Supplements

DIM (Diindolylmethane)

Updated · 25 sources · Editorial policy

DIM (3,3’-diindolylmethane) is a compound that forms in the stomach when people eat cruciferous vegetables such as broccoli, cabbage and Brussels sprouts. It is sold as a dietary supplement for uses such as “cancer prevention” and “augmentation of physical fitness” (Bui et al., Case Rep Med 2016), and it is often promoted for “estrogen control,” including among men who use testosterone or other anabolic-androgenic steroids (AAS).

The most important fact is that no human study shows DIM working as an aromatase inhibitor. Its best-documented effect is a shift in how estrogen is broken down, measured in urine. In the largest placebo-controlled trial, 12 months of DIM did not change blood estradiol. By contrast, prescription aromatase inhibitors such as anastrozole lower estradiol by roughly 70–95% in postmenopausal women. No controlled trial has studied DIM in men using testosterone or AAS.

This page summarizes what the clinical trials, pharmacokinetic studies and regulators report. It is for education only and is not medical advice.

Property Detail
Class Dietary indole; condensation product of indole-3-carbinol from cruciferous vegetables
Chemistry C₁₇H₁₄N₂, molecular weight 246.31 g/mol (PubChem CID 3071)
US status Sold as a dietary supplement; no FDA-approved drug application. FDA does not approve supplements before they are marketed
Route Oral (capsules, often in an absorption-enhanced formulation)
Doses in trials Most controlled trials used about 75–300 mg DIM per day; one phase I cancer study went up to 300 mg twice daily
Half-life About 2.6–4.5 h (mean by dose group, single doses in healthy adults)
Main documented effect Raises the urinary ratio of 2-hydroxyestrone to 16α-hydroxyestrone
Effect on blood estradiol No significant change vs placebo over 12 months in the largest randomized trial
WADA status Not named on the 2026 Prohibited List

What it is

Cruciferous vegetables contain glucobrassicin, a sulfur-containing plant compound. When the plant is cut or chewed, glucobrassicin breaks down to indole-3-carbinol (I3C). In stomach acid, I3C molecules join together, and DIM is the main product: two indole rings linked by a single carbon (Reed et al., Cancer Epidemiol Biomarkers Prev 2008; Sanderson et al., Toxicol Sci 2001). Its chemical name is 3-(1H-indol-3-ylmethyl)-1H-indole (PubChem).

When women took I3C itself in a phase I trial, I3C could not be found in their blood. DIM was the only I3C-derived product detected (Reed et al., Cancer Epidemiol Biomarkers Prev 2006). This finding is one reason researchers moved on to studying DIM itself (Reed et al., 2008).

DIM was developed as a possible cancer-prevention agent, mainly for breast, cervical and prostate cancer. The mechanisms proposed come largely from cell and animal studies:

  • Estrogen metabolism. In cell culture, DIM induces CYP1A1 and CYP1B1, enzymes involved in estrogen metabolism (Sanderson et al., Toxicol Sci 2001). In people, DIM shifts estrogen breakdown toward 2-hydroxylation and away from 16α-hydroxylation. Researchers have described the 2-hydroxy metabolites as anti-tumorigenic and the 16α-hydroxy metabolites as pro-tumorigenic (Thomson et al., Breast Cancer Res Treat 2017). This is the effect most consistently seen in trials, measured as a higher urinary 2/16α-hydroxyestrone ratio.
  • Aryl hydrocarbon receptor (AhR). DIM is a weak AhR agonist. AhR is a sensor protein that switches on drug-metabolizing enzymes (Sanderson et al., Toxicol Sci 2001).
  • Androgen receptor. In prostate cancer cells, DIM competed with DHT (dihydrotestosterone) for the androgen receptor and blocked the receptor from moving into the nucleus. The authors described it as a strong androgen antagonist in cell culture (Le et al., J Biol Chem 2003). This has not been shown in people.

Does DIM block aromatase?

Aromatase is the enzyme that converts testosterone to estradiol. The cell data on DIM and aromatase point in both directions:

Study (cell culture only) Cells Effect of DIM on aromatase
Sanderson et al., Toxicol Sci 2001 H295R human adrenal cancer cells Increased aromatase activity, up to about 2-fold at 10 µM
Licznerska et al., Eur J Nutr 2013 MCF7 breast cancer cells Decreased aromatase expression
Licznerska et al., Eur J Nutr 2013 MDA-MB-231 breast cancer cells Increased aromatase expression, 1.5–2.0-fold

We found no human study that measured DIM’s effect on whole-body aromatization, the test used to characterize prescription aromatase inhibitors.

Pharmacokinetics

DIM itself is poorly absorbed, so most trials used an absorption-enhanced formulation called BioResponse-DIM (BR-DIM). It contains DIM with vitamin E succinate, phosphatidylcholine and silica, microencapsulated in starch (Reed et al., Cancer Epidemiol Biomarkers Prev 2008).

