Milk Thistle

Review of Milk Thistle

What is Milk Thistle (Silymarin)?

Milk Thistle (Silymarin) contains a number of antioxidant flavonoligans including isosilybin, silybin, silydianin, silychristin and one flavonoid, taxifolin. Silybin is generally believed to be the most potent and bioactive of the flavonoids present in milk thistle. However, recent research suggests there are other flavonolignans in silymarin that are equal to, or possibly more potent than silibinin, including: isosilybin A and taxifolin (Polyak et al., 2010). Milk Thistle has a number of positive effects on health including improved liver function, protection against liver damage, antiviral activity, anticancer activity, enhanced antioxidant levels, anti-inflammatory effects, protection against hepatitis C, and may even offer protection against Alzheimers disease. The main medicinal/therapeutic interest in Milk Thistle has been for its liver protecting properties.

Who Should Consider Taking Milk Thistle (Silymarin)?

Milk thistle may be of benefit to anyone looking to protect their liver, either from an existing condition (e.g. hepatitis C, alcoholic liver disease, or diabetes), or due to long or short term use of certain drugs/medications that are known to be hepatoxic. 

Summary of Milk Thistle's Phyiological Effects:

  • Milk Thistle has potent antioxidant activity and helps to maintain/increase levels of important antioxidant molecules like glutathione and catalase. 
  • Milk thistle acts to protect the liver against hepatoxicity damage
  • Provides protection against the short and long term effects of certain hepatoxic drugs
  • Milk thistle protects the liver from the damaging effects of the hepatitis C virus
  • Is known to have anti-viral activity
  • Milk Thistle has a cancer chemopreventative role and has the potential to inhibit all stages of carcinogenesis 
  • May offer protection against the development of beta-amyloid plaques in alzheimers disease
  • Milk thistle may help to improve liver function and glucose levels in diabetes patients as well protecting against diabetic neuropathy. 
  • Milk thistle appears to be safe and well tolerated.

Milk Thistle (Silymarin) Research

Milk Thistle Antioxidant Activity

The various flavonoligans and the flavonoid taxifolin found within Milk Thistle extract are known to have potent antioxidant activity. Milk thistle extract has antioxidant properties through its ability to: 1) inhibit free-radical formation, 2) by binding some radical species, 3) through interference with lipid peroxidation of membranes, and 4) increasing/maintaining the intracellular content of important antioxidant scavengers such as catalase, glutathione, glutathione peroxidase, glutathione reductase, and superoxide dismutase (Loguercio and Festi 2011). Interestingly, an oxidized form of silybin (2,3-dehydrosilybin) has been shown to have greater antioxidant activity than silybin (Huber et al., 2008) – Normally when an antioxidant is oxidized it loses antioxidant potential.

Milk Thistle and Liver Protection

Milk Thistle extract is believed to protect liver cells in a number of ways: 1) protection against damage by free radicals, 2) helps to stabilize liver cell membranes, 3) stimulating hepatocyte protein synthesis, and 4) modulating the immune response (Mira et al., 1994). Research has shown that milk thistle has a liver protective activity and can even promote the regeneration of damaged liver cells (Das et al., 2011).

A number of studies have shown that milk thistle protects against hepatoxicity damage caused by certain drugs including those used in the treatment of tuberculosis (Eminzade et al., 2008), chemoprevenative drugs (Loguercio and Festi 2011), as well as paracetamol induced hepatoxicity (Das et al., 2011) and can even protect against poisoning by the Amanita mushroom (death cap) (Ganzert et al., 2008). Milk Thistle has also shown to improve liver function and blood platelet counts in workers that were exposed to chemical toxins (Szilard et al., 1988) and appears to be effective against liver damage caused by hepatitis C (Kalantari et al., 2011). Milk thistle is sometimes used by bodybuilders in order to protect against liver toxicity during and after a cycle of steroids or pro-hormones.

Milk Thistle and Hepatitis C

Recent research looked at the effects of Milk Thistle supplementation (630mg/daily of Milk Thistle, for six months) in patients with chronic hepatitis C. Following the supplementation period the hepatitis C patients were found to have significantly improved serum liver enzymes, improved hepatic fibrosis and improved quality of life (Kalantari et al., 2011). Milk thistle was also found to have antiviral effects against hepatitis C (Wagoner et al., 2010) which might further explain the beneficial effects of milk thistle in patients with hepatitis C.

