Milk Thistle Silybum marianum

In laboratory tests a range of effects have been demonstrated including:

• silymarin reduced the harmful actions on the liver of hepatotoxins such as carbon tetrachloride, thioacetamide, a-amanitin and phalloidin.
• a protective effect against carbon tetrachloride induced liver damage in rats.
• a reduction of the prolongation of hexobarbital sleeping time produced by carbon tetrachloride. This is a common method for assessing protective effects on the liver against the effects of chemical toxins. Hexobarbital causes a consistent pattern of sleep in the unfortunate experimental animals, and any change in sleep time reflects some disturbance of the liver ability to metabolize the sedative. An increase in sleeping time implies impairment of the livers ability to metabolize the hexobarbital. Carbon tetrachloride produces such a change. When Milk Thistle is added the increase in sleeping time normally produced by the carbon tetrachloride is reduced by up to 60%, suggesting that the herb is protecting liver function from the toxin.
• prevention of the inhibition of hepatic metabolism of p-oxyphenylpyruvic acid (OH) caused by carbon tetrachloride. This chemical is metabolized exclusively in the liver during the degradation of tyrosine. Any unmetabolized OH is excreted in the urine, thus, its level in the urine increases following the administration of a liver toxin. Substances that counteract the toxin bring urine OH levels back to normal. Histological studies of the liver reveal how much structural damage has occurred. The histological finds from carbon tetrachloride poisoning is very similar to that of hepatitis, and it increases OH levels in the urine dramatically. Milk Thistle significantly counteracts the effects of the carbon tetrachloride, so much so, that the results are almost indistinguishable from controls.
• carbon tetrachloride raises serum levels of enzymes such as glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT) and sorbitol dehydrogenase (SDH), but under treatment with silymarin these increases were significantly diminished.
• i.p. injection of D-galactosamine (GalN) to rats causes an acute hepatitis that is similar to viral hepatitis in humans. Silymarin has a protective action against such liver lesions.
• poisoning with DL-ethionine leads to accumulation of triglycerides in the liver of rats. Silymarin inhibited such increases.
• it counteracted the effects of cadmium, an pollutant that accumulates in human tissues over time, causing hypertension, liver, kidney & neural damage, and hemorrhagic necrosis of the liver and testes. Milk Thistle pretreatment almost completely prevented death and necrosis whilst reducing nerve damage.
• the hepatotoxic salts of such rare earth metals as praseodymium, indium and cerium cause necrosis and fatty degeneration in the liver. Pretreatment with Milk Thistle reduces or prevented this altogether. The researchers suggest a number of possible mechanism:
  • that it facilitates a more rapid elimination of the metals from the body
  • it stimulates the formation of metal-binding proteins which detoxify the metals
  • it may inhibit the binding of these metals with cells at receptor sites
• thioacetamide is a hepatotoxin which causes a development of conditions in rats that are similar to human liver. When silymarin was given with the poison in the feed, animals lost less weight and their survival times increased. Injecting thioacetamide increases the serum levels of the enzymes GPT, GOT, SDH, and glutamate dehydrogenase, which were also prevented by silymarin.
• it partially counteracts alcohol damage to the liver.
• mitochondrial changes caused by ethanol are almost completely prevented by silymarin.
• ethanol increases malondialdehyde formation and spontaneous chemiluminescence in the rat liver. Silymarin given prior to the ethanol suppresses both effects completely.
• Milk thistle has an extraordinary hepato-protective effect, blocking damage from the toxins of the Avenging Angel mushroom Amanita phalloides, phalloidin and a-amanitin. It has both protective and curative effects on survival time and death rate of mice after administration of a-amanitin, also antagonizing the toxicity of phalloidin. It inhibits the loss of weight observed in poisoned animals. Animals fed sub-lethal doses of amanitine lose weight very rapidly and gain it back very slowly. Animals fed a combination of amanitine and Milk Thistle lose weight much more slowly and gain it back much more rapidly. It greatly increased life-span in the poisoned animals. When administered later than 20 minutes after poisoning, it was no longer possible to detect any anti-hepatotoxic effect, suggesting that silymarin prevents penetration of the toxins by competing for the same receptor sites on cell membranes.
• it has blocked the hepatotoxic effects of some viruses on laboratory animals.
• silybin enhances ribosomal RNA synthesis as a result of the stimulation of DNA-dependent RNA-polymerase A.

Such impressive effect upon toxic damage to liver cells is probably due to a combination of two main mechanisms:

1. an alteration of cell membranes, such that only small amounts of toxins may penetrate into the cell
2. an acceleration of protein synthesis, thus stimulating cell regeneration.

Mechanisms that may explain the inhibition of ethanol induced changes by silymarin include scavenging of free radicals and increases levels of both reduced and oxidized glutathione.

 

This remarkable herb has therapeutic effects, not only in toxic and metabolic liver damage, but also in liver diseases. Clinical trials have replicated the laboratory evidence of its ability to reverse many liver disorders from acute viral hepatitis to cirrhosis. It stimulates hepatocytes to replace diseased tissue. The liver can regenerate but this innate ability slows or stops altogether when infected or damaged by alcohol or other drugs.

