Milk Thistle Abstracts

Title: PHYTOGENIC AGENTS IN THE THERAPY OF LIVER DISEASE

Abstract: Plant extracts have been used by traditional medical

practitioners for the treatment of liver disorders for centuries. This

article reviews the clinical trials carried out with thirteen plants and

their constituents in patients with liver disease, including acute viral

hepatitis, chronic viral hepatitis, chronic cholecystitis, alcoholic Liver

disease and mushroom poisoning. There is considerable scientific evidence

that phytogenic agents can have significant beneficial effects on liver

dysfunction and the course of liver disease. At present, silymarin has the

most proven overall clinical hepatoprotective effects, although

glycyrrhizin appears to be more beneficial in chronic viral hepatitis. With

the high worldwide incidence of viral hepatitis, further study of isolated

phytochemicals is important in relation to their potential antiviral

activity against the different hepatitis viruses.

Author: THABREW MI, UNIV LONDON KINGS COLL, SCH MED & DENT, INST LIVER

STUDIES, BESSEMER RD, LONDON SE5 9PJ, ENGLAND Source: PHYTOTHERAPY RESEARCH

1996 SEP;10(6):461-467

Title: A pilot study on the liver protective effect of

silybin-phosphatidylcholine complex (IdB1016) in chronic active hepatitis.

Author: Buzzelli G; Moscarella S; Giusti A; Duchini A; Marena C; Lampertico

M; Source: Int J Clin Pharmacol Ther Toxicol Date of Pub: 1993 Sep Issue: 9

Volume: 31 Pagination: 456-60

Abstract: In order to assess the liver protective activity and the

antioxidant properties of a new silybin complex (IdB1016), we carried out a

short-term pilot study on 20 patients with chronic active hepatitis (CAH),

randomly assigned to 240 mg of silybin b.i.d. (10 patients, 4 m/6 f, mean

age: 50 years) or placebo (10 patients, 2 m/8 f, mean age: 55 years). Blood

samples were collected before and after 7 days of treatment for liver

function tests (LFTs), malonaldehyde (MDA) as an index of lipid

peroxidation, and copper (Cu) and zinc (Zn), two trace elements involved in

protecting cells against free radical-mediated lipid peroxidation. In the

treated group, there was a statistically significant reduction of mean (+/-

SEM) serum concentrations of aspartate aminotransferase (AST) from 88.0

(+/- 13.3) to 65.9 (+/- 7.5) u/l, (p < 0.01), of alanine aminotransferase

(ALT) from 115.9 (+/- 12.9) to 82.5 (+/- 10.6) u/l (p < 0.01), of

gamma-glutamyltranspeptidase (gamma-GT) from 51.4 (+/- 9.3) to 41.3 (+/-

4.2) u/l (p < 0.02) and of total bilirubin (TB) from 0.76 (+/- 0.08) to

0.53 (+/- 0.04) mg/dl (p < 0.05). Alkaline phosphatase (AP) fell slightly

from 143.4 (+/- 6.4) to 137.5 (+/- 7.8) u/l. There were no significant

changes in MDA, Cu or Zn serum concentrations. These results show that

IdB1016 may improve LFTs related to hepatocellular necrosis and/or

increases membrane permeability in patients affected by CAH.

Abstract By: Author

Address: Istituto di Clinica Medica II, Universitá degli Studi di Firenze,

Italy.

Title: [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)]

Author: Magliulo E; Gagliardi B; Fiori GP; Issue/Part/Supplement: 28-29

Source: Med Klin

Date of Pub: 1978 Jul 14 Volume: 73 Pagination: 1060-5

Abstract: In a double blind study carried out under standard conditions at

two treatment centers silymarin, 2 sugar-coated tablets 70 mg three times

daily, showed a definite therapeutic influence on the characteristic

increased serum levels of bilirubin, GOT and GPT associated with acute

viral hepatitis. The above mentioned values in 28 patients treated with

silymarin were compared with those in 29 patients treated with placebo. The

laboratory parameters in the silymarin group regressed more than in the

placebo group after the 5th day of treatment. The number of patients having

attained normal values after 3 weeks' treatment was higher in the silymarin

group than in the placebo group. A statistical comparison revealed a

difference between bilirubin and GOT values in the placebo and silymarin

groups and a definite trend in the regression of GPT values in favour of

silymarin. The course of the immune reaction in HBS Ag patients was not

influenced by silymarin. As already proved by other investigators, the use

of silymarin in acute viral hepatitis can lead to an accelerated regression

in pathological values, thus indicating its use in the treatment of this

liver disease.

