Natural Standard Bottom Line Monograph, Copyright © 2013 (www.naturalstandard.com). Commercial distribution prohibited. This monograph is intended for informational purposes only, and should not be interpreted as specific medical advice. You should consult with a qualified healthcare provider before making decisions about therapies and/or health conditions.
While some complementary and alternative techniques have been studied scientifically, high-quality data regarding safety, effectiveness, and mechanism of action are limited or controversial for most therapies. Whenever possible, it is recommended that practitioners be licensed by a recognized professional organization that adheres to clearly published standards. In addition, before starting a new technique or engaging a practitioner, it is recommended that patients speak with their primary healthcare provider(s). Potential benefits, risks (including financial costs), and alternatives should be carefully considered. The below monograph is designed to provide historical background and an overview of clinically-oriented research, and neither advocates for or against the use of a particular therapy.
1,1-Bis[3'-(5-methoxyindolyl)]-1-(p-t-butylphenyl) methane, 1,1-bis(3'-indolyl)-1-(p-substituted phenyl)methane, 1,1-bis(3'-indolyl)-1-(p-t-butylphenyl)methane, 2-carboxy-5-nitrobenzne sulfonic acid, 3-(1H-indol-3-ylmethyl)-1H-indole, 3-(1H-indole-3-ylmethyl)-2-oxindole (2-ox-DIM), 3,3'-diindolylmethane, 3,3'-methanediylbis(1H-indole), 3,3'-methylene-bis-1H-indole, 3,3'-methylene-bisindole, 3,3'-methylenebisindole, 3,3'-methylenediindole, 3-diindolul methane, 3-[hydroxy-(1H-indol-3-yl)-methyl]-1,3-dihydro-2-oxindole (3-methylenehydroxy-2-ox-DIM), 3-hydroxy-3-(1H-indole-3-ylmethyl)-2-oxindole (3-hydroxy-2-ox-DIM), 3-indolylmethyl glucosinolate, arundine, B-DIM, BioResponse BR-DIM, BioResponse DIM®, bis(1H-indol-3-yl)methanol (3-methylenehydroxy-DIM), bis(3-indolyl)methane, Brassica spp., Brassicaceae, BR-DIM, C-DIMs, di-indoylmethane, diinolylmethane, DIM, DIM-C-pPhtBu, glucobrassicin, I33', I3C, indole dimer diindole methane, indole-3-carbinol, indoles, indolplex, indolyl-CH2-indolyl.
3,3'-Diindolylmethane (DIM or I33') is produced by indole-3-carbinol (I3C). I3C may be found in many vegetables in the Brassica family, like broccoli, cabbage, or brussels sprouts. I3C forms DIM when it comes into contact with stomach acid.
DIM is commonly used as a dietary supplement and is believed to have anticancer activity. The anticancer effects of DIM have been observed in many cancer cell lines, particularly breast and prostate cancer lines. According to one study, DIM may not be clinically superior to I3C, but it may enhance the effects of I3C.
There is increasing evidence that shows a link between estrogen metabolism and cancer, as well as increasing evidence showing that estrogen metabolism may be changed through increasing supplements such as DIM and I3C in the diet. Dietary intervention may be a potential way to change estrogen metabolism for cancer prevention. Some studies, however, caution that I3C may promote estrogen metabolite formation or activate estrogen receptors, which may cause tumors. More research is needed before a strong conclusion may be made.
These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.
Preliminary research on early-stage breast cancer shows that diindolylmethane may have an effect on estrogen metabolism, but it is unclear whether this translates to a reduced risk of cancer. Higher-quality evidence is needed before further conclusions can be made.
Preliminary evidence shows that diindolylmethane may improve cervical intraepithelial neoplasia. More research is needed before a conclusion can be made.
Preliminary research shows that diindolylmethane may improve prostate cancer without causing significant toxicity. However, more research is needed before a conclusion can be made.
