How can DIM help you? What the research says

Diindolylmethane (DIM) is created naturally when you digest cruciferous vegetables, and it’s also a nutritional supplement with possible anticancer effects.

How can DIM help you? What the research says

We summarize the clinical evidence for each medical benefit here. We begin with our assessment of the strength of evidence within each category, followed by a brief summary of individual studies or reviews of several studies. In assessing the strength of evidence, we consider the study design, number of participants, and the size of the treatment effect (how much outcomes changed with treatment).

To see more details, click the plus sign to the right of any section.

Our assessments of evidence for each medical benefit fall into one of these categories:

Strong evidence: consistent, significant effects in several large (or at least one very large) well designed clinical studies or at least two meta-analysesa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of clinical studies of moderate or better quality (or one large meta-analysis) finding similar results
Good evidence: significant effects in one large or several mid-sized and well-designed clinical studies ( randomized controlled trialsa study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects with an appropriate placebo or other strong comparison control or observational studies that control for confounds)
Modest evidence: significant effects in at least three small but well-designed randomized controlled trials (RCTs), or one or more well-designed, mid-sized clinical studies of reasonably good quality (RCTs or observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods studies), or several small studies aggregated into a meta-analysis
Preliminary evidence: significant effects in small or poorly designed clinical studies OR conflicting results in adequate studies but a preponderance of evidence of an effect
Weak evidence: one or more case studies, supported by animal evidence OR small treatment effects of limited clinical significance OR studies with no controls OR weak trends of effects
Insufficient evidence: preclinical evidence only OR clinical studies with such poor or unclear methodology that no conclusion can be drawn OR conflicting findings across clinical studies with no preponderance of evidence in one direction; conflicting evidence occurs when studies find conflicting effects (positive effect vs no effect or negative effect) with the same treatment and the same general study population (same cancer type, for example)

Learn more about how we research and rate therapies and practices in How We Rate Therapies ›

Improving treatment outcomes

Is DIM linked to improved survival? Is it linked to less cancer growth or metastasis? Does it enhance the anticancer action of other treatments or therapies? We present the evidence.

Breast cancer

Prostate cancer

Preliminary evidencesignificant effects in small or poorly designed clinical studies OR conflicting results in adequate studies but a preponderance of evidence of an effect (this is the CancerChoices definition; other researchers and studies may define this differently) of anticancer effects among people with prostate cancer or prostatic intraepithelial neoplasia (PIN) treated with DIM

Lower morphological index of prostate biopsy specimens, with complete regression of high-grade prostatic intraepithelial neoplasia (PIN) in 45.5% of people, among people with a high-grade PIN treated with Infemin, a drug derivative of DIM with enhanced bioavailability, at a dose of 900 mg DIM a day for 12 months compared to placebo in a small RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects²Paltsev M, Kiselev V et al. First results of the double-blind randomized placebo-controlled multicenter clinical trial of DIM-based therapy designed as personalized approach to reverse prostatic intraepithelial neoplasia (PIN). EPMA Journal. 2016;7(1):5.
Lower prostate-specific antigen (PSA) and other markersa chemical or substance, such as certain proteins or genetic material, that are associated with the presence of cancer or a change in status or prognosis; these markers can be detected in blood, urine, or tissue. Tumor markers are not direct measures of clinical outcomes such as survival or metastasis, and if a therapy or treatment shows an impact only on tumor markers, we cannot surmise that it will affect survival. of anticancer activity (lower protein expression of the androgen receptor, exclusion of the androgen receptor from the cell nucleus), and among people with clinical T1 or T2 prostate cancer suitable for prostatectomy treated with 225 mg oral DIM twice daily for a minimum of 14 days and up to 72 days compared to baseline in a small uncontrolled triala study in which a therapy is used, but without a comparison group against which to judge outcomes; an uncontrolled trial is considered a weak study design³Hwang C, Sethi S et al. Anti-androgenic activity of absorption-enhanced 3, 3′-diindolylmethane in prostatectomy patients. American Journal of Translational Research. 2016 Jan 15;8(1):166-76.
Short-term slower rise in PSA among people with castrate-resistant, non-metastatic, PSA relapse prostate cancer treated with DIM in 4 dose levels: 75 mg twice daily (150 mg per day); 150 mg twice daily (300 mg per day); 225 mg twice daily (450 mg per day); and 300 mg twice daily (600 mg per day) compared to baseline in a small uncontrolled trial⁴Heath EI, Heilbrun LK et al. A phase I dose-escalation study of oral BR-DIM (BioResponse 3,3′- Diindolylmethane) in castrate-resistant, non-metastatic prostate cancer. American Journal of Translational Research. 2010 Jul 23;2(4):402-11.

