Indole-3-Carbinol Benefits: What the Research Says

Indole-3-carbinol (I3C) is a compound that forms from broccoli, cabbage and other cruciferous vegetables, and it’s also sold as a supplement for “estrogen balance,” cancer prevention and as an add-on in testosterone boosters. Here’s what the research on indole-3-carbinol actually shows, how strong it is, and what to know about safety.

In short: Indole-3-carbinol reliably changes the way your body breaks down estrogen, but large studies haven’t shown that this change predicts a lower risk of breast cancer. One small placebo-controlled trial in women with cervical precancer looked promising, but it hasn’t been confirmed in bigger trials. The supposed indole-3-carbinol benefits for men using testosterone boosters haven’t been tested at all, and high-dose animal studies raise safety questions.

What is indole-3-carbinol?

Cruciferous vegetables such as broccoli, Brussels sprouts, cabbage, cauliflower, kale and collards contain glucobrassicin, a glucosinolate (a sulfur-containing plant compound). When you chop or chew the raw vegetable, a plant enzyme called myrosinase turns glucobrassicin into indole-3-carbinol [1]. Cooking inactivates myrosinase, although some I3C can still form in the colon [1].

I3C doesn’t stay as I3C for long. In stomach acid it joins together into other compounds, especially 3,3′-diindolylmethane (DIM) [1]. In a study where women swallowed single doses of 400 to 1,200 mg, I3C itself couldn’t be detected in their blood at all; DIM was the only I3C product the researchers found [2]. Supplement doses used in studies have ranged from 200 to 800 mg a day [1].

How indole-3-carbinol changes estrogen metabolism

Your body breaks estrogen down along several routes. One route, called 2-hydroxylation, makes 2-hydroxyestrone, which is thought to have little or no estrogen activity. Another route makes 16α-hydroxyestrone, which still switches on the estrogen receptor (the protein that tells cells to respond to estrogen) [3]. The idea behind indole-3-carbinol is to push more estrogen down the first route.

Small human studies show it does that:

• In a 1990 study, 500 mg of I3C a day for one week raised the share of estradiol (the main form of estrogen) broken down by 2-hydroxylation from 29.3% to 45.6% [4].
• In 12 healthy volunteers taking about 6–7 mg per kg of body weight a day for 7 days, 2-hydroxylation rose by roughly 50%, in men and women equally [5].
• In 7 men (1 week) and 10 women (2 months), urine levels of 2-hydroxy estrogens went up, while urine levels of estradiol and two other estrogens, estrone and estriol, plus 16α-hydroxyestrone went down [6].
• In a placebo-controlled dose-ranging study, 57 of 60 women at higher risk of breast cancer completed 4 weeks. Doses of 300 and 400 mg a day shifted the urine ratio of 2-hydroxyestrone to 16α-hydroxyestrone more than placebo; 50 to 200 mg a day did not [7].

The only one of these studies to measure hormones in the blood was a phase I trial (an early safety study) in 17 women at high risk of breast cancer. After 4 weeks on a placebo, they took 400 mg a day for 4 weeks, then 800 mg a day for 4 weeks; there was no separate control group. The urine 2-to-16 ratio rose by 66%, with the full effect already at 400 mg. But blood levels of estradiol, progesterone, sex hormone binding globulin (SHBG, a protein that carries sex hormones in the blood) and the pituitary hormones LH and FSH (luteinizing hormone and follicle-stimulating hormone, which signal the ovaries and testes) didn’t change [8]. In other words, indole-3-carbinol mainly changes the mix of estrogen breakdown products in urine. It hasn’t been shown to lower the amount of estrogen circulating in your blood.

Does indole-3-carbinol lower breast cancer risk?

The theory was that a higher 2-to-16 ratio would mean a lower risk of breast cancer. That hasn’t held up well. A 2011 systematic review (a structured summary of all the relevant studies) looked at nine studies (six of them prospective, meaning they measured women before any cancer was diagnosed), covering about 1,870 women with breast cancer. A higher urine ratio showed, at best, a weak link that could have been due to chance (statistically non-significant) with lower risk before menopause and none after menopause, and the blood ratio wasn’t linked to risk at all. The authors concluded the prospective studies don’t support using the ratio to predict breast cancer risk [3].

