Health Care Professional Information
Clinical Summary
Diindolylmethane (DIM) is a metabolite of Indole-3-carbinol (I3C), a compound found in cruciferous vegetables including broccoli, cabbage and cauliflower. It is the most studied of all I3C metabolites and is thought to be superior to IC3 as a chemoprotective compound for breast cancer and prostate cancer (3). DIM demonstrated anti-proliferative effects in animal and cancer cell models through various mechanisms.
In contrast to I3C which has been used in over a dozen clinical trials, few studies have been published using DIM. In one study, daily supplementation with DIM led to changes in estrogen metabolism in post menopausal women with a history of early stage breast cancer (4); DIM supplementation, did not, however, have any effects in women with cervical cell abnormalities (13).
DIM's effects have not been confirmed in cancer patients. Further studies are warranted.
Food Sources
Vegetables including broccoli, Brussels sprouts, cauliflower and cabbage (1)
Purported Uses
- Cancer prevention
- Estrogen metabolism
- Detoxification
Mechanism of Action
Diindolylmethane (DIM), a metabolite of I3C, can induce apoptosis by modulating the expression of the Bax/Bcl-2. It demonstrated antiproliferative effects in animal and cancer cell models (1). It was also shown to inhibit invasion of normal tissue by cancer cells and to inhibit angiogenesis in cell culture models (5). Both DIM and I3C induce the activity of phase I and phase II enzymes involved in biotransformation and elimination of steroid hormones and carcinogens in vitro. Physiological concentrations of I3C and DIM induce cytochrome P450 enzymes in cancer cells in vitro. The increased CYP450 activity of these enzymes leads to increased metabolism of estrogen and degradation of estradiol needed for the growth of estrogen receptor-alpha positive cancer cells. DIM induces apoptosis in pancreatic cancer cells (6)and enhances the effect of erlotinib (7). In colon cancer and prostate cancer cells, DIM inhibits CDK activities (8) (9) and induces apoptosis by down regulating survivin (10) (11). DIM supplementation alters estrogen urinary metabolite profiles in women (4). DIM has androgen antagonistic effect (14). It inhibits prostate cancer cells proliferation and induces apoptosis through Akt activation, NF-KB DNA binding, and androgen receptor phosphorylation (15).
Pharmacokinetics
Diindolylmethane is a metabolic byproduct of I3C resulting from gastric acid conversion. On average 10-20% of I3C is metabolized to DIM (1). Following oral administration of I3C in mice, both I3C and DIM were detectable at mmol/L concentrations in organs and blood. I3C was quickly absorbed and cleared from tissues and blood in one hour while DIM had a slightly later peak concentration and was more persistent (2). An absorption-enhanced form of DIM was absorbed in a linear dose-dependent manner up to 200mg and a serum level of 104ng/ml was achieved. Higher doses did not result in increased serum concentration (12).
Herb-Drug Interactions
Theoretically, DIM and I3C can induce cytochrome P450 1 enzyme and may reduce serum concentration of medications that it metabolizes.
Herb Lab Interactions
DIM supplementation has been shown to alter estrogen urinary metabolites in women (4).
Literature Summary and Critique
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):161-167.
In a prospective placebo-controlled pilot study 19 post-menopausal women with a history of early stage breast cancer were randomized to receive 108mg DIM or placebo for thirty days. Urinary metabolite analysis was conducted for 2-hydroxyestrone (2OHE-1), 16-alpha hydroxyestrone (16alpha=OHE-1), DIM, estrone (E1), estradiol (E2), estriol (E3), 6beta-hydroxycortisol (6betaOHC) and cortisol. The treatment group demonstrated significant increases in levels of 2-OHE1 (P=0.020), DIM (P=0.045), and cortisol (P=0.039) and a non-significant increase in the 2-OHE1/16alpha-OHE1 ratio from 1.46 to2.14 (P=0.059). The results of this study demonstrate that DIM supplementation increases 2-hydroxylation of urinary estrogen metabolites. But whether this translates to reduced cancer risk has not been confirmed.
Dosage (Inside MSKCC Only)
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References
- Minich DM, Bland JS. A review of the clinical efficacy and safety of cruciferous vegetable phytochemicals. Nutr Rev 2007;65(6 Pt 1):259-267.
