Indole-3-carbinol (I3C)

Plant indole derivative from cruciferous vegetables (food supplement under Spanish RD 1487/2009)

ATC code: A11JA-I3C (Indole-3-carbinol (I3C, broccoli-derived))

Brand names – supplements

Solgar Indole-3-Carbinol, Source Naturals Indole-3-Carbinol, Pure Encapsulations I3C

Supplements are not tested in clinical trials and are not registered as medications.

Mechanism of action

Derived from broccoli and other cruciferous vegetables. In the acidic stomach it spontaneously condenses into diindolylmethane (DIM) and other oligomers – these enter the systemic circulation. Affects estrogen metabolism through CYP1A1 induction and shifts the 2-hydroxyestrone to 16α-hydroxyestrone ratio toward 2-OH. Animal models show apoptosis induction in estrogen-dependent cell lines. In humans the clinical data quality is low: small samples, short follow-up, no dose standardisation. On iHerb and Spanish online pharmacies I3C and DIM are sold separately – DIM appears in the Evigrade catalogue as its own card.

Indications

Cervical dysplasia support and prevention

Individual decision

I3C was tested in a small placebo-controlled RCT (Bell 2000) in 30 patients with CIN II-III: doses of 200 and 400 mg/day for 12 weeks produced lesion regression more often than placebo. That remains the only relatively quality study. The 2018 review of nutraceuticals with alleged cancer-prevention activity noted that the data are insufficient for clinical recommendations. SEGO 2024 and AEPCC do not mention I3C in cervical dysplasia management. If a patient receives a CIN diagnosis, the standard of care is observation, colposcopy and, when indicated, conization; I3C replaces neither observation nor active treatment. Discuss with the gynaecologist the standard of care for your case.

Sources

Marketing claims without evidence base

The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.

Breast cancer prevention via supplements

Not recommended

Marketing promotes I3C as breast cancer protection and as liver help to clear estrogens. The 2018 review found no systematic human evidence base – all recommendations rest on preclinical experiments and indirect biomarkers (the 2-OH/16α-OH ratio). The issued a warning letter to BioResponse in 2008 for unsupported cancer-prevention claims and withdrew marketing authorization for DIM supplements positioned for cancer prevention. In patients with a history of hormone-receptor-positive breast cancer, I3C may interact unpredictably with tamoxifen and aromatase inhibitors – clinical data on co-use are absent. If I3C is recommended for cancer protection or to continue after a treated HR+ cancer, consider seeking a second opinion from a breast oncologist.

Sources

NCI PDQ: Chlorophyll and chlorophyllin – PDQ Cancer Information Summaries (2024)

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Safety

Contraindications

Hypersensitivity to I3C or other indole derivatives
History of hormone-receptor-positive breast or endometrial cancer without oncologic review
Tamoxifen or aromatase inhibitor treatment (theoretical interaction)
Warfarin and other CYP1A2 substrates without monitoring
Pregnancy and lactation
Under 18 years of age

Serious adverse effects

Potential interaction with tamoxifen and aromatase inhibitors
Altered metabolism of CYP1A2 substrates (theoretical)
Severe allergic reactions

Common adverse effects

Gastrointestinal discomfort
Urine color change
Headache
Skin rash

PregnancyFDA N

Contraindicated. Concentrated I3C shows estrogen-modulating activity; pregnancy safety data are absent. AEMPS classifies it as do not use in pregnancy.

Breastfeeding

Not recommended. Lactation data are absent. eLactancia rates this as high risk due to theoretical effects on maternal estrogen status.

Calculate RID

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

Frequently asked

What is Indole-3-carbinol (I3C) used for?

Indole-3-carbinol (I3C) is evaluated for the following indications with varying evidence strength: Cervical dysplasia support and prevention (evidence tier D), Breast cancer prevention via supplements (evidence tier F). See the full indication matrix with dosing and citations above on this page.

What are the side effects of Indole-3-carbinol (I3C)?

Common side effects of Indole-3-carbinol (I3C) (≥ 1 in 100): Gastrointestinal discomfort, Urine color change, Headache, Skin rash. See the Safety section for uncommon and serious reactions.

Is Indole-3-carbinol (I3C) safe during pregnancy?

FDA category N. Contraindicated. Concentrated I3C shows estrogen-modulating activity; pregnancy safety data are absent. AEMPS classifies it as do not use in pregnancy.

Is Indole-3-carbinol (I3C) compatible with breastfeeding?

Not recommended. Lactation data are absent. eLactancia rates this as high risk due to theoretical effects on maternal estrogen status.

Who should not take Indole-3-carbinol (I3C)?

Indole-3-carbinol (I3C) is contraindicated in: Hypersensitivity to I3C or other indole derivatives; History of hormone-receptor-positive breast or endometrial cancer without oncologic review; Tamoxifen or aromatase inhibitor treatment (theoretical interaction); Warfarin and other CYP1A2 substrates without monitoring; Pregnancy and lactation. Full list in the Safety section.

Mechanism of action

Indications

Cervical dysplasia support and prevention

Individual decision

Sources

Safety

Contraindications

Hypersensitivity to I3C or other indole derivatives
History of hormone-receptor-positive breast or endometrial cancer without oncologic review
Tamoxifen or aromatase inhibitor treatment (theoretical interaction)
Warfarin and other CYP1A2 substrates without monitoring
Pregnancy and lactation
Under 18 years of age

Serious adverse effects

Potential interaction with tamoxifen and aromatase inhibitors
Altered metabolism of CYP1A2 substrates (theoretical)
Severe allergic reactions

Common adverse effects

Gastrointestinal discomfort
Urine color change
Headache
Skin rash

PregnancyFDA N

Contraindicated. Concentrated I3C shows estrogen-modulating activity; pregnancy safety data are absent. AEMPS classifies it as do not use in pregnancy.

Breastfeeding

Not recommended. Lactation data are absent. eLactancia rates this as high risk due to theoretical effects on maternal estrogen status.

Calculate RID

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

Frequently asked

What is Indole-3-carbinol (I3C) used for?

What are the side effects of Indole-3-carbinol (I3C)?

Common side effects of Indole-3-carbinol (I3C) (≥ 1 in 100): Gastrointestinal discomfort, Urine color change, Headache, Skin rash. See the Safety section for uncommon and serious reactions.

Is Indole-3-carbinol (I3C) safe during pregnancy?

FDA category N. Contraindicated. Concentrated I3C shows estrogen-modulating activity; pregnancy safety data are absent. AEMPS classifies it as do not use in pregnancy.

Is Indole-3-carbinol (I3C) compatible with breastfeeding?

Not recommended. Lactation data are absent. eLactancia rates this as high risk due to theoretical effects on maternal estrogen status.

Who should not take Indole-3-carbinol (I3C)?