No trial has tested whether indole-3-carbinol supplements actually prevent breast cancer. The Linus Pauling Institute at Oregon State University says the effect of I3C or DIM on breast cancer risk is unknown [1], and Memorial Sloan Kettering Cancer Center notes that I3C hasn’t been shown to treat cancer in humans and that it’s unclear whether supplements benefit people [9].

Indole-3-carbinol for cervical precancer and HPV-related growths

This is where the most interesting, but still small, human evidence sits. In a placebo-controlled trial, 30 women with CIN II–III (moderate to severe precancerous changes on the cervix, usually linked to human papillomavirus, or HPV) were randomly assigned to placebo, 200 mg or 400 mg of I3C a day for 12 weeks. Results were reported for 27 women: none of 10 on placebo had complete regression, compared with 4 of 8 on 200 mg and 4 of 9 on 400 mg [10]. That’s encouraging, but it’s one tiny trial, and the Linus Pauling Institute describes the results as preliminary [1].

A small randomized trial of 12 women with vulvar intraepithelial neoplasia (precancerous changes of the vulva) also reported improvement over 6 months, and more trials are needed there too [1].

For recurrent respiratory papillomatosis (RRP; noncancerous, wart-like growths in the airway caused by HPV), an open-label study (everyone knew they were taking I3C) with no comparison group followed 33 patients for an average of 4.8 years after they started I3C. Eleven (33%) had remission, 10 (30%) had slower regrowth and 12 (36%) had no response; another 12 patients were lost to follow-up [11]. Without a control group, it’s hard to know how much of this was due to I3C.

None of this replaces regular cervical screening and the treatments your doctor recommends.

Indole-3-carbinol in testosterone boosters

Indole-3-carbinol and its breakdown product diindolylmethane (DIM) are often added to testosterone boosters, on the idea that they “control estrogen” in men. The evidence doesn’t really support that use. The men in the studies above took I3C for only about a week, and researchers measured how they broke down estrogen, not their blood hormone levels [5, 6]. In women, I3C changed urine estrogen products without changing blood estradiol [8]. We couldn’t find any trial testing indole-3-carbinol for testosterone, muscle, strength or gynecomastia (breast tissue growth in men).

If you’re looking at testosterone supplements more broadly, see our reviews of D-aspartic acid and calcium D-glucarate, another supplement marketed for estrogen.

Blood clotting: lab and mouse findings only

In lab tests with human platelets (the blood cells that help clots form), indole-3-carbinol reduced platelet clumping, and in mice it reduced deaths from induced blood clots in the lungs [12]. This hasn’t been tested in people, so it isn’t known whether it matters in practice.

Indole-3-carbinol side effects and safety

• In trials, women tolerated 400 to 800 mg a day for several weeks [8].
• Reported side effects include skin rash and small rises in ALT, a liver enzyme [1, 9]. Doses of 800 mg a day have been linked to disequilibrium (feeling off balance) and tremor, which went away when the dose was lowered, and some women had stomach upset after single doses of 600 mg or more [1].
• Indole-3-carbinol speeds up CYP1A2, a liver enzyme that breaks down caffeine and some medicines. In the phase I trial, CYP1A2 activity rose in 94% of women, on average 4.1-fold [8]. Memorial Sloan Kettering advises against taking I3C if you use medicines broken down by CYP1A2 [9]. Acid-reducing medicines would likely stop I3C from forming DIM in the stomach [1].
• In some animal studies, I3C given after a cancer-causing chemical made tumors more likely, while given before or alongside it, it reduced tumors [1]. Neither the protective nor the tumor-promoting effects seen in animals have been shown in humans [9].
• In two-year studies by the US National Toxicology Program, rats got 75 to 300 mg per kg and mice 62.5 to 250 mg per kg by mouth, 5 days a week. There was clear evidence of cancer-causing activity in male mice (liver tumors), some evidence in female rats (uterine tumors), and no evidence in male rats or female mice [13]. These doses are far higher than a typical supplement (400 mg a day is about 6 mg per kg for a 70 kg, or 154 lb, adult), and animal results don’t always apply to people, but they’re a reason long-term safety is uncertain.
• Safety in pregnancy and breastfeeding hasn’t been established [1].