Clinical indicators of improvement in the health of the liver include:

• assessment of general condition, appetite, epigastric discomfort, enlargement and consistency of the liver,
• blood plasma tests.
• changes in membrane permeability are deduced from measurements of glutamic-pyruvic transaminase (GPT), glutamic-oxaloacetic transaminase (GOT), lactic acid dehydrogenase (LDH), sorbitol dehydrogenase, and gamma glutamyl transpeptidase (GGT)
• membranotropic properties and the excretory functions of the liver are assessed through measurements of bilirubin, LAP, gamma-GT, alkaline phosphatase, and bromethalein
• synthesizing ability is assessed through prothrombin, triglycerides, and cholesterin
• measurements of mesenchymic activity include clotting factors, alpha, beta and gamma globulin, immunoglobulins IgA, and IgG.

Clinical studies have demonstrated its value in therapy:
 

• One study involved 129 patients and a control group of 56 for a period of about one month. Their conditions included toxic-metabolic liver damage, fatty degeneration of the liver for various reasons, and chronic hepatitis. Milk Thistle markedly changed both subjective and objective symptoms, brought a return to normal enzymatic activities, and improved digestive disorders. Enlarged livers diminished substantially in volume. A 50% regression in pathological symptoms, versus 25% in controls, occurred. No cases of intolerance, side effects, or allergic reactions were observed.
• in a double-blind study, serum bilirubin, GOT, and GPT in 28 patients treated with silymarin were compared with those in 29 patients treated with a placebo. The silymarin treated group were more improved than those in the control group after the 5th day of treatment. The number of patients having attained normal values after 3 weeks' treatment was higher in the silymarin-treated group than in the control group.
• Toxic damage was tested in 33 patients treated with silymarin. The parameters GOT, GPT, and g-glutamyltranspeptidase (g-GTP) were improved significantly by silymarin, sometimes returning to normal in a much shorter time than in the control group.
• 106 patients with liver disease, mostly induced by alcohol, were selected on the basis of elevated serum transaminase levels and randomly allocated into the silymarin-treated and control groups. Decreases of serum GPT and GOT in the treated group were statistically significant over those of the controls.
• in chronic liver disease, silymarin prevented the decrease of seralbumin from 3 months of therapy to the end of the study. The histopathological findings of focal necrosis and fibrosis were also much improved. Silymarin proved to be beneficial in the parameters of parenchymal disorders, intralobular mesenchymal reaction, and fibrosis.
• Long-term treatment with silymarin on chronic hepatopathies caused by psycho-pharmaceuticals resulted in significant improvements in the liver function parameters such as GOT, GPT, and BSP during treatment.
• two cases of food poisoning caused by flagellates responded very rapidly to Milk Thistle, showing subjective, biochemical and histological improvements.

This wonderful plant is effective in many types of liver disease. The clinical findings highlight such problems as:

• toxic/metabolic liver disease (including both alcohol & drug induced forms),
• acute viral hepatitis,
• chronic-persistent hepatitis,
• chronic-aggressive hepatitis,
• cirrhosis of the liver,
• fatty degeneration of the liver

The best results are found in toxic-metabolic hepatitis and cirrhosis. It shortens the course of viral hepatitis and minimizes post hepatitis complications and also protects the liver against problems resulting from liver surgery. This all goes to make it is an excellent remedy to use in the prevention and treatment of many liver disorders. The earlier treatment is commenced the better the prognosis, but effective treatment is possible at virtually every stage. Milk Thistle arrests the course of these diseases as well as stimulating hepatocyte regeneration.

Over time, complete restoration of the liver is possible, with regeneration at four times the normal rate. Many psychopharmacologic drugs and agents are detoxified by the liver. The cumulative effect of drug use on the liver can be devastating. Thus Milk Thistle should be taken by people who want or need to take such drugs. It has been shown to prevent liver damage caused by such drugs.

This all suggest that taking the herb regularly will provide protection to either the sick or healthy liver during the course of daily life. By stabilizing cell membranes, by encouraging the regeneration of cells destroyed during the normal detoxification process, Milk Thistle provides the liver and the body with the ability to cope with the deleterious effects of daily encounters with air- water- and food-borne toxins. Using Milk Thistle daily, and combining it with other hepatics, offers an effective and safe approach to liver protection.

Hikino & Kiso (1988) Natural Products for Liver Diseases. In "Economic and Medicinal Plant Research Vol.2." (Wagner, Hikino & Farnsworth) Academic Press, London.

Murray, M.T. (1995) The Healing Power of Herbs. Prima Publishing, Rocklin.

Vogel, G. (1977) Natural Substances with Effects on the Liver. In "New Natural Products and Plant Drugs with Pharmacological, Biological or Therapeutic Activity." (Wagner & Wolff) Springer-Verlag, Heidelberg.
 

Clinical Trials (26 available from PubMed)

Prospective open-label drug interaction study found milk thistle in commonly administered dosages should not interfere with indinavir therapy in patients infected with the human immunodeficiency virus. Piscitelli 2002

6 months of 420 mg/d silymarin, in a double blind study of cirrhotic patients, restored the diminished superoxide dismutase activity of erythrocytes and lymphocytes [Article in Hungarian] Muzes 1990

A 6 month double blind clinical trial with 36 patients showed normalization of serum bilirubin, aspartate aminotransferase and alanin-aminotransferase [Article in Hungarian] Feher 1989

4-year survival rate was 58% in treatment group (140 mg silymarin 3 times daily) vs. 39% in placebo group in a double blind study of 170 cirrhosis patients Ferenci 1989

14 type-II hyperlipidaemic outpatients treated with 420 mg Legalon daily for three months had decreased cholesterol and apolipoprotein Somogyi 1989

Liver function tests and the platelet counts improved for 30 workers exposed to organic solvents taking Legalon compared with the 19 left without treatment Szilard 1988