zombiemuscle
Active member
When taking an ai your body may make more testosterone due to low levels of estrogen. Using indole3carbinol can lower estrogen... Could this cause the hpta to kick in and make testosterone?
I3C
- Thread starter zombiemuscle
- Start date
CrazyChemist
Well-known member
Hey I just read some journal literature on IC3. Yes it shows a shift in estrogen metabolites as a negative estrogen regulator. The mechanism of this action, however, is presently unknown. No study I've found has been done on testosterone levels and IC3.
My opinion: It is very liekly that IC3 will act as a natural test booster. However, while there are several studies indication IC3 down regulates estrogen, there are no studies which indicate the up regulation of testosterone.
UNCnate
Board Sponsor
I3C doesn't lower estrogen in an AI like fashion, it shifts estrogen towards the more beneficial metabolites.
zombiemuscle
Active member
I3C can increase conversion of estradiol into estriol by up to 50% says one study. Estriol is weaker and the conversion would offset the hormone balance. The hpta should react in some way. Also, studies show that the weaker estriol can block estrogen receptors from the stronger estradiol... This presents very weak serm like properties. Serms and serm like supplements are known to upregulate hpta function. I'm stacking it with resveratrol right now, so far so good.
CrazyChemist
Well-known member
Right but by what mechanism? Its a promising compound. Hopefully more research in the near future will elucidate its full potential.
protempsfish
Member
Does one have to cycle 13C or can you incorporate this into an everyday supp?
UNCnate
Board Sponsor
I'll see if I can find something more concrete.
I3C hasn't been around that long, so not many studies are out there.
Probably isnt essential that you cycle it. I3C has a ton of benefits outside of estrogen modulation. Would you cycle broccoli or cabbage?
BBB
Well-known member
I have DIM as a means of estrogen control for years. I3C is converted to DIM and many beleive DIM to be the superior version. I have used both and I believe they are equally effective however, DIM is twice as strong as I3C so you need less. I have not found that either has resulted in any increase in testosterone.
Jordinator
Member
Have you done research on how much I3C is in cabbage, say one head of broccoli? I did some brief searching and didn't find much, but it appears to be a small amount.
zombiemuscle
Active member
Can I3C give you hot flashes?
kitchenstud
New member
I3c seems like a really promising compound. I know theres a growing number of people out there that seem to think its better than standard AI's.
arowji
New member
from what i have read I3C works by increasing certain liver enzymes. there are 3 paths estrone can take in terms of estrogen metabolism. it can be converted into estradiol, into 16 OH estrone, or into 2 OH estrone. I3C increases the enzyme that converts estrone into the 2 OH metabolite, thus lowering total estrone and shifting equilibrium away from estradiol.
in spite of this, I3C is often praised for increasing the 2OH to 16OH, or good to bad, estrogen ratio. from what I have been able to find regarding these metabolites (in terms of what makes 2OH good and 16OH bad) is related solely to breast and other estrogen dependent cancers. i see two possibilities here. 1. 2OH estrogen has lower affinity or lower efficacy at the estrogen receptor (probably varies for alpha or beta), or 2. 16OH is somehow implicated in tumor growth. scenario one is the more favorable option here, but, considering what little research has been done on this unpatentable compound, I do not see a definitive answer in sight soon.
either way, I3C definitely has some potential on paper, but it will be hard to tell before we see some lab work, so if anyones got it let us know.
in spite of this, I3C is often praised for increasing the 2OH to 16OH, or good to bad, estrogen ratio. from what I have been able to find regarding these metabolites (in terms of what makes 2OH good and 16OH bad) is related solely to breast and other estrogen dependent cancers. i see two possibilities here. 1. 2OH estrogen has lower affinity or lower efficacy at the estrogen receptor (probably varies for alpha or beta), or 2. 16OH is somehow implicated in tumor growth. scenario one is the more favorable option here, but, considering what little research has been done on this unpatentable compound, I do not see a definitive answer in sight soon.
either way, I3C definitely has some potential on paper, but it will be hard to tell before we see some lab work, so if anyones got it let us know.
SonicSWOLE
Member
CrazyChemist
Well-known member
Hey bro - not disagreeing with you on that one but could you provide a citation or journal ref supporting that statement?
zombiemuscle
Active member
I3c or dim is an effective serm, not ai. Furthermore, studies indicate that they may be more effective than prescription serms.
zombiemuscle
Active member
I3c or dim is an effective serm, not ai. Furthermore, studies indicate that they may be more beneficial than prescription serms.
CrazyChemist
Well-known member
Please post the studies - what journals? what author name? what title? etc.
zombiemuscle
Active member
I'm at work in the bathroom lol! I'll find the studies at home later today. Stay tuned...
SonicSWOLE
Member
Invalid Link Removed
Invalid Link Removed
Invalid Link Removed
Here is just a few studies, there are numerous.
If prostate cancer is an issue, it looks very promising. As far as a bodybuilding agent....the EXACT opposite.
SonicSWOLE
Member
Effective for what? I posted studies relevant to my post, I hope to see yours. I3c/DIM are estrogen receptor antagonist, so it does work on the level of a SERM as opposed to an aromatase inhibiting fashion, but.....more effective than a prescription? I won't be using them for my PCT, but then I guess I already stated that.
zombiemuscle
Active member
Aromatase inhibitors block the aromatase enzyme, NOT the estrogen receptor. Therefore estrogen receptor antagonists act SERM-like; in this case the estriol blocks the estradiol from the estrogen receptor. Which is a totally seperate mechanism in contrast to the aromatase inhibiting drugs.
AIs are categorized into two types:
-Irreversible steroidal inhibitors such as exemestane form a permanent bond with the aromatase enzyme complex.
-Non-steroidal inhibitors (such as anastrozole, letrozole) inhibit the enzyme by reversible competition.
AIs are categorized into two types:
-Irreversible steroidal inhibitors such as exemestane form a permanent bond with the aromatase enzyme complex.
-Non-steroidal inhibitors (such as anastrozole, letrozole) inhibit the enzyme by reversible competition.
zombiemuscle
Active member
The FDA's recent approval of tamoxifen for the reduction of the risk of breast cancer in highrisk
healthy women prompted us to take a closer look at the drug. What we discovered may
surprise you. Tamoxifen works by blocking estrogen, but blocking estrogen is not its only, or
in some cases, most important action. The anti-cancer effects of tamoxifen are found in other
substances that are far less toxic and just as powerful. Stay with us-what you learn may save
your life.
Estrogen and breast cancer
Genuine human estrogen is a hormone with important functions in multiple areas of the body.
Essentially a chemical messenger, estrogen interacts with cells as diverse as skin, gut,
breast and brain.
Estrogen sends messages to cells through what are known as estrogen receptors. Receptors
are essentially "doors" on cells that allow entry of substances like estrogen. In the case of estrogen, the "door" is very big, and it
will also allow molecules that resemble estrogen to enter as well. This is why fake estrogens and estrogen blockers can provoke
cells to react. If the receptor was very small or very particular, it wouldn't allow the fakes in.
Receptors are not like doors, however, in the sense that they're not square. They're curvy-like a jigsaw puzzle. When a molecule of
the right shape comes along, it fits in the receptor and makes contact with points just inside the receptor's "door jamb." Touching
these contact points sets off a series of chemical reactions that send a signal inside the cell.
One of the most important messages estrogen delivers is to grow-divide, multiply. For this reason, estrogen is crucial in the
development of the fetus. For the same reason, it's usually found at the scene of breast cancer, where it eggs on hormoneresponsive
cancer cells. It's estimated that 50-70% of all breast cancers are estrogen receptor-positive-they grow in the presence of
estrogen. And according to Dr. Kent Osborne of Baylor University, this figure could be much higher because of problems in the
classification system.
