Diindolylmethane DIM supplement pill research, studies regarding cancer prevention or treatment, dosage and safety, side effects, 100 mg and 300 mg dosage

Diindolylmethane is a natural substance formed during the breakdown of glucobrassicin present in food plants of the Brassica genus. The Brassica genus includes cabbage, broccoli, Brussels sprouts, cauliflower and kale.
Epidemiological studies have shown that a diet rich in fruits and cruciferous vegetables is associated with a lower risk of cancer. Indole-3-carbinol (I3C) and its dimeric product 3,3′-diindolylmethane (DIM) have been shown to exhibit anti-tumor activity both in vitro and in vivo.

Benefits and uses
3,3′-Diindolylmethane is a compound derived from the digestion of indole-3-carbinol, found in Brassica vegetables. It has anti cancer benefits in lab studies but, as of May 2010, no human studies with this supplement could be found in terms of its use in prevention or treatment of various forms of cancer.

DIM supplement products
There are dozens of DIM supplements on the market, some of these include:

DIM blend complex 100 mg (Providing 25 mg of Diindolylmethane)
Diindolylmethane 100 mg
DIM 200 mg
BioResponse DIM 300 mg (A patented complex), starch, diindolylmethane, vitamin E (as d-alpha tocopheryl succinate), soy phosphatidyl choline, silica.

Purchase DIM Diindolylmethane pills, 100 mg, 60 Tablets

In animal and in-vitro studies. DIM has been shown to lead to the preferential formation of estrogen, and cervical tissues. This unique property sets it apart from other plant nutrients. Source Naturals DIM is combined with phosphatidyl choline, vitamin E and bioperine for enhanced absorption.

Purchase DIM pills, tablets – Diindolylmethane pills, or get a free newsletter on the topic of alternative medicine

Absorption
Single-dose pharmacokinetics and tolerability of absorption-enhanced 3,3′-diindolylmethane in healthy subjects.
Cancer Epidemiol Biomarkers Prev. 2008. Departments of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS, USA.
We have completed a single ascending dose clinical study of the proposed chemopreventive agent diindolylmethane (DIM). The study agent was nutritional-grade, absorption-enhanced BioResponse 3,3′-diindolylmethane (BR-DIM). We determined the safety, tolerability, and pharmacokinetics of single doses of BR-DIM in drug-free, non-smoking, healthy men and women. Groups of four subjects were enrolled for each dose level. After randomization, one subject in each group received placebo whereas three received active BR-DIM. The doses administered were 50, 100, 150, 200, and 300 mg, with the 300-mg dose repeated in an additional group. No diindolylmethane related adverse effects were reported at doses up to 200 mg. At the 300-mg dose, one of six subjects reported mild nausea and headache and one also reported vomiting. Only the latter effect was judged as probably related to the study agent. Analysis of serial plasma samples showed that only one subject at the 50-mg dose had detectable concentrations of diindolylmethane. We conclude that BR-DIM is well tolerated at single doses of up to 200 mg, and that increasing the diindolylmethane dose to 300 mg did not result in an increase in C(max).

Single-dose and multiple-dose administration of indole-3-carbinol to women: pharmacokinetics based on 3,3′-diindolylmethane.
Cancer Epidemiol Biomarkers Prev. 2006. Department of Internal Medicien, University of Kansas Medical Center, MS, Kansas City, KS, USA.
We have completed a phase I trial in women of the proposed chemopreventive natural product indole-3-carbinol (I3C). Women received oral doses of 400, 600, 800, 1,000, and 1,200 mg I3C. Serial plasma samples were analyzed by high-performance liquid chromatography-mass spectrometry for I3C and several of its condensation products. I3C itself was not detectable in plasma. The only detectable I3C-derived product was 3,3′-diindolylmethane (DIM). Mean Cmax for diindolylmethane increased from 61 ng/mL at the 400-mg I3C dose to 607 ng/mL following a 1,000-mg dose. No further increase was observed following a 1,200-mg dose. A similar result was obtained for the area under the curve, which increased from 329 h ng/mL at the 400-mg dose to 3,376 h ng/mL after a 1,000-mg dose of I3C. Significant interindividual quantitative variation was seen in plasma diindolylmethane values within each dosing group, but the overall profiles were qualitatively similar, with no quantifiable diindolylmethane before dosing, tmax at approximately 2 h, and diindolylmethane levels near or below 15 ng/mL (the limit of quantitation), by 24 h. Different results were obtained for 14 subjects who received a 400-mg dose of I3C after 8 weeks of twice-daily I3C dosing. Although the predose sampling occurred at least 12 h after the last known ingestion of I3C, 6 of 14 subjects exhibited Cmax for DIM in their predose plasma. Despite this high initial value, plasma diindolylmethane for all subjects decreased to near or below the limit of quantitation within the 12-h sampling period. Possible reasons for this disparity between apparent t1/2 of diindolylmethane and the high predose values are discussed.

