What is Milk Thistle?

Milk Thistle, also known as Silybum Marianum, is a herbal flower known for its liver protecting remedies. Milk Thistle contains silymarin which is composed of complex isomer flavonolignans: silybin, silydianin, and silychristin. Milk Thistle is said to have antioxidant, anti-inflammation, anti-fibrotic activity, and liver detoxification effects.

Researchers have undergone extensive research trying to decipher Milk Thistle’s framework. Only a handful of results and confirmations have yet determined the exact mechanisms in treating alcoholic liver diseases, acute and chronic hepatitis and toxin-induced liver problems. Milk Thistle should not be used as a personal cure to treat liver disease, but nonetheless a great supplementary herb to improve liver function. (1)

What does Milk Thistle do?

Over the years, countless studies and clinical findings have discovered Milk Thistle to a beneficial supplement for the liver. Its active ingredient, silymarin, is suggested to perform numerous liver protection and antioxidant functions. Various studies discovered Silymarin to protect against DNA impairment, support hepatocyte protein synthesis, and maintain the integrity of the liver's membrane. Antioxidant and anti-inflammatory benefits include inhibition of cyclooxygenase cycle (for anti-platelet activity), reduce high levels of leukotrienes, and remedy the production of free radicals. (2)

These findings suggest a potential benefit in improving hepatic processes against cirrhosis, non-alcoholic hepatic steatosis ethanol, acetaminophen, and carbon tetrachloride.(3)

In clinical trials for treating viral liver diseases such as Hepatitis C, Milk Thistle has yielded inconclusive and ineffective results. A 2008 study was conducted pooling 154 patients with chronic HCV infection. For 24 weeks, groups were split and assigned dosage of 420mg and 700mg of silymarin. At the end of the treatment, researchers observed levels of ALT, HCV RNA, and quality of life. ALT serum levels decreased more than the placebo group although the 700mg group did NOT reduce more than the 420mg group. HCV RNA and quality of life, which test the virus in the bloodstream, did not show any significant difference between the silymarin and placebo groups. This concludes silymarin to be an unsuccessful treatment against Hepatitis C. (4) 

Although it was confirmed ineffective against Hepatitis C other various studies has also garnered positive findings for treating jaundice, cirrhosis, liver cancer, and fatty liver disease. We’ll go over all the Milk Thistle’s liver protection and antioxidant mechanisms based on previous findings. (5)

How does Milk Thistle improve the liver?

Protects Genomic injury (DNA/RNA)

Keep in mind Silymarin is not an effective treatment for Hepatitis C. But hope is not lost, Milk Thistle is still a great supplement for liver support and maintenance. Let’s dive into the benefits of Milk Thistle and how it may improve liver health.

The most common type of liver cancer is Hepatocellular Carcinoma. It can primarily occur in people with Hepatitis B & C which is also the leading cause of death in people with cirrhosis. Cancer has the ability to cause cell proliferation and induce dysregulation in the cell cycle. The main function of cell cycle is for the cells the divide, replicate DNA and produce healthy cells. When the process is disrupted, it can pose DNA injury which leads to cellular dysfunctions and tumor growth. Clinical studies were conducted including 40 patients with HCC and 20 healthy patients. Upon further analysis, researchers studied key genes, TOPBP1, NUSAP1 and CDCA3, and analyze the treatment with Milk Thistle. (6)

TOPBP1, which stands for DNA topoisomerase 2-binding protein 1, basically plays a role in DNA replication. Silymarin presented inhibitory progression in HCC by reducing the expression TOPBP1. This displays anti-tumor like characteristic by controlling DNA damages caused by HCC. (7)

NUSAP1, nucleolar-spindle-associated protein, plays a role in the process of cell division or mitosis. In HCC, cancer upregulates NUSAP1 which can lead to an overproduction of cell replication. Treatment with silymarin has speculated to decrease the activity of this protein specifically inhibiting the formation of toxicity-induce cell division in the liver. Silymarin may contain anti-HCC effects by inducing cell cycle arrest or cellular death in liver tumors. (8)

CDCA3, another protein regulator in mitosis, has shown to support HCC progression by increasing cell proliferation. Silymarin was also suggested to play a role in down stimulating this protein during cell cycle process. Silymarin treated in various cancers such as prostate, ovarian and liver cancer which may suggest cell cycle arrest via CDCA3 and potentially slow the growth of tumors. (9)

Although Silymarin treatments may possess anti-tumor like benefits but this clinical study was very limited due to the sample size, narrow testing methods, and data retrieved. In summary, Silymarin may theoretically possess anti-HCC benefits and tumor suppression based on this study. (10)

Increases liver protein cells regeneration

When the liver undergoes surgery or accidental toxicity, it results in partial liver tissue loss. Our liver possesses the ability to regenerate loss tissue to maintain its function. In a regenerative state, the liver increases its cell numbers and proliferates to promote cellular growth. After this process the liver returns to homeostasis or a state of equilibrium. The loss of liver cells can be remedied by regenerative growth drugs. Silymarin has shown to be a significant candidate in restoring liver cells.

To investigate Silymarin’s liver regenerative ability, a study was conducted on rats with hepatectomy or partial liver surgery. Liver resections were performed on rats and removed 70% of their liver mass. The rats were then sacrificed at different intervals 6hrs, 24hrs, and 72hrs. Their livers were extracted and examined. Silymarin was discovered to have a strong influence and enhancement in protein expressions such as cyclin D1, pRb, cyclin E, and E2F. These protein markers help indicate the liver’s regeneration strength. Silymarin was determined to increase the cell cycle process during cell division and potentiate cell DNA replication of the liver. (11)

This further suggests Silymarin's regenerative effect at intervals 6hrs, 24hrs, and 72hrs. After 72hrs, Silymarin’s effects began to cease which suggest the end of liver regeneration. Additionally, Silymarin was able to enhance growth factors such as HGF. In summary Silymarin maybe a potential treatment in expediting cell cycle processes, accelerating protein synthesis, and restoring loss liver tissue. (12)

Reduction in Alanine Aminotransferase (ALT) and Aspartame Aminotransferase (AST) and γ-glutamyl transpeptidase.

