DIM (Diindolylmethane)

Evidence Level
Preliminary
2 Clinical Trials
5 Documented Benefits
1/5 Evidence Score

DIM (3,3'-diindolylmethane) is a metabolite of indole-3-carbinol (I3C) — formed in the stomach from cruciferous vegetables (broccoli, cabbage, kale, cauliflower, brussels sprouts). In small human studies DIM changed the mix of estrogen breakdown products measured in urine, shifting it toward 2-hydroxyestrone and away from 16-alpha-hydroxyestrone. That is a chemical change on a lab test, not a proven health benefit. DIM is widely sold for hormonal balance, PMS, skin and menopause, but no trial has tested those uses, and the one large trial of DIM (551 women, 150 mg a day for 6 months) found no effect on what it set out to measure. It is often combined with calcium D-glucarate.

Studied Dose Products commonly supply 100-300 mg a day. The cited human studies used 108 mg a day for 30 days and 150 mg a day of an absorption-enhanced form (BioResponse DIM) for 6 months. Neither dose has been shown to produce a health benefit.
Active Compound 3,3'-diindolylmethane (DIM)

Benefits

Estrogen Metabolism Modulation

In a pilot study of 19 postmenopausal women who had been treated for early-stage breast cancer, DIM at 108 mg a day for 30 days raised the urinary 2-hydroxyestrone to 16-alpha-hydroxyestrone ratio. A second small pilot study, in patients with thyroid disease, found a similar shift. Both measured estrogen breakdown products in urine, which is a lab marker and not a health outcome. The idea that one of these pathways is 'protective' and the other 'proliferative' is a hypothesis that has not been shown to translate into any benefit for people taking DIM, and both studies were run in patients rather than healthy consumers.

PMS / Premenstrual Symptom Support

DIM is a popular ingredient in PMS products, but none of the human studies behind DIM looked at PMS, mood, breast tenderness or fluid retention. There is no clinical trial evidence that it helps with premenstrual symptoms. This use rests only on the theory that changing estrogen breakdown products matters, and that theory has not been tested for these symptoms.

Fibrocystic Breast Support

None of the human research on DIM has measured breast tenderness or fibrocystic breast changes, so there is no clinical trial evidence that it helps with them. This use is a practitioner tradition only. Breast changes, pain or lumps should be assessed by a doctor rather than self-treated with a supplement.

What the Large Cervical Trial Actually Found (No Effect)

The largest DIM trial tested exactly this and found nothing. In 551 women with newly found low-grade cervical cell changes, 150 mg a day of BioResponse DIM for 6 months did not meet its main goal: more serious changes (CIN2 or worse) occurred in 9 percent on DIM versus 12 percent on placebo, which was not statistically significant (relative risk 0.7, 95 percent confidence interval 0.4 to 1.2), and HPV was still present at 6 months in 69 percent on DIM versus 61 percent on placebo. The authors concluded that DIM is unlikely to have an effect on cytology or HPV infection. DIM is not a treatment for abnormal Pap results, HPV or cancer, and it should not delay or replace cervical screening or the care a doctor recommends.

Detoxification Support / Phase II Conjugation

This is a laboratory idea, not a tested benefit. DIM interacts with liver enzyme systems in cell and animal research, but no human study of DIM has measured clearance of environmental toxins or any other 'detox' outcome. The only thing measured in people was the mix of estrogen breakdown products in urine.

Mechanism of action

1

CYP1A1 / CYP1A2 Induction (Estrogen 2-Hydroxylation)

DIM induces CYP1A1 and CYP1A2 enzymes — these convert estradiol to 2-hydroxyestrone (vs the alternative 16-alpha-hydroxyestrone pathway via CYP3A4). 2-hydroxyestrone is a weaker estrogen than 16-alpha-hydroxyestrone, and the idea that the ratio between them matters for health is a hypothesis that human trials have not confirmed. Small studies show DIM shifts this ratio; they do not show that the shift makes anyone better off.

2

Aromatase Modest Inhibition

Laboratory work suggests DIM may weakly slow the enzyme that converts androgens into estrogens. This has not been measured in people taking DIM supplements, so claims about lowering estrogen for physique or hormone goals are unproven.