*Key to grades:A: Strong scientific evidence for this use; B: Good scientific evidence for this use; C: Unclear scientific evidence for this use; D: Fair scientific evidence against this use (it may not work); F: Strong scientific evidence against this use (it likely does not work).
The below uses are based on tradition or scientific theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious and should be evaluated by a qualified health care professional.
Antibacterial, antioxidant, antiparasitic, antiviral, arthritis, atherosclerosis (clogged arteries), breast pain (mastalgia), cancer (general), cervical dysplasia (abnormal pap smear), colon cancer, detoxification from alcohol or toxins, endometrial cancer, endometriosis, enlarged prostate, estrogenic effects, hormonal effects, human papilloma virus, immunomodulation, inflammation, leukemia, liver cancer, lung cancer, pancreatic cancer, Parkinson's disease, premenstrual syndrome, sexual activity enhancement, strength, tumor, uterine cancer.
The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.
Adults (18 years and older)
To treat cervical cancer, two milligrams of DIM per kilogram have been taken by mouth daily for 12 weeks.
Children (under 18 years old)
There is no proven safe or effective dose for DIM in children.
The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.
Avoid with known allergy or sensitivity to DIM or to any part of the formula.
Side Effects and Warnings
DIM is likely safe when used in doses of two milligrams per kilogram daily for up to 12 weeks.
Avoid with known allergy or sensitivity to DIM or to any part of the formula.
Avoid in children and in pregnant or breastfeeding women, due to a lack of safety data.
DIM may affect blood sugar levels. Caution is advised in people with diabetes or hypoglycemia, and in those taking drugs, herbs, or supplements that affect blood sugar. Blood glucose levels may need to be monitored by a qualified healthcare professional, including a pharmacist, and medication adjustments may be necessary.
Use cautiously in single doses of 300 milligrams or more.
Use cautiously in people who have conditions that may change sodium or sodium levels. Use cautiously in people who have estrogen-sensitive cancer.
Use cautiously in people who take laxatives.
DIM may also cause changes in estrogen metabolism, changes in sodium levels, diarrhea, headache, hot flashes, joint pain, nausea, skin rash, upset stomach, and vomiting.
Pregnancy and Breastfeeding
There is currently a lack of scientific evidence on the use of DIM during pregnancy or breastfeeding.
Most herbs and supplements have not been thoroughly tested for interactions with other herbs, supplements, drugs, or foods. The interactions listed below are based on reports in scientific publications, laboratory experiments, or traditional use. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy.
Interactions with Drugs
DIM may affect blood sugar levels. Caution is advised when using medications that may also affect blood sugar. People taking drugs for diabetes by mouth or insulin should be monitored closely by a qualified healthcare professional, including a pharmacist. Medication adjustments may be necessary.
DIM may interfere with the way the body processes certain drugs using the liver's cytochrome P450 enzyme system. As a result, the levels of these drugs may be increased in the blood and may cause increased effects or potentially serious adverse reactions. People using any medications should check the package insert and speak with a qualified healthcare professional, including a pharmacist, about possible interactions.
DIM may also interact with agents that may affect electrolyte levels, agents that may affect the immune system, agents that may affect PPAR-gamma, agents that may affect protein kinase A, anticancer agents, anti-inflammatory agents, antiparasitic agents, estrogens, interferons, laxatives, and nicotine.
Interactions with Herbs and Dietary Supplements
DIM may affect blood sugar levels. Caution is advised when using herbs or supplements that may also affect blood sugar. Blood glucose levels may require monitoring, and doses may need adjustment.
DIM may interfere with the way the body processes certain herbs or supplements using the liver's cytochrome P450 enzyme system. As a result, the levels of other herbs or supplements may become too high in the blood. It may also alter the effects that other herbs or supplements possibly have on the P450 system.
DIM may also interact with anticancer herbs and supplements, anti-inflammatory herbs and supplements, antioxidants, antiparasitic herbs and supplements, fat-soluble vitamins, genistein, herbs and supplements that may affect electrolyte levels, herbs and supplements that may affect the immune system, herbs and supplements that may affect PPAR-gamma, herbs and supplements that may affect protein kinase A, indole [3,2-b]carbazole (ICZ), inositol, phosphatidylcholine, phytoestrogen, quercetin, and tobacco.
