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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 believed to be the most potent and bioactive of the flavonoids present in milk thistle and makes up around 60-70% of silymarin. 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
Milk thistle is known to possess potent antioxidant and anti-inflammatory properties (El-Lakkany et al., 2012; Loguercio and Festi 2011). It appears to exert its antioxidant, anti-inflammatory, and protective properties through a combination of: 1) trapping and neutralising free-radicals; 2) enhancement of glucuronidation – a process through which toxins, pollutants, drugs etc can be detoxified and removed from the body; 3) protection against the depletion of antioxidant scavengers such as catalase, glutathione, glutathione peroxidases, glutathione reductase , and superoxide dismutases; 4) protection and stabilizing of cytoplasmic membranes; 5) protection against lipid peroxidation; 6) regeneration of the liver, and; 7) enhancement of protein synthesis (El-Lakkany et al., 2012; Mesallamy et al., 2011; Loguercio and Festi 2011).

Researchers (Mesallamy et al., 2011) have demonstrated that pre-treatment with silymarin significantly protected the levels and activity of endogenous antioxidants (glutathione, glutathione peroxidases, glutathione reductase and superoxide dismutase) following administration with N-nitrosodiethylamine (NDEA) – a known carcinogen that increases free-radicals, oxidative stress and peroxidation. Treatment with silymarin also lowered levels of malondialdehyde – an indication of reduced lipid peroxidation. It appears that milk thistle possesses antioxidant activity on a number of levels including a direct antioxidant activity as well as protection of endogenous antioxidant scavenging molecules.

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) increases endogenous antioxidants and enzymes, 3) protects liver cell membranes by reducing lipid peroxidation, 4) stimulates protein synthesis, 5) enhances toxin removal, and 6) and can help to regenerate the liver (El-Lakkany et al., 2012; 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), poisoning by the Amanita mushroom (death cap) (Ganzert et al., 2008), exposure 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 also appears to have and anti-fibrotic effect and may help to prevent the progression from liver fibrosis to the irreversible liver cirrhosis (El-Lakkany et al., 2012). Milk thistle is a popular supplement amongst bodybuilders who take the supplement 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 has also been found to have antiviral effects against hepatitis C (Wagoner et al., 2010; Ashfaq et al., 2011) and appeared to inhibit the hepatitis C RNA expression (Ashfaq et al., 2011).

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; Ashfaq et al., 2011). Milk thistle appears to exert its antiviral effects by inhibiting viral entry into the cell (Wagoner et al., 2010) as well as inhibiting viral RNA expression and synthesis (Ashfaq et al., 2011; Song and Choi 2011; Wagoner et al., 2010).

Milk Thistle and Chemoprevention
A number of studies have established the chemopreventative role of Milk Thistle extract (Mesallamy et al., 2011; Ramasamy and Agarwal 2008). Milk Thistle extract has been reported to possess a chemopreventive effect in a number of different types of cancers including liver (Mesallamy et al., 2011), prostrate (Singh & Agarwal 2006), skin (Deep & Agarwal 2007), and bladder (Tyagi et al., 2004). Milk Thistle appears to exert it’s chemopreventative activity through anti-angiogenic (inhibiting the growth of new blood vessels to tumours), antigenotoxic (protection against substances that damage DNA and may result in cancers), antioxidant, anti-metastatic activity (protection against the spread of cancer from one organ to another) and through regulation of apoptosis (programmed cell death) (Mesallamy et al., 2011; Ramasamy & Agarwal 2008).

Since chemotherapy drugs may have a damaging effect on the liver, Milk thistle could also prove to be an important addition to cancer patients undergoing chemotherapy. The livers of patients undergoing chemotherapy are put under increased strain since the liver is the organ that breaks down the chemotherapy drugs and a number of chemotherapy drugs are known to have a level of liver toxicity. Research looking at milk thistle has reported a liver protective effect against chemotherapy drugs in humans (McBride et al., 2012; Ladas et al., 2010) and animals (Rašković et al., 2011).

Milk Thistle and Alzheimers Disease
Recent research suggests that milk thistle extract may provide protection against the development of Alzheimers through the inhibition of Beta Amyloid aggregation, reducing the levels of oxidative stress and neurotoxicity associated with Beta amyloid aggregation (Yin et al., 2011; Murata et al., 2010; Lu et al., 2009).

