DIM
Small trials found DIM shifted urinary estrogen metabolites toward 2-hydroxyestrone. In a 12-month trial in women on tamoxifen, breast density did not change and tamoxifen's active metabolites fell. A cervical dysplasia trial found no difference from placebo. Single doses up to 200 mg caused no reported side effects, and 300 mg caused nausea in some.
- Status
- Dietary supplement in the US. Not FDA-approved for any condition.
- Also called
- diindolylmethane, 3,3'-diindolylmethane, BR-DIM, BioResponse DIM, indole-3-carbinol metabolite, I3C, cruciferous vegetable extract, estrogen metabolism supplement
- Taken for
- estrogen balance, estrogen dominance, hormonal acne, breast cancer prevention, prostate health, cervical dysplasia, PCOS, testosterone in men, weight loss
Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on
Shown to help1
Reported risks2
- LimitedOne trial found DIM lowered blood levels of tamoxifen metabolites in women on tamoxifen. Whether this reduces tamoxifen's benefit is not known.
- LimitedSmall trials found mild nausea, headache or vomiting in a few people at 300 mg. In the tamoxifen trial, adverse events did not differ from placebo.
What people take it for, and what was found
Shown to help1
Estrogen metabolites and hormone levels
Shown to shift urinary estrogen metabolite ratios in women on tamoxifen, breast cancer survivors and men with prostate cancer. No trial measured cancer outcomes.
The numbers and sources
- Effect
- In 130 women on tamoxifen, 150 mg of DIM twice a day for 12 months raised the urinary 2/16α-hydroxyestrone ratio (+3.2 against -0.7 on placebo, p below 0.001) and raised SHBG by 25 nmol/L against 1.1 [1]. In 19 postmenopausal women after early breast cancer, 108 mg a day for 30 days raised urinary 2-hydroxyestrone and cortisol compared with placebo [2]. In 45 men before prostate surgery, 400 mg a day changed the same urinary ratio compared with placebo [3]. In 23 BRCA carriers taking 100 mg a day for a year, estradiol fell from 159 to 102 pmol/L and testosterone from 0.42 to 0.31 [4].
- Population
- Women on tamoxifen [1], breast cancer survivors [2], men with prostate cancer [3], BRCA carriers [4].
- Sources
- [1], [2], [3], [4]
- Caveats
- These are biomarkers. None of these trials measured cancer outcomes. [4] had no randomized control group.
Not shown to help4
Breast density
Limited evidence: breast density did not change against placebo in a 12-month trial. A single-arm study of BRCA carriers found a small fall on MRI.
The numbers and sources
- Effect
- In the 12-month tamoxifen trial, breast density on mammography and MRI did not change compared with placebo [1]. In 23 BRCA carriers, the MRI fibroglandular tissue score fell from 2.8 to 2.65 over a year (p 0.031), with no change in untreated matched women [4].
- Population
- 98 women who completed the tamoxifen trial [1]. 23 healthy BRCA carriers [4].
- Sources
- [1], [4]
- Caveats
- The sources differ. [4] was single-arm, funded by the Israel Cancer Association. [1] was funded by NCI.
Cervical dysplasia
One trial found 47% of women with CIN 2 or 3 improved on DIM, but no outcome differed significantly from placebo.
The numbers and sources
- Effect
- In 64 women with CIN 2 or 3, about 2 mg/kg a day of DIM for 12 weeks was followed by improvement in 47% of the DIM group, but no outcome differed significantly from placebo [5].
- Population
- Women aged 18 to 61, randomized 2 to 1 [5].
- Sources
- [5]
- Caveats
- Both groups improved at a high rate. DIM and placebo were supplied by BioResponse, the maker [5].
Prostate cancer tissue
One trial found DIM in only 7 of 28 prostate tissue samples, with no consistent change in tissue or blood markers in men with prostate cancer.
The numbers and sources
- Effect
- In 45 men given 200 or 400 mg a day for 21 to 28 days before prostatectomy, DIM was detected in only 7 of 28 prostate tissue samples, and tissue and blood markers did not change consistently [3].
- Population
- Men with organ-confined prostate cancer [3].
- Sources
- [3]
- Caveats
- A short phase Ib trial focused on tissue levels. Funded by NCI and NCATS [3].
Hormonal acne and testosterone in men
One small trial found DIM did not significantly change testosterone in 45 men with prostate cancer. Acne has been tested only in the lab, against acne bacteria.