This information is based on a systematic review of scientific literature edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).
Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.
Ahmad A, Ali S, Wang Z, et al. 3,3'-Diindolylmethane enhances taxotere-induced growth inhibition of breast cancer cells through downregulation of FoxM1. Int.J.Cancer 10-1-2011;129(7):1781-1791. View Abstract
Ahmad A, Sakr WA, Rahman KM. Anticancer properties of indole compounds: mechanism of apoptosis induction and role in chemotherapy. Curr.Drug Targets. 2010;11(6):652-666. View Abstract
Ali S, Banerjee S, Schaffert JM, et al. Concurrent inhibition of NF-kappaB, cyclooxygenase-2, and epidermal growth factor receptor leads to greater anti-tumor activity in pancreatic cancer. J.Cell Biochem. 2010;110(1):171-181. View Abstract
Dong L, Xia S, Gao F, et al. 3,3'-Diindolylmethane attenuates experimental arthritis and osteoclastogenesis. Biochem.Pharmacol. 3-1-2010;79(5):715-721. View Abstract
Huang J, Plass C, Gerhauser C. Cancer chemoprevention by targeting the epigenome. Curr.Drug Targets. 2011;12(13):1925-1956. View Abstract
Huang Z, Zuo L, Zhang Z, et al. 3,3'-Diindolylmethane decreases VCAM-1 expression and alleviates experimental colitis via a BRCA1-dependent antioxidant pathway. Free Radic.Biol.Med. 1-15-2011;50(2):228-236. View Abstract
Jin Y, Zou X, Feng X. 3,3'-Diindolylmethane negatively regulates Cdc25A and induces a G2/M arrest by modulation of microRNA 21 in human breast cancer cells. Anticancer Drugs 2010;21(9):814-822. View Abstract
Kandala PK and Srivastava SK. Activation of checkpoint kinase 2 by 3,3'-diindolylmethane is required for causing G2/M cell cycle arrest in human ovarian cancer cells. Mol.Pharmacol. 2010;78(2):297-309. View Abstract
Kassie F, Melkamu T, Endalew A, et al. Inhibition of lung carcinogenesis and critical cancer-related signaling pathways by N-acetyl-S-(N-2-phenethylthiocarbamoyl)-l-cysteine, indole-3-carbinol and myo-inositol, alone and in combination. Carcinogenesis 2010;31(9):1634-1641. View Abstract
Lee SO, Li X, Khan S. Targeting NR4A1 (TR3) in cancer cells and tumors. Expert.Opin.Ther.Targets. 2011;15(2):195-206. View Abstract
Li Y, Kong D, Wang Z, et al. Regulation of microRNAs by natural agents: an emerging field in chemoprevention and chemotherapy research. Pharm.Res. 2010;27(6):1027-1041. View Abstract
Li Y, Li X, Guo B. Chemopreventive agent 3,3'-diindolylmethane selectively induces proteasomal degradation of class I histone deacetylases. Cancer Res. 1-15-2010;70(2):646-654. View Abstract
Rahimi M, Huang KL, Tang CK. 3,3'-Diindolylmethane (DIM) inhibits the growth and invasion of drug-resistant human cancer cells expressing EGFR mutants. Cancer Lett. 9-1-2010;295(1):59-68. View Abstract
Rajoria S, Suriano R, Wilson YL, et al. 3,3'-diindolylmethane inhibits migration and invasion of human cancer cells through combined suppression of ERK and AKT pathways. Oncol.Rep. 2011;25(2):491-497. View Abstract
Sarkar FH, Li Y, Wang Z, et al. Implication of microRNAs in drug resistance for designing novel cancer therapy. Drug Resist.Updat. 2010;13(3):57-66. View Abstract
Copyright © 2013 Natural Standard (www.naturalstandard.com)
The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.
March 22, 2017