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DIM (3,3’-diindolylmethane) is the stable, bioactive metabolite formed when stomach acid breaks down indole-3-carbinol (I3C), a sulfur-containing glucosinolate present in cruciferous vegetables.[1] Supplementation with DIM is preferred over I3C due to I3C’s undesirable breakdown products, including the dioxin-like molecule indolo[3,2-b]carbazole (ICZ). [2] DIM has been found to support hormone metabolism and immune activity, and stimulate antioxidant and detoxification systems.[3] Curcumin and BioPerine® provide complementary support for DIM’s role in healthy cell function.*

Support of Hormone Metabolism Healthy metabolism of exogenous and endogenous estrogens can be pivotal for hormonal balance.[4] DIM promotes metabolism of estrogen into the favorable and protective 2-hydroxyestrone (2-OHE) metabolite versus production of 4-hydroxyestrone (4-OHE) and 16-alpha-hydroxyestrone (16-alpha- OHE) metabolites.[5] DIM’s influence on 2-OHE production creates

a more desirable ratio of 2-OHE to 16-alpha-OHE. Assessment
of 2:16-alpha-OHE ratio appears to be useful in evaluating breast health.[6] DIM has been studied for its role in supporting prostate health as well, by reducing dihydrotestosterone binding to androgen receptors.*[7,8]

Support of Cell Function and Metabolism Orchestration of metabolism by the thyroid gland is dependent on hormone balance. DIM was found to target proteolytic enzymes (MMP-2 and MMP-9), thus supporting the normal function and activity of thyroid cells in vitro.[9] Ongoing research reveals DIM’s positive role in regulation of gene expression, protein production, and cell function. Downregulation of certain proteins (survivin, Bcl-2, and cdc25A) and upregulation
of protective proteins (NRF2 and cyclin-dependent kinase inhibitor p21waf1) promoted healthy cell growth.*[10,11]

Antioxidant and Detoxification Support DIMension 3 provides support for both antioxidant and detoxification systems which, in turn, support cellular function and integrity. Antioxidant activity is crucial to counteracting oxidative molecules normally produced during phase I

Clinical Applications 

  •  Supports Healthy Estrogen Metabolism in Females and Males*
  • Supports Detoxification of Xenoestrogens*
  • Provides Support for Antioxidant Mechanisms*

Healthy Hormone Metabolism represents a three-dimensional approach to supporting healthy estrogen metabolism. Research suggests that diindolylmethane (DIM), curcumin (from turmeric extract), and the patented black pepper extract BioPerine® support balanced estrogen metabolism.*

detoxification. Research on DIM suggests that it plays an important role in activating detoxification enzymes in human hepatocytes, further supporting biotransformation at a primary site in the body.*[12]

Curcumin As the major curcuminoid found in turmeric, curcumin is valued for its promotion of antioxidant activity, support of metabolic detoxification, and modulation of cytokine production.[13] Research studying genotoxic estrogen metabolites suggests that curcumin’s inhibitory effect on anchorage-independent growth and on CYP enzymes following dioxin exposure helps support healthy cell-life regulation in human embryonic kidney cells and normal prostate cells.*[14]

BioPerine is a patented form of piperine, the main alkaloid from black and long pepper plants that has been found to effectively support the absorption of nutrients. After a dose of 2 g of curcumin, human serum levels of curcumin were either undetectable or very low. When the same dose was given along with 20 mg of piperine (4:1 ratio), there was a 2000% increase in the bioavailability of the curcumin without adverse effects.*[15]

References 

  1. Bradlow HL. Review. Indole-3-carbinol as a chemoprotective agent in breast and prostate cancer. In Vivo. 2008 Jul-Aug;22(4):441-5. [PMID: 18712169]
  2. Herrmann S, Seidelin M, Bisgaard HC, et al. Indolo[3,2-b]carbazole inhibits gap junctional intercellular communication in rat primary hepatocytes and acts as a potential tumor promoter. Carcinogenesis. 2002 Nov;23(11):1861-8. [PMID: 12419834]
  3. Riby JE, Xue L, Chatterji U, et al. Activation and potentiation of interferon- gamma signaling by 3,3′-diindolylmethane in MCF-7 breast cancer cells. Mol Pharmacol. 2006 Feb;69(2):430-9. [PMID: 16267208]
  4. Lord RS, Bongiovanni B, Bralley JA. Estrogen metabolism and the diet-cancer connection: rationale for assessing the ratio of urinary hydroxylated estrogen metabolites. Altern Med Rev. 2002 Apr;7(2):112-29. [PMID: 11991791]
  5. Cavalieri E, Frenkel K, Liehr JG, et al. Estrogens as endogenous genotoxic agents–DNA adducts and mutations. J Natl Cancer Inst Monogr. 2000;(27):75- 93. [PMID: 10963621]
  6. Im A, Vogel VG, Ahrendt G, et al. Urinary estrogen metabolites in women at high risk for breast cancer. Carcinogenesis. 2009 Sep;30(9):1532-5. [PMID: 19502596]
  7. Fares F, Azzam N, Appel B, et al. The potential efficacy of 3,3′-diindolylmethane in prevention of prostate cancer development. Eur J Cancer Prev. 2010 May;19(3):199-203. [PMID: 20010430]
  8. Le HT, Schaldach CM, Firestone GL, et al. Plant-derived 3,3’-Diindolylmethane is a strong androgen antagonist in human prostate cancer cells. J Biol Chem. 2003 Jun 6;278 (23): 21136-45. [PMID: 12665522]
  9. Rajoria S, Suriano R, George A, et al. Estrogen induced metastatic modulators MMP-2 and MMP-9 are targets of 3,3′-diindolylmethane in thyroid cancer. PLoS One. 2011 Jan 18;6(1):e15879. [PMID: 21267453]
  10. Ahmad A, Sakr WA, Rahman KM. Anticancer properties of indole compounds: mechanism of apoptosis induction and role in chemotherapy. Curr Drug Targets. 2010 Jun;11(6):652-66. [PMID: 20298156]
  11. Rahman KW, Li Y, Wang Z, et al. Gene expression profiling revealed survivin as a target of 3,3′-diindolylmethane-induced cell growth inhibition and apoptosis in breast cancer cells. Cancer Res. 2006 May 1;66(9):4952-60. [PMID: 16651453]
  12. Gross-Steinmeyer K, Stapleton PL, Liu F, et al. Phytochemical-induced changes in gene expression of carcinogen-metabolizing enzymes in cultured human primary hepatocytes. Xenobiotica. 2004 Jul;34(7):619-32. [PMID: 15672752]
  13. Jurenka JS. Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: a review of preclinical and clinical research. Altern Med Rev. 2009 Jun;14(2):141-53. [PMID: 19594223]
  14. Choi H, Chun YS, Shin YJ, et al. Curcumin attenuates cytochrome P450 induction in response to 2,3,7,8-tetrachlorodibenzo-p-dioxin by ROS- dependently degrading AhR and ARNT. Cancer Sci. 2008 Dec;99(12):2518-24. [PMID: 19018768]
  15. Shoba G, Joy D, Joseph T, et al. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med. 1998 May; 64 (4):353-6. [PMID: 9619120]

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