Diindoylmethane is a molecule which is named after its structure, two indole groups attached to a methane group. It is commonly found in broccoli, and holds promise as being a molecule for anti-cancer effects and as an aromatase inhibitor.

This page features 45 unique references to scientific papers.

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All Essential Benefits/Effects/Facts & Information

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Diindoylymethane (DIM) is a component of Indole-3-carbinol (I3C) found in members of the Brassica family. Most notably broccoli, kale, and cauliflower.

It has potent effects on estrogen metabolism and is able to keep the body relatively balanced (by preventing either drastic increases or decreases in estrogen). In small amounts, it can both inhibit the aromatase enzyme (and prevent conversion of testosterone into estrogen) and it can act on more potent forms of estrogen and convert them into less potent forms; this conversion reduces the overall effects of estrogen in the body. However, taking too much DIM at once can actually induce the aromatase enzyme and act in the opposite manner and increase estrogen synthesis.

DIM also exerts numerous anti-carcinogenic (anti-cancer) effects in the body and is one of the reasons this vegetable family is seen as healthy.

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Things to Know

Also Known As

DIM, 3, 3'-diindolylmethane

Do Not Confuse With

Indole-3-Carbinol (it's precursor), Sulforaphane (another Broccoli Bioactive)

Things to Note

Diindolylmethane is non-stimulatory

Goes Well With

  • Phenyl Isothiocyanate

Caution Notice

Examine.com Medical Disclaimer

How to Take

Recommended dosage, active amounts, other details

A supplemental dose of approximately 100mg DIM has been noted to alter urinary estrogens in a manner thought to reflect less estrogenicity.

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Scientific Research

Table of Contents:

  1. 1 Sources and Structure
    1. 1.1 General
    2. 1.2 Sources
    3. 1.3 Cooking and Processing
  2. 2 Molecular Targets
  3. 3 Pharmacology
    1. 3.1 Absorption
    2. 3.2 Phase I Enzyme Interactions
  4. 4 Obesity and Fat Mass
    1. 4.1 Weight and Body Fat
  5. 5 Inflammation and Immunology
    1. 5.1 Natural Killer Cells
  6. 6 Interactions with Hormones
    1. 6.1 Estrogen
  7. 7 Interactions with Oxidation
    1. 7.1 DNA Damage
  8. 8 Interactions with Cancer Metabolism
    1. 8.1 Breast
    2. 8.2 Cervical and Uterine
    3. 8.3 Prostate
  9. 9 Nutrient-Nutrient Interactions
    1. 9.1 Other Glucosinolates

1Sources and Structure

1.1. General

Diindolylmethane (DIM) is the primary pharmaceutically active acid-derived metabolic of Indole-3-Carbinol (I3C) which is found in many Brassica vegetables via the mother compound glucobrassicin.[1][2][3] Ingested glucobrassicin is catalyzed via the enzyme Myrosinase (stored in vegetables) and turns into Indole-3-Carbinol, which is rapidly digested into both DIM and various other metabolites in the human stomach via acid-mediated condensation reacitons.[4][5]

1.2. Sources

Sources of Glucosinolates (in general) are listed below, with any source mentioning diindolylmethane or its precursor (Indole-3-Carbinol) specifically being mentioned in bold:

  • Brussel Sprouts, at 104mg per 44g (half cup)[6]

  • Garden Cress, 98mg at 25g (half cup)[6]

  • Mustard Greens, 79mg at 28g (half cup, chopped)[6]

  • Turnip, 60mg at 65g (half cup, cubes)[6]

  • Savoy Cabbage, 35mg at 45g (half cup, chopped)[6]

  • Kale, 67mg per 67g (1 cup, chopped)[6]

  • Watercress, 32mg per 34g (1 cup, chopped)[6]

  • Kohlrabi, 31mg per 67g (half cup, chopped)[6]

  • Red Cabbage, 29mg per 45g (half-cup, chopped)[6]

  • Broccoli, 27mg per 44g (half cup, chopped)[6]

  • Horseradish, 24mg per 15g (tablespoon)[6]

  • Cauliflower, 22mg per 50g (half-cup chopped)[6]

  • Bok Choy, 19mg per 35g (half cup, chopped)[6]

1.3. Cooking and Processing

As glucobrassicin degrades into I3C by the plant-contained enzyme Myrosinase, deactivation of this enzyme by heat-treatment (cooking) can reduce the oral bioavailability of any glucosinolate including DIM.[7][8] Some bioavailability is retained, however, due to human intestines expressing Myrosinase as well.[9]

