By Ori Hofmekler, Author of The Warrior Diet (www.warriordiet.com)

The connection between derived ingredients and estrogen metabolism is just beginning to emerge. Studies at the Strang Cancer Prevention Laboratory, N.Y., were the first to establish the link between phytonutrients from cruciferous vegetables and estrogen metabolism. They showed that supplemental use of a single cruciferous compound can dramatically induce beneficial effects on estrogen metabolism. This beneficial effect has the power to greatly reduce the risk for estrogen related cancer for both genders (i.e. breast, ovarian, prostate).

Diindolymethane (DIM), the most active cruciferous indole, can help restore and maintain a favorable balance of estrogen metabolites.

It became evidently clear that metabolism and growth promoting activity of estrogen can be modified by milligram amounts of dietary indoles from crucifers. Cruciferous indoles were found to shift estrogen metabolism into predominantly 2-hydroxy and 2-methoxy estrogens. Known as “good estrogens”, these active metabolites act as antioxidants and have the power to eliminate damaged or cancerous cells throughout the body. Deficiency in these phytonutrients may cause an increased production of adverse groups of estrogen metabolites (i.e. 16 hydroxy and 16 methoxy estrogens). These adverse metabolites, also known as “bad estrogens,” cause increased oxidative stress, DNA damage and promotion of cancer cell formation.

Much epidemiological evidence shows that imbalanced estrogen metabolism, due to phytonutrient deficiencies caused by low vegetables diets, is associated with a high prevalence of estrogen related disease, such as breast, ovarian or prostate cancer. Imbalanced estrogen metabolism may also cause fat gain particularly in estrogen sensitive adipose tissue, such as abdominal or chest for men; hips, lower butt and upper thighs for women.

Supplemental use of diindolymethane (DIM), the most active cruciferous indole, can help restore and maintain a favorable balance of estrogen metabolites.

Diindolymethane (DIM) – first defense against estrogen’s adverse effects

Diindolymethane (DIM) is the most bioactive compound in crucifers to help defend women and men against estrogen’s adverse metabolites. DIM is found in cruciferous vegetables including: broccoli, cauliflower, cabbage and brussel sprouts. DIM is derived from Indol-3 carbinol (I3c), which is synthesized from parent glucosilates found in cruciferous vegetables. Early studies in animals revealed that supplemental DIM, IN3 and a high intake of cruciferous vegetables helped prevent chemically induced cancer. DIM, which has been used since 1987 in animal studies, proved to be non-toxic and a potent aid against estrogen adverse effects.

The mechanism by which DIM induces its beneficial actions has been shown to involved a reduction in estrogen receptors activity, promotion of healthy estrogen metabolites and support for selective cells apoptosis (cell suicide), which removes damaged or sick cells.

Early studies in animals revealed that supplemental DIM, IN3 and a high intake of cruciferous vegetables helped prevent chemically induced cancer.

Supplemental use of DIM in humans helps shift estrogen metabolism to favor the production of 2 hydroxy or 2 methoxy estrogen metabolites over 16 hydroxy or 16 methoxy estrogen metabolites. Note that increased ratios of 2 / 16 hydroxy (or methoxy) estrogens is correlated with protection against cancer. This relationship has been documented in several case-control studies.

It has been widely established that risk factors, for estrogen related cancer include obesity, high animal fat diets, and diets deficient in omega 3 oils (n-3 EFA), all of which have been correlated with low 2 hydroxy estrogens. DIM has the unique ability to favorably increase the production of 2 hydroxy or 2 methoxy estrogens and thus help defend the body against estrogen’s adverse effects.

Note that DIM is not a phytoestrogen. Not like soy flavones which mimic estrogen and are believed to cause mild estrogenic activity DIM has no inherent estrogen activity. DIM is an estrogen modulator, positively affecting estrogen metabolism with estrogen inhibitory properties (i.e. lowering estrogen-receptors activity).

Supplemental DIM is highly recommended in cases correlated with the following conditions:

• Exposure to estrogen chemicals (pesticides, herbicides, petroleum based products)
• Estrogen therapy
• Steroid use (on or off drugs)
• Aging
• Obesity
• Elevated PSA
• Pre- and post-menopausal women
• Deficient diet (low vegetables, low n-3 oil)
• Increased inherited risk for estrogen related cancer

References

Adlercreutz H, Western diet and Western diseases: some hormonal and biochemical mechanisms and associations. Scand J Clin Lab Invest. 1990; 50 (Suppl 21): 3-23.

Michnovicz JJ, et al., Dietary and pharmacological control of estradiol metabolism in humans. Ann N Y Acad Sci. 1990; 595:291-9.

Michnovicz JJ, et al., Altered estrogen metabolism and excretion in humans following consumption of indole-3-carbinol. Nutr Cancer. 1991;16(1):59-66.

Michnovicz JJ, et al., Changes in levels of urinary estrogen metabolites after oral indole-3-carbinol treatment in humans. J Natl Cancer Inst. 1997 May 21; 89(10):718-23.

