LinkBack URL
About LinkBacks
Hi folks,
As you many of you know, I'm keen to use natural products whenever possible, especially in the area of testosterone support and estrogen management. I've started a trial, after the abortive attempt at a cycle as detailed in the Diary section, of natural test/estrogen products. A key one in the estrogen area is Diindolylmethane. Following is a summary of what it is and what it does.
Apologies if this has been posted before.
To save CS asking, no, there are no clincial trial quotes in this article, but should the need arise, I'll happily post ones I've seen.
Cheers.
__________________________________________________ _______________
DIINDOLYLMETHANE
"Diindolylmethane, or DIM for short, is a plant indole—a plant compound with health-promoting properties. DIM and other plant indoles are found in all cruciferous vegetables. Cruciferous vegetables include cabbage, broccoli, brussels sprouts, and cauliflower.
These plant indoles such as DIM affect estrogen metabolism in ways that might help prevent breast cancer, by modifying the rate of synthesis of estrone metabolites. It is also popular as an antioxidant.
DIM provides benefits in two ways:
1) the indole group binds to chemical carcinogens and activate enzymes which, in turn detoxify these harmful chemicals.
2) Acts as a catalyst to direct estradiol down a benign pathway to 2-hydroxyestrone thus decreasing levels of the carcinogenic 16-alpha hydroxyestrone, “bad estrogen” and also reducing the conversion of estrogens to Estrone.
There are 3 estrone metabolites
2-hydroxy-estrone which is shown to be beneficial
4-hydroxy-estrone which is shown to be carcinogenic
16-alpha-hydroxyestrone is implicated in cancer promotion
WHAT DOES DIM DO?
DIM shows great potential in preventing cancer, especially hormone-related cancers such as those of the breast and prostate. Researchers have been able to show that these plant indoles have powerful and diverse ways of stopping cancer. In 1991 researchers at the Institute for Hormone Research in New York City proved that plant indoles such as DIM significantly reduced the incidence and number of tumours in female mice prone to developing breast cancer. In human studies, levels of a carcinogenic estrogen declined and levels of a benign estrogen increased. Most important, there was a marked decrease in the level of the estrogen metabolite associated with breast and endometrial cancer (16-alphahydroxyestrone).
A summary of recent studies shows that plant indoles such as DIM
Increase the conversion of estradiol to “weaker” (2-hydroxyestrone) estrogen, which has been shown to reduce the incidence of breast cancer.
Works in estrogen receptor negative breast cancer cells.
Stops human cancer cells from growing (54-61%) and provokes the cells to self-destruct (apoptosis).
Provides antioxidant protection
Inhibits MCF7 human breast cancer cells better than tamoxifen under laboratory conditions.
Protects against the environmental toxin, dioxin
Diindolylmethane & Estrogen Balance
Diindolylmethane (DIM) is the most active cruciferous derived substance for promoting beneficial, estrogen metabolism in both women and men. DIM is formed from cruciferous vegetables including broccoli, cauliflower, cabbage and brussels sprouts.
DIM is actually formed in vivo (in the body) from its precursor indole, Indole-3-carbinol (I3C), after the enzymatic release of I3C from parent glucosinolates found in all cruciferous vegetables.
The supplemental use of DIM began with early experiments which demonstrated that animal diets with added diindolylmethane, like diets with added cruciferous vegetables, prevented chemically induced cancer.
Pure diindolylmethane was first used in 1987 as a dietary supplement in animals, shown to be non-toxic, and to prevent breast cancer caused by the well known human carcinogen, dimethybenz[a]anthracene. Similarly, the initiation pathway to chemically induced colon cancer was inhibited with the diindolylmethane precursor, I3C.
The mechanisms by which DIM prevents cancer in animals has subsequently been shown to involve a reduction in activity of the estrogen receptor system, promotion of beneficial estrogen metabolism, and support for selective apoptosis, or “programmed cell death” which removes damaged cells.
Supplemental use of DIM in humans is effective in adjusting the pathways of estrogen metabolism to favor the production of 2-hydroxyestrogen metabolites (see diagram below).
These shifts in estrogen metabolites were significant and showed an approximate 75% increase in production of 2-hydroxyestrone and a 50% decrease in 16-hydroxyestrone. An increased proportion of 2-hydroxy metabolites is correlated to protection from breast cancer.