Boiling[10] and microwaving (750-900 watts)[11][12] seem most suspect in reducing glucosinolate bioavailability; the former due to excess water sapping water-soluble bioactives from the food. Along these lines, cooking methods that utilize less water retain more glucosinolates than do those using lots of water.[13]

Glucosinolates can have their absorption rates reduced by cooking, and low temperature steaming may be the most efficient way to preserve glucosinolate content of vegetables

2Molecular Targets

DIM has been shown to active nuclear factor kappa-beta (NF-kB) signalling, caspase activation, cytochrome P450 activation (specifically CYP1A1, CYP1A2, and CYP19), DNA repair, the aryl hydrocarbon receptor (AHR) and various protein kinases.[14][15][16]


3.1. Absorption

Indole-3-carbinol (I3C) primarily acts via its major metabolite, diindolylmethane (DIM) (may comprise up to a third of I3C products[4]) and some other metabolites which can be spontaneously produced from the unstable I3C (such as indolo{3,2-b}carbazole,[17] a minor constituent[4]). The precise formation of these metabolites involves I3C catalyzing to form reactive indoles which then combine with one another to 'build' up a larger yet stable molecule, DIM being the result of two of these indoles forming.[4]

3.2. Phase I Enzyme Interactions

Dietary indole-3-carbinol (I3C), via the metabolite DIM, can increase the weight of the liver thought to be reflective of a general increase in P450 enzyme production;[18] this appears to be dose dependent between low dietary concentrations (250ppm) up to very high ones (5,000ppm) with the 2-hydroxylation of estrogen increasing in relation to overall liver weight.[18]

4Obesity and Fat Mass

4.1. Weight and Body Fat

One study using Indole-3-Carbinol noted that 5mg injections into the gut daily was able to attenuate the expected gain in body fat associated with a high fat/calorie diet.[19]

5Inflammation and Immunology

5.1. Natural Killer Cells

The aryl hydrocarbon receptor (AhR) has been noted to have a role in some immune cells, and in natural killer (NK) cells activation of this receptor (seen with 10µM 3,3′-diindolylmethane[20]) can increase the production of IFN-γ and effector function, thereby increasing their inhibition of cancer cell growth.[20]

6Interactions with Hormones

6.1. Estrogen

3,3'-diindolylmethane (DIM) has been noted to activate both the alpha subset of the estrogen receptor (ERα)[21] and the beta subset (ERβ),[22][23] with DIM promoting cellular growth via ERα[21]not due to being a direct ligand[24] while increased signalling via ERβ (15μM) also seems to be mediated indirectly.[22][23]

Activation of ERα may be dependent on the cell type, as similar concentrations (10-15μM; the lower concentration being proposed to be attained via a cruciferous rich diet[25]) have shown efficacy in acting on this receptor in MCF7 and T47D breast cancer cells[21] yet not MDA-MB-231 or HeLa cells,[22] or may be due to sensitivity, as even in responsive cells higher concentrations (50μM) fail to cause a response.[21] The indirect activation is known to be mediated predominately via activation of PKA[21][24] which then activates MAPK and CREB.[24]

DIM can activate both subsets of the estrogen receptor (in tested breast cancer cells) in an indirect manner, secondary to activating a protein known as PKA. At this moment in time these effects have only been observed in cancerous cells, and it may be exclusive to low (dietary) concentrations of DIM

The higher concentration of DIM seems to induce AhR responsive genes in breast cancer cells (CYP1A1 and CYP1B1[21]) suggesting a differing mechanisms dependent on concentration. Activation of AhR per se induces production of some of these Phase I enzymes[26] which is a mechanism of estrogenicity (via increasing aromatase activity) seen with a few environmental estrogens[27] but due to the lesser affinity of DIM towards the AhR than select environmental estrogens (PCBs, Dioxins, and PAHs) combination of the two may result in less overall estrogenicity relative to the environmental estrogens alone.[28][29][30]

Activation of AhR is in and of itself proestrogenic via increasing the expression of the aromatase enzyme (CYP1A1), but due to a lesser competitive activation from DIM it seems that when it is taken alongside more potent ligands found in the environment (ex. PAHs from smoked meat products) may result in less net estrogenicity

