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Human/Clinical Studies
There are no published clinical trials of milk thistle or silymarin in patients with cancer. Two published case reports describe the use of milk thistle as either a treatment or an adjunctive therapy in individuals with cancer. One case report describes the use of milk thistle in a 34-year-old woman with promyelocytic leukemia.[1] The investigators administered 800 mg of silymarin during the patient’s maintenance therapy, which consisted of treatment with methotrexate and 6-mercaptopurine. During the 4 months of treatment with silymarin, the patient who previously required intermittent breaks in therapy due to abnormal liver enzyme levels had normal liver enzyme levels with no further interruption of therapy. A second case report describes a 52-year-old man with hepatocellular carcinoma.[2] The patient began taking 450 mg of silymarin per day, and spontaneous regression of the tumor was reported in the absence of initiation of anticancer therapy. These findings have not been reproduced in a clinical trial.
Most clinical trials of milk thistle have been conducted in patients with either hepatitis or cirrhosis. Other studies have investigated milk thistle in patients with hyperlipidemia, diabetes, and Amanita phalloides mushroom poisoning. Eight randomized trials [3-10] have been reported in patients with hepatitis or cirrhosis, and one randomized trial has reported the use of silymarin as a prophylaxis to iatrogenic hepatic toxicity.[11] Endpoints for these trials have included serum levels of bilirubin and/or the liver enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT), as higher levels are an indicator of liver inflammation, damage, or disease. The lowering of these serum levels is a sign of an improving condition. In patients with hepatitis A and B, one clinical trial found silymarin (140 mg daily for 3–4 weeks) resulting in lower levels of AST, ALT, and bilirubin by day 5, compared with a placebo group.[12] In another randomized, placebo-controlled study of patients with viral hepatitis B, silymarin (210 mg daily) had no effect on course of disease or enzyme levels.[6]
In patients with chronic liver disease, a randomized, placebo-controlled study found normalization of serum AST, ALT, and bilirubin levels after 1 month of treatment with silymarin (140 mg 3 times a day) in comparison to treatment with a placebo.[13] In one of the largest observational studies involving 2,637 patients with chronic liver disease, 8-week treatment with 560 mg/day of silymarin resulted in reductions of serum AST, ALT, and gamma-glutamyltranspeptidase ([GGT], a marker of bile duct disease) and a decrease in the frequency of palpable hepatomegaly.[14]
Another published report describes the use of silybin as the only effective antidote in patients with liver damage from Amanita phalloides (Fr.) Link poisoning.[15] Patients were administered doses of 35 to 55 mg/kg body weight, with no reports of adverse events. A recent retrospective review of the treatment for Amanita phalloides poisoning suggests that silymarin continues to be a promising drug in the treatment of this rare mushroom poisoning.[16] The beneficial effect of silymarin on liver histology suggests it has a role in the prevention of hepatitis and/or hepatocellular carcinoma; however, no clinical trials in humans have investigated the use of silymarin for prevention.
Clinical Studies Investigating Silymarin in the Treatment or Prevention of Liver Disease
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Reference Citation
|
Type of Study
|
Type of Disease
|
No. of Patients: Enrolled; Treated; Controla
|
Strongest Benefit Reported
|
| [4] |
Double-blind, placebo-controlled, randomized clinical trial |
Acute and subacute liver disease |
106b; 47; 50 |
Decreased LFTs; improved histology |
| [8] |
Double-blind, placebo-controlled, randomized clinical trial |
Cirrhosis |
170; 87; 83 |
Increased survival |
| [3] |
Phase II randomized open trial |
Viral or alcoholic hepatitis |
60c; 60; 0 |
Reduction in ALT and gamma-glutamyl transpeptidase |
| [6] |
Controlled, randomized trial |
Viral hepatitis B |
52d; 20-silymarin, 20-misoprostol;
12 |
No significant findings |
| [5] |
Double-blind, placebo-controlled, randomized clinical trial |
Alcohol-induced cirrhosis |
200e; 58; 67 |
No significant findings |
| [9] |
Double-blind, placebo-controlled, randomized clinical trial |
Alcohol-induced cirrhosis |
60f; 24; 25 |
Significant increases in erythrocyteglutathione and decreased platelet MDA values; no significant
differences in liver function tests |
| [7] |
Nonrandomized
pilot study
|
Primary biliary cirrhosis |
27; 27; 0 |
No significant findings |
| [10] |
Controlled, randomized trial |
Diabetic patients with cirrhosis |
60; 30; 30 |
Decrease in lipid peroxidation and insulin resistance |
| [11] |
Double-blind, placebo-controlled, randomized clinical trial |
Patients treated with silymarin as a prophylaxis to psychotropic drug-induced hepatic damage |
60; 15-psychotropic drug+silymarin; 15-silymarin alone; 15-psychotropic drug+placebo; 15-placebo alone |
Silymarin effective at reducing hepatotoxicity associated with psychotropic drug use |
|
ALT = alanine aminotransferase; LFT = liver function test
; No. = number.
