St Mary’s thistle: Clinical Use. Dosage
DYSPEPSIA
Although St Mary’s thistle has been most commonly investigated for its effects as a hepatoprotective agent, it is commonly used to treat dyspeptic complaints, such as loss of appetite, poor digestion and upper gastrointestinal discomfort. Animal studies have identified a dose-dependent increase in bile flow and bile salt secretion for silymarin, achieved by stimulating the synthesis of bile salts.
Commission E approves the use of crude milk thistle preparations for dyspeptic complaints.
TOXIC LIVER DAMAGE
Mushroom poisoning (Amanita phalloides)
One of the best documented uses of milk thistle is in the treatment of poisoning by the mushroom Amanita phalloides (death cap). Nausea, vomiting, abdominal cramps and severe diarrhea usually occur 8-12 hours after ingestion with extensive hepatic necrosis occurring 1-2 days later. A mortality rate of 20-30% has been observed but can be as high as 50% in children under 10 years of age. Several clinical studies have shown silybin (20-50 mg/kg/day IV) to protect against hepatotoxicity when administered within 48 hours. One report of pooled data from 452 case reports of A. phalloides poisoning showed a highly significant difference in mortality in favour of silybin.
Environmental toxins and drugs
In animals, milk thistle reduces acute liver injury caused by paracetamol, carbon tetrachloride, radiation, iron overload, phenylhydrazine and D-galactosamine.
One, randomised double-blind study involving 222 patients showed that silymarin improves the tolerability of tacrine without altering the drug’s cognitive effects. Two other clinical trials have documented the effectiveness of silymarin in improving or preventing hepatotoxicity from chronic administration of phenothiazines or butyrophenone.
Hepatocyte repair
The effects of a commercial silymarin product (Legalon 120 mg three times daily) on liver function tests and liver histology were studied in 36 patients with chronic alcoholic liver disease in a 6-month, double-blind clinical trial. Treatment not only produced significant improvements in liver function test results, but also positive effects on histology, while these parameters remained unchanged in the placebo group. Salmi and Sarna (1982) found similar results in a RCT of 106 patients with liver disease. After just 4 weeks’ treatment, histological changes began to normalise significantly more often in the treated group than in controls.
Commission E approves the use of standardised St Mary’s thistle extracts (70-80% silymarin content) for toxic liver damage.
SUPPORTIVE TREATMENT IN CHRONIC LIVER DISEASES
Numerous clinical trials have been conducted with St Mary’s thistle preparations in various chronic liver diseases. The most studied treatments are Legalon (Madaus Corporation, Cologne, Germany) and Silipide (Inverni Delia Beffa Research and Development Laboratories, Milan, Italy) designed to improve oral absorption of silymarin.
Clinical note — Hepatic fibrosis
Hepatic fibrosis is a pathological wound-healing process that occurs when the liver is injured chronically, such as in chronic alcohol abuse. The oxidative metabolite of ethanol, acetaldehyde, often in conjunction with viral or metabolic liver disease, is implicated as the major cause for liver fibrogenesis, which ultimately leads to cirrhosis. Antifibrotic agents, which interrupt the continuous process of wound healing in the liver, are being investigated as strategies to prevent or reverse liver cirrhosis.
A 1998 clinical review of St Mary’s thistle concluded that it may be effective in improving the clinical courses of both acute and chronic viral, drug-induced, toxin-induced and alcoholic hepatitis. A more recent systematic review of efficacy for St Mary’s thistle in chronic liver diseases stated that data are still too limited to detect a substantial benefit on mortality or recommend the herb in liver disease.
Eleven clinical studies were located in which researchers have attempted to clarify the role of St Mary’s thistle in the treatment of various liver diseases. Much of the research focuses on the different forms of hepatitis and alcoholic liver cirrhosis with doses ranging from 100-300 mg three times daily, usually given in a standardised extract of 70-80% silymarin. Overall, results have been mixed, with eight trials showing generally positive results and three negative, suggesting more research is still required.