DIM has been implicated in modifying preexisting estrogen steroids into other metabolites. The process of 2-hydroxylation, likely secondary to AhR activation,[31] may increase the ratio of 2-hydroxyestrone to 16α-hydroxyestrone which is thought to be a less estrogenic profile of estrogen steroids.[32] The processes of 4-hydroxylation and 16-hydroxylation do not appear significantly affected.[33]

Indole-3-carbinol has been noted to induce 2-hydroxyestrone secondary to an increase in the process of 2-hydroxylation[34] and oral supplementation of DIM (108mg) in women with histories of early stage breast cancer has been noted to increase urinary 2-hydroxyestrone concentrations (alongside a nonsignificant increase of the 2-hydroxyestrone to 16α-hydroxyestrone ratio.[35] In rats given dietary I3C for a prolonged period of time 200-1,000ppm appeared to be effective in increasing 2-hydroxylation of estradiol with efficacy peaking to a near double around 600-1,000ppm (17.6-36.3mg/kg),[25] translating to around 3-6mg/kg in an adult human.

Secondary to activating AhR activity, it is possible for DIM to increase the process of 2-hydroxylation and cause a shift in preexisting estrogen metabolites to a profile which is seen as less estrogenic; evidence for this has been seen in women given low dose supplements

7Interactions with Oxidation

7.1. DNA Damage

Injections of DIM in rats for two weeks prior to total body irradiation noted dose-dependent improvements in survivial (up to 60% from 75mg/kg), and while 7.5mg/kg was ineffective when given over this time period a single dose one day before radiation appeared to confer 55% survival.[36] This protective effect was thought to be due to activation of ataxia-telangiectasia mutated (ATM), a repair enzyme which increases in activity in response to genetic damage,[37] seen with 300nM DIM thought to be secondary to inhibiting PP2A (MRE11 and BRCA1 also required);[36] PP2A normally complexes with ATM keeping it in an inactive state, and its inhibition allows ATM to become hyperactive in response to genetic damage.[38]

Low concentrations of DIM appear to allow a genetic repair enzyme (ATM) to be more responsive when incubated alongside an oxidative stressor that damages DNA

8Interactions with Cancer Metabolism

8.1. Breast

In normal tissue, DIM (300nM) can activate the ATM genetic repair pathway in response to irradiation damage in a manner dependent on BRCA1 (one of its targets[36]) without increasing survival of breast cancer cells (MDA-MB-231[36]); there are known alterations in this pathway in some breast cancers where BRCA1 is reduced while ATM itself seems to be hyperactive, and oral supplementation of 300mg DIM has been noted to increase BRCA1 mRNA levels after 4-6 weeks supplementation (measured in white blood cells) in women who had a low activity mutation.[39]

A few animal studies (using DIM or its precursor I3C) finding anticancer effects on breast cancer cells note that these changes occur alongside increases in 2-hydroxylation of estradiol,[40][18] which appears to be dose-dependent up to very large oral doses (5,000ppm in mice or over 10g/kg relative to bodyweight).[18]

Mechanistically, DIM appears to increase the activity of a genetic repair enzyme which is reduced in some breast cancers which is thought to confer protective effects. The actions on 2-hydroxylation also appear to be relevant as they may confer an antiestrogenic effect

In rats, oral ingestion of indole-3-carbinol (I3C) for a week prior to induction of mammary cancer via DMBA significantly reduced incidence (70-90%) and multiplicity (91-96%) relative to carcinogen control,[40] also showing efficacy on the direct acting carcinogen N-Nitroso-N-methylurea but to a lesser degree (65% reduction in multiplicity).[40]

Spontaneous rather than toxin-induced tumor growth also appears to be just under halved in one study (lasting 250 days) in rats fed 64-128mg/kg I3C in the diet (estimated intake relative to bodyweight being 4.8-9.6g/kg) compared to control, with multiplicity also being somewhat reduced.[18]

8.2. Cervical and Uterine

In rats predisposed to endometrial cancer (Donryu rats) given dietary levels of indole-3-carbinol (I3C; 200-1,000ppm) and assessed for a prolonged experimental period, rates of spontaneous neoplasms in the uterus after 660 days were significantly higher in controls (38%) rather than the low dose of I3C (25%) with 600-1,000ppm performing equally (14-16%);[25] this effect was seen alongside increased 2-hydroxylation of estradiol.[25]

