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Alternative Names: 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.
Source
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.
Function; Reasons For Use
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.
Directions
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.
Side-Effects; Counter-Indicators and Warnings
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.
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DIM (di-indolmethane)/I3C (Indole-3-Carbinol) can help with the following: | | | | | Autoimmune |  Lupus, SLE (Systemic Lupus Erythromatosis) | 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. |
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Hormones |
Progesterone Low or Estrogen Dominance| | DIM encourages the conversion of estrogens to safer forms and helps reduce elevated levels. |
Low Male Testosterone Level| | 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. |
Not recommended for:
 Low Sex Hormone Binding Globulin| | Aromatase inhibitors such as DIM, I3C, and Chrysin should be avoided, as they will enhance any preexisting androgen/estrogen dominance. |
High Female Testosterone Level| | Aromatase inhibitors such as DIM, I3C, and Chrysin should be avoided, as they will enhance any preexisting androgen/estrogen dominance. |
High Male Testosterone Level| | Aromatase inhibitors such as DIM, I3C, and Chrysin should be avoided, as they will enhance any preexisting androgen/estrogen dominance. |
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Infections |
 Herpes Simplex Type I| | 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. |
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Laboratory Test Needed |
 Elevated Insulin Levels| | DIM has been reported to enhance insulin sensitivity and encourage abdominal fat loss. |
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Tumors, Malignant |
Breast Cancer| | 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). |
Prostate Cancer| | 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." |
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Uro-Genital |
Andropause/Male Menopause| | 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. |
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KEY | | May do some good | | | Likely to help | | | Highly recommended | | | Reasonably likely to cause problems |
GLOSSARY
Abdomen (Abdominal)
That part of the body between the chest and the hips that contains the stomach, intestines, liver, bladder, pancreas and other organs.
Androgen
Any steroid hormone that increases male characteristics.
Antigen (Antigenic, Antigens)
A substance, usually protein or protein-sugar complex in nature, which, being foreign to the bloodstream or tissues of an animal, stimulates the formation of specific blood serum antibodies and white blood cell activity. Re-exposure to similar antigen will reactivate the white blood cells and antibody programmed against this specific antigen.
Antioxidant (Antioxidants)
A chemical compound that slows or prevents oxygen from reacting with other compounds. Some antioxidants have been shown to have cancer-protecting potential because they neutralize free radicals. Examples include vitamins C and E, beta carotene, the minerals selenium and germanium, superoxide dismutase (SOD), coenzyme Q10, catalase, and some amino acids.
Apoptosis
Programmed cell death as signaled by the nuclei in normally functioning human and animal cells when age or state of cell health and condition dictates. Cancerous cells, however, are unable to experience the normal cell transduction or apoptosis-driven natural cell death process.
Atherosclerosis
Common form of arteriosclerosis associated with the formation of atheromas which are deposits of yellow plaques containing cholesterol, lipids, and lipophages within the intima and inner media of arteries. This results in a narrowing of the arteries, which reduces the blood and oxygen flow to the heart and brain as well as to other parts of the body and can lead to a heart attack, stroke, or loss of function or gangrene of other tissues.
Benign Prostatic Hypertrophy (Benign Prostatic Hyperplasia, BPH)
The benign buildup in the prostate of "warts" or epithelial neoplasias that can block or interrupt urination, and which are usually concurrent with moderate prostate enlargement. They cause a dull ache on urination, ejaculation, and/or defecation. The diagnosis is medical, since the same subjective conditions can result fromcancer of the prostate. BPH is common in men over fifty and can be the result either of diminished production of complete testosterone or poor pelvic circulation. Alcohol, coffee, speed, and antihistamines can all aggravate the problem.
Cancer
Refers to the various types of malignant neoplasms that contain cells growing out of control and invading adjacent tissues, which may metastasize to distant tissues.
Carcinogen (Carcinogenic, Carcinogenicity)
Any agent that is cancer-causing.
Chemotherapy
A treatment of disease by any chemicals. Used most often to refer to the chemical treatments used to combat cancer cells. Chemotherapy is usually given in cycles: a treatment period followed by a recovery period, then another treatment period, and so on. Most anticancer drugs are given by injection into a blood vessel (IV); some are given by mouth. Chemotherapy is a systemic therapy, meaning that the drugs enter the bloodstream and travel throughout the body. Usually, a patient has chemotherapy as an outpatient (at the hospital, at the doctor's office, or at home). However, depending on which drugs are given and the patient's general health, a short hospital stay may be needed.
DHEA (DHEA-S)
Dehydroepiandrosterone (DHEA) is a steroid produced by the adrenal glands and is the most abundant one found in humans. DHEA may be transformed into testosterone, estrogen or other steroids. It is found in the body as DHEA or in the sulfated form known as DHEA-S. One form is converted into the other as needed.
Dihydrotestosterone (DHT)
A highly active form of testosterone, which influences many aspects of manly behavior, from sex drive to aggression. The conversion from testosterone to DHT is driven by an enzyme called 5-alpha reductase, which is produced in the prostate, various adrenal glands, and the scalp.
DNA
Deoxyribonucleic acid, the large molecule that is the main carrier of genetic information in cells. DNA is found mainly in the chromosomes of cells.
Endothelium (Endothelia, Endothelial, Endothelioid)
A thin layer of flat epithelial cells that lines serous cavities, lymph vessels, and blood vessels.
