Milk Thistle

Overview

Milk thistle is a common weed that has a long history as a traditional medicine and food. Its potent activity in restoring and protecting the liver has been confirmed in a number of studies, and it is often included in herbal medicines intended to act as “detoxification” formulas. The main active constituents of milk thistle are the flavonolignans, and the bioactive flavonolignans are generally called silymarin as an umbrella term. Silymarin has 3 isomers: silybin (also called silibinin), silydianin, and silychristin (McKenna et al., 2001).

Silymarin has exhibited cholesterol lowering and normalizing activity, reduced high blood pressure in hypertensive patients, antiproliferative activity in cancer cells, and chemoprotective activity. However, the preclinical data that most relates to the traditional use and current herbal use of milk thistle is focused on hepatic functions and its antioxidant activity (McKenna et al., 2001). Some highlights of this preclinical data follows:

•Silymarin has shown hepatoprotective activity against a number of toxins, including carbon tetrachloride, galactosamine, ethanol, paracetamol, Amanita toxins, thioacetamide, microcystin-LR, heavy metals, poisons of lanthanden, sulfur acetamide, and the FU3 virus (a hepatotoxic virus of cold blooded animals) (Morazzoni and Bombardelli, 1995; Bone, 1996).

•Silymarin has shown activity against peroxidation in liver microsomes of the rat (Bosisio et al., 1992).

•Silymarin has hepatorestorative properties, and the primary mechanism it is thought to accomplish this through is the stimulation of protein synthesis. Silymarin stimulates the activity of RNA polymerase which synthesizes ribosomal RNA (Sonnenbichler and Zetl, 1986).

•In the process of liver cirrhosis and damage caused by ethyl alcohol and paracetamol, the depletion of glutathione levels causes most of the damage to the liver. Silymarin has been found to increase glutathione levels, thus protecting the liver (Valenzuela et al., 1985).

•Also involved in the hepatoprotective activity of silymarin, certain cytosol enzymes (including alanine amino transferase (ALT/GPT) and lactic dehydrogenase (LDH)) are inhibited by silymarin, preventing the destruction of the cell membranes. In addition, certain intoxicants have been found to block phospholipid synthesis on rat livers, and silymarin is capable of counteracting this effect (Castigli et al., 1977).

•Silybin was found to partially or completely block the toxic effects of cisplatin on the kidney functions of rats (Gaedeke et al., 1996).

•Silymarin (especially silybin) acts as free radical and reactive oxygen species (ROS) scavengers. Free radical formation is known to be one of the key processes in hepatotoxicity, contributing to lipid peroxidation on the cellular membranes (Valenzuela et al., 1989).

Comments

Milk thistle is safe and efficacious leading herb in a therapeutic area that lacks many good pharmaceutical alternatives: liver restoration and protection. Although the major public has been slow to catch on, liver health may be one of the most pertinent issues to our evolving unhealthy lifestyles, and the growing concern of toxins from the environment affecting our health.

Scientific Support

A study by Lang et al. (1990) investigated the effect of milk thistle extract (Legalon, 140 mg p.o., three times daily) in cirrhotic patients (from alcohol consumption). The study was conducted in 4-weeks, and was a randomized, double-blind, placebo-controlled design, and also used a second active treatment for comparison (Acia-P, Chinoin, Budapest, 200 mg p.o., three times daily). Both of the active treatments showed significant improvements in hepatic functions, and no change was found for the placebo group. In the milk thistle group, bilirubin (SEBI), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) had all normalized during treatment (they were moderately elevated before the study). Another study by Lang et al. (1990a) found similar results.

A two-year, double-blind, placebo-controlled study examined the effect of an oral dose of 200 mg 70% silymarin extract, three times daily, in cirrhotic patients (91 due to alcohol, and 79 not related to alcohol). At the termination of the study, there was a 23% mortality rate, and a cumulative survival rate of 58% in the treatment group, compared to a 33% mortality rate, and a 38% cumulative survival rate in the placebo group (Ferenci et al., 1989).

Further studies have found that silymarin exhibits a hepatoprotective action in people prior to alcohol consumption, and improves hepatic function in alcoholic patients. Silymarin has been found to be most effective for milder cases of alcohol cirrhosis (Salmi and Sarna, 1982; McKenna et al., 2001).