8.3. Prostate

DIM has been noted to antagonize the effects of dihydrotestosterone (DHT) in prostatic cancer cells (LNCaP and PC-3) by more than 50% at a concentration of 1μM in a manner dependent on the androgen receptor, it appeared to be a direct antagonist at the receptor with similar affinity as Casodex.[41]

The anticancer effects of DIM at the level of the prostate cell do not appear to be wholly dependent on this receptor though nor are they dependent on p53 (DU145 cells[42]) and can induce cell arrest in a manner dependent on inducing p27(Kip1) via Sp1 (10μM),[42] two proteins that tend to have lower activity in androgen-independent prostate cells.[43] This was downstream p38 activation[42] known to occur with DIM in other cancer cells as well.[44]

9Nutrient-Nutrient Interactions

9.1. Other Glucosinolates

DIM shows potential synergism with Phenethyl Isothiocyanate (PEITC, derived from Gluconasturtiin and found in Brassica vegetables like watercress) in regards to inducing the antioxidant enzyme Nrf2.[45]

Scientific Support & Reference Citations


  1. Aggarwal BB, Ichikawa H Molecular targets and anticancer potential of indole-3-carbinol and its derivatives. Cell Cycle. (2005)
  2. Pappa G, et al. Quantitative combination effects between sulforaphane and 3,3'-diindolylmethane on proliferation of human colon cancer cells in vitro. Carcinogenesis. (2007)
  3. Bradfield CA, Bjeldanes LF Structure-activity relationships of dietary indoles: a proposed mechanism of action as modifiers of xenobiotic metabolism. J Toxicol Environ Health. (1987)
  4. Grose KR, Bjeldanes LF Oligomerization of indole-3-carbinol in aqueous acid. Chem Res Toxicol. (1992)
  5. De Kruif CA, et al. Structure elucidation of acid reaction products of indole-3-carbinol: detection in vivo and enzyme induction in vitro. Chem Biol Interact. (1991)
  6. McNaughton SA, Marks GC Development of a food composition database for the estimation of dietary intakes of glucosinolates, the biologically active constituents of cruciferous vegetables. Br J Nutr. (2003)
  7. Shapiro TA, et al. Chemoprotective glucosinolates and isothiocyanates of broccoli sprouts: metabolism and excretion in humans. Cancer Epidemiol Biomarkers Prev. (2001)
  8. Conaway CC, et al. Disposition of glucosinolates and sulforaphane in humans after ingestion of steamed and fresh broccoli. Nutr Cancer. (2000)
  9. Shapiro TA, et al. Human metabolism and excretion of cancer chemoprotective glucosinolates and isothiocyanates of cruciferous vegetables. Cancer Epidemiol Biomarkers Prev. (1998)
  10. Rouzaud G, Young SA, Duncan AJ Hydrolysis of glucosinolates to isothiocyanates after ingestion of raw or microwaved cabbage by human volunteers. Cancer Epidemiol Biomarkers Prev. (2004)
  11. Verkerk R, Dekker M Glucosinolates and myrosinase activity in red cabbage (Brassica oleracea L. var. Capitata f. rubra DC.) after various microwave treatments. J Agric Food Chem. (2004)
  12. Rungapamestry V, et al. Changes in glucosinolate concentrations, myrosinase activity, and production of metabolites of glucosinolates in cabbage (Brassica oleracea Var. capitata) cooked for different durations. J Agric Food Chem. (2006)
  13. Song L, Thornalley PJ Effect of storage, processing and cooking on glucosinolate content of Brassica vegetables. Food Chem Toxicol. (2007)
  14. Weng JR, et al. Indole-3-carbinol as a chemopreventive and anti-cancer agent. Cancer Lett. (2008)
  15. Aromatic hydrocarbon responsiveness-receptor agonists generated from indole-3-carbinol in vitro and in vivo: comparisons with 2,3,7,8-tetrachlorodibenzo-p-dioxin.
  16. 2,3,7,8-Tetrachlorodibenzo-p-dioxin and Diindolylmethanes Differentially Induce Cytochrome P450 1A1, 1B1, and 19 in H295R Human Adrenocortical Carcinoma.
  17. Riby JE1, et al. The major cyclic trimeric product of indole-3-carbinol is a strong agonist of the estrogen receptor signaling pathway. Biochemistry. (2000)
  18. Effects of dietary indole-3-carbinol on estradiol metabolism and spontaneous mammary tumors in mice.