In a single ascending-dose study in healthy men and women (three on DIM and one on placebo per dose group; six on DIM at 300 mg), DIM was detectable in only one subject at the 50 mg dose. Results at higher doses:

Single dose Subjects on DIM Time to peak (h) Half-life (h) Peak level (ng/mL)
100 mg 3 2.7 3.7 32
150 mg 3 1.8 3.0 79
200 mg 3 2.5 2.6 104
300 mg 6 2.2 4.5 108

Two points stand out. First, the half-life is short, a few hours. Second, going from 200 mg to 300 mg did not raise the peak level. The authors also note that DIM is poorly absorbed from the gut without such a formulation.

In castrate-resistant prostate cancer patients taking BR-DIM twice daily, first-dose peak levels rose from 41.6 to 236.4 ng/mL across doses of 75–300 mg, and twice-daily dosing gave fairly stable exposure (Heath et al., Am J Transl Res 2010).

DIM is also metabolized more than early studies suggested. In seven adults who took BR-DIM for a week, blood and urine contained two monohydroxylated and one dihydroxylated metabolite, plus their sulfate and glucuronide conjugates. One metabolite was a more potent AhR agonist than DIM in a cell assay (Vermillion Maier et al., Drug Metab Dispos 2021).

Regulatory status

  • United States. DIM is sold as a dietary supplement. Under the Dietary Supplement Health and Education Act, FDA does not have the authority to approve dietary supplements before they are marketed (FDA). A search of Drugs@FDA returns no approved drug application for diindolylmethane (openFDA).
  • Sport. DIM is not named on the WADA 2026 Prohibited List. Class S4.1 (aromatase inhibitors) names anastrozole, letrozole, exemestane and others, and is an open list (“including, but not limited to”).

What the research shows

Urinary estrogen metabolites

The urinary 2/16α-hydroxyestrone ratio was the main outcome in most DIM trials. A higher ratio has been proposed, but not proven, to lower breast cancer risk.

Trial Design and n DIM dose and duration Result
Dalessandri et al., Nutr Cancer 2004 Pilot RCT, 19 postmenopausal women with past breast cancer 108 mg/day, 30 days 2-hydroxyestrone rose (p = 0.020); the ratio rose 47%, from 1.46 to 2.14, not significant (p = 0.059)
Thomson et al., Breast Cancer Res Treat 2017 Double-blind RCT, 130 women on tamoxifen (98 completed) 150 mg twice daily, 12 months Ratio +3.2 vs −0.7 on placebo (p under 0.001)
Gee et al., Eur J Cancer Prev 2016 Double-blind RCT, 45 men before prostate cancer surgery BR-DIM 100 or 200 mg twice daily, 21–28 days Ratio rose vs placebo only at 400 mg/day
Godínez-Martínez et al., Nutr Cancer 2023 Double-blind RCT, 60 premenopausal women 75 mg/day, 30 days No significant increase in the ratio

The effect on how estrogen is broken down is fairly consistent at higher doses. It is a different thing from lowering the amount of estrogen in the blood.

Blood estradiol, and how DIM compares with aromatase inhibitors

Products sold for “estrogen control” are often presented as a natural alternative to aromatase inhibitors. The trial data do not support that comparison.

In the 12-month Thomson trial, DIM did not change serum estradiol or estrone compared with placebo (estradiol p = 0.297; measured in 33 women). What did change was SHBG (sex hormone-binding globulin, the blood protein that carries testosterone and estradiol): +25 nmol/L on DIM vs +1.1 nmol/L on placebo (Thomson et al., Breast Cancer Res Treat 2017).

In a single-arm study of 23 BRCA carriers taking DIM 100 mg/day for a year, mean estradiol fell from 159 to 102 pmol/L. There was no placebo group, and the authors noted that the decline may partly reflect aging (Yerushalmi et al., Carcinogenesis 2020).

Prescription aromatase inhibitors work on a different scale:

Agent and dose Source and population Effect on estrogen
Anastrozole 1 mg/day Arimidex label; postmenopausal women Estradiol down about 70% within 24 h and about 80% after 14 days
Letrozole 0.1–5 mg/day Femara label; postmenopausal women Estradiol, estrone and estrone sulfate down 75–95% within 2–3 days
Exemestane 25 mg/day Aromasin label Plasma estrogens down at least 85–95%
Anastrozole 1 mg vs letrozole 2.5 mg Geisler et al., JCO 2002; crossover, 12 women Whole-body aromatization blocked 97.3% vs over 99.1%; estradiol down 84.9% vs 87.8%
Anastrozole 1 mg/day, 12 weeks Leder et al., JCEM 2004; RCT, 37 older men Estradiol 26 to 17 pg/mL; total testosterone 343 to 572 ng/dL
DIM 150 mg twice daily, 12 months Thomson et al., 2017; RCT, women on tamoxifen No significant change in estradiol vs placebo

About “DIM is a natural aromatase inhibitor.” This claim is common in supplement marketing and online advice. In cell culture, DIM increased aromatase in some cell types and decreased it in others. In people, no study has shown that DIM blocks aromatization, and the largest randomized trial found no change in blood estradiol. Its documented effects (a shift in urinary estrogen metabolites and a rise in SHBG) are different in kind and size from what anastrozole, letrozole or exemestane do.

