Diindolylmethane (DIM): Microencapsulated Phytonutrient Supports Hormone Metabolism and Weight Loss

 
As we age, many tissues in our bodies become inflamed, resulting in an increased risk of weight gain, difficulty balancing blood glucose, and impacting the normal turnover of cells. By aiding healthy hormone metabolism and assisting the body to recognize and support stressed cells, we can balance the general inflammatory response and slow the progress of aging-related concerns.

DIM (Diindolylmethane) is a natural antioxidant and phytonutrient found in cruciferous vegetables, and research has shown it to have powerful inflammation-balancing activity. DIM is an indole that is highly insoluble. To be absorbed optimally, pure DIM must be microencapsulated. This has been demonstrated to significantly increase the gastrointestinal absorption of DIM.1 When absorbed, DIM promotes estrogen metabolism to produce healthy and beneficial 2-hydroxy estrogens,2 and minimizes the activity of pro-inflammatory enzymes,3 thereby balancing the cellular inflammatory response. Activating these pathways encourages remarkable weight loss and hormonal balance and provides many other benefits towards healthy aging.

Maintaining Healthy Cells by Resolving Inflammation

The epidemic of “Metabolic Syndrome” is now recognized as a constellation of difficulties to maintain blood glucose, blood lipids, blood pressure, and bodyweight in healthy ranges. Evidence shows that low levels of generalized inflammation and cellular stress are linked to decreased cell sensitivity to insulin and associated weight gain. This creates an avenue for the Metabolic Syndrome to develop. This cycle of inflammation has been associated with “high-glycemic” processed starches and sugars, trans fats, and lack of exercise, but research shows that exposure to environmental pollutants can also cause inflammation.4 Population studies show that blood levels of organo-chlorine pesticides and polychlorinated biphenyls (PCBs) are significantly associated with imbalanced fasting glucose and greater waist circumferences in US adults who are otherwise considered healthy.5 Dietary exposure from environmental chemicals ranging from plastics to pesticides, tobacco, hydrocarbons, and petrochemicals, can contribute to inflammation, and therefore contribute to aging-related disorders such as weight gain, blood glucose imbalances, and impact the normal development of cells.

Microencapsulated DIM has shown specific activity to modulate inflammatory receptors and mediators, as well as support the antioxidant enzymes within cells. Recent research shows that even at low doses, DIM suppresses the inflammatory response from certain white blood cells, called macrophages.3 Macrophages are present in tissue and derived from precursor monocyte white cells in blood. Macrophages accumulate in fat deposits, particularly intra-abdominal fat, and other sites of inflammation. Known as the conductors of the immune response, macrophages produce and secrete an array of pro-inflammatory hormones and cytokines, which, in excess, may contribute to the factors tied to the metabolic syndrome.6 In the research, DIM was shown to specifically inhibit the production and release of inflammation-promoting cytokines from macrophages. Taking supplemental DIM supports the metabolic pathway for DIM, which helps to stimulate the metabolism of other poorly soluble substances. This activity assists the body in eliminating poorly soluble, pro-inflammatory environmental chemicals helping to support a balanced inflammatory response.

DIM Specifically Benefits Estrogen Metabolism

Estrogen is an essential sex hormone present in women and men. Due to its potent capability to deliver messages on a cellular level, poorly metabolized estrogen has the potential to contribute to the factors associated with the Metabolic Syndrome. Estrogen is metabolized into several different post-estrogen hormones, namely 2-hydroxy, 4-hydoxy and 16-hydroxy estrogens. Research has shown 4-hydroxy and 16-hydroxy estrogens to be promoters of inflammation and impact the normal growth of cells.7 Being overweight is also associated with unfavorable estrogen metabolites.8 On the other hand, 2-hydroxy estrogens have been shown to be powerfully protective of tissues, helping to support healthy cell growth.9

