Tag Archive for: DIM

How to Reduce Your Risk for Breast and Prostate Cancer

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There’s a time of life when many men and women begin to experience unwelcome changes in hormonal health. Women notice worsening PMS, painful periods, hot flashes, or painful intercourse. Men face less frequent and shorter erections and loss of energy. This time of life is also when we become increasingly aware of the risks of a hormone-related cancer diagnosis. It’s not a theoretical concern, either! If you’re a woman, you have a lifetime chance of developing breast cancer of one in seven. Men have a one in three chance of developing prostate cancer. Yikes!! These statistics can make you feel like a walking time bomb!

In this article, I’d like to share a promising way to help reduce your risk of breast and prostate cancer while improving your sexual health and function.

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Facts About DIM and Men’s Health

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Several classes of chemical compounds that naturally occur in fruits and vegetables possess anticarcinogenic properties. The cruciferous vegetables, such as cabbage and broccoli are particularly rich sources of such compounds, including Indole derivatives [indole-3-carbinol (I3C) and indole-3-acetonitrile], dithilthiones, and isothiocyanates. Increased consumption of cruciferous vegetables is associated with reduced tumor incidents in humans and experimental animals.

Diindolylmethane (DIM, in short) is the principal breakdown product of indole 3-carbinol (I3C), the phytochemical found in cruciferous vegetables like cabbage, cauliflower, broccoli, brussels sprouts, kale, collards, mustard greens, radishes, watercress, and turnips. DIM, has been shown in scientifi­c studies to reduce the risk of prostate and other hormone-driven cancers by helping the body to make a better balance of the hormones.*

Can taking 250 – 300 mg. of DIM (or its equivalent in raw cruciferous vegetables) reduce your risk for prostate cancer?

Yes, according to Dr. Michael Zeligs, M.D. author of All About DIM. “A recent study of Seattle men showed that three or more servings of cruciferous vegetables a week can reduce prostate cancer risk almost by half.” His statement is based on an article by J. H. Cohen, et. al. Fruit and vegetable intakes and prostate cancer risk. Natl. Cancer Inst. Jan 2000; 5;92 (1): 61-8.

The following quotations are taken from All about DIM by Michael A. Zeligs, M.D. and A. Scott Connelly, M.D., based on research related to men’s use of diindolylmethane (DIM) and the phytochemical compounds (indole-3-carbinol) found in cruciferous vegetables from which DIM is derived.  Following the quotations is a partial bibliography substantiating the claims made in the article.

DIM & Testosterone

What is Testosterone?

Testosterone is an important contributor to healthy hormonal balance in both men and women. Testosterone is known as an androgen because when its effect dominates, male characteristics are seen. These include male distribution of body hair, a deeper voice, and male genital development. Testosterone is also identified as an anabolic hormone due to its ability to promote protein synthesis. Active protein synthesis produces bigger muscles and stronger bones, especially in response to exercise. This process also increases metabolic rate and consumes fat, resulting in a leaner physique. The more subtle effects of testosterone have to do with its action as a support for mood and libido. Testosterone has a clear anti-depressant action and promotes interest in sex and men and women.

How does DIM benefit testosterone activity?

Testosterone acts differently depending on whether it is free or bound to carrier proteins in the blood. DIM, through its effects on estrogen metabolism, supports testosterone by helping to maintain the level of free or active testosterone. Free testosterone refers to the defraction of testosterone that circulates in the blood and is not associated with or bound by SHBG (Sex Hormone Binding Globulin), its carrier protein. Since only free testosterone easily crosses into the brain, muscles, and fat cells much of the desirable action of testosterone has to do with the free portion. However, this represents only a tiny amount of the total testosterone equal to only 2% of the total in men and even less in women.

High levels of SHBG lock up free testosterone making it unavailable to support mood or metabolism. Interestingly, unmetabolized estrogen is the body’s primary signal to increase the production and levels of the testosterone-binding protein. Low levels of free testosterone have been identified during perimenopause and are most dramatic in women with severe premenstrual syndrome (PMS) symptoms. (24)

How can DIM help with age-related reduced levels of free testosterone?

