Alternative Names: Di-indolmethane, Indole-3-Carbinol, Diindolylmethane.
DIM has been shown to help regulate and promote a more efficient metabolism of estrogen, and an optimal ratio of estrogen metabolites. DIM is thought to be responsible for the health effects of dietary Indole-3-Carbinol (I3C).
Research since the 1970s has determined that disrupted estrogen metabolism is closely linked to several health risks in men and women, particularly those involving the breast, uterus, prostate and other reproductive tissue. Genetics, excess weight, poor diet and other lifestyle factors may result in an imbalance of estrogen metabolites. Xenoestrogenic compounds of the modern world, such as organochlorine pesticides, can significantly disrupt healthy estrogen metabolism.
The phytochemicals in cruciferous vegetables have been shown to beneficially affect the body's hormonal and detoxification systems. Epidemiological studies have supported the health benefits of consuming these vegetables.
The stronger form of estrogen (estradiol) can be converted into the weaker form (estriol) without using drugs. Estriol is considered to be a more desirable form of estrogen; it is less active than estradiol, so when it occupies the estrogen receptor it effectively blocks estradiol's strong "grow" signals.
Using a natural substance (IC3, or DIM), researchers were able to increase the conversion of estradiol to estriol by 50% in 12 healthy people. Next, they tested the natural substance in female mice prone to developing breast cancer. The incidence of cancer and the number of tumors fell significantly. Additionally, the level of an estrogen metabolite associated with breast and endometrial cancer (16-alpha-hydroxyestrone) fell.
In 1997, researchers at Strang Cancer Research Laboratory at Rockefeller University discovered that when DIM changes "strong" estrogen to "weak" estrogen, it stops human cancer cells from growing and provokes the cells to self-destruct (apoptosis). Subsequent studies done at the University of California at Berkeley show that DIM inhibits some human breast cancer cells from growing by as much as 90% in culture. Growth arrest does not depend on estrogen receptors.
DIM is a major active acid-catalyzed derivative of one of the phytochemicals in cruciferous vegetables, indole-3-carbinol (I3C). Cruciferous vegetables include broccoli, cauliflower, Brussels sprouts, turnips, kale, green cabbage and mustard seed.
DIM is generally much more effective than I3C – and less expensive. In the mid-1990s it was determined that IC3 was biologically inactive until converted to DIM, which in humans occurs in the digestive tract. I3C is converted into DIM through a process involving gastric hydrochloric acid (HCL). If a person is deficient in HCL, as commonly occurs in the elderly, I3C will not effectively convert into DIM. In contrast to I3C, DIM is highly stable, does not need any conversion in stomach acid, and is by far the most active phytochemical in promoting the synthesis of protective 2OHE. However, DIM is poorly absorbed unless "absorption enhanced" in some way. Please look for such wording on any DIM product you consider purchasing.
It is generally agreed that 300mg of IC3 converts to 30-40mg of DIM.
The mechanisms for DIM's health benefits primarily involve the induction of mixed function oxidases and phase II detoxification enzyme systems by the binding and activation of the arylhydrocarbon receptor. Some have suggested that DIM may also positively affect cellular signaling pathways, and thus regulate tumor promotion and progression.
Research using human breast cells (MCF-7) has shown that DIM not only inhibits cell growth, but also induces apoptosis. These results involve DIM binding to the aryl hydrocarbon receptor (AhR) resulting in rapid formation of the nuclear AhR complex and consequent induction of gene expression and synthesis of cytochrome P450 detoxification enzyme (CyP450A1). DIM consequently produces increased levels of the protective hydroxylated estrogen 2-OHE1.
16-alpha-hydroxyestrone (16OHE) and 2-hydroxyestrone (2OHE) are metabolites of estrogens. 2OHE is biologically inactive, while 16OHE is biologically active meaning that, like estradiol, it can send "grow" signals. In cases of breast cancer, the 'bad' 16OHE is often elevated and the 'good' 2OHE is decreased. Interestingly, cancer-causing chemicals change the metabolism of estrogen so that 16OHE is elevated. Studies show that people who take DIM not only have beneficial increases in estriol, they also have beneficial increases in 2OHE.
Low levels of the 2OHE have been linked to breast cancer (in both women and men), uterine cancer, cervical cancer and lupus. An immune disorder that affects mostly women, lupus appears related to estrogen metabolism.
It is becoming increasingly apparent that dietary supplements such as DIM may provide an important mechanism for maintaining successful aging despite the increasing levels of xenoestrogenic compounds in our modern world.
As little as 0.5-2mg per kg of body weight per day of DIM has been demonstrated to be an effective dose. A typical dose is 40-60mg once or twice a day.
Harmless changes in urine color may occur. Increased water consumption reverses this side-effect.
Do not use this product if you are pregnant or lactating, or using birth control pills.
There is an acceleration of the testosterone-to-estradiol conversion by an increase in aromatase activity in healthy SLE patients when compared to controls. According to [Lupus 1992;1(3): pp.191-5], "among SLE patients the aromatase activity varied inversely with the disease activity. Patients with SLE had decreased androgen and increased estrogen levels. Aromatase activity in SLE patients had significant direct correlation with estrogen levels. These data suggest that abnormal regulation of aromatase activity may partially explain the abnormalities of estrogen synthesis in SLE." These patients are relatively testosterone deficient. Aromatase blockers such as DIM and Chrysin should be considered in such cases.
DIM encourages the conversion of estrogens to safer forms and helps reduce elevated levels.
