By Christopher Tack | Clinical Specialist Physiotherapist
Milk thistle (in Latin named Silybum Marianum) has been used across Europe since the first century and has even been documented in historical texts including the works of Pliny the Elder, a Roman historian and author who wrote the first encyclopaedia of natural history (1). This plant’s leaves, flowers and roots have been eaten as a vegetable, and its seed-like fruits have been consumed for hundreds of years as a coffee alternative.
However now it seems to make a resurgence in popularity as a health aid. This article will examine the scientific theory supporting its benefits and help you decide whether it is worth adding to your health regime.
What Is Milk Thistle?
Milk thistle is a tall herb which grows to approximately 10 feet high in various corners of the globe, including Southern and Western Europe, South America and the Eastern United States. It characteristically has large purplish flowers and small hard seed-like fruits (called achenes) which are the source of its medicinal properties.
In fact, the dried seeds contain approximately 1-4% of the flavonoid mixture, silymarin (2). It is these seeds which are used to create the concentrated silymarin extract that has a higher percentage of 65-80% flavonolignans, flavonoids, fatty acids and other natural plant compounds which have various regulatory effects on our metabolism (3).
The most important of these various compounds seems to be silibinin, which was discovered in 1959 and designated the primary active ingredient in silymarin (4-5). As such you will always see the concentration or amount of silymarin and silibinin stated on packets of milk thistle extract.
Milk Thistle Benefits
The benefits of silymarin have long been recognised in people with liver disorders (6), in fact, it is often considered the gold standard drug to treat liver problems, and milk thistle has long been a traditional herbal alternative for this population (7). Research indicates that silymarin provides both anti-oxidant and chemoprotective benefits for the liver (8-14).
However, its benefits have also been extended through research in its use for the heart, nervous system and kidneys (15-17). We will examine the proposed benefits of silymarin more closely.
Is Milk Thistle An Anti-Oxidant?
It is worth describing why anti-oxidants are so important. We are reliant on oxygen for our survival. However, a by-product of the use of oxygen for metabolism is the formation of reactive oxygen species (ROS) or free radicals, which we use for cellular signalling and homeostasis.
ROS include peroxides, superoxide and hydroxyl radical, which all have negative effects on our body as facilitators of oxidative damage, aging and age-related diseases (18).
Of course in order to survive, we have developed specific protective mechanisms to deal with ROS and prevent oxidative stress (19), and it is the presence of natural anti-oxidants in organisms which enable these mechanisms to work.
Silymarin contributes to our oxidative protection in various ways.
? Directly scavenging free radicals (and in essence removing free radicals from the cellular environment)
? By inhibiting enzymes which allow free radical formation
? By maintaining the electron transport chain during stress conditions
? By activating anti-oxidant enzymes and transcription factors which are responsible for the synthesis of protective molecules (such as thioredoxin and HSP)
? By reducing the inflammatory response through inhibition of NF-?B pathways (which is a protein complex which regulates the immune response). (20).
Based upon these mechanisms there is a vast array of research examining the influence of silymarin in both animals and humans (15-17, 21-22).
For example, experiments in rats demonstrated that a two-week course of silibinin prevented drug-induced lipid peroxidation (23), which is supported by laboratory experiments examining the preventative effect of silibinin on low-density lipoprotein peroxidation (24).
In other experiments, silibinin also showed a significant anti-oxidant protective benefit for rats exposed to chronic iron overload and prevented liver toxicity (25). In human studies, the anti-oxidant benefits of silymarin have been shown in people with alcoholic cirrhosis by silymarin enhancing the levels of the enzyme superoxide dismutase in both red and white blood cells. This enzyme breaks down the free radical superoxide, as such preventing oxidative cellular damage (26).
Milk Thistle (Silymarin) | Evidence-Based Uses
As stated earlier, historically the key target of milk thistle supplementation has been the reduction of liver disease. In fact in Europe silymarin is used to manage the impact of various toxins which cause liver damage (27). These would include alcohol, chemotherapy agents and paracetamol (28-30).