Optimizing your body terrain

Does DIM promote an environment within your body that is less supportive of cancer development, growth, or spread? We present the evidence.

See Optimizing Your Body Terrain ›

Find medical professionals who specialize in managing body terrain factors: Finding Integrative Oncologists and Other Practitioners ›

Hormone levels

Changes in hormone levels seen in the studies here may not be beneficial in every situation. Your oncology team needs to determine whether any changes would be favorable for your condition.

Preliminary evidencesignificant effects in small or poorly designed clinical studies OR conflicting results in adequate studies but a preponderance of evidence of an effect (this is the CancerChoices definition; other researchers and studies may define this differently) of favorable changes in sex hormones among people with hormone-sensitive cancers (breast and prostate), or at risk of these cancers, or with thyroid proliferative disease treated with DIM

Higher sex hormone-binding globulin among women prescribed tamoxifen treated with BioResponse-DIM® (BR-DIM) providing 150 mg DIM twice a day compared to placebo in a small RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects⁵Thomson CA, Chow HHS et al. A randomized, placebo-controlled trial of diindolylmethane for breast cancer biomarker modulation in patients taking tamoxifen. Breast Cancer Research and Treatment. 2017 Aug;165(1):97-107.
Higher levels of 2-hydroxyestrone (2-OHE1)―an estrogen modulator that may be protective against breast cancer―and cortisol among postmenopausal women with a history of early stage breast cancer treated with 108 mg BioResponse-DIM® per day for 30 days compared to placebo in a small RCT⁶Dalessandri 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. Nutrition and Cancer. 2004;50(2):161-7.
No evidence of an effectoverall, one or more studies did not demonstrate that a treatment or intervention led to an expected outcome; this does not always mean that there is no effect in clinical practice, but that the studies may have been underpowered (too few participants) or poorly designed. Larger, well-designed studies provide more confidence in making assessments. on the 2-hydroxyestrone/16-hydroxyestrone ratio―a biomarker related to breast cancer development―among healthy women with a BRCA1 mutation treated with 300 mg DIM from Rx Balance BioResponse DIM per day for 4–6 weeks compared to controls in a small RCT⁷Nikitina D, Llacuachaqui M, Sepkovic D, Bradlow HL, Narod SA, Kotsopoulos J. The effect of oral 3, 3′-diindolylmethane supplementation on the 2: 16α-OHE ratio in BRCA1 mutation carriers. Familial Cancer. 2015;14(2):281-286.
A favorable change in urinary 2-hydroxyestrone/16-hydroxyestrone ratios among people diagnosed with prostate cancer and scheduled for radical prostatectomy treated with 100 or 200 mg of an absorption-enhanced formulation of DIM (BR-DIM) twice a day compared to placebo in a small RCT⁸Gee JR, Saltzstein DR, Messing E, et al. Phase Ib placebo-controlled, tissue biomarker trial of diindolylmethane (BR-DIMNG) in patients with prostate cancer who are undergoing prostatectomy. European Journal of Cancer Prevention. 2016;25(4):312-320.
Higher 2-hydroxyestrone and lower 16α-hydroxyestrone levels among people with thyroid proliferative disease scheduled for a partial or total thyroidectomy treated with 300 mg DIM (BioResponse-DIM®) per day for 14 days compared to baseline in a small uncontrolled triala study in which a therapy is used, but without a comparison group against which to judge outcomes; an uncontrolled trial is considered a weak study design⁹Rajoria S, Suriano R et al. 3,3′-diindolylmethane modulates estrogen metabolism in patients with thyroid proliferative disease: a pilot study. Thyroid. 2011 Mar;21(3):299-304.
Lower estradiol and testosterone levels among healthy female BRCA carriers treated with 100 mg oral DIM per day for 1 year compared to baseline in a small uncontrolled trial;¹⁰Yerushalmi R, Bargil S et al. 3,3-Diindolylmethane (DIM): a nutritional intervention and its impact on breast density in healthy BRCA carriers. A prospective clinical trial. Carcinogenesis. 2020;41(10):1395-1401. women who carry the BRCA gene mutation are at high risk of breast cancer