This relationship has been documented in two prospective studies. Additional case-control studies have also documented that low levels of 2-hydroxy metabolites are associated with breast cancer in women, breast cancer in men, familial risk of breast cancer, uterine cancer, cervical cancer, and systemic lupus erythematosis.
An increase in the rate of breast cancer has now been associated with lupus.
Many established risk factors for breast cancer including obesity, high fat diets, and diets deficient in omega-3-fatty acids have also been correlated with low 2-hydroxy metabolite production.
Diindolylmethane is uniquely active with regard to its ability to favorably modify estrogen metabolism in the direction of greater 2-hydroxy estrogen production, whereas I3C is highly unstable, chemically reactive, and unpredictable.
It’s safe, long term use in dietary supplements is of questionable value. I3C has been shown to be a precursor dietary indole, without activity until converted to DIM in the acid environment of the stomach. This process can be inefficient, especially with diminished gastric acid production.
Therefore, in addition to lacking shelf life, I3C has little or no biological activity until it is converted to DIM.
In contrast to I3C, diindolylmethane is highly stable, requires no conversion in the stomach, and is the most active cruciferous indole in promoting beneficial estrogen metabolism.
Unlike soy isoflavones, genistein and daidzein, DIM is not an estrogen mimic or “phytoestrogen” and has no inherent estrogenic activity. DIM acts to balance the natural response to estrogen by adjusting the activity of metabolic cytochrome enzymes and specialised estrogen receptor molecules.
In dividing cells this limits the growth promoting signal from estrogens by reducing the level of activity of the estrogen receptor system. The compound 2-methoxyestrogen inhibits cell division by slowing the organisation of tubulin, the subcellular cytoskeleton necessary for division of chromosomes.
DIM enhances the protective mechanism of apoptosis, or programmed cell death, promoting beneficial elimination of damaged cells. The combination of these effects on cell behaviour, sets DIM apart from all other dietary substances and gives diindolylmethane a unique capability to promote beneficial actions of the estrogens.
Active apoptosis is central to preventing the initiation and promotion of breast, colon, and other cancers. Since these effects are specific to rapidly dividing cells, diindolylmethane does not prevent the beneficial effects of estrogen in supporting the health of the central nervous and skeletal systems.
In a nutshell, DIM creates a safer cellular environment for estrogen.
The Importance of Diindolylmethane Supplementation for Pre and Postmenopausal Women
In premenopausal women, the first age-related hormonal imbalance involves a decreased production of progesterone. This reduction in progesterone output during the second half or luteal phase of the menstrual cycle can cause irregular periods and contribute to premenstrual mood disorders.
The “good estrogen” metabolites, 2-hydroxy and 2-methoxy estrogen are notable in that they stimulate increased progesterone production from ovarian cells. By promoting this 2-hydroxy production, supplementation with DIM can help support progesterone production and maintain progesterone levels throughout the perimenopause.
This balancing effect can benefit disorders associated with estrogen-progesterone imbalance including chronic, recurring breast pain, fibrocystic disease, and endometriosis.
The fearful nature of breast cancer makes hormonal replacement unacceptable to many post-menopausal women. Adding to this dilemma is the current wider availability of dehydroepiandrosterone (DHEA), a precursor adrenal steroid and the natural source of estrogen in post menopausal women.
DHEA has been shown in long term clinical studies to promote bone mineralization without uterine stimulation, and has demonstrated protection to breast tissue from cancer initiation and growth.
The importance of supplementation with diindolylmethane is that this approach can decrease estrogen-related breast cancer risk in the majority of women. This includes women taking estrogen, DHEA, phytoestrogen supplements, or no hormonal replacement at all.
The increased risk of breast cancer from postmenopausal estrogen administration can be eliminated by the complementary step of adding cruciferous based supplements like diindolylmethane.
The Importance of Healthy Estrogen Metabolism in Men’s Health
Recent work shows that estradiol, the active form of estrogen, provokes increases in prostate specific antigen (PSA) production in human prostate tissue.
This increase in PSA is as great as that seen with testosterone. Increased PSA production was specifically inhibited by 2-methoxyestradiol, the beneficial estrogen metabolite whose production is promoted by DIM.