Milk Thistle and Diabetes
Milk thistle appears to be beneficial in the treatment of diabetes by helping to control blood glucose levels (Jose et al., 2011; Huseini et al., 2006), protecting against diabetic neuropathy (Baluchnejadmojarad et al., 2010; Soto et al., 2010; Vessal et al., 2010;), maintaining pancreatic function (Soto et al., 2004), and protecting against oxidative stress (Marrazzo et al., 2011; Soto et al., 2010).

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

Ashfaq U A, Javed T, Rehman S, Nawaz Z. and Riazuddin S. (2011) Inhibition of HCV 3a core gene through Silymarin and its fractions. Virology Journal 2011, 8:153 doi:10.1186/1743-422X-8-153

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.

El Mesallamy HO, Metwally NS, Soliman MS, Ahmed KA, Abdel Moaty MM. (2011) The chemopreventive effect of Ginkgo biloba and Silybum marianum extracts on hepatocarcinogenesis in rats. Cancer Cell Int. 2011 Oct 31;11(1):38.

El-Lakkany N M, Hammam O A, El-Maadawy W H, Badawy A A , Ain-Shoka A A and Ebeid F A (2012) Anti-inflammatory/anti-fibrotic effects of the hepatoprotective silymarin and the schistosomicide praziquantel against Schistosoma mansoni-induced liver fibrosis. Parasites & Vectors 2012, 5:9 (11 January 2012)

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.

Huseini HF, Larijani B, Heshmat R, Fakhrzadeh H, Radjabipour B, Toliat T, Raza M. (2006) The efficacy of Silybum marianum (L.) Gaertn. (silymarin) in the treatment of type II diabetes: a randomized, double-blind, placebo-controlled, clinical trial. Phytother Res. 2006 Dec;20(12):1036-9.

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. 

Ladas EJ, Kroll DJ, Oberlies NH, Cheng B, Ndao DH, Rheingold SR, Kelly KM. (2010) A randomized, controlled, double-blind, pilot study of milk thistle for the treatment of hepatotoxicity in childhood acute lymphoblastic leukemia (ALL). Cancer. 2010 Jan 15;116(2):506-13.

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.

Lu P, Mamiya T, Lu LL, Mouri A, Zou L, Nagai T, Hiramatsu M, Ikejima T, Nabeshima T. (2009) Silibinin prevents amyloid beta peptide-induced memory impairment and oxidative stress in mice. Br J Pharmacol. 2009 Aug;157(7):1270-7. Epub 2009 Jun 22.

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.

McBride A, Augustin KM, Nobbe J, Westervelt P. (2012) Silybum marianum (milk thistle) in the management and prevention of hepatotoxicity in a patient undergoing reinduction therapy for acute myelogenous leukemia. J Oncol Pharm Pract. 2012 Feb 29. [Epub ahead of print]

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.

Rašković A, Stilinović N, Kolarović J, Vasović V, Vukmirović S, Mikov M. (2011) The protective effects of silymarin against doxorubicin-induced cardiotoxicity and hepatotoxicity in rats. Molecules. 2011 Oct 12;16(10):8601-13.

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

Song JH and Choi HJ. (2011) Silymarin efficacy against influenza A virus replication. Phytomedicine. 2011 Jul 15;18(10):832-5. Epub 2011 Mar 5.

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.

Soto C, Pérez J, García V, Uría E, Vadillo M, Raya L. (2010) Effect of silymarin on kidneys of rats suffering from alloxan-induced diabetes mellitus. Phytomedicine. 2010 Dec 1;17(14):1090-4. Epub 2010 Jun 25.

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.

Vessal G, Akmali M, Najafi P, Moein MR, Sagheb MM. (2010) Silymarin and milk thistle extract may prevent the progression of diabetic nephropathy in streptozotocin-induced diabetic rats. Ren Fail. 2010 Jul;32(6):733-9.

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.
 

Yin F, Liu J, Ji X, Wang Y, Zidichouski J, Zhang J. (2011) Silibinin: a novel inhibitor of Aβ aggregation. Neurochem Int. 2011 Feb;58(3):399-403. Epub 2010 Dec 24.