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Diindoylmethane (DIM) 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.

Our evidence-based analysis on diindolylmethane features 45 unique references to scientific papers.

Research analysis led by and reviewed by the Examine team.
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Research Breakdown on Diindolylmethane

1Sources and Structure


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]


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]

1.3Cooking 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]



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]

3.2Phase 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

4.1Weight 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

5.1Natural 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


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

7.1DNA 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


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]

8.2Cervical 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]


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

9.1Other 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]


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