Diindolylmethane and environmental estrogens, high fat diets and pesticide residues in food all serve as additional sources of ele-vated estrogen exposure (often referred to a xenoestrogens - "foreign estrogens"). In addition, high fat diets, especially those rich in animal fats or omega-6 fatty acids can shift the metabolic pathways of estrogen towards the 16-hydroxy metabolites.
These “bad estrogens” are associated with higher rates of benign breast disease, and cancer in both women and men.
A study of European women confirmed that dietary exposure to the estrogenic pesticide, Dieldrin (a now banned organochlorine that is an environmental contaminant), was associated with increased risk of subsequent breast cancer. Exposure of breast cells in culture to organochlorine pesticides like Dieldrin increases the production of 16-hydroxy estrogen metabolites.
Alternatively, diets rich in omega-3 fatty acids from fish or supplemented with diindolylmethane produce more of the “good estrogens” identified as the 2-hydroxy metabolites of estradiol and estrone. The use of cruciferous indoles in test animals has been shown to be associated with the prevention of spontaneous, estrogen related cancers of the breast and uterus.
When tested in animals, DIM is unique in its effectiveness to favorably shift estrogen metabolism and decrease the over activity of the estrogen receptor system. The supplemental use of DIM allows women to promote and maintain a safer metabolism of estrogen. Diindolylmethane also increases the safety of exposure to estrogen derived from DHEA.
This supports the rationale for long term supplementation with DHEA by both men and women. Documented, age related changes in men support their need for an improved metabolism of estrogen. Diindolylmethane use by men provides a promising dietary means to minimise the impact of increased estrogen on atherosclerosis and prostate disorders characteristic of andropause ("male menopause").
These important benefits for successful aging in men and women all relate to an optimal and safer “estrogen balance”.
FAQs
“Q: How does DIM benefit testosterone activity?”
“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 ‘good’ estrogen metabolites along with increased free testosterone promoted by DIM increase fat mobilization and a fat-burning metabolism.”
“Q: DIM for Women—How does it achieve optimal estrogen metabolism?:
“Breast tenderness, endometriosis, and uterine cervical dysplasia have been shown to improve with DIM supplementation. The use of both DIM and progesterone is recommended for women in their forties who have evidence of progesterone deficiency, such as irregular menstrual periods. DIM can help support natural progesterone production.”
“Q: Can DIM supplementation make hormone replacement therapy (HRT) safer?”
“The proven scientific benefits of DIM make it a logical choice as a dietary supplement for use with HRT.”
“Q: Is testosterone really important in women’s health?”
“While the exact contribution of testosterone to mood and sexual health has been more difficult to define in women who have intact ovaries, it has been shown that testosterone supports physiologic responses in sexual arousal. In studies of mood and depression, testosterone alone or with estrogen was most effective in reducing depression.”
“Q: How does DIM “unlock” testosterone? in women”
“DIM promotes a consistent rise in the levels of ‘good’ estrogen metabolites. Even a small increase in the concentration of ‘good’ estrogen metabolites results in higher levels of free testosterone. Even tiny increases in amounts of free testosterone are capable of influencing mood and behavior since the brain possesses a multitude of hormone receptors that can be influenced by testosterone.”
“Q: Does DIM make DHEA a safer supplement?”
“DIM’s action ensures that the estrogen produced from DHEA is metabolised into ‘good’ estrogen metabolites.”
“Q: DIM for Men—Activating Testosterone?”:
“DIM helps to eliminate active estrogen from the male body by promoting its conversion into the ‘good’ estrogen metabolites. These metabolites then free up testosterone by bumping it off the testosterone-binding proteins.”
“Q: Why is optimum hormone balance so important for men?”
“Optimum hormone balance for men is defined by strong testosterone activity and the lowest possible level of unmetabolised estrogen.”
“Q: What role does supplemental DIM play in an aging-intervention plan for men?”
