Diindolylmethane

Purported Benefits, Side Effects & More
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Diindolylmethane

Purported Benefits, Side Effects & More
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Diindolylmethane

Common Names

  • DIM

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For Patients & Caregivers

Tell your healthcare providers about any dietary supplements you’re taking, such as herbs, vitamins, minerals, and natural or home remedies. This will help them manage your care and keep you safe.

What is it?

Lab studies suggest diindolylmethane (DIM) has anticancer effects, but clinical data are limited.

Diindolylmethane is a compound found in cruciferous vegetables including broccoli, cabbage, and cauliflower. Laboratory studies suggest anti-inflammatory and anticancer effects, but data in humans are quite limited. A few clinical studies suggest DIM may benefit patients with castration-resistant prostate cancer or help reverse abnormal cervical changes in cells. However, more studies are needed to determine safety and effectiveness, as DIM may affect the levels of certain hormones in the body.

What are the potential uses and benefits?
  • Cancer prevention
    Preliminary studies suggest that DIM may benefit patients with castration-resistant prostate cancer and help reverse cervical intraepithelial neoplasia, but additional studies are needed.
  • Estrogen metabolism
    DIM supplementation resulted in changes in estrogen urinary metabolites in post menopausal women with a history of early stage breast cancer.
  • Detoxification
    There is no scientific evidence to back this claim.
What are the side effects?

Case reports

Visual impairment: Occurred in a healthy female patient after excessive daily intake of DIM for 2 months. Symptoms resolved 8 weeks after discontinuing use of DIM.

Rash: Along with an increased white blood cell count following use of DIM.

What else do I need to know?

Patient Warnings:

Because of potential hormonal effects, women who are pregnant, planning to get pregnant, or nursing should not take DIM. Women who use birth control pills should consult with a healthcare professional before taking this product.

Do Not Take if:

  • You are pregnant, planning to get pregnant, nursing or use birth control pills: DIM may have hormone modulation effects.
  • You are taking CYP450 substrate drugs: DIM may make them less effective.
  • You are taking MDR1 substrate drugs: DIM may reduce their effectiveness.

Special Point:

Both DIM and I3C may alter estrogen urinary metabolite profiles in women. However, their effects on breast cancer risk are unknown.

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For Healthcare Professionals

Scientific Name
3,3'-diindolylmethane
Clinical Summary

Diindolylmethane (DIM) is a metabolite of Indole-3-carbinol (I3C), a compound found in cruciferous vegetables including broccoli, cabbage, and cauliflower. It is the most studied of all I3C metabolites and is thought to be superior to IC3 as a chemoprotective against breast and prostate cancers (3).

Preclinical studies suggest DIM has anti-inflammatory (16) (17), antiproliferative (16) and chemopreventive (18) effects and may also help increase bone mass (19).

Limited human data indicate daily supplementation with DIM may benefit patients with castration-resistant prostate cancer by inhibiting the androgen receptor (20), but studies are mixed on whether it exerts positive effects in women with cervical cell abnormalities (13) (21). Small studies suggest DIM may lead to changes in estrogen metabolism in premenopausal (26), and postmenopausal women with a history of early stage breast cancer (4). In an RCT of estrogen receptor-positive breast cancer patients taking tamoxifen, daily DIM promoted an increase in the metabolite ratio of 2-hydroxyestrone (2-OHE1, anti-tumorigenic) to 16α-hydroxyestrone (16α-OHE1, pro-tumorigenic) (25). However, this increase was coupled with a reduction in metabolites from tamoxifen. More research is needed to elucidate the pharmacokinetics and clinical efficacy of tamoxifen when taken with DIM.

Food Sources

Vegetables including broccoli, Brussels sprouts, cauliflower and cabbage (1)

Purported Uses and Benefits
  • Cancer
  • Estrogen metabolism
  • Detoxification
Mechanism of Action

In preclinical models, DIM induced apoptosis in pancreatic cancer cells (6) and enhanced effects of erlotinib (7). In colon cancer and prostate cancer cells, DIM inhibited CDK activities (8) (9) and induced apoptosis by downregulating survivin (10) (11). 

