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Principal Proposed UsesOther Proposed Uses


Diindolylmethane

  • DIM

Uses

Principal Proposed Uses

Other Proposed Uses

Diindolylmethane (DIM) is produced when the substance indole-3-carbinol (I3C) is digested. Indole-3-carbinol, found in broccoli and other vegetables, has shown considerable promise for cancer prevention . Some of its benefits in this regard may occur after it is converted by the body to DIM.
DIM also has complex interactions with the hormone estrogen, which could lead to either positive or negative effects on cancer risk.

Requirements/Sources

There is no dietary requirement for DIM. Good natural sources include broccoli, Brussels sprouts, cabbage, and cauliflower.

Therapeutic Dosages

Manufacturers selling DIM products typically recommend about 500 to 1,000 mg daily. The optimal dose (if there is any) is not known.

Therapeutic Uses

Numerous test-tube and animal studies hint that DIM is might help prevent various types of cancer, especially breast, cervical, prostate, and uterine cancer. 1-16
However, this evidence is far too preliminary to serve as the basis for recommending that anyone use DIM. As with many proposed cancer-preventing substances, there are also circumstances in which DIM might actually increase the risk of cancer. 17-19
Some of DIM’s apparent anticancer benefits appear to derive from its complex interactions with estrogen. 20-27
DIM appears to alter liver function in such a manner that an increased amount of estrogen becomes metabolized into inactive forms. In addition, DIN blocks certain effects of estrogen on cells; however, it may enhance other effects of estrogen. The overall effect is far too complex and poorly understood to be described as “balancing estrogen in the body,” which is what many websites say about DIM.
DIM also appears to have an anti-testosterone effect, which could make it helpful for preventing or treating breast cancer. 28 Again, on some websites this effect has been over-optimistically termed “balancing testosterone levels.”
Highly preliminary evidence hints that DIM may offer benefit for diseases caused by human papilloma virus (HPV). These include cervical dysplasia and respiratory papillomatosis. 29,30
According to some manufacturers, DIM can enhance sexual function in men or women , and also enhance sports performance . However, there is no evidence that it actually works.

Safety Issues

DIM is thought to be a relatively nontoxic substance. However, comprehensive safety studies have not been completed. Due to DIM’s complex interactions with estrogen and testosterone, it has the potential for causing hormonal disturbances. Safety in young children, pregnant or nursing women, or people with severe liver or kidney disease has not been established.
Although there are no known drug interactions with DIM, the substance has shown considerable potential for interacting with many medications. 31-33
For this reason, we recommend that if you use any medication that is critical for your health, do not use DIM except under a physician's supervision.

References

1 Chang YC, Riby J, Chang GH, Peng BC, Firestone G, Bjeldanes LF. Cytostatic and antiestrogenic effects of 2-(indol-3-ylmethyl)-3,3'-diindolylmethane, a major in vivo product of dietary indole-3-carbinol. Biochem Pharmacol . 1999;58:825–34.

2 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;131:3294–302.

3 Chen I, Hsieh T, Thomas T, Safe S. Identification of estrogen-induced genes downregulated by AhR agonists in MCF-7 breast cancer cells using suppression subtractive hybridization. Gene . 2001;262:207–14.

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

5 Dalessandri KM, Firestone GL, Fitch MD, Bradlow HL, Bjeldanes LF. 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;50:161–7.

6 Gamet-Payrastre L, Lumeau S, Gasc N, Cassar G, Rollin P, Tulliez J. Selective cytostatic and cytotoxic effects of glucosinolates hydrolysis products on human colon cancer cells in vitro. Anticancer Drugs 1998;9:141–8.

7 Ge X, Yannai S, Rennert G, Gruener N, Fares FA. 3,3'-Diindolylmethane induces apoptosis in human cancer cells. Biochem Biophys Res Commun . 1996;228:153–8.

8 Hong C, Firestone GL, Bjeldanes LF. Bcl-2 family-mediated apoptotic effects of 3,3'-diindolylmethane (DIM) in human breast cancer cells. Biochem Pharmacol . 2002;63:1085–97.

9 Le HT, Schaldach CM, Firestone GL, Bjeldanes LF. Plant-derived 3,3'-diindolylmethane is a strong androgen antagonist in human prostate cancer cells. J Biol Chem . 2003;278:21136–45. Epub 2003 Mar 27.

10 Leong H, Firestone GL, Bjeldanes LF. Cytostatic effects of 3,3'-diindolylmethane in human endometrial cancer cells result from an estrogen receptor-mediated increase in transforming growth factor-alpha expression. Carcinogenesis . 2001;22:1809–17.

11 Lord RS, Bongiovanni B, Bralley JA. Estrogen metabolism and the diet-cancer connection: rationale for assessing the ratio of urinary hydroxylated estrogen metabolites. Altern Med Rev . 2002;7:112–29.