Men, testosterone and androgen effects

There are no controlled trials of DIM in healthy men, in men on testosterone therapy, or in AAS users. The available data in men come from prostate cancer studies:

  • In the Gee trial of 45 men awaiting prostate surgery, changes in blood testosterone, PSA (prostate-specific antigen) and the other blood markers were not statistically significant. DIM was found in only 7 of 28 prostate tissue samples (Gee et al., Eur J Cancer Prev 2016).
  • In the Heath phase I study of 12 men with castrate-resistant prostate cancer, one man had a 50% PSA decline and one had PSA stabilization. The others eventually progressed (Heath et al., Am J Transl Res 2010).

The androgen-receptor blocking seen in cell culture (Le et al., J Biol Chem 2003) has not been tested in people. Likewise, whether the SHBG rise seen in women would lower free testosterone in men has not been studied.

Cancer prevention outcomes

Biomarker shifts have not translated into clear clinical benefit so far:

  • Cervical abnormalities. In a double-blind trial, 551 women with newly found low-grade abnormalities took DIM 150 mg/day or placebo for 6 months. CIN2 or worse (moderate or worse precancerous change) was found in 9% vs 12% (RR 0.7, 95% CI 0.4–1.2). The authors concluded that DIM is unlikely to affect cytology or HPV infection, while uncertainty remains about its effect on CIN2 or worse (Castañon et al., Br J Cancer 2012).
  • Breast density. In the Thomson trial, DIM did not change breast density on mammography or MRI.
  • Body fat. In the 30-day Godínez-Martínez trial, body fat percentage fell more on DIM than placebo (p = 0.04). This was a secondary outcome in 60 women and has not been replicated.

Side effects and risks

Tolerability in trials

DIM was generally well tolerated in short and medium-length trials:

Study Dose Adverse effects reported
Reed et al., 2008 Single doses 50–300 mg None up to 200 mg; at 300 mg, 1 of 6 had mild nausea and headache, and one had vomiting
Thomson et al., 2017 150 mg twice daily, 12 months No difference from placebo except discolored urine in 40% of DIM users
Yerushalmi et al., 2020 100 mg/day, 1 year All grade 1 (mild): bowel changes, headache, nausea, one case of skin redness
Heath et al., 2010 75–300 mg twice daily 2 of 4 men at 300 mg twice daily had grade 3 asymptomatic hyponatremia (low blood sodium)

In the Dalessandri pilot, urinary cortisol also rose on DIM compared with placebo (p = 0.039) (Dalessandri et al., Nutr Cancer 2004).

Interaction with tamoxifen

This is the best-documented interaction. In the Thomson trial, DIM lowered blood levels of tamoxifen’s active metabolites, endoxifen and 4-hydroxytamoxifen, as well as N-desmethyltamoxifen (p under 0.001 for the first two). More women on DIM fell below a proposed therapeutic threshold for endoxifen of 5.6 ng/mL. The authors called this “concerning” and said it is unknown whether it reduces tamoxifen’s benefit (Thomson et al., Breast Cancer Res Treat 2017).

The trial studied women with breast cancer, but the finding is relevant to anyone combining DIM with tamoxifen. DIM’s induction of drug-metabolizing enzymes (Sanderson et al., 2001) and its active metabolites (Vermillion Maier et al., 2021) mean other drug interactions are possible but have not been studied in people.

Case reports

Single case reports cannot prove that DIM caused the problem, but they include:

  • Blood clots. A 65-year-old man who had taken DIM daily for 3–4 months developed deep vein thrombosis and bilateral pulmonary embolism. He also had other risk factors, including smoking, age and a possible earlier pulmonary embolism (Bui et al., Case Rep Med 2016).
  • Severe drug rash. A case of DRESS (drug rash with eosinophilia and systemic symptoms), a serious drug reaction, was attributed to DIM (Le et al., J Allergy Clin Immunol Pract 2016).
  • Eye. A woman taking excessive daily doses of DIM for acne for 2 months developed central serous chorioretinopathy (fluid under the retina) in both eyes. Her vision returned to baseline 8 weeks after stopping (Bussel et al., Ophthalmic Surg Lasers Imaging Retina 2014).

