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"Behold, I have given you every plant yielding seed that is on the surface of all the earth, and every tree which has fruit yielding seed; it shall be food for you."

Gen 1:29

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INTRODUCTION

Cruciferous vegetables, such as cabbage, cauliflower, and broccoli, have been cultivated since antiquity as medicinal plants. Once ingested, the Cruciferae release unique phytochemical constituents able to modify the activity of cellular enzymes effecting carcinogen clearance and estrogen metabolism. The most active of these phytochemicals with regard to estrogen is the dietary indole, diindolylmethane. Understanding the dietary influences of cruciferous phytochemicals on estrogen status provides a basis for nutritional approaches to estrogen-related concerns that accompany aging in women and men.

GENERAL GUIDELINES

Men and women find absorption-enhances diindolylmethane a useful dietary supplement to promote women's and men's health. Its use as a supplement can help to:

Replace or support daily dietary intake of cruciferous vegetables.
Help balance and "un-block" hormone metabolism in association with perimenopause and with hormonal replacement (HRT) in women and men. This includes use with estrogen replacement in women, and with DHEA, Pregnenolone, and Testosterone replacement in both men and women.
Beneficially adjust estrogen metabolism where a cancer-resistant metabolism is desirable, especially in women with a family history of breast, uterine, endometrial, or cervical caner. This extends to men with a family history of prostate cancer.
Beneficially impact conditions in women related to estrogen dominance, these include: recurrent premenstrual breast pain (mastalgia), painful fibrocystic breast, premenstrual syndrome (PMS) including mood disorders, bloating or weight gain, painful or excessive periods, endometriosis, estrogen-related enlargement of the uterus, and cervical dysplasia.
Beneficially impact hormonal conditions in men: especially, early benign prostatic hypertrophy associated with increased night-time urination.
Generally support a more active metabolism for more effective weight loss in women and men especially in conjunction with a reduced carbohydrate diet and exercise program.

SUGGESTED DOSAGE

Absorbable DIM is best taken with a small amount of food.

Basic Indication for Use	Typical Dose (mg/day) Taken as a single dose with meal or snack
Cruciferous Vegetable Support or Replacement	75
Combination with HRT (estrogen, DHEA, testosterone)	75 -150
Perimenopausal Metabolic Support ¹	75
Middle Aged Men - Metabolic Support	150 - 300
Weight Loss Promotin in Women and Men ²	300 - 450

¹ The basic dose in women who are perimenopausal (30 - 45 years) in 150 mg/day. Women who have symptoms of early menopause (hot flashes) in this age group should start at a dose of only 75 mg/day. This can be adjusted upward based on symptoms.
²The us of Absorbable DIM for promoting weight loss requires 300 - 450 mg/day. 450 mg/day is recommended for a period of 3 months during a weight loss program based on reduced carbohydrate intake and regular exercise. The weight loss use is best taken in two divided doses consumed with a mid morning and mid afternoon snack.

Condition to be supported with Absorbable DIM	Typical Dose (mg/day) Taken as a single dose with meal or snack
Premenstrual Breast Pain	150 - 300
Painful Breast Cysts	150 - 300
Premenstrual Syndrome (PMS)	150 - 300
Use with Tamoxifen	75 - 150
Painful Endometriosis	150 - 300
Painful Menstruation	150 - 300
Cervical Health (Start at higher dose for moderate abnormalities on Pap Smear)	300 - 450
Elevated Estrogen in Men, associated with obesity or testosterone, or DHEA replacement	75 - 300
Prostate Health (Nighttime Urination) [the daily dose can be taken before bed}	150 - 300

* The above doses represent milligram (mg) amounts of a patented absorption-enhancing formulation containing 25% pure DIM. Content verified by independent HPLC assay.