Successful communication between the messenger and the cell depends on the messenger (estrogen) fitting the door (receptor)
exactly so as to make all the contact points. Estrogen produced naturally in the body fits inside the estrogen receptor perfectly and
sends certain predetermined signals. Estrogen look-alikes such as tamoxifen fit in the door, but don't make all the contacts
because they're not exactly the right shape. As a result, they send odd signals or block them altogether.
What's disturbing about these synthetic look-alikes is that scientists don't know what signals they actually do send once they get
into the receptor. They know some of the signals. For example, they know that tamoxifen blocks the "grow" signal in breast tissue.
They know the same molecule promotes the "grow" signal in uterine tissue. They know Premarin sends a "grow" signal to bone.
But what signals, for example, does the estrogen mimicker/blocker, raloxifene, send to the brain through its estrogen receptors?
Nobody knows.
Secrets of tamoxifen
The most well-publicized aspect of tamoxifen's mode of action against breast cancer is that it blocks estrogen. What's not usually
appreciated is that tamoxifen has other modes of action. The other actions are just as important, or in some cases more important,
than the estrogen-blocking effect. And they are not unique to tamoxifen.
Tamoxifen also works in estrogen receptor-negative breast cancers and progesterone receptor-positive breast cancers. This is
because tamoxifen not only blocks the estrogen "grow" signal, it blocks another type of "grow" signal known as protein kinase C
(PKC). PKC is another one of those contact points inside the door jamb, and blocking this signal stops oncogenes (cancer genes)
from activating. PKC also controls cell growth and transformation signals.
Tamoxifen promotes free radicals
A surprising study was published in the Journal of Biological Chemistry in 1996. Using estrogen receptor-negative breast cancer
cells, researchers from the University of Southern California showed that tamoxifen uses free radicals to inhibit PKC. How it
generates the radicals is not known. Researchers do know, however, that it takes very low doses of tamoxifen to create this effect.
Estrogen receptor-positive cancer cells require much higher doses of tamoxifen. A very important finding of this study is that
antioxidant vitamins E, C and beta-carotene (but not glutathione) kept tamoxifen from working in estrogen receptor-negative cells. If
confirmed in vivo, this could mean that women with receptor-negative breast cancer taking tamoxifen should not take antioxidants.
A group at Zeneca Pharmaceuticals, the manufacturer of tamoxifen, has reported a similar phenomenon. In estrogen receptornegative
ovarian and leukemia cells, tamoxifen depletes the body's natural antioxidants and provokes free radicals. The radicals
then cause the cancer cells to self-destruct. An important caveat of both this and the above study is that both have only been done
in the test tube and only in estrogen receptor-negative cancer cells.
Tamoxifen also stops free radicals
It's not surprising that tamoxifen generates free radicals since most, if not all, chemotherapies do. However, it is surprising that
tamoxifen is also a powerful antioxidant. The antioxidant effect is found in its metabolite, 4-hydroxytamoxifen.
Women who take tamoxifen for 6 months have far fewer free radicals in their blood than before they took it. They also have higher
levels of antioxidant vitamins and enzymes, indicating that tamoxifen conserves the body's own antioxidant defenses (except in the
above studies in estrogen receptor-negative cells).
Numerous studies show that 4-hydroxytamoxifen strongly inhibits oxidative damage to a broad range of important substances-lipids,
DNA and protein. This ability to stop free radicals is part of its anti-cancer effect. In studies on animals treated with the chemical
TPA, tamoxifen was effective at inhibiting free radicals so that not enough DNA damage occurred to transform the cells.
Another aspect of tamoxifen's anti-cancer action is its ability to interfere with the cell cycle. The cell cycle is a predetermined
program a cell goes through to make a new cell. Normal cells "put on the brakes" at certain points during the process so that things
can be checked for accuracy. This ensures that abnormal cells don't get duplicated. However, cancer cells "override" the brakes.
They duplicate themselves at break-neck speed with no checks on accuracy. Chemotherapy works by "setting" the brakes.
Tamoxifen is one of the chemotherapies that does this.
What's wrong with tamoxifen
All this sounds great. Why not ake tamoxifen and be happy? Because tamoxifen has severe drawbacks, some of which are just
now coming to light. While some studies show that tamoxifen works better at five years than two, other research confirms that
tamoxifen always "turns" on its user in months or years, and begins feeding new, tamoxifen-dependent cancer. A new chemical is
being tested to combat this "problem." But the new chemical may create problems of its own.
Meanwhile, there are hints that tamoxifen "resistance," as it's known, is the result of permanent damage caused by the drug. One
area that might be damaged is tumor suppressor gene p53, a player in the process that stops the cell cycle and makes sure
cancer cells don't get replicated. In the healthy person, p53 sends signals that stop the cell cycle when abnormal cells are involved,
and causes them to self-destruct. Using human breast cancer cells, researchers in France showed that tamoxifen stops p53 from
working. While this may sensitize cancer cells to the effects of chemotherapy, the same phenomenon in a healthy person would
cripple their ability to stop cancer.
The National Cancer Institute and Sloan Kettering Cancer Center have both reported that tamoxifen causes mutations in endometrial
cells, including mutations in p53. More than one group has called for more research in this area, but it hasn't been done.
There is evidence that tamoxifen causes another problem which hasn't been adequately investigated. Constant exposure to the drug
may permanently alter the estrogen receptor. Receptors have "plasticity"-their shape can change depending on what "fits in the
door jamb." Tamoxifen doesn't fit into the estrogen receptor just right. As a result, the estrogen receptor changes its shape to fit
tamoxifen. The same phenomenon happens in people who chronically take mood-altering drugs. Their neurons adapt to the drug.
This is part of the phenomenon of drug tolerance and withdrawal-the receptors have adapted to the artificial drug and depend on it to
function. No one knows whether tamoxifen permanently damages the estrogen receptor in the same way.
These unknowns, coupled with the elevated risk of life-threatening blood clots and uterine cancer, the lack of evidence that
tamoxifen prevents breast cancer at all in healthy women, plus the lack of an accurate risk assessment tool of who is really at risk
(see "Tamoxifen: Cancer-causing Drug Approved for Healthy Women," Life Extension magazine, May 1999), make tamoxifen risky
as a cancer prevention strategy.
Indole-3-Carbinol: The thinking person's cancer prevention
Tamoxifen is a chemical proven to provide short-term delay in the reemergence of breast cancer in women who have already had
breast cancer. There is no evidence that it prevents breast cancer in women who have never had it. There is evidence, however, that
tamoxifen stops working within months and starts feeding new, tamoxifen-dependent tumors, and causes an elevated risk of uterine
cancer and blood clots.
Despite these drawbacks, however, the drug possesses some very desirable characteristics. It has powerful antioxidant action, plus
the ability to inhibit PKC. Its ability to block estrogen's "grow signal," and stop cancer cells from growing are very important
characteristics. Yet who wants to take a drug that can potentially cause cancer and a host of other ills? Is there anything better?
In 1991 researchers at the Institute for Hormone Research in New York City announced that they had been able to induce the dy to
convert the stronger form of estrogen (estradiol) into a weaker form (2-hydroxy- estrone) without using drugs. 2OHE is considered to
be a more desirable form of estrogen. It is less active than estradiol, so when it occupies the estrogen receptor, it effectively blocks
estradiol's strong "grow" signals.
Natural substance changes the way estrogen is metabolized
It took only one week to prove that the conversion of estradiol to 2OHE can be accomplished without drugs. Using a natural
substance, researchers were able to increase the conversion of estradiol to weak estrogen by 50% in twelve healthy people.