A 2005 Cochrane review of 13 randomised clinical trials assessed milk thistle in 915 patients with alcoholic and/or hepatitis B or C virus liver diseases. The authors stated that the methodological quality of the trials was low and although liver-related mortality was significantly reduced by milk thistle in patients with alcoholic liver disease, milk thistle versus placebo or no intervention had no significant effect on complications of liver disease, or liver histology. Milk thistle was not associated with a significantly increased risk of adverse events. Acute viral hepatitis Several studies have investigated the use of milk thistle in this disease, reporting beneficial effects on serological outcomes. However, several studies were not clearly blinded and further research is required to determine whether St Mary’s thistle can provide significant benefits in this population.
Hepatitis C infection A 2003 systematic review of medicinal herbs for hepatitis C virus (HCV) infection concluded that compared with placebo, none of the herbs showed effects on HCV RNA or liver enzyme, except for silybin, which showed a significant reduction of serum AST and gamma-glutamyltranspeptidase levels in one trial. Overall, the review concluded that further randomised trials are justified.
Commission E approves the use of standardised St Mary’s thistle extracts (70-80% silymarin content) as supportive treatment in chronic inflammatory liver disease and hepatic cirrhosis.
Diabetes
Silymarin has also been investigated in diabetic patients with cirrhosis. Velussi et al (1997) investigated whether long-term treatment with silymarin is effective in reducing lipoperoxidation and insulin resistance in diabetic patients with cirrhosis. The 6-month open trial found that silymarin treatment had several benefits. After the first month’s treatment, fasting glucose levels showed a progressive and significant decline that, interestingly, did not lead to an increase in the frequency of hypoglycaemic episodes. Other observations revealed decreased glucosuria and levels of glycosylated haemoglobin also decreased significantly, indicating an overall improvement in glucose control. The dose used was 600 mg/day silymarin.
St Mary’s thistle: Other Uses
Traditionally, the seeds have been used to treat jaundice, hepatitis, haemorrhoids and psoriasis, as a tonic for nursing mothers, and as a general ‘liver cleansing’ agent.
HYPERCHOLESTEROLAEMIA
In clinical practice, it is not unusual to find treatment with St Mary’s thistle at the higher end of the dose range results in cholesterol lowering effects. Several in vivo studies confirm that St Mary’s thistle increases LDL-cholesterol clearance and raises HDL-cholesterol levels; however, only one clinical trial is available to determine whether the effect is clinically significant. An open trial involving 14 subjects with type 2 hyperlipidaemia found that treatment with silymarin (420 mg/day) slightly reduced total cholesterol and HDL-cholesterol levels.
SKIN CANCER PREVENTION
In vivo research suggests that silymarin and/or its major active constituent silibinin could be an effective agent for prevention and/or supportive treatment of human skin cancer. Topical application of silymarin provided significant protection against different stages of UV-B induced skin carcinogenesis in mouse skin tumorigenesis models.
CHEMOTHERAPY SUPPORT
The role of St Mary’s thistle as adjunctive therapy in a range of cancer treatments has received much interest in the past few years. Silybin appears to have nephroprotective activity effective against cisplatin and vincristine toxicity in vitro. Protection against cisplatin nephrotoxicity has been confirmed in vivo by Gaedeke et al (1996), who showed the adverse effects of cisplatin on creatinine clearance and proteinuria were totally prevented by silybin pretreatment. Bokemeyer et al (1996) confirmed the nephroprotection afforded by silybin in a rat animal model and observed that it did not alter the clinical efficacy of cisplatin. According to an in vivo study by Karimi et al (2005), both silymarin and St Mary’s thistle extract are also effective when given as pretreatment before cisplatin.
In vitro and in vivo research has further shown that a combination of silybin with cisplatin produces a dose-dependent and statistically significant increase of drug activity, resulting in a potentiation of antitumour activity.
Clinical note — Cisplatin
Cisplatin is one of the most active cytotoxic agents in the treatment of testicular cancer, but its clinical use is associated with side-effects, such as severe nausea, ototoxicity, neurotoxicity and nephrotoxicity. It is also used in the treatment of head and neck, gastrointestinal, cervical, lung and bladder cancer.
St Mary’s thistle: Dosage Range
• The average daily recommended dose is 12-15 g (practitioners have used doses as high as 18 g/day) of milk thistle seed, usually in divided doses (equivalent to 200-400 mg silymarin).
• Liquid extract (1:1): 4-9 mL/day.
• Liquid extract (1:2): 30-60 mL/week.
