Silymarin, obtained from the milk thistle plant Silybum marianum, has been used over the centuries to treat mainly liver diseases and its mixture of active flavonolignans and flavonoids exerts anti-inflammatory, antioxidant and antifibrotic activity on the liver organ, showing positive results with remarkable safety.
A 2009 randomized controlled trial with patients with NAFLD, or nonalcoholic hepatic steatosis, concluded that silymarin was effective in reducing alanine aminotransferase (Alt) and aspartate aminotransferase (Ast) levels compared with placebo. In another coeval double-blind controlled study with adults with Nash, nonalcoholic liver steatosis, and biopsy-proven nonalcoholic steatohepatitis, 48-week treatment with silymarin did not lead to an improvement in Nafld activity score compared with the placebo group, but did result in significant improvement in fibrosis after a repeat liver biopsy.
In 2014, another clinical trial with Nafdl patients examined the effect of silymarin after an 8-week treatment period and showed a marked improvement in transaminase levels compared with placebo. A systematic review and meta-analysis published a few weeks ago showed that supplementation with silymarin resulted in a statistically significant reduction in transaminase levels compared with placebo treatment, independent of weight loss.
Additional subgroup and sensitivity analyses revealed that the reduction in Alt values after silymarin treatment was approximately the same – statistically and clinically significant – regardless of the dosage administered, short- or long-term follow-up time. These data make the clinical use of silymarin more robust, but it remains critical to examine whether this reduction in transaminase levels corresponds to histologic improvement.
While it is well known on the hepatic front, silymarin has also been studied for its beneficial effects in cardioprotection, neuroprotection, and immune modulation. In particular, the most relevant research focuses on its effect on lipid and carbohydrate metabolism, particularly on insulin resistance, known to play a crucial role in the progression of metabolic disease.
In the early 1990s, one of the first clinical trials in humans with silymarin treatment related to insulin resistance tested its effect (600 mg per day for 6 months) in 60 diabetic patients with cirrhosis, in addition to standard therapy. Mean levels of fasting blood glucose, daily blood glucose, daily glycosuria, HbA1c, daily insulin requirement, and fasting blood insulin, among other parameters, were reduced in patients treated with silymarin.
A few years later, the same research group conducted a 12-month open controlled study of 60 diabetic patients with cirrhosis, treated with silymarin or placebo as in the previous study and standard therapy. The results showed the same results after four months of treatment.
In a subsequent study, a different complex of silybin, the main active component of silymarin, with vitamin E and phospholipids (188 mg of silybin per day) or placebo was given to 85 patients with Nafld with or without hepatitis C virus (the latter not responding to treatment with interferon and ribavirin) for six months. Parameters of carbohydrate metabolism and liver fibrosis were analyzed and treatment was found to improve insulin resistance. Results showed a significant decrease in Homa-Ir and insulinemia, as well as Alt, gamma-glutamyl transferase (Ggt) levels and liver fibrosis in both groups.
A different formulation of silymarin combined with another nutraceutical, berberine, was administered to 22 diabetic patients with suboptimal glycemic control despite the use of standard therapy showed after 90 days to have reduced levels of HbA1c, basal insulin, Homa-Ir, triglycerides and Ldl cholesterol.
The same formulation tested in another clinical trial with 105 overweight, euglycemic, and dyslipidemic patients at low cardiovascular risk for three months in a double-blind, placebo-controlled design confirmed the ability to improve insulin resistance and various lipid metabolism parameters. In the same year, three other studies, characterized by different formulations, published the results of the effect of silymarin on insulin resistance. Not only that: the results collected over the years suggest that treatment with silymarin can help to accelerate detoxification from Bpa (bisphenol A), improve cellular antioxidant power in patients with NAFLD and, equally important, reduce insulin resistance.
Of note, only a fraction of oral silymarin is absorbed because of its extensive phase II metabolism, reduced permeability in the intestine, low aqueous solubility, and rapid excretion in bile and urine. Given, therefore, the low bioavailability, the strategies of the integrative formulas adopted are relevant.
Bibliography
Impact of Silymarin in individuals with nonalcoholic fatty liver disease: a systematic review and meta-analysis. Nutrition – 25 November 2020. Volume 83.
Silymarin is an ally against insulin resistance: a review. Annals of hepatology – 17 september 2020. Volume 23.
The effects of silymarin supplementation on metabolic status and oxidative stress in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of clinical trials. Complementary therapies in medicine – 3 September 2018 – Volume 41 Pages 311-319.
Antioxidant effects and mechanism of silymarin in oxidative stress induced cardiovascular diseases. Biomedicine & Pharmacotherapy – 5 April 2018 – Volume 102 Pages 689-698
Silymarin impacts on immune system as an immunomodulator: one key for many locks. International immunopharmacology – 30 June 2017 – Volume 50 Pages 194-201.
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