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Home > Health Conditions > Di-indolylmethane

Di-indolylmethane

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News & Research:

  • Vegetable-derived compound effective in treating triple-negative breast cancer, research suggests - Science Daily, 10/17/12 - "TNBC accounts for approximately 15-20 percent of all breast cancer cases in the U.S. It is one of the most aggressive forms of breast cancer; it grows faster, spreads to other parts of the body earlier, is harder to detect on a mammogram and recurs more often ... Sachdeva's study reveals that these synthetic compounds derived from diindolylmethane (DIM), commonly found in various types of cruciferous vegetables, can be used to treat several types of cancer, including triple-negative breast cancer. C-DIMs are also being investigated for their cancer prevention activity"
  • Compound In Broccoli Could Boost Immune System, Says Study - Science Daily, 8/20/07 - "This study shows that there is a whole new universe of cancer regulation related to DIM ... There are virtually no other agents known that can both directly shut down the growth of cancer cells and enhance the function of the immune system at the same time"
  • Broccoli, soy anti-cancer benefits suggested - Nutra USA, 4/16/07 - "this attraction between CXCR4 and CXCL12 draws cancer cells to the organs they spread to ... exposure with either DIM or genistein cut movement by 80 per cent"
  • I3C & DIM - Natural, Dual-Action Protection Against Deadly Cancers - Life Extension Magazine, 1/06 - "Mounting preclinical and clinical evidence indicate[s] that indole-3-carbinol (I3C), a key bio-active food component in cruciferous vegetables, has multiple anticarcinogenic and antitumorigenic properties" - See indole-3-carbinol at Amazon.com.
  • I have read that Indole-3-Carbinol (I3C) actually increases the activity of aromatase enzyme and that DIM does not - Life Extension Magazine, 3/01 - "In one study, men received I3C for one week; a profile of 13 estrogens was measured. The results were that I3C significantly increased the urinary excretion of C-2 estrogens. The urinary concentrations of nearly all other estrogen metabolites, including levels of estradiol, estrone, estriol and 16 alpha-hydroxyestrone, were lower after I3C treatment [J Natl Cancer Inst 1997 May 21;89(10):718-23]. On the other hand, studies have shown that DIM can actually induce aromatase activity with a two-fold increase [Toxicol Sci 2001 May;61(1):40-8]" - The following are the two references for that statement:
  • I3C vs DIM - Life Extension Foundation, 1/02
  • Natural estrogen replacement article by Jonathan Wright MD. - IAS - "DIM may reduce prostate cancer incidence as it has been shown to stop human cancer cells from growing by (54-61%) and provoking the cells to self-destruct (apoptosis). DIM also improves prostate function, enhances insulin sensitivity and increases abdominal fat loss."
  • I3C and DIM: Keys to Cancer Prevention? - Nutrition Science News, 4/01 - "Increased 16-alpha-hydroxyestrone production has been linked to an increase in breast cancer. Based on estrogen metabolism's influence on breast-cancer risk, researchers speculate that reducing hydroxylation of estrone's 16th carbon and increasing hydroxylation of the second carbon would be a wise, protective measure ... The minimum effective dose to increase the ratio of 2-hydroxyestrone to 16-alpha-hydroxyestrone was 300 mg/day ... Most of the research thus far has focused on I3C, a phytonutrient converted by stomach acid to DIM, indolylcarbazole, and other metabolites ... A 350­500 mg dose of I3C is roughly equal to 300­500 mg of raw cabbage or brussels sprouts or about 3 cups of broccoli"