- Howells LM, Moiseeva EP, Neal CP et al. Predicting the physiological relevance of in vitro cancer preventive activities of phytochemicals. Acta Pharmacol Sin 2007;28(9):1274-1304.
- Bradlow HL. Review. Indole-3-carbinol as a chemoprotective agent in breast and prostate cancer. In Vivo 2008;22(4):441-445.
- 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), 161-167.
- Higdon JV, Delage B, Williams DE, Dashwood RH. Cruciferous vegetables and human cancer risk: epidemiologic evidence and mechanistic basis. Pharmacol Res 2007;55(3):224-236.
- Azmi AS, Ahmad A, Banerjee S et al. Chemoprevention of pancreatic cancer: characterization of Par-4 and its modulation by 3,3' diindolylmethane (DIM). Pharm Res 2008;25(9):2117-2124.
- Ali S, Banerjee S, Ahmad A et al. Apoptosis-inducing effect of erlotinib is potentiated by 3,3'-diindolylmethane in vitro and in vivo using an orthotopic model of pancreatic cancer. Mol Cancer Ther 2008;7(6):1708-1719.
- Choi HJ, Lim DY, Park JH. Induction of G1 and G2/M cell cycle arrests by the dietary compound 3,3'-diindolylmethane in HT-29 human colon cancer cells. BMC Gastroenterol 2009;9(1):39.
- Chinnakannu K, Chen D, Li Y et al. Cell cycle-dependent effects of 3,3'-diindolylmethane on proliferation and apoptosis of prostate cancer cells. J Cell Physiol 2009;219(1):94-99.
- Bhatnagar N, Li X, Chen Y et al. 3,3'-Diindolylmethane Enhances the Efficacy of Butyrate in Colon Cancer Prevention through Down-Regulation of Survivin.Cancer Prev Res (Phila Pa) 2009;2(6):581-589.
- Rahman KM, Banerjee S, Ali S et al. 3,3'-Diindolylmethane enhances taxotere-induced apoptosis in hormone-refractory prostate cancer cells through survivin down-regulation. Cancer Res 2009;69(10):4468-4475.
- Reed GA, Sunega JM, Sullivan DK et al. Single-dose pharmacokinetics and tolerability of absorption-enhanced 3,3'-diindolylmethane in healthy subjects. Cancer Epidemiol Biomarkers Prev 2008;17(10):2619-2624.
- Castañon A, Tristram A, Mesher D, et al. Effect of diindolylmethane supplementation on low-grade cervical cytological abnormalities: double-blind, randomised, controlled trial. Br J Cancer. 2012 Jan 3;106(1):45-52.
- Le HT, Schaldach CM, Firestone GL, et al. 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.
- Bhuiyan MM, Li Y, Banerjee S, et al. Down-regulation of androgen receptor by 3,3'-diindolylmethane contributes to inhibition of cell proliferation and induction of apoptosis in both hormone-sensitive LNCaP and insensitive C4-2B prostate cancer cells. Cancer Res. 2006 Oct 15;66(20):10064-72.
Consumer Information
How It Works
Bottomline: Diindolylmethane (DIM) may have anticancer effects, but this has not been studied in humans.
Diindolylmethane is a compound found in cruciferous vegetables including broccoli, cabbage, and cauliflower. It showed anticancer effects in laboratory and animal studies. However, human studies are limited.
Purported Uses
- Cancer Prevention
Lab studies suggest anticancer activities. But evidence from human studies is lacking.
Research Evidence
In a prospective placebo-controlled study, 19 post-menopausal women with a history of early stage breast cancer were randomized to receive 108mg DIM or placebo for thirty days. Urinary metabolite analysis was conducted for 2-hydroxyestrone (2OHE-1), 16-alpha hydroxyestrone (16alpha=OHE-1), DIM, estrone (E1), estradiol (E2), estriol (E3), 6beta-hydroxycortisol (6betaOHC) and cortisol. The treatment group demonstrated significant increases in levels of 2-OHE1, DIM, and cortisol and a non-significant increase in the 2-OHE1/16alpha-OHE1 ratio. These results demonstrate that DIM supplementation increases 2-hydroxylation of urinary estrogen metabolites.
