Diindolylmethane DIM supplement pill research, studies regarding cancer prevention or treatment, dosage and safety, side effects, 100 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 or DIM 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 2009, 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 (DIM) - 100 mg
DIM 200 mg
BioResponse DIM 300 mg (A patented diindolylmethane 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 DIM apart from other plant nutrients. Source Naturals
DIM is combined with phosphatidyl choline, vitamin E and bioperine for enhanced
absorption.
Absorption
Single-dose pharmacokinetics and tolerability of absorption-enhanced
3,3'-diindolylmethane in healthy subjects.
Cancer Epidemiol Biomarkers Prev. 2008 Oct; Reed GA, Sunega JM, Sullivan DK,
Gray JC, Mayo MS, Crowell JA, Hurwitz A. Departments of Pharmacology,
Toxicology, and Therapeutics, University of Kansas Medical Center, 3901 Rainbow
Boulevard, Kansas City, KS 66160, 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. The single 100-mg dose of BR-DIM resulted in
a mean maximum plasma concentration (C(max)) of 32 ng/mL and a mean area under
the curve (AUC) of 128 h ng/mL, and a single 200-mg dose produced a mean C(max)
of 104 ng/mL and a mean AUC of 553 h ng/mL. The single 300-mg dose of BR-DIM
resulted in a mean C(max) of 108 ng/mL and a mean AUC of 532 h ng/mL. 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 Dec; Reed GA, Arneson DW, Putnam WC,
Smith HJ, Gray JC, Sullivan DK, Mayo MS, Crowell JA, Hurwitz A. Department of
Internal Medicien, University of Kansas Medical Center, MS 1018, 3901 Rainbow
Boulevard, Kansas City, KS 66160, 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 Feb; Wang Z, Yu BW, Rahman KM, Ahmad F, Sarkar FH.
Department of Pathology, Karmanos Cancer Institute, Wayne State University
School of Medicine, Detroit, MI 48201, USA.
3,3'-Diindolylmethane (DIM) is a stable condensation product of
indole-3-carbanol, a potential breast cancer chemoprevention agent. 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.
Lung cancer
Enhancement of docetaxel anticancer activity by a novel diindolylmethane
compound in human non-small cell lung cancer.
Clin Cancer Res. 2009 Jan 15; Ichite N, Chougule MB, Jackson T, Fulzele SV, Safe
S, Singh M. College of Pharmacy and Pharmaceutical Sciences. Florida A&M
University, Tallahassee, Florida 32307, 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 Res. 2009 Jul Banerjee S, Wang Z, Kong D, Sarkar FH. Department of
Pathology, Barbara Ann Karmanos Cancer Institute, Wayne State University School
of Medicine, Detroit, Michigan 48201, 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 (DIM), 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. Our results provide
strong in vivo evidence in support of our hypothesis that 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.
The potential efficacy of 3,3'-diindolylmethane in
prevention of prostate cancer development.
Eur J Cancer Prev.. Fares F, Azzam N, Appel B, Fares B, Stein A. aDepartment of
Biology, Faculty of Science and Science Education, University of Haifa
bDepartment of Molecular Genetics, Carmel Medical Center cDepartment of Urology,
Carmel Medical Center, Faculty of Medicine, Technion-Israel Institute of
Technology, Haifa, Israel.
The objective of this study was to examine the efficacy of 3,3'-diindolylmethane
(DIM) in prevention of prostate cancer tumor development in an animal model.
Mouse prostate cancer cells (TRAMP-C2, 2x10) 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 Apr; Chinnakannu K, Chen D, Li Y, Wang Z, Dou QP, Reddy GP,
Sarkar FH. 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.
Diindolylmethane and genistein decrease the adverse
effects of estrogen in LNCaP and PC-3 prostate cancer cells.
J Nutr. 2008 Dec; Smith S, Sepkovic D, Bradlow HL, Auborn KJ. Department of
Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY
10461, USA.
Evidence suggests that 17beta-estradiol (E2) contributes to the risk of prostate
cancer, whereas the phytochemicals genistein from soy and diindolylmethane
(DIM), derived from indole-3-carbinol in cruciferous vegetables, decrease the
risk of prostate cancer. Our results show that DIM and genistein decrease the
effects of 17beta-estradiol that have the potential to promote prostate cancer.
DIM enhances the growth inhibition effect of idarubicin on human prostate cancer cells by the mechanism of induction of apoptosis.
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 March. Ciska E, Verkerk R, Honke J. Division of Food
Science, 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 (DIM) 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.