Since DIM promotes a more active metabolism of estrogen, unmetabolized estrogen levels fall and the 2-hydroxy-estrogens increase. The 2-hydroxy-estrogens possess the unique ability to displace testosterone from SHGB and set it free. Therefore, the combined effect of DIM to reduce unmetabolized estrogen and increase 2-hydroxy-estrogens can reduce elevations in SHGB and allow for more free testosterone. Both of these changes help maintain and restore a youthful balance between estrogen and free testosterone. This balance is a key to a healthy and active metabolism. (25)

Does DIM help maintain a healthy testosterone level in older men?

Zelligs: “The same dynamics for maintaining higher total and free testosterone levels apply to healthy aging in men.  Estrogen metabolism is slowed during aging in men, especially in association with obesity and regular alcohol use.” [translation: As we age, our bodies take longer to “clear” the estrogen in our cells and higher than healthy levels of estrogen are common, especially in men who are obese or who are regular social drinkers.]

“Avoiding overactive testosterone metabolism, [clearing the testosterone too quickly] and reducing the conversion of testosterone into estrogen are goals of nutritional support in middle-aged and older men.”

“It is well documented that estrogen accumulates in the prostate gland starting at age 50 (42) and that estrogen is associated with the degree of prostate enlargement.” (43)

“Based on animal and human testing, DIM is again preferable to I3C in the area of men’s health.  Using DIM in men avoids accelerating testosterone metabolism, especially regarding unwanted conversion of testosterone into estrogen.”

Does DIM help improve prostate health and reduce nighttime urination in older men?

“Regarding men’s health, supplementation with absorbable DIM has resulted in reports of improved prostate function based on reduced nighttime urination in symptomatic older men.”

“Once absorbed, DIM is uniquely active in promoting healthy estrogen metabolism and improving symptoms of estrogen-related imbalance in both men and women.”

“Apart from therapeutic potential, dietary supplement use of DIM and I3C relates to hormonal balance and symptoms of “estrogen dominance.”

Even more impressive is research showing that unmetabolized estrogen accumulates in prostate tissue in men as they age. Exposure of human prostate tissue to unmetabolized estrogen in the laboratory did indeed result in activation and increased production of prostate-specific antigen protein (PSA). The PSA protein level in men’s blood is now used as a screening test to determine the severity of prostate enlargement or to determine the chance of prostate cancer.

Recent studies also have shown that estradiol, the active form of estrogen, causes the prostate gland to increase its production of prostate-specific antigen (PSA). Increased PSA production, however, can be inhibited by the “good” estrogen metabolites promoted by DIM. This indicates that “good” estrogen metabolites are more beneficial for prostate health than unmetabolized estrogen-like estradiol. (53)

Various supplements, including DIM, can now be used to reduce the risk of prostate enlargement and promote a healthy prostate. Optimum testosterone-2-estrogen hormonal balance achieved with the use of DIM can help to preserve a youthful urinary tract, prevent age-related prostate growth, and perhaps reduce the risk of prostate cancer.

Long term safety has been demonstrated in DIM.

Partial Bibliography of Dr. Zeligs’ Book, All About DIM

Integrated Cancer Therapy 2004 March; 3(1): 5-12
“Cruciferous vegetables: cancer protective mechanisms of glucosinolate hydrolysis products and selenium.”  Authors:  Keck A S, Finley J W.

“Epidemiological studies provide evidence that the consumption of cruciferous vegetables protects against cancer more effectively than the total intake of fruits and vegetables.  This review describes the anticarcinogenic bioactivities of glucosinolate hydrolysis products, the mineral selenium derived from crucifers, and the mechanisms by which they protect against cancer.  These mechanisms include altered estrogen metabolism, protection against reactive oxygen species, alterned detoxification by induction of phase II enzymes, decreased carcinogen activation by inhibition of phase I enzymes, and slowed tumor growth and induction of apoptosis.”

Journal of Nutrition 2003 Apr; 133(4):1011-9
“Gene expression profiles of I3C- and DIM-treated PPC3 human prostate cancer cells determined by DNA microarray analysis.

“Studies from our laboratory and others have shown that indole-3-carbinol (I3C) and its in vivo dimeric product, 3,3′-diindolylmethane (DIM), inhibit the growth of PC3 prostate cancer cells and induce apoptosis by inhibiting nuclear factor (NF)-kappaB and Akt pathways.”