Next, they tested the natural substance in female mice prone to developing breast cancer. Both the incidence of cancer and the
mber of tumors fell significantly. What was the substance? Indole-3-carbinol (IC3), a phytochemical isolated from cruciferous
vegetables (broccoli, cauliflower, Brussels sprouts, turnips, kale, green cabbage, mustard seed, etc.).
I3C was then given to 25 women for two months. Again, levels of strong estrogen declined, and levels of weak estrogen increased.
But more importantly, the level of an estrogen metabolite associated with breast and endometrial cancer (16alpha-hydroxyestrone)
fell.
In 1997, researchers at Strang Cancer Research Laboratory at Rockefeller University discovered that when I3C changes "strong"
estrogen to "weak," it stops human cancer cells from growing (54-61%) and provokes the cells to self-destruct (apoptosis).
Subsequent studies done at the University of California at Berkeley, show that I3C inhibits MCF7 human breast cancer cells from
growing by as much as 90% in culture. Growth arrest does not depend on estrogen receptors.
I3C does more than just turn strong estrogen to weak. 16alpha-hydroxyestrone (16OHE) is an estrogen metabolite that is
biologically active-i.e., like estradiol, it can send "grow" signals. In breast cancer, the bad 16OHE is elevated, and the good 2OHE
is decreased. Cancer-causing chemicals change the metabolism of estrogen so that 16OHE is elevated. I3C changes them back so
that 2OHE is increased.
In an experiment at New York University, researchers gave African-American women I3C, 400 mg for five days. Most of them
experienced an increase in the "good" 2OHE and a decrease of the "bad" 16OHE. However, some did not. It turns out that those
who did not have a mutation in a gene that helps metabolize estrogen to the 2OHE version. Those women have an eight times
higher risk of breast cancer.
The I3C receptor
A startling discovery shows that I3C controls estrogen metabolism through the same receptor that allows dioxin into the cell-the
"Ah" receptor (aryl hydrocarbon). Ah is similar to the estrogen receptor in that it can induce cellular growth. Unlike the estrogen
receptor, however, scientists haven't found the body's natural "Ah" that fits into the Ah receptor. The only substances known to
activate Ah are certain phytochemicals, including I3C-and the proven cancer promoter, dioxin. Dioxin is a chemical made from
chlorine. It's so toxic that scientists measure it in trillionths of a gram. It's used in all kinds of things-from Saran Wrap(r) to
pesticides to wood preservative. It has been detected in McDonald's Big Macs(r), Haagen-Daz(r) ice cream and Kentucky Fried
Chicken(r). Meat, dairy products and fish are the most concentrated sources. When paper is bleached or plastic is burned, dioxin is
released into the environment. Because it lodges in fat, it's almost impossible to remove from the human body. Losing weight
simply causes it to hunker down in the remaining fat.
A study on people who worked in a dioxin plant shows that women exposed to the chemical have more than twice the risk of breast
cancer, but some studies don't show any association at all. Part of the problem with dioxin studies is that there are hundreds of
similar chemicals, with hundreds of different metabolites that may interact in ways we don't currently understand.
Dioxin, like I3C, affects estrogen metabolism. For this reason, it has been called an estrogen blocker (like tamoxifen). But it esn't
work through the estrogen receptor. Dioxin and I3C both affect estrogen metabolism through the Ah receptor. But just as tamoxifen
sends a different signal that genuine estrogen when it gets in the estrogen receptor, so does dioxin send a different signal than I3C
in the Ah receptor. In addition to changing the metabolism of estrogen, dioxin also disrupts other important growth regulatory
factors. Among those factors are insulin, IGF-1 (insulin-like growth factor), and tumor necrosis factor (TNF). It also activates cancer
genes and suppresses tumor suppressor genes.
I3C, on the other hand, fits into the Ah receptor, but instead of sending signals that help cancer grow, it sends signals that stop it.
I3C uses the Ah receptor to indirectly affect estrogen metabolism also, but in a beneficial way. Not only does it positively affect
estrogen, it can also keep dioxin out of cells. When researchers at Texas A & M University treated breast cancer cells with I3C and
dioxin at the same time, dioxin's adverse effects were reduced 90% by I3C.
I3C prevents chemically-induced breast cancer in rodents by 70-96%. It also prevents other types of cancer, including aflatoxininduced
liver cancer, leukemia and colon cancer. Studies show that I3C inhibits free radicals, particularly those that cause the
oxidation of fat.
I3C stops cancer cells from growing
I3C not only weakens estrogen and keeps chemicals out of cells, it also goes after cancer in ways similar to tamoxifen. It, like
tamoxifen, interrupts the cell cycle. In studies from the University of California mentioned above, I3C inhibited the growth of estrogen
receptor-positive breast cancer cells by 90% compared to tamoxifen's 60% by stopping the cell cycle. (Adding tamoxifen to I3C
gave a 5% boost.) In estrogen receptor-negative cells I3C stopped the synthesis of DNA for new cells by about 50% whereas
tamoxifen had no significant effect. I3C also restores p21 and other tumor suppressors that act as check points during synthesis of
a new cell. Tamoxifen, by contrast, has no effect on p21. I3C also inhibits cancers caused by other chemicals, in addition to dioxin.
If animals are fed I3C before exposure to certain other cancer-causing chemicals, DNA damage and cancer will be virtually
eliminated. A study on rodents shows that damaged DNA in breast cells is reduced 91% by I3C. Similar results happen in the liver.
And in a study from New York University Medical Center, female smokers taking 400 mg of I3C significantly reduced their levels of a
major lung carcinogen. Chemicals in cigarrettes are known to affect estrogen metabolism.
While there is no proven breast cancer preventive, the best and most comprehensive scientific evidence so far stands behind
phytochemicals such as I3C. I3C beat out more than 80 other substances, including tamoxifen, for anti-cancer potential in an assay
done at the National Cancer Institute.
Recently, researchers at the Hoechst Marrion Roussel drug company staked patent claims to dozens of indole-3 look-alikes. They
claim that the indoles, which down-regulate estrogen receptors, can be used to treat and prevent cancer and autoimmune diseases
such as multiple sclerosis, arthritis and lupus. They hope to replace all the chemically-altered estrogen drugs such as tamoxifen
with a new generation of chemically-altered indole drugs that fit in the Ah receptor, and regulate estrogen indirectly. Will the fake
indoles create cancer in other organs as tamoxifen does? Will they lead to chemical tumor dependency as tamoxifen does?
Time will tell if the constant stream of chemical lookalikes will continue to stop/feed cancer. In the meantime, those wishing to get
off the chemical merry-go-round, and get serious cancer prevention without the side effects have a terrific option: I3C.
Currently there are two government-sponsored trials underway involving estrogen metabolism and vegetables. One is going to
assess the "interactive effects of dietary fat and fruits and vegetables on the levels of oxidative DNA damage and cholesterol
oxides in women at high risk for breast cancer." This study is enrolling a grand total of 160 women in the next two and a half
years. The other plans to look at how fiber affects estrogen metabolism in postmenopausal women. This study is enrolling a
phenomenal 40 women over four years. Should the government ever get serious about preventing breast cancer, and spend
$100 million of your tax dollars on testing I3C as they have on testing tamoxifen, we would be able to give you the proof. For
now, we can only give you the best evidence and let you decide.
Recommended Dosage/Precautions:
Note that while a little is good, a lot is not necessarily better. As with certain antioxidants that can actually promote oxidation
at high levels, too much I3C can have the opposite effect of what you want. Therefore, don't exceed the dosage. The effective
dose established in human studies is 6-7 mg per kg of weight per day. For a 120 lb. woman, this is just under 400 mg/day.
