Resveratrol.. might not be so good afterall

[drksun]

I found these two studies showing how resveratrol acts as a estrogen receptor antagonist and agonist depending on the type of estrogen receptor. It also causes an increase in breast cancer growth, can't that also cause gyno then, don't they both have the same type of receptors?

Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Medical School, 303 E. Chicago Avenue, Chicago, IL 60611, USA.

The phytochemical resveratrol, which is found in grapes and wine, has been reported to have a variety of anti-inflammatory, anti-platelet, and anti-carcinogenic effects. Based on its structural similarity to diethylstilbestrol, a synthetic estrogen, we examined whether resveratrol might be a phytoestrogen. At concentrations (approximately 3-10 microM) comparable to those required for its other biological effects, resveratrol inhibited the binding of labeled estradiol to the estrogen receptor and it activated transcription of estrogen-responsive reporter genes transfected into human breast cancer cells. This transcriptional activation was estrogen receptor-dependent, required an estrogen response element in the reporter gene, and was inhibited by specific estrogen antagonists. In some cell types (e.g., MCF-7 cells), resveratrol functioned as a superagonist (i.e., produced a greater maximal transcriptional response than estradiol) whereas in others it produced activation equal to or less than that of estradiol. Resveratrol also increased the expression of native estrogen-regulated genes, and it stimulated the proliferation of estrogen-dependent T47D breast cancer cells. We conclude that resveratrol is a phytoestrogen and that it exhibits variable degrees of estrogen receptor agonism in different test systems. The estrogenic actions of resveratrol broaden the spectrum of its biological actions and may be relevant to the reported cardiovascular benefits of drinking wine.
PMID: 9391166 [PubMed - indexed for MEDLINE]

Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, Kentucky 40292, USA.

Epidemiological evidence indicates that phytoestrogens inhibit cancer formation and growth, reduce cholesterol levels, and show benefits in treating osteoporosis. At least some of these activities are mediated through the interaction of phytoestrogens with estrogen receptors alpha and beta (ERalpha and ERbeta). Resveratrol, trans-3,5,4'-trihydroxystilbene, is a phytoestrogen in grapes that is present in red wine. Resveratrol was shown to bind ER in cytosolic extracts from MCF-7 and rat uteri. However, the contribution of ERalpha vs. ERbeta in this binding is unknown. Here we report that resveratrol binds ERbeta and ERalpha with comparable affinity, but with 7,000-fold lower affinity than estradiol (E2). Thus, resveratrol differs from other phytoestrogens that bind ERbeta with higher affinity than ERalpha. Resveratrol acts as an estrogen agonist and stimulates ERE-driven reporter gene activity in CHO-K1 cells expressing either ERalpha or ERbeta. The estrogen agonist activity of resveratrol depends on the ERE sequence and the type of ER. Resveratrol-liganded ERbeta has higher transcriptional activity than E2-liganded ERbeta at a single palindromic ERE. This indicates that those tissues that uniquely express ERbeta or that express higher levels of ERbeta than ERalpha may be more sensitive to resveratrol's estrogen agonist activity. For the natural, imperfect EREs from the human c-fos, pS2, and progesterone receptor (PR) genes, resveratrol shows activity comparable to that induced by E2. We report that resveratrol exhibits E2 antagonist activity for ERalpha with select EREs. In contrast, resveratrol shows no E2 antagonist activity with ERbeta. These data indicate that resveratrol differentially affects the transcriptional activity of ERalpha and ERbeta in an ERE sequence-dependent manner.
PMID: 11014220 [PubMed - indexed for MEDLINE]

 

[metroba]

bump

 

[nelix]

I would love to hear someone who knows there **** on this one

 

[ECTOmorph]

I read some of those as well the other day. Perhaps this is somewhat like how Nolva is an E Agonist in some places (liver i think) and antagonist in others

Ive been reading alot that resverstrol has serm capabiltie tho?????

 

[drksun]

I read some of those as well the other day. Perhaps this is somewhat like how Nolva is an E Agonist in some places (liver i think) and antagonist in others

Ive been reading alot that resverstrol has serm capabiltie tho?????

well yeah by definition its ture, its a SLECTIVEerm, what im trying to say is, it might act as an agonist in breast tissue. Idk where the ERa and ERb are most present, but its just something to open discussion about. What types of tissue is it an antagonist and agonist towards?

 

[metroba]

well yeah by definition its ture, its a SLECTIVEerm, what im trying to say is, it might act as an agonist in breast tissue. Idk where the ERa and ERb are most present, but its just something to open discussion about. What types of tissue is it an antagonist and agonist towards?

I love your sig:toofunny:

 

[Guest]

I found these two studies showing how resveratrol acts as a estrogen receptor antagonist and agonist depending on the type of estrogen receptor. It also causes an increase in breast cancer growth, can't that also cause gyno then, don't they both have the same type of receptors?