Carcinogenesis 2005 26(11): 1896-1904; doi:10. 1093/carcin/bgil55

“Indole-3-carbinol inhibition of androgen receptor expression and down-regulation of androgen responsiveness in human prostate cancer cells
Authors: Hsu Jocelyn C, Dev Anurupa, Wing Aimee, Bjeldanes Leonard F, Firestone Gary L

“Indole-3-carbinol (I3C), a naturally occurring compound found in vegetables of the Brassica genus, such as broccoli and cabbage, is a promising anticancer agent previously sown to induce a G1 cell-cycle arrest in the cells of human lymph node carcinoma of prostate (LNCaP) through regulation of specific G1-acting cell-cycle components.  Since the androgen receptor (AR) mediates proliferation and differentiation in the prostate and is expressed in nearly all human prostate cancers, the effects of I3C on AR expression and function were examined in LNCaP cells….Taken together, our results demonstrate that I3C represses AR expression and responsiveness in LNCaP cells as a part of its antiproliferative mechanism.”

“Consult your doctor, practitioner, and/or pharmacist for any health problem and before using any supplements or before making any changes in prescribed medications….”

“Indole-3-carbinol…a chemical found in vegetables of the broccoli family, is thought to possess cancer preventive properties.

“[I3C] appears to work in several ways: 1. it facilitates the conversion of estrogen to a less cancer-promoting form, 2. it partially blocks the effects of estrogen on cells, 3. it directly kills or inhibits cancer cells, 4. it reduces levels of free radicals, which can promote cancer by damaging DNA.

Bradlow, HL, Telang NT, Sepkovic DW, Osborne MP, 2-hydroxyestrone: the ‘good’ estrogen, J Endocrinol. 1996 Sep; 150 Supple: 5259-65.

Chen, I, McDougal A, Wang F, Safe S; Aryl hydrocarbon receptor-mediated anti-estrogenic and anti- tumorigenic activity of diindolylmethane (DIM). Carcinogenesis 1998 Sep; 19(9): 1631-9.

Krieg M, Nass R, and Tunn S, Effect of aging on endogenous level of 5 alpha-dihydrotestosterone, testoterone, estradiol, and estrone in epithelium and stroma of normal and hyperplastic human prostate. J Clin Endocrine Metab 1993 Aug; 77(2): 375-81.

Bradlow H L, Teland NT, Sepkovic DW, Osborne MR, et. Al., Phytochemicals as modulators of cancer risk.  Adv Exp Med Biol. 1999; 472:207-21.

“Besides being the active phytonutrient promoting beneficial estrogen metabolism, DIM has now been shown to actually treat breast cancer in animals. (21)

“No side effects of any sort are seen when pure DIM is used even in huge doses in animals, or when the usual dose of 40 mg/day of DIM (contained in 150 mg of absorbable, patented (DIM) is tripled to 450 mg/day in human subjects. (25)

Featured image courtesy of Pexels

Facts About DIM and Women’s Health

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What is DIM?

Diindolylmethane (DIM, in short) is the principal breakdown product of indole 3-carbinol (I3C), the phytochemical found in cruciferous vegetables like cabbage, cauliflower, broccoli, brussel sprouts, kale, collards, mustard greens, radishes, watercress, and turnips. DIM, has been shown in scientifi­c studies to reduce the risk of breast, cervical and other estrogen-driven cancers cancer by helping the body to make a better balance of the “good estrogen” (2-hydroxy-estrone) compared to the “bad estrogen” (16-alpha-hydroxy-estrone).*

Royal Maca Plus for Women™ with DIM is an ideal product combining the hormone-regulating effects of maca with the estrogen metabolite regulating effect of DIM. It relieves PMS and painful periods and alleviates peri-menopausal, menopausal and postmenopausal symptoms. Maca & DIM together help your body make healthy estrogen metabolites and a healthy progesterone level. Progesterone is important for healthy hormonal function and helps provide protection against cell proliferation in estrogen-sensitive tissue. There are many scienti­fic studies which show that indole 3-carbinol and DIM can improve the ratio of healthy estrogen metabolites produced in 87% of women.