In clinical studies the use of silymarin has been shown to facilitate protection against liver damage, and one of the primary attributes of silymarin has been identified are its anti-oxidant functions (31-32).
However, this is not its only benefit. Another key function identified is its reduction of specific liver enzymes which are involved in liver cell damage.
In a large study of 2,637 people with liver disease treatment with a milk thistle extract for 8 weeks resulted in substantial decreases in liver enzymes and a boost in physician satisfaction of treatment in 88% of cases (33).
Similar findings have been found in a number of randomised controlled trials of the same extract in those with the alcohol-induced liver disease over a period of 4 weeks (34-37).
Additionally, milk thistle has further influences in the regenerative capacity of the liver; assists in the formation of new liver cells and provides further cellular protection by stabilising liver cell membranes to prevent toxins moving into the cells (6). The larger impact of these physiological benefits is the impediment of fibrosis and cirrhosis due to excessive liver inflammation (commonly seen in alcoholism) (38); improved immune function and response to liver damage (39); and significantly reduced mortality (20%) (40-41).
Both animal and human studies show that silymarin provides a protective benefit for the pancreas in diabetes (42-43).
In experiments with rats exposed induced- diabetes the pancreas was provided protection by silymarin against oxidative stress and sustained levels of glucose whilst inhibiting insulin secretion (42,44).
In human studies with people with alcoholic cirrhosis and insulin-dependent diabetes, milk thistle extract showed significant reductions in mean daily blood glucose, fasting blood sugar, loss of glucose in urine, and insulin needs over 6 months (43,45). Of course, all these factors indicate better glycaemic control and less risk associated with uncontrolled diabetes.
Immune System: Anti-inflammatory
Another benefit of milk thistle is silibinin’ effect on our immune system, therefore its ability for us to fight off infection and inflammation.
For example, in those with alcoholic cirrhosis, a variety of components of the immune system are enhanced when silymarin is provided (46). This includes the transformation of lymphoblasts which are immature white blood cells which can develop into our natural killer cells (lymphocytes) and assist removal of infection agents via our lymphatic system.
Additionally in this population silymarin also induces a significant reduction of lymphocytotoxicity indicating the greater health of the lymph cells and more effective immune system response (46).
In healthy people, silibinin provides similar benefits however notably it is found that milk thistle extract supplementation can increase the motility (movement) of our most potent immune system m white blood cells (leukocytes). This would suggest an enhanced immune response to infection or inflammatory reaction (e.g. through injury) (47).
A final benefit of milk thistle and its constituent parts are amazingly a chemopreventative effect- which is where it is used to treat cancer.
The predominant amount of research of silymarin and silibinin has been in laboratory experiments with cells (rather than in human test subjects). For example, cancer treatment benefits have been seen in both human and mouse skin, prostate and breast cancer cell lines (48-55).
Additionally, cell protection effects are seen in rodent liver and trachea cells when exposed to carcinogens, and similar protection was seen in human testicular cells (56-57).
Probably most impressively there has also been one documented case study of a 52-year-old man who underwent a biopsy and was diagnosed with the most common form of liver cancer, a malignant hepatoma (58).
Astonishingly, this cancer was seen to spontaneously resolve following the self-medication by 450mg silymarin by the gentleman in question. Now whilst I wouldn’t advise self-medication for known cancer, this does emphasise the truly active health advantageous afforded to you if milk thistle was to become part of your health supplement regime.
Safety & Side Effects
Studies involving several thousand subjects have been unable to show any significant cautions or side effects to consuming milk thistle (59). In fact, the prevalence of side effects are low and generally limited to mild stomach upset (33).
As always caution is always wise in certain populations (e.g. during pregnancy and childhood)- however, it is presumed safe as it has long been consumed as a food source and no negative effects have been reported historically (60).
A range of doses have been described in the literature between 280-800mg of silymarin daily, and the average concentration of silymarin in milk thistle extract is described as between 70-80% (6).