Following oral supplementation for one week, mono- and dihydroxylated metabolites as well as their sulfate and glucuronide conjugates were found in human plasma and urine within 10-12 hours (27). DIM supplementation altered estrogen urinary metabolite profiles in women (4) and had androgen-antagonistic effects (14). It also inhibited prostate cancer cell proliferation and induced apoptosis through Akt activation, NF-KB DNA binding, and androgen receptor phosphorylation (15).

Contraindications

Because of DIM’s potential hormonal effects, women who are pregnant, planning to get pregnant, or nursing should not take it. Women who use birth control pills should consult with a healthcare professional before taking this product.

Adverse Reactions

Case reports

Visual impairment: Central serous chorioretinopathy, an idiopathic disease, in a healthy female patient after excessive daily intake of DIM for 2 months. Symptoms resolved 8 weeks after discontinuing use of DIM (22).

Rash: With eosinophilia and systemic symptoms following use of DIM (23).

Ischemic Stroke: Associated with DIM supplement use in a 38-year-old woman (28).

Herb-Drug Interactions

Tamoxifen: DIM modulates Phase I metabolism through several CYP isoenzymes, resulting in favorable estrogen metabolism and sex hormone-binding globulin (SHBG) levels.  However, one clinical study showed a significant decrease in serum endoxifen, without adversely affecting breast density or SHBG (24). Endoxifen is an active metabolite of tamoxifen during Phase I metabolism, and exhibits higher affinity for ER.

Herb Lab Interactions

DIM supplementation has been shown to alter estrogen urinary metabolites in women (4).