|
|
aNumber of patients treated plus number of patients controlled may not equal number of patients enrolled; number of patients enrolled = number of patients initially recruited/considered by the researchers who conducted a study; number of patients treated = number of enrolled patients who were administered the treatment being studied AND for whom results were reported; historical control subjects are not included in number of patients enrolled.
|
|
bNine patients were excluded from the final analysis (seven patients missed appointments, and two patients were missing data requirements).
|
|
cStudy investigated dose-response relationships. Patients were randomly assigned to receive 80 mg 2 times a day (n = 20), 120 mg 2 times a day (n = 20), or 120 mg 3 times a day (n = 20). The effective dose was 120 mg 2 times a day and 120 mg 3 times a day.
|
|
dPatients were randomly assigned to the misoprostol and silymarin groups. Twelve nonrandomized patients served as controls.
|
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eFifteen patients were lost to follow-up, 18 patients were deceased, and 42 patients withdrew from the study (adverse events, noncompliance, and voluntary withdrawal).
|
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fEleven patients did not complete the trial (voluntary withdrawal, disease progression, and one adverse event).
|
References
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Invernizzi R, Bernuzzi S, Ciani D, et al.: Silymarine during maintenance therapy of acute promyelocytic leukemia. Haematologica 78 (5): 340-1, 1993 Sep-Oct.
[PUBMED Abstract]
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Grossmann M, Hoermann R, Weiss M, et al.: Spontaneous regression of hepatocellular carcinoma. Am J Gastroenterol 90 (9): 1500-3, 1995.
[PUBMED Abstract]
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Vailati A, Aristia L, Sozzé E, et al.: Randomized open study of the dose-effect relationship of a short course of IdB 1016 in patients with viral or alcoholic hepatitis. Fitoterapia 64 (3), 219-28, 1993.
-
Salmi HA, Sarna S: Effect of silymarin on chemical, functional, and morphological alterations of the liver. A double-blind controlled study. Scand J Gastroenterol 17 (4): 517-21, 1982.
[PUBMED Abstract]
-
Parés 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 28 (4): 615-21, 1998.
[PUBMED Abstract]
-
Flisiak R, Prokopowicz D: Effect of misoprostol on the course of viral hepatitis B. Hepatogastroenterology 44 (17): 1419-25, 1997 Sep-Oct.
[PUBMED Abstract]
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Angulo P, Patel T, Jorgensen RA, et al.: Silymarin in the treatment of patients with primary biliary cirrhosis with a suboptimal response to ursodeoxycholic acid. Hepatology 32 (5): 897-900, 2000.
[PUBMED Abstract]
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Ferenci P, Dragosics B, Dittrich H, et al.: Randomized controlled trial of silymarin treatment in patients with cirrhosis of the liver. J Hepatol 9 (1): 105-13, 1989.
[PUBMED Abstract]
-
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 40 (1): 2-8, 2002.
[PUBMED Abstract]
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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 26 (4): 871-9, 1997.
[PUBMED Abstract]
-
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. Current Therapeutic Research 55 (5): 537-45.
-
Magliulo E, Gagliardi B, Fiori GP: [Results of a double blind study on the effect of silymarin in the treatment of acute viral hepatitis, carried out at two medical centres (author's transl)] Med Klin 73 (28-29): 1060-5, 1978.
[PUBMED Abstract]
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Trinchet JC, Beaugrand M, Callard P, et al.: Treatment of alcoholic hepatitis with colchicine. Results of a randomized double blind trial. Gastroenterol Clin Biol 13 (6-7): 551-5, 1989.
[PUBMED Abstract]
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Albrecht M, Frerick H, Kuhn U, et al.: Therapy of toxic liver pathologies with Legalon®. Z Klin Med 47: 87-92, 1992.
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Hruby K, Csomos G, Fuhrmann M, et al.: Chemotherapy of Amanita phalloides poisoning with intravenous silibinin. Hum Toxicol 2 (2): 183-95, 1983.
[PUBMED Abstract]
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Enjalbert F, Rapior S, Nouguier-Soulé J, et al.: Treatment of amatoxin poisoning: 20-year retrospective analysis. J Toxicol Clin Toxicol 40 (6): 715-57, 2002.
[PUBMED Abstract]
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