Some studies describe a dosage of 100mg of silymarin three times per day as the supplements absorption is seen to be optimal with this regime (61). As such most recommendations suggest 100-200mg three times daily alongside your meals (62-63).
Take Home Message
Often when you delve into the scientific theory surrounding herbal supplements you find yourself wanting. Sometimes the natural remedy gurus will overestimate the impact of some herbal supplements, however this is not the case for milk thistle.
Historical use and scientific backing are in favour of the use of this herb as an anti-oxidant and cellular protective agent. Two good reasons to consider its use in your daily nutrition regime.
Our articles should be used for informational and educational purposes only and are not intended to be taken as medical advice. If you’re concerned, consult a health professional before taking dietary supplements or introducing any major changes to your diet.
- Luper S. A review of plants used in the treatment of liver disease: part 1. Altern Med Rev 1998; 3:410-21.
- Schulz V, Hansel R, Tyler VE. Rational Phytotherapy: A Physicians’ Guide to Herbal Medicine. Berlin: Springer, 1997:306
- Comelli, M.C.; Mengs, U.; Prosdocimi, M.; Schneider, C. Toward the definition of the mechanism of action of silymarin: Activities related to cellular protection from toxic damage induced by chemotherapy. Integr. Cancer Ther. 2007, 6, 120–129.
- Křen, V.; Marhol, P.; Purchartová, K.; Gabrielová, E.; Modrianský, M. Biotransformation of silybin and its congeners. Curr. Drug MeTable 2013, 14, 1009–1021.
- Hackett, E.S.; Twedt, D.C.; Gustafson, D.L. Milk thistle and its derivative compounds: A review of opportunities for treatment of liver disease. J. Vet. Intern. Med. 2013, 27, 10–16.
- Bruno G. (2009). Milk Thistle: Smart Supplementation. Literature Education Series On Dietary Supplements; Huntington College of Health Sciences.
- Testino, G.; Leone, S.; Ansaldi, F.; Borro, P. Silymarin and S-adenosyl-L-methionine (SAMe): Two promising pharmacological agents in case of chronic alcoholic hepathopathy. A review and a point of view. Minerva Gastroenterol. Dietol. 2013, 59, 341–3
- Post-White, J.; Ladas, E.J.; Kelly, K.M. Advances in the use of milk thistle (Silybum marianum). Integr. Cancer Ther. 2007, 6, 104–109.
- Loguercio, C.; Federico, A.; Trappoliere, M.; Tuccillo, C.; de Sio, I.; di Leva, A.; Niosi, M.; D’Auria, M.V.; Capasso, R.; del Vecchio Blanco, C.; et al. The effect of a silybin-vitamin E-phospholipid complex on nonalcoholic fatty liver disease: A pilot study. Dig. Dis. Sci. 2007, 52, 2387–2395.
- Federico, A.; Niosi, M.; del Vecchio Blanco, C.; Loguercio, C. Emerging drugs for non-alcoholic fatty liver disease. Exp. Opin. Emerg. Drugs 2008, 13, 145–158.
- Trappoliere, M.; Caligiuri, A.; Schmid, M.; Bertolani, C.; Failli, P.; Vizzutti, F.; Novo, E.; di Manzano, C.; Marra, F.; Loguercio, C.; et al. Silybin, a component of sylimarin, exerts anti-inflammatory and anti-fibrogenic effects on human hepatic stellate cells. J. Hepatol. 2009, 50, 1102–1111.
- Loguercio, C.; Festi, D. Silybin and the liver: From basic research to clinical practice. World J. Gastroenterol. 2011, 17, 2288–2301.
- Loguercio, C.; Andreone, P.; Brisc, C.; Brisc, M.C.; Bugianesi, E.; Chiaramonte, M.; Cursaro, C.; Danila, M.; de Sio, I.; Floreani, A.; et al. Silybin combined with phosphatidylcholine and vitamin E in patients with nonalcoholic fatty liver disease: A randomized controlled trial. Free Radic. Biol. Med. 2012, 52, 1658–1665.
