Milk Thistle Silybum marianum by Steven Foster
Milk thistle (Silyburn marianurn (L.) Gaertner), a member of the
Aster family (Asteraceae or Compositae), is a widespread wayside herb
of uncultivated ground and waste places throughout much of Europe.
The plant, carried to North America by European colonists at an early
date (Pickering, 1879), is naturalized in the Eastern United States,
California, and South America. In the last 30 years milk thistle seed
extracts have been intensively researched, confirming its 2,000 year
old therapeutic use in liver disease.
"Milk thistle" has emerged as the most widely known English common
name for the plant. Older works list it as Mary thistle, St. Mary
thistle, Marian thistle, Lady's thistle, and Holy thistle (not to be
confused with Blessed thistle, Cnicus benedictus). Latin synonyms
include Carduus marianus L. and Cnicus marianus. Silybum derives from
a name applied to some edible thistles by the first century Greek
physician Dioscorides. The genus contains two species. The other
species is S. eburneum, indigenous to the Mediterranean region. The
specific name marianum preserves the legend that the white mottling
of the leaves was caused by a drop of the Virgin Mary's milk
(Nicholson, 188687). The plant is also traditionally used as a
galactogogue (stimulating milk production), perhaps contributing to
word origins of the common name.
Food Use and Safety
In European gardens the plant has been cultivated as a vegetable. It
was still grown in old-fashioned British gardens at the end of the
nineteenth century (Henderson, 1889). The young leaves (with spines
removed) were used in spring salads and as a spinach substitute.
Young stalks, peeled and soaked, are eaten like asparagus. The roots,
soaked in water overnight to remove bitterness, are eaten like
salsify. Milk thistle's flower receptacle, resembling an artichoke,
was cooked and eaten like artichokes (Hedrick, 1919; Grieve, 193 1).
Roasted seeds have been employed as a coffee substitute (Uphof,
1968). Adverse effects from ingesting any plant part are generally
lacking from the literature. Animal experiments have shown that seed
extracts are safe, even in large doses, with practically no side
effects, as well as no embryo toxic effect (Weiss, 1988). Adverse
effects in human studies with the seed extract (silymarin) are also
generally absent (Der Marderosian and Liberti, 1988). A mild laxative
effect has been observed in isolated cases (Blumenthal, et al., 1996).
In one form or another, variouspreparations of milk thistle,
especially the seeds, have been usedmedicinally for over 2,000 years.
In modern research scientists oftenattempt to find new biologically
active plant substances through randomscreening methods. However,
Silybum is a classic example of the value of utilizing historical
records for the development of modern herbproducts. Its use as a
liver-protecting agent dates to early Greek references. The first
century Roman writer Pliny the Elder (A.D. 23-79)noted that the juice
of the plant mixed with honey is excellent for"carrying off bile"
(Jones, 1966). Historical references onthe plant are particularly
abundant in the herbal literature of the Middle Ages, including the
anti-liver toxic activity of the seeds (Halbach,1976).
While native to Southern Europe, the plant was found in England by
the end of the sixteenth century. Grieve (1931) quotes Gerard
(1597), "My opinion is that this is the best remedy that grows
against all melancholy diseases"[diseases of the liver].
The British herbalist, Nicholas Culpepper(1787 ed.) notes that it is
effectual "to open the obstructions of the liver and spleen, and
thereby is good against the jaundice." Healso 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
The plant is absent from most American works on medicinal plants
until the end of the nineteenth century. Eclectic physicians Felter
and Lloyd (1898) list the seeds as Carduus marianus. They
write, "[It] is an old remedy which had nearly passed out of use and
has more recently been revived." They alsostate,"Congestion of the
liver, spleen, and kidneys is relieved byits use."
A tincture of the whole plant is an official preparation of the first
United States Homeopathic Pharmacopeia (Anon. 1878). In homeopathy
the seed tincture is used for liver disorders, jaundice, gall stones,
peritonitis, coughs, bronchitis, varicose veins, and congestion of
the uterus (Schauenberg and Paris, 1977). A 1985 German monograph on
the use of Silybum marianum in homeopathy includes indications for
diseases of the gall bladder and liver.
