DIM-Evail

DIM-Evail™ provides 100 mg of DIM (Diindolylmethane) - a type of compound known as a ‘plant indole.’ Plant indoles, also called glucosinolates, found in cruciferous vegetables provide health benefits to humans. Cruciferous vegetables are known for their cancer protection. Two such indoles provided by cruciferous vegetables are I3C (Indole-3-Carbinol) and DIM (Diindolylmethane). DIM is not naturally present in these plants. It gets released with the help of enzymes upon crushing of the broccoli, cauliflower, cabbage or brussel sprouts or during human digestion (1, 3). Stomach acid, or HCl, can also aid the joining of two indole-3 carbinols to make diindolylmethane. Lack of HCl may hinder one’s ability to make DIM from I3C (2).

DIM is two molecules of I3C combined together. I3C in a capsule is not shelf stable because it is sensitive to light, heat and moisture. I3C may also be irritating to the stomach, and research tells us that it can have negative side effects in doses over 300 mg daily, such as dizziness and unsteady gait, which may be due to nervous system toxicity. One study shows evidence that 90% of orally consumed I3C converts to other compounds, which may be the cause of the side effects. For instance, one compound I3C converts to is ICZ, or indolocarbazole, which causes DNA damage (4). DIM studies show no toxicity when given triple the dose in humans.

What Does DIM Do?

Research clearly shows that 4-hydroxyoestrogen and 16-hydroxyoestrogen are not favorable when elevated. Many doctors are now performing clinical tests on their patients to screen for risk of breast cancer. Low risk for breast cancer is marked by a high 2/16 ratio (2 hydroxy- to 16 hydroxy-oestrogen). It is clearly established by research that DIM raises the 2/16 ratio without elevating 4-hydroxyoestrogen. DIM helps men too because it is an aromatase inhibitor. DIM helps to block the conversion of testosterone to oestrogen (10). Regarding dosing, I3C needs to be given at 3-4 times the dosage of DIM to provide the same positive benefits. (Note: 300-400 mg I3C as compared to 60-100 mg DIM). I3C in low doses, like the amounts found in cruciferous vegetables is safe. I3C ingested at the higher doses needed to shift oestrogen ratios, may be problematic.


DIM-Evail™

Benefits of DIM-Evail™

  • Helps maintain beneficial ratio of 2/16 hydroxyoestrogen
  • Supports healthy balance of testosterone and oestrogen
  • Provides antioxidant properties
  • Has none of the side effects associated with I3C
  • Specifically formulated for maximum absorption and bioavailability

DIM-Evail

What Actions Does DIM Have on the Body that Make it Beneficial to our Health?

It has been suggested that a low level of the 2-hydroxyoestrone metabolites (2-OHE) and a high level of 16 alpha-hydroxyoestrone (16 alpha-OHE1) is associated with an enhanced risk of breast cancer. DIM increases 2 hydroxyoestrone and therefore improves the 2/16 hydroxyoestrone ratio, making it protective for women at high risk for this condition (6). 

Research by Bradlow says that DIM also reduces availability of 4-androstenedione for aromatisation to oestrone (7). DIM was concluded to be more potent than I3C at protecting against mammary carcinoma due to decreased formation of 16 alpha-hydroxyoestrone from oestrone (6).

Should We Just Eat Cruciferous Vegetables?

Eating 1kg of cruciferous vegetables like raw cabbage or broccoli can ultimately supply (via I3C conversion into DIM), about 20-30 mg of DIM. Therefore, supplementation is ideal along with consuming cruciferous vegetables.

Doesn’t Research Support the Use of I3C for Cancer Prevention Such as Breast Cancer?

There are positive studies on supplementation of I3C when looking at parameters such as improvement in the 2/16 hydroxyoestrone ratio. When we take a broader look, however, I3C raises 4-hydroxy oestrogen with the potential of aggravating cancers such as breast, endometrial and prostate cancer. I3C increases 4-hydroxyoestrogen production in animals and in humans (8). 4-hydroxy oestrogens and CYP1B1, the only CYP source of 4-hydroxyoestrogen, have both been implicated in the causation of prostate and breast cancer in humans. 4-hydroxy oestrogens and CYP1B1 are also implicated in the causation and growth of uterine fibroid tumors and endometriosis. 