The bottom line on indole-3-carbinol benefits

Indole-3-carbinol does what its fans say at the chemical level: in small, short studies it shifts estrogen breakdown toward 2-hydroxyestrone. But that urine marker hasn’t been shown to predict breast cancer risk, blood estrogen levels didn’t change in the one trial that measured them, and no trial has shown that I3C prevents cancer. The cervical precancer result is promising but comes from one trial of about 30 women. Indole-3-carbinol benefits for testosterone or “estrogen control” in men are untested.

On the safety side, it may change how some medicines are broken down, and high-dose animal studies found tumors in some groups. Eating broccoli, cabbage and their relatives is a different matter from taking hundreds of milligrams of a single compound. If you’re thinking about an I3C supplement, especially for a health condition, talk it through with your doctor first.

This article is for general information only and isn’t medical advice. Talk to your doctor or another qualified health professional before starting a new supplement. See our medical disclaimer.

References

1. Linus Pauling Institute Micronutrient Information Center. Indole-3-Carbinol. Oregon State University. Updated January 2017; reviewed July 2017. Accessed October 2026.
2. Reed GA, Arneson DW, Putnam WC, 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):2477-2481. doi:10.1158/1055-9965.EPI-06-0396
3. Obi N, Vrieling A, Heinz J, Chang-Claude J. Estrogen metabolite ratio: Is the 2-hydroxyestrone to 16α-hydroxyestrone ratio predictive for breast cancer? Int J Womens Health. 2011;3:37-51. doi:10.2147/IJWH.S7595
4. Michnovicz JJ, Bradlow HL. Induction of estradiol metabolism by dietary indole-3-carbinol in humans. J Natl Cancer Inst. 1990;82(11):947-949. doi:10.1093/jnci/82.11.947
5. Michnovicz JJ, Bradlow HL. Altered estrogen metabolism and excretion in humans following consumption of indole-3-carbinol. Nutr Cancer. 1991;16(1):59-66. doi:10.1080/01635589109514141
6. Michnovicz JJ, Adlercreutz H, Bradlow HL. Changes in levels of urinary estrogen metabolites after oral indole-3-carbinol treatment in humans. J Natl Cancer Inst. 1997;89(10):718-723. doi:10.1093/jnci/89.10.718
7. Wong GY, Bradlow L, Sepkovic D, Mehl S, Mailman J, Osborne MP. Dose-ranging study of indole-3-carbinol for breast cancer prevention. J Cell Biochem Suppl. 1997;28-29:111-116. PubMed 9589355
8. Reed GA, Peterson KS, Smith HJ, et al. A phase I study of indole-3-carbinol in women: tolerability and effects. Cancer Epidemiol Biomarkers Prev. 2005;14(8):1953-1960. doi:10.1158/1055-9965.EPI-05-0121
9. Memorial Sloan Kettering Cancer Center. About Herbs: Indole-3-Carbinol. Updated August 2, 2023. Accessed October 2026.
10. Bell MC, Crowley-Nowick P, Bradlow HL, et al. Placebo-controlled trial of indole-3-carbinol in the treatment of CIN. Gynecol Oncol. 2000;78(2):123-129. doi:10.1006/gyno.2000.5847
11. Rosen CA, Bryson PC. Indole-3-carbinol for recurrent respiratory papillomatosis: long-term results. J Voice. 2004;18(2):248-253. doi:10.1016/j.jvoice.2003.05.005
12. Park MK, Rhee YH, Lee HJ, et al. Antiplatelet and antithrombotic activity of indole-3-carbinol in vitro and in vivo. Phytother Res. 2008;22(1):58-64. doi:10.1002/ptr.2260
13. National Toxicology Program. Toxicology studies of indole-3-carbinol in F344/N rats and B6C3F1/N mice and toxicology and carcinogenesis studies of indole-3-carbinol in Harlan Sprague Dawley rats and B6C3F1/N mice (gavage studies). Natl Toxicol Program Tech Rep Ser. 2017;(584). doi:10.22427/NTP-TR-584