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Diindolylmethane (DIM) and PCOS: Is there a benefit?

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DIM is a phytonutrient which is formed when indole-3-carbinol (I3C) is broken down.  I3C can be found in cruciferous vegetables such as those in the Brassica family like red cabbage, kale, broccoli, Brussel sprouts and cauliflower.  Diindoylmethane derives its name from its molecular structure, two indole groups attached to a methane group.  It is primarily an oestrogen regulating compound, having the ability to either increase or decrease oestrogen synthesis depending upon the dose.  In addition to its effects on oestrogen metabolism, DIM is also being studied for its anti-inflammatory effects, anti-cancer properties and its ability to stimulate the immune system.  In particular it may offer some benefit to diseases which are caused by the human papilloma virus or HPV, such as cervical dysplasia and respiratory papillomatosis.  It’s anti-cancer properties and cancer-preventative properties are related predominantly to its effect on regulating the hormones oestrogen and testosterone, affecting the development of hormonally-driven cancers such as those of the breast, prostate, ovaries and uterus.

DIM or diindolylmethane has been found to improve estrogen metabolism by altering liver function in a way which increases the rate at which oestrogens are metabolised into inactive forms, thus clearing excess from the body, which is generally beneficial in PCOS as most women with the condition also have a relative oestrogen dominance.  It also blocks some effects of oestrogen, though it may increase others.  It is also an anti-androgen, reducing the amount of testosterone in the body, which is also usually a hallmark feature of PCOS.

 ”We have focussed our attention on indole-3-carbinol, a compound found in cruciferous vegetables, and its further metabolites in the body, diindolylmethane (DIM) and indolylcarbazole (ICZ), because of its relative safety and multifaceted activities. It has been shown that it induces CyP4501A1, increasing 2-hydroxylation of estrogens, leading to the protective 2-OHE1, and also decreases CyP1B1 sharply, inhibiting 4-hydroxylation of estradiol, thereby decreasing the formation of the carcinogenic 4-OHE1. In addition to these indirect effects as a result of altered estrogen metabolism, indole-3-carbinol has been shown to have direct effects on apoptosis and cyclin D, resulting in blockage of the cell cycle. In addition to its antitumor activity in animals, it has also been shown to be effective against HPV-mediated tumors in human patients. All of these responses make the study of its behavior as a therapeutic agent of considerable interest.”  Bradlow et al, 1999

Because cooking reduces the bioavailability of DIM in foods through destruction of the myrosinase enzyme which is stored in vegetables and converts I3C into DIM, a supplement may be beneficial in moderate doses, however, in the first instance increasing the amount of Brassicas in the diet should be considered.  It should be noted, that whilst DIM has been found to inhibit the aromatase enzyme in small doses, preventing the conversion of testosterone into oestrogen, converting potent forms of oestrogen into less potent forms and reducing the effects of oestrogen excess on the body, in higher doses it can actually increase the activity of the aromatase enzyme, increasing oestrogen synthesis and the effects that oestrogen has on the human body.

The human intestines also produce small amounts of the enzyme required to convert I3C into DIM, so even cooked Brassicas will provide some DIM.

DIM may assist in managing some of the symptoms of PCOS which are due to oestrogen dominance, however, it is only an auxiliary treatment.  Addressing the root cause of the oestrogen dominance should be of primary importance in treating PCOS.  The hormonal abnormalities which present in PCOS generally result from insulin resistance, which then disrupts other hormones.

Sources:

Acharya A, Das I, Singh S, & Saha T. (2010) Chemopreventive properties of indole-3-carbinol, diindolylmethane and other constituents of cardamom against carcinogenesis.Recent patents on food, nutrition & agriculture, 2(2), 166-77. PMID: 20653562

Bradlow HL, Sepkovic DW, Telang NT, & Osborne MP. (1999) Multifunctional aspects of the action of indole-3-carbinol as an antitumor agent. Annals of the New York Academy of Sciences, 204-13. PMID: 10668495

Castañon, A.; Tristram, A.; Mesher, D.; Powell, N.; Beer, H.; Ashman, S.; Rieck, G.; Fielder, H. et al. (2011). “Effect of diindolylmethane supplementation on low-grade cervical cytological abnormalities: Double-blind, randomised, controlled trial”British Journal of Cancer 106 (1): 45–52. PMID 22075942

Chen I, McDougal A, Wang F, & Safe S. (1998) Aryl hydrocarbon receptor-mediated antiestrogenic and antitumorigenic activity of diindolylmethane. Carcinogenesis, 19(9), 1631-9. PMID: 9771935

Chen I, Hsieh T, Thomas T, & Safe S. (2001) Identification of estrogen-induced genes downregulated by AhR agonists in MCF-7 breast cancer cells using suppression subtractive hybridization. Gene, 262(1-2), 207-14. PMID: 11179685

Dalessandri KM, Firestone GL, Fitch MD, Bradlow HL, & Bjeldanes LF. (2004) Pilot study: effect of 3,3?-diindolylmethane supplements on urinary hormone metabolites in postmenopausal women with a history of early-stage breast cancer. Nutrition and cancer, 50(2), 161-7. PMID: 15623462

Ge X, Yannai S, Rennert G, Gruener N, & Fares FA. (1996) 3,3?-Diindolylmethane induces apoptosis in human cancer cells. Biochemical and biophysical research communications, 228(1), 153-8. PMID: 8912651

Gong Y. Sohn H. Xue L. Firestone GL. Bjeldanes LF (2006). “3,3?-Diindolylmethane is a novel mitochondrial H(+)-ATP synthase inhibitor that can induce p21(Cip1/Waf1) expression by induction of oxidative stress in human breast cancer cells”. Cancer Research 66 (9): 4880–4887. PMID 16651444

Kim YS. Milner JA (2005). “Targets for indole-3-carbinol in cancer prevention”. Journal of Nutritional Biochemistry 16 (2): 65–73. PMID 15681163

Le HT, Schaldach CM, Firestone GL, & Bjeldanes LF. (2003) Plant-derived 3,3?-Diindolylmethane is a strong androgen antagonist in human prostate cancer cells. The Journal of biological chemistry, 278(23), 21136-45. PMID: 12665522

Lord RS, Bongiovanni B, & Bralley JA. (2002) Estrogen metabolism and the diet-cancer connection: rationale for assessing the ratio of urinary hydroxylated estrogen metabolites.Alternative medicine review : a journal of clinical therapeutic, 7(2), 112-29. PMID: 11991791

McDougal A, Gupta MS, Morrow D, Ramamoorthy K, Lee JE, & Safe SH. (2001) Methyl-substituted diindolylmethanes as inhibitors of estrogen-induced growth of T47D cells and mammary tumors in rats. Breast cancer research and treatment, 66(2), 147-57. PMID: 11437101

Rajoria S, Suriano R, Parmar PS, Wilson YL, Megwalu U, Moscatello A, Bradlow HL, Sepkovic DW, Geliebter J, Schantz SP…. (2011) 3,3?-diindolylmethane modulates estrogen metabolism in patients with thyroid proliferative disease: a pilot study. Thyroid : official journal of the American Thyroid Association, 21(3), 299-304. PMID: 21254914

Rogan EG (2006). “The natural chemopreventive compound indole-3-carbinol: state of the science”. In Vivo 20 (2): 221–228. PMID 16634522
http://examine.com/supplements/Diindolylmethane/
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