Modern Medicinal Use
Intensive research in the hepatoprotectant (liver protecting) effects
of milk thistle began about 40 years ago. In Germany, milk thistle
seed extracts have been marketed for many years. Attempts to isolate
the primary active chemical components were under way by 1958, but
there had been few attempts to characterize the chemical components
prior to 1965 (Vogel, 1976). Wagneret al. (1968) first isolated
silymarin from the seeds, providing an opportunity for establishing a
scientific basis for use in treating liver diseases. Later it was
found that silymarin was not a single component, but a mixture of
complex compounds known as flavonolignans. Silymarin is found in
concentrations of 4 to 6 percent in the ripe seeds(Der Marderosian
and Liberti, 1988). The first chemical compounds isolated and
structurally characterized were silybin, silydianin, andsilychristin
(Wagner and Seligmann, 1985). A number of other flavonolignans have
also been found in the seeds, in addition to apigenin, silybonol, and
myristic, palmitic, stearic, and oleic acids (DerMarderosian and
Compared with silymarin, few plant principles have been as
extensively investigated in recent years (Weiss, 1988). Research
using animal models has demonstrated liver protectant effects of
proprietary German seed extracts, and extensive clinical,
histological, and laboratory data have confirmed the efficacy of
silymarin (Weiss, 1988). Early pharmacological studies by Keppler et
al. (1968) and Hahn et al. (1968) showed that silymarin has a
protective effect on the liver when exposed to varioustoxic compounds
in laboratory models. The liver protectant activity of silymarin has
been demonstrated in numerous experimental models of toxic liver
damage, including damage from carbon tetrachloride, galactosamine,
thioacetamide, hepatotoxic: cold-blood frog virus (FV3),
lanthanides,and the poisonous substances of the death cap fungus,
phalloidin andalpha-amanitin (Blumenthal, et al., 1996). Further
studies havesuggested that pretreatment with silymarin inhibits
alcohol-inducedliver damage and has also established pharmacological
mechanisms for theinhibitory action, including scavenging of free
radicals, leukotrienes,and an ability to stimulate liver protein
synthesis. These studies arereviewed by Hikino and Kiso (1988).
The therapeutic efficacyis 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 death cap fungus, cannot enter the cell. Silymarin also
stimulates RNA polymerase A (also known aspolymerase I), enhancing
ribosome protein synthesis, resulting inactivating 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 (Blumenthal,et al., 1996).
Remarkable studies have shown that certain milk thistle preparations
can produce both aprotective and curative effect on liver damage
resulting from the highly toxic compounds, phalloidin and alpha-
amanitin (from the death cap Amanitaphalloides, one of the most
deadly of poisonous mushrooms). Poisoning from ingestion of the
mushroom, given its severe damage to the liver, has been very
difficult to treat (Weiss, 1988). Vogel and Temme(1969) note that
earlier experiments showed that silymarin had an antihepatotoxic:
(anti-liver toxic) effect, when it was administered before poisoning
by phalloidin. In their 1969 study, Vogel and Ternmeshowed a curative
anti-hepatotoxic effect when silymarin was administered after
exposure to phalloidin, establishing a model for therapeutic use in
humans. This study suggested that silymarin could both prevent and
cure liver damage. Silymarin was considered to have high anti-
hepatotoxic activity, given the fact that phalloidin is one of the
substances most toxic to the liver. The anti-hepatotoxic effect of
silymarin was found to be dependent upon the time interval in which
poisoning and therapy took place, as well as the degree of liver
damage. It is suggested that silymarin prevents penetration of the
two Amanitatoxins by competing with the toxins for the same receptor
on cellmembranes (Hikino and Kiso, 1988).
A multicenter trial involving 220 cases of Amanita poisoning treated
in German, French, Swiss, and Austrian hospitals was carried out from
1979 to 1982 using silibinin in supportive treatment. (Silibinin, the
product form used in the above studies, is a water soluble compound
derived from milk thistle seeds that is used in intravenous infusion
therapy. It should not be confused with the oral dosage forms of
silymarin.) According to the author of the study, Karl Hruby of the
University of Vienna Poison Information Center, the mortality rate
was 12.8 percent. This compares with a mortality rate of 22.4 percent
carried out in a study involving 205 patients by Floersheim et al.
(1982), in which only 16 patients were treated with 20 to 50
mg/kg/day of silibinin. Hruby (1984)concluded that the use of
silibinin as an adjunct to current methods of treating Amanita
poisoning can lower mortality rates below any levels which have
previously been achieved.