Abstract By: Author

Transliterated/Vernacular Title: Zur Wirkung von Silymarin bei der

Behandlung der akuten Virushepatitis.

Ergebnis einer an zwei medizinischen Zentren durchgeführten Doppelblindstudie.

Cytoprotection in the nineties: Experience with ursodeoxycholic acid

and silymarin in chronic liver disease

Author Lirussi F.; Okolicsanyi L.

Address Institute of Internal Medicine, University of Padua, Via Giustiniani, 2, 35100 Padova, Italy

Source

ACTA PHYSIOL. HUNG., 80/1-4 (363-367):1992

Abstract

The authors report their experience in the use of ursodeoxycholic acid

and silymarin in patients with active cirrhosis of different aetiology.

Both drugs seemed safe and ameliorated the biochemical indices of

cytolysis; however, the former did not appear to be effective when

hepatic dysfunction was associated to hepatitis C infection [the

implication being that silymarin was effective in hepatitis C-related

cirrhosis - ND]. The

residual functional liver mass, as assessed by quantitative liver

function tests, was not affected by either cytoprotective agent.

Language of Publication

English

Unique Identifier

94085703

Randomized controlled trial of silymarin treatment in patients with

cirrhosis of the liver

Silymarin, the active principle of the milk thistle Silybum marianum,

protects experimental animals against various hepatotoxic substances. To

determine the effect of silymarin on the outcome of patients with

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

170 patients with cirrhosis. 87 patients (alcoholic 46, non-alcoholic 41;

61 male, 26 female; Child A, 47; B, 37; C, 3; mean age 57) received 140 mg

Silymarin three times daily. 83 patients (alcoholic 45, non-alcoholic 38;

62 male, 21 female; Child A, 42; B, 32; C, 9: mean age 58) received a

placebo. Non-compliant patients and patients who failed to come to a

control were considered as Ôdrop outsÕ and were withdrawn from the study.

All patients received the same treatment until the last patient entered had

finished 2-years of treatment. The mean observation period was 41 months.

There were 10 drop outs in the placebo group and 14 in the treatment group.

In the placebo group, 37 (+ 2 drop outs) patients had died, and in 31 of

these, death was related to liver disease. In the treatment group, 24 (+ 4

drop outs) had died, and in 18 of these, death was related to liver

disease. The 4-year survival rate was 58 plus or minus 9% (S.E.) in

silymarin-treated patients and 39 plus or minus 9% in the placebo group (P

= 0.036). Analysis of subgroups indicated that treatment was effective in

patients with alcoholic cirrhosis (P = 0.01) and in patients initially

rated ÔChild AÕ (P = 0.03). No side effects of drug treatment were

observed. The results of this study suggest that mortality of patients with

cirrhosis was reduced by treatment with silymarin. However, as this effect

was more pronounced in alcoholic cirrhosis, the interrelation of patterns

of alcohol consumption and of drug treatment affecting survival must be

addressed by future studies.Ferenci P, Dragosics B, Dittrich H, Frank H, et

al. Randomized controlled trial of silymarin treatment in patients with

cirrhosis of the liver. J Hepatol (Netherlands) 9:105-113; 1989.

Effect of silymarin on chemical, functional, and morphological alterations

of the liver. A double-blind controlled study

One hundred and six consecutive patients with liver disease were selected

on the basis of elevated serum transaminase levels. The patients were

randomly allocated into a group treated with silymarin (treated) and a

group receiving placebo (controls). Ninety-seven patients complete the

4-week trial-47 treated and 50 controls. In general, the series represented

a relatively slight acute and subacute liver disease, mostly induced by

alcohol abuse. There was a statistically highly significantly greater

decrease of S-SGPT (S-ALAT) and S-SGOT (S-ASAT) in the treated group than

in controls. Serum total and conjugated bilirubin decreased more in the

treated than in controls, but the differences were not statistically

significant. BSP retention returned to normal significantly more often in

the treated group. The mean percentage decrease of BSP was also markedly

higher in the treated. Normalization of histological changes occurred

significantly more often in the treated than in controls.Salmi HA, Sarna S.

Effect of silymarin on chemical, functional, and morphological alterations

of the liver. A double-blind controlled study. Scand J Gastroenterol

17:517-521; 1982.

Milk Thistle, Nature's Liver Protector

Author: Michael Castleman

As printed in The Herb Quarterly, Summer 1995 issue

Mainstream medicine has little to offer those with diseases of the liver.

"Most liver treatment," says herbal medicine authority Varro Tyler, PhD,

the Lily distinguished professor of pharmacognosy (natural product

medicine) at Purdue University, "is simply supportive." Doctors keep

patients comfortable and away from liver-damaging drugs, alcohol, and

viruses, until the organ can heal itself (if it can).

However, liver healing could be significantly spurred by a remarkable herb

that has been hiding in plain sight for almost 2,000 years. It's milk

thistle (Silybum marianum). This common herb's value against liver disease

has been demonstrated in more than 100 rigorous scientific experiments.

Unfortunately, the vast majority of these studies has been European, mostly

German, and few mainstream American physicians read German botanical

medicine journals. As a result, they are in the dark about milk thistle's

astonishing liver-protective powers.

Mary's Milk

Milk Thistle is native to the Kashmir region of India and Pakistan, but it

now flourishes throughout the temperate world. The plant grows from five to

ten feet tall, and has large prickly leaves and reddish purple flowers with

sharp spines that resemble artichokes. When despined, milk thistle leaves

are edible, and some vegetable gardeners cultivate the plant as a

substitute for spinach. When broken or crushed, the stems and leaves exude

a milky white juice, hence this herb's common name. Milk thistle's specific

name, marianum, comes from an ancient legend that its leaf veins turned

white after being touched by a drop of the Virgin Mary's breast milk.

Milk thistle has been used in traditional herbal medicine since the first

century, when the Roman naturalist, Pliny the Elder (AD 23-79), wrote that

the plant's milky juice was good for "carrying off bile." (Today "bile"

denotes a product of the gall bladder, part of the liver, which assists in

the digestion of fats, but in ancient times, bile was used more generally

to describe any internal fluid.) The noted 16th-century British herbalist,

John Gerard, was the first to recommend milk thistle for liver problems,

though his prescription was oblique. He actually suggested the herb for

"expelling melancholy," which physicians at the time considered a liver

ailment. Half a century later, Britain's most famous herbalist, Nicholas

Culpeper, was the first to recommend milk thistle specifically for liver

disorders. By the 19th century, German physicians were using a tincture

prepared from milk thistle seeds (actually the plant's seed-like fruits) to

treat jaundice and other liver diseases. America's 19th-century eclectic

physicians, who specialized in botanical medicines, adopted the herb for

liver ailments and for internal cleansing.

With the rise of the modern pharmaceutical industry, research of herbal

medicines declined considerably in the United States. Fortunately, this did

not happen in Germany, where in 1949, scientists noticed that milk thistle

seemed to protect animal livers from poisoning from highly toxic carbon

tetrachloride. In 1968, scientists isolated the three specific liver

protective molecules in milk thistle -- silibinin, silidianin, and

silicristin -- now collectively known as silymarin.

Silymarin is not very soluble in water, which means that very little find

its way into a tea made from the milk thistle plant. It is also poorly

absorbed from the digestive tract, which severely limits its

bioavailability from tinctures because they are not sufficiently

concentrated to deliver a therapeutic dose. To rectify this problem, German

researchers bred a special variety of milk thistle. When carefully

cultivated, this medicinal variety produces a high-potency standardized

extract of silymarin, which is processed into tablets or capsules. This

standardized milk thistle seed extract is 70-percent silymarin. It is

widely prescribed by German physicians, who practice the world's most

advanced scientific herbal medicine. German silymarin sales now top $180

million a year. Most silymarin marketed in the US comes from German sources

and is also 70-percent silymarin. Standard tablets and capsules contain 200

mg of milk thistle seed extract, which contains 140 mg of silymarin.