Straight from our science department.

This has been covered a number of times. Resveratrol acts as an estrogen antagonist at the ER-alpha subtype, while acting as an agonist or having neutral activity at the ER-beta. This is how SERMs such as clomiphene and tamoxifen work. They too work as an estrogen antagonist or agonist, depending upon the estrogen receptor subtype.

The study states exactly that:

"We report that resveratrol exhibits E2 antagonist activity for ERalpha with select EREs. In contrast, resveratrol shows no E2 antagonist activity with ERbeta."

Breast cancer cell lines aren't normal cell lines and shouldn't be used to determine what will or will not cause gynecomastia. If it's obvious that it's acting directly and primarily through estrogen receptors, then yes, but breast cancer often involves mechanisms that are independent of estrogen receptors.

Resveratrol has in fact been shown to inhibit breast cancer cell lines in studies. For example:
Mol Pharmacol. 2007 Sep 11;
Mitochondria, Calcium, and Calpain are Key Mediators of Resveratrol-Induced Apoptosis in Breast Cancer.
Sareen D, Darjatmoko SR, Albert DM, Polans AS.
University of Wisconsin - Madison.
Resveratrol (RES), a natural plant polyphenol, has gained interest as a non-toxic chemopreventive agent capable of inducing tumor cell death in a variety of cancer types. However, the early molecular mechanisms of RES-induced apoptosis are not well defined. Using the human breast cancer cell lines MDA-MB-231 and MCF-7, we demonstrate that RES is anti-proliferative and induces apoptosis in a concentration- and time-dependent manner. Preceding apoptosis, RES instigates a rapid dissipation of mitochondrial membrane potential (DeltaPsim) by directly targeting mitochondria. This is followed by release of cytochrome c and Smac/DIABLO into the cytoplasm and substantial increase in the activities of caspases-9 and -3 in MDA-MB-231 cells. Additionally, live cell microscopy demonstrates that RES causes an early biphasic increase in the concentration of free intracellular calcium ([Ca(2+)]i), likely resulting from depletion of the endoplasmic reticulum (ER) stores in breast cancer cells. In caspase-3 deficient MCF-7 cells apoptosis is mediated by the Ca(2+)- activated protease, calpain, leading to the degradation of plasma membrane Ca(2+)-ATPase isoform 1 (PMCA1) and fodrin; the degradation is attenuated by buffering [Ca(2+)]i and blocked by calpain inhibitors. Mitochondrial permeability transition pore antagonists also blocked calpain activation. In vivo mouse xenograft studies demonstrate that RES treatment inhibits breast cancer growth with no systemic toxicities. Collectively, these results suggest a critical role for mitochondria not only in the intrinsic apoptotic pathway but also in the Ca(2+) and calpain-dependent cell death initiated by RES. Thus, RES may prove useful as a non-toxic alternative for breast cancer treatment

 

[thebigt]

ive heard nothing but good stuff about resveratrol. if you dig deep enough you can throw dirt on anything.

 

[matthew76]

There's a Thread that thesinner put together on RES... just got to search for it


“In determining whether the substantiation standard has been met with competent and reliable scientific evidence, we recommend that firms consider the following issues in their assessment:

-The meaning of the claim(s) being made;
-The relationship of the evidence to the claim;
-The quality of the evidence; and
-The totality of the evidence. ”

Substantiation for Dietary Supplement Claims Made Under Section 403(r) (6) of the Federal Food, Drug, and Cosmetic Act

 

[Outside Backer]

interesting thread

id like to see more info

 

[drksun]

Straight from our science department.

This has been covered a number of times. Resveratrol acts as an estrogen antagonist at the ER-alpha subtype, while acting as an agonist or having neutral activity at the ER-beta. This is how SERMs such as clomiphene and tamoxifen work. They too work as an estrogen antagonist or agonist, depending upon the estrogen receptor subtype.

The study states exactly that:

"We report that resveratrol exhibits E2 antagonist activity for ERalpha with select EREs. In contrast, resveratrol shows no E2 antagonist activity with ERbeta."

Breast cancer cell lines aren't normal cell lines and shouldn't be used to determine what will or will not cause gynecomastia. If it's obvious that it's acting directly and primarily through estrogen receptors, then yes, but breast cancer often involves mechanisms that are independent of estrogen receptors.