Also note that pregnant women should not take I3C, due to its modulation of estrogen. The reported aversion to cruciferous
vegetables by pregnant women may be associated with their ability to change estrogen metabolism.
healthy women prompted us to take a closer look at the drug. What we discovered may
surprise you. Tamoxifen works by blocking estrogen, but blocking estrogen is not its only, or
in some cases, most important action. The anti-cancer effects of tamoxifen are found in other
substances that are far less toxic and just as powerful. Stay with us-what you learn may save
your life.
Estrogen and breast cancer
Genuine human estrogen is a hormone with important functions in multiple areas of the body.
Essentially a chemical messenger, estrogen interacts with cells as diverse as skin, gut,
breast and brain.
Estrogen sends messages to cells through what are known as estrogen receptors. Receptors
are essentially "doors" on cells that allow entry of substances like estrogen. In the case of estrogen, the "door" is very big, and it
will also allow molecules that resemble estrogen to enter as well. This is why fake estrogens and estrogen blockers can provoke
cells to react. If the receptor was very small or very particular, it wouldn't allow the fakes in.
Receptors are not like doors, however, in the sense that they're not square. They're curvy-like a jigsaw puzzle. When a molecule of
the right shape comes along, it fits in the receptor and makes contact with points just inside the receptor's "door jamb." Touching
these contact points sets off a series of chemical reactions that send a signal inside the cell.
One of the most important messages estrogen delivers is to grow-divide, multiply. For this reason, estrogen is crucial in the
development of the fetus. For the same reason, it's usually found at the scene of breast cancer, where it eggs on hormoneresponsive
cancer cells. It's estimated that 50-70% of all breast cancers are estrogen receptor-positive-they grow in the presence of
estrogen. And according to Dr. Kent Osborne of Baylor University, this figure could be much higher because of problems in the
classification system.
Successful communication between the messenger and the cell depends on the messenger (estrogen) fitting the door (receptor)
exactly so as to make all the contact points. Estrogen produced naturally in the body fits inside the estrogen receptor perfectly and
sends certain predetermined signals. Estrogen look-alikes such as tamoxifen fit in the door, but don't make all the contacts
because they're not exactly the right shape. As a result, they send odd signals or block them altogether.
What's disturbing about these synthetic look-alikes is that scientists don't know what signals they actually do send once they get
into the receptor. They know some of the signals. For example, they know that tamoxifen blocks the "grow" signal in breast tissue.
They know the same molecule promotes the "grow" signal in uterine tissue. They know Premarin sends a "grow" signal to bone.
But what signals, for example, does the estrogen mimicker/blocker, raloxifene, send to the brain through its estrogen receptors?
Nobody knows.
Secrets of tamoxifen
The most well-publicized aspect of tamoxifen's mode of action against breast cancer is that it blocks estrogen. What's not usually
appreciated is that tamoxifen has other modes of action. The other actions are just as important, or in some cases more important,
than the estrogen-blocking effect. And they are not unique to tamoxifen.
Tamoxifen also works in estrogen receptor-negative breast cancers and progesterone receptor-positive breast cancers. This is
because tamoxifen not only blocks the estrogen "grow" signal, it blocks another type of "grow" signal known as protein kinase C
(PKC). PKC is another one of those contact points inside the door jamb, and blocking this signal stops oncogenes (cancer genes)
from activating. PKC also controls cell growth and transformation signals.
Tamoxifen promotes free radicals
A surprising study was published in the Journal of Biological Chemistry in 1996. Using estrogen receptor-negative breast cancer
cells, researchers from the University of Southern California showed that tamoxifen uses free radicals to inhibit PKC. How it
generates the radicals is not known. Researchers do know, however, that it takes very low doses of tamoxifen to create this effect.
Estrogen receptor-positive cancer cells require much higher doses of tamoxifen. A very important finding of this study is that
antioxidant vitamins E, C and beta-carotene (but not glutathione) kept tamoxifen from working in estrogen receptor-negative cells. If
confirmed in vivo, this could mean that women with receptor-negative breast cancer taking tamoxifen should not take antioxidants.
A group at Zeneca Pharmaceuticals, the manufacturer of tamoxifen, has reported a similar phenomenon. In estrogen receptornegative
ovarian and leukemia cells, tamoxifen depletes the body's natural antioxidants and provokes free radicals. The radicals
then cause the cancer cells to self-destruct. An important caveat of both this and the above study is that both have only been done
in the test tube and only in estrogen receptor-negative cancer cells.
Tamoxifen also stops free radicals
It's not surprising that tamoxifen generates free radicals since most, if not all, chemotherapies do. However, it is surprising that
tamoxifen is also a powerful antioxidant. The antioxidant effect is found in its metabolite, 4-hydroxytamoxifen.
Women who take tamoxifen for 6 months have far fewer free radicals in their blood than before they took it. They also have higher
levels of antioxidant vitamins and enzymes, indicating that tamoxifen conserves the body's own antioxidant defenses (except in the
above studies in estrogen receptor-negative cells).
Numerous studies show that 4-hydroxytamoxifen strongly inhibits oxidative damage to a broad range of important substances-lipids,
DNA and protein. This ability to stop free radicals is part of its anti-cancer effect. In studies on animals treated with the chemical
TPA, tamoxifen was effective at inhibiting free radicals so that not enough DNA damage occurred to transform the cells.
Another aspect of tamoxifen's anti-cancer action is its ability to interfere with the cell cycle. The cell cycle is a predetermined
program a cell goes through to make a new cell. Normal cells "put on the brakes" at certain points during the process so that things
can be checked for accuracy. This ensures that abnormal cells don't get duplicated. However, cancer cells "override" the brakes.
They duplicate themselves at break-neck speed with no checks on accuracy. Chemotherapy works by "setting" the brakes.
Tamoxifen is one of the chemotherapies that does this.
What's wrong with tamoxifen
All this sounds great. Why not ake tamoxifen and be happy? Because tamoxifen has severe drawbacks, some of which are just
now coming to light. While some studies show that tamoxifen works better at five years than two, other research confirms that
tamoxifen always "turns" on its user in months or years, and begins feeding new, tamoxifen-dependent cancer. A new chemical is
being tested to combat this "problem." But the new chemical may create problems of its own.
Meanwhile, there are hints that tamoxifen "resistance," as it's known, is the result of permanent damage caused by the drug. One
area that might be damaged is tumor suppressor gene p53, a player in the process that stops the cell cycle and makes sure
cancer cells don't get replicated. In the healthy person, p53 sends signals that stop the cell cycle when abnormal cells are involved,
and causes them to self-destruct. Using human breast cancer cells, researchers in France showed that tamoxifen stops p53 from
working. While this may sensitize cancer cells to the effects of chemotherapy, the same phenomenon in a healthy person would
cripple their ability to stop cancer.
The National Cancer Institute and Sloan Kettering Cancer Center have both reported that tamoxifen causes mutations in endometrial
cells, including mutations in p53. More than one group has called for more research in this area, but it hasn't been done.
There is evidence that tamoxifen causes another problem which hasn't been adequately investigated. Constant exposure to the drug
may permanently alter the estrogen receptor. Receptors have "plasticity"-their shape can change depending on what "fits in the
door jamb." Tamoxifen doesn't fit into the estrogen receptor just right. As a result, the estrogen receptor changes its shape to fit
tamoxifen. The same phenomenon happens in people who chronically take mood-altering drugs. Their neurons adapt to the drug.
This is part of the phenomenon of drug tolerance and withdrawal-the receptors have adapted to the artificial drug and depend on it to
function. No one knows whether tamoxifen permanently damages the estrogen receptor in the same way.
These unknowns, coupled with the elevated risk of life-threatening blood clots and uterine cancer, the lack of evidence that
tamoxifen prevents breast cancer at all in healthy women, plus the lack of an accurate risk assessment tool of who is really at risk
(see "Tamoxifen: Cancer-causing Drug Approved for Healthy Women," Life Extension magazine, May 1999), make tamoxifen risky
as a cancer prevention strategy.
Indole-3-Carbinol: The thinking person's cancer prevention
Tamoxifen is a chemical proven to provide short-term delay in the reemergence of breast cancer in women who have already had
breast cancer. There is no evidence that it prevents breast cancer in women who have never had it. There is evidence, however, that
tamoxifen stops working within months and starts feeding new, tamoxifen-dependent tumors, and causes an elevated risk of uterine
cancer and blood clots.
Despite these drawbacks, however, the drug possesses some very desirable characteristics. It has powerful antioxidant action, plus
the ability to inhibit PKC. Its ability to block estrogen's "grow signal," and stop cancer cells from growing are very important
characteristics. Yet who wants to take a drug that can potentially cause cancer and a host of other ills? Is there anything better?
In 1991 researchers at the Institute for Hormone Research in New York City announced that they had been able to induce the dy to
convert the stronger form of estrogen (estradiol) into a weaker form (2-hydroxy- estrone) without using drugs. 2OHE is considered to
be a more desirable form of estrogen. It is less active than estradiol, so when it occupies the estrogen receptor, it effectively blocks
estradiol's strong "grow" signals.
Natural substance changes the way estrogen is metabolized
It took only one week to prove that the conversion of estradiol to 2OHE can be accomplished without drugs. Using a natural
substance, researchers were able to increase the conversion of estradiol to weak estrogen by 50% in twelve healthy people.
Next, they tested the natural substance in female mice prone to developing breast cancer. Both the incidence of cancer and the
mber of tumors fell significantly. What was the substance? Indole-3-carbinol (IC3), a phytochemical isolated from cruciferous
vegetables (broccoli, cauliflower, Brussels sprouts, turnips, kale, green cabbage, mustard seed, etc.).
I3C was then given to 25 women for two months. Again, levels of strong estrogen declined, and levels of weak estrogen increased.
But more importantly, the level of an estrogen metabolite associated with breast and endometrial cancer (16alpha-hydroxyestrone)
fell.
In 1997, researchers at Strang Cancer Research Laboratory at Rockefeller University discovered that when I3C changes "strong"
estrogen to "weak," it stops human cancer cells from growing (54-61%) and provokes the cells to self-destruct (apoptosis).
Subsequent studies done at the University of California at Berkeley, show that I3C inhibits MCF7 human breast cancer cells from
growing by as much as 90% in culture. Growth arrest does not depend on estrogen receptors.
I3C does more than just turn strong estrogen to weak. 16alpha-hydroxyestrone (16OHE) is an estrogen metabolite that is
biologically active-i.e., like estradiol, it can send "grow" signals. In breast cancer, the bad 16OHE is elevated, and the good 2OHE
is decreased. Cancer-causing chemicals change the metabolism of estrogen so that 16OHE is elevated. I3C changes them back so
that 2OHE is increased.
In an experiment at New York University, researchers gave African-American women I3C, 400 mg for five days. Most of them
experienced an increase in the "good" 2OHE and a decrease of the "bad" 16OHE. However, some did not. It turns out that those
who did not have a mutation in a gene that helps metabolize estrogen to the 2OHE version. Those women have an eight times
higher risk of breast cancer.
The I3C receptor
A startling discovery shows that I3C controls estrogen metabolism through the same receptor that allows dioxin into the cell-the
"Ah" receptor (aryl hydrocarbon). Ah is similar to the estrogen receptor in that it can induce cellular growth. Unlike the estrogen
receptor, however, scientists haven't found the body's natural "Ah" that fits into the Ah receptor. The only substances known to
activate Ah are certain phytochemicals, including I3C-and the proven cancer promoter, dioxin. Dioxin is a chemical made from
chlorine. It's so toxic that scientists measure it in trillionths of a gram. It's used in all kinds of things-from Saran Wrap(r) to
pesticides to wood preservative. It has been detected in McDonald's Big Macs(r), Haagen-Daz(r) ice cream and Kentucky Fried
Chicken(r). Meat, dairy products and fish are the most concentrated sources. When paper is bleached or plastic is burned, dioxin is
released into the environment. Because it lodges in fat, it's almost impossible to remove from the human body. Losing weight
simply causes it to hunker down in the remaining fat.
A study on people who worked in a dioxin plant shows that women exposed to the chemical have more than twice the risk of breast
cancer, but some studies don't show any association at all. Part of the problem with dioxin studies is that there are hundreds of
similar chemicals, with hundreds of different metabolites that may interact in ways we don't currently understand.
Dioxin, like I3C, affects estrogen metabolism. For this reason, it has been called an estrogen blocker (like tamoxifen). But it esn't
work through the estrogen receptor. Dioxin and I3C both affect estrogen metabolism through the Ah receptor. But just as tamoxifen
sends a different signal that genuine estrogen when it gets in the estrogen receptor, so does dioxin send a different signal than I3C
in the Ah receptor. In addition to changing the metabolism of estrogen, dioxin also disrupts other important growth regulatory
factors. Among those factors are insulin, IGF-1 (insulin-like growth factor), and tumor necrosis factor (TNF). It also activates cancer
genes and suppresses tumor suppressor genes.
I3C, on the other hand, fits into the Ah receptor, but instead of sending signals that help cancer grow, it sends signals that stop it.
I3C uses the Ah receptor to indirectly affect estrogen metabolism also, but in a beneficial way. Not only does it positively affect
estrogen, it can also keep dioxin out of cells. When researchers at Texas A & M University treated breast cancer cells with I3C and
dioxin at the same time, dioxin's adverse effects were reduced 90% by I3C.
I3C prevents chemically-induced breast cancer in rodents by 70-96%. It also prevents other types of cancer, including aflatoxininduced
liver cancer, leukemia and colon cancer. Studies show that I3C inhibits free radicals, particularly those that cause the
oxidation of fat.
I3C stops cancer cells from growing
I3C not only weakens estrogen and keeps chemicals out of cells, it also goes after cancer in ways similar to tamoxifen. It, like
tamoxifen, interrupts the cell cycle. In studies from the University of California mentioned above, I3C inhibited the growth of estrogen
receptor-positive breast cancer cells by 90% compared to tamoxifen's 60% by stopping the cell cycle. (Adding tamoxifen to I3C
gave a 5% boost.) In estrogen receptor-negative cells I3C stopped the synthesis of DNA for new cells by about 50% whereas
tamoxifen had no significant effect. I3C also restores p21 and other tumor suppressors that act as check points during synthesis of
a new cell. Tamoxifen, by contrast, has no effect on p21. I3C also inhibits cancers caused by other chemicals, in addition to dioxin.
If animals are fed I3C before exposure to certain other cancer-causing chemicals, DNA damage and cancer will be virtually
eliminated. A study on rodents shows that damaged DNA in breast cells is reduced 91% by I3C. Similar results happen in the liver.
And in a study from New York University Medical Center, female smokers taking 400 mg of I3C significantly reduced their levels of a
major lung carcinogen. Chemicals in cigarrettes are known to affect estrogen metabolism.
While there is no proven breast cancer preventive, the best and most comprehensive scientific evidence so far stands behind
phytochemicals such as I3C. I3C beat out more than 80 other substances, including tamoxifen, for anti-cancer potential in an assay
done at the National Cancer Institute.
Recently, researchers at the Hoechst Marrion Roussel drug company staked patent claims to dozens of indole-3 look-alikes. They
claim that the indoles, which down-regulate estrogen receptors, can be used to treat and prevent cancer and autoimmune diseases
such as multiple sclerosis, arthritis and lupus. They hope to replace all the chemically-altered estrogen drugs such as tamoxifen
with a new generation of chemically-altered indole drugs that fit in the Ah receptor, and regulate estrogen indirectly. Will the fake
indoles create cancer in other organs as tamoxifen does? Will they lead to chemical tumor dependency as tamoxifen does?
Time will tell if the constant stream of chemical lookalikes will continue to stop/feed cancer. In the meantime, those wishing to get
off the chemical merry-go-round, and get serious cancer prevention without the side effects have a terrific option: I3C.
Currently there are two government-sponsored trials underway involving estrogen metabolism and vegetables. One is going to
assess the "interactive effects of dietary fat and fruits and vegetables on the levels of oxidative DNA damage and cholesterol
oxides in women at high risk for breast cancer." This study is enrolling a grand total of 160 women in the next two and a half
years. The other plans to look at how fiber affects estrogen metabolism in postmenopausal women. This study is enrolling a
phenomenal 40 women over four years. Should the government ever get serious about preventing breast cancer, and spend
$100 million of your tax dollars on testing I3C as they have on testing tamoxifen, we would be able to give you the proof. For
now, we can only give you the best evidence and let you decide.
Recommended Dosage/Precautions:
Note that while a little is good, a lot is not necessarily better. As with certain antioxidants that can actually promote oxidation
at high levels, too much I3C can have the opposite effect of what you want. Therefore, don't exceed the dosage. The effective
dose established in human studies is 6-7 mg per kg of weight per day. For a 120 lb. woman, this is just under 400 mg/day.
Also note that pregnant women should not take I3C, due to its modulation of estrogen. The reported aversion to cruciferous
vegetables by pregnant women may be associated with their ability to change estrogen metabolism.
zombiemuscle
Active member
References
Anonymous. 1997. Tamoxifen has a characteristic mutation spectrum in human endometrial cancers
(Meeting abstract). Proc Annu Meet Am Assoc Cancer Res 38:A3008.
Arnao MB, et al. 1996. Indole-3-carbinol as a scavenger of free radicals. Biochem Mol Biol Int 39:1125-34. Barakat RR, et al.
1997. Evaluation of p53, Bcl-2 and c-Ki-ras status in endometrial cancers occurring after breast cancer with or without
tamoxifen treatment (Meeting abstract). Proc Annu Meet Am Soc Clin Oncol 16:A1289.
Bitonti AJ, et al. 1999. US Patent 5,877,202. Bradlow HL, et al. 1991. Effects of dietary indole-3-carbinol on estradiol
metabolism and spontaneous mammary tumors in mice. Carcinogenesis 12:1571-74.
Chen I, et al. 1996. Indole-3-carbinol and diindolylmethane as aryl hydrocarbon (Ah) receptor agonists and antagonists in T47D
human breast cancer cells. Biochem Pharmacol 51:1069-76.
Chen I, et al. 1998. Aryl hydrocarbon receptor-mediated antiestrogenic and antitumorigenic activity of diindolylmethane.
Carcinogenesis 19:1631-9.
Cover CM, et al. 1998. Indole-3-carbinol inhibits the expression of cyclin-dependent kinase-6 and induces a G1 cell cycle
arrest of human breast cancer cells independent of estrogen receptor signaling. J Biol Chem 273:3838-47.
Cover M, et al. 1999. Indole-3-carbinol and tamoxifen cooperate to arrest the cell cycle of MCF-7 human breast cancer cells.
Cancer Res 59:1244-51.
Custodio JB, et al. 1994. Tamoxifen and hydroxytamoxifen as intramembraneous inhibitors of lipid peroxidation. Evidence for
peroxyl radical scavenging activity. Biochem Phearmacol 47:1989-98.
Devanaboyina U, et al. 1997. Effects of indole-3-carbinol (I3C) and phenethyl isothiocyanate (PEITC) on 7,12-dimethylbenz[a]
anthracene (DMBA)-induced DNA adducts in rat mammary glands and liver (Meeting abstract). Proc Annu Meet am Assoc.
Cancer Res 38:A2427.
Ferlini C, et al. 1999. Tamoxifen induces oxidative stress and apoptosis in oestrogen receptor-negative human cancer cell
lines. Br J Cancer 79:257-63.
Grubbs CJ, et al. 1995. Chemoprevention of chemically-induced mammary carcinogenesis by indole-3-carbinol. Anticancer
Res 15:709-16.Guillot C, et al. 1996. Alteration of p53 damage response by tamoxifen treatment. Clin Cancer Res 2:1439-44.
Gundimeda U, et al. 1996. Tamoxifen modulates protein kinase C via oxidative stress in estrogen receptor-negative breast
cancer cells. Biol Chem 271:13504-14.
He YH, et al. 1997. Chemopreventive properties of indole-3-carbinol (I3C): inhibition of DNA adduct formation of the dietary
carcinogen, 2-amino-1-methyl-6-pehnylimidazo [4,5-b]pyridine (PhIP), in female F344 rats. J Cell Biochem Suppl 27:42-51.
Lim JS, et al. 1992. Tamoxifen suppresses tumor promoter-induced hydrogen peroxide formation by human neutrophils.
Cancer Res 52:4969-72.
Manson MM, et al. 1998. Chemoprevention of afatoxin B1-induced carcinogenesis by indole-3-carbinol in rat liver-predicting the
outcome using early biomarkers. Carcinogenesis 19:1829-36.
Manz, et al. Cancer mortality among workers in chemical plant contaminated with dioxin. Lancet 338:959-64.
Michnovicz JJ, et al. 1991. Altered estrogen metabolism and excretion in humans following consumption of I3C. Nutr Cancer
16:59-66.
Michnovicz JJ, et al. 1997. Changes in levels of urinary estrogen metabolites after oral I3C treatment in humans. J Natl Cancer
Inst 89:718-23.
Michnovicz JJ. 1998. Increased estrogen 2- hydroxylation in obese women using oral indole-3-carbinol. Int J Obes Relat Metab
Disord 22:227-9.
Norris JD, et al. 1999. Peptide antagonists of the human estrogen receptor. Science 285:744-46. Paige LA, et al. 1999.
Estrogen receptor (ER) modulators each induce distinct conformational changes in ER alpha and ER beta. Proc Natl Acad Sci
USA 96:3999-4004.
Ricci MS, et al. 1999. Estrogen receptor reduces CYP1A1 induction in cultured human endometrial cells. J Biol Chem
274:3430-38.
Schecter A, et al. 1997. Dioxins, dibenzofurans, dioxin-like PCBs and DDE in U.S. fast food, 1995. Chemosphere 34:1449-57.
Sharma S, et al. 1994. Screening of potential chemopreventive agents using biochemical markers of carcinogenesis. Cancer s
54:5848-55.
Shertzer HG, et al. 1988. Intervention in free radical mediated hepatotoxicity and lipid peroxidation by indole-3-carbinol.
Biochem Pharmacol 37:333-38.
Taioli E, et al. 1997. Effects of indole-3-carbinol (I3C) on the metabolism of the tobacco-specific lung carcinogen 4-
(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in smokers (Meeting abstract). Proc Annu Meet am Assoc Cancer Res
38:A1413.
Taioli E, et al. 1999. Role of estradiol metabolism and CYP1A1 polymorphisms in breast cancer risk. Cancer Detect Prev
23:232-7.
Telang NT, et al. 1997. Inhibition of proliferation and modulation of estradiol metabolism: novel mechanisms for breast cancer
prevention by the phytochemical I3C. Proc Soc Exp Biol Med 216:246-52.
Thangaraju M, et al. 1994. Effect of tamoxifen on lipid peroxide and antioxidative system in postmenopausal women with
breast cancer. Cancer 74:78-82.
Vancutsem PM, et al. 1994. Frequent and specific mutations of the rat p53 gene in hepatocarcinomas induced by tamoxifen.
Cancer Res 54:3864-7.
Verhagen H, et al. 1995. Reduction of oxidative DNA-damage in humans by brussels sprouts. Carcinogenesis 16:969-70.
Verhoeven DT, et al. 1996. Epidemiological studies on brassica vegetables and cancer risk. Cancer Epidemiol Biomarkers
Prev 733-48.
Wattenberg LW, et al. 1978. Inhibition of polycyclic aromatic hydrocarbon-induced neoplasia by naturally occurring indoles.
Cancer Res 38:1410-13.
Wei H, et al. 1998. Tamoxifen reduces endogenous and UV light-induced oxidative damage to DNA, lipid and protein in vitro
and in vivo. Carcinogenesis 19:1013-8.
Yang JH, et al. 1999. A malignant transformation of human cells by 2,3,7,8-tetrachlorodibenzo-p-dioxin exhibits altered
expression of growth regulatory factors. Carcinogenesis 20:13-18.
Anonymous. 1997. Tamoxifen has a characteristic mutation spectrum in human endometrial cancers
(Meeting abstract). Proc Annu Meet Am Assoc Cancer Res 38:A3008.
Arnao MB, et al. 1996. Indole-3-carbinol as a scavenger of free radicals. Biochem Mol Biol Int 39:1125-34. Barakat RR, et al.
1997. Evaluation of p53, Bcl-2 and c-Ki-ras status in endometrial cancers occurring after breast cancer with or without
tamoxifen treatment (Meeting abstract). Proc Annu Meet Am Soc Clin Oncol 16:A1289.
Bitonti AJ, et al. 1999. US Patent 5,877,202. Bradlow HL, et al. 1991. Effects of dietary indole-3-carbinol on estradiol
metabolism and spontaneous mammary tumors in mice. Carcinogenesis 12:1571-74.
Chen I, et al. 1996. Indole-3-carbinol and diindolylmethane as aryl hydrocarbon (Ah) receptor agonists and antagonists in T47D
human breast cancer cells. Biochem Pharmacol 51:1069-76.
Chen I, et al. 1998. Aryl hydrocarbon receptor-mediated antiestrogenic and antitumorigenic activity of diindolylmethane.
Carcinogenesis 19:1631-9.
Cover CM, et al. 1998. Indole-3-carbinol inhibits the expression of cyclin-dependent kinase-6 and induces a G1 cell cycle
arrest of human breast cancer cells independent of estrogen receptor signaling. J Biol Chem 273:3838-47.
Cover M, et al. 1999. Indole-3-carbinol and tamoxifen cooperate to arrest the cell cycle of MCF-7 human breast cancer cells.
Cancer Res 59:1244-51.
Custodio JB, et al. 1994. Tamoxifen and hydroxytamoxifen as intramembraneous inhibitors of lipid peroxidation. Evidence for
peroxyl radical scavenging activity. Biochem Phearmacol 47:1989-98.
Devanaboyina U, et al. 1997. Effects of indole-3-carbinol (I3C) and phenethyl isothiocyanate (PEITC) on 7,12-dimethylbenz[a]
anthracene (DMBA)-induced DNA adducts in rat mammary glands and liver (Meeting abstract). Proc Annu Meet am Assoc.
Cancer Res 38:A2427.
Ferlini C, et al. 1999. Tamoxifen induces oxidative stress and apoptosis in oestrogen receptor-negative human cancer cell
lines. Br J Cancer 79:257-63.
Grubbs CJ, et al. 1995. Chemoprevention of chemically-induced mammary carcinogenesis by indole-3-carbinol. Anticancer
Res 15:709-16.Guillot C, et al. 1996. Alteration of p53 damage response by tamoxifen treatment. Clin Cancer Res 2:1439-44.
Gundimeda U, et al. 1996. Tamoxifen modulates protein kinase C via oxidative stress in estrogen receptor-negative breast
cancer cells. Biol Chem 271:13504-14.
He YH, et al. 1997. Chemopreventive properties of indole-3-carbinol (I3C): inhibition of DNA adduct formation of the dietary
carcinogen, 2-amino-1-methyl-6-pehnylimidazo [4,5-b]pyridine (PhIP), in female F344 rats. J Cell Biochem Suppl 27:42-51.
Lim JS, et al. 1992. Tamoxifen suppresses tumor promoter-induced hydrogen peroxide formation by human neutrophils.
Cancer Res 52:4969-72.
Manson MM, et al. 1998. Chemoprevention of afatoxin B1-induced carcinogenesis by indole-3-carbinol in rat liver-predicting the
outcome using early biomarkers. Carcinogenesis 19:1829-36.
Manz, et al. Cancer mortality among workers in chemical plant contaminated with dioxin. Lancet 338:959-64.
Michnovicz JJ, et al. 1991. Altered estrogen metabolism and excretion in humans following consumption of I3C. Nutr Cancer
16:59-66.
Michnovicz JJ, et al. 1997. Changes in levels of urinary estrogen metabolites after oral I3C treatment in humans. J Natl Cancer
Inst 89:718-23.
Michnovicz JJ. 1998. Increased estrogen 2- hydroxylation in obese women using oral indole-3-carbinol. Int J Obes Relat Metab
Disord 22:227-9.
Norris JD, et al. 1999. Peptide antagonists of the human estrogen receptor. Science 285:744-46. Paige LA, et al. 1999.
Estrogen receptor (ER) modulators each induce distinct conformational changes in ER alpha and ER beta. Proc Natl Acad Sci
USA 96:3999-4004.
Ricci MS, et al. 1999. Estrogen receptor reduces CYP1A1 induction in cultured human endometrial cells. J Biol Chem
274:3430-38.
Schecter A, et al. 1997. Dioxins, dibenzofurans, dioxin-like PCBs and DDE in U.S. fast food, 1995. Chemosphere 34:1449-57.
Sharma S, et al. 1994. Screening of potential chemopreventive agents using biochemical markers of carcinogenesis. Cancer s
54:5848-55.
Shertzer HG, et al. 1988. Intervention in free radical mediated hepatotoxicity and lipid peroxidation by indole-3-carbinol.
Biochem Pharmacol 37:333-38.
Taioli E, et al. 1997. Effects of indole-3-carbinol (I3C) on the metabolism of the tobacco-specific lung carcinogen 4-
(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in smokers (Meeting abstract). Proc Annu Meet am Assoc Cancer Res
38:A1413.
Taioli E, et al. 1999. Role of estradiol metabolism and CYP1A1 polymorphisms in breast cancer risk. Cancer Detect Prev
23:232-7.
Telang NT, et al. 1997. Inhibition of proliferation and modulation of estradiol metabolism: novel mechanisms for breast cancer
prevention by the phytochemical I3C. Proc Soc Exp Biol Med 216:246-52.
Thangaraju M, et al. 1994. Effect of tamoxifen on lipid peroxide and antioxidative system in postmenopausal women with
breast cancer. Cancer 74:78-82.
Vancutsem PM, et al. 1994. Frequent and specific mutations of the rat p53 gene in hepatocarcinomas induced by tamoxifen.
Cancer Res 54:3864-7.
Verhagen H, et al. 1995. Reduction of oxidative DNA-damage in humans by brussels sprouts. Carcinogenesis 16:969-70.
Verhoeven DT, et al. 1996. Epidemiological studies on brassica vegetables and cancer risk. Cancer Epidemiol Biomarkers
Prev 733-48.
Wattenberg LW, et al. 1978. Inhibition of polycyclic aromatic hydrocarbon-induced neoplasia by naturally occurring indoles.
