Indole-3-carbinol (I3C) is a compound found in cruciferous vegetables that has attracted attention for its potential effects on oestrogen metabolism and cancer prevention. But how much of this interest is justified by actual clinical evidence? This article examines what the research shows and what remains uncertain.

What is indole-3-carbinol?

Indole-3-carbinol is an indole compound formed when glucosinolates in cruciferous vegetables break down. When you chew raw broccoli, cabbage, kale, Brussels sprouts, or cauliflower, an enzyme called myrosinase converts glucosinolates into I3C.

Epidemiological studies have consistently found associations between diets rich in cruciferous vegetables and lower rates of certain cancers [1]. Researchers trying to identify what makes these vegetables potentially protective have focused on glucosinolates and their breakdown products.

Glucosinolates give cruciferous vegetables their characteristic bitter taste and pungent smell. In the plant, they function as natural pest deterrents. In humans, they undergo further chemical changes.

When I3C reaches the acidic environment of your stomach, it rapidly undergoes condensation reactions that produce several compounds. The most studied of these is diindolylmethane (DIM). Both I3C and DIM appear to influence liver detoxification enzymes and may affect how the body processes oestrogen [2].

Laboratory research suggests I3C and DIM work through multiple pathways, including effects on cell cycle control, apoptosis (programmed cell death), hormone signalling, and DNA repair mechanisms. The challenge is determining whether these laboratory findings translate into meaningful clinical benefits.

What are the evidence-based benefits of indole-3-carbinol?

1. May improve oestrogen metabolism (moderate evidence)

This is the area with the most human research. I3C appears to shift how the body breaks down oestrogen, favouring a metabolic pathway that produces 2-hydroxyestrone rather than 16alpha-hydroxyestrone. Some researchers believe this shift may reduce oestrogen-related cancer risk, though this remains theoretical.

A study in 17 women at high risk for breast cancer found that I3C supplementation increased the activity of cytochrome P450 1A2 and glutathione S-transferase enzymes, and improved the ratio of oestrogen metabolites [3]. The sample size is small, but the findings are consistent with what laboratory studies predicted.

Another randomised, double-blind, placebo-controlled trial tested DIM (the main metabolite of I3C) in 130 patients taking anti-oestrogen breast cancer medications over one month. The participants showed favourable changes in oestrogen metabolism and increased sex hormone-binding globulin [4].

My assessment: The evidence that I3C affects oestrogen metabolism in humans is reasonably consistent. Whether this translates into cancer prevention remains unproven. Measuring metabolite ratios is not the same as preventing disease.

2. May improve cervical intraepithelial neoplasia (mixed evidence)

Cervical intraepithelial neoplasia (CIN) refers to abnormal cell changes on the cervix that can precede cervical cancer. These lesions are graded from CIN I (mild) to CIN III (severe) based on how much of the cervical lining is affected.

A randomised, placebo-controlled trial gave I3C to 30 patients with CIN grade II-III for 12 weeks. Four of eight women taking 200 mg daily and four of nine taking 400 mg daily showed complete regression of their lesions. None of the 10 placebo patients showed regression [5].

This sounds promising, but a larger trial tells a different story. A double-blind randomised trial of 551 women with low-grade cervical lesions tested DIM supplementation for six months. The study found no significant effect on preventing lesion progression or clearing human papillomavirus (HPV) infection [6].

My honest take: The early small trial generated excitement, but the larger, more rigorous trial did not confirm the benefit. This pattern appears frequently in supplement research. Until more large trials replicate positive findings, I would not recommend I3C specifically for cervical lesions.

3. May help recurrent respiratory papillomatosis (limited evidence)

Recurrent respiratory papillomatosis is a rare condition where HPV causes wart-like growths in the throat and airways. It requires repeated surgical removal and can be life-threatening if growths obstruct breathing.

A pilot study followed 18 patients with recurrent respiratory papillomatosis who took I3C (400 mg daily for adults, 10 mg/kg for children) for an average of 17 months. About one-third showed reduced tumour growth rates and needed fewer surgeries. The study also reported increased oestrogen metabolite ratios [7].

The catch: 18 patients, no control group, and variable follow-up times. This counts as preliminary evidence at best. The disease is rare enough that conducting large randomised trials is difficult, but that does not make weak evidence stronger.

4. May improve vulvar intraepithelial neoplasia (limited evidence)

Vulvar intraepithelial neoplasia (VIN) refers to abnormal cells on the external female genitalia that can develop into vulvar cancer if untreated. It most commonly affects women under 50 and may cause symptoms like itching, burning, or visible skin changes.

A small study gave I3C (200 or 400 mg daily) to 12 patients with VIN for six months. The researchers reported improvements in symptoms, lesion size, and disease severity in some participants [8].

The problems here are the same as with the respiratory papillomatosis study: tiny sample size, no placebo control, and no way to account for natural variation in disease course. Some VIN lesions improve spontaneously, so attributing improvement to the supplement requires a controlled comparison.

What the evidence does not support

I should be clear about what remains unproven despite popular claims:

Direct cancer prevention: No randomised trial has demonstrated that I3C supplements prevent breast cancer, cervical cancer, or any other cancer. The oestrogen metabolism changes are surrogate markers, not actual cancer outcomes.

Treatment for established cancers: I3C is not a cancer treatment. If you have cancer, follow your oncologist’s recommendations rather than hoping supplements will help.

General health benefits: The research focuses narrowly on hormone-responsive conditions. There is no evidence I3C improves immune function, detoxification capacity, or general health in healthy people.

What are the side effects of indole-3-carbinol?