In a double-blind, crossover clinical study on the effect of silymarin (420 mg daily) vs. ursodeoxycholic acid (UDCA- 600 mg daily) in chronic hepatitis patients, significant improvements were found in both treatment groups. Significant declines in the serum levels of several elevated liver enzymes were noted for both groups, and the group receiving UDCA also had a significant reduction in γ–GT levels. The crossover phase of the study used a combination therapy of UDCA and silymarin vs. placebo, but the combined treatment showed no advantage over either single treatment (Lirussi and Okolicsanyi, 1992).

A review of clinical studies performed by Hikino and Kiso (1988) found silymarin to work therapeutically through three main activities in protecting the liver from toxic agents. Silymarin is able to stabilize the cell membrane and stimulate protein synthesis, while accelerating the regeneration of damaged liver tissue.

An open-label study involving 975 patients with various causes of liver damage examined the effect of 140 mg of a 70% standardized milk thistle extract (p.o., 2-3 times daily for 12 weeks). Five hundred and seventy of the patients were diagnosed with a fatty liver, with 143 confirmed to have fatty liver hepatitis and 214 confirmed to have hepatic cirrhosis. A mean reduction in the levels of serum liver enzymes (SGOT dropped from 46.0 µg/L to 28.8 µg/L; SGPT from 48.0 µg/L to 31.0 µg/L; and γ–GT from 112.0 µg/L to 60.6 µg/L) and a normalization of total bilirubin concentration was found at the end of the study (Grungreiff et al., 1995).

A double-blind study using silymarin (800 mg p.o daily for 90 days) found therapeutic effects in female patients with hepatopathies who had been taking psychopharmaceutical drugs such as phenothiazines or butrophenones for 5 years. A decline in the level of malodialdehyde (MDA) levels were found in the treatment group (Palasciano et al., 1994).

A study involving 2,169 patients with hepatotoxicities found improved or normalized clinical readings after taking silymarin orally for 8 weeks (at an average of 264 mg daily) (Frerick et al., 1990).

A study involving 49 workers who had been exposed to toluene and/or xylene vapors on the job for 5-20 years tested the therapeutic effect of silymarin on liver function. All the patients had low blood platelet counts and abnormal liver function before the study, and after taking silymarin for 30 days (at 140 mg p.o., three times daily) showed significant improvement in the liver and hematological tests. Symptoms reported as headaches were ameliorated after treatment, as well as parameters of leukocytosis, relative lymphocytosis, serum, γ–GT , ALT, and AST. In addition, platelet counts were increased after treatment (Szilard et al., 1988).

A 12 month open controlled study involving diabetic patients with alcoholic liver cirrhosis examined the therapeutic effect of silymarin (600 mg/day) with standard therapy for 4 months. Significant improvements in those receiving silymarin were found: a significant decrease in fasting and daily blood glucose levels, daily HbA1c levels, and glucosuria levels. Levels of MDA were also decreased. In addition, blood insulin levels were improved significantly, as well as the amount of insulin needed by injection (Velussi et al., 1997).

Safety / Dosage

Dosage of milk thistle is usually based on an 80% standardized (silymarin flavonoids- silybin, silydianin and silychristin) extract and is 175 mg daily. Other dosage recommendations vary depending on the preparation, for example: 200-400 mg (70% silymarin standardized extract- calculated as silybin); 600 mg/day (for advanced cirrhosis of a 70:1 extract); or 3-5 mL (1:1 liquid extract) (McKenna et al., 2001).

Milk thistle is safe and well tolerated, as it also has a long history as a food. Most of the side effects that have been reported in clinical trials are thought to be not significantly different from placebo or of a mild and transient nature. There have been a few cases reported of a mild laxative effect and a pruitic skin rash produced by milk thistle (McKenna et al., 2001).

References

1.Bone K. Silybum marianum. MediHerb 1996; 2: 22-23. ISSN: 1322-2775.

2.Bosisio E, Benelli C, and Pirola O. Effect of the flavonolignans of Silybum marianum L. on lipid peroxidation in rat liver microsomes and freshly isolated hepatocytes. Pharmacological Research 1992; 25: 147-154.