Managing side effects and promoting wellness

Is DIM linked to fewer or less severe side effects or symptoms? Is it linked to less toxicity from cancer treatment? Does it support your quality of life or promote general well-being? We present the evidence.

Symptoms not specific to cancer

Preliminary evidencesignificant effects in small or poorly designed clinical studies OR conflicting results in adequate studies but a preponderance of evidence of an effect (this is the CancerChoices definition; other researchers and studies may define this differently) of fewer and shorter bleeding episodes and less pelvic pain among women with endometriosis treated with DIM

Reducing cancer risk

Is DIM linked to lower risks of developing cancer or of recurrence? We present the evidence.

Breast cancer

Weak evidenceone or more case studies, supported by animal evidence OR small treatment effects of limited clinical significance OR studies with no controls OR weak trends of effects (this is the CancerChoices definition; other researchers and studies may define this differently) of less fibroglandular tissue but no evidence of an effect on a markera chemical or substance, such as certain proteins or genetic material, that are associated with the presence of cancer or a change in status or prognosis; these markers can be detected in blood, urine, or tissue. Tumor markers are not direct measures of clinical outcomes such as survival or metastasis, and if a therapy or treatment shows an impact only on tumor markers, we cannot surmise that it will affect survival. of cancer risk among female BRCA carriers treated with DIM

Weak evidence of better BRCA1 mRNA expression in white blood cells (related to lower risk of breast cancer) among women BRCA mutation carriers treated with DIM

Gynecological cancer

Preliminary evidencesignificant effects in small or poorly designed clinical studies OR conflicting results in adequate studies but a preponderance of evidence of an effect (this is the CancerChoices definition; other researchers and studies may define this differently) of regression of cervical lesions among women with grade 1–2 cervical intraepithelial neoplasia (CIN) treated with DIM as a vaginal suppository

No evidence of an effectoverall, one or more studies did not demonstrate that a treatment or intervention led to an expected outcome; this does not always mean that there is no effect in clinical practice, but that the studies may have been underpowered (too few participants) or poorly designed. Larger, well-designed studies provide more confidence in making assessments. on markersa chemical or substance, such as certain proteins or genetic material, that are associated with the presence of cancer or a change in status or prognosis; these markers can be detected in blood, urine, or tissue. Tumor markers are not direct measures of clinical outcomes such as survival or metastasis, and if a therapy or treatment shows an impact only on tumor markers, we cannot surmise that it will affect survival. of cervical cancer among women treated with oral DIM

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Authors

Nancy Hepp, MS

Lead Researcher

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Laura Pole, MSN, RN, OCNS

Senior Clinical Consultant

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Last update: December 10, 2023

Last full literature review: December 2022

We are grateful for research assistance from Adriana Rocio Gutierrez Galvis.