Liver injuries such as non-alcoholic fatty liver diseases, hepatitis, infection, cirrhosis, and liver cancer usually indicate high levels of Alanine Aminotransferase (ALT) and Aspartame Aminotransferase (AST). These enzymes, located in the liver, are released by damaged liver cells into the blood stream. Milk Thistle was used to study the effects on liver enzymes.

One clinical study, 64 patients with non-alcoholic steatohepatitis were treated with Silymarin and a placebo. One group received 70 mg tablet of Silymarin 3 times a day for 8 weeks. Results concluded significant reductions of 58% in ALT levels and 51% in AST levels with the group before and after treated with Silymarin. In comparison with the control, the levels before and after the placebo saw reductions 38% in ALT and 48% in AST. Researchers have confirmed Silymarin a potential treatment of NASH by lowering their ALT and AST levels. (13)

Another study of 72 patients with non-alcoholic fatty liver disease. For 6 months participants received a supplement combination that contained Vitamin E, L-gluthatione, L-cysteine, L-methionine and Silybum Marianum. At the end of the study, researchers analyzed alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase levels were significantly reduced. The treatment resulted a decrease in ALT and AST which could be due to Silymarin's antioxidant function in the liver. Given that this supplement mixture was tested we can only speculate other ingredients may play a factor in ALT and AST reduction. This further suggests Milk Thistle and other ingredients to be a possible supplement in early stages of liver damages and antioxidant protection. (14) 

What is Milk Thistle's antioxidant effect on the liver?

Silymarin is famously known for its potent antioxidant effect on the liver. Its mechanism of actions includes direct/indirect scavenging free radicals, reducing lipid peroxidation, promoting antioxidant enzymes, and eliminating drug intoxication in the liver.

Milk Thistle’s active components, (Silybin, silydianin, and silychristin), are the key ingredients in its antioxidant effect. Silybin has shown to be a scavenging agent by reducing oxidative and nitric oxide stresses in hepatocytes. It also has the ability to decrease low density lipid-protein oxidation and inhibit oxygen and hydrogen peroxide stressors produced by an inflammatory cytokine, TNF-α. (15) 

Silybin can exert cellular protection in the mitochondria due to its antioxidant nature. It can optimize electron transport chain by donating electrons to stabilize free radicals. It also can reduce deformation of reactive oxygen species (ROS) which can exert alter proteins, lipid peroxidation and mitochondria damage. Silybin’s efforts to inhibit cellular damage by ROS helps improve ATP production in the mitochondria and maintains a healthy liver activity. (16) 

Silymarin’s main antioxidant force is its activation of Nrf2. Nrf2 activation plays an important role in antioxidant defenses. It’s the main driver in reducing oxidative damage and improving mitochondria dysfunction. In one study, rats were supplemented with silybin, researchers discovered the rat’s kidney had increased levels of Nrf2. This boost subsequently elevated levels of GSH, vitamins E and C suggesting that Silymarin increases the rally with other antioxidants. To observe the effects Nrf2 activation, a recent study of ethanol induced mice was administered with silybin and discovered a significant increase in Nrf2 and other antioxidant pathways. While the rats’ liver were compromised, Silymarin remained effective in activating antioxidant defenses and alleviating liver toxicity. (17) 

In a study involving rats with high fat diets, the rats were subjugated to an increase in body weight, glucose intolerance, and insulin resistance. A high fat diet also produces lipid peroxidation which causes oxidative damages from lipids around the body. This can lead to liver dysfunction and an increase risk of inflammation. The experiment administered 30mg of Silymarin to rats for 12 weeks. Results revealed that Silymarin reduced oxidative stress indicators such as lipid peroxidation and ROS. It also helped restore antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase that were affected by the high fat diet. This may suggest Silymarin to have anti-diabetic benefits in alleviating hepatic oxidation. (18)

Maintains liver cell membrane and hinders toxic invasion of substances and drugs biotics

Milk Thistle’s antioxidant properties may help prevent drug induce intoxication and other chemical substances in the liver. Drug prescriptions, alcohol, and mycotoxins can cause oxidative liver injuries. Silymarin’s antioxidant effect may display countereffects caused by toxins due to inhibiting cellular damages, increasing antioxidant enzymes (Vitamin E & C, Glutathione, SOD GSH-Px, CAT, GR, GST) and reduce DNA fragmentation. A list of toxins treated by Silymarin include but not limited to are Amanita caps, arsenic, acetaminophen, ethanol, Cisplatin, Carbone tetrachloride and Doxorubicin. If not immediately treated hepatoxicity can ensue. Silymarin was found to potentially help treat liver toxicity by acting as a liver cleanse by direct scavenging of free radicals, preventing the formation of ROS enzymes and maintaining mitochondria functionality. (19)

When it comes to antioxidant protection, Milk Thistle is no stranger to this health-promoting benefit. Its support for overall liver health, reduction in oxidative damages, and alleviation in liver toxicity can be a great add-on supplement for your daily life. So does Milk Thistle improve liver health? Answer is yes and no. It is definitely not a cure for liver diseases such as Hepatitis B & C but it does have liver supporting properties to improve overall function. Note that these findings are to better understand the effects of Milk Thistle. These are only clinical findings and results may differ in various situations which is also prudent to not rely on Milk Thistle as a cure or treatment if you have liver diseases. We highly suggest consulting with a medical professional on the potential treatment measures.