Anti-Estrogen Indole-3-carbinol

Indole-3-carbinol inhibits estrogen metabolism

Cruciferous vegetables - Indole-3-Carbinol (I3C)

Indole-3-carbinol (I3C) is a cruciferous vegetable-derived bioactive phytochemical. Indole-3-carbinol is also available as a dietary supplement and is promising agent for the prevention of estrogen-enhanced cancers.


I3C is abundant in cruciferous vegetables such as cabbage, broccoli, cauliflower, brussels sprouts, collard greens, kale, etc. It is also available in