HER2 Support Group Forums - View Single Post - Results of Chat on Nutrition and Supplements

sarah · 09-25-2006, 05:10 AM

Cathya,
I am now conflictewd about Milk thistle - check under search for other opinions but this was posted uneder a Milk Thistle discussion by Heblaj01:

Potential undesirable side effects of Silybin In previous posts in this thread Tom & myself highlighted the lab experiments which showed beneficial activity of Silybin (an extract of Silymarin, the main ingredient in Milk Thistle) against various cancer cell lines (primary lung, liver,brain).
In follow up search for more info on the subject I discovered a few disquieting bits of data regarding two negative aspects of Silybin (& its related parent compounds).
None of the info I read is definitive since no human study has been done to confirm the lab findings & my limited understanding of the data may be flawed, but caution is of the order.

The first bit is the inhibition of P450 3A4 (ref 1 below) which is necessary for the proper metabolism of some chemo drugs such as Vinorelbine(Navelbine).
However since inhibition of P450 3A4 is in some cases limited to the guts (& does not always extend to the liver) Silybin & the chemo drug would have to be both taken by mouth. So in the case of Vinorelbine which taken by I.V. the risk of interaction is perhaps nil. (There is a pill version of Vinorelbine which would appear to be more problematic if taken with Silybin).
In addition Silybin inhibits UGT1A1 which has been associated with protection against some cancers (Ref.2) & is necessary for the metabolism of the drug Irinotecan(would increase its toxicity by lengthening its stay in the body).

The second bit of negative info is related to the potential effect on ER+ cancer cells. In all of the papers I have read so far about the beneficial activity of Silybin no estrogen positive cells were tested. The beneficial effects were demonstrated on primary cancer cells in lung, liver etc...not on metastatic cells from breast in these organs.
I found two papers demonstrating adverse effects of Silymarin on the proliferation of ER+ cells (Ref.3 & 4).
Since experiments showing anticancer activity used pure Silybin while those showing adverse effects were using the parent Silymarin there was still the possibility that adverse effects were caused by chemicals in Silymarin other than Silybin. Trying to find an answer to that question on internet proved fruitless & I had to querry by E-mail one of the researchers involved in the Silybin studies. His reply was that he knew of no study on this matter but that he assumed that the negative effects on ER+ cells caused by Silymarin would be the same for pure Silybin (& consequently for milk thistle as well).

If all of these findings & speculations are applicable to women with ER+ or at risk of ER+ cancer then taking Milk Thistle or Silymarin or Silybin is potentially increasing the risk of proliferation.

It is quite disappointing that these supplements may be double edge swords perhaps helpfull against some cancers & appearing adverse for others.

Ref.1
http://dmd.aspetjournals.org/cgi/content/full/32/6/587
SILYBIN INACTIVATES CYTOCHROMES P450 3A4 AND 2C9 AND INHIBITS MAJOR HEPATIC GLUCURONOSYLTRANSFERASES
Ref.2
http://breast-cancer-research.com/content/7/6/r909
Genetic polymorphisms in human SULT1A1 and UGT1A1 genes associate with breast tumor characteristics: a case-series study.
Ref.3
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlu s&list_uids=14568570&query_hl=23&itool=pubmed_docs um
Silymarin is a selective estrogen receptor beta (ERbeta) agonist and has estrogenic effects in the metaphysis of the femur but no or antiestrogenic effects in the uterus of ovariectomized (ovx) rats.
Ref.4
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlu s&list_uids=16597642&query_hl=26&itool=pubmed_docs um
Enhancement of mammary carcinogenesis in two rodent models by silymarin dietary supplements.

09-25-2006, 05:10 AM	#31
sarah Senior Member Join Date: Sep 2005 Location: france Posts: 1,648	Cathya, I am now conflictewd about Milk thistle - check under search for other opinions but this was posted uneder a Milk Thistle discussion by Heblaj01: Potential undesirable side effects of Silybin In previous posts in this thread Tom & myself highlighted the lab experiments which showed beneficial activity of Silybin (an extract of Silymarin, the main ingredient in Milk Thistle) against various cancer cell lines (primary lung, liver,brain). In follow up search for more info on the subject I discovered a few disquieting bits of data regarding two negative aspects of Silybin (& its related parent compounds). None of the info I read is definitive since no human study has been done to confirm the lab findings & my limited understanding of the data may be flawed, but caution is of the order. The first bit is the inhibition of P450 3A4 (ref 1 below) which is necessary for the proper metabolism of some chemo drugs such as Vinorelbine(Navelbine). However since inhibition of P450 3A4 is in some cases limited to the guts (& does not always extend to the liver) Silybin & the chemo drug would have to be both taken by mouth. So in the case of Vinorelbine which taken by I.V. the risk of interaction is perhaps nil. (There is a pill version of Vinorelbine which would appear to be more problematic if taken with Silybin). In addition Silybin inhibits UGT1A1 which has been associated with protection against some cancers (Ref.2) & is necessary for the metabolism of the drug Irinotecan(would increase its toxicity by lengthening its stay in the body). The second bit of negative info is related to the potential effect on ER+ cancer cells. In all of the papers I have read so far about the beneficial activity of Silybin no estrogen positive cells were tested. The beneficial effects were demonstrated on primary cancer cells in lung, liver etc...not on metastatic cells from breast in these organs. I found two papers demonstrating adverse effects of Silymarin on the proliferation of ER+ cells (Ref.3 & 4). Since experiments showing anticancer activity used pure Silybin while those showing adverse effects were using the parent Silymarin there was still the possibility that adverse effects were caused by chemicals in Silymarin other than Silybin. Trying to find an answer to that question on internet proved fruitless & I had to querry by E-mail one of the researchers involved in the Silybin studies. His reply was that he knew of no study on this matter but that he assumed that the negative effects on ER+ cells caused by Silymarin would be the same for pure Silybin (& consequently for milk thistle as well). If all of these findings & speculations are applicable to women with ER+ or at risk of ER+ cancer then taking Milk Thistle or Silymarin or Silybin is potentially increasing the risk of proliferation. It is quite disappointing that these supplements may be double edge swords perhaps helpfull against some cancers & appearing adverse for others. Ref.1 http://dmd.aspetjournals.org/cgi/content/full/32/6/587 SILYBIN INACTIVATES CYTOCHROMES P450 3A4 AND 2C9 AND INHIBITS MAJOR HEPATIC GLUCURONOSYLTRANSFERASES Ref.2 http://breast-cancer-research.com/content/7/6/r909 Genetic polymorphisms in human SULT1A1 and UGT1A1 genes associate with breast tumor characteristics: a case-series study. Ref.3 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlu s&list_uids=14568570&query_hl=23&itool=pubmed_docs um Silymarin is a selective estrogen receptor beta (ERbeta) agonist and has estrogenic effects in the metaphysis of the femur but no or antiestrogenic effects in the uterus of ovariectomized (ovx) rats. Ref.4 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlu s&list_uids=16597642&query_hl=26&itool=pubmed_docs um Enhancement of mammary carcinogenesis in two rodent models by silymarin dietary supplements.