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$2 Off with your online purchase (regular $42.99)
I•3•C 200 is indole-3-carbinol (I3C), a phytonutrient found in cruciferous vegetables such as broccoli, Brussels sprouts, cabbage, and bok choi. Research suggests that I3C is responsible for many of the health benefits of cruciferous vegetables, by supporting a better balance of estrogen metabolite formation.
60 Vegi-Caps
100% Vegetarian
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SUPPLEMENT FACTS:
Serving Size: 1 Capsule %DRI
Indole-3-Carbinol (I3C) ..................200 mg *
*Dietary Reference Intake not established.
Other ingredients: Mixed dietary indoles (including diindolylmethane (DIM), indolocarbazole, and linear and cyclic indole trimers and tetramers), microcrystalline cellulose. Capsule: vegetarian (hydroxypropylmethylcellulose).
NOTE: I-3-C can have a strong, characteristic smell that may be unpleasant to some people.
AOR guarantees that no ingredients not listed on the label have been added to the product. Contains no wheat, gluten, corn, nuts, dairy, soy, eggs, fish, or shellfish.
Suggested Use
Take one capsule twice a day. Do not take I•3•C 200 at the same time as antacids, H2-receptor blockers (eg. Zantac®), or proton-pump inhibitors (eg. Nexium®), as these drugs may impede the conversion of I3C to some active metabolites. Or as directed by a qualified health consultant.
Main Applications
As reported by literature:
•Safer estrogen metabolism.
•Risk reduction for women’s cancers.
•Respiratory Papillomatosis (RP)
Source
Synthesis from indole.
Pregnancy / Nursing
No studies have been conducted. Best to avoid.
Cautions
•Because I3C enhances some detoxification enzymes, it may change the bioavailability of many drugs, including, but not limited to, methadone, cyclosporine, codeine, statin drugs, and most of the protease inhibitors used to treat HIV. Consult with your physician if you are taking any medications before taking I3C.
•I3C and DIM exert powerful and pluripotent effects on estrogen metabolism and biotransformative enzymes. Consult with a physician.
•Have regular mammograms and Pap smears.
•Do not attempt to self-diagnose or self-medicate reproductive cancers.
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Indole-3-carbinol, or I3C, is a phytonutrient found in Brassica vegetables — relatives of the mustard plant, like broccoli, cabbage, Brussels sprouts. For years, we’ve known that people who eat the most Brassica vegetables are less likely to develop many different kinds of cancer. In the last decade, evidence has been quietly accumulating to suggest that I3C (and substances made in the body from I3C, like diindolylmethane (DIM [see “I3C vs DIM: Myths and Facts,” below]), ascorbigen, and indolylcarbazole (ICZ)) is one of the key active cancer-fighting ingredient in these foods (along with sulforaphane and D-Glucarate). This evidence has suggested that I3C might have potent powers to prevent — and perhaps even to treat — the killers women fear most.
Studies have shown that I3C and its metabolites have wide-ranging effects on factors that affect the risk of breast and other cancers. Animal and test-tube experiments have shown that I3C can stop the growth of, or even kill, existing breast cancer cells. Reports have been trickling in that I3C (and substances made in the body from I3C) blocks the activation of cancer cells by estrogen and deadly organic pollutants like dioxins; that it can turn on the genes that activate cancer cells’ internal suicide mechanisms, and prevent DNA damage from cancer-causing chemicals.
But the key risk factor in the development of most women’s reproductive cancers — and the point for I3C to play a role in risk reduction— is exposure to estrogen. “Estrogen” is actually not one substance, but a family of hormones that stimulate the growth and development of women’s reproductive systems. And in fact, the effect of estrogens on the risk of many women’s cancers is as much a product of which estrogens and estrogen metabolites a woman is exposed to, as it is of how much estrogen her body makes.
