Evigrade

Indole-3-carbinol (I3C)

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

ATC code: A11JA-I3C

Brand names – supplements: Solgar Indole-3-Carbinol, Source Naturals Indole-3-Carbinol, Pure Encapsulations I3CSupplements are not tested in clinical trials and are not registered as medications.

Updated · Methodology

Indications

D

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.

ICD-10: N87 · ICD-11: GA15.7

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.

F

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.

How to read tiers A–F
  • AStrong evidence – first or second line in international guidelines
  • BRecommended in selected cases
  • CStudy data contradict each other
  • DBenefit not proven, no documented harm
  • FDocumented harm, or risk without benefit

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.

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

Pregnancy: can you take Indole-3-carbinol (I3C)?

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

Breastfeeding: can you take Indole-3-carbinol (I3C)?

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

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

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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?

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.

Other drugs in this group

Lecithin (soy or sunflower phosphatidylcholine), Lion's mane (Hericium erinaceus), Lutein, Lycopene, Omega-6 polyunsaturated fatty acids (linoleic acid and GLA), Royal jelly, Cholecalciferol + menaquinone-7 (D3+K2 combo), Chaga (Inonotus obliquus)