Patient Warnings
Although DIM (and I3C) were shown to alter estrogen urinary metabolite profiles in women, their effects on breast cancer risk are unknown.
Side Effects
Rash, arthralgia, nausea, vomiting, headache and hot flashes have been reported.
Last updated: April 26, 2012
administration (ad-MIH-nih-STRAY-shun)
In medicine, the act of giving a treatment, such as a drug, to a patient. It can also refer to the way it is given, the dose, or how often it is given.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)Akt
A group of enzymes involved in several processes related to cell growth and survival. Akt enzymes help to transfer signals inside cells. An Akt enzyme is a type of serine/threonine protein kinase. Also called protein kinase B.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)analysis (uh-NA-lih-sis)
A process in which anything complex is separated into simple or less complex parts.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)androgen (AN-droh-jen)
A type of hormone that promotes the development and maintenance of male sex characteristics.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)angiogenesis (AN-jee-oh-JEH-neh-sis)
Blood vessel formation. Tumor angiogenesis is the growth of new blood vessels that tumors need to grow. This is caused by the release of chemicals by the tumor.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)apoptosis (A-pop-TOH-sis)
A type of cell death in which a series of molecular steps in a cell leads to its death. This is the body’s normal way of getting rid of unneeded or abnormal cells. The process of apoptosis may be blocked in cancer cells. Also called programmed cell death.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)arthralgia (ar-THRAL-juh)
Joint pain.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)blood (blud)
A tissue with red blood cells, white blood cells, platelets, and other substances suspended in fluid called plasma. Blood takes oxygen and nutrients to the tissues, and carries away wastes.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)breast (brest)
Glandular organ located on the chest. The breast is made up of connective tissue, fat, and breast tissue that contains the glands that can make milk. Also called mammary gland.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)breast cancer (brest KAN-ser)
Cancer that forms in tissues of the breast, usually the ducts (tubes that carry milk to the nipple) and lobules (glands that make milk). It occurs in both men and women, although male breast cancer is rare.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)cancer (KAN-ser)
A term for diseases in which abnormal cells divide without control and can invade nearby tissues. Cancer cells can also spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is a cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is a cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is a cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord. Also called malignancy.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)cell (sel)
The individual unit that makes up the tissues of the body. All living things are made up of one or more cells.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)cell culture (sel KUL-cher)
The growth of microorganisms such as bacteria and yeast, or human, plant, or animal cells in the laboratory. Cell cultures may be used to diagnose infections, to test new drugs, and in research.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)cervical (SER-vih-kul)
Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck. Cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the “neck”) of the uterus.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)chemoprotective (KEE-moh-proh-TEK-tiv)
A quality of some drugs used in cancer treatment. Chemoprotective agents protect healthy tissue from the toxic effects of anticancer drugs.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)clinical (KLIH-nih-kul)
Having to do with the examination and treatment of patients.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)colon (KOH-lun)
The longest part of the large intestine, which is a tube-like organ connected to the small intestine at one end and the anus at the other. The colon removes water and some nutrients and electrolytes from partially digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)compound (KOM-pownd)
In science, a substance that is made up of more than one ingredient.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)concentration (KON-sen-TRAY-shun)
In science, the amount of a substance, such as a salt, that is in a certain amount of tissue or liquid, such as blood. A substance becomes more concentrated when less water is present. For example, the salt in urine may become more concentrated when a person doesn’t drink enough water.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)cortisol (KOR-tih-sol)
A hormone made by the adrenal cortex (the outer layer of the adrenal gland). It helps the body use glucose (a sugar), protein, and fats. Cortisol made in the laboratory is called hydrocortisone. It is used to treat many conditions, including inflammation, allergies, and some cancers. Cortisol is a type of glucocorticoid hormone.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)diindolylmethane (dy-IN-doh-lil-MEH-thayn)
A substance being studied in the treatment of prostate cancer and in the prevention of cervical cancer. Diindolylmethane is found in cruciferous vegetables like broccoli, brussels sprouts, cauliflower, cabbage, and kale. It is a type of plant indole. Also called DIM.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)DIM