The estrogen metabolite 16 alpha-hydroxyestrone (16OHE) is a “bad” estrogen: it can powerfully promote the development of breast cancer. On the other hand, “good” estrogens also exist, in the form of 2-hydroxyestrone (2OHE), along with 2-methoxyestradiol. These estrogen metabolites are either harmless, or may actually be protective against women’s cancers.
Enter I3C
This is where I3C comes into the picture. Following up on extensive animals experimentation, the intriguing finding of several human studies has been that, by shifting the balance of metabolic enzymes that process estrogens in the body, I3C reduces the formation of “bad” estrogens, and increases the formation of “good” ones. There are profound implications for this fact for women’s cancers (such as those of the cervix, breast, and endometrium).
Knowing the role of “bad” estrogen in the progression of cervical cancer, and I3C’s ability to change estradiol metabolism from “bad” to “good,” a series of experiments have been run to see how I3C might reduce the risk. Favorable results ultimately led up to a prospective, randomized, double-blind, placebo-controlled trial of I3C in women with localized cancer (“carcinoma in situ”). The end result: in the August 2000 issue of Gynecologic Oncology, a journal specializing in the study of women’s reproductive cancers, Dr. Maria Bell and colleagues at the Louisiana State University Medical Center report that indole-3-carbinol reverses localized cancer of the cervix in human women.
Dr. Bell and her colleagues recruited thirty women with carcinoma in situ of the cervix (CIN II-III) as proven by biopsy. For twelve weeks, one third of these women received 200 mg of I3C; a second group got 400 mg; the remaining women were given a dummy pill. The women’s 2OHE:16OHE ratios were tested to see what effect the I3C would have on their metabolism of estrogen. At the end of the trial, all women’s CIN was assessed again, and women whose CIN persisted were treated with loop electrosurgical excision procedure (LEEP), which uses electricity to remove the abnormal tissue.
As you might expect, there were no changes in estrogen metabolism, or total reversals of CIN, in the women who received a dummy pill, although some of these women’s CIN did show some signs of improvement. By contrast, there was a dose-dependent increase in the ratio of “good” to bad” estrogens in the two I3C groups. More importantly, there was also a dose-dependent regression in degree of CIN, with the women who received the lower dose having the severity of their CIN cut by an average of 1.38 points (on a three-point scale), and the women receiving the higher dose experiencing an average reduction of 1.78 points. And astoundingly, carcinoma in situ had completely vanished in 47% of the women on I3C — without surgery, freezing, or laser therapy!
Breast Cancer
Only about 5% of breast cancer is caused by inherited genetic mutations in genes active in the breast itself. Most breast cells become cancerous in response to the things to which they are exposed. “Good” and “bad” estrogens appear to be key players in this process. The enzyme that is active in making the “bad” 16OHE from estradiol is eightfold higher in high-risk women than in a control group. Likewise, in a study that compared AfroAmerican with and without breast cancer, it was found that the presence of a genetic mutation which reduces a woman’s ability to make “good” 2OHE makes such a woman eight times more likely to have breast cancer than women with the normal form of the gene. Women with breast cancer, or who are from families prone to it, have higher levels of 16OHE than healthy women and women not from such families.
Since I3C is known to decrease the production of “bad” estrogen and to increase the production of the “good” 2OHE, you’d expect that it might have potent effects against breast cancer, just as it does against cancer of the cervix. In animal studies, I3C has been repeatedly shown to prevent the development of breast cancer, whether the cancer occurs because of exposure to chemical carcinogens or spontaneously. I3C has also been found to prevent the appearance of the abnormal growths that lead up to breast cancer, and of early biochemical markers of its development.
Other Mechanisms
But there’s more to I3C’s breast cancer prevention powers than its effects on the “good” and “bad” estrogens. I3C also stops normal and cancerous breast cells from multiplying more directly, by halting cell division in its earliest stages. It accomplishes this by actually influencing how cells express their genetic code. I3C increases the expression of cancer-fighting genes like the tumor-suppressing gene p53 and genes that suppress the activity of the “cancer gene” p21. At the same time, I3C stops the expression of a gene (cyclin D) that promotes cell proliferation.