Cancer Res 38:1410-13.
Wei H, et al. 1998. Tamoxifen reduces endogenous and UV light-induced oxidative damage to DNA, lipid and protein in vitro
and in vivo. Carcinogenesis 19:1013-8.
Yang JH, et al. 1999. A malignant transformation of human cells by 2,3,7,8-tetrachlorodibenzo-p-dioxin exhibits altered
expression of growth regulatory factors. Carcinogenesis 20:13-18.
SonicSWOLE
Member
"I3C not only weakens estrogen and keeps chemicals out of cells, it also goes after cancer in ways similar to tamoxifen. It, like
tamoxifen, interrupts the cell cycle. In studies from the University of California mentioned above, I3C inhibited the growth of estrogen
receptor-positive breast cancer cells by 90% compared to tamoxifen's 60% by stopping the cell cycle. (Adding tamoxifen to I3C
gave a 5% boost.) In estrogen receptor-negative cells I3C stopped the synthesis of DNA for new cells by about 50% whereas
tamoxifen had no significant effect. I3C also restores p21 and other tumor suppressors that act as check points during synthesis of
a new cell. Tamoxifen, by contrast, has no effect on p21. I3C also inhibits cancers caused by other chemicals, in addition to dioxin."
I'm sorry, but this in no way is a comparison of it's 'selective estrogen receptor modulation' with tamoxifen or the other handful of SERM's out there. While this study is intriguing in it's own right, it doesn not relay any benefit to this thread.
tamoxifen, interrupts the cell cycle. In studies from the University of California mentioned above, I3C inhibited the growth of estrogen
receptor-positive breast cancer cells by 90% compared to tamoxifen's 60% by stopping the cell cycle. (Adding tamoxifen to I3C
gave a 5% boost.) In estrogen receptor-negative cells I3C stopped the synthesis of DNA for new cells by about 50% whereas
tamoxifen had no significant effect. I3C also restores p21 and other tumor suppressors that act as check points during synthesis of
a new cell. Tamoxifen, by contrast, has no effect on p21. I3C also inhibits cancers caused by other chemicals, in addition to dioxin."
I'm sorry, but this in no way is a comparison of it's 'selective estrogen receptor modulation' with tamoxifen or the other handful of SERM's out there. While this study is intriguing in it's own right, it doesn not relay any benefit to this thread.
zombiemuscle
Active member
I've provided all the info needed to show that i3c is not an ai, and is suitable for use as a serm. The studies directly compare i3c to tamoxifen. Your failure to take in this information is your own flaw.
CrazyChemist
Well-known member
Zombie.... bro - major copy and paste fail. I don't want to see a bunch of stuff you pulled from a website and pasted into the reply.
Post 1 (one, one, one) - one single article that supports your claim:
Or post 1 single article that indicates I3C behaves at all like a SERM, let alone is more effective than a prescription SERM.
I am not trying to say you are wrong. I just couldn't find any studies indicating you were right.
DO NOT POST MORE THAN ONE REFERENCE AND MAYBE THE REFERENCE'S ABSTRACT. PLEASE DO NOT PASTE ANOTHER 30 PAGES INTO THIS THREAD OR I'LL JUST UNSUBSCRIBE.
Post 1 (one, one, one) - one single article that supports your claim:
Or post 1 single article that indicates I3C behaves at all like a SERM, let alone is more effective than a prescription SERM.
I am not trying to say you are wrong. I just couldn't find any studies indicating you were right.
DO NOT POST MORE THAN ONE REFERENCE AND MAYBE THE REFERENCE'S ABSTRACT. PLEASE DO NOT PASTE ANOTHER 30 PAGES INTO THIS THREAD OR I'LL JUST UNSUBSCRIBE.
SonicSWOLE
Member
Actually, you could've just quoted me instead of posting a bunch of unneeded info (that states zilch on ER modulation comparison) if you were working the SERM vs. AI angle. LOL.
zombiemuscle
Active member
It is one SINGLE article...
And sonic, why do you say that I3C is an AI when it does not interact with the aromatase enzyme??
And sonic, why do you say that I3C is an AI when it does not interact with the aromatase enzyme??
Delita420
Active member
SonicSWOLE
Member
I didn't say that. You need to reread my posts. Thank you very much.
Delita420
Active member
Sorry sonicswole, I thought this post was from you all day lol!
zombiemuscle
Active member
I had to resurrect an old profile to post the article link, AM does not allow new users to post links. Which explains the copy and paste.
It is a long article, but I found lots of useful information within. It explains how I3C works and how it can be compared to tamoxifen. It describes how I3C can be more beneficial than tamoxifen, and it also sheds light on the downsides of tamoxifen. I found the article to be very informing. I'll leave it at that, and I hope everyone will click the link and check it out for themselves.
marco wolf
Member
I've seen studies that show that I3C is antiandrogenic towards cancer cells in the prostrate. My question is this. Does this necessarily mean that it is antiandrogenic in the rest of the body?
Personally, I've tried DIM a few times and never have liked it, even at low doses. It kills my libido and makes my unit shrink.
Personally, I've tried DIM a few times and never have liked it, even at low doses. It kills my libido and makes my unit shrink.
SonicSWOLE
Member
You should read through this whole thread. I provided some good links. While DIM/I3C work in an apoptosis manner towards cancer cells of the prostate, they also (and more importanly in this context) have shown to down regulate androgen receptors.
marco wolf
Member
I did read the whole thread and the studies. All the studies I have read were performed on androgen induced cancer cells. Not being a scientist, I would like to know *where* in these studies I can read *how* they determined that it is a "pure androgen antagonist" of cells other than cancer cells.
SonicSWOLE
Member
You are confusing funcionality and mechanics. I refer you again to this post I made. Re-read this and then read the studies understanding the differences in actions.
marco wolf
Member
*Where* in the study does it show this? I am not refuting what you advocate. Please copy and paste the relevant section.
Anybody who can explain it, feel free to.
SonicSWOLE
Member
"These results suggest that B-DIM-induced cell proliferation inhibition and apoptosis induction are partly mediated through the down-regulation of AR, Akt, and NF-κB signaling."
Here you go, an example, I am not doing anymore of your homework for you.
Here you go, an example, I am not doing anymore of your homework for you.
marco wolf
Member
First of all, you're taking this too personally. I put my original question out to all, not just you. Second, I don't think you are grasping what my actual question is. Third, I have done my "homework" and am looking for clarification from someone who can and is willing to explain it.
SonicSWOLE
Member
I think I fully understand and answered your question. As far as taking it personally, no, lol. I just think it is way too easy with the world wide web to get the answers you seek yourself (aside from the fact they are already in this thread). If it is a matter of grasping concepts, then..... I'm not sure that there is help for you on that (nothing personal).
marco wolf
Member
You just think you answered it, so we'll just leave it at that. :fest30:
zombiemuscle
Active member
How do you feel about the divanil I3C stack? It may down regulate androgenic receptors, but won't lower testosterone... Right?
For example: atd like novedex xt (god forbid I mention an ai in this thread lol!) is anti androgenic by blocking androgen receptors, but still allows testosterone to exist.
CrazyChemist
Well-known member
You can have all the free testosterone in the world, if you don't have an androgen receptor for the testosterone to bind it won't do ****.
zombiemuscle
Active member
Well, I'm sure that it can't block all the angrogen receptors... Or products like testopro would be ineffective.
CrazyChemist
Well-known member
Think of it like this.... you can have all the estrogen in the world but if you are on a SERM then the estrogen is blocked. Even if the SERM doesn't block all estrogen receptors. If a cmpd down regulates androgen receptors then you are moving in the wrong direction, right?