The Safety of Milk Thistle for Breast Cancer

The Safety of Milk Thistle for Breast Cancer

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The Safety of Milk Thistle for Breast Cancer

Milk thistle (Silybum marianum) is a wonderful healing herb, most commonly used to treat liver complaints and to assist with liver detoxification. I get asked about this herb all the time, because there’s some information on the internet that tells women with breast cancer to avoid milk thistle because of its supposed “estrogenic” and possibly “carcinogenic” (cancer-causing) properties. 
 
I’ve read these articles about the supposed estrogenic properties of milk thistle, and they make me feel really irritated because they are misguided and come to incorrect conclusions. Telling women with breast cancer to avoid milk thistle is not only misguided, it is probably doing them a great disservice.
 
As usual, annoyance and irritation prods me to write an article in order to set the matter straight.
 
If you look at the scientific literature, the overwhelming majority of research studies show positive results using milk thistle. No estrogenic effects have been noted in human clinical trials. The warning stems from a couple of studies on rodents. A 2006 study [1] performed in both test tubes and with animals found that silymarin (discussed below) caused estrogen levels to rise and appeared to be carcinogenic. On the other hand, the same study found that silibinin (also discussed below) strongly inhibited the development of mammary tumors as well as lung metastasis in HER-2+ transgenic mice. Also, a 2001 Czech study found silymarin had estrogenic effects on rats that had had their ovaries removed (I feel sorry for the rats – their bodies were probably trying to create estrogen out of whatever they could – just my guess.)
 
A Discussion of Silymarin and Silibinin
 
You will see the words silymarin and silibinin being used with reference to milk thistle, but what are they? The best description I found comes from a paper titled “Milk Thistle Nomenclature: Why It Matters in Cancer Research and Pharmacokinetic Studies” [3]
 
In this paper silymarin is described as the crude commercial product of milk thistle. Silymarin is a complex of at least seven flavonolignans and one flavonoid that comprises 65-80% of milk thistle extract. 
 
Silibinin comes from silymarin – it is a semi-purified component of silymarin. Silibinin was once thought to be a single compound but is now recognized as a 1:1 mixture of 2 diastereoisomers, silybin A and silybin B. According to the authors of this paper, “The distinction between silymarin and silibinin is not only important to understanding the historical literature, but thorough characterization and use of chemically defined mixtures in preclinical and clinical studies are essential to the progress of these botanical compounds as human therapeutics.”
 
The Research on Milk Thistle
 
I delved into the research on milk thistle (one of my favorite things to do) and this is what I found. Following are the studies that I found most impressive with regard to the safety of milk thistle for breast cancer survivors. Many of them are preclinical studies as funds are usually lacking to perform human trials in most instances. Having said that, a 2007 review of clinical trials on milk thistle [4], while not deeply investigative of the benefits of milk thistle, did conclude that milk thistle extracts were known to be safe and well tolerated, and that toxic or adverse effects observed in the reviewed clinical trials were minimal.
 
A 2008 review of medical studies [5] found good evidence that silymarin from milk thistle may be beneficial for cancer patients. It was found to target several steps of carcinogenesis including tumor cell proliferation (rapid growth), cell cycle regulation, differentiation, apoptosis (planned cell death – common to all cells but lacking in cancer cells), angiogenesis (the ability of a tumor to create a system of blood vessels to feed itself), invasion and metastasis (spread to other areas of the body). In addition, silymarin was found to have anti-inflammatory and antioxidative properties and also reduced the toxicity of chemotherapy drugs.
 
A comprehensive 2011 study [6] administered milk thistle extracts at various (and often high) dosages to both male and female mice and rats for periods of up to two years, the human equivalent of lifelong exposure. They found no evidence of carcinogenic activity, and in fact found a reduced incidence of liver cancer. 
 
A 2011 review of medical studies [7] by Italian researchers found that there were ample studies to indicate that milk thistle was a potent antioxidant, inhibited the binding of toxins to liver cells, reduced liver injury in animals caused by certain drugs and radiation, and inhibited liver fibrosis.
 
A 2011 preclinical study [8] of estrogen-receptor-positive breast cancer cells found that silibinin enhanced apoptosis (defined above) and reduced tumor cell viability.
 
Another 2011 preclinical study [9] found that silibinin inhibited EGFR (Epidermal Growth Factor Receptor, a protein-coding gene, the overexpression of which is implicated in at least 30% of breast cancers). Silibinin also inhibited CD-44, a cell surface adhesion receptor that is highly expressed in many cancers, regulates metastasis and is also a bio-marker for cancer stem cells. Silibinin also reduced MMP-9, an enzyme shown to be involved in the invasion (metastasis) of other tissues, thus leading to the spread of breast cancer. 
 