Even more remarkably, I3C activates the inbuilt “suicide program” (apoptosis) in at least one line of breast cancer cells. And I3C increases expression of BRCA1, a gene which is absolutely vital in the prevention of breast cancer — so important, in fact, that 85% of women carrying mutations in BRCA1 will develop breast cancer at some point in their lives, while 60% will develop ovarian cancer by the age of 70.
I3C vs DIM: Myths and Facts
Recently, an artificial controversy about the relative advantages of I3C, as compared with one of its condensation products, DIM (diindolylmethane), has been created by persons connected with DIM sales. There is so much misinformation that has been propagated that we lack space to address it all. However, some key points can – and must – be made. First, and most importantly: no human studies have been published which used DIM. All of the human research in the scientific literature to date has been on I3C. We have studies to prove that I3C increases the formation of “good” estrogens, and decreases the formation of “bad” ones, in humans; we also have a controlled trial to show that I3C reverses carcinoma in situ, in human women. We don’t have any such data to tell us what DIM is doing to the women that take it. To suggest that DIM is a safer, or more effective, supplement for women than I3C is a completely groundless statement.
There are animal and test-tube studies on DIM– but much more evidence exists for I3C: the Medline scientific database lists nearly 300 such studies on I3C, but less than fifty for DIM. We have a much better understanding of I3C, and its effects on the body, than we do of DIM. The fact is, nearly all of the research being cited to support the use of DIM is actually research performed using I3C.
On top of this, no peer-reviewed research – in human women, in lab rats, or even in test tubes – has appeared in the scientific literature on “Phytosorb-DIM.” Phytosorb-DIM – the form being marketed by those who make some of the more absurd claims about DIM and I3C – is a combination of DIM with
d-alpha-tocopheryl polyethylene glycol-1000 succinate (also known as vitamin-E TPGS, or tocophersolan), along with emulsifiers and solvents. This amalgamation supposedly increases the absorption of DIM – although there are no studies in the scientific literature to actually prove this allegation.
That makes it especially irresponsible to push this untested product on women in the place of I3C. Animal studies have shown completely opposite effects on cancer when it’s given at different doses: at one dose, DIM will prevent cancer ...while at another dose, it will promote it! Again, we don’t even yet know what effects regular DIM has on human women’s estrogen metabolism, or what its bioavailability is. And bioavailability can vary greatly from animals to humans – especially in the case of phytochemicals, which are often metabolized by the bodies of animals and humans at wildly different rates. To cite just one example: curcumin, the potent antioxidant and COX-2 inhibitor from turmeric, is metabolized 18 times as quickly in the human intestine, and 5 times as quickly in the liver, as it is in rodents. And adding an absorption-enhancing substance to curcumin increases its absorption by 154% in rodents ... but by 2000% in humans! Without a clear idea as to how much more DIM women will take into their systems from the DIM/tocophersolan mixture, dosing is inevitably a wild roll of the dice, with a woman’s health hanging in the balance – all the more so when (again) we don’t even yet know what effects regular DIM has on human women’s estrogen metabolism.
In fact, some research does suggest that the effects of DIM may be as likely to promote cancer as to prevent it. Part of the mechanism whereby I3C may fight cancer is through its effects on the aryl hydrocarbon receptor, a receptor of unknown function in breast cells. By weakly binding to this receptor, I3C prevents it from being stimulated by dioxins, a family of persistent organic pollutants widely implicated in breast cancer that bind to the aryl hydrocarbon receptor. But studies have reported that DIM is an even stronger stimulator of the aryl hydrocarbon receptor than are dioxins themselves!
Likewise, while I3C stops the growth of breast cancer cells in culture whether they are stimulated by estrogen or not, some studies have found that DIM actually stimulates estrogen-positive breast cancer cells to grow in culture, with about 60% as much effect as estradiol itself.