Resveratrol has in fact been shown to inhibit breast cancer cell lines in studies. For example:
Mol Pharmacol. 2007 Sep 11;
Mitochondria, Calcium, and Calpain are Key Mediators of Resveratrol-Induced Apoptosis in Breast Cancer.
Sareen D, Darjatmoko SR, Albert DM, Polans AS.
University of Wisconsin - Madison.
Resveratrol (RES), a natural plant polyphenol, has gained interest as a non-toxic chemopreventive agent capable of inducing tumor cell death in a variety of cancer types. However, the early molecular mechanisms of RES-induced apoptosis are not well defined. Using the human breast cancer cell lines MDA-MB-231 and MCF-7, we demonstrate that RES is anti-proliferative and induces apoptosis in a concentration- and time-dependent manner. Preceding apoptosis, RES instigates a rapid dissipation of mitochondrial membrane potential (DeltaPsim) by directly targeting mitochondria. This is followed by release of cytochrome c and Smac/DIABLO into the cytoplasm and substantial increase in the activities of caspases-9 and -3 in MDA-MB-231 cells. Additionally, live cell microscopy demonstrates that RES causes an early biphasic increase in the concentration of free intracellular calcium ([Ca(2+)]i), likely resulting from depletion of the endoplasmic reticulum (ER) stores in breast cancer cells. In caspase-3 deficient MCF-7 cells apoptosis is mediated by the Ca(2+)- activated protease, calpain, leading to the degradation of plasma membrane Ca(2+)-ATPase isoform 1 (PMCA1) and fodrin; the degradation is attenuated by buffering [Ca(2+)]i and blocked by calpain inhibitors. Mitochondrial permeability transition pore antagonists also blocked calpain activation. In vivo mouse xenograft studies demonstrate that RES treatment inhibits breast cancer growth with no systemic toxicities. Collectively, these results suggest a critical role for mitochondria not only in the intrinsic apoptotic pathway but also in the Ca(2+) and calpain-dependent cell death initiated by RES. Thus, RES may prove useful as a non-toxic alternative for breast cancer treatment

yeah but the study from Northwestern University Medical School i posted shows that Resveratrol acts as a super-agonist twords MCF-7 cells, those are cells that are part of breast cancer cell lines.

 

[matthew76]

Just look at the source debating your study...

yeah but the study from Northwestern University Medical School i posted shows that Resveratrol acts as a super-agonist twords MCF-7 cells, those are cells that are part of breast cancer cell lines.

 

[UNCfan1]

ive heard nothing but good stuff about resveratrol. if you dig deep enough you can throw dirt on anything.

Thats so true.

 

[drksun]

found this from on of dr.d's posts..

Resveratrol 50% 1200mg
There is high estrogenic activity in the cis-isomer (also called the Z-isomer) of resveratrol, which is quite abundant in the 50% extract it seems. 'Superagonists of estradiol' is what this article states! (see link below) Unless this material has been cold processed, stored away from heat and protected from sunlight, you can bet it's not all trans-resveratrol. That means any botanical source likely has high amounts of estrogenic activity from cis isomerization. I'd like to see some data showing the cis/trans ratio and total percentages in this product before I put 1200mg of it in my body.
PubMed Home

i assume hes talking about the article i posted, im gonna read thesinner posts.

 

[djbombsquad]

I give it to patients all the time at the Dr's office I work at. We carry the stuff in our office and give it all the time. No problems.

 

[thebigt]

I give it to patients all the time at the Dr's office I work at. We carry the stuff in our office and give it all the time. No problems.

there is no guarantee that what you buy online is going to be of same quality as what a doctor's office would carry. that is the point dr.d is making.

 

[djbombsquad]

Your correct that what you get online is good or not good. Your correct.

 

[saludable24]

My Aunt had breast cancer and is now on arimadex (AI). She is very interested in supplements that could also help. Res seems interesting as do DIM and GSE.

Can we derive what would be an effective dose of resveratrol as well as the type to use from these studies?

 

[djbombsquad]

The stuff we carry costs more because of the quality of it compared to store brand.

 

[djbombsquad]

Any thing threw a dr will cost more but at the same time you get what you pay for.

 

[TripDog]

Any thing threw a dr will cost more but at the same time you get what you pay for.

agreed!!

 

[thebigt]

another thing to consider is the storage, handling and shipping. from what ive read, sunlight/temperature even air can effect it. i dont think online retailers will be storing in dark cool room. shipping is also a biggie as it will be exposed to extreme conditions, at least where i live in indiana. just wonder what below freezing temps will do to it, or +90 in summer.

 

[drksun]

from the way i read it UV light can change the trans- isomer to a cis- isomer, the cis- isomer is highly estrogenic in a bad way, also i read something about our livers converting some to the cis- isomer, i'm working on finding accurate information on this. I'm not trying to single out any product or company, but it seems that the purity is crucial to the products claims.

 

[djbombsquad]

agreed!!

The stuff we carry in the office is done strictly via blood work so there is no if ands or buts.

 

[RisingAgainst]

FWIW, estrogen is always made out to be the bad guy, (as well as cortisol and the like)... in our industry, it's not always a GOOD thing, but neither is it always a bad thing. I believe people should overlook this stuff if they don't fully comprehend the differences, instead of NITPICKING at this and that as if they actually get it. (this was not directed at anybody, or anything in this thread, just a quick rant)

 

[Mass_69]

Just drink red wine (Pinot Noir).

:drunk: