In June of 1997, I saw an
excellent news report aired by ABC 20/20 on St.
John's wort's usefulness in treating mild to
moderate depression. One of the physicians
interviewed for the piece said that St. John's wort
was the flagship of herbal medicine, and the
best-researched herb in the world. I sat there in
my chair and said to myself. "Wrong." When I think
of the best-researched herb in the world from the
standpoint of known active constituents, proven
pharmacological mechanisms of action, proven
clinical effectiveness through dozens of controlled
clinical studies and decades of experience, and an
excellent safety record, there is only one herb
that can fit all of those criteria. It is milk
thistle.
Milk thistle preparations
are from the seeds of Silybum marianum, a
member of the sunflower family native to a narrow
area of the Mediterranean, but grown for centuries
throughout Europe and naturalized on that
continent. It is also naturalized in the United
States. In fact, it is a common weed in California.
From time to time, I see television ads, obviously
shot in California in a field. Milk thistle is
often seen in the ads. It was brought to America by
early settlers, probably as a food plant, and
became established in the eastern United States, as
well as the West. By the turn of the century, it
was already common in California, in abandoned
fields, old pastures, and by roadsides. It is also
naturalized in some areas of South America, and
Australia, where it is a nuisance weed forming
thickets.
Milk Thistle has black
shiny seeds, crowned with feathery tufts like those
of dandelion seeds. It is the seed that have been
the subject of interest among herbalists.
Traditionally, seeds have been roasted for use as a
coffee substitute, but it is their historical and
modern use in the supportive treatment of liver
disease that has attracted attention. Use of the
plant as a liver protecting agent dates at least to
the first century.
Dioscorides, a first
century Greek physician who served the Roman army,
gave the name Silybum to a number of edible
thistles. Now the genus name Silybum is
given to two species originating from the
Mediterranean region, including our subject Silybum marianum. The name milk thistle
refers to the white streaks along the leaf veins.
In Germany where the plant is often depicted as a
religious symbol associated with the Virgin Mary,
legend ascribes the white mottling to a drop of the
Virgin Mary's milk. The species name
"marianum" honors the symbolic association
of the plant with the Virgin Mary.
Modern use of milk thistle
in medicine is limited to the seeds. The plant has
gained prominence based on scientific research in
the past thirty years. However, its use is not the
result of new biological screening that catapults
it into prominence as a "new" medicinal plant.
Rather, its use as a liver-protecting herb dates to
the earliest Greek references to the plant. Pliny
the Elder (A.D. 23-79), the first century Roman
physician/naturalist wrote about use of the plant
as a vegetable, but warned it was not worth the
effort to boil it, as it was troublesome to cook.
He also mentioned that the juice of the plant,
mixed with honey, is excellent for "carrying off
bile." This is perhaps the first reference to the
use of Milk Thistle for liver-related
conditions.
A thousand years later,
the plant was already well-known in Germany. It is
mentioned in an important medieval German
manuscript, the Physica of Hildegarde of
Bingen, the first herbal written by a woman,
composed about 1150 then first published in 1533.
Hildegarde, theologian, music composer, and writer
was herself a "renaissance women," before the age
of the Renaissance. She wrote about the uses of the
roots, whole plant and leaves of Milk Thistle,
which she called "vehedistel" or Venus
Thistle.
Still used in the
eighteenth century, Culpepper (1787 ed.) notes that
it is effectual "to open the obstructions of the
liver and spleen, and thereby is good against the
jaundice." He also writes, "The seed and distilled
water are held powerful to all the purposes
aforesaid, and besides, it is often applied both
inwardly to drink, and outwardly with cloths or
spunges [sic.], to the region of the liver,
to cool the distemper thereof
"
Reinvestigating the value
of traditional herbal remedies, in 1929, H.
Schultz, a German scientist, began to look into the
value of milk thistle. He found that a famous
eighteenth century German physician, Rademacher,
had advocated use of milk thistle preparations for
chronic liver diseases, acute hepatitis, and
jaundice. By the 1930s once again clinical interest
in milk thistle was beginning to emerge.
Intensive research into
the liver-protecting (hepatoprotectant) properties
of the plant, the responsible chemical components,
and mechanisms of action, began about 30 years ago.
Attempts to isolate the active components of the
seed were begun in 1958. Ten years later a research
team headed by H. Wagner at the University of
Munich was successful in isolating a compound
termed silymarin, which was believed to be a single
compound. Improved chemical separation methods
later revealed that silymarin was not a single
component but a complex of chemicals known as
flavonolignans. The primary components isolated and
structurally characterized from silymarin include
silybinin, silydianin and silychristin.
Collectively, these isoflavonolignans are found in
concentrations of 4 to 6 percent in the ripe seeds.
European Milk Thistle products, some of which are
available on the American market, are standardized
to 70 - 80 percent silymarin.
In perhaps the best book
on clinical use of phytomedicine, Herbal
Medicine (English edition 1988) by the late
physician, Rudolf Fritz Weiss, he notes that
compared with silymarin, few plant principles have
been as extensively researched in recent years.
According to Weiss, the efficacy of silymarin has
been confirmed by the extensive laboratory,
histological and clinical data. Numerous
well-designed clinical trials have been conducted
in Europe, primarily Germany, on the therapeutic
efficacy of silymarin in the treatment of metabolic
liver damage, chronic hepatitis, and bile duct
inflammation, often induced by alcohol, drugs
(psycopharmaceuticals), and chronic liver disease
including certain forms of hepatitis. The
hepatoprotective effects of silymarin have been
demonstrated in accelerating normalization of
impaired liver function. Accelerated improvement in
measures of liver function, including serum levels
of GOT (glutamic&emdash;oxalacetic transaminase),
GPT (glutamic&emdash;pyruvic transaminase) and
Gamma&emdash;GT
(gamma&emdash;glutamyl&emdash;transpeptidase) have
been consistently observed. Dosages involved in
clinical trials have often been 420 mg./day, used
for a period of 4 to 8 weeks.
The therapeutic efficacy
is based on several separate mechanisms of action.
Silymarin alters the outer liver membrane cell
structure in such a way that certain toxins, as
demonstrated with the toxins of the Deathcap
mushroom, cannot enter the cell. Silymarin also
stimulates RNA polymerase A (also known as
polymerase I), enhancing ribosome protein
synthesis, resulting in activating the regenerative
capacity of the liver through cell development.
Clinical use of silymarin today applies to toxic
liver damage for the supportive treatment of
chronic inflammatory liver disorders and cirrhosis
of the liver, such as in chronic hepatitis, and
fatty infiltration of the liver by alcohol and
other chemicals.
According to a recent
review article by Morazzoni and Bombardelli (1995),
in Germany the primary causes of liver intoxication
include alcohol (71 percent), psychopharmaceuticals
(18 percent) and industrial exposure to chemicals
(11 percent). While removal of the liver
disease-causing substance is important in
management of toxic liver situations, silymarin is
the best documented drug for treatment of liver
intoxication. Previously, oral clinical application
of silybin has been limited by bioavailability.
These authors report on a new silybin complex that
has been shown to have markedly improved
bioavailability, hence pharmacodynamic activity in
both animal and human studies.
The German Health
Authorities, equivalent to the U.S. FDA, have
established a separate panel, known as Commission E
to develop acceptable uses, contraindications, and
dosages for well-defined herbal medicines in
Germany. The Commission E monographs serve as the
basis for regulation of herb products in Germany,
and serve as the model for European Union
harmonization of laws on phytomedicines. Their
positive monograph on milk thistle seed allows
preparations of the seeds for the supportive
treatment of chronic inflammatory liver disorders
and cirrhosis of the liver, such as chronic
hepatitis, and fatty infiltration of the liver by
alcohol and other chemicals. The monograph also
notes that pretreatment with silymarin inhibits
alcohol&emdash;induced liver damage, suggesting
that it is useful in both a preventative and
curative sense.
In 1996, I recall a case
that hit the news in which an Asian immigrant died
from mistakenly wild-harvesting a death-cap
(Amanita) mushroom, thinking it was an edible
mushroom. It was sad to realize that special milk
thistle preparations were unavailable to treat this
case in California. Let me explain. A few years ago
I was sitting in a meeting with a friend of mine in
Germany, a physician who is a hepatologist - a
specialist in liver disease. Our meeting was
interrupted several times by phone calls. An
emergency room in Prague was attempting to arrange
for her to get a milk thistle preparation to them
as soon as possible to treat a case of deathcap
mushroom poisoning. She made several phone calls
and arranged for a pilot on a commercial airline to
deliver the preparation to Prague on the next
flight in an hour. In western Europe a special
water soluble chemical fraction derived from the
seeds of Milk Thistle, known as silibinin (not to
be confused with silymarin or other oral dosage
forms), is stocked in most emergency rooms and
poison control centers for use as an adjunct
therapy to the treatment of Amanita (Deathcap)
mushroom poisoning. If administered in time, the
use of this preparation in intravenous drip
infusion therapies has helped lower mortality rates
from Deathcap mushroom poisoning below any levels
that have previously been achieved.
Milk Thistle seed
preparations have been used for the treatment of
liver disease since antiquity. At one time or
another, virtually all parts of the plant have been
used as both food and medicine with virtually no
reports of toxicity, aside from a mild laxative
effect in some patients. The extensive chemical,
pharmacological, and clinical research that has
been conducted over the past thirty years, has
revealed the active components, mechanism of
action, and proven its efficacy in human liver
disease. Milk Thistle is one of those fascinating
plants, whose use, supported by 2000 years of
historical use, has emerged as an important example
of how traditional information can be used for the
development of modern herb products.
References
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H. Colbert.
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and L. Liberti. 1988. Natural Product
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Farini, L. Okolicsanyi, and R. Naccarato. 1981.
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