DIM supplementation - Anti-Estrogen / Anti-Cancer "Tool"

As a supplement, DIM is generally considered safer and more effective than I3C

 I3C is a break-down product of cruciferous vegetables.    DIM is a health-beneficial reaction product of I3C formed in the stomach and intestines

The I3C reaction product DIM showing good results with cancer

• The original discoverer of the importance of cruciferous indoles for breast health advocates DIM over I3C - Leon Bradlow, Ph.D. now supports and advocates absorbable DIM, and not I3C, as the preferred supplement, even though he initiated and performed the majority of human and animal testing of I3C.
• DIM cannot be converted to undesireable ICZ in vivo (see notes on ICZ above)
• DIM blocks dioxin receptor.   Dioxin is a well-known carcinogen

Chen I, Safe S, Bjeldanes L. "Indole-3-carbinol and diindolylmethane as aryl hydrocarbon (Ah) receptor agonists and antagonists in T47D human breast cancer cells." Biochem Pharmacol. 1996 Apr 26;51(8):1069-76.

• DIM is not estrogenic or a growth promoter of cancer cells.   DIM exerts its control over cancer growth without inducing unwanted enzymes and their production of highly estrogenic16OHE1from I3C
• "DIM is a more effective inducer of apoptosis than I3C"

Chen DZ, Qi M, Auborn KJ, Carter TH, "Indole-3-Carbinol and Diindolylmethane Induce Apoptosis of Human Cervical Cancer Cells and in Murine HPV16-Transgenic Preneoplastic Cervical Epithelium." J Nutr. 2001 Dec;131(12):3294-3302.

• DIM controls growth in experimental breast cancer

Kang JS, Kim DJ, Ahn B, Nam KT, Kim KS, Choi M, Jang DD. "Post-initiation treatment with Indole-3-carbinol did not suppress N-methyl-N-nitrosourea induced mammary carcinogenesis in rats." Cancer Lett. 2001 Aug 28;169(2):147-54.

Chen I, McDougal A, Wang F, Safe S"Aryl hydrocarbon receptor-mediated antiiestrogenic and antitumorigenic activity of diindolylmethane." Carcinogenesis 1998 Sep;19(9):1631-9.

NOTE that Cell Culture studies showing DIM as a contributor to breast cancer cell growth were done in an artificial estrogen-free environment never seen in vivo.   In the article "DIM and I3C: The Real Facts on Safety" by Michael A. Zeligs, M.D., he writes:

" In the presence of estrogen, DIM is consistently anti-proliferative and reduces the growth signal provided by estrogen (2). This includes growth-inhibiting activity in both estrogen receptor positive and negative cancer cell types (3). The estrogen-independent activation pathway described by Riby et al (1) involves the increased phosphorylation of estrogen receptor proteins, and not the direct interaction of DIM with the estrogen receptor. This action may actually be of benefit in cancer control. Understood in context, this receptor activation pathway contributes to the control of abnormal cell growth in living animals through enhanced "programmed-cell-death" (apoptosis) and a reduced tendency for the metastatic spread of cancer (4). Unlike ICZ, LTR, CTR or ASG, DIM exerts its control over cancer cell growth without activating the dioxin receptor or inducing unwanted enzymes.Direct control over cancer cell growth by DIM has now been shown in breast, uterine, cervical, ovarian, and colon cancer cells.I3C has been noted to control cancer cell growth in these cell types as well. However, in cell culture media at 37 degrees Centigrade, most of the I3C is converted to DIM in 24 hours. Since no ICZ and the other condensation products formed in gastric acid occur in cell culture media, DIM may very well be responsible for much of the activity attributed to I3C in prior cell culture studies".

1. 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.

2. Chibo Hong, Gary L. Firestone, and Leonard F. Bjeldanes, "3,3'Diindolylmethane (DIM), a dietary indole, has multiple cell suppressive effects on MCF-7, human breast cancer cells." The American Society for Cell Biology, Fortieth Annual Meeting, December 2000, San Francisco, California.

3. Chibo Hong, Gary L. Firestone and Leonard F. Bjeldanes. "Induction of apoptosis in MCF-7 and MDA-MB-231 human breast cancer cells by 3,3'-diindolylmethane (DIM)." Experimental Biology 2001, March 31-April 4, 2001, Orlando, Florida.

4. Platet N, Cunat S, Chalbos D, Rochefort H, Garcia M."Unliganded and liganded estrogen receptors protect against cancer invasion via different mechanisms." Mol Endocrinol. 2000 Jul;14(7):999-1009.

How to Supplement DIM for hormonal balance

DIM balances hormones and aids in the breakdown of estrogen.

Choose a DIM supplement where the label indicates that it has been formulated in such a way as to increase its absorption in the body.   The enhanced-absorption, micro-encapsulated form patented by Bio-Response is probably the best choice, available under various labels:

• Nature's Way "DIM-plus"  available at:  Vitacost,   Swanson's

Dose range of DIM (not including the absorption-aid ingredients) for hormonal balance:

Women - 25 - 50 mg per day of DIM

Men - 50 - 100 mg /day of DIM .

1 ½ pounds of cruciferous vegetables produces approx. 10-30 mg of DIM

Use of absorbable DIM has been shown effective in amounts close to that obtainable from our diet (0.3 mg/kg/day of DIM)

Zeligs MA, Sepkovic DW, Manrique CA, Macksalka M, Williams DE, Bradlow HL, "Absorption-enhanced 3,3-Diindolylmethane: human use in HPV-related, benign and pre-cancerous conditions." American Association of Cancer Research, (42) 2002, #103483.

Safety issues of DIM Supplementation

Even very high doses of DIM are well-tolerated.   Human studies, often at 10 times the typical supplement dose of DIM which benefits estrogen metabolism, have reported no side effects, unlike I3C, where higher doses produce side effects such as dizziness and unsteady gait

Rosen CA; Woodson GE; Thompson JW; Hengesteg AP; Bradlow HL, "Preliminary results of the use of indole-3-carbinol for recurrent respiratory papillomatosis,"Otolaryngol Head Neck Surg 1998 Jun;118(6):810-5.

May interfere with the breakdown of some drugs in the liver.    This could lead to increased or decreased absorption of certain drugs, as well as increased side effects. Ask your health care provider about possible drug interactions with DIM if you take any prescription medication.

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