CancerChoices provides information about integrativein cancer care, a patient-centered approach combining the best of conventional care, self care, and evidence-informed complementary care in an integrated plan cancer care. We review complementaryin cancer care, complementary care involves the use of therapies intended to enhance or add to standard conventional treatments; examples include supplements, mind-body approaches such as yoga or psychosocialtherapy, and acupuncture therapies and self carelifestyle actions and behaviors that may impact cancer outcomes; examples include eating health-promoting foods, limiting alcohol, increasing physical activity, and managing stress practices to help patients and professionals explore and integrate the best combination of conventionalthe cancer care offered by conventionally trained physicians and most hospitals; examples are chemotherapy, surgery, and radiotherapy and complementary therapies and practices for each person.

Our staff have no financial conflicts of interest to declare. We receive no funds from any manufacturers or retailers gaining financial profit by promoting or discouraging therapies mentioned on this site.

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References[+]

References
1, 5	Thomson CA, Chow HHS et al. A randomized, placebo-controlled trial of diindolylmethane for breast cancer biomarker modulation in patients taking tamoxifen. Breast Cancer Research and Treatment. 2017 Aug;165(1):97-107.
2	Paltsev M, Kiselev V et al. First results of the double-blind randomized placebo-controlled multicenter clinical trial of DIM-based therapy designed as personalized approach to reverse prostatic intraepithelial neoplasia (PIN). EPMA Journal. 2016;7(1):5.
3	Hwang C, Sethi S et al. Anti-androgenic activity of absorption-enhanced 3, 3′-diindolylmethane in prostatectomy patients. American Journal of Translational Research. 2016 Jan 15;8(1):166-76.
4	Heath EI, Heilbrun LK et al. A phase I dose-escalation study of oral BR-DIM (BioResponse 3,3′- Diindolylmethane) in castrate-resistant, non-metastatic prostate cancer. American Journal of Translational Research. 2010 Jul 23;2(4):402-11.
6	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. Nutrition and Cancer. 2004;50(2):161-7.
7	Nikitina D, Llacuachaqui M, Sepkovic D, Bradlow HL, Narod SA, Kotsopoulos J. The effect of oral 3, 3′-diindolylmethane supplementation on the 2: 16α-OHE ratio in BRCA1 mutation carriers. Familial Cancer. 2015;14(2):281-286.
8	Gee JR, Saltzstein DR, Messing E, et al. Phase Ib placebo-controlled, tissue biomarker trial of diindolylmethane (BR-DIMNG) in patients with prostate cancer who are undergoing prostatectomy. European Journal of Cancer Prevention. 2016;25(4):312-320.
9	Rajoria S, Suriano R et al. 3,3′-diindolylmethane modulates estrogen metabolism in patients with thyroid proliferative disease: a pilot study. Thyroid. 2011 Mar;21(3):299-304.
10, 12	Yerushalmi R, Bargil S et al. 3,3-Diindolylmethane (DIM): a nutritional intervention and its impact on breast density in healthy BRCA carriers. A prospective clinical trial. Carcinogenesis. 2020;41(10):1395-1401.
11	Morales-Prieto DM, Herrmann J, Osterwald H, et al. Comparison of dienogest effects upon 3, 3′–diindolylmethane supplementation in models of endometriosis and clinical cases. Reproductive Biology. 2018;18(3):252-258.
13	Kotsopoulos J, Zhang S, Akbari M, et al. BRCA1 mRNA levels following a 4-6-week intervention with oral 3,3′-diindolylmethane. British Journal of Cancer. 2014;111(7):1269-1274.
14	Ashrafian L, Sukhikh G et al. Double-blind randomized placebo-controlled multicenter clinical trial (phase IIa) on diindolylmethane’s efficacy and safety in the treatment of CIN: implications for cervical cancer prevention. EPMA Journal. 2015 Dec 21;6:25.
15	Castañon A, Tristram A et al. Effect of diindolylmethane supplementation on low-grade cervical cytological abnormalities: double-blind, randomised, controlled trial. British Journal of Cancer. 2012 Jan 3;106(1):45-52.
16	Del Priore G, Gudipudi DK et al. Oral diindolylmethane (DIM): pilot evaluation of a nonsurgical treatment for cervical dysplasia. Gynecological Oncology. 2010 Mar;116(3):464-7.