Studies Galore

More than 100 studies have confirmed silymarin's liver-protective value.

Here's a brief overview of what researchers have discovered:

Alcoholic Cirrhosis. A 1989 report in the Journal of Hepatology (the study

of the liver) described a study involving 170 people with advanced

alcoholic cirrhosis, an often-fatal condition, and the nation's 11th

leading cause of death, claiming 25,000 lives each year. The study

participants were divided into two groups. One received 200 mg of milk

thistle extract (140 mg of silymarin) three times a day, the other received

a medically inactive look-alike placebo. Both groups were followed for four

years. During that time, the death rate in the placebo group was about 60

percent, but among those taking silymarin, only 40 percent died, a highly

statistically significant difference. Other studies have shown that

silymarin provides similar benefits for people suffering cirrhosis.

Death Cap Mushroom Poisoning. The common wild mushroom, Amanita phalloides,

is known as the "death cap" for a good reason. It takes only a handful of

this widely distributed fungus to kill an adult, even less to kill a child.

Standard medical treatment -- activated charcoal -- is not particularly

effective. Amanita mushroom ingestion proves fatal in about half of the

reported cases. Twenty years ago, pilot studies showed that silymarin

treatment substantially reduced amanita-poisoning deaths in animals fed the

mushroom. Subsequently, several human studies were launched. In one German

hospital test, 60 consecutive people with amanita poisoning were given

intravenous silymarin. None died. Other studies have produced results that

are similar, though not as spectacular. (However, the success of silymarin

in treating mushroom poisoning should not encourage anyone to go mushroom

hunting without training in amanita avoidance. Unless you're an experienced

mycophile, the only place to pick mushrooms is at a produce market.)

Hepatitis. The word means liver inflammation, and the condition is not one

disease, but several, most of which are caused by different viruses that

attack liver cells. The three most common forms are hepatitis A, B, and C.

Hepatitis A is food-borne. Hepatitis B and C are blood-borne and can be

sexually transmitted. Mainstream medicine treats all forms of hepatitis

with rest and the avoidance of alcohol and other drugs and toxins that tax

the liver.

However, silymarin is a more effective approach. In one study, 77 people

with hepatitis were divided into two groups, one treated with silymarin,

the other with a placebo. Average recovery time for the placebo-takers was

43 days, but those who took silymarin recovered in an average of just 29

days.

Gallstones. Up to ten percent of Americans are estimated to have

gallstones, little pebbles that develop in the gallbladder. Some cause no

symptoms, but many cause abdominal pain, sometimes severe enough to require

surgical removal of the gallbladder. Most gallstones are formed from

cholesterol, which saturates the bile produced by the gallbladder, and then

precipitates out as stones. A low-fat, low-cholesterol diet helps prevent

gallstones. So does silymarin. In one study, people with gallstones were

given 420 mg of silymarin a day. Without diet changes, after several weeks,

they showed significant reductions in the cholesterol concentration of

their bile, which minimized risk of stone formation.

Liver Function Tests. The liver metabolizes all drugs, and powerful

medications often stress the liver, producing abnormal liver function tests

that sometimes require physicians to stop the drug treatment that people

need. Silymarin helps normalize liver function, allowing those who must

take liver-harming medications to do so with less risk of liver damage. In

one study, 66 women taking anti-convulsant or psychiatric medications

showed abnormal liver-function tests. They began taking silymarin in

addition to their medication, and 52 percent of them showed significant

improvement in liver function.

Occupational Toxic Chemical Exposure. Like drugs, toxic chemicals also

stress the liver, causing liver-function tests to register abnormal

results. European studies show that silymarin renormalizes liver-function

tests in workers who produce pesticides, and in those exposed to toxic

heavy metals, for example, lead and cadmium.

Psoriasis. A few European studies suggest that silymarin may even help

treat the scaly skin patches of psoriasis.

How Silymarin Works

Silymarin works in three ways. It strengthens the outer membranes of liver

cells, preventing penetration by liver-damaging substances. This accounts

for its effectiveness against amanita mushroom poisoning. Both silymarin

and the mushroom toxins bind to the same sites on liver cell membranes. As

silymarin blood levels increase, the milk thistle extract occupies the

cell-membrane receptor cites, displacing the amanita toxins.