Product labeling

The milligram figure on a DIM product does not always mean the same thing. In the Vermillion Maier study, each “BR-DIM 150 mg” capsule contained 45.3 mg of DIM; the Reed study described its BR-DIM 150 capsules as containing 50 mg DIM each. In the Godínez-Martínez trial, 300 mg of DIM-BR provided 75 mg of DIM. Trial doses on this page refer to DIM content when the study reported it. Doses of “BR-DIM” in the Gee trial and single doses in the Reed study are given as the papers state them.

Key takeaways

  • A vegetable-derived compound, sold as a supplement. DIM forms from indole-3-carbinol in stomach acid. It has no FDA-approved drug use, and FDA does not approve supplements before they are marketed.
  • Changes estrogen breakdown, not estrogen levels. Trials show a higher urinary 2/16α-hydroxyestrone ratio and higher SHBG. The largest randomized trial found no change in blood estradiol over 12 months.
  • Not comparable to aromatase inhibitors. Anastrozole, letrozole and exemestane lower estradiol by roughly 70–95%. Cell studies show DIM can raise or lower aromatase depending on cell type.
  • No data in men on testosterone or AAS. Studies in men are limited to prostate cancer, where testosterone and PSA did not change significantly over 3–4 weeks.
  • Short half-life, limited absorption. About 2.6–4.5 hours, with no rise in peak level from 200 mg to 300 mg.
  • Lowers active tamoxifen metabolites. DIM reduced endoxifen levels in women on tamoxifen. Case reports include blood clots, a severe drug rash and a retinal disorder.

Sources

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  2. Reed GA, Arneson DW, Putnam WC, et al. Single-dose and multiple-dose administration of indole-3-carbinol to women: pharmacokinetics based on 3,3’-diindolylmethane. Cancer Epidemiol Biomarkers Prev. 2006;15(12):2477–2481. PubMed.
  3. Vermillion Maier ML, Siddens LK, Uesugi SL, et al. 3,3’-Diindolylmethane exhibits significant metabolism after oral dosing in humans. Drug Metab Dispos. 2021;49(8):694–705. PubMed.
  4. National Center for Biotechnology Information. 3,3’-Diindolylmethane, PubChem CID 3071. PubChem.
  5. Sanderson JT, Slobbe L, Lansbergen GW, et al. 2,3,7,8-Tetrachlorodibenzo-p-dioxin and diindolylmethanes differentially induce cytochrome P450 1A1, 1B1, and 19 in H295R human adrenocortical carcinoma cells. Toxicol Sci. 2001;61(1):40–48. PubMed.
  6. Licznerska BE, Szaefer H, Murias M, et al. Modulation of CYP19 expression by cabbage juices and their active components: indole-3-carbinol and 3,3’-diindolylmethene in human breast epithelial cell lines. Eur J Nutr. 2013;52(5):1483–1492. PubMed.
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  9. Thomson CA, Chow HHS, Wertheim BC, et al. A randomized, placebo-controlled trial of diindolylmethane for breast cancer biomarker modulation in patients taking tamoxifen. Breast Cancer Res Treat. 2017;165(1):97–107. PubMed; PMC.
  10. 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. Eur J Cancer Prev. 2016;25(4):312–320. PubMed.
  11. Heath EI, Heilbrun LK, Li J, et al. A phase I dose-escalation study of oral BR-DIM (BioResponse 3,3’-diindolylmethane) in castrate-resistant, non-metastatic prostate cancer. Am J Transl Res. 2010;2(4):402–411. PubMed.
  12. Godínez-Martínez E, Santillán R, Sámano R, et al. Effectiveness of 3,3’-diindolylmethane supplements on favoring the benign estrogen metabolism pathway and decreasing body fat in premenopausal women. Nutr Cancer. 2023;75(2):510–519. PubMed.
  13. Yerushalmi R, Bargil S, Ber Y, 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. PubMed.
  14. Castañon A, Tristram A, Mesher D, et al. Effect of diindolylmethane supplementation on low-grade cervical cytological abnormalities: double-blind, randomised, controlled trial. Br J Cancer. 2012;106(1):45–52. PubMed.
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  19. Leder BZ, Rohrer JL, Rubin SD, et al. Effects of aromatase inhibition in elderly men with low or borderline-low serum testosterone levels. J Clin Endocrinol Metab. 2004;89(3):1174–1180. PubMed.
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  21. Le TM, Sanders CJ, van de Corput L, et al. Drug rash with eosinophilia and systemic symptoms caused by the dietary supplement diindolylmethane. J Allergy Clin Immunol Pract. 2016;4(1):175–176. PubMed.
  22. Bussel II, Lally DR, Waheed NK. Bilateral central serous chorioretinopathy associated with estrogen modulator diindolylmethane. Ophthalmic Surg Lasers Imaging Retina. 2014;45(6):589–591. PubMed.
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