Enzymes (Enzyme)
Specific protein catalysts produced by the cells that are crucial in chemical reactions and in building up or synthesizing most compounds in the body. Each enzyme performs a specific function without itself being consumed. For example, the digestive enzyme amylase acts on carbohydrates in foods to break them down.
Estrogen (Oestrogen)
One of the female sex hormones produced by the ovaries.
Gastric
Of, relating to, or associated with the stomach.
Gland (Glands)
The glandular system is one of the most important and complicated systems of the body. Gland tissue can be either an organ or general tissue that secretes chemicals and there are two types of gland: exocrine and endocrine. Those glands which secrete chemicals through tubules or ducts are called exocrine and include sweat, tear and salivary glands. Ductless glands - part of the endocrine system - secrete special chemicals (hormones) directly into the blood.
Herpes Simplex
An infection, often recurrent, caused by herpes virus type 1 and 2. It causes cold sores around the lips and mouth, and also causes painful blisters on the genitals and in the pubic area, thighs, and buttocks.
Hormones (Hormone)
Chemical substances secreted by a variety of body organs that are carried by the bloodstream and usually influence cells some distance from the source of production. Hormones signal certain enzymes to perform their functions and, in this way, regulate such body functions as blood sugar levels, insulin levels, the menstrual cycle, and growth. These can be prescription, over-the-counter, synthetic or natural agents. Examples include adrenal hormones such as corticosteroids and aldosterone; glucagon, growth hormone, insulin, testosterone, estrogens, progestins, progesterone, DHEA, melatonin, and thyroid hormones such as thyroxine and calcitonin.
Hydrochloric Acid (HCl)
An inorganic acidic compound, excreted by the stomach, that aids in digestion.
Insulin
A hormone secreted by the pancreas in response to elevated blood glucose levels. Insulin stimulates the liver, muscles, and fat cells to remove glucose from the blood for use or storage.
Kilogram (kg, kgs, Kilogramme, Kilogrammes, Kilograms)
1000 grams, 2.2lbs.
Lactation (Lactate, Lactates, Lactating)
Production of milk; period after giving birth during which milk is secreted in the breasts.
Lipoproteins (Lipoprotein)
Molecules composed of lipids and proteins that carry fats and cholesterol through the bloodstream.
Menopause (Menopausal)
The cessation of menstruation (usually not official until 12 months have passed without periods), occurring at the average age of 52. As commonly used, the word denotes the time of a woman's life, usually between the ages of 45 and 54, when periods cease and any symptoms of low estrogen levels persist, including hot flashes, insomnia, anxiety, mood swings, loss of libido and vaginal dryness. When these early menopausal symptoms subside, a woman becomes postmenopausal.
Metabolism (Metabolic, Metabolize, Metabolizes, Metabolizing)
The chemical processes of living cells in which energy is produced in order to replace and repair tissues and maintain a healthy body. Responsible for the production of energy, biosynthesis of important substances, and degradation of various compounds. Also defined as the sum total of changes in an organism in order to achieve a balance (homeostasis): Catabolic burns up, anabolic stores and builds up; the sum of their work is metabolism.
Metabolite (Metabolites)
Any product (foodstuff, intermediate, waste product) of metabolism.
Milligram (mg, Milligrams)
0.001 or a thousandth of a gram.
Phytochemicals (Phytochemical)
Substances such as vitamins and minerals that occur naturally in plants and have been shown in research to possibly prevent or cure disease.
Prostate
The prostate gland in men that surrounds the neck of the bladder and the urethra and produces a secretion that liquefies coagulated semen.
Protein (Proteins)
Compounds composed of hydrogen, oxygen, and nitrogen present in the body and in foods that form complex combinations of amino acids. Protein is essential for life and is used for growth and repair. Foods that supply the body with protein include animal products, grains, legumes, and vegetables. Proteins from animal sources contain the essential amino acids. Proteins are changed to amino acids in the body.
Serum
The cell-free fluid of the bloodstream. It appears in a test tube after the blood clots and is often used in expressions relating to the levels of certain compounds in the blood stream.
Stomach
A hollow, muscular, J-shaped pouch located in the upper part of the abdomen to the left of the midline. The upper end (fundus) is large and dome-shaped; the area just below the fundus is called the body of the stomach. The fundus and the body are often referred to as the cardiac portion of the stomach. The lower (pyloric) portion curves downward and to the right and includes the antrum and the pylorus. The function of the stomach is to begin digestion by physically breaking down food received from the esophagus. The tissues of the stomach wall are composed of three types of muscle fibers: circular, longitudinal and oblique. These fibers create structural elasticity and contractibility, both of which are needed for digestion. The stomach mucosa contains cells which secrete hydrochloric acid and this in turn activates the other gastric enzymes pepsin and rennin. To protect itself from being destroyed by its own enzymes, the stomach’s mucous lining must constantly regenerate itself.
Testosterone
The principal male sex hormone that induces and maintains the changes that take place in males at puberty. In men, the testicles continue to produce testosterone throughout life, though there is some decline with age. A naturally occurring androgenic hormone.
Uterus (Uterine)
The part of the female reproductive system specialized to allow the implantation, growth and nourishment of a fetus during pregnancy.
Vascular
Relating to the blood vessels of the body. The blood vessels of the body, as a group, are referred to as the vascular system. They are composed of arteries, veins and capillaries - arteries that pass oxygen-rich blood to the tissues of the body; veins which return oxygen-depleted blood from the tissues to the lungs for oxygen; and the capillaries that are the tiniest vessels and are between the arteries and veins.
Last updated: Jun 08, 2008
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