Bradlow HL, et al., 2-hydroxyestrone: the ‘good’ estrogen. J Endocrinol. 1996 Sep; 150 Suppl:S259-65.

Zhu BT, et al., Is 2-Methoxyestradiol an endogenous estrogen metabolite that inhibits mammary carcinogenesis? Cancer Research 1998 June 1; 58:2269-2277.

Steinmetz KA, Vegetables, fruit, and cancer prevention: a review. J American Dietetic Assoc. 1996; 10: 1027-39.

Farnsworth WE, Roles of estrogen and SHBG in prostate physiology. The Prostate 1996; 28:17-23.

Zeligs MA, Diet and estrogen status: the cruciferous connection. J of Medicinal Food 1998 Nov 2; 1: 67-82.

Bradfield CA and Bjeldanes LF, High performance liquid chromatographic analysis of anticarcinogenic indoles in Brassica oleracea. J Agric. Food Chem. 1987; 35:46-49.

McDanell R, et al., Differential induction of mixed-function oxidase (MFO) activity in rat liver and intestine by diets containing processed cabbage: correlation with cabbage levels of glucosinolates and glucosinolate hydrolysis products. 1987 Food. Chem. Toxicicol.; 25: 363-368.

Chen I, et al., Aryl hydrocarbon receptor-mediated antiestrogenic and antitumorigenic activity of diindolylmethane. Carcinogenesis 1998; 19: 1631-1639.

Telang NT, et al., Inhibition of proliferation and modulation of estradiol metabolism: novel mechanisms for breast cancer prevention by the phytochemical indole-3-carbinol. Proceedings of the Society for Experimental Biology and Medicine 1997; 216: 246-252.

Kabat GC, et al., Urinary estrogen metabolites and breast cancer: a case-control study.

Cancer Epidemiol Biomarkers Prev. 1997 Jul;6(7):505-9.

Ho GH, et al. Urinary 2/16 alpha-hydroxyestrone ratio: correlation with serum insulin-like growth factor binding protein-3 and a potential biomarker of breast cancer risk. Ann Acad Med Singapore 1998; 27:294-299.

23. Schneider J., et al., Abnormal oxidative metabolism of estradiol in women with breast cancer. Proc Natl Acad Sci USA 1982; 79: 3047-3051.

Bradlow HL, et al., 16a hydroxylation of estradiol: a possible risk marker for breast cancer. Annals NY Acad. Sci. 1986; 464: 138-151.

Sepkovic DW, et al., Estrogen metabolite ratios and risk assessment of hormone related cancers: assay validation and prediction of cervical cancer risk. Annals of the N.Y. Acad. of Science 1995; 768: 312-316.

Hershcopf RJ, et al., Obesity, diet, endogenous estrogens, and the risk of hormone-sensitive cancer. Amer. J. of Clinical Nutrition. 1987; 45 (Supplement 1): 283-289.

Verhoeven, DTH, et al., Epidemiological studies on brassica vegetables and cancer risk. Cancer Epidemiology, Biomarkers & Prevention. 1996; 5: 733-748.

Kall, M.A., et al. Effects of dietary broccoli on human drug metabolizing enzymes : evaluation of caffeine, oestrone and chlorzoxazone metabolism. Carcinogenesis 1996; 17: 793-799.

Bradlow HL, et al., Long-term responses of women to inole-3-carbinol or a high fiber diet. Cancer, Epidemiology, Biomarklers & Prevention 1994; 3:591-595.

Klauber N, et al. Inhibition of angiogenesis and breast cancer in mice by the microtubule inhibitors 2-methoxyestradiol and taxol. Cancer Research 1997; 57:81-86.

Ge X, Yannai, S, Rennert, G, Gruener, N, and Fares, FA, 3,3′-Diindolylmethane induces apoptosis in human cancer cells. Biochemical and Biophysical Research Communications 1996; 228: 153-165.

Ettinger B, Overview of estrogen replacement therapy: a historical perspective. Proc. Soc. Exp. Biol. Med. 1998; 217:2-5.

Colditz GA, Relationship between estrogen levels, use of hormone replacement therapy and breast cancer. J. Natl. Cancer Inst. 1998; 90: 814-23.

Labrie F., DHEA as physiological replacement therapy at menopause. J. Endocrinol. Invest. 1998; 21:399-401.

Ginsburg EL, et al., Effects of alcohol ingestion on estrogens in postmenopausal women. JAMA 1996; 276:1747-51.

Krieg M., et al., Effect of aging on endogenous levels of 5-alpha-dihydrotestosterone, testosterone, estradiol and estrone in epithelium and stroma of normal and hyperplastic human prostate. J. Clin. Endocrinol. Metab 1993; 77: 375-381.

Nakhla AM, et al., Estradiol activates the prostate androgen receptor and prostate-specific antigen secretion through the intermediacy of sex hormone binding globulin. J. of Biological Chemistry 1997; 272: 6838-6841