Benefits of diindolemethane in research studies

Breast cancer
Induction of growth arrest and apoptosis in human breast cancer cells by 3,3-diindolylmethane is associated with induction and nuclear localization of p27kip.
Mol Cancer Ther. 2008. Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA.
Human breast cancer cell lines were studied to better understand its mechanisms. In vitro experiments were done in MCF-7, T47D, BT-20 and BT-474 cells using MTT, ELISA, immunoblotting assays, reverse transcription-PCR, protein half-life, confocal microscopy, cell fractionation, and immunoprecipitation assays. We found that Diindolylmethane inhibited the growth of all four breast cancer cell lines. These effects appear to be independent of Her-2, Akt, or estrogen receptor status and should support further study for the chemoprevention potential of Diindolylmethane in breast cancer.

Cervical cancer
Oncol Rep. 2012. Anti-proliferative and pro-apoptotic effects of 3,3′-diindolylmethane in human cervical cancer cells.

Lung cancer
Enhancement of docetaxel anticancer activity by a novel diindolylmethane compound in human non-small cell lung cancer.
Clin Cancer Res. 2009. College of Pharmacy and Pharmaceutical Sciences. Florida A&M University, Tallahassee, Florida, USA.
This study was conducted to examine the cytotoxic effects of a peroxisome proliferator-activated receptor gamma (PPARgamma) agonist, diindolylmethane, alone and in combination with docetaxel in vitro in A549 lung cancer cells and in vivo in nude mice bearing A549 orthotopic lung tumors. Our findings suggest potential benefit for use of docetaxel and diindolylmethane combination in lung cancer treatment.

Pancreatic cancer
3,3′-Diindolylmethane enhances chemosensitivity of multiple chemotherapeutic agents in pancreatic cancer.
Cancer Research. 2009. Department of Pathology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan, USA.
Clinical management of pancreatic cancer is a major problem, which is in part due to both de novo and acquired resistance to conventional therapeutics. Here, we present in vitro and in vivo preclinical evidence in support of chemosensitization of pancreatic cancer cells by 3,3-diindolylmethane, a natural compound that can be easily obtained by consuming cruciferous vegetables. DIM pretreatment of pancreatic cancer cells led to a significantly increased apoptosis with suboptimal concentrations of chemotherapeutic agents (cisplatin, gemcitabine, and oxaliplatin) compared with monotherapy. DIM could abrogate chemotherapeutic drug (cisplatin, gemcitabine, and/or oxaliplatin)-induced activation of NF-kappaB, resulting in the chemosensitization of pancreatic tumors to conventional therapeutics.

Prostate cancer
Thus far, in vitro studies indicate that this nutrient could help reduce the risk for prostate cancer.

J Recept Signal Transduct Res. 2012. Effect of diindolylmethane on Ca2+ homeostasis and viability in PC3 human prostate cancer cells. Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan. Diindolylmethane caused cell death in which apoptosis may participate.

