Highlights
Milk Thistle Extract/Silymarin and its key component Silibinin have many impressive health benefits due to its antioxidant, anti-inflammatory and anti-cancer properties. Different in vitro/in vivo and animal studies have investigated the health benefits of milk thistle extract and its ability to inhibit a variety of cancers and found promising results. Few human trials also suggested that milk thistle and its active ingredients may be beneficial in reducing some of the dangerous side-effects of chemotherapy and radiotherapy such as cardiotoxicity, hepatotoxicity and brain edema in certain cancer types treated with specific chemo.
What is Milk Thistle?
Milk thistle is a flowering plant that has been used for centuries as a natural remedy to treat liver and bile disorders mostly in European countries. Milk thistle is also available as a dietary supplement. Milk thistle got its name from the milky sap which comes out of the leaves when they are broken.
Key Active Ingredients of Milk Thistle
The key active constituents of dried milk thistle seeds are flavonolignans (natural phenols composed of a part flavonoid and a part lignan) which include:
- Silibinin (silybin)
- Isosilybin
- Silychristin
- Silydianin.
A mixture of these flavonolignans extracted from milk thistle seeds is collectively known as Silymarin. Silibinin which is also known as silybin, is the major active constituent of silymarin. Silymarin has antioxidant, antiviral and anti-inflammatory properties. Milk Thistle/Silymarin is available as a dietary supplement and is commonly used for its beneficial properties in treating liver disorders. Many supplements are also standardized based on their silibinin content. There are also special formulations of silymarin or silibinin available which can increase their bioavailability by conjugating with phosphatidylcholine.
General Health Benefits of Milk Thistle
Many animal studies and few clinical studies have been carried out to evaluate the benefits of milk thistle. Some of the suggested health benefits of milk thistle are:
- May help in Liver problems include cirrhosis, jaundice, hepatitis
- May help in Gall bladder disorders
- When taken in combination with conventional treatments, it may improve diabetes
- May help improving cholesterol levels in diabetic patients
- May help with heartburn and indigestion
- May help with inhibiting cancer
Benefits of Milk Thistle in Cancer
Over the last two decades, there has been increasing interest in understanding the clinical benefits of milk thistle in cancer. Some of the in vitro/in vivo/animal/human studies which evaluated the applications/effects of milk thistle in cancer are summarized below:
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In Vitro/In Vivo/Animal Studies
1. May Inhibit Pancreatic Cancer Growth & Reduce Pancreatic Cancer-Induced Cachexia/Weakness
In vitro studies showed that milk thistle active silibinin has the potential to inhibit pancreatic cancer cell growth in a dose-dependent manner. Other in vivo studies also suggest that silibinin reduces tumor growth and proliferation of pancreatic cancer and may help prevent loss of body weight and muscle. (Shukla SK et al, Oncotarget., 2015)
In short, in vitro and animal studies suggest that milk thistle/silibinin may benefit in reducing pancreatic cancer growth and pancreatic cancer-Induced cachexia/weakness. Clinical trials are needed to establish the same in humans.
2. May Inhibit Breast Cancer Growth
In vitro studies showed that silibinin inhibited breast cancer cell growth and induced apoptosis/cell death in breast cancer cells. Findings from different studies suggest that silibinin has effective anti-breast cancer properties. (Tiwari P et al, Cancer Invest., 2011)
3. May Inhibit Prostate Cancer Growth
In another study, the anti-cancer effects of Silibinin were evaluated in a combination therapy along with DOX/Adriamycin . In this study, prostate carcinoma cells were treated with silibinin and DOX in combination.The findings showed that silibinin-DOX combination resulted in a 62–69% inhibition of growth in the treated cells. (Prabha Tiwari and Kaushala Prasad Mishra, Cancer Research Frontiers., 2015)
4. May Inhibit Skin Cancer
Many studies have also been carried out to evaluate the effects of Milk Thistle active Silibinin on skin cancer. Findings from these in vitro studies showed that Silibinin treatment may have preventive effects in human skin cancer cells. An in vivo study found that Silibinin can also prevent UVB radiation-induced skin cancer and can help in repairing UV-induced DNA damage in mouse skin.(Prabha Tiwari and Kaushala Prasad Mishra, Cancer Research Frontiers., 2015)
These studies are promising and suggest that milk thistle/silibinin may be safe and benefit skin cancer.
