DIM 100mg 60 capsules - Physiologics

Promotes Healthy Estrogen Metabolism*

HOW PATIENTS MAY BENEFIT

• Patented formulation designed to promote healthy estrogen metabolism*
• Stabilized, bioavailable form of Diindolylmethane (DIM®)

PRODUCT DISCUSSION
PhysioLogics DIM (bioavailable 3,3-Diindolylmethane) is a patented, stabilized formula that helps promote cellular health and supports the enzymatic basis of healthy estrogen metabolism.*

STRUCTURE AND FUNCTION
The compound 3,3-Diindolylmethane is a dietary indole which occurs naturally in Brassica vegetables. Brassica vegetables are also known as cruciferous vegetables and include broccoli, cauliflower, cabbage, turnips, kale and brussels sprouts. These vegetables are considered by many scientists to be among the most metabolically healthful foods because of their unique profile of naturally occurring biochemicals. Diindolylmethane is a stable dimer (double molecule) of indole-3-carbinol (I3C), which is generated upon hydrolysis of glucobrassicin, the indole glucosinolate in Brassica vegetables. Dehydration of I3C results in a mixture of oligomeric products, including diindolylmethane. Diindolylmethane has been shown to have beneficial enzymatic interactions in vitro, which is believed to help mediate its positive effects on estrogen metabolism.*

CLINICAL EVIDENCE

• A randomized, double-blind, placebo controlled, clinical study analyzed healthy estrogen metabolism in 20 postmenopausal women. Subjects were given either 108 mg/day of Diindolylmethane as DIM® or a placebo. DIM® treated subjects showed a significant increase in levels of 2-hydroxyestrone (p=0.020) and diindolylmethane (p=0.045), and an increase of 47% in the 2-hydroxyestrone/16-alpha hydroxyestrone ratio (p=0.059). Based on these results, the authors concluded that DIM® had positive effects on estrogen metabolite ratios. (Dalessandri et al, 2004)
• In a double-blind, placebo-controlled, crossover study, 33 subjects received 60 mg of DIM® or placebo per day in four divided doses. Each study period lasted three months. At three months, a significant positive effect was observed on estrogen metabolism in the treatment group. No significant effect was observed in the placebo group. (Zeligs et al, 2005)

SUMMARY
PhysioLogics DIM® utilizes BioResponse-DIM®, a bioavailable form of Diindolylmethane, that helps promote healthy estrogen metabolism and cellular health.*

SUGGESTED DOSAGE
For adults, take one (1) capsule with a meal up to three times daily or follow the advice of your health care professional.

DIM® and BioResponse-DIM® are trademarks of BioResponse.

REFERENCES
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Bradfield CA, Bjeldanes LF. High-performance liquid chromatographic analysis of anticarcinogen indoles in Brassica oleracea. J Agric Food Chem. 1987;35:46-9

Chen DZ, Qi M, Auborn KJ, Carter TH. Indole-3-carbinol and diindolylmethane induce apoptosis of human cervical cancer cells and in murine HPV16-transgenic preneoplastic cervical epithelium. J Nutr. 2001;131:3294-302

Chen, I, et al. Indole-3-carbinol and Diindolylmethane as Arly Hydrocarbon (Ah) Receptor Agonists and Antagonists in T47D Human Breast Cancer Cells. Biochem Pharmacol. 1996. 51(8): 1069-1076

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

Chintharlapalli S, Smith R 3rd, Samudio I, et al. 1,1-Bis(3'indolyl)-1-(p-substitutedphenyl)methanes induce peroxisome proliferator-activated receptor gamma-mediated growth inhibition, transactivation, and differentiation markers in colon cancer cells. Cancer Res. 2004;64:5994-6001

Dalessandri KM, Firestone GL, Fitch MD, et al. Pilot study: effect of 3,3'- diindolylmethane supplements on urinary hormone metabolites in postmenopausal women with a history of early-stage breast cancer. Nutr Cancer. 2004;50:161-7

Firestone GL, Bjeldanes LF. Indole-3-carbinol and 3-3'-diindolylmethane antiproliferative signaling pathways control cellcycle gene transcription in human breast cancer cells by regulating promoter-Sp1 transcription factor interactions. J Nutr. 2003;133(7 Suppl):2448S-2455S

Gamet-Payrastre L, Lumeau S, Gasc N, et al. Selective cytostatic and cytotoxic effects of glucosinolates hydrolysis products on human colon cancer cells in vitro. Anticancer Drugs. 1998;9:141-8

Ge X, Yannai S, Rennert G, et al. 3,3'-Diindolylmethane induces apoptosis in human cancer cells. Biochem Biophys Res Commun. 1996;228:153-8

Hong C, Kim HA, Firestone GL, Bjeldanes LF. 3,3'- Diindolylmethane (DIM) induces a G(1) cell cycle arrest in human breast cancer cells that is accompanied by Sp1-mediated activation of p21(WAF1/CIP1) expression. Carcinogenesis. 2002;23:1297-305

Hong C, Firestone GL, Bjeldanes LF. Bcl-2 family-mediated apoptotic effects of 3,3'-diindolylmethane (DIM) in human breast cancer cells. Biochem Pharmacol. 2002;63:1085-97

Lee SH, Kim JS, Yamaguchi K, et al. Indole-3-carbinol and 3,3'diindolylmethane induce expression of NAG-1 in a p53-independent manner. Biochem Biophys Res Commun. 2005;328:63-9

Leong H, Firestone GL, Bjeldanes LF. Cytostatic effects of 3,3'diindolylmethane in human endometrial cancer cells result from an estrogen receptor-mediated increase in transforming growth factor-alpha expression. Carcinogenesis. 2001;22:1809-17

Leong H, Riby JE, Firestone GL, Bjeldanes LF. Potent ligandindependent estrogen receptor activation by 3,3'-diindolylmethane is mediated by cross talk between the protein kinase A and mitogen-activated protein kinase signaling pathways. Mol Endocrinol. 2004;18:291-302. Epub 2003 Nov 26

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;7:112-29

Qin C, Morrow D, Stewart J, et al. A new class of peroxisome proliferator-activated receptor gamma (PPARgamma) agonists that inhibit growth of breast cancer cells: 1,1-Bis(3'-indolyl)-1-(psubstituted phenyl)methanes. Mol Cancer Ther. 2004;3:247-60

Riby JE, Chang GH, Firestone GL, Bjeldanes LF. Ligand-independent activation of estrogen receptor function by 3, 3'-diindolylmethane in human breast cancer cells. Biochem Pharmacol. 2000;60:167-77

Staub RE, Feng C, Onisko B, et al. Fate of indole-3-carbinol in cultured human breast tumor cells. Chem Res Toxicol. 2002;15:101-9

Sun S, Han J, Ralph WM Jr, et al. Endoplasmic reticulum stress as a correlate of cytotoxicity in human tumor cells exposed to diindolylmethane in vitro. Cell Stress Chaperones. 2004;9:76-87

Zeligs MA, et al. Managing cyclical mastalgia with absorbable diindolymethane: A randomized, placebo-controlled trial. JAMA. 2005. 8(1): 5-15

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