Diindolylmethane DIM supplement health benefit 100 mg pills, side effects and safety, for estrogen dominance? research study results and review
Cancer prevention or treatment, dosage and safety, side effects, influence on estrogen metabolism
February 15 2017 by
Ray Sahelian, M.D.

DIM is an indole phytochemical that is a natural metabolic of compounds found in cruciferous vegetables such as broccoli, Brussels sprouts and cabbage. When an indole 3 carbinol supplement is ingested, it converts in the gut into diindolylmethane.

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.

Source Naturals - buy DIM Diindolylmethane supplement 100 mg per pill, 120 Tablets
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Buy DIM diindolylmethane

Supplement Facts
Serving Size: 1 Tablet
  Amount Per Serving %DV
Vitamin E (as d-alpha tocopheryl succinate) 50 IU 167%
Diindolylmethane (DIM) 100 mg
Lecithin (from soybeans) 100 mg
Black Pepper Fruit Extract (BioPerine) 3 mg
Daily Value not established.

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 DIM apart from other plant nutrients.  Source Naturals DIM is combined with phosphatidyl choline, vitamin E and bioperine for enhanced absorption.

Buy DIM supplement Diindolylmethane supplement tablets or see a list of high quality supplements
DIM Supplement Facts
Vitamin E (as D-alpha tocopheryl)
Diindolylmethane (DIM)
Phosphatidyl Choline
Pepper Fruit Extract (Bioperine)

Suggested Use: 1 to 2 diindolymethane tablets per day with meals, or as recommended. by your health care professional.

Additional nutrients and supplements that may play a role in cancer prevention or treatment
AHCC
is a mushroom extract that has been tested as an anti-cancer agent.
Calcium D Glucarate is a natural supplement.
Indole3Carbinol I3C is available as a supplement.
   For a full list of natural supplements, herbs, nutritional substances and dietary factors that influence tumor prevention or treatment, see cancer.

DIM 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.

Breast, ovarian cancer prevention
Researchers at the University of California, Los Angeles, found in lab studies that diindolymethane, a compound resulting from digestion of cruciferous vegetables, and genistein, an isoflavone in soy, reduce the production of two proteins needed for breast and ovarian cancer to spread. The UCLA team plans to evaluate the theory in mice.Cancer cell membranes have high levels of a surface receptor known as CXCR4, while the organs to which the cancers spread secrete high levels of CXCL12, a ligand that binds to that particular receptor. This attraction stimulates the invasive properties of cancer cells and acts like a homing device, drawing the cancer cells to organs like the liver or brain. When cancer cells were treated with either DIM or genistein, movement toward CXCL12 was significantly reduced compared to untreated cells.

Pilot study: effect of diindolylmethane supplements on urinary hormone metabolites in postmenopausal women with a history of early-stage breast cancer.
Nutr Cancer. 2004. Department of Molecular and Cell Biology, University of California, Berkeley, USA.
Dietary indoles, present in Brassica plants such as cabbage, broccoli, and Brussels sprouts, have been shown to provide potential protection against hormone-dependent cancers. 3,3'-Diindolylmethane is under study as one of the main protective indole metabolites. Postmenopausal women aged 50-70 yr from Marin County, California, with a history of early-stage breast cancer, were screened for interest and eligibility in this pilot study on the effect of absorbable DIM (BioResponse- diindolylmethane) supplements on urinary hormone metabolites. The treatment group received daily DIM (108 mg /day) supplements for 30 days, and the control group received a placebo capsule. Urinary metabolite analysis included 2-hydroxyestrone (2-OHE1), 16-alpha hydroxyestrone (16alpha-OHE1), diindolylmethane, estrone (El), estradiol(E2), estriol (E3), 6beta-hydroxycortisol, and cortisol in the first morning urine sample before intervention and 31 days after intervention. DIM-treated subjects showed a significant increase in levels of 2-OHE1, diindolylmethane, and cortisol, and a nonsignificant increase in the 2-OHE1/16alpha-OHE1 ratio. In this pilot study, DIM increased the 2-hydroxylation of estrogen urinary metabolites.

Combining diindolylmethane and paclitaxel for breast cancer
3,3'-diindolylmethane and paclitaxel act synergistically to promote apoptosis in HER2/Neu human breast cancer cells.
J Surg Res. 2006. Department of Surgery, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
About 25 to 30% of invasive breast tumors overexpress the HER2 / neu oncogene. These tumors are aggressive and become resistant to chemotherapeutic drugs. 3'3'-diindolylmethane (DIM), the active metabolite of indole-3-carbinol, a naturally occurring compound found in cruciferous vegetables, has been found to have anti-cancer properties in both humans and animals. DIM has been shown to induce cell cycle arrest and apoptosis in animal breast cancer models. Diindolylmethane in combination with paclitaxel synergistically inhibits growth of Her2 / neu human breast cancer cells through G2M phase cell-cycle arrest and induction of apoptosis / necrosis. The Her2 / neu receptor and its downstream signaling protein ERK1/2 appear to be involved in DIM's affect on cell growth and differentiation, whereas apoptosis appears to be mediated through the mitochondrial pathway (Bcl-2/PARP). It appears diindolylmethane, a naturally occurring, nontoxic compound, may be a beneficial addition to a traditional (taxane-based) chemotherapy regimen.