Research shows that absorbable DIM specifically directs metabolism to produce much higher levels of the 2-hydroxy “Good Estrogens.”10 A second clinical trial confirms this activity in individuals concerned with thyroid health.20 Encouraging this favorable hormone metabolism produces remarkable results in the body, and invigorates the process of weight loss as well. Adipocyte lipolysis is the process by which fat cells release stored fat to serve as a primary energy supply. “Good Estrogens” (2-hydroxy) help maintain healthy levels of the catecholamine hormones (epinephrine and nor-epinephrine) that specifically stimulate enzymes in fat cells to release stored fat for energy.11 2-hydroxy estrogen metabolites are now known to be much more active than unmetabolized estrogen in triggering the release of stored fat.21 When given over a period of months in animal studies, 2-hydroxy estrogen prevented weight issues and development of the Metabolic Syndrome.12 Research with absorbable DIM has shown that supplementation before exercise results in greater lipolysis in the hours following exercise. This effect was associated with enhanced weight loss in adults on a weight loss program.13

Use of microencapsulated DIM supplements by thousands of women and men has demonstrated benefits for occasional breast tenderness,14 improvement in mild menstrual cramps,15 support in uterine cervical health,16 and maintenance of prostate health. Prostate health is the subject of two clinical trials supported by the National Cancer Institute where supportive benefits in men are anticipated. Effectively balancing hormone metabolism is essential for better health and avoidance of the Metabolic Syndrome. It is advised and easy to test your body’s 2/16 estrogen metabolite ratio in order to see if you are in need of further hormone balance. A ratio of less than 2.0 may indicate the need for support for estrogen metabolism.

DIM Contributes to Increased Well-being

DIM is compatible with other nutritional interventions to aid healthy aging. Absorbable DIM added to a diet further enriched with other natural indoles may offer additional help for weight maintenance through better appetite control and a more sensitive sense of satiety or fullness. This is possible by increasing cruciferous vegetable intake as a dietary means of supporting levels of the essential amino acid, tryptophan. Adding broccoli sprouts and lightly cooked cruciferous vegetables to meals on a regular basis provides sulforaphane and brassinins, which are complementary phytonutrient relatives of DIM.17 Together DIM and these phytonutrients inhibit inflammation-induced breakdown of tryptophan by inhibiting inflammation related enzymes.18 Adding these other phytonutrients to supplemental DIM may help maintain optimal tryptophan levels.

Healthy tryptophan levels are central to well-being and help maintain production of the brain chemical, serotonin. Serotonin is necessary for better mood and appetite control. Tryptophan can be further supported by including tryptophan-rich dietary ingredients in our diets. These include spirulina, soy nuts, cottage cheese, turkey and tofu. Individuals who are fighting serious carbohydrate cravings and mild mood fluctuations can consider adding 5-HTP supplements taken with absorbable DIM for more predictable and consistent support of brain serotonin, supporting better mood and more successful appetite control.19

Aging-Intervention with DIM

Microencapsulated DIM has been the subject of scientific research for more than 10 years, and more than 25 metric tons of this patented formulation of DIM have been safely consumed by humans. Absorbable DIM provides unique capabilities to promote a healthy, balanced inflammatory response and support hormone metabolism, both of which have been directly measured in research studies. Balancing inflammation and normalizing estrogen metabolism may be further connected to a reduced risk of being overweight and enhance the ability to support normal cell development, as well as providing remarkable support for mood, weight maintenance, and hormonal balance. Supplemental DIM, as offered through VRP in the form of microencapsulated BioDIM®, is part of a natural and effective approach to healthy aging.

© 2011, Michael A. Zeligs, MD. All Rights Reserved.

References:

1. Zeligs MA and Jacobs IC. Compositions and methods of adjusting steroid hormone metabolism through phytochemicals. US Patent #6,086,915. 2000, July.

2. Zeligs MA. Diet and estrogen status: the cruciferous connection. J Medicinal Foods. 1998;1:67 82.

3. Cho HJ, Seon MR, Lee YM, Kim J, Kim JK, Kim SG, Park JH. 3,3’-Diindolylmethane suppresses the inflammatory response to lipopolysaccharide in murine macrophages. J Nutr. 2008 Jan;138(1):17-23.

4. Baillie-Hamilton PF. Chemical toxins: a hypothesis to explain the global obesity epidemic. J Altern Complement Med. 2002 Apr;8(2):185-92.

5. Lee DH, Lee IK, Porta M, Steffes M, Jacobs DR Jr. Relationship between serum concentrations of persistent organic pollutants and the prevalence of metabolic syndrome among non-diabetic adults: results from the National Health and Nutrition Examination Survey 1999-2002.Diabetologia. 2007 Sep;50(9):1841-51.