A follow-up biopsy studyby G. Poser (1971) reported that 67 subjects
who had been treated as outpatients for toxic-metabolic liver damage,
chronic hepatitis, and bileduct inflammation showed a drop in
chemical parameters associated with liver disease. Chronic hepatitis
was bioptically found to be significantly improved after three months
of silymarin administration(525 mg/day of silymarin). Conditions
associated with bile duct inflammation responded particularly well.
In several controlled trials the hepatoprotective effects of
silymarin in toxic liver disease could be demonstrated as
accelerating normalization of impaired liver function. In a double-
blind study conducted by Fintelmann and Albert(1980), 66 patients,
mainly with alcohol-induced toxic liver disease, received either
silymarin (420 mg/day) or a placebo for a four week period. Patients
who received silymarin showed an accelerated improvement of increased
serum levels of liver enzymes GOT (glutamic-oxalacetictransaminase),
GPT (glutamic-pyruvic transaminase) and Gamma-GT (ganma-glutamyl-
Several other placebo-controlled double-blind studies in alcohol- and
drug-induced liver disease showed a clear superiority of treatment
with 420 mg silymarin for 4 to 8 weeks compared with placebo (Di
Mario, 198 1; Feherand Lang, 1988; Salmi and Sarna, 1982). In a
further double-blind study with 36 patients suffering from alcohol-
induced liver disease, pathological liver parameters (GOT, GPT,
Ganima-GT, and bilirubin) were significantly reduced after 6 months
of treatment with silymarin compared to placebo (Feher et al., 1990).
References cited above represent a small sampling of the dozens of
clinical studies that have been conducted on silymarin. Double-blind
studies on the effect of silymarin on toxic liver damage (mostly
induced by alcohol), chronic liver disease, and disease caused by
psycho- pharmaceuticals are reviewed by Hikino and Kiso (1988). They
concluded that basic laboratory and clinical data suggest that
silymarin is a therapeutically useful medicinal plant product that
stabilizes the cell membrane and stimulates protein synthesis while
accelerating the process of regeneration indamaged liver tissue, and
that these effects are important in the therapeutic efficacy of
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. 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.
While silymarin has primarily been used as a phytomedicine, recent
studies reviewed by Morazzoni and Bombardelli (1995), suggest future
use in dermatological and cosmetic products based on a number of
activities including promoting healing at wound sites, improved bum
healing, and counteracting skin degeneration and aging via
antiinflammatory and free radical scavenging mechanisms.
For over 2,000 years Europeans have used milk thistle seeds as an
herbal treatment for liver disorders. The plant has been grown both
as an ornamental and a vegetable. Virtually all parts of the plant
have been used as food with no reports of toxicity. Over the past 40
years, intensive chemical, pharmacological, and clinical research has
confirmed mechanisms of action and therapeutic value of silymarin in
a wide range of human liver disease including toxic metabolic liver
damage (such as fatty degeneration of the liver) and supportive
treatment of chronic hepatitis and cirrhosis. Silymarin, derived from
the seeds of the plant, has shown both protective and restorative
effects in liver disease. Other components of the seed have proven
useful in supportive therapy for death cap mushroom poisoning. The
plant is a primary example of the usefulness of using historical
efficacy as a starting point for the development of modern
applications for medicinal plants.
Anon. 1878. The United States Homeopathic Pharmacopeia. Chicago:
Duncan Brothers, Publishers.
Blumenthal, M.; T. Hall, R. Rister, B. Steinhoff (eds.), S. Klein, R.
Rister (trans.). 1996. The German Commission E Monographs. Austin,
Texas, American Botanical Council.
Morazzoni, P. and E. Bombardelli. 1995. Silybum marianum (Carduus
marianus). Fiototerapia, 66(l):3-49.
Culpepper, N. 1787. The English Physician Enlarged. Dublin: H.
Der Marderosian, A. and L. Liberti. 1988. Natural Product Medicine: A
Scientific Guide to Foods, Drugs, Cosmetics. Philadelphia: George F.
Di Mario, F., R. Farini, L. Okolicsanyi, and R. Naccarato. 1981. "The
Effects of Silymarin on the Liver Function Parameters of Patients
with Alcohol-Induced Liver Disease: A Double Blind Study" In: F. de
Ritis, G. Csomos and R. Braatz (eds.). Der Toxisch-metabolische
Leberschaden. Hans. Verl.-Kontor, Lfibeck, pp. 54-58.
Feher, J. and 1. Lang. 1988. Bay. Internist 4:3-7.