5. May Inhibit Colorectal Cancer
Some of the in vitro studies showed that Silibinin can induce the cell death in human colorectal cancer cells. In vitro studies also found that Silibinin treatment for 24h can reduce the growth of the cancer cells by 30–49%. (Prabha Tiwari and Kaushala Prasad Mishra, Cancer Research Frontiers., 2015)
Benefits of Milk Thistle/Silibinin were also evaluated in combination with other therapies such as histone-deacetylase(HDAC) inhibitors. The combination showed synergistic effects in colorectal cells.
6. May inhibit Lung Cancer
In vitro studies showed that Silibinin may have inhibitory effects in the human lung cancer cell lines. Studies also showed that Silibinin in combination with DOX inhibited lung cancer cell growth in vitro. Silibinin along with indole-3-carbinol also caused stronger antiproliferative effects than the individual agents. (Prabha Tiwari and Kaushala Prasad Mishra, Cancer Research Frontiers., 2015)
These findings suggest that Milk Thistle active Silibinin may also have a therapeutic benefit against lung cancer.
7. May inhibit Bladder Cancer
In vitro studies showed that Silibinin induced apoptosis/cell death of human bladder cancer cells. Studies also showed that Silibinin may also suppress the migration and spread of bladder cancer cells. (Prabha Tiwari and Kaushala Prasad Mishra, Cancer Research Frontiers., 2015)
8. May inhibit Ovarian Cancer
In vitro studies showed that silibinin can inhibit the growth of human ovarian cancer cells, and also induced apoptosis/cell death. Studies also found that Silibinin may enhance the sensitivity of ovarian cancer cells to PTX (Onxal). Silibinin when used in combination with PTX (Onxal) can also enhance apoptosis/cell death. (Prabha Tiwari and Kaushala Prasad Mishra, Cancer Research Frontiers., 2015)
These findings suggest that silibinin may be used as part of combinatorial therapies against ovarian cancer.
9. May inhibit Cervical Cancer
Studies show that Silibinin can inhibit the proliferation of human cervical cells. In addition, silibinin along with MET, a well-known anti-diabetic agent, show synergistic effects on the inhibition of cervical cancer cells and cell death. Thus, silibinin may be effective as a chemopreventive agent against cervical cancer. Further studies should explore the possibilities of developing better therapeutic strategies against cervical cancer.
Clinical Studies in Humans
Let us have a look at different clinical studies to understand whether including milk thistle as part of cancer patients’ diet is beneficial or not.
1. Benefits of Milk Thistle in reducing Cardiotoxicity in Acute Lymphoblastic Leukemia Children Treated with DOX(Adriamycin)
Silymarin, one of the key active ingredients of milk thistle, has been shown experimentally to have cardioprotective effects when given along with DOX. Silymarin can reduce oxidative stress, the root cause of cardiotoxicity. It is an antioxidant and can reduce damage to the membranes and proteins by the reactive species, that are created as part of DOX mechanism of action, by preventing depletion of the inherent antioxidant machinery of healthy cells. (Roskovic A et al, Molecules 2011)
A clinical study from the Tanta University in Egypt evaluated the cardioprotective effect of Silymarin from Milk Thistle in children with Acute Lymphoblastic Leukemia (ALL), who were treated with DOX. The study used data from 80 children with ALL, out of which 40 patients were treated with DOX along with Silymarin at 420 mg/day and the remaining 40 were treated only with DOX (placebo group). The study found that in the Silymarin group, there was a ‘decreased early DOX-induced left ventricular systolic function disturbances’ over the placebo group. This clinical study, although with a small number of ALL children, provides some confirmation of the cardioprotective effects of Silymarin as seen in experimental disease models. (Adel A Hagag et al, Infect Disord Drug Targets., 2019)
2. Benefits of Milk Thistle in reducing Liver Toxicity in Acute Lymphoblastic Leukemia Children Treated with Chemotherapy
Treatment of children with acute lymphoblastic leukemia (ALL) using chemotherapy drugs is usually interrupted due to hepatotoxicity/liver toxicity induced by chemotherapy drugs. This conundrum of eliminating the cancer using chemotherapy drugs vs. dealing with severe and sometimes irreversible side-effects of these drugs is an ongoing dilemma in the cancer community. Hence, there are continuous efforts to find approaches that can help alleviate or protect the patient from the severe side-effects.