“Supplemental DIM reduces the effects of unmetabolised estrogen and promotes testosterone action. It does this by maximizing the testosterone-to-estrogen ratio in the body, thus increasing the activity of testosterone. DIM can improve mood, fight depression, and support memory. DIM also can be used to help address many of the unwanted side effects of estrogen in men—particularly those that occur with the age-related accumulation of estrogen. DIM can now be used to reduce the risk of prostate enlargement and promote a healthy prostate. Optimum testosterone-to-estrogen hormonal balance achieved with the use of DIM can help to preserve a youthful urinary tract and prevent age-related prostate enlargement.”
“Q: Why is DIM in demand by elite male athletes?”
“DIM supplementation is the key to eliminating unwanted estrogen in men. For athletes, this means increasing the metabolism of estrogen that is naturally present as well as any estrogen that arises from the use of testosterone prohormone supplements. With DIM use, you should see rapid muscle-building results from your training as well as more efficient reduction in body fat.”
“Q: What is the best way to combine supplemental DIM with a plan to build muscle?”
“DIM promotes an upward shift in the body’s critical balance between testosterone and estrogen levels. In scientific studies, high testosterone-to-estrogen ratios have been linked to lean body mass, a fat-burning metabolism, and low abdominal obesity.”
“Q: Can DIM alone benefit strength training without the additional use of testosterone prohormones?”
“DIM provides benefits to male and female athletes, since its estrogen-clearing action occurs whether or not there is increased estrogen production as seen with prohormone use. DIM, by helping to convert estrogen to ‘good’ estrogen metabolites, protects stressed muscle cells and allows more efficient repair and growth.”
“Q: How does better estrogen metabolism results in improved fat metabolism?”
“DIM reduces the levels of estradiol, or active estrogen, by promoting its conversion into ‘good’ estrogen metabolites. These ‘good’ estrogen metabolites are fat burners. When DIM is used, a second important fat-burning shift in metabolism also occurs—an increase in free testosterone and, consequently, an increase in the testosterone-to-estrogen ratio.”
“Q: Can DIM supplements help me lose weight without a strict diet and regular exercise?”
“DIM is not a ‘magic bullet’ that cancels out dietary and lifestyle indiscretion. The key to fat loss with DIM is carbohydrate restriction and an emphasis on aerobic exercise. When using DIM to assist fat loss, the preferred diet limits carbohydrate intake to low-glycemic foods, including broccoli, celery, green beans, zucchini, and salad greens. These produce the smallest increase in blood sugar levels. . . . Along with DIM supplements, an exercise routine that includes long aerobic workouts will put you solidly in a fat-burning mode and step up your metabolic rate. With DIM, you will increase the release of stored fatty acids and speed up your fat loss. The goal of fat loss with DIM is to preserve muscle mass while reducing body fat with a healthy but carbohydrate-restricted diet.”
“Q: Are DIM supplements safe?”
“The earlier research on these phytochemicals as a cancer preventive in animals used huge amounts of DIM for many months. Despite the continuous use of these phytochemicals in multiple generations of animals, no safety problems were noted. Recently, DIM was again shown to be safe when it was used successfully to treat chemically induced breast cancer. As with all fat-soluble nutrients, taking DIM with a light meal encourages absorption even more because this group of nutrients requires the activation of bile secretion from the liver to promote absorption.”
“Q: What about the other cruciferous indole, indole-3-carbinol (I3C)?”
Though used by some people as a dietary supplement, it turns out the I3C is not active in your body until it is converted into DIM. DIM is formed as I3C combines with itself, that is two molecules of I3C combine to form DIM (a chemical process called dimerisation). This occurs only if just the right amount of stomach acid is present. The usual dose of DIM for women is 100 to 200 mg per day taken with food. Women using DIM to help with weight loss have used up to 400 mg per day to achieve the greatest support for the burning of stored fat. DIM at 400 mg per day can be of benefit during the first one or two months of weight loss, especially in association with carbohydrate restriction and exercise. The usual dose range of DIM for men is 200 to 400 mg per day taken with food. For men involved in a plan of muscular development or fat loss, the dose of DIM should be increased to 400 to 500 mg per day.”
“Q: Are there any reported side effects associated with supplemental DIM?”
“Some people taking DIM have noticed a darkening of their urine to a brownish color. This has been seen when DIM is taken by someone who drinks little water throughout the day. This is a normal, harmless occurrence and is not associated with any abnormalities in kidney function or health status.”
Reply With Quote
Originally Posted by M1CH43L 