Milk Thistle and Anti-Viral activity

Milk thistle extract has been shown to have anti-viral activity in a number of studies (Biermer & Berg 2009; Ferenci et al., 2008; Wagoner et al., 2010). Recently researchers determined that milk thistle extract had antiviral effects including inhibition of virus entry, RNA and protein expression, and virus production (Wagoner et al., 2010). They researchers found that milk thistle was able to inhibit the entry of viral pseudoparticles and their fusion with liposomes.

Milk Thistle and Chemoprevention

A number of studies have established the cancer chemopreventative role of Milk Thistle extract (Ramasamy and Agarwal 2008). Milk Thistle extract has been reported to suppress cancer cell proliferation in a number of different types of cancers including prostrate (Singh & Agarwal 2006), skin (Deep & Agarwal 2007), and bladder (Tyagi et al., 2004). Milk Thistle also appears to have potential anti-invasive, anti-metastatic potential, and may help to regulate cancer cell death (Ramasamy & Agarwal 2008). In summary, Silymarin exerts its anticancer effects through multiple molecular mechanisms that have the potential to block all stages of carcinogenesis, through initiation, promotion and progression (Ramasamy & Agarwal 2008).

Milk thistle could also prove to be an important adjunct to cancer patients since chemotherapeutic agents are metabolized by the liver and can exert hepatotoxicity. As such many Cancer patients, undertaking chemotherapy, will self-medicate with milk thistle because of its known reputation as a liver protectant. Many Clinicians also prescribe milk thistle to cancer patients to provide additional support to the liver while it performs multiple functions associated with the increased metabolic demands caused by tumor growth, assisting in metabolizing products generated during both chemotherapy and radiation, and aiding in the processing of drugs prescribed to cancer patients (Loguercio & Festi 2011).

Milk Thistle and Alzheimers Disease

Silymarin may offer protection against the development of Alzheimers through its anti-amyloid properties, and protective effect against beta-amyloid accumulation (Murata et al., 2010). In this study the researchers looked at the effect of a Milk Thistle extract on a model of Alzheimers disease in mice using a dose equivalent to 16mg/kg/day in humans – this equates to 1120mg of milk thistle extract for someone weighing 70kg. The researchers concluded that silymarin is a safe natural product that can be used for Alzheimers disease prevention.

Milk Thistle and Diabetes

Milk thistle has been shown to have a restorative effect on liver function whilst helping to control blood glucose levels in diabetes patients with liver disease (Jose et al., 2011). In addition milk thistle may offer protection against diabetic neuropathy (Baluchnejadmojarad et al., 2010), induce recovery of pancreatic function (Soto et al., 2004), provides DNA protection and may counteract oxidative stress in the central nervous system of diabetes patients (Marrazzo et al., 2011).

Is Milk Thistle effective?

Milk thistle appears to be an effective antioxidant that protects liver cells from damage from a number of sources including hepatitis C, certain drugs including chemotherapy drugs and paracetamol. Milk Thistle also appears to have anti-cancer activity, protects againts liver fibrosis, diabetic neuropathy, pancreatic function and may even offer protection against the development of beta-amyloid plaques in Alzheimers disease. 

How to take Milk Thistle?

Current research suggests that patients with an existing liver condition may benefit from a dose of between 400 - 600mg of Silybin per day (Loguercio & Festi 2011; Kalantari et al., 2011; Kidd & Head 2005;) .

Milk Thistle's Side Effects

Milk thistle appears to be safe and well tolerated even at high doses (Loguercio & Festi 2011; Wagoner et al., 2010). 

Milk Thistle References

Baluchnejadmojarad T, Roghani M, Khastehkhodaie Z. (2010) Chronic treatment of silymarin improves hyperalgesia and motor nerve conduction velocity in diabetic neuropathic rat. Phytother Res. 2010 Aug;24(8):1120-5.

Biermer M, Berg T. Rapid suppression of hepatitis C viremia induced by intravenous silibinin plus ribavirin. Gastroenterology. 2009;137:390–391.

Das S, Roy P, Auddy RG, Mukherjee A. (2011) Silymarin nanoparticle prevents paracetamol-induced hepatotoxicity. Int J Nanomedicine. 2011;6:1291-301. doi: 10.2147/IJN.S15160. Epub 2011 Jun 22.

Deep G, Agarwal R. Chemopreventive efficacy of silymarin in skin and prostate cancer. Integr. Cancer Ther. 2007;6:130–145.

Eminzade S, Uraz F, Izzettin FV. (2008) Silymarin protects liver against toxic effects of anti-tuberculosis drugs in experimental animals. Nutr Metab (Lond). 2008 Jul 5;5:18.