FREQUENTLY ASKED QUESTIONS

Q. What is DIM, and how can it help hormones?

Q. What is estrogen dominance?

Q. What benefits can DIM offer?

Q. Why not just eat more cruciferous vegetables?

Q. How much DIM is recommended?

Q. What’s exciting about the effect of DIM on premenstrual syndrome (PMS)?

Q. What's the best supplementation approach to PMS?

Q. How can helping estrogen metabolism benefit men?

Q. Can DIM help improve the safety of hormone replacement therapy (HRT)?

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REFERENCES

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

2. Santoro N. Characteristic of reproductive hormonal dynamics in the perimenopause. J Clin Endocrinol Metab. 1996; 81: 1495-1501.

3. Farnsworth WE. Estrogen in the etiopathogenesis of BPH. Prostate, 1999, 41:263-74.

4. Fishman J, Schneider J, Hershcope RJ, Bradlow HL. Increased estrogen 16hydroxylase activity in women with breast and endometrial cancer. J Steroid Biochem. 1984; 20: 1077-1081.

5. Sepkovic DW, Bradlow HL, Ho G, et al. Estrogen metabolite ratios and risk assessment of hormone related cancers: assay validation and prediction of cervical cancer risk. Ann NY Acad Sci. 1995; 768:312-316.

6. Muti P, et al. Metabolism and risk of breast cancer: A prospective analysis of 2:16 hydroxyestrone ratio in premenopausal and postmenopausal women. Cancer Epidemiol Biomarkers Prev, 2000; in press.

7. Hershcope RJ, Bradlow HL. Obesity, diet, endogenous estrogens, and the risk of hormone-sensitive cancer. Am J Clin Nutl: 1987;45(1 Supp1):283-289.

8. Musey PI, Collins DC, Bradlow HL, Gould KG, Preedy JR. Effect of diet on oxidation of 17-Beta-estradiol in vivo. J Clin Endoc Metab. 1987;65:792-795.

9. Bradlow HL, Davis DL, Lin G, Sepkovic D, Tiwari R. Effects of pesticides on the ratio of 16/2-hydroxyestrone' a biologic marker of breast cancer risk. Environ Health Perspect. 1995; 103(SuppI7): 147-150.

10. Cohen JH, Krista1 AR, Stanford JL. Fruit and vegetable intakes and prostate cancer risk. J Natl Cancer Inst. 2000; 92: 61-68.

11. Jacobs IC, Zeligs MA. Facilitated absorption of a hydrophobic dietary ingredient. Proceed Int'l Symp Control Rei Bioact Matel: Controlled Release, Society, Inc., 1998; 26: 958-959.

12. Chen I, McDougal A, Wang F, Safe S. Aryl hydrocarbon receptor-mediated antiestrogenic and antitumorigenic activity of DIM (DIM). Carcinogenesis, 1998; 19:1631-1639.

13. Jin L, Qi M, Chen DZ, et al. Indole-3-carbinol prevents cervical cancer in human papilloma virus type 16 (HPV16) transgenic mice. Cancer Res. 1999; 59: 3991-3997.

14. Baker B. Pilot study: cruciferous veggies may induce cervical dysplasia regression. Db Gyn News. 1999; 15:13.

15. Zeligs MA, Connelly AS. All About DIM. New York, NY: Avery; 2000; 75-76.

16. O'Brien PM, Wyatt K, Dimmock P. Premenstrual syndrome is real and treatable. Practicionel: 2000; 244:185-195.

17. Barnard ND, Scialli AR, Hurlock D, Bertron P. Diet and sex-hormone binding globulin, dysmenorrhea, and premenstrual symptoms. Dbstet Gynecol. 2000; 95 :245-250.

18. Thys-Jacobs S. Micronutrients and the premenstrual syndrome: the case for calcium. JAm Coli Nutl: 2000; 19: 220-227.

19. Loch EG, Selle H, Boblitz N. Treatment of premenstrual syndrome with a phytopharmaceutical formulation containing Vitex agnus castus. J Womens Health Gend Based Med. 2000; 9: 315-320.

20. Hammarback S, Damber JE, Backstrom T. Relationship between symptom severity and hormone changes in women with premenstrual syndrome. J Clin Endocrinol Metab. 1989; 68: 125-130.