Researchers from the Department of Pathology, Sasaki Institute, Tokyo, Japan concluded the following:

“These results suggest that induction of the CYP 1 family in the liver and sequential modulation of estrogen metabolism to increase 4HE might play a crucial role in promoting the effects of dietary I3C on endometrial adenocarcinoma development.” (8).

Should Men Take DIM?

It may be beneficial for men who wish to prevent prostate cancer and men with a family history of prostate cancer to take DIM. Research published in the British Journal of Cancer, 2004 states,“Prostate cancer mortality results from metastases to the bones and lymph nodes and progression from androgen-dependent to androgen-independent disease. Although androgen ablation was found to be effective in treating androgen-dependent prostate cancer, no effective life-prolonging therapy is available for androgen-independent cancer.”  Results of this study suggest that DIM induces apoptosis in PC3 cells, through the mitochondrial pathway suggesting that DIM is hopeful as a therapeutic strategy for the treatment of androgen-independent prostate cancer (11). According to UC Berkeley researchers, “DIM exhibits potent anti-proliferative and anti-androgenic properties in androgen-dependent human prostate cancer cells. DIM suppresses cell proliferation of LNCaP cells and inhibits dihydrotestosterone (DHT) stimulation of DNA synthesis.” DIM is a strong competitive inhibitor of DHT binding to the androgen receptor. This study is titled: Plant derived 3,3-Diindolylmethane Is a Strong Androgen Antagonist in Human Prostate Cancer Cells (10). An in vivo study in rats showed that DIM cut in half testosterone 16 alpha and 2 alpha-hydroxylation (12).


How Does DIM-Evail™ Offer Superior Absorption? 

DIM is made up of a crystalline structure that makes it difficult for the body to absorb. To overcome this hurdle, DIM-Evail™ is manufactured using an all-natural process that helps to optimise the absorption of this nutrient by the body. This delivery technology increases the absorption rate and reduces the absorption time for DIM, and as a result, it may allow for superior effects through lower dosages.

DIM-Evail


Can DIM be Taken with Medications?

DIM is safe when taken with Tamoxifen, birth control pills and other herbs such as St. John’s Wort that affect cytochrome p450 enzymes. Because of its effects on CYP enzymes, I3C, however, should not be taken with any of these. I3C blocks ovulation, can interfere with birth control pills and may alter the effects of many herbs such as St John’s Wort and could lead to Tamoxifen toxicity if taken simultaneously. Researchers in Minneapolis found that DIM does not affect the metabolism of Tamoxifen. I3C on the other hand, converts Tamoxifen into N-desmethyl-Tamoxifen 3 fold, which itself gets transformed into a genotoxic metabolite (13). Research titled Endocrine Disruption by I3C and Tamoxifen: Blockage of Ovulation may be disturbing to some. This is a quote from the Gao ovulation study: “In the current study, I3C disrupted ovulation already at doses that did not elicit systemictoxicity as indicated by a lack of reduced body weight gain, which was then observed at higher doses.” Gao asserts that “I3C appears to have TCDD-like inhibitory effects on ovulation.” (14) TCDD is a strong dioxin chemical. 


Researchers in Denmark state “Indolo[3,2-b]carbazole (ICZ), which is formed in the acidic environment of the stomach after intake of I3C, has a similar structure to, and shares biological effects with, the well-known tumor promoter 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD).” This is the conclusion of their study: “Further studies are needed in order to clarify the anticarcinogenic/carcinogenic effects of I3C and ICZ before high doses of I3C may be recommended as a dietary supplement.” They feel that ICZ’s tumor promoting activity is due to its activation of the Ah receptor and stimulation of certain cytochrome p450 enzymes mainly Cyp1a1, Cyp1a2 and Cyp1b1 (15).

DIM’s proven safety means that DIM can be used by women wishing to get pregnant but should be discontinued during pregnancy and lactation. There are no known contraindications for DIM supplementation.



Other products in the Evail™ Series:



These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure or prevent any disease.