  • I've heard quite a bit about a broccoli extract called indole-3-carbinol (I3C). What is the difference between it and the other broccoli extract called diindolylmethane (DIM)? - Nutrition Science News, 2/01 - "Certainly DIM by itself has an effect, but these other products may also be important for the overall cancer-inhibiting action. As most of the research to date has focused on I3C, it seems prudent at this time to use supplements containing I3C instead of DIM"
  • The Cruciferous Choice: DIM or I3C? - Michael A. Zeligs, M.D. - "It is well documented that estrogen accumulates in the prostate gland starting at age 50 (42) and that estrogen is associated with the degree of prostate enlargement ... Using DIM in men avoids accelerating testosterone metabolism, especially regarding unwanted conversion of testosterone into estrogen. In the safety study reported (11), I3C and not DIM increased activity of "aromatase" (CYP19), the enzyme responsible for converting testosterone into estrogen"
  • DIM FAQ - "DIM helps to eliminate active estrogen from the male body by promoting its conversion into the "good" metabolites. These metabolites then free up testosterone by bumping it off the testosterone-binding proteins. The end result is a healthier balance of testosterone to estrogen and more free testosterone circulating in the body. In scientific studies, high levels of testosterone and low levels of estrogen have been linked to lean body mass, an efficient fat-burning metabolism, and low abdominal obesity. Other benefits from testosterone are improved mood, more interest in sex, and better physical conditioning. In this chapter, we'll explore these issues in more detail."
  • Di-indolylmethane - Jonathan Wright MD's, International Anti-aging Systems
  • Reducing the Hormone Related Cancer Risk (Or cabbages, sex hormones and their metabolites) - Jonathan Wright M.D., International Anti-aging Systems - "Among other things, estradiol is metabolized into estrone, which in turn can be metabolized into either 2-hydroxyestrone or 16 alpha-hydroxyestrone. Importantly, there's an “inverse” relationship here: if more 2-hydroxyestrone is made, less 16 alpha-hydroxyestrone is usually made, and vice-versa. In at least one of his publications, Dr. Bradlow has termed 2-hydroxyestrone “good estrogen”, and has given us evidence that 16 alpha hydroxyestrone is “bad estrogen”. He writes: “Evidence from a long series of studies has demonstrated a specific role for 16a-hydroxyestrone as a transforming estrogen, which is more potent than estradiol itself.” (“Transforming” refers to the tendency of 16a-hydroxyestrone to increase cellular growth and proliferation, and even cancerous transformation in estrogen-responsive tissues). He goes on to note that the preponderance of evidence shows that, by contrast, 2-hydroxyestrone is non-carcinogenic or even anti-carcinogenic. He also notes that treatment which reduces the 2/16a hydroxyestrone ratio has been shown to reverse the growth of human larygneal papillomas, caused by the same family of viruses (HPV) implicated in cervical cancers.  Other researchers hypothesize that cancer in other tissues, including uterus, prostate, liver and kidney, may be affected by the 2/16a hydroxyestrone ratio as well as other estrogen metabolites"
  • Estrogen Levels Linked To Head And Neck Cancers - Doctor's Guide, 9/28/99 - "Similar effects (to alter estrogen metabolic pathways) could be exerted by vegetables including broccoli and cauliflower, which contain the phytochemical compound indole-3-carbinol."
  • I3C/DIM - Recurrent Respiratory Papillomatosis Foundation