21. Redei E., Daily plasma estradiol and progesterone levels over the menstrual cycle and their relation to premenstrual symptoms. Psychoneuroendocrinology. 1995; 20: 259-267.

22. Seippel L, Backstrom T. Luteal-phase estradiol relates to symptom severity in patients with premenstrual syndrome. J Clin Endocrinol Metab. 1998; 83: 1988-1992.

23. Doostzadeh J. Pregnenolone-7beta-hydroxylating activity of human cytochrome P450-1A1. J Steroid Biochem Molec Bioi. 1997; 60: 147-152.

24. Wang M, Seippel L, Purdy RH, Backstrom T. Relationship between symptom severity and steroid variation in women with premenstrual syndrome: study on serum pregnenolone, pregnenolone sulfate, 5 alpha-pregnane-3, 20-dione and 3 alpha-hydroxy-5 alpha-pregnan-20-one. J Clin Endocrinol Metab. 1996; 81: 1076-1082.

25. Spicer LJ, Kao LC, Strauss JF 3d, Hammond JM. 2-hydroxyestradiol enhanced progesterone production by porcine granulosa cells: dependence on de novo cholesterol synthesis and stimulation of cholesterol side-chain cleavage activity and cytochrome P450scc messenger ribonucleic acid levels. Endocrinology. 1990; 127: 2763-2770.

26. Milewicz A., Gejde1 E, Sworen H, et al. Vitex agnus castus extract in the treatment of luteal phase defects due to latent hyperprolactinemia. Results of a randomized placebo-controlled double-blind study. Arzneimittelforschung 1993; 43: 752-756.

27. Purohit A, Singh A, Ghi1chik MW, Reed MJ. Inhibition of tumor necrosis factor alpha-stimulated aromatase activity by microtubule-stabilizing agents, pac1itaxel and 2-methoxyestradiol. Biochem Biophys Res Commun. 1999; 261: 214-217.

28. Dulloo AG, Duret C, Rohrer D, et a1. Efficacy of a green tea extract rich in catechin polyphenols and caffeine in increasing 24-h energy expenditure and fat oxidation in humans. Am J Clin Nutl: 1999; 70:1040-1045.

29. Yoshioka M, St-Pierre S, Suzuki M, Tremblay A. Effects of red pepper added to high-fat and high-carbohydrate meals on energy metabolism and substrate utilization in Japanese women. Br J Nutl: 1998; 80: 503-510.

30. Krieg M, Nass R, Tunn S. Effect of aging on endogenous level of 5 alphadihydrotestosterone, testosterone, estradiol, and estrone in epithelium and stroma of normal and hyperplastic human prostate. J Clin Endocrinol Metab. 1993; 77: 375-381.

31. Boehm S, Nirnberger G, Ferrari P. Estrogen suppression as a pharmacotherapeutic strategy in the medical treatment of benign prostatic hyperplasia: Evidence for its efficacy from studies with mepartricin. Wien Klin Wochenschl: 1998; 110: 817-823.

32. Schairer C, Lubin J, Troisi R, Sturgeon S, Brinton L, Hoover R. Menopausal estrogen and estrogen-progestin replacement therapy and breast cancer risk. JAMA, 2000; 283: 485-491.

33. Grady D, Wenger NK, Herrington D, et al. Postmenopausal hormone therapy increases risk for venous thromboembolic disease. The heart and estrogen/progestin replacement study. Ann Intern Med. 2000; 132: 689-696.

34. Wenger NK, Knatterud GL, Canner PL. Early risks of hormone therapy in patients with coronary heart disease. JAMA, 2000; 284: 41-43.

35. Philips GB, et al. Association of hyperestrogenemia and coronary heart disease in men in the Framingham cohort. Am J Med. 1983; 74: 863-869.

36. Seeger H, Mueck AO, Lippert TH. Effect of estradiol metabolites on the susceptibility of low-density lipoprotein to oxidation. Life Sciences, 1997; 61: 865-868.

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