Who can benefit from taking Royal Maca Plus with DIM for Women?

Most women experiencing hormonal imbalances associated with menstruation, PMS, peri-menopause, menopause or post-menopause may bene­fit from Royal Maca Plus for Women with a family history of breast cancer or other estrogen-dependent cancers and women who have been tested and have learned that they have an unhealthy ratio of “good estrogen” to “bad estrogen” will be especially interested.

The following quotations have been taken from All About DIM by Michael A. Zeligs, MD & A. Scott Connelly, MD

Can DIM be a substitute for hormone replacement therapy (HRT)?

DIM has no estrogenic activity in itself. Although it helps to convert estrogen to useful metabolites, it does not directly mimic or replace estrogen. Using DIM will promote a more desirable estrogen metabolism, but it will not make up for estrogen deficiency. However, combining organic maca root with DIM will produce a better metabolism and better utilization of a woman’s estrogen.

Maca alone, however, can be successfully used as a hormone balancer, reducing or eliminating hot flashes, vaginal dryness, depression due to low estrogen, supporting a healthy libido, without any of the dangerous side effects of estrogen supplementation (HRT). The Maca-DIM combination is particularly helpful for both reducing the risk of developing estrogen-dependent cancer as well as relieving hot flashes and other menopausal symptoms. Furthermore, this combination supports the health of the adrenal glands, thyroid, pancreas and neurotransmitter hormone production, including melatonin.

DIM helps women optimize their estrogen metabolism.

What makes optimal estrogen metabolism so important for women?

Optimal estrogen metabolism in women is defined by the ample production of “good” estrogen metabolites. These metabolites help lower the risk of cancer and decrease the symptoms of estrogen over-stimulation, or dominance-symptoms of which include breast tenderness, rapidly growing uterine fibroid tumors, uterine cervix problems (as seen with abnormal PAP smears) and endometriosis, a painful condition caused by persistent uterine tissue growing in abnormal locations within the abdomen.

Anti-oxidant properties of “good estrogen” metabolites.

Finally, the “good” estrogen metabolites have important antioxidant activity exceeding the potency of Vitamin E. The antioxidant activity of the “good” estrogen metabolites may explain why estrogen in women can slow the course of some age-related diseases. These include heart disease, arthritis, and cancer.

“Good estrogen” metabolites affect just metabolism and libido.

Having higher levels of the “good” estrogen metabolites is also important for sustaining an active fat-burning metabolism. “Good” metabolites help fat cells release stored fat. They are important in preserving the activity of the small amount of testosterone present in all women. This provides additional support for fat utilization, as well as support for mood and libido. Healthy levels of testosterone in women may also help to reduce the symptoms of premenstrual syndrome.

How does proper hormonal balance help with weight loss?

The “good” estrogen metabolites along with increased free testosterone promoted by DIM increased fat mobilization and a fat-burning metabolism. The effects of free testosterone in women and men are similar. In each case, testosterone promotes the building of new protein. When hormonal balance shifts to favor building new proteins, metabolite rate is increased and fat metabolism is promoted. Part of the protein-building effect of testosterone is to gear up the cellular enzymes needed to burn fat. Fat contains the stored energy needed to support the formation of new proteins as well as the fuel for sustained aerobic exercise. Together with exercise, DIM provides the best hormonal balance to create the protein machinery for active fat utilization.

The good estrogen metabolites also directly facilitate the release of stored fat in a number of ways. First, these metabolites assist the specific fat-burning hormones called catecholamines that are produced during exercise to release stored fat. These released fatty acids circulate in the bloodstream as a primary energy source. Second, the “good” estrogen metabolites actually can increase the number of protein receptors for the catecholamines that appear on the surface of fat cells. As circulating catecholamines released during exercise occupy these receptors, stored fat is more actively released from fat cells. DIM and a hormonal balance favoring the “good” estrogen metabolites assist catecholamines in supporting a more active fat-burning metabolism.

The following abstracts of published scientific studies involve the consumption by human beings and animals of indole-3-carbinol. The conversion to DIM occurs in the stomach of living beings in the presence of sufficient stomach acid.

