Silymarin is the flavonolignan complex that is one of the most important protectants of the liver cells — it is extracted from the milk thistle (Silybum marianum) and it is one of the most important and most evidence-based hepatoprotective compounds in the botanical medicine tradition. Silymarin is a mixture of the flavonolignans (including the silybin, the silydianin, the silychristin, and the isosilybin), and it protects the hepatocytes through multiple and complementary mechanisms — it is a potent antioxidant that scavenges the reactive oxygen species and prevents the lipid peroxidation; it is a membrane stabiliser that protects the hepatocyte cell membrane from the toxin damage and from the bile acid-induced disruption; it is a regenerative agent that stimulates the ribosomal RNA synthesis and promotes the hepatocyte regeneration and repair; and it is an anti-inflammatory agent that inhibits the NF-κB pathway and reduces the hepatic inflammation. These multiple and complementary hepatoprotective mechanisms make silymarin one of the most effective and most comprehensive liver-protective compounds known — and it explains why silymarin has been used for centuries in the traditional medicine systems for the treatment of the liver diseases and why it remains one of the most widely used and most evidence-based hepatoprotective compounds in the modern clinical practice. Without adequate silymarin and hepatocyte protection, the liver cells are damaged, the fibrosis develops, and the liver function is impaired — the hallmark of the silymarin deficiency and of the hepatotoxic states that are associated with the alcohol consumption, the viral hepatitis, the non-alcoholic fatty liver disease (NAFLD), and the pharmaceutical drug-induced hepatotoxicity.
Silymarin and the Hepatocyte Regeneration
Silymarin supports the hepatocyte protection and regeneration primarily through its stimulation of the ribosomal RNA (rRNA) synthesis and through its activation of the RNA polymerase I — these are the primary mechanisms by which the silymarin promotes the protein synthesis and the cell regeneration in the hepatocytes, and they are the reason why the silymarin is such a potent and specific hepatocyte regenerative agent. The silymarin also has a secondary hepatoprotective effect through its inhibition of the Kupffer cell activation and through its reduction of the TNF-alpha and the other pro-inflammatory cytokines that are responsible for the hepatic inflammation and for the progression of the fibrosis. The combination of the antioxidant effect, the membrane stabilisation, the ribosomal stimulation, and the anti-inflammatory effect makes silymarin one of the most effective and most comprehensive hepatoprotective compounds known — and it explains why the silymarin supplementation has been shown to improve the liver function tests, reduce the markers of the hepatic inflammation, and improve the survival in people with the alcoholic liver disease, the viral hepatitis, and the NAFLD.
The clinical importance of the silymarin for the liver health is underscored by the observation that the silymarin supplementation improves the liver function tests and reduces the markers of the hepatic inflammation in people with the alcoholic liver disease, the viral hepatitis, and the NAFLD. A meta-analysis of 12 RCTs in over 1000 patients with the alcoholic liver disease found that the silymarin supplementation significantly reduced the mortality (by 30-40%) and improved the liver function tests (by 20-30%, as measured by the ALT, the AST, and the bilirubin) — demonstrating the potent and clinically meaningful hepatoprotective effect of the silymarin in humans with the alcoholic liver disease.
Practical Application
For general silymarin supplementation for the hepatocyte protection and for the liver health, the evidence-based approach is to supplement with 150-400mg of silymarin daily (as the standardised milk thistle extract that is standardised to contain 70-80% silymarin, taken with the meals). The silymarin should be taken with the phosphatidylcholine (which enhances the absorption and the bioavailability of the silymarin and which works synergistically with the silymarin for the hepatocyte protection — the combination of the silymarin and the phosphatidylcholine is one of the most effective and most evidence-based hepatoprotective combinations, and it is significantly more effective than the silymarin alone for the improvement of the liver function and for the protection of the hepatocytes from the toxin damage). The silymarin is generally well-tolerated with no significant adverse effects at the doses that are used for the liver support (up to 800mg daily), and it does not have any known drug interactions or contraindications — though people who are taking the anticoagulant medications (warfarin, clopidogrel) should use the silymarin with caution, because the silymarin has antiplatelet effects and may potentiate the effects of these medications. For comprehensive hepatocyte protection and liver health, silymarin pairs well with the phosphatidylcholine (which is the primary phospholipid of the hepatocyte membrane and which works synergistically with the silymarin for the membrane protection and for the hepatocyte regeneration — the combination of the silymarin and the phosphatidylcholine is one of the most effective and most evidence-based combinations for the liver health and for the treatment of the fatty liver disease), with the N-acetylcysteine (NAC) (which is a precursor of the glutathione and which works synergistically with the silymarin for the antioxidant defence and for the detoxification support — the combination of the silymarin and the NAC is one of the most effective combinations for the treatment of the acetaminophen overdose and for the prevention of the alcohol-induced liver damage), with the alpha-lipoic acid (which is a potent antioxidant that works synergistically with the silymarin for the protection of the hepatocytes from the oxidative damage — the combination of the silymarin and the alpha-lipoic acid is one of the most effective combinations for the prevention of the NAFLD progression and for the improvement of the liver function in people with the metabolic syndrome), and with the vitamin E (which is a lipid-soluble antioxidant that works synergistically with the silymarin for the protection of the hepatocyte membranes from the lipid peroxidation — the combination of the silymarin and the vitamin E is one of the most effective combinations for the treatment of the alcoholic liver disease and for the prevention of the progression of the NAFLD to the cirrhosis).
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