Silymarin also protects liver cells because of its powerful antioxidant

action. Antioxidants neutralize cell damage caused by chemically unstable

oxygen molecules caused by a high-fat diet, smoking, and other toxic

substances. The best known antioxidants are vitamin A (beta-carotene),

vitamin C, vitamin E, and the mineral selenium. However, in the liver,

silymarin is more than ten times as potent an antioxidant as vitamin E.

Finally, silymarin inhibits the action of the enzyme largely responsible

for inflammation in hepatitis.

As far as scientists know, silymarin does not interfere with the liver's

metabolism of drugs, so it does not interfere with the action of

medications.

Safe, But...

According to Dr Tyler's excellent new clinical guide to herbal medicines,

"Herbs Of Choice", silymarin is safe and non-toxic in doses of 200 to 400

mg up to three times per day. However, minor side effects are possible --

primarily headache, irritability, and minor intestinal upset. To minimize

the possibility of side effects, Paul Bergner, editor of the newsletter

"Medical Herbalism", recommend starting with a low dose and working up

slowly. It typically takes about one month of daily silymarin use to see

improvements in hepatitis and other liver conditions. Clinicians who

prescribe silymarin usually keep people on it for one to three months.

Preventive Medicine?

You don't have to munch amanita mushrooms to stress your liver. Every day

we're exposed to pollutants, pesticides, food additives, and other

substances that the liver must detoxify. In addition, anyone who drinks

alcohol or takes any medication -- either prescription or over the counter

drugs -- boosts the liver's workload, and damages some liver cells in the

process. Fortunately for all of us, the liver is quite large. It's the

second largest organ, after the skin, so you can lose millions of liver

cells and still function normally. But why lose even a single liver cell if

you don't have to?

Recently, Scandinavian researchers tested silymarin's effect on livers that

were stressed but not seriously diseased. They selected 106 consecutive

patients who had abnormal liver function tests from alcohol, but who did

not have cirrhosis. Half took silymarin; the other half received a placebo.

After four weeks, the placebo group showed no change in liver function, but

the silymarin group showed highly significant improvement, in some cases,

complete normalization of liver function, despite their alcohol

consumption.

Perhaps we all should take some silymarin. Robert McCaleb, president of the

Herb Research Foundation, in Longmont, Colorado,, does: "If I worked in an

occupation [that stressed the liver], I would take milk thistle regularly,

one tablet each workday morning. [But I don't, so] I take two tablets

before working with paints or solvents, and I never take aspirin or

acetaminophen (Tylenol) without also taking a milk thistle tablet. Finally,

I always take milk thistle along when traveling because almost invariably I

find myself at a cocktail party." Sage counsel. Silymarin is available at

herb shops and natural food stores.

SILYMARIN COMPLEX FOR LIVER DISORDERS

by Michael T. Murray, N.D.

published in "Health World" spring 1987

The liver is the most important organ of metabolism. Disruption of normal

liver function results in significant disruption of all metabolic

processes. The metabolic functions of the liver include regulation of

carbohydrate, fat and protein metabolism, storage of vitamins and minerals,

and detoxification reactions.

Since the liver is the major site of detoxification of toxic chemicals in

the body, it is also at a very high risk against damage by such chemicals

as DDT; dioxin; 2,4,5-T; 4-D; PCB; and PCP. It is not known to what degree

Americans are exposed to these toxic compounds, but it is probably quite

high as yearly production of synthetic pesticides alone exceeds 1.4 billion

pounds. In addition, many drugs and alcohol are also known to damage the

liver.

Avoidance of these damaging chemicals is the first defense against liver

damage. The second defense may be the use of a Silymarin Comples. Silymarin

Comples is composed of concentrated extracts of herbs which have

demonstrated remarkable effects in protecting the liver from chemical

damage and in improving liver function in experimental studies. These herbs

have a long history of use in a wide variety of conditions. Their success

is probably related to a common property: they improve the function of the

liver.

SILYBUM MARIANUM (MILK THISTLE)

The common milk thistle contains some of the most potent liver-protecting

substances known. The concentration of these components is highest in the

fruit. Silybum's effect of preventing liver destruction derives from its

ability to inhibit those factors that are responsible for the damage. Liver

destruction occurs primarily as a result of certain toxins producing or

acting as free radicals: highly reactive compounds that damage other

molecules. Silybum components prevent free radical damage by acting as

antioxidants.