References

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2. McDanell R, McLean AE, Hanley AB, Heaney RK, Fenwick GR. Chemical and biological properties of indole glucosinolates. J Agric Food Chem. 1999 Apr;47(4):1541-8.
3. Grose, KR, and Bjeldanes, LF. Oligermization of indole-3-carbinol in aqueous acid. Chem Res Toxicol 1992: 5:188-193. (glucobrassicins): a review. Food Chem Toxicol. 1988Jan;26(1):59-70. Review.
4. Park JY, Shigenaga MK, Ames BN. Induction of cytochrome P4501A1 by 2,3,7,8-tetrachlorodibenzo-p-dioxin or indolo(3,2-b)carbazole is associated with oxidative DNA damage.
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6. Dalessandri KM, Firestone GL, Fitch MD, Bradlow HL, Bjeldanes LF. Pilot study: effect of 3,3’-diindolylmethane supplements on urinary hormone metabolites in postmenopausalwomen with a history of early-stage breast cancer. Nutr Cancer. 2004;50(2):161-7.
7. Jellinck PH, Makin HL, Sepkovic DW, Bradlow HL. Influence of indole carbinols and growth hormone on the metabolism of 4-androstenedione by rat liver microsomes. J SteroidBiochem Mol Biol. 1993 Dec;46(6):791-8.
8. Yoshida M, Katashima S, Ando J, Tanaka T, Uematsu F, Nakae D, Maekawa A. Dietary indole-3-carbinol promotes endometrial adenocarcinoma development in rats initiated withN-ethyl-N’-nitro-N-nitrosoguanidine, with induction of cytochrome P450s in the liver and consequent modulation of estrogen metabolism. Carcinogenesis. 2004 Nov;25(11):2257-64.Epub 2004 Jul 7.
9. Shertzer HG, Sainsbury M. Intrinsic acute toxicity and hepatic enzyme inducing properties of the chemoprotectants indole-3-carbinol and 5,10-dihydroindeno[1,2-b]indole in mice.Food Chem Toxicol. 1991 Apr;29(4):237-42.
10. Hien T. Le, Charlene M. Schaldach, Gary L. Firestone, and Leonard F. Bjeldanes. Plant-derived 3,3_-Diindolylmethane Is a Strong Androgen Antagonist in Human Prostate CancerCells. Journal of Biological Chemistry Vol. 278, No. 23, Issue of June 6, pp. 21136-21145, 2003.
11. Nachshon-Kedmi M, Yannai S, Fares FA Induction of apoptosis in human prostate cancer cell line, PC3, by 3,3’-diindolylmethane through the mitochondrial pathway. Br J Cancer.2004 Oct 4;91(7):1358-63.
12. Wortelboer HM, van der Linden EC, de Kruif CA, Noordhoek J, Blaauboer BJ, van Bladeren PJ, Falke HE. Effects of indole-3-carbinol on biotransformation enzymes in the rat: in vivochanges in liver and small intestinal mucosa in comparison with primary hepatocyte cultures. Food Chem Toxicol. 1992 Jul;30(7):589-99.
13. Parkin DR, Malejka-Giganti D. Differences in the hepatic P450-dependent metabolism of estrogen and tamoxifen in response to treatment of rats with 3,3’-diindolylmethane and itsparent compound indole-3-carbinol. Cancer Detect Prev. 2004;28(1):72-9.
14. Gao X, Petroff B, Oluola O, Georg G, Terranova P, Rozman K. Endocrine Disruption by Indole-3-carbinol and Tamoxifen: Blockage of Ovulation. Toxicol Appl Pharmacol. 2002 Sep15;183(3):179.
15. Herrmann S, Seidelin M, Bisgaard HC, Vang O. Indolo[3,2-b]carbazole inhibits gap junctional intercellular communication in rat primary hepatocytes and acts as a potential tumorpromoter Carcinogenesis. 2002 Nov;23(11):1861-8.
16. Lambert JD, Hong J, Kim DH, Mishin VM, Yang CS.Piperine enhances the bioavailability of the tea polyphenol (-)-epigallocatechin-3-gallate in mice. J Nutr. 2004 Aug;134(8):1948-52.
17. Effect of piperine on the epididymis of adult male rats. D’cruz SC, Mathur PP. Asian J Androl. 2005 Dec;7(4):363-8.
18. Effects of piperine on gastric acid secretion in albino rats. Ononiwu IM, Ibeneme CE, Ebong OO. Afr J Med Med Sci. 2002 Dec;31(4):293-5.