Feher, H. et al. 1990. "Hepatoprotective Activity of Silymarin
Therapy in Patients with Chronic Alcoholic Liver Disease." Orvosi
Hetilap 130:5 1.
Fetter, H. W. and J. U. Lloyd. 1898. King's American Dispensatory. 2
vols. reprinted ed. 1983. Portland, OR: Eclectic Medical Publications.
Fintelmann, V. and A. Albert. 1980. Therapiewoche 30:5589-94.
Floersheim, G. L., 0. Weber, P. Tschumi, and M. Ulbrich.
1982. "Poisoning by the Deathcap Fungus (Amanita phalloides):
Prognostic Factors and Therapeutic Measures." Schwiz. Med.
Grieve, M. 1931. A Modern Herbal. 2 vols. New York: Harcourt, Brace &
Halbach, G. 1976. "Chemistry of Silymarin and Water-soluble
Derivatives" In: R. Braatz and C.C. Schneider (eds.) Symposiurn on
the Pharmacodynamics of Silymarin. Munich: Urban & Schwarzenberg.
Hedrick, U. P. (ed.) 1919. Sturtevant's Notes on Edible Plants. State
of New York, Dept. of Agriculture, Twenty-seventh Annual Report. Vol.
2, Part II.
Henderson, P. 1889. Henderson's Handbook of Plants and General
Horticulture. New York: Peter Henderson & Company.
Hikino, H. and Y. Kiso. 1988. "Natural Products for Liver Disease."
pp. 39-72. In H. Wagner, H. Hikino and N. R. Farnsworth. Economic and
Medicinal Plant Research. Vol. 2. New York: Academic Press.
Hruby, C. 1984. "Silibinin in the Treatment of Deathcap Fungus
Poisoning." Forum 6:23-26.
Jones, W. H. S. 1966. Pliny Natural History with an English
Translation in Ten Volumes. Vol. VII. Cambridge: Harvard University
Keppler, D., R. Lesch, W. Reutter and K. Decker. 1968. Exp. Mil.
Pathol. 9:279."Monographien Homoopathischer Arzneimittel." 1985. 19.
Erg. -Lieferung ZRvA, Dec. 1986.
Nicholson, G. 1886-87. Dictionary of Gardening. Vol. 3. London: L.
Pickering, C. 1879. Chronological History of Plants. 2 vols. Boston:
Little, Brown and Co.
Poser, G. 1971. "Experience in the Treatment of Chronic Hepatopathies
with Silymarin." Arzneim-Forsch. 21(8): 1209-1212.
Salmi, H. A. and S. Sarna. 1982. "Effect of Silymarin on Chemical,
Functional, and Morphological Alterations of the Liver: A Double-
blind Controlled Study" Scad. J. Gastroenterol. 17:517-21.
Schauenberg, P. and F. Paris. 1977. Guide to Medicinal Plants. New
Canaan, CT: Keats Publishing, Inc.
Uphof, J. C. Th. 1968. Dictionary of Economic Plants. Lehre: Verlag
Von J. Cramer.
Vogel, G. and I. Temme. 1969. "Curative Antagonization of a Liver
Damage Caused by Phalloidin by the Use of Silymarin as a Model of
Anti-hepatotoxic Therapy." Arzneim-Forsch. 19: 613-615.
Vogel, G. 1976. "Pharmacological properties of silymarin, the anti-
hepatotoxic agent from the seeds of the Milk Thistle, Silybum
marianum (L.) Gaertn" In R. Braatz and C. C. Schneider (eds.)
Symposium on the Pharmacodynamics of Silymarin. Munich: Urban &
Vogel, G. 198 1. Proceedings of the International Bioflavonoid
Wagner, H., L. Horhammer and R. Munster. 1968. "The chemistry of
silymarin (silybin), the active principle of the fruits of Silybum
marianum (L.) Gaertn. (Carduus marianus L.)" Arzneim-Forsch. 18: 688-
Wagner, H. and O. Seligmann. 1985. "Liver therapeutic Drugs from
Silybum marianum." In H. M. Chang, H.W. Yeung, W. W. Tso and A. Koo
(eds.) Advances in Chinese Medicinal Materials Research. Singapore:
World Scientific Publ. Co.
Weiss, R. F. 1988. Herbal Medicine (translated from German by A. R.
Meuss). Beaconsfield, England: Beaconsfield Publishers Ltd.
1990 American Botanical Council
Revised edition 1996 American Botanical Council