- Stiuso, P.; Scognamiglio, I.; Murolo, M.; Ferranti, P.; de Simone, C.; Rizzo, M.R.; Tuccillo, C.; Caraglia, M.; Loguercio, C.; Federico, A. Serum oxidative stress markers and lipidomic profile to detect NASH patients responsive to an antioxidant treatment: A pilot study. Oxid. Med. Cell Longev. 2014, 2014, 169216.
- Milić, N.; Milosević, N.; Suvajdzić, L.; Zarkov, M.; Abenavoli, L. New therapeutic potentials of milk thistle (Silybum marianum). Nat. Prod. Commun. 2013, 8,1801–1810.
- Zholobenko, A.; Modriansky, M. Silymarin and its constituents in cardiac preconditioning. Fitoterapia 2014, 97, 122–132.
- Mohd Fozi, N.F.; Mazlan, M.; Shuid, A.N.; Isa Naina, M. Milk thistle: A future potential anti-osteoporotic and fracture healing agent. Curr. Drug Targets 2013, 14, 1659–1666.
- Romano, A.D., Serviddio, G., de Matthaeis, A., Bellanti, F. and Vendemiale, G., 2009. Oxidative stress and aging. Journal of nephrology, 23, pp.S29-36.
- Surai, P.F.; Fisinin, V.I. Antioxidant Systems of the Body: From Vitamin E to Polyphenols and Beyond. In Proceedings of the 35th Western Nutrition Conference, Edmonton, Canada, 24–25 September 2014; pp. 265–277.
- Surai, P.F., 2015. Silymarin as a natural antioxidant: An overview of the current evidence and perspectives. Antioxidants, 4(1), pp.204-247.
- Madrigal-Santillán, E.; Madrigal-Bujaidar, E.; Álvarez-González, I.; Sumaya-Martínez, M.T.; Gutiérrez-Salinas, J.; Bautista, M.; Morales-González, Á.; García-Luna, Y.; González-Rubio, M.; Aguilar-Faisal, J.L.; et al. Review of natural products with hepatoprotective effects. World J. Gastroenterol. 2014, 20, 14787–14804.
- Vargas-Mendoza, N.; Madrigal-Santillán, E.; Morales-González, A.; Esquivel-Soto, J.; Esquivel-Chirino, C.; García-Luna, Y.; González-Rubio, M.; Gayosso-de-Lucio, J.A.; Morales-González, J.A. Hepatoprotective effect of silymarin. World J. Hepatol. 2014, 6, 144–149.
- Zima T, Kamenikova, L., Janebova, M., Buchar, E., Crkovska, T., Tesar, V. The effect of silibinin on experimental cyclsporine nephrotoxicity. Renal Failure 1998; 20:471-479.
- Locher R, Suter PM, Weyhenmeyer R, Vetter W. Inhibitory action of silibinin on low density lipoprotein oxidation. Arzneimittelforschung 1998; 48:236-9
- Pietrangelo A, Borella F, Casalgrandi G, Montosi G, Ceccarelli D, Gallesi D, et al. Antioxidant activity of silybin in vivo during long-term iron overload in rats. Gastroenterology 1995; 109:1941-9.
- Feher J, Lang I, Nekam K, Gergely P, Muzes G. In vivo effect of free radical scavenger hepatoprotective agents on superoxide dismutase (SOD) activity in patients. Tokai J Exp Clin Med 1990; 15:129-34.
- Flora K, Hahn M, Rosen H, Benner K. Milk thistle (Silybum marianum) for the therapy of liver disease. Am J Gastroenterol 1998; 93:139-43.
- Brinker F. Herb Contraindications and Drug Interactions, 2nd ed. Sandy (OR): Eclectic Med; 1998.
- Kohno H, et al. Silymarin, a naturally occurring polyphenolic antioxidant flavonoid, inhibits azoxymethane-induced colon carcinogenesis in male F344 rats. Int J Cancer 2002; 101(5):461-8.