Yet another 2011 preclinical study [10] with triple negative breast cancer cells found that silibinin inhibited the metastatic potential of this line of cells. It worked by reducing the stickiness of these cells, and worked in several other ways to reduce the ability of these cells to move to other parts of the body.
 
A 2012 cell study [11] involving both estrogen-receptor positive and -negative breast cancer cells (and prostate cancer cells) found that silibinin had anti-cancer activity, and inhibited a pathway (the Wnt/ß-catenin pathway) associated with the spread of these cancer cell lines to other parts of the body.
 
A 2013 preclinical study [12] with animals found that milk thistle extract protected the bones of mice that had ovaries removed by promoting the activity of bone-building cells (osteoblasts) and inhibiting the activity of bone resorption cells (osteoclasts). And a 2013 review of medical studies [13] on milk thistle found that silymarin played a crucial role in helping to prevent bone loss. Researchers specifically stated that silymarin could be beneficial for fracture healing, and could be considered beneficial for post menopausal women in the treatment of osteoporosis.
 
A 2013 cell study [14] performed by Iranian researchers found that silymarin had a synergistic effect on the therapeutic potential of doxorubicin (a chemotherapy drug commonly used for breast cancer, also known as Adriamycin). Researchers found that combining silymarin with doxorubicin was more effective against cancer cells, and also decreased the side effects of the drug. Remember, milk thistle is known to be a great detoxifier for the liver.
 
A 2015 preclinical study [15] found that silibinin inhibited a gene known as STAT3 which known to be involved in cancer tumor growth and spread (metastasis).
 
Another 2015 preclinical study [16] found that silibinin induced autophagy (a complex metabolic process by which cells are broken down and reused to make new cells) in a line of estrogen- and progesterone-receptor positive breast cancer cells.
 
Milk thistle appears to be beneficial in estrogen metabolism when combined with other ingredients, as well. A small 2010 clinical study [17] involving 47 pre-menopausal and 49 post-menopausal women investigated the use of a health supplement which incorporated a combination of indole-3-carbinol, lignans, calcium glucarate, milk thistle, Schisandra chinesis and stinging nettle. Each woman either took the supplement or a placebo for 28 days. Researchers found that those taking the supplement had significantly increased urinary output of estrogen – meaning that it helped the body to break down and excrete estrogen.
 
Milk Thistle as a Phytoestrogen
 
I have discussed phytoestrogens in several other articles (see my article: Phytoestrogens – Harmful or Beneficial for Hormone Driven Breast Cancer?). So yes, milk thistle does act as a phytoestrogen, meaning that it can dock with estrogen receptors on cells and mimic the effects of estrogen. If you’ve read my other articles, you will know that this is a good thing, and that it’s okay for someone with hormone driven breast cancer.
 
I’ve said this before, and no doubt I’ll say it again: phytoestrogens have to be amongst the most misunderstood plant compounds on the planet. Phytoestrogens include flaxseeds, soy, and milk thistle (among many others), and what we have learned about them is that because their estrogenic effects are much weaker than our own estrogen, they actually protect against the effects of stronger estrogens and also xenoestrogens (external estrogens like pesticides and other hormone disrupting chemicals). YES – that means phytoestrogens are protective for both breast and uterine tissues.
 
Also, studies have shown that many phytoestrogens have beneficial effects on bone metabolism, including milk thistle. As mentioned above, preclinical studies with milk thistle have demonstrated great promise in helping to rebuild bones by preventing the breakdown of bone by osteoclasts, while at the same time improving the building of bone by osteoblasts. 
 
Bottom Line: I have discovered NO evidence that milk thistle extract has negative estrogenic effects in humans. The preponderance of studies shows it may have tremendous benefits for breast cancer patients. 
 
The Other Benefits of Milk Thistle
 
In addition to its benefits for breast cancer, milk thistle extracts have been shown to have all of these actions:
 
• promotes improved liver health in double-blind, human clinical trials, benefits several types of liver disease, including hepatitis and cirrhosis
• liver protective 
• liver detoxifier
• antioxidant and free radical scavenger, so anti-aging
• anti-inflammatory 
• neuroprotective 
• protects against depletion of glutathione 
• stimulates the formation of new liver cells (hepatocytes) 
• reduces cholesterol levels
• reduces insulin resistance and improves blood sugar levels
 
Taking Milk Thistle
 
Milk thistle is very well tolerated by most and at the right dosage is free of major side effects. If you are using milk thistle, try to find it in a standardized extract to get the results you want. Around 150 mg three times daily is a good dosage for promoting liver health and detoxification (it may have a mild laxative effect at this dose). For general use and liver support take 150 mg once daily.
 
Milk thistle as a tea is generally not very well absorbed.
 
Some supplement makers are creating phytosomal milk thistle. Phytosomes are a combination of silymarin with phosphatidylcholine molecules to aid their absorption. If taking phytosomal milk thistle the typical dosage is 80-120 mg two to three times per day.
 