Michnovicz, Jon, J., Bradlow, H. Leon, “Induction of estrodial metabolism by dietary indole-3-carbinol in humans” Journal of the National Cancer Institute, Vol. 82, No. 11, (June 6, 1990): 947-949 Study of the effect of indole-3-carbinol on estrodial metabolism

Abstract

Dietary indoles in cruciferous vegetables induce cytochrome P450 enzymes and have prevented tumors in various animal models. Because estrodial metabolism is also cytochrome P450 mediated and linked to breast cancer risk, indoles may similarly reduce estrogen-responsive tumors in humans. We examined several indoles in female SPRAGUE-DAWLEY in hepatic estrodial 2-hydroxylation. The most potent inducer common Indole -3- carbinol, was administered to humans (500mg daily for 1 wk). it significantly increased the extent (mean +- SEM) of estrodial 2- hydroxylation from 29.3% +- 2.1% to 45.6% +-2.1% (P < .001). these results indicate that indole-3-carbinol strongly influences estrodial metabolism in humans and may provide a new chemopreventive approach to estrogen- hyphen dependent diseases.

Bell, Maria C. et. al., “Effect of indole-3- carbinol on the treatment of precancerous lesions of the cervix” Gynecologic Oncology Vol. 78, (2000): 123-129Placebo-controlled trial of indole-3-carbinol in the treatment of CIN (pre-cancerous cervical

Abstract

Objective. Most precancerous lesions of the cervix are treated with surgery or ablative therapy. Chemoprevention, using natural and synthetic compounds, may intervene in the early stages of carcinogenesis and prevent the development of invasive disease. Our trial used indole-3- carbinol (I-3-C) administered orally to treat women with CIN as a therapeutic for cervical CIN.

Methods. Thirty patients with biopsy proven CIN II-III were randomized to receive placebo or 200, or 400 mg/day I-3-C administered orally for 12 weeks. if persistent CIN was diagnosed by biopsy at the end of the trial loop electrocautery exclXXion procedure of the transformation zone was performed. HPV status was assessed in all patients.

Results. None (0 of 10) of the patients had complete regression of CIN. In contrast 4 of 8 patients of 200 mg/day arm and 4 of 9 patients in the 400 mg/day arm had complete regression based on their 12-week biopsy. This protective effect of I-3-C is shown by a relative risk (RR) of 0.50 ((95% CI, 0.25 to 0.99) P=0.023) for the 200 mg/day group and an RR of 0.55 ((95% (I,0.31 to 0.99) P=0.032) for the 400mg/day group. HPV was detected in 7 of 10 patients, in 7 of 8 of 200 mg/day group and 8 of 9 in the 400 mg/day group.

Conclusion. There was a statistically significant regression of CIN in patients treated with I-3-C compared with placebo. The 2/16 alpha- hydroxyestrone ratio changed in a dose dependent fashion.

Bradlow, H. Leon, et.al., “Effects of dietary indole-3-carbinol on estrodial metabolism and spontaneous memory tumors in mice.” Carcinogenesis Vol. 12 No. 9 (1991): 1571-1574Effects of dietary indole-3-carbinol on development of breast tumors in mice

Abstract

Indole 3 Carbinol (I3C) is a potent inducer of cytochrome P450 enzymes in many species, including humans. We, therefore, studied alterations in the cytochrome P450-dependent metabolism of estrodial in different strains of mice consuming I3C in semisynthetic powdered diets at doses ranging from 250-5000 ppm (34-700mg/kg/day) for different periods of time. In short- term metabolic studies (3 weeks), wet liver weight increased in SW and C3H/OuJ mice in a dose responsive manner.

Dietary I3C increased the cytochrome P450 content measured in hepatic microsomes, as well as the extent of estrodial 2-hydroxylation up to 5-fold. In a long-term feeding experiment (8 months), female C3H/OuJ mice consumed synthetic diets containing I3C at 0, 500 or 2000 ppm. Mammary tumor incidents and multiplicity were significantly lower at both doses of I3C and tumor latency was prolonged in the high dose group. We conclude that I3C is an inducer of hepatic P450-dependent estrogen metabolism in mice, and that it is chemopreventive in the C3H/OuJ mouse mammary tumor model. This protective effect may be mediated in part by the increase in part 2- hydroxylation and consequent in activation of endogenous estrogens.