- Tyagi A, et al. Antiproliferative and apoptotic effects of silibinin in rat prostate cancer cells. Prostate 2002; 53(3):211-217.
- Badr FM, El Habit OH, Harraz MM. Radioprotective effect of silymarin against radiation induced hepatotoxicity. Pharmacol Res. 2002; 45(6):447.
- Buzzelli G, Moscarella S, Giusti A, et al. A pilot study on the liver protective effect of ilybinphosphatidylcholine complex (IdB 1016) in chronic active hepatitis. Int J Clin Pharmacol Ther Toxicol 1993; 31:456-60.
- Albrecht M. Therapy of toxic liver pathologies with Legalon. Z Klin Med 1992; 47:87-92.
- Salmi HA, Sarna, S. Effect of silymarin on chemical, functional, and morphological alterations of the liver: A double-blind controlled study. Scand J Gastroenterol 1982; 17:517-521.
- Lang I, Nekam, K., Gonzalez-Cabello, R., Gergely, P., Feher, J. Hepatoprotective and immunolical effects of antioxidant drugs. Tokai J Exp Clin Med 1990; 15:123-127.
- Feher J, Deak G, Muzes G, Lang I, Niederland V, Nekam K, et al. Liver-protective action of silymarin therapy in chronic alcoholic liver diseases. Orv Hetil 1989; 130:2723-7.
- Lang I, Deak G, Nekam K, Muzes G, Gonzalez-Cabello R, Gergely P, et al. Hepatoprotective and immunomodulatory effects of antioxidant therapy. Acta Med Hung 1988; 45:287-95.
- Schuppan D, Strosser W, Burkard G, Walosek G. LegalonR lessens fibrosing activity in patients with chronic liver diseases. Zeits Allgemeinmed 1998; 74:577-84.
- Deak G, Muzes, G., Land, I., Niederland, V., Kristof, N., Gonzalez Cabello, R., Gergely, P., Feher, J. Immunomodulatory effects of silymarin treatment in chronic alcoholic liver disease. Orvosi Hetilap 1990; 131:1291-1292, 1295-1296.
- Ferenci P, Dragosics, B., Dittrich, H., Benda, L., Lochs, H., Meryn, S., Base, W., Schneider, B. Randomized controlled trial of silymaring treatment in patients with cirrhosis of the liver. Journal of Hepatology 1989; 9:105-113.
- Benda L, Dittrich H, Ferenzi P, Frank H, Wewalka F. The influence of therapy with silymarin on the survival rate of patients with liver cirrhosis. Wien Klin Wochenschr 1980 92:678-83
- Soto CP, Perez, B.L., Favari, L.P., Reyes, J.L. Prevention of alloxan-induced diabetes mellitus in the rat by silymarin. Comparative Pharmacolgy & Toxicology 1998; 119:125- 129.
- Velussi M, Cernigoi AM, De Monte A, Dapas F, Caffau C, Zilli M. Long-term (12 months) treatment with an anti-oxidant drug (silymarin) is effective on hyperinsulinemia, exogenous insulin need and malondialdehyde levels in cirrhotic diabetic patients. J Hepatol 1997; 26:871-9.
- von Schonfeld J, Weisbrod B, Muller MK. Silibinin, a plant extract with antioxidant and membrane stabilizing properties, protects exocrine pancreas from cyclosporin A toxicity. Cell Mol Life Sci 1997; 53:917-20.
- Velussi M, Cernigoi, A.M., Viezzoli, L., Dapas, F., Caffau, C., Zilli, M. Silymarin reduces hyperinsulinemia, malondialdehyde levels, and daily insulin needs in cirrhotic diabetic patients. Current Therapeutic Research 1993; 53:533-545.
- Lang I, Nekam K, Gonzalez-Cabello R, Muzes G, Gergely P, Feher J. Hepatoprotective and immunological effects of antioxidant drugs. Tokai J Exp Clin Med 1990; 15:123-7.