Abstracts:

  • Synergistic anti-cancer activity of Capsaicin and 3,3'-Diindolylmethane in human colorectal cancer - J Agric Food Chem. 2015 Apr 15 - "The present study suggests capsaicin and DIM work synergistically to inhibit cell proliferation and induce apoptosis in colorectal cancer through modulating transcriptional activity of NF-κB, p53 and target genes associated with apoptosis" - See capsaicin supplements at Amazon.com and diindolylmethane at Amazon.com.
  • Dietary diindolylmethane suppresses inflammation-driven lung squamous cell carcinoma in mice - Cancer Prev Res (Phila). 2014 Nov 17 - "Dietary administration of DIM (10 µmol/g diet or 2460 ppm) to mice treated with NTCU plus LPS reduced the incidence of LSCC by 2-fold, suppressed activation/expression of proinflammatory and procarcinogenic proteins and NF-κB- and STAT3-DNA binding, but not the expression of cytokines and p53. This study highlights the potential significance of our mouse model to identify promising drugs or dietary agents for the chemoprevention of human LSCC and that DIM is a very good candidate for clinical lung cancer chemoprevention trials"
  • Diindolilmethane (DIM) selectively inhibits cancer stem cells - Biochem Biophys Res Commun. 2012 Jun 19 - "Epidemiologic studies repeatedly have shown chemopreventive effects of cruciferous vegetables. Indole-3-carbinol (I3C) and its metabolite diindolylmethane (DIM) were identified in these plants as active ingredients and theirs anti-tumor activities were confirmed in multiple in vitro and in vivo experiments. Here, we demonstrate that DIM is a selective and potent inhibitor of cancer stem cells (CSCs). In several cancer cell lines, DIM inhibited tumor sphere formation at the concentrations 30-300 times lower than concentrations required for growth inhibition of parental cells cultured as adherent culture. We also found that treatment with DIM overcomes chemoresistance of CSCs to cytotoxics, such as paclitaxel, doxorubicin, and SN-38 ... DIM can potentially be used in cancer patients, either alone, or in combinations with existing drugs"
  • B-DIM Impairs Radiation-Induced Survival Pathways Independently of Androgen Receptor Expression and Augments Radiation Efficacy in Prostate Cancer - Cancer Lett. 2011 Dec 9 - "Increased consumption of cruciferous vegetables is associated with decreased risk in prostate cancer (PCa). The active compound in cruciferous vegetables appears to be the self dimerized product [3,3'-diindolylmethane (DIM)] of indole-3-carbinol (I3C). Nutritional grade B-DIM (absorption-enhanced) has proven safe in a Phase I trial in PCa ... B-DIM inhibited cell growth in a dose-dependent manner in both PC-3 (AR-) and C4-2B (AR+) cell lines. B-DIM was effective at increasing radiation-induced cell killing in both cell lines, independently of AR expression. B-DIM inhibited NF-κB and HIF-1α DNA activities and blocked radiation-induced activation of these transcription factors in both PC-3 and C4-2B cells. In C4-2B (AR+) cells, AR expression and nuclear localization were significantly increased by radiation. However, B-DIM abrogated the radiation-induced AR increased expression and trafficking to the nucleus, which was consistent with decreased PSA secretion. In vivo, treatment of PC-3 prostate tumors in nude mice with B-DIM and radiation resulted in significant primary tumor growth inhibition and control of metastasis to para-aortic lymph nodes. These studies demonstrate that B-DIM augments radiation-induced cell killing and tumor growth inhibition. B-DIM impairs critical survival signaling pathways activated by radiation, leading to enhanced cell killing. These novel observations suggest that B-DIM could be used as a safe compound to enhance the efficacy of radiotherapy for castrate-resistant PCa"
  • CXCR4 and CXCL12 down-regulation: A novel mechanism for the chemoprotection of 3,3'-diindolylmethane for breast and ovarian cancers - Cancer Lett. 2008 Mar 28 - "Our data suggest that one mechanism whereby DIM protects against breast, ovarian, and possibly other cancers is through the repression of CXCR4 and/or CXCL12, thereby lowering the invasive and metastatic potential of these cells"
  • Indole-3-carbinol as a chemopreventive and anti-cancer agent - Cancer Lett. 2008 Feb 29 - "Indole-3-carbinol and its metabolite 3,3'-diindoylmethane (DIM) target multiple aspects of cancer cell-cycle regulation and survival including Akt-NFkappaB signaling, caspase activation, cyclin-dependent kinase activities, estrogen metabolism, estrogen receptor signaling, endoplasmic reticulum stress, and BRCA gene expression. This broad spectrum of anti-tumor activities in conjunction with low toxicity underscores the translational value of indole-3-carbinol and its metabolites in cancer prevention/therapy. Furthermore, novel anti-tumor agents with overlapping underlying mechanisms have emerged via structural optimization of indole-3-carbinol and DIM, which may provide considerable therapeutic advantages over the parental compounds with respect to chemical stability and anti-tumor potency. Together, these agents might foster new strategies for cancer prevention and therapy"
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