MILK THISTLE: Silybum marianum

The article reports on the health benefits offered by the herbal plant milk thistle, also known as Silybum marianum. The herbal plant has been found to prevent and treat several diseases, includi...

Milk thistle (Silybum marianum (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.

Nomenclature

"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, 1886-87). 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, 1931). 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).

Medical History

In one form or another, various preparations of milk thistle, especially the seeds, have been used medicinally for over 2,000 years. In modern research scientists often attempt to find new biologically active plant substances through random screening methods. However, Silybum is a classic example of the value of utilizing historical records for the development of modern herb products. 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 on the 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." 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...."

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 also state,"Congestion of the liver, spleen, and kidneys is relieved by its 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). Wagner et 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, and silychristin (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 (Der Marderosian and Liberti, 1988).

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 various toxic 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 (FV(3)), lanthanides, and the poisonous substances of the death cap fungus, phalloidin and alpha-amanitin (Blumenthal, et al., 1996). Further studies have suggested that pretreatment with silymarin inhibits alcohol-induced liver damage and has also established pharmacological mechanisms for the inhibitory action, including scavenging of free radicals, leukotrienes, and an ability to stimulate liver protein synthesis. These studies are reviewed by Hikino and Kiso (1988).

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 death cap fungus, 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 (Blumenthal, et al., 1996).

Remarkable studies have shown that certain milk thistle preparations can produce both a protective and curative effect on liver damage resulting from the highly toxic compounds, phalloidin and alpha-amanitin (from the death cap Amanita phalloides, 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 anti-hepatotoxic (anti-liver toxic) effect, when it was administered before poisoning by phalloidin. In their 1969 study, Vogel and Temme showed 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 Amanita toxins by competing with the toxins for the same receptor on cell membranes (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 study by G. Poser (1971) reported that 67 subjects who had been treated as out patients for toxic-metabolic liver damage, chronic hepatitis, and bile duct 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-oxalacetic transaminase), GPT (glutamic-pyruvic transaminase) and Gamma-GT (gamma-glutamyl-transpeptidase).

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, 1981; Feher and 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, Gamma-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 psychopharmaceuticals 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 in damaged liver tissue, and that these effects are important in the therapeutic efficacy of silymarin.

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.

Summary

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.

References:

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(1):3-49.

Culpepper, N. 1787. The English Physician Enlarged. Dublin: H. Colbert.

Der Marderosian, A. and L. Liberti. 1988. Natural Product Medicine: A Scientific Guide to Foods, Drugs, Cosmetics. Philadelphia: George F. Stickley Co.

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, Lübeck, pp. 54-58.

Feher, J. and I. 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 130:51.

Felter, 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., O. Weber, P. Tschumi, and M. Ulbrich. 1982. "Poisoning by the Deathcap Fungus (Amanita phalloides): Prognostic Factors and Therapeutic Measures." Schwiz. Med. Wochenschrift 112:1164-1177.

Grieve, M. 1931. A Modern Herbal. 2 vols. New York: Harcourt, Brace & Company.

Halbach, G. 1976. "Chemistry of Silymarin and Water-soluble Derivatives" In: R. Braatz and C.C. Schneider (eds.) Symposium 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 Press.

Keppler, D., R. Lesch, W. Reutter and K. Decker. 1968. Exp. Mil. Pathol. 9:279.

"Monographien Homöopathischer Arzneimittel." 1985. 19. Erg.-Lieferung ZRvA, Dec. 1986.

Nicholson, G. 1886-87. Dictionary of Gardening. Vol. 3. London: L. Upcott Gill.

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 & Schwarzenberg.

Vogel, G. 1981. Proceedings of the International Bioflavonoid Symposium, Munich.

Wagner, H., L. Hörhammer 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: 688-696.

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.

American Botanical Council.

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By Steven Foster

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