3

Aryl Hydrocarbon Receptor (AhR) Modulation

DIM binds the aryl hydrocarbon receptor, a cell receptor that switches on genes involved in processing foreign compounds. This comes from cell and animal research, and what it means for someone taking a DIM capsule has not been tested.

4

Anti-Estrogen Receptor Effects

In test-tube studies DIM shows weak anti-estrogen activity at the estrogen receptor, competing with estradiol for binding. This is laboratory work only and has not been shown to produce any effect in people.

Clinical trials

1
Urinary Estrogen Markers: 19-Person Pilot Study

Pilot study of DIM at 108 mg a day versus placebo in 19 postmenopausal women who had been treated for early-stage breast cancer, over 30 days.

19 postmenopausal women with breast cancer history.

The ratio of 2-hydroxyestrone to 16-alpha-hydroxyestrone in urine went up. That is a lab measurement, not a symptom or health outcome, and the study measured nothing else. With 19 participants, 30 days of use, and a group of breast cancer survivors rather than general consumers, it cannot show that DIM helps anyone feel or function better.

2
Largest DIM Trial: No Effect on Cervical Cell Changes or HPV

Double blind randomized placebo controlled trial of 150 mg a day of BioResponse DIM for 6 months in 551 women with newly diagnosed low-grade cervical cell changes (Castanon 2012, British Journal of Cancer).

551 women with newly diagnosed low-grade cervical cytological abnormalities.

The trial missed its main goal. Worse changes (CIN2 or above) were found in 9 percent of the DIM group versus 12 percent on placebo, which was not statistically significant (relative risk 0.7, 95 percent confidence interval 0.4 to 1.2). CIN3 or above was 4.6 percent versus 5.1 percent, also not significant, and HPV was still detected at 6 months in 69 percent on DIM versus 61 percent on placebo. The authors wrote that DIM is unlikely to have an effect on cytology or HPV infection. This is a large, properly sized negative result, and it carries more weight than the small biomarker pilot studies.

Side effects and drug interactions

Common Potential side effects

Usually well tolerated in the studies done so far, though the longest ran only 6 months and long-term safety is not established.
Yellow-orange discoloration of urine — common, harmless (DIM metabolite).
GI distress.
Headache.
Skin reactions / rash rare.
Estrogen-mimetic OR antagonistic symptoms in sensitive individuals — mood changes, menstrual irregularities, breast tenderness initially.
Body odor changes (sulfur-based metabolites).
Some sellers describe early fatigue or headache as 'detox' symptoms. There is no evidence for that explanation, and symptoms that persist are a reason to stop and check with a doctor.

Important Drug interactions

Estrogen-containing medications (oral contraceptives, HRT) — DIM may change how the body processes estrogen, so it could in theory make the pill less reliable. This has not been formally tested. Talk to your prescriber and consider backup contraception.
Tamoxifen — theoretical interaction; mixed effects on tamoxifen metabolism; consult oncologist.
CYP1A2 substrates (caffeine, tizanidine, theophylline, mexiletine, certain antidepressants) — DIM induces CYP1A2; may reduce levels of these medications.
CYP1A1 substrates — similar concerns.
Hormone-sensitive cancers — theoretical complex effects; consult oncologist before use.
Pregnancy/lactation — limited safety data; avoid supplementation.

Frequently asked questions about DIM (Diindolylmethane)

What is DIM used for?

DIM (diindolylmethane) is a compound formed when the body digests cruciferous vegetables like broccoli. It is sold for hormonal balance, hormone-related skin problems and PMS in both women and men, but none of those uses have been tested in a trial. The only human research measured estrogen breakdown products in urine in small groups of patients, and the one large trial, in women with abnormal cervical cells, found no effect.

What is DIM good for?

Small studies show it changes the balance of estrogen breakdown products measured in urine, which is why it is marketed for hormonal acne, PMS, menopause and estrogen balance in men. No study has tested any of those uses, so treat them as unproven, and note that no trial has tested DIM in men for hormone balance. Its parent compound is I3C, and DIM is the more stable form.

