Diindolylmethane

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 28 unique references to scientific papers.

Confused about what actually Works?
Check Out The Supplement-References Guide

   

Confused about Supplements? Get Your Questions Answered Immediately

In Progress

This page on Diindolylmethane is currently marked as in-progress. We are still compiling research.

You can help contribute by:



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.

Follow this Page for updates

Also Known As

DIM, 3,3'-diindolylmethane


Do Not Confuse With

Indole-3-Carbinol, Sulforaphane (another Broccoli Bioactive)


Things to Note

Diindolylmethane is non-stimulatory

Goes Well With

  • Phenyl Isothiocyanate

Caution Notice

Examine.com Medical Disclaimer
Table of Contents:


Edit1. Sources and Structure

1.1. General

Diindolylmethane (henceforth 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 sources of Indole-3-Carbinol and DIM in bold. A source of DIM may contain less than the listed glucosinolate total:

  • 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, 32g 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


Edit2. Molecular 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]


Edit4. Interactions with Hormones

4.1. Estrogen

DIM appears to be an estrogen regulatory compound, as it possesses both pro-estrogenic and anti-estrogenic mechanisms of action.

In a pro-estrogenic sense, DIM is known as an estrogen receptor beta agonist, and exerts these effects through non-ligand (binding) means, theorized to be through protein kinases.[17][18]

In the liver, activation of the Aryl Hydrocarbon receptor (AhR) is an area of focus when looking at estrogenic effects of DIM.[19] Binding to the Ah receptor (in general) can cause more aromatase to be synthesized and cause greater conversion of testosterone to estroge, and DIM can bind to the Ah receptor as well as directly induce the aromatase enzyme causing it to increase.[20] However, its binding to the AhR is weak, and coingestion of DIM alongside PCBs or Dioxins (common industrial estrogenic compounds) causes less of a spike in estrogen than isolated PCBs or Dioxins, and relatively less estrogenic activity.[21][22]

When looking at the enzymes of P450 and liver detoxification, DIM appears to inherently be pro-estrogenic but may act as an antagonist in the presence of stronger estrogens and thus cause a relative decline

Beyond liver enzyme interactions, the modification of estrogen metabolites also produces an ultimate state in which more of the 2-hydroxyestrogens relative to 16a-hydroxyestrogens and 4-hydroxyestrogens results in less overall estrogenic actions in vivo.[23] This is due to induction (activation) of the estradiol-2-hydroxylase enzyme, an enzyme that converts estrogens and estrones to their 2-hydroxylated form which is seen as chemoprotective [23][24] and in some cases anti-estrogenic[25] while not influencing 4 and 16a-hydroxlyation, two metabolites which are genotoxic and retain estrogenic properties.[26]

'Estrogen' is a term used to refer to a class of molecules with similar activities (sort of like how 'Androgen' is a blanket statement for many molecules), and DIM can cause a shift in estrogen ratios to cause less estrogenic effects

4.2. Testosterone

In regards to androgen metabolism, DIM appears to be a strong antagonist in human prostate cancer cells.[27]


Edit5. Nutrient-Nutrient Interactions

5.1. Other Glucosinolates

DIM shows potential synergism with Phenethyl Isothiocyanate (PEITC, derived from Gluconasturtiin and found in watercress), a compound found in Brassica vegetables alongside I3C.[28]

References

  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. Chang HP, et al. Antiobesity activities of indole-3-carbinol in high-fat-diet-induced obese mice. Nutrition. (2011)
  17. Selective Activation of Estrogen Receptor-β Target Genes by 3,3′-Diindolylmethane
  18. Lo R, Matthews J. A new class of estrogen receptor beta-selective activators. Mol Interv. (2010)
  19. Ah receptor agonists as endocrine disruptors: antiestrogenic activity and mechanisms
  20. 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)
  21. Okino ST, et al. Toxic and chemopreventive ligands preferentially activate distinct aryl hydrocarbon receptor pathways: implications for cancer prevention. Cancer Prev Res (Phila). (2009)
  22. 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)
  23. Bradlow HL, et al. 2-hydroxyestrone: the 'good' estrogen. J Endocrinol. (1996)
  24. Jellinck PH, et al. Ah receptor binding properties of indole carbinols and induction of hepatic estradiol hydroxylation. Biochem Pharmacol. (1993)
  25. Estrogenic and antiestrogenic activities of 16α- and 2-hydroxy metabolites of 17β-estradiol in MCF-7 and T47D human breast cancer cells
  26. 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)
  27. Le HT, et al. Plant-derived 3,3'-Diindolylmethane is a strong androgen antagonist in human prostate cancer cells. J Biol Chem. (2003)
  28. 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)

(Common phrases used by users for this page include how much dim supplement should i take, dim supplement testimonials, dim diindolylmethane examine.com, dim content vegetables, dim content of broccoli, Dim anti aromatase supplement)

(Users who contributed to this page include , )