3.Castigli E, Montanini I, Roberti R. et al. The activity of silybin on phospholipid metobolism of normal and fatty liver in vivo. Pharmacological Research Communications 1977; 9: 59-69.

4.Ferenci P, Dragosics B, Dittroch H. et al. Randomized controlled trial of silymarin treatment in patients with cirrhosis of the liver. Journal of Hepatology1989; 9: 105-113.

5.Frerick H, Kuhn U, Strenge-Hesse A. Silymarin – ein phytopharmakon zur behandlung von toxischen leberschäden. Der Kassenarzt 1990; 33/34: 36-41.

6.Gaedeke, J.; L.M. Fels; C. Bokemeyer et al. 1996. Cisplatin nephrotoxicity and protection by silibinin. Nephrology, Dialysis, Transplantation 11:55-62.

7.Grungreiff, K.; M. Albrecht; and A. Strenge-Hesse. 1995. The value of drug therapy for liver disease in general practice. Medizinische Welt 46:222-227.

8.Hikino, H and Y. Kiso. 1988. Natural products for liver disease, in: Wagner, H.; H. Hikino and N.R. Farnsworth (eds.), Economic and Medicinal Plant Research, 2. London, England: Academic Press.

9.Láng I, Nékám K, Deák G. et al. Immunomodulatory and hepatoprotective effects of in vivo treatment with free radical scavengers. International Journal of Gastroenterology 1990; 22: 283-287.

10.Láng I, Nékám K, Gonzalex-Cabello R. et al. 1990a. Hepatoprotective and immunological effects of antioxidant drugs. Tokai Journal of Experimental and Clinical Medicine 1990; 15:123-127.

11.Lirussi F, Okolicsanyi L. 1992. Cytoprotection in the nineties. Experience with ursodeoxycholic acid and silymarin in chronic liver disease. Acta Physiologica Hungarica 80:363-367.

12.McKenna DJ, Jones K, Hughes K (eds). Botanical Medicines: A Desktop Reference for the Major Herbal Supplements. 2001 Haworth Press: New York

13.Morazzoni P, Bombardelli E. Silybum marianum (Carduus marianus). 1995; Fitoterapia 66: 3-42.

14.Palasciano G, Portincasa P, Palmieri V. et al. The effect of silymarin on plasma levels of malondialdehyde in patients receiving long-term treatment with psychotropic drugs. Current Therapeutic Research 1994; 55:537-545.

15.Salmi H, Sarna S. Effect of silymarin on chemical, functional and morphological alterations of the liver: a double-blind controlled study. Scandinavian Journal of Gastroenterology 1982; 17:517-521.

16.Sonnenbichler J, Zetl, I. Specific binding of a flavonolignane derivative to an estradiol receptor, in: Cody, V.; E. Middleton, Jr. and J.B. Harborne. (eds.), Plant Flavonoids in Biology and Medicine: Biochemical, Pharmacological and Structure-activity Relationships. 1988; New York, NY: Alan R. Liss, pp. 319-331.

17.Szilard S, Szentgyorgyi D, Demeter D. Protective effect of Legalon® in workers exposed to organic solvents. Acta Medica Hungarica 1988; 45:249-246.

18.Valenzuela A, Aspillaga M, Vial S. et al. Selectivity of silymarin on the increase of the glutathione content in different tissues of the rat. Planta Medica 1989; 55:420-442.

19.Valenzuela A, Lagos C, Schmidt K. et al. Silymarin protection against hepatic lipid peroxidation induced by acute ethanol intoxication in the rat. Biochemical Pharmacology 1985; 34:2209-2212.

20.Velussi M, Cernigoi CM, Viezzoli L. et al. Silymarin reduces hyperinsulinemia, malondialdehyde levels, and daily insulin need in cirrhotic diabetic patients. Current Therapeutic Research 1993; 53:533-545.

EDITOR'S NOTE: This monograph can be found in The Health Professional's Guide to Dietary Supplements (Lippincott, Williams & Wilkins) by Shawn M. Talbott, PhD and Kerry Hughes, MS