The potential efficacy of 3,3′-diindolylmethane in prevention of prostate cancer development.
Eur J Cancer Prev. Department of Biology, Faculty of Science and Science Education, University of Haifa Department of Molecular Genetics, Carmel Medical Center Department of Urology, Carmel Medical Center, Technion-Israel Institute of Technology, Haifa, Israel.
The objective of this study was to examine the efficacy of 3,3′-diindolylmethane in prevention of prostate cancer tumor development in an animal model. Mouse prostate cancer cells (TRAMP-C2, 2×10) were injected subcutaneously into three groups of C57BL/6 mice (10 mice in each group). Two groups were treated earlier with DIM; 2 or 10 mg/kg each, and an additional control group was injected with medium. Our results indicated that the DIM agent is not toxic and has an in-vivo preventive effect against the development of prostate cancer in a mouse model.

Cell cycle-dependent effects of 3,3′-diindolylmethane on proliferation and apoptosis of prostate cancer cells.
J Cell Physiol. 2009. Vattikuti Urology Institute, Henry Ford Health System, Detroit, Michigan, USA.
Recently, we have reported that a formulated diindolylmethane induced apoptosis and inhibited growth, angiogenesis, and invasion of prostate cancer cells by regulating Akt, NF-kappaB, and the androgen receptor signaling pathway. However, the precise molecular mechanism(s) by which diindolylmethane inhibits prostate cancer cell growth and induces apoptosis have not been fully elucidated. Our results show for the first time the cell cycle-dependent effects of diindolylmethane on proliferation and apoptosis of synchronized prostate cancer cells progressing from G(1) to S phase. Diindolylmethane inhibited this progression by induction of p27(Kip1) and down-regulation of androgen receptors. Our results suggest that DIM could be a potent agent for the prevention and/or treatment of both hormone sensitive as well as hormone-refractory prostate cancer.

DIM enhances the growth inhibition effect of idarubicin on human prostate cancer cells by the mechanism of induction of apoptosis.

Stomach cancer
J Exp Clin Cancer Res. 2012. A selective aryl hydrocarbon receptor modulator 3,3′-Diindolylmethane inhibits gastric cancer cell growth.

Boiling cauliflower and DIM
Effect of boiling on the content of ascorbigen, indole-3-carbinol, indole-3-acetonitrile, and 3,3′-diindolylmethane in fermented cabbage.
J Agric Food Chem. 2009. Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Poland.
The aim of the study was to investigate the effect of the boiling process on the content of ascorbigen, indole-3-carbinol, indole-3-acetonitrile, and 3,3′-diindolylmethane in fermented cabbage. The cabbage was boiled for 5 to 60 min. Boiling resulted in a decrease of the total content of the compounds analysed. The changes were mainly caused by leaching of ascorbigen predominating in cabbage into cooking water and by its thermal hydrolysis. Ascorbigen losses resulting from thermal hydrolysis accounted for 30% after 10 min of boiling and for 90% after 60 min of boiling. One of the ascorbigen breakdown products was indole 3 carbinol; the decrease in ascorbigen content was accompanied by a drastic increase in the content of diindolylmethane, a condensation product of indole-3-carbinol. After 40 and 50 min of boiling, the total content of diindolylmethane in cabbage and cooking water was approximately 6-fold higher than that in uncooked cabbage. Diindolylmethane synthesis proceeded within the plant tissue. After 10 min of boiling, the content of free indole-3-carbinol and indole-3-acetonitrile stabilized at the level of about 80% as compared to the uncooked cabbage.

Inquiries by email
I would like to buy this product but, I have read that “Bio-Response DIM has the ONLY proven absorbtion and benefits” and “all DIM trials use the Bio-Response DIM”. So my question to you: How is the absorption of your product compared to Bio-Response?
We did a search in December 2009 on Medline, the medical site that lists all the millions of studies published around the world, and there was no mention of a clinical trial using Bio-Response DIM. Often claims are made by manufacturers that want to sell their products and such claims are made without foundation. You may wish to ask the company that promotes Bio-Response to provide you wish the actual published research that proves their claims.

Does cordyceps mushroom extract interfere with DIM supplement use?
Not that we are aware of but we have not seen such combination studies.