At typical supplement doses (200-400 mg daily), I3C appears reasonably well tolerated in short-term studies. Reported side effects include:

Skin rashes
Diarrhoea
Balance problems
Tremors
Nausea

These side effects seem more common at higher doses. Long-term safety data beyond a few months of use is lacking.

One case report documented a slight increase in ALT (a liver enzyme) in someone taking I3C, though the clinical significance is unclear [9].

Safety precautions (4 contraindications)

1. Pregnancy, breastfeeding, and liver or kidney impairment

There is no safety data for I3C supplementation during pregnancy or breastfeeding. Given its effects on hormone metabolism, caution is appropriate. Similarly, people with compromised liver or kidney function should avoid I3C supplements since these organs metabolise and excrete the compound.

If you are pregnant, planning pregnancy, breastfeeding, or have liver or kidney disease, eating cruciferous vegetables as part of a normal diet is different from taking concentrated supplements.

2. Liver enzyme effects

The case report of elevated ALT mentioned above warrants caution. Anyone with existing liver problems or taking medications that stress the liver should discuss I3C supplementation with their doctor and consider monitoring liver function tests.

3. Medications metabolised by cytochrome P450 1A2

I3C increases the activity of the liver enzyme CYP1A2. This can speed up the breakdown of medications that depend on this enzyme, potentially reducing their effectiveness.

Medications affected include: clozapine, cyclobenzaprine, fluvoxamine, haloperidol, imipramine, mexiletine, olanzapine, pentazocine, propranolol, tacrine, theophylline, zileuton, and zolmitriptan [10].

If you take any of these medications, do not add I3C supplements without consulting your prescriber. The interaction could make your medication less effective.

4. Medications that reduce stomach acid

I3C requires stomach acid for the chemical reactions that convert it to DIM and other active compounds. Medications that reduce stomach acid may interfere with this conversion.

Antacids, H2 blockers (like ranitidine), and proton pump inhibitors (like omeprazole) could theoretically reduce the effectiveness of I3C supplements. If you take these medications regularly, I3C supplementation may not work as expected.

How does indole-3-carbinol compare to eating cruciferous vegetables?

A reasonable question: can you just eat more broccoli instead of taking supplements?

The amount of I3C in cruciferous vegetables varies considerably depending on the vegetable, how it is prepared, and how long it is cooked. Raw vegetables contain more active myrosinase enzyme, so they likely produce more I3C than cooked vegetables.

Most clinical trials have used I3C doses of 200-400 mg daily. To get this amount from food, you would need to eat substantial quantities of raw cruciferous vegetables daily. Whether the compounds from food and supplements behave identically in the body remains uncertain.

There is a reasonable argument that eating cruciferous vegetables provides I3C along with fibre, vitamins, minerals, and other beneficial compounds without the unknowns of concentrated supplementation. The epidemiological evidence linking cruciferous vegetables to health benefits comes from food consumption, not supplement use.

For most people, increasing cruciferous vegetable intake is safer and has more evidence behind it than taking I3C supplements.

Bottom line

Indole-3-carbinol has plausible mechanisms and some preliminary human evidence suggesting it can shift oestrogen metabolism. However, the clinical evidence for actual disease prevention or treatment remains weak.

The trials showing benefits are generally small and uncontrolled. The one large, rigorous trial testing DIM for cervical lesions found no benefit.

If you are interested in the potential benefits of cruciferous vegetable compounds, eating more broccoli, cabbage, and kale is a reasonable first step. Supplementation with I3C remains experimental and carries drug interaction risks that dietary intake does not.

Anyone considering I3C supplements should discuss this with their doctor, particularly if they take medications metabolised by CYP1A2 or have hormone-sensitive conditions.

References

Verhoeven DT, et al. Epidemiological studies on brassica vegetables and cancer risk. Cancer Epidemiol Biomarkers Prev. 1996;5(9):733-48. PubMed
Aggarwal BB, Ichikawa H. Molecular targets and anticancer potential of indole-3-carbinol and its derivatives. Cell Cycle. 2005;4(9):1201-15. PubMed
Reed GA, et al. Single-dose and multiple-dose administration of indole-3-carbinol to women: pharmacokinetics based on 3,3’-diindolylmethane. Cancer Epidemiol Biomarkers Prev. 2006;15(12):2477-81. PubMed
Thomson CA, et al. Chemopreventive properties of 3,3’-diindolylmethane in breast cancer: evidence from experimental and human studies. Nutr Rev. 2016;74(7):432-43. PubMed
Bell MC, et al. Placebo-controlled trial of indole-3-carbinol in the treatment of CIN. Gynecol Oncol. 2000;78(2):123-9. PubMed
Castañón A, et al. Effect of diindolylmethane supplementation on low-grade cervical cytological abnormalities: double-blind, randomised, controlled trial. Br J Cancer. 2012;106(1):45-52. PubMed
Rosen CA, et al. A preliminary study of the use of indole-3-carbinol for recurrent respiratory papillomatosis. Otolaryngol Head Neck Surg. 1998;118(6):810-5. PubMed
Naik R, et al. A randomized phase II trial of indole-3-carbinol in the treatment of vulvar intraepithelial neoplasia. Int J Gynecol Cancer. 2006;16(2):786-90. PubMed
Laidlaw M, et al. Effects of 3,3’-diindolylmethane on hepatic gene expression profiles and liver health. Nutr Cancer. 2010;62(7):904-14.
Natural Medicines Comprehensive Database. Indole-3-Carbinol Drug Interactions. Available from: therapeuticresearch.com