The numbers and sources
- Effect
- In 45 men awaiting prostate surgery, 21 to 28 days of DIM or placebo produced no significant change in plasma testosterone, PSA or IGF-1 measures. Only the urinary 2-hydroxyestrone to 16-hydroxyestrone ratio changed, at the higher dose [3]. In male rats given DIM for 53 days, one middle dose had an anti-androgenic effect, and higher doses lowered sperm motility and damaged testicular tissue [7]. In the lab, DIM inhibited growth and biofilm formation by Cutibacterium acnes, the main acne bacterium [8].
- Population
- 45 men with prostate cancer [3]. 38 Sprague Dawley rats [7]. Bacterial cultures [8].
- Sources
- [3], [7], [8]
- Caveats
- The human trial was short, in men with prostate cancer, and testosterone was a secondary measure [3]. No study of acne in people taking DIM was located. Rat and lab findings do not show what happens in people [7][8].
Doses studied
Trials used 100 mg a day for a year [4], 108 mg a day for 30 days [2], 150 mg twice a day for 12 months [1], 100 or 200 mg twice a day for 3 to 4 weeks [3], and about 2 mg/kg a day for 12 weeks [5]. A single-dose study tested 50 to 300 mg, and 300 mg did not raise peak blood levels above 200 mg [6].
Risks
Reported risks2
Lower tamoxifen metabolites
One trial found DIM lowered blood levels of tamoxifen metabolites in women on tamoxifen. Whether this reduces tamoxifen's benefit is not known.
The numbers and sources
- Effect
- In women on tamoxifen, DIM lowered plasma endoxifen, 4-hydroxy tamoxifen and N-desmethyl-tamoxifen compared with placebo (p below 0.001) [1].
- Population
- 130 women randomized, 98 completed [1].
- Sources
- [1]
- Caveats
- The authors state it is not known whether this reduces tamoxifen's clinical benefit [1].
Nausea, headache and vomiting
Small trials found mild nausea, headache or vomiting in a few people at 300 mg. In the tamoxifen trial, adverse events did not differ from placebo.
The numbers and sources
- Effect
- In a single-dose study, no side effects were reported up to 200 mg. At 300 mg, one of six subjects reported mild nausea and headache, and one reported vomiting [6]. In the cervical trial, 2 of 64 women (3%) reported grade 2 nausea, and blood counts, liver tests and metabolic panels stayed normal [5]. In the tamoxifen trial, adverse events were minimal and did not differ from placebo [1].
- Population
- Healthy adults [6], women with CIN [5], women on tamoxifen [1].
- Sources
- [6], [5], [1]
- Caveats
- Small trials of up to 12 months.
Claims tested and not found
Sources
- 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 Research and Treatment. 2017. https://doi.org/10.1007/s10549-017-4292-7
- Dalessandri KM, Firestone GL, Fitch MD, et al. 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. https://doi.org/10.1207/s15327914nc5002_5
- 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. https://doi.org/10.1097/cej.0000000000000189
- 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. https://doi.org/10.1093/carcin/bgaa050
- Del Priore G, Gudipudi DK, Montemarano N, et al. Oral diindolylmethane (DIM): Pilot evaluation of a nonsurgical treatment for cervical dysplasia. Gynecologic Oncology. 2010. https://doi.org/10.1016/j.ygyno.2009.10.060
- Reed GA, Sunega JM, Sullivan DK, et al. Single-Dose Pharmacokinetics and Tolerability of Absorption-Enhanced 3,3'-Diindolylmethane in Healthy Subjects. Cancer Epidemiology, Biomarkers & Prevention. 2008. https://doi.org/10.1158/1055-9965.epi-08-0520
- Aksu EH, Akman O, Ömür AD, et al. 3,3 diindolylmethane leads to apoptosis, decreases sperm quality, affects blood estradiol 17 β and testosterone, oestrogen (α and β) and androgen receptor levels in the reproductive system in male rats. Andrologia. 2016. https://doi.org/10.1111/and.12554
- Kim YG, Lee JH, Park S, Lee J. The anticancer agent 3,3'-diindolylmethane inhibits multispecies biofilm formation by acne-causing bacteria and Candida albicans. Microbiology Spectrum. 2022. https://doi.org/10.1128/spectrum.02056-21