- Kalmar L, Kadar, J., Somogyi, A. et al. Silibinin (Legalon-70) enhances the motility of human neutrophils immobilzed by formyl-tripeptide, calcium ionophore, lymphokine and by normal human serum. Agents and Actions 1990; 29:239-246.
- Ahmad N, Gali H, Javed S, Agarwal R. Skin cancer chemopreventive effects of a flavonoid antioxidant silymarin are mediated via impairment of receptor tyrosine kinase signaling and perturbation in cell cycle progression. Biochem Biophys Res Commun 1998; 247:294-301.
- Katiyar SK, Korman NJ, Mukhtar H, Agarwal R. Protective effects of silymarin against photocarcinogenesis in a mouse skin model. J Natl Cancer Inst 1997; 89:556-66.
- Mehta RG, Moon RC. Characterization of effective chemopreventive agents in mammary gland in vitro using an initiation-promotion protocol. Anticancer Res 1991; 11:593-6.
- Lahiri-Chatterjee M, Katiyar SK, Mohan RR, Agarwal R. A flavonoid antioxidant, silymarin, affords exceptionally high protection against tumor promotion in the SENCAR mouse skin tumorigenesis model. Cancer Res 1999; 59:622-32.
- Zi X, Mukhtar H, Agarwal R. Novel cancer chemopreventive effects of a flavonoid antioxidant silymarin: inhibition of mRNA expression of an endogenous tumor promoter TNF alpha. Biochem Biophys Res Commun 1997; 239:334-9.
- Zi X, Grasso AW, Kung HJ, Agarwal R. A flavonoid antioxidant, silymarin, inhibits activation of erbB1 signaling and induces cyclin-dependent kinase inhibitors, G1 arrest, and anticarcinogenic effects in human prostate carcinoma DU145 cells. Cancer Res 1998; 58:1920-9.
- Zi X, Feyes DK, Agarwal R. Anticarcinogenic effect of a flavonoid antioxidant, silymarin, in human breast cancer cells MDA-MB 468: induction of G1 arrest through an increase in Cip1/p21 concomitant with a decrease in kinase activity of cyclin-dependent kinases and associated cyclins. Clin Cancer Res 1998; 4:1055-64.
- Zi X, Agarwal R. Silibinin decreases prostate-specific antigen with cell growth inhibition via G1 arrest, leading to differentiation of prostate carcinoma cells: Implications for prostate cancer intervention. Proc Natl Acad Sci U S A 1999; 96:7490-7495.
- Zhang JP, Hu ZL, Feng ZH, Lin W, Yu XB, Qian DH. Effect of silymarin on mouse liver damage, production and activity of tumor necrosis factor. Yao Hsueh Hsueh Pao 1996; 31:577-80.
- Steele VE, Kelloff GJ, Wilkinson BP, Arnold JT. Inhibition of transformation in cultured rat tracheal epithelial cells by potential chemopreventive agents. Cancer Res 1990; 50:2068-74.
- Grossmann M, Hoermann R, Weiss M, Jauch KW, Oertel H, Staebler A, et al. Spontaneous regression of hepatocellular carcinoma. Am J Gastroenterol 1995; 90:1500-3
- McGuffin M, Hobbs C, Upton R, Goldberg A (eds). American Herbal Products Association’s Botanical Safety Handbook: Boca Raton:CRC Press; 1997
- Giannola C, Buogo F, Forestiere G, Scaffidi L, Ferrigno V, Scaffidi A. A two-center study on the effects of silymarin in pregnant women and adult patients with so-called minor hepatic insufficiency. Clin Ter 1985; 114:129-35.
- Pepping J. Milk thistle: Silybum marianum. Am J Health-System Pharm 1999; 56:1195-7.
- Ottariano SG. Medicinal herbal therapy : a pharmacist’s view. Portsmouth, NH: Nicoln Fields Pub., 1999
- Flynn R, Roest M. Your guide to standardized herbal products. Prescott, AZ: One World Press, 1995.[/su_spoiler]