Drug interactions: Milk thistle may possibly interact with some medications, including anti-anxiety drugs, some allergy medicines, and blood thinners, among others. If you are taking medications, be sure to discuss the use of milk thistle with your health care provider to prevent any possible interactions.
 
NOTE: Do not rely upon milk thistle on its own to treat breast cancer, or any other sort of cancer. However, in combination with other treatments, both conventional and natural, milk thistle can be very beneficial.
 
References:
 
[1] Enhancement of Mammary Carcinogenesis in Two Rodent Models by Silymarin Dietary Supplements – https://pubmed.ncbi.nlm.nih.gov/16597642/
 
[2] Estrogenic effects of silymarin on ovariectomized rats – http://www.vri.cz/docs/vetmed/46-1-17.pdf
 
[3] Milk Thistle Nomenclature: Why It Matters in Cancer Research and Pharmacokinetic Studies –  https://journals.sagepub.com/doi/abs/10.1177/1534735407301825
 
[4] Review of Clinical Trials Evaluating Safety and Efficacy of Milk Thistle (Silybum marianum [L.] Gaertn.) – https://journals.sagepub.com/doi/pdf/10.1177/1534735407301942
 
[5] Multitargeted therapy of cancer by silymarin – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2612997/
 
[6] Toxicology and carcinogenesis studies of milk thistle extract (CAS No. 84604-20-6) in F344/N rats and B6C3F1 mice (Feed Studies) – https://pubmed.ncbi.nlm.nih.gov/21685957/
 
[7]  Milk thistle in liver diseases: past, present, future – https://hal.archives-ouvertes.fr/hal-00599834/document
 
[8] Silibinin Enhances Ultraviolet B-Induced Apoptosis in MCF-7 Human Breast Cancer Cells – https://synapse.koreamed.org/DOIx.php?id=10.4048/jbc.2011.14.1.8&vmode=FULL
 
[9] Silibinin Suppresses EGFR Ligand-induced CD44 Expression through Inhibition of EGFR Activity in Breast Cancer Cells – http://ar.iiarjournals.org/content/31/11/3767.short
 
[10] Inhibition of silibinin on migration and adhesion capacity of human highly metastatic breast cancer cell line, MDA-MB-231, by evaluation of ß1-integrin and downstream molecules, Cdc42, Raf-1 and D4GDI – https://link.springer.com/article/10.1007/s12032-011-0113-8
 
[11] Silibinin inhibits Wnt/ß-catenin signaling by suppressing Wnt co-receptor LRP6 expression in human prostate and breast cancer cells – https://www.sciencedirect.com/science/article/abs/pii/S0898656812002057
 
[12] Antiosteoclastic Activity of Milk Thistle Extract after Ovariectomy to Suppress Estrogen Deficiency-Induced Osteoporosis – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3678416/
 
[13] Milk Thistle: A Future Potential Anti-Osteoporotic and Fracture Healing Agent – https://pubmed.ncbi.nlm.nih.gov/24093748/
 
[14] The role of milk thistle extract in breast carcinoma cell line (MCF-7) apoptosis with doxorubicin – http://acta.tums.ac.ir/index.php/acta/article/view/4369
 
[15] Silibinin and STAT3: A natural way of targeting transcription factors for cancer therapy – https://pubmed.ncbi.nlm.nih.gov/25944486/
 
[16] Silibinin, a natural flavonoid, induces autophagy via ROS-dependent mitochondrial dysfunction and loss of ATP involving BNIP3 in human MCF7 breast cancer cells – https://www.spandidos-publications.com/or/33/6/2711?text=fulltext
 
[17] Effects of A Breast-Health Herbal Formula Supplement on Estrogen Metabolism in Pre- and Post-Menopausal Women not Taking Hormonal Contraceptives or Supplements: A Randomized Controlled Trial – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3018890/
 
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About Marnie Clark

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Hi I’m Marnie Clark, breast cancer survivor turned coach. I have 20 years of experience in natural medicine.  In 2004/05 I battled breast cancer myself. You can see more about my journey on my page Breast Cancer Diary.

I’ve been healthy and recurrence-free since 2004 and in 2012 I became a Breast Cancer Coach because I became aware of the fact that whilst there is now a wealth of information on the Internet, much of it is confusing, conflicting, and sometimes just wrong!

So it is my duty to help you unconfuse and untangle all that information, and find what works for YOU.

GET MY BEST TIPS on healthy ways to beat breast cancer and prevent recurrences by signing up for my free e-newsletters and eBooks.

You can also “like” me on Facebook (Marnie Clark, Breast Health Coach) to get my inspirational snippets, news and updates. I promise to do my utmost to keep you informed and empowered on your healing journey… and beyond.

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