Milk Thistle (Silybum marianum)

Background
Silybum marianum is currently the most researched herb in the treatment of liver disease (with over 450 published peer review papers). The active constituent of silybum is silymarin, a mixture of flavonolignans consisting chiefly of silibin, silidianin, and silichristine. Silibin is the most active of the three and is largely responsible for the benefits attributed to the silymarin complex.

Pharmacology
Silybum exerts a protective and restorative effect on the liver. The hepato-protective effects include anti-oxidation, anti-lipid peroxidation, enhanced detoxification, and protection against glutathione depletion. Silybum inhibits the enzyme lipoxygenase, thereby inhibiting the formation of the hepato-destructive leukotrienes. In damaged livers, silymarin has been shown to increase protein synthesis, which might account for its hepatorestorative action. Silymarin has been shown in animal studies to possess antifibrotic activity. Animal and in-vitro studies have shown silybum to possess anti-diabetic, anti-tumor, anti-atherosclerotic, and anti-nephrotoxic activity.

Clinical Studies
A number of studies have shown that silymarin may be valuable in the prophylaxis and treatment of diabetes and its complications.

Blood Sugar and Insulin Control
In treatment with the milk thistle flavonoid silymarin, fasting blood glucose levels, mean daily blood glucose levels, daily glucosuria, and HbA1c levels were all reduced. In addition, fasting insulin levels and mean exogenous insulin requirements were reduced. Silymarin may reduce the lipo-peroxidation of cell membranes and insulin resistance, significantly decreasing endogenous insulin overproduction and the need for exogenous insulin administration.
     Silymarin also decreased basal and glucagon-stimulated C-peptide levels. In treatment with silibin, there was a highly significant reduction in RBC sorbitol, though no effect on fasting blood glucose, and an improved nerve conduction velocity, though not statistically significant. Silibin may be a potent aldose reductase inhibitor and may be valuable in the prophylaxis and treatment of diabetic complications. In the treatment of rats, silibin prevented the onset of diabetic neuropathy, possibly by inhibiting excessive protein mono-ADP-ribosylation.
     Silymarin may also reduce lipo-oxidation of hepatic cell membranes and help reverse insulin resistance. Silibin, which is one of the three flavolignans in silymarin, was studied on patients with NIDDM. The sorbitol red blood cell (RBC) level for 14 patients with NIDDM averaged 72.5 mmol/g; this was two times higher than the control group that didn’t have diabetes. In this study, 231 mg of silibin was administered for 4 weeks to the NIDDM patients: their sorbitol RBC level dropped to 39.53 mmol/g. The study also found slightly improved nerve conduction velocity in the silibin group. Silibin, a potent aldose reductase inhibitor, is valuable in the prophylaxis and prevention of complications in diabetes.
     The adrenal gland has a function in the regulation of insulin called the Somogyi phenomenon. In response to hypoglycemia, epinephrine, norepinephrine, and cortisol are secreted by the adrenal gland. In diabetic rats, a short-term diabetic state lowered the activity of their adrenal cortex. Thus, sub-clinical adrenal hypofunction should be assessed in NIDDM patients.

Diabetic Neuropathy
Milk thistle is also effective in the treatment of neuropathy. Silibin is a flavonoid, which is a mono-adenoid di-phosphate-lipoxyl-transferase inhibitor. It helps to prevent protein ADP ribosylation. ADP ribosylation causes an increase in P-like substance that causes an immunoreactivity level that is found in diabetic neuropathy. In the treatment of diabetic rats, silibin was found to prevent the increase of ADP ribosylation in Schwann cells.

Secondary Diabetes
Milk thistle has been shown to be an effective treatment for patients with diabetes secondary to cirrhosis. In a trial done in Italy, 30 diabetic patients were given a regime of conventional therapy and 600 mg daily of silymarin, while 30 other patients were given only conventional therapy. After 4 months, the group who using 600 mg daily of silymarin had decreased fasting glucose levels, decreased glucosuria, decreased HbA1c values, and decreased fasting insulin levels, with a decreased exogenous insulin requirement. The control group had increased insulin levels after the study and stabilization of exogenous insulin needs. This study demonstrated that silymarin decreased endogenous insulin overproduction and decreased exogenous insulin requirements in patients with liver disease. Milk thistle stimulates protein synthesis, resulting in the regeneration of hepatic cells and new liver tissue.

Contraindications
Silybum is virtually free of toxicity and can be used during pregnancy and lactation. In animals, silymarin was shown to be non-toxic when administered at high doses for short periods. Long-term administration to rats also demonstrated an absence of toxicity. Silybum can stimulate liver and gallbladder activity and can therefore produce a transient laxative effect. Mild allergic reactions have been noted.

Dosage
Since silymarin is not water soluble, administration as an infusion is not recommended. The standard dose of silybum is based on its silymarin content (70 to 210 mg capsules three times daily). A higher dosage will likely yield better results. Several animal and human studies have shown that silymarin bound to phosphatidylcholine yields better absorption and clinical effect (dose 100 to 200 mg twice daily).