How much DIM should I take?

Products commonly supply about 100 to 200 mg a day, and the human studies used 108 mg and 150 mg a day. Follow the product label. DIM is fat soluble, so taking it with food helps absorption.

Is DIM safe?

It was well tolerated in the studies done so far, and a harmless effect is a temporary orange tint to urine. Those studies were short, so long-term safety is unknown. Because it affects hormone processing and may interact with some medications, anyone who is pregnant or breastfeeding, anyone with a hormone-sensitive condition and anyone on prescription medicines should check with a doctor first.

What is DIM?

DIM (3,3'-diindolylmethane) is a metabolite of indole-3-carbinol (I3C) — formed in the stomach from cruciferous vegetables (broccoli, cabbage, kale, cauliflower, brussels sprouts).

What is the recommended dosage of DIM?

The clinically studied dose is Products commonly supply 100-300 mg a day. The cited human studies used 108 mg a day for 30 days and 150 mg a day of an absorption-enhanced form (BioResponse DIM) for 6 months. Neither dose has been shown to produce a health benefit. Always follow the product label and check with a healthcare provider for personal advice.

Is DIM safe, and does it have side effects?

For most healthy adults, DIM is well tolerated at studied doses. Reported effects can include: Usually well tolerated in the studies done so far, though the longest ran only 6 months and long-term safety is not established. Yellow-orange discoloration of urine — common, harmless (DIM metabolite). It may also interact with some medications. DIM is not right for everyone, so check with a healthcare provider first if you are pregnant or breastfeeding, have a medical condition, or take prescription medication.

Does DIM interact with any medications?

Possible interactions include: Estrogen-containing medications (oral contraceptives, HRT) — DIM may change how the body processes estrogen, so it could in theory make the pill less reliable. This has not been formally tested. Talk to your prescriber and consider backup contraception. If you take prescription medication, check with a pharmacist or doctor before using it.

How strong is the scientific evidence for DIM?

NutraSmarts rates the evidence for DIM as Preliminary (1 out of 5). It is backed by 2 clinical trials and 3 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies.

References(3 citations)

Evidence ratings on NutraSmarts are based on the totality of human clinical research, with emphasis on randomized controlled trials, meta-analyses, and systematic reviews. The references below directly support claims made throughout this page.

  1. Castañon A, Tristram A, Mesher D, Powell N, Beer H, Ashman S, Rieck G, Fielder H, Fiander A, Sasieni P Effect of diindolylmethane supplementation on low-grade cervical cytological abnormalities: double-blind, randomised, controlled trial. British Journal of Cancer. 2012;106(1):45-52. doi: 10.1038/bjc.2011.496.PubMedUsed to support: Large double blind randomized placebo controlled trial: 551 women with low-grade cervical cell changes took 150 mg a day of BioResponse DIM for 6 months. The trial was negative. It missed its primary endpoint and showed no significant effect on cervical cytology or on HPV, and the authors concluded DIM is unlikely to have an effect. It does not support any benefit claim.
  2. 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. doi: 10.1207/s15327914nc5002_5.PubMedUsed to support: Pilot study in 19 postmenopausal breast cancer survivors showing DIM shifted urinary estrogen metabolites toward 2-hydroxyestrone and away from 16-alpha-hydroxyestrone. This is a biomarker change only. It does not show a detoxification benefit or any health benefit.
  3. Rajoria S, Suriano R, Parmar PS, Wilson YL, Megwalu U, Moscatello A, Bradlow HL, Sepkovic DW, Geliebter J, Schantz SP, Tiwari RK 3,3'-diindolylmethane modulates estrogen metabolism in patients with thyroid proliferative disease: a pilot study. Thyroid. 2011;21(3):299-304. doi: 10.1089/thy.2010.0245.PubMedUsed to support: Phase I pilot study in patients with thyroid proliferative disease showing DIM changed the urinary 2-OHE1 to 16-alpha-OHE1 ratio. A small biomarker study in a patient group, not evidence of a benefit in healthy people.