12 McDougal A, Gupta MS, Morrow D, Ramamoorthy K, Lee JE, Safe SH. Methyl-substituted diindolylmethanes as inhibitors of estrogen-induced growth of T47D cells and mammary tumors in rats. BreastCancer Res Treat . 2001;66:147–57.

13 McDougal A, Sethi Gupta M, Ramamoorthy K, Sun G, Safe SH. Inhibition of carcinogen-induced rat mammary tumor growth and other estrogen-dependent responses by symmetrical dihalo-substituted analogs of diindolylmethane. Cancer Lett . 2000;151:169–79.

14 Nachshon-Kedmi M, Yannai S, Fares FA. Induction of apoptosis in human prostate cancer cell line, PC3, by 3,3'-diindolylmethane through the mitochondrial pathway. Br J Cancer . 2004;91:1358–63.

15 Nachshon-Kedmi M, Yannai S, Haj A, Fares FA. Indole-3-carbinol and 3,3'-diindolylmethane induce apoptosis in human prostate cancer cells. Food Chem Toxicol . 2003;41:745–52.

16 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;60:167–77.

17 Ritter CL, Prigge WF, Reichert MA, Malejka-Giganti D. Oxidations of 17beta-estradiol and estrone and their interconversions catalyzed by liver, mammary gland and mammary tumor after acute and chronic treatment of rats with indole-3-carbinol or beta-naphthoflavone. Can J Physiol Pharmacol . 2001;79:519–32.

18 Dashwood RH. Indole-3-carbinol: anticarcinogen or tumor promoter in brassica vegetables? Chem Biol Interact. 1998;110:1–5.

19 Kim DJ, Han BS, Ahn B, Hasegawa R, Shirai T, Ito N, Tsuda H. Enhancement by indole-3-carbinol of liver and thyroid gland neoplastic development in a rat medium-term multi-organ carcinogenesis model. Carcinogenesis . 1997;18:377–81.

20 Dalessandri KM, Firestone GL, Fitch MD, Bradlow HL, Bjeldanes LF. 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;50:161–7.

21 Bradlow HL, Sepkovic DW, Telang NT, Osborne MP. Multifunctional aspects of the action of indole-3-carbinol as an antitumor agent. Ann N Y Acad Sci . 1999;889:204–13.

22 Ge X, Yannai S, Rennert G, Gruener N, Fares FA. 3,3'-Diindolylmethane induces apoptosis in human cancer cells. Biochem Biophys Res Commun . 1996;228:153–8.

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

24 Chen I, Hsieh T, Thomas T, Safe S. Identification of estrogen-induced genes downregulated by AhR agonists in MCF-7 breast cancer cells using suppression subtractive hybridization. Gene . 2001;262:207–14.

25 McDougal A, Gupta MS, Morrow D, Ramamoorthy K, Lee JE, Safe SH. Methyl-substituted diindolylmethanes as inhibitors of estrogen-induced growth of T47D cells and mammary tumors in rats. Breast Cancer Res Treat . 2001;66:147–57.

26 Le HT, Schaldach CM, Firestone GL, Bjeldanes LF. Plant-derived 3,3'-diindolylmethane is a strong androgen antagonist in human prostate cancer cells. J Biol Chem . 2003;278:21136–45. Epub 2003 Mar 27.

27 Lord RS, Bongiovanni B, Bralley JA. Estrogen metabolism and the diet-cancer connection: rationale for assessing the ratio of urinary hydroxylated estrogen metabolites. Altern Med Rev . 2002;7:112–29.

28 Le HT, Schaldach CM, Firestone GL, Bjeldanes LF. Plant-derived 3,3'-diindolylmethane is a strong androgen antagonist in human prostate cancer cells. J Biol Chem . 2003;278:21136–45. Epub 2003 Mar 27.

29 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;131:3294–302.

30 Auborn KJ. Therapy for recurrent respiratory papillomatosis. Antivir Ther . 2002;7:1–9.

31 Katchamart S, Stresser DM, Dehal SS, Kupfer D, Williams DE. Concurrent flavin-containing monooxygenase down-regulation and cytochrome P-450 induction by dietary indoles in rat: implications for drug-drug interaction. Drug Metab Dispos . 2000;28:930–6.

32 Lake BG, Tredger JM, Renwick AB, Barton PT, Price RJ. 3,3'-Diindolylmethane induces CYP1A2 in cultured precision-cut human liver slices. Xenobiotica . 1998;28:803–11.

33 Sanderson JT, Slobbe L, Lansbergen GW, Safe S, van den Berg M. 2,3,7,8-Tetrachlorodibenzo-p-dioxin and diindolylmethanes differentially induce cytochrome P450 1A1, 1B1, and 19 in H295R human adrenocortical carcinoma cells. Toxicol Sci . 2001;61:40–8.

Revision Information

This content is reviewed regularly and is updated when new and relevant evidence is made available. This information is neither intended nor implied to be a substitute for professional medical advice. Always seek the advice of your physician or other qualified health provider prior to starting any new treatment or with questions regarding a medical condition.

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