MILK THISTLE (Silybum marianum, Carduus marianum)

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MILK THISTLE (Silybum marianum, Carduus marianum) JoAnn Guest Apr 26, 2005

17:08 PDT

 

 

CLINICAL SUMMARY

Derived from the seed, pod, or fruit of the plant. Milk thistle is used

primarily to manage various liver diseases. Placebo-controlled clinical

studies show efficacy in reducing aminotransferases in alcoholic liver

disease, but studies in other types of hepatic disease have been flawed.

 

 

Animal models suggest that flavonoids in milk thistle have antioxidant

and anticancer effects. Flavonoids isolated from milk thistle have been

shown to inhibit colon and prostate cancer cells in rats. To date there

is no evaluation of survival or quality of life.

One case report regarding toxicity (sweating, nausea, vomiting, and

weakness) was uncovered in the literature, but there are no other

reports of toxicity or significant adverse events. Milk thistle inhibits

cytochrome p450 3A4. Therefore, increased levels of medications

metabolized via this enzyme may occur.

 

SCIENTIFIC NAME

Silybum marianum, Carduus marianum. Also known as: Holy thistle, lady’s

thistle, Mary thistle, Marian thistle

 

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 interior of the cell.

 

The stimulation effect on nucleolar polymerase A results in an increase

in ribosomal protein synthesis, and thus increase 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.

 

An animal study performed in rats demonstrated a reduction in kidney

damage following administration of cisplatin without diminished

anti-tumor activity.

 

Other studies indicate the flavonoids in milk thistle has anticancer

effects by inducing G1 and S phase arrest in cells. Anecdotal data

suggests that milk thistle may prevent liver damage from hepatotoxic

medications including butyrophenones, phenothiazines, and phenytoin. (2)

(6) (7) (

 

 

PHARMACOKINETICS

Following oral administration, milk thistle is poorly absorbed from the

GI tract with a bioavailability of approximately 23-47%. Peak plasma

concentrations occur within 2-4 hours. 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. (3)

(4)

 

DRUG INTERACTIONS

Cytochrome P-450 3A4: Milk thistle has been shown to inhibit cytochrome

P-450 3A4. Although no interactions have been reported, inhibition of

drug metabolism may occur for several agents (e.g. ketoconazole,

itraconazole, erythromycin, triazolam). (4)

LAB INTERACTIONS

Liver function tests may be altered. Reduced aminotransferases.

LITERATURE SUMMARY AND CRITIQUE

The majority of human studies with milk thistle have been performed for

the treatment of alcoholic hepatitis.

 

 

Feher J, et al. Liver-protective action of silymarin therapy in chronic

alcoholic liver diseases. Orv Hetil 1989;130: 2723-7.

The effects of silymarin therapy on liver function tests, serum

procollagen III, peptide level and liver disease were studied in 36

patients with chronic alcoholic liver disease in a six month

double-blind clinical trial.

During silymarin treatment, serum bilirubin, aspartate aminotransferase

and alanine-aminotransferase values were normalized, while

gamma-glutamyl transferase activity and procollagen III peptid levels

decreased.

 

The changes were significant, and there was a significant difference

between post-treatment values of the two groups, as well. The

histological alterations showed an improvement in the silymarin group,

while remaining unchanged in the placebo group. These results suggest

that silymarin exerts hepato-protective activity and is able to improve

liver function in alcoholic patients.

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.

 

Ninety-seven patients with alcoholic liver disease and persistently

abnormal liver function tests following at least 1 month of abstinence

from alcohol were enrolled in a placebo-controlled trial. After 4 months

of treatment, AST and ALT levels decreased by 30% and 41% with silymarin

and increased 5% and 3% with placebo, respectively. The study did not

monitor abstinence from alcohol. No changes in bilirubin were noted.

 

Ferenci P, et al. Randomized controlled trial of silymarin treatment in

patients with cirrhosis of the liver. J Hepatol 1989;1:105-13.

To determine the effect of silymarin on the outcome of patients with

cirrhosis, a double-blind, prospective, randomized study was performed

on 170 patients with cirrhosis. Eighty-seven received 140 mg silymarin

three times a day and 83 received placebo. Analysis of subgroups

indicated that treatment was effective in patients with alcoholic

cirrhosis.

 

REFERENCES

(1) Bissett N, et al. Herbal Drugs and Phytopharmaceuticals. New York:

Medpharm, CRC Press; 1994.

(2) Blumenthal M. Herbal Medicine, Expanded Commission E Monographs, 1st

ed. Austin: American Botanical Council; 2000.

(3) 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.

(4) 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.

(5) Adverse Drug Reactions Advisory Committee. An adverse reaction to

the herbal medication milk thistle (Silybum marianum). Med J Aust

1999;170:218-9.

(6) Brinker F. Herb Contraindications and Drug Interactions, 2nd ed.

Sandy (OR): Eclectic Med; 1998.

(7) Kohno H, et al. Silymarin, a naturally occurring polyphenolic

antioxidant flavonoid, inhibits azoxymethane-induced colon

carcinogenesis in male F344 rats.Int J Cancer. 2002 Oct 10;101(5):

461-8.

( Tyagi A, et al. Antiproliferative and apoptotic effects of silibinin

in rat prostate cancer cells.Prostate. 2002 Nov 1;53(3):211-217.

 

 

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