Dosage (OneMSK Only)
References
  1. Minich DM, Bland JS. A review of the clinical efficacy and safety of cruciferous vegetable phytochemicals. Nutr Rev 2007;65(6 Pt 1):259-267.
  2. Howells LM, Moiseeva EP, Neal CP et al. Predicting the physiological relevance of in vitro cancer preventive activities of phytochemicals. Acta Pharmacol Sin 2007;28(9):1274-1304.
  3. Bradlow HL. Review. Indole-3-carbinol as a chemoprotective agent in breast and prostate cancer. In Vivo 2008;22(4):441-445.
  4. 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(2), 161-167.
  5. Higdon JV, Delage B, Williams DE, Dashwood RH. Cruciferous vegetables and human cancer risk: epidemiologic evidence and mechanistic basis. Pharmacol Res 2007;55(3):224-236.
  6. Azmi AS, Ahmad A, Banerjee S et al. Chemoprevention of pancreatic cancer: characterization of Par-4 and its modulation by 3,3’ diindolylmethane (DIM). Pharm Res 2008;25(9):2117-2124.
  7. Ali S, Banerjee S, Ahmad A et al. Apoptosis-inducing effect of erlotinib is potentiated by 3,3’-diindolylmethane in vitro and in vivo using an orthotopic model of pancreatic cancer. Mol Cancer Ther 2008;7(6):1708-1719.
  8. Choi HJ, Lim DY, Park JH. Induction of G1 and G2/M cell cycle arrests by the dietary compound 3,3’-diindolylmethane in HT-29 human colon cancer cells. BMC Gastroenterol 2009;9(1):39.
  9. Chinnakannu K, Chen D, Li Y et al. Cell cycle-dependent effects of 3,3’-diindolylmethane on proliferation and apoptosis of prostate cancer cells. J Cell Physiol 2009;219(1):94-99.
  10. Bhatnagar N, Li X, Chen Y et al. 3,3’-Diindolylmethane Enhances the Efficacy of Butyrate in Colon Cancer Prevention through Down-Regulation of Survivin.Cancer Prev Res (Phila Pa) 2009;2(6):581-589.
  11. Rahman KM, Banerjee S, Ali S et al. 3,3’-Diindolylmethane enhances taxotere-induced apoptosis in hormone-refractory prostate cancer cells through survivin down-regulation. Cancer Res 2009;69(10):4468-4475.
  12. Reed GA, Sunega JM, Sullivan DK et al. Single-dose pharmacokinetics and tolerability of absorption-enhanced 3,3’-diindolylmethane in healthy subjects. Cancer Epidemiol Biomarkers Prev 2008;17(10):2619-2624.
  13. Castañon A, Tristram A, Mesher D, et al. Effect of diindolylmethane supplementation on low-grade cervical cytological abnormalities: double-blind, randomised, controlled trial. Br J Cancer. 2012 Jan 3;106(1):45-52.
  14. Le HT, Schaldach CM, Firestone GL, 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.
  15. Bhuiyan MM, Li Y, Banerjee S, et al. Down-regulation of androgen receptor by 3,3’-diindolylmethane contributes to inhibition of cell proliferation and induction of apoptosis in both hormone-sensitive LNCaP and insensitive C4-2B prostate cancer cells. Cancer Res. 2006 Oct 15;66(20):10064-72.
  16. Prabhu B, Balakrishnan D, Sundaresan S. Antiproliferative and anti-inflammatory properties of diindolylmethane and lupeol against N-butyl-N-(4-hydroxybutyl) nitrosamine induced bladder carcinogenesis in experimental rats. Hum Exp Toxicol. 2016 Jun;35(6):685-92.
  17. Ye Y, Miao S, Wang Y, Zhou J, Lu R. 3,3’-diindolylmethane potentiates tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis of gastric cancer cells. Oncol Lett. 2015 May;9(5):2393-2397.
  18. Qian X, Song JM, Melkamu T, Upadhyaya P, Kassie F. Chemoprevention of lung tumorigenesis by intranasally administered diindolylmethane in A/J mice. Carcinogenesis. 2013 Apr;34(4):841-9.
  19. Yu TY, Pang WJ, Yang GS. 3,3’-Diindolylmethane increases bone mass by suppressing osteoclastic bone resorption in mice. J Pharmacol Sci. 2015 Jan;127(1):75-82.
  20. Li Y, Sarkar FH. Role of BioResponse 3,3’-Diindolylmethane in the Treatment of Human Prostate Cancer: Clinical Experience. Med Princ Pract. 2016;25 Suppl 2(Suppl 2):11-7.
  21. Ashrafian L, Sukhikh G, Kiselev V, et al. Double-blind randomized placebo-controlled multicenter clinical trial (phase IIa) on diindolylmethane’s efficacy and safety in the treatment of CIN: implications for cervical cancer prevention. EPMA J. 2015 Dec 21;6:25.
  22. Bussel II, Lally DR, Waheed NK. Bilateral central serous chorioretinopathy associated with estrogen modulator diindolylmethane. Ophthalmic Surg Lasers Imaging Retina. 2014 Nov-Dec;45(6):589-91.
  23. Le TM, Sanders CJ, van de Corput L, van Erpecum KJ, Röckmann H. Drug rash with eosinophilia and systemic symptoms caused by the dietary supplement diindolylmethane. J Allergy Clin Immunol Pract. 2016 Jan-Feb;4(1):175-6.
  24. Pondugula SR, Flannery PC, Abbott KL, et al. Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR. Toxicol Lett. 2015 Feb 3;232(3):580-9.
  25. Thomson CA, Chow HHS, Wertheim BC, et al. A randomized, placebo-controlled trial of diindolylmethane for breast cancer biomarker modulation in patients taking tamoxifen. Breast Cancer Res Treat. 2017 Aug;165(1):97-107.
  26. Vermillion Maier ML, Siddens LK, Uesugi SL, et al. 3,3’-Diindolylmethane Exhibits Significant Metabolism after Oral Dosing in Humans.  Drug Metab Dispos. 2021 Aug;49(8):694-705.
  27. Godínez-Martínez E, Santillán R, Sámano R, Chico-Barba G, Tolentino MC, Hernández-Pineda J. Effectiveness of 3,3’-Diindolylmethane Supplements on Favoring the Benign Estrogen Metabolism Pathway and Decreasing Body Fat in Premenopausal Women.  Nutr Cancer. 2023;75(2):510-519.
  28. Pence ST, Mehta K, Crum-Bailey J. The Serious Side of Supplements: An Ischemic Stroke in a Healthy 38-year-old Female.  Mil Med. 2023 Aug 29;188(9-10):e3273-e3275.
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