  19. Chang HP, et al. Antiobesity activities of indole-3-carbinol in high-fat-diet-induced obese mice. Nutrition. (2011)
  20. Shin JH1, et al. Modulation of natural killer cell antitumor activity by the aryl hydrocarbon receptor. Proc Natl Acad Sci U S A. (2013)
  21. Marques M, et al. Low levels of 3,3'-diindolylmethane activate estrogen receptor α and induce proliferation of breast cancer cells in the absence of estradiol. BMC Cancer. (2014)
  22. Selective Activation of Estrogen Receptor-β Target Genes by 3,3′-Diindolylmethane.
  23. Lo R, Matthews J A new class of estrogen receptor beta-selective activators. Mol Interv. (2010)
  24. Leong H1, et al. Potent ligand-independent estrogen receptor activation by 3,3'-diindolylmethane is mediated by cross talk between the protein kinase A and mitogen-activated protein kinase signaling pathways. Mol Endocrinol. (2004)
  25. Leong H1, 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)
  26. Sanderson JT, et al. 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)
  27. Ah receptor agonists as endocrine disruptors: antiestrogenic activity and mechanisms.
  28. Okino ST, et al. Toxic and chemopreventive ligands preferentially activate distinct aryl hydrocarbon receptor pathways: implications for cancer prevention. Cancer Prev Res (Phila). (2009)
  29. Parkin DR, et al. Inhibitory effects of a dietary phytochemical 3,3'-diindolylmethane on the phenobarbital-induced hepatic CYP mRNA expression and CYP-catalyzed reactions in female rats. Food Chem Toxicol. (2008)
  30. Wattenberg LW, Loub WD Inhibition of polycyclic aromatic hydrocarbon-induced neoplasia by naturally occurring indoles. Cancer Res. (1978)
  31. Jellinck PH1, et al. Ah receptor binding properties of indole carbinols and induction of hepatic estradiol hydroxylation. Biochem Pharmacol. (1993)
  32. Estrogenic and antiestrogenic activities of 16α- and 2-hydroxy metabolites of 17β-estradiol in MCF-7 and T47D human breast cancer cells.
  33. Sepkovic DW, et al. Catechol estrogen production in rat microsomes after treatment with indole-3-carbinol, ascorbigen, or beta-naphthaflavone: a comparison of stable isotope dilution gas chromatography-mass spectrometry and radiometric methods. Steroids. (1994)
  34. Bradlow HL, et al. 2-hydroxyestrone: the 'good' estrogen. J Endocrinol. (1996)
  35. Dalessandri KM1, 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)
  36. Fan S1, et al. DIM (3,3'-diindolylmethane) confers protection against ionizing radiation by a unique mechanism. Proc Natl Acad Sci U S A. (2013)
  37. Kitagawa R1, Kastan MB The ATM-dependent DNA damage signaling pathway. Cold Spring Harb Symp Quant Biol. (2005)
  38. Goodarzi AA1, et al. Autophosphorylation of ataxia-telangiectasia mutated is regulated by protein phosphatase 2A. EMBO J. (2004)
  39. Kotsopoulos J1, et al. BRCA1 mRNA levels following a 4-6-week intervention with oral 3,3'-diindolylmethane. Br J Cancer. (2014)
  40. Grubbs CJ1, et al. Chemoprevention of chemically-induced mammary carcinogenesis by indole-3-carbinol. Anticancer Res. (1995)
  41. Le HT, et al. Plant-derived 3,3'-Diindolylmethane is a strong androgen antagonist in human prostate cancer cells. J Biol Chem. (2003)
  42. Vivar OI1, et al. 3,3'-Diindolylmethane induces a G(1) arrest in human prostate cancer cells irrespective of androgen receptor and p53 status. Biochem Pharmacol. (2009)
  43. Karan D1, et al. Expression profile of differentially-regulated genes during progression of androgen-independent growth in human prostate cancer cells. Carcinogenesis. (2002)
  44. Xue L1, Firestone GL, Bjeldanes LF DIM stimulates IFNgamma gene expression in human breast cancer cells via the specific activation of JNK and p38 pathways. Oncogene. (2005)
  45. Saw CL, et al. Pharmacodynamics of dietary phytochemical indoles I3C and DIM: Induction of Nrf2-mediated phase II drug metabolizing and antioxidant genes and synergism with isothiocyanates. Biopharm Drug Dispos. (2011)

(Common misspellings for Diindolylmethane include dindoylmethane, diindoylmethane, dindolylmethane, diindolilmethane, dindoilmethane)