dialdehyde in patients receiving long-term treatment with psychotropic drugs. Curr Ther Res 1994;55(5):537-545.
17. Pares A, Planas R, Torres M, et al. Effects of silymarin in alcoholic patients with cirrhosis of the liver: results of a controlled, double-blind, randomized and multicenter trial. J Hepatol 1998;28(4):615-621.
18. Piscitelli SC, Formentini E, Burstein AH, Alfaro R, Jagannatha S, Falloon J. Effect of milk thistle on the pharmacokinetics of indinavir in healthy volunteers. Pharmacotherapy 2002;22(5):551-6.
19. Salmi HA, Sarna S. Effect of silymarin on chemical, functional, and morphological alterations of the liver. A double-blind controlled study. Scand J Gastroenterol 1982;17(4):517-521.
20. Szilard S, Szentgyorgyi D, Demeter I. Protective effect of Legalon in workers exposed to organic solvents. Acta Med Hung 1988;45(2):249-256.
21. Velussi M, Cernigoi AM, De Monte A, et al. Long-term (12 months) treatment with an anti-oxidant drug (silymarin) is effective on hyperinsulinemia, exogenous insulin need and malondialdehyde levels in cirrhotic diabetic patients. J Hepatol 1997;26(4):871-879.
22. Velussi M, Cernigoi AM, Viezzoli L, et al. Silymarin reduces hyperinsulinemia, malondialdehyde levels, and daily insulin need in cirrhotic diabetic patients. Curr Ther Res 1993;53(5):533-545.
April 01, 2004 
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