6. Harman-Boehm I, Blüher M, Redel H, Sion-Vardy N, Ovadia S, Avinoach E, Shai I, Klöting N, Stumvoll M, Bashan N, Rudich A. Macrophage infiltration into omental versus subcutaneous fat across different populations: effect of regional adiposity and the comorbidities of obesity. J Clin Endocrinol Metab. 2007 Jun;92(6):2240-7.

7. Coffey DS. Similarities of prostate and breast cancer: Evolution, diet, and estrogens. Urology. 2001 Apr;57(4 Suppl 1):31-8.

8. Schneider J, Bradlow HL, Strain G, Levin J, Anderson K, Fishman J. Effects of obesity on estradiol metabolism: decreased formation of nonuterotropic metabolites. J Clin Endocrinol Metab. 1983 May;56(5):973-8.

9. Le HT, Schaldach CM, Firestone GL, Bjeldanes LF. 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.

10. Dalessandri, KM, Firestone GL, Fitch MD, Bradlow HL, Bjeldanes LF. 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(2):161-7.

11. Ackerman GE, et al., Potentiation of epinephrine-induced lipolysis by catechol estrogens and their methoxy derivatives, Endocrinology. 1981;109:2084-8.

12. Tofovic SP, Dubey RK, Jackson EK. 2-Hydroxyestradiol attenuates the development of obesity, the metabolic syndrome, and vascular and renal dysfunction in obese ZSF1 rats. J Pharmacol Exp Ther. 2001 Dec;299(3):973-7.

13. Zeligs MA. Phytochemicals for promoting weight loss. US Patent #6,534,085, 2003, March.

14. Zeligs MA, Brownstone PK, Sharp ME, Westerlind K,Wilson SM, Johs S. Managing Cyclical Mastalgia with Absorbable Diindolylmethane: A Randomized, Placebo-controlled Trial. JANA. 2005;7(3): 5-14.

15. Zeligs, MA, Fulfs, JC, Peterson, R, Wilson, SM, McIntyre, L, Sepkovic, DW, and Bradlow, HL. In vivo, uterine-protective activity of absorption-enhanced diindolylmethane: Animal and preliminary human use in combination with Tamoxifen. Proc Am Assoc Cancer Res. 2003;44(6347):1268.

16. Zeligs MA, Sepkovic DW, Manrique C, Macsalka M, Williams DE, Bradlow HL. Absorption-enhanced 3,3’-Diindolylmethane: Human Use in HPV-related, Benign and Pre-cancerous Conditions. Proc. Am. Assoc. Cancer Res. 2002;43(3198):644.

17. Banerjee T, Duhadaway JB, Gaspari P, Sutanto-Ward E, Munn DH, Mellor AL, Malachowski WP, Prendergast GC, Muller AJ. A key in vivo anti-tumor mechanism of action of natural product-based brassinins is inhibition of indoleamine 2,3-dioxygenase (IDO). Oncogene. 2007 Nov 19 (E-pub).

18. Brandacher G, Hoeller E, Fuchs D, Weiss HG. Chronic immune activation underlies morbid obesity: is IDO a key player? Curr Drug Metab. 2007 Apr;8(3):289-95.

19. Cangiano C, Ceci F, Cascino A, Del Ben M, Laviano A, Muscaritoli M, Antonucci F, Rossi-Fanelli F. Eating behavior and adherence to dietary prescriptions in obese adult subjects treated with 5-hydroxytryptophan. Am J Clin Nutr. 1992 Nov;56(5):863-7.

20. Rajoria S, Suriano R, Parmar PS, Wilson YL, Megwalu U, Moscatello A, Bradlow HL, Sepkovic DW, Geliebter J, Schantz SP, Tiwari RK. 3,3’-diindolylmethane modulates estrogen metabolism in patients with thyroid proliferative disease: a pilot study. Thyroid. 2011 Mar;21(3):299-304.

21. D’Eon TM, Rogers NH, Stancheva ZS, Greenberg AS. Estradiol and the estradiol metabolite, 2-hydroxyestradiol, activate AMP-activated protein kinase in C2C12 myotubes. Obesity (Silver Spring). 2008 Jun;16(6):1284-8.
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