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Indole-3-Carbinol (I3C) Side Effects & Safety

Evidence:Moderate
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This content is for informational purposes only and does not constitute medical advice. Statements about dietary supplements have not been evaluated by the FDA and are not intended to diagnose, treat, cure, or prevent any disease. Individual results may vary — consult your healthcare provider before starting any supplement. Full disclaimer

Safety Profile

Overall safety rating: Generally Safe

Potential Side Effects

  • GI symptoms — nausea, gas, bloating, and diarrhea (more common than with DIM due to stomach acid reactions)
  • Skin rash (uncommon)
  • Unsteadiness or balance issues at high doses (rare, reported in one trial)
  • Variable metabolite production — individual stomach pH differences create inconsistent conversion profiles

Drug & Supplement Interactions

  • CYP1A2 substrates — I3C strongly induces CYP1A2; may reduce levels of caffeine, theophylline, clozapine, and other 1A2 substrates
  • Estrogen-sensitive medications — modulates estrogen metabolism; consult oncologist if on hormonal therapies
  • Antacids and proton pump inhibitors — reduced stomach acid impairs I3C conversion to active metabolites; may reduce efficacy
  • Hormonal contraceptives — theoretical interaction with estrogen metabolism

Maximum Dose

Do not exceed: 400mg daily; higher doses may cause GI side effects and unpredictable metabolite formation

Full Indole-3-Carbinol (I3C) Guide

References

  1. ObservationalRosen CA, Bryson PC (1998). Indole-3-carbinol for recurrent respiratory papillomatosis: long-term results. Journal of Voice. DOI PubMed
  2. RCTBell MC, Crowley-Nowick P, Bradlow HL, et al. (2000). Placebo-controlled trial of indole-3-carbinol in the treatment of CIN. Gynecologic Oncology. DOI PubMed
  3. ObservationalReed GA, Arneson DW, Putnam WC, et al. (2006). Single-dose and multiple-dose administration of indole-3-carbinol to women: pharmacokinetics based on 3,3'-diindolylmethane. Cancer Epidemiology, Biomarkers & Prevention. DOI PubMed
  4. ReviewHigdon JV, Delage B, Williams DE, Dashwood RH (2007). Cruciferous vegetables and human cancer risk: epidemiologic evidence and mechanistic basis.. Pharmacological research. DOI PubMed