Clinical studies using testosterone injections, creams, or patches have often failed to provide a long-lasting, libido-enhancing effect in aging men. This is because testosterone can be converted to estrogen, which is then taken up by testosterone receptor sites in cells throughout the body. When an estrogen molecule occupies a testosterone receptor site on a cell membrane, it blocks the ability of serum testosterone to induce a healthy hormonal signal. It does not matter how much serum free testosterone is available if excess estrogen is competing for the same cellular receptor sites.
Aromatization is the process of converting testosterone to estrogens. This process increases with age. Aromatase blockers such as DIM and Chrysin can reduce estrogen levels and enhance testosterone levels. If these fail to increase free testosterone and lower excess estradiol, then consider asking your doctor to prescribe the potent aromatase inhibiting drug Arimidex (anastrozole) in the very low dose of 0.5mg, twice per week. Arimidex reduced estradiol by approximately 70% within 24 hours and by approximately 80% after 14 days of daily use.
The usual dose range of DIM for men is 200-400mg per day taken with food. For men involved in a plan of muscular development or fat loss, the dose of bioavailable DIM should be increased to 400-500mg per day.
Researchers are finding a tremendous link between increased intake of broccoli, cabbage and Brussels sprouts and the reduction in severity and frequency of herpes simplex. A nutrient combination that includes the active substance in these three vegetables, Indole 3 Carbinol, is available in a professionally manufactured combination called DIM/13-C. This formulation is effective at inhibiting the growth and reproduction of the herpes simplex cells.
There is a new appreciation of the effects of changing estrogen metabolism that come with male aging, now identified as andropause. German researchers have clearly documented a dramatic, aging-related accumulation of estrogen in human prostate glands. This work correlated age, estrogen accumulation, and the presence of benign prostatic hypertrophy (BPH). This underscores the role of estrogen as a growth promoting hormone in men as well as women.
Tissue accumulation of estrogen is a unique hallmark of andropause, distinct from estrogen deficiency which characterizes menopause. 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.
Accumulation of estrogen during andropause is amplified by obesity since fat tissue is the site of conversion of both testosterone and DHEA into estrogen. In case control studies, higher levels of circulating estrogen predict the degree of prostate enlargement. More importantly, increased estrogen levels have been repeatedly noted as a risk factor for early atherosclerosis and heart attack. The risks of elevated estrogen in men further correlate to decreased ability to dissolve blood clots. The specific deficiency in men of an active, beneficial metabolism of estrogen leading to 2-methoxy estrogens would explain many, if not all, of these observations.
In studies culturing human vascular endothelial cells, it has been shown that 2-methoxy estradiol is a primary regulator of cell growth and apoptosis. Active and regulated apoptosis may contribute to the prevention of atherosclerotic plaque formation. At the basic level of lipoprotein status, 2-hydroxy and 2-methoxy estrogens are powerful antioxidants. In recent experiments, these metabolites, whose production is promoted by DIM, have been shown to prevent the oxidation of human lipoproteins. Lipoprotein oxidation is now accepted as an early, initiating event in atherosclerosis. While it remains to be demonstrated through intervention studies that DIM supplementation can slow the progression of prostate disease and atherosclerosis, it is clear that DIM supplementation in men can beneficially shift estrogen metabolism.
Phytochemicals such as indole-3-carbinol (I3C) and sulforaphane are components of cruciferous vegetables which exhibit antitumorigenic activity associated with altered carcinogen metabolism and detoxification. Diindolylmethane (DIM) is a major metabolite of I3C formed in the gut and represents a new class of antiestrogens that inhibit breast cancer growth. It also encourages cells that are abnormally multiplying to stop reproducing and die.
Researchers have found that DIM and genistein (a major isoflavone in soy) reduce production of two proteins whose chemotactic attraction to each other is necessary for the spread of breast and ovarian cancers.
When applying purified versions of DIM and genistein to motile cancer cells, the researchers could literally watch these cells come to a near halt. When either compound was applied, migration and invasion were substantially reduced.
Both DIM and genistein are already being developed for use as a preventive and a chemotherapy treatment for breast cancer, although more extensive toxicological studies are necessary as at the time of writing (2007).
See the link between Breast Cancer and DIM.
DIM may reduce prostate cancer incidence as it has been shown to stop human cancer cells from growing (by 54-61%) and provokes the cells to self-destruct (apoptosis). DIM also improves prostate function.
In two papers published in the Journal of Biological Chemistry (Mar 27, 2003) researchers reported that DIM significantly halted proliferation of androgen-dependent human prostate cancer cells. In one of the studies, androgen-dependent prostate cancer cells treated with DIM grew 70% less than androgen-dependent untreated cells. DIM also inhibited dihydrotestosterone (DHT) stimulation of DNA synthesis in the androgen-dependent cancer cells. These effects were not seen in androgen-independent prostate cancer cells.
To determine whether men are at risk for prostate cancer, they are usually tested for levels of prostate-specific antigen (PSA), a growth factor for prostate cancer. In prostate cancer cells, DIM reduced intracellular and secreted PSA protein levels caused by DHT. The researchers determined that DIM's molecular structure is similar to Casodex, a synthetic anti-androgen drug.
"As far as we know, this is the first plant-derived chemical discovered that acts as an anti-androgen," said Leonard Bjeldanes, professor and chair of nutritional sciences and toxicology at UC Berkeley's College of Natural Resources and principal investigator of the study. "This is of considerable interest in the development of therapeutics and preventive agents for prostate cancer."