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DIM and I3C
Indole-3-carbinol (I3C) is a phytonutrient found in high levels in cruciferous vegetables, such as broccoli, cabbage, and cauliflower.
Indole-3-carbinol is the precursor to another indole and phytonutrient, diindolylmethane (DIM).
I3C and DIM are frequently taken to promote metabolism of estrogen and to help manage estrogen-related conditions, such as prostate cancer and BPH (enlarged prostate).
As men age, they experience a decline in testosterone and, in many cases, increases in estrogen levels. The result is a testosterone/estrogen imbalance that directly causes many of the debilitating health problems associated with normal aging. Estrogen is metabolized into several different post-estrogen hormones, namely 2-hydroxy, 4-hydoxy and 16-hydroxy estrogens. Research has shown 4-hydroxy and 16-hydroxy estrogens to be powerful growth and inflammation promoters, with direct connections to cancer, especially in estrogen-sensitive tissues such as the prostate. Obesity is also associated with unfavorable estrogen metabolites. (Schneider 1983) On the other hand, 2-hydroxy estrogens have been shown to be powerfully protective of those same tissues, helping to prevent cancer and resolve disorders including elevated PSA from prostate tissue. (Le 2003)
Balanced estrogen levels in men are essential to encourage a healthy libido, improved brain function, protect the heart and strengthen the bones. However, aging, body fat, hormone replacement, pesticides, prescription medications, and excessive alcohol intake can lead to high estrogen levels, which in turn can cause reduced testosterone levels, fatigue, loss of muscle tone, increased body fat, loss of libido and sexual function, and an enlarged prostate.
DIM acts to promote and support favorable metabolism of estrogen and related hormones by enhancing the liver’s ability to metabolize estrogen to “weaker” 2-hydroxyestrone. DIM may reduce prostate cancer incidence by inhibiting the growth of human cancer cells and provoking cell self-destruction (apoptosis). In addition, DIM may improve prostate function, enhance insulin sensitivity, and increase abdominal fat loss.
I3C and Cancer (Prostate Cancer)
Research shows that I3C has potential value as an anticancer agent for breast cancer through its effect on estrogen receptors. (Wong 1997) Several studies have also shown that I3C can promote cancer cell death (apoptosis), including prostate cancer cells. For example, a study at Wayne State University examined the molecular mechanisms by which DIM has an effect on prostate cancer cells. The authors noted that they had “previously shown that I3C induces apoptosis and inhibits the activation of NF-kappaB pathway, which could be mediated via Akt signaling pathway.” In the new study, the investigators found that DIM inhibited cell growth and induced apoptosis in PC-3 prostate cancer cells via inhibition of Akt and NF-kappaB activity and their cross-talk. (Li 2005) In a 2006 laboratory study, scientists showed that I3C helped arrest the cell cycle of human prostate cancer cells. (Hsu 2006)
At Wayne State University School of Medicine, researchers reviewed laboratory experiments in which they found that I3C and DIM inhibited prostate cancer cell growth and promoted apoptosis. Among their findings was that I3C and DIM upregulated the expression of Phase I and II enzymes, which indicates an increased ability to detoxify and inhibit carcinogens. They also reported that I3C can induce G1 cell-cycle arrest and cell death in prostate cancer cells, and that both I3C and DIM regulate many genes that play a critical role in the control of cell cycle, cell proliferation, signal transduction, and other cellular processes, suggesting I3C and DIM have the ability to impact prostate cancer cells in multiple ways. Based on the results from their laboratory and others, they concluded there is “ample evidence for the benefit of I3C and DIM for the prevention and the treatment of prostate cancer.” (Sarkar 2004)
DIM and BPH (enlarged prostate)
DIM has also been identified as being potentially beneficial for men who have BPH (enlarged prostate). In a safety study of both I3C and DIM, supplementation with absorbable DIM resulted in reports of an improvement in prostate function, based on a reduction in nighttime urination, in older men with symptoms of BPH. (Zeligs)
DIM and Weight Loss
Research shows that absorbable DIM specifically directs metabolism to produce much higher levels of 2-hydroxy, (Dalessandri 2004) which produces remarkable results in the body, and invigorates the process of weight loss. Lipolysis is the process by which fat cells release stored fat to serve as a primary energy supply. The good estrogen 2-hydroxy helps maintain healthy levels of the catecholamine hormones (epinephrine and norepinephrine) that specifically stimulate enzymes in fat cells to release stored fat for energy. (Ackerman 1981) When given over a period of months in animal studies, 2-hydroxy estrogen prevented obesity and the Metabolic Syndrome. (Tofovic 2001) Research with absorbable DIM has shown that supplementation before exercise results in greater lipolysis in the hours following exercise and enhances weight loss in adults on a weight loss program. (Zeligs 2003)
Both indole-3-carbinol and DIM are available in supplement form, although absorbable DIM is generally recommended as the more direct and effective form, as only about 10 percent of I3C supplement is converted to DIM in the gut. Use of indole-3-carbinol is also associated with side effects, such as dizziness and unsteady gait, while DIM is not.
References
Ackerman GE, et al. Potentiation of epinephrine-induced lipolysis by catechol estrogens and their methoxy derivatives, Endocrinology. 1981; 109:2084-88.
Dalessandri KM et al. Pilot study: effect of 3,3’-diindolylmethane supplements on urinary hormone metabolites in postmenopausal women with a history of early-stage breast cancer. Nutr Cancer. 2004; 50(2):161-67.
Hsu JC et al. Indole-3-carbinol mediated cell cycle arrest of LNCaP human prostate cancer cells requires the induced production of activated p53 tumor suppressor protein. Biochem Pharmacol 2006 Dec 15; 72(12): 1714-23
Le HT et al. Plant-derived 3,3’-Diindolylmethane is a strong androgen antagonist in human prostate cancer cells. J Biol Chem. 2003 Jun 6; 278(23):21136-45.
Li Y et al. Selective growth regulatory and pro-apoptotic effects of DIM is mediated by AKT and NF-kappaB pathways in prostate cancer cells. Front Biosci. 2005 Jan 1;10:236-43.
Sarkar FH, Li Y. Indole-3-carbinol and prostate cancer. J Nutr 2004 Dec; 134(12 Supp): 3493S-98S
Schneider J et al. Effects of obesity on estradiol metabolism: decreased formation of nonuterotropic metabolites. J Clin Endocrinol Metab. 1983 May; 56(5):973-78.
Tofovic SP et al. 2-Hydroxyestradiol attenuates the development of obesity, the metabolic syndrome, and vascular and renal dysfunction in obese ZSF1 rats. J Pharmacol Exp Ther. 2001 Dec; 299(3):973-77.
Wong GY et al. Dose-ranging study of indole-3-carbinol for breast cancer prevention. J Cell Biochem Suppl 1997; 28-29: 111-16
Zeligs MA. The cruciferous choice: diindolylmethane or I3C? Access at http://www.dimfaq.com/site/cruchoice.htm
Zeligs MA. Phytochemicals for promoting weight loss. US Patent #6,534,085, 2003, March.