In a clinical study, acute lymphoblastic leukemia (ALL) children with hepatic toxicity were either treated with chemotherapy alone (placebo) or a combination of milk thistle capsule containing 80 mg of silibinin along with chemotherapy (MTX/6-MP/VCR) orally (Milk Thistle Group) for 28 days. 50 children were enrolled from May 2002 to August 2005 for this study, with 26 subjects in the placebo group and 24 in the Milk Thistle Group. 49 out of the 50 children were evaluable for the study. Liver toxicity was monitored throughout the treatment period. (EJ Ladas et al, Cancer., 2010)
The findings from the study suggested that taking Milk Thistle along with chemotherapy by ALL patients may be associated with a significant reduction in liver toxicity. The study found no unexpected toxicities, need for reducing doses of chemotherapy, or any delays in therapy during the milk thistle supplementation period. The studies also showed that milk thistle did not impact the efficacy of the chemotherapy agents used for ALL treatment.
The researchers however suggested future studies to find out the most effective dose of Milk Thistle and its effect on hepatotoxicity/liver toxicity and leukemia-free survival.
3. Benefits of Milk Thistle active Silibinin for reducing brain edema in Lung Cancer Patients with Brain Metastasis
Studies suggest that the use of milk thistle active silibinin-based nutraceutical named Legasil® may improve Brain Metastasis from NSCLC/lung cancer patients which progressed post treatment with radiotherapy and chemotherapy. The findings of these studies also suggest that silibinin administration can significantly reduce brain edema. However, these inhibitory effects of silibinin on brain metastasis may not affect the primary tumor outgrowth in lung cancer patients. (Bosch-Barrera J et al, Oncotarget., 2016)
4. Benefits of Milk Thistle in reducing Liver Toxicity in a Breast Cancer Patient
A case study was published on a breast cancer patient who was treated with 5 different chemotherapy treatments and had progressive liver failure. The report mentioned that the liver test results deteriorated to life-threatening levels after four cycles chemotherapy treatment. The patient was then supplemented with Silibinin-based nutraceutical named Legasil® post which clinical and liver improvement was observed, which helped the patient to continue palliative chemotherapy. (Bosch-Barrera J et al, Anticancer Res., 2014)
This study indicated possible clinical benefit of silibinin in reducing liver toxicity in breast cancer patients treated with chemotherapy.
5. Benefits of Milk Thistle in Improving Survival Outcomes in Brain Metastatic Patients Treated with Radiotherapy
Studies show that Milk thistle may benefit brain metastatic patients undergoing radiotherapy. A clinical study included data from patients with brain metastases who were treated either with radiotherapy alone or radiotherapy along with omega 3 fatty acids and silymarin. The study found that the patients who were taking omega 3 fatty acids and silymarin had longer survival times as well as reduced radionecrosis. (Gramaglia A et al, Anticancer Res., 1999)
Conclusion
Milk Thistle Extract/Silymarin and its key component Silibinin has many health benefits due to its antioxidant, anti-inflammatory and anti-cancer properties. Milk thistle extract/Silymarin usually does not have many side effects when taken by mouth in right quantities. However, in some people, taking milk thistle extract may lead to diarrhea, nausea, intestinal gas, bloating, fullness or pain, and loss of appetite. Also, since milk thistle extract might lower blood sugar level in people with diabetes, doses of diabetes medications may have to be readjusted. Milk thistle extract may also have estrogenic effects which may worsen hormone-sensitive conditions, including certain types of breast cancer.
Different invitro/invivo and animal studies have investigated the health benefits of milk thistle extract and its ability to inhibit a variety of cancers. Promising results have been reported by many of these studies suggesting protective effects of milk thistle in certain types of cancer. Few human trials also support that milk thistle and its active ingredients may be beneficial in reducing some of the dangerous side-effects of chemotherapy and radiotherapy such as cardiotoxicity, hepatotoxicity and brain edema in certain cancer types treated with specific chemo. However, taking a natural supplement such as milk thistle extract randomly with any chemotherapy for any cancer is not recommended as it can cause adverse herb-drug interactions. Hence, one should always consult their physician before taking any natural supplement along with a chemotherapy.
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