While research into both DIM and I3C should continue, there are just too many unknowns to recommend DIM for human women at this time. Someday, with more research, DIM may indeed emerge to be the better supplement; on the other hand, the uninformed use of DIM could also eventually turn out to have been a terrible, preventable tragedy. But from the research that has been performed today, the bottom line is that we know I3C works in human women. We don’t yet know what the effects of DIM on humans will be: good, bad, or ugly.
Based on years of detailed analysis of the role of estrogen metabolites in women’s reproductive cancers, extensive animal experiments, and now a successful controlled trial in human women, I3C represents a revolution in natural support for safer estrogen metabolism, and thus for women’s health.
References
i. Taioli E, Bradlow HL, Garbers SV, Sepkovic DW, Osborne MP, Trachman J, Ganguly S, Garte SJ. “Role of estradiol metabolism and CYP1A1 polymorphisms in breast cancer risk.” Cancer Detect Prev. 1999; 23(3): 232-7.
ii. Bradlow HL, Telang NT, Sepkovic DW, Osborne MP. “2-hydroxyestrone: the 'good' estrogen.” J Endocrinol. 1996 Sep; 150 Suppl: S259-65.
iii. Bell MC, Crowley-Nowick P, Bradlow HL, Sepkovic DW, Schmidt-Grimminger D, Howell P, Mayeaux EJ, Tucker A, Turbat-Herrera EA, Mathis JM. “Placebo-controlled trial of indole-3-carbinol in the treatment of CIN.” Gynecol Oncol. 2000 Aug; 78(2): 123-9.
iv. Wong GY, Bradlow L, Sepkovic D, Mehl S, Mailman J, Osborne MP. “Dose-ranging study of indole-3-carbinol for breast cancer prevention.” J Cell Biochem Suppl. 1997; 28-29:111-6.
v. Michnovicz JJ, Adlercreutz H, Bradlow HL. “Changes in levels of urinary estrogen metabolites after oral indole-3-carbinol treatment in humans.” J Natl Cancer Inst. 1997 May 21; 89(10): 718-23.
vi. Michnovicz JJ. “Increased estrogen 2-hydroxylation in obese women using oral indole-3-carbinol.” Int J Obes Relat Metab Disord. 1998 Mar; 22(3): 227-9.
vii. Bradlow HL, Michnovicz JJ, Halper M, Miller DG, Wong GY, Osborne MP. “Long-term responses of women to indole-3-carbinol or a high fiber diet.” Cancer Epidemiol Biomarkers Prev. 1994 Oct-Nov; 3(7): 591-5.
viii. Michnovicz JJ, Bradlow HL. “Altered estrogen metabolism and excretion in humans following consumption of indole-3-carbinol.” Nutr Cancer. 1991; 16(1): 59-66.
ix. Riby JE, Chang GH, Firestone GL, Bjeldanes LF. “Ligand-independent activation of estrogen receptor function by 3, 3'-diindolylmethane in human breast cancer cells.” Biochem Pharmacol. 2000 Jul 15; 60(2): 167-77.
x. Chen I, McDougal A, Wang F, Safe S. “Aryl hydrocarbon receptor-mediated antiestrogenic and antitumorigenic activity of diindolylmethane.” Carcinogenesis. 1998 Sep; 19(9): 1631-9.
xi. Sanderson JT, Slobbe L, Lansbergen GW, Safe S, van den Berg M. “2,3,7,8-Tetrachlorodibenzo-p-dioxin and diindolylmethanes differentially inducecytochrome P450 1A1, 1B1, and 19 in H295R human adrenocortical carcinoma cells.” Toxicol Sci. 2001 May; 61(1): 40-8.
xii. Jellinck PH, Forkert PG, Riddick DS, Okey AB, Michnovicz JJ, Bradlow HL. “Ah receptor binding properties of indole carbinols and induction of hepatic estradiol hydroxylation.” Biochem Pharmacol. 1993 Mar 9; 45(5): 1129-36.
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