A substance being studied in the treatment of prostate cancer and in the prevention of cervical cancer. DIM is found in cruciferous vegetables like broccoli, brussels sprouts, cauliflower, cabbage, and kale. It is a type of plant indole. Also called diindolylmethane.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)DNA
The molecules inside cells that carry genetic information and pass it from one generation to the next. Also called deoxyribonucleic acid.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)dose-dependent (dose-deh-PEN-dent)
Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose-dependent.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)enzyme (EN-zime)
A protein that speeds up chemical reactions in the body.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)erlotinib (er-LOH-tih-nib)
A drug used to treat certain types of non-small cell lung cancer. It is also used together with gemcitabine to treat pancreatic cancer and is being studied in the treatment of other types of cancer. Erlotinib is a type of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. Also called CP-358,774, erlotinib hydrochloride, OSI-774, and Tarceva.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)estradiol (es-truh-DY-ol)
A form of the hormone estrogen.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)estrogen (ES-truh-jin)
A type of hormone made by the body that helps develop and maintain female sex characteristics and the growth of long bones. Estrogens can also be made in the laboratory. They may be used as a type of birth control and to treat symptoms of menopause, menstrual disorders, osteoporosis, and other conditions.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)in vitro (in VEE-troh)
In the laboratory (outside the body). The opposite of in vivo (in the body).
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)metabolism (meh-TA-buh-lih-zum)
The chemical changes that take place in a cell or an organism. These changes make energy and the materials cells and organisms need to grow, reproduce, and stay healthy. Metabolism also helps get rid of toxic substances.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)metabolite (meh-TA-boh-lite)
A substance made or used when the body breaks down food, drugs or chemicals, or its own tissue (for example, fat or muscle tissue). This process, called metabolism, makes energy and the materials needed for growth, reproduction, and maintaining health. It also helps get rid of toxic substances.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)nausea (NAW-zee-uh)
A feeling of sickness or discomfort in the stomach that may come with an urge to vomit. Nausea is a side effect of some types of cancer therapy.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)oral (OR-ul)
By or having to do with the mouth.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)pancreatic (PAN-kree-A-tik)
Having to do with the pancreas.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)phosphorylation (fos-FOR-ih-LAY-shun)
A process in which a phosphate group is added to a molecule, such as a sugar or a protein.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)pilot study (PY-lut STUH-dee)
The initial study examining a new method or treatment.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)placebo (pluh-SEE-boh)
An inactive substance or treatment that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)placebo-controlled (pluh-SEE-boh-kun-TROLD)
Refers to a clinical study in which the control patients receive a placebo.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)prospective (pruh-SPEK-tiv)
In medicine, a study or clinical trial in which participants are identified and then followed forward in time.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)prostate (PROS-tayt)
A gland in the male reproductive system. The prostate surrounds the part of the urethra (the tube that empties the bladder) just below the bladder, and produces a fluid that forms part of the semen.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)prostate cancer (PROS-tayt KAN-ser)
Cancer that forms in tissues of the prostate (a gland in the male reproductive system found below the bladder and in front of the rectum). Prostate cancer usually occurs in older men.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)randomized
Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments.
(http://www.cancer.gov/dictionary)receptor (reh-SEP-ter)
A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)serum (SEER-um)
The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)significant (sig-NIH-fih-kunt)
In statistics, describes a mathematical measure of difference between groups. The difference is said to be significant if it is greater than what might be expected to happen by chance alone. Also called statistically significant.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)stage (stayj)
The extent of a cancer in the body. Staging is usually based on the size of the tumor, whether lymph nodes contain cancer, and whether the cancer has spread from the original site to other parts of the body.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)steroid (STAYR-oyd)
Any of a group of lipids (fats) that have a certain chemical structure. Steroids occur naturally in plants and animals or they may be made in the laboratory. Examples of steroids include sex hormones, cholesterol, bile acids, and some drugs.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)supplementation (SUH-pleh-men-TAY-shun)
Adding nutrients to the diet.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)tissue (TIH-shoo)
A group or layer of cells that work together to perform a specific function.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)urinary (YOOR-ih-NAYR-ee)
Having to do with urine or the organs of the body that produce and get rid of urine.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)