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. 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.

Leukemia
PLoS One. 2012. 3,3'-Diindolylmethane induces G1 arrest and apoptosis in human acute T-cell lymphoblastic leukemia cells. Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, Oregon, United States of America.

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.

Nasal cancer
Mol Med Rep. 2015. Pro-apoptotic and anti-proliferative effects of 3,3'-diindolylmethane in nasopharyngeal carcinoma cells via downregulation of telomerase activity.

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
Diindolymethane appears to have antiproliferative and proapoptotic effects in prostate cancer cells. DIM -induced cell proliferation inhibition and apoptosis induction are partly mediated through the down-regulation of androgen receptors and NF-kappaB signaling. 

3,3'-Diindolylmethane induces a G(1) arrest in human prostate cancer cells irrespective of androgen receptor and p53 status.
Biochem Pharmacol. 2009. Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA, USA.
In this study we characterized the effect of DIM on cell cycle regulation in both androgen-dependent LNCaP and androgen receptor negative p53 mutant DU145 human prostate cancer cells. DIM had an anti-proliferative effect on both LNCaP and DU145 cells, as it significantly inhibited [3H]-thymidine incorporation. Our results indicate that DIM is able to stop the cell cycle progression of human prostate cancer cells regardless of their androgen-dependence and p53 status, by differentially modulating cell cycle regulatory pathways. The Sp1 and p38 MAPK pathways mediate the DIM cell cycle regulatory effect in DU145 cells.

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.

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.

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

Radiation exposure
Proc Natl Acad Sci U S A. 2013. DIM (3,3'-diindolylmethane) confers protection against ionizing radiation by a unique mechanism.

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

Role in cancer research and trials
Cancer Epidemiol Biomarkers Prev. 2014. Urinary 3,3'-diindolylmethane: a biomarker of glucobrassicin exposure and indole-3-carbinol uptake in humans. Brassica vegetable consumption may confer a protective effect against cancer, possibly attributable to their glucosinolates. Glucobrassicin is a predominant glucosinolate and is the precursor of indole-3-carbinol (I3C), a compound with anticancer effects. DIM is a measure of I3C uptake from Brassica vegetables, a finding that can be utilized in prospective epidemiologic and chemoprevention studies.

Side effects, safety
I am not aware of any major side effects thus far that have been reported in medical journals.

Q. I took about a 1/8 tsp. of DIM powder, from Bulk Naturals, last night. In the middle of the night I peed bright pink urine. This morning the color was just a bit pinker than normal. Red beets have a similar result. With asparagus, it's the odor. Do you have any thoughts/suggestions on this? Harmful? It's a good thing I'm a woman.
   A. I am not aware of such reports from other users but will keep my eyes open for such feedback.

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 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. 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).

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.

Hormone influence, testosterone
Is DIM diindolylmethane product for women only? Or, can it be used by men to help raise their testosterone?
   Not enough human research has been done with DIM diindolylmethane to determine which clinical conditions this supplement is useful for and how it effects hormone levels.

What would be the benefit for a woman that has had a complete hysterectomy (20 years ago) to take DIM. Also is it useful for men that take testosterone?
    There is not enough research on these topics to have a good answer at this time.

 

I am a chiropractor in San Diego, CA. Is this product pharmaceutical grade?
   The DIM product is made by Source Naturals and you can visit their website to ask them directly.

I tried several times to take diindolylmethane do address estrogen dominance but was getting really bad headaches and had to stop. Any ideas as to why I'm getting headaches and is there any way to overcome this side effect?
    It is difficult to know the reason, but you may consider taking a quarter or half a tablet with food.

Dim Source Naturals may have certain estrogen metabolizing effects. Does Passion Rx have any specific herbs that are known to have similar effects? If not, what is the thought about taking Passion Rx at the same time as Dim Source Naturals.
    We have not tested the combination. It is best to first try each supplement separately for a week or so before considering combining them. The sexual enhancing formula is not likely to have a major effect on estrogen metabolism.

I would like to buy this product but, I have read that "Bio-Response DIM has the ONLY proven absorption and benefits" and "all DIM trials use the Bio-Response DIM. How is the absorption of your product compared to Bio-Response?
    We did a search 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.

I would like to buy a stable form of DIM. Is the Bioresponse Dim supplement in some products the only DIM supplement that should be considered by consumers wishing to use a safe and effective form?
    We are not aware of any studies that have examined the different forms of DIM diindolylmethane products on the market to determine which are the most effective. As far as we know, Source Naturals DIM product is of high quality.