Here is a little piece written by Scott Stevenson:
3,3’-Diindolylmethane (DIM)
DIM is the primary metabolite of Indole 3 Carbinol(I3C), a compound found in cruciferous vegetables (like broccoli, cauliflower, radishes and turnips)(1). It has been widely studied for its anticancer effects(2), in particular in protecting against or halting the progression of estrogen and androgen-sensitive cancers like breast and prostate cancer. DIM is also used to treat respiratory papillomas(3) and has an anti-proliferative effect on thyroid goiter cells, contrary to the belief that DIM is goitrogenic(4).
DIM demonstrates an anti-androgenic effect in prostate cancer by inhibiting effects of dihydrotestosterone (DHT)(5), likely by directly competing for DHT at the androgen receptor(5, 6). Like its parent compound I3C, DIM has diverse effects on estrogen metabolism, favoring the formation of anti-estrogenic metabolites at the expense of estrogenic ones(7, 8). Interestingly, DIM in and of itself is actually an agonist (activator) of the human estrogen receptor (6), which may explain the notion that DIM “balances” estrogen’s effects. DIM may be superior as a supplement to I3C for those minimizing estrogenic effects, because, unlike I3C, DIM does not affect metabolism of the anti-breast cancer drug (estrogen receptor antagonist) tamoxifen or increase its toxic metabolites(8). Additionally, at least in rats, DIM does not disrupt the hypothalamic pituitary ovarian axis (involved in estrogen synthesis) in the manner that I3C does(9).
The effects of DIM are largely attributed to its diverse effects on the cytochromes p450 (CYP)(10-12), a large hepatic enzyme group involved in metabolism of a great many drugs and toxins by the liver(13). Because of this, please consult your healthcare professional about possible interactions DIM may have with any medications you are taking.
Benefits and Risks
DIM may be helpful in minimizing possible cancer risks of hormone replacement (both estrogen and testosterone based) by affecting the actions of these hormones on the breast and prostate, as well as confer anti-tumor effects on the thyroid, lung and colon(14). On the other hand, it should be noted that excessively high doses seem to be associated with toxicity and pro-tumor effects in animal research(15). However, when the equivalent of a human dose of ~600mg / day (for a 220lb bodybuilder; 2-3 times the typically suggested dose), was given to rats for 32 days, neither body weight, blood chemistry nor histology of liver, kidney or bone(16) were affected, suggesting minimal adverse consequences, at least for rodents, at this dose.
In one study of healthy adults(15), increasing the dose of DIM from 200mg to 300mg did not further elevate DIM blood levels. Additionally, side effects below 300mg/day were not found to be dose-dependent. As reviewed by Reed et al.(15), compared to an equivalent dose of I3C, oral supplementation with DIM produces 2-3 times higher DIM, and is well tolerated in the 200-400mg / day range, when split over two doses.
Supplement Use
The above suggests that a daily dose of 100-200mg, spread over two doses, DIM could be used to protect against potential adverse effects of supplements that may elevate blood hormone levels, such as D-Aspartic Acid , Tribulus Terrestris or MG’s Super Test Booster. Patients concerned with possible elevation of cancer risk associated with hormone replacement therapy (estrogen(17) or testosterone (18)should check with their respective physicians to see if DIM may be a useful adjunctive prophlactic against tumorigenesis. Naturally, the anti-cancer benefits of DIM make it an attractive addition to a supplement regime geared toward health and longevity, especially in the face of familial history of cancer. PLEASE CONSULT YOUR HEALTHCARE PROVIDER before taking DIM if you are current taking any prescribed or over-the-counter medications, as DIM may affect drug metabolism and necessitate dosage adjustment.
DISCLAIMER: The above description is provided for information only and does not constitute medical advice. Please consult your physician or the appropriately licensed professional before engaging in a program of exercise of nutritional supplementation.
References
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2. Weng, J.R., et al., Indole-3-carbinol as a chemopreventive and anti-cancer agent. Cancer letters, 2008. 262(2): p. 153-63. Indole-3-carbinol as a chemopreventive and anti-cancer agent. - PubMed - NCBI
3. Wiatrak, B.J., Overview of recurrent respiratory papillomatosis. Current opinion in otolaryngology & head and neck surgery, 2003. 11(6): p. 433-41. Overview of recurrent respiratory papillomatosis. - PubMed - NCBI
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12. Lake, B.G., et al., 3,3'-Diindolylmethane induces CYP1A2 in cultured precision-cut human liver slices. Xenobiotica; the fate of foreign compounds in biological systems, 1998. 28(8): p. 803-11.
3,3'-Diindolylmethane induces CYP1A2 in cultured precision-cut human liver slices. - PubMed - NCBI
13. Rendic, S., Summary of information on human CYP enzymes: human P450 metabolism data. Drug metabolism reviews, 2002. 34(1-2): p. 83-448.
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14. Bonnesen, C., et al., Dietary indoles and isothiocyanates that are generated from cruciferous vegetables can both stimulate apoptosis and confer protection against DNA damage in human colon cell lines. Cancer research, 2001. 61(16): p. 6120-30.
Dietary indoles and isothiocyanates that are generated from cruciferous vegetables can both stimulate apoptosis and confer protection against DNA d... - PubMed - NCBI
15. Reed, G.A., et al., Single-dose pharmacokinetics and tolerability of absorption-enhanced 3,3'-diindolylmethane in healthy subjects. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2008. 17(10): p. 2619-24.
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