These components are many times more potent in antioxidant activity than

Vitamin E.

Another way in which the liver can be damaged is by the action of

leukotrienes. These compounds are produced by the transfer of oxygen to a

polyunsaturated fatty acid. This reaction is catalyzed by the enzyme

lipoxygenase. Silybum components inhibit this enzyme, thereby inhibiting

the formation of damaging leukotrienes.

Perhaps the most interesting effect of silybum components on the liver is

their ability to stimulate protein synthesis. The result is an increase in

the production of new liver cells to replace the damaged old ones.

CLINICAL TRIALS OF SILYBUM MARIANUM

The protective effects of silybum angainst liver damage have been

demonstrated in a number of experimental and clinical studies. Experimental

liver damage in animals is produced by such diverse toxicants as carbon

tetracloride, galactosamine and praseodymium nitrate. Silymarin, a complex

of three compounds isolated from Silybum marianum, has been shown to

protect against liver damage by all of these agents.

Perhaps the most impressive of silybum's protective effects is in

protection against severe poisoning of Amanita phalloides, the death cup or

toadstool mushroom. Interestingly enough, silybum has a long folk history

of treating death cap ingestion. Ingestion of Amanita phalloides or its

toxins causes severe poisoning, and a death rate of approximately 30%. In

the animal experiments, if silymarin was administered before amanita toxin

poisoning, it was 100% effective in preventing the toxicity of the

mushroom. Even if the silymarin was given 10 minutes after the amanita

toxin, it was able to completely counteract the toxic effects. If given

within 25 hours, silymarin will prevent death and greatly reduce the amount

of damage to the liver.

In human studies, silymarin has been shown to have significant positive

effects in treating several liver diseases, including cirrhosis and chronic

hepatitis. In summary concentrated silybum marianum extract offers

significant protection against liver damage: 1. by preventing free radical

damage; 2. by preventing formation of damaging leaukotrienes; and 3. by

stimulating the production of new liver cells.

REFERENCES:

Hikino, H. Kiso, Y., Wagner, H. and Fiegig, M., "Antihepatotoxic actions of

flavonolignans from Silybum marianum fruits", Planta Medica, 1984, 50, pp

248-50

Vogel, G., Trost, W., Braatz, R., et al., "Studies on pharmacodynamics,

site and mechanism of action of silymarin the antihepatotoxic principle

from Silybum marianum (L.) Gaert"., Arzneim-Forsch, 1975, 25, pp 179-85

Wagner, H., "Antihepatotoxic flavonoids", in Cody, V., Middleton, E. and

Harbourne, J.D. (eds), Plant flavinoids in Biology and Medicine:

Biochemical, Pharmacological and Structure-Activity relationships, Alan R.

Liss, New York, NY 1986, pp545-58

Wagner, H., "Plant constituents with antihepatotoxic activity", in Beal,

J.L. and Reinhard, E. (eds) Natural Products as Medicinal Agents,

Hippokrates-Verlang, Stuttgart, 1981

Sarre, H., "Experience in the treatment of chronic hepatopathies with

silymarin", Arzneim-Forsch, 1971, 21, pp 1,209-12

Canini, F., Bartolucci, A., Cristallini, E., et al., "Use of silymarin in

the treatment of alcoholic hepatic stenosis", Clin. Ther., 1985, 114, pp

307-14

Salmi, H.A., and Sarna, S., "Effect of silymarin on chemical, functional,

and morphological alteration of the liver. A double-blind controlled study"

Scand.J.Gastroenterol., 1982, 17, pp 417-21

Scheiber, V., and Wohlzogen, F.X., "Analysis of a certain type of 2 x 3

tables, exemplified by biopsy findings in a controlled clinical trial",

Int.J.Clin.Pharmacol., 1978, 16, pp 533-5

Boari, C., Montanari, M., Galleti, G.P., et al., "Occupational toxic liver

diseases. Therapeutic effects of silymarin", Min.Med., 1985, 72, pp

2,679-88.

HepC BC