Ferenci P, Scherzer TM, Kerschner H, Rutter K, Beinhardt S, Hofer H, Schöniger-Hekele M, Holzmann H, Steindl-Munda P. Silibinin is a potent antiviral agent in patients with chronic hepatitis C not responding to pegylated interferon/ribavirin therapy. Gastroenterology. 2008;135:1561–1567.
Dtsch Med Wochenschr. 2008 Oct;133(44):2261-7. Epub 2008 Oct 22.

Ganzert M, Felgenhauer N, Schuster T, Eyer F, Gourdin C, Zilker T. (2008) Amanita poisoning--comparison of silibinin with a combination of silibinin and penicillin. Dtsch Med Wochenschr. 2008 Oct;133(44):2261-7. Epub 2008 Oct 22.

Huber A, Thongphasuk P, Erben G, Lehmann WD, Tuma S, Stremmel W, Chamulitrat W. Significantly greater antioxidant anticancer activities of 2,3-dehydrosilybin than silybin. Biochim Biophys Acta. 2008;1780:837–847.

Jose MA, Abraham A, Narmadha MP. (2011) Effect of silymarin in diabetes mellitus patients with liver diseases. J Pharmacol Pharmacother. 2011 Oct;2(4):287-9.

Kalantari H, Shahshahan Z, Hejazi SM, Ghafghazi T, Sebghatolahi V. (2011) Effects of silybum marianum on patients with chronic hepatitis C. J Res Med Sci. 2011 Mar;16(3):287-90.

Kidd P, and Head K (2005) A Review of the Bioavailability and Clinical Efficacy of Milk Thistle Phytosome: A Silybin-Phosphatidylcholine Complex (Siliphos) Alternative Medicine Review .Volume 10, 3, 193-203. 

Loguercio C, Festi D. (2011) Silybin and the liver: from basic research to clinical practice. World J Gastroenterol. 2011 May 14;17(18):2288-301.

Marrazzo G, Bosco P, La Delia F, Scapagnini G, Di Giacomo C, Malaguarnera M, Galvano F, Nicolosi A, Li Volti G. (2011) Neuroprotective effect of silibinin in diabetic mice. Neurosci Lett. 2011 Oct 31;504(3):252-6. Epub 2011 Sep 28.

Mira L, Silva M, Manso CF. Scavenging of reactive oxygen species by silibinin dihemisuccinate.Biochem Pharmacol. 1994;48(4):753–9.

Murata N, Murakami K, Ozawa Y, Kinoshita N, Irie K, Shirasawa T, Shimizu T. (2010) Silymarin attenuated the amyloid β plaque burden and improved behavioral abnormalities in an Alzheimer's disease mouse model. Biosci Biotechnol Biochem. 2010;74(11):2299-306. Epub 2010 Nov 7.

Polyak SJ, Morishima C, Lohmann V, Pal S, Lee DY, Liu Y, Graf TN, Oberlies NH. (2010) Identification of hepatoprotective flavonolignans from silymarin. Proc Natl Acad Sci U S A. 2010 Mar 30;107(13):5995-9. Epub 2010 Mar 15.

Ramasamy K, Agarwal R. (2008) Multitargeted therapy of cancer by silymarin. Cancer Lett. 2008 Oct 8;269(2):352-62. Epub 2008 May 9.

Soto C, Mena R, Luna J, Cerbón M, Larrieta E, Vital P, Uría E, Sánchez M, Recoba R, Barrón H, Favari L, Lara A (2004) Silymarin induces recovery of pancreatic function after alloxan damage in rats. Life Sci. 2004 Sep 17;75(18):2167-80.

Singh RP, Agarwal R. (2006) Prostate cancer chemoprevention by silibinin: bench to bedside. Mol. Carcinog. 2006;45:436–442.

Szilard S, Szentgyorgyi G, Dhanalakshmi S et al. (1988). Protective effect of Legalon in workers exposed to organic solvents. Acta Med Hung. 45: 249-256.

Tyagi A, Agarwal C, Harrison G, Glode LM, Agarwal R. Silibinin causes cell cycle arrest and apoptosis in human bladder transitional cell carcinoma cells by regulating CDKI-CDK-cyclin cascade, and caspase 3 and PARP cleavages. Carcinogenesis. 2004;25:1711–1720.

Wagoner J, Negash A, Kane OJ, Martinez LE, Nahmias Y, Bourne N, et al. Multiple effects of silymarin on the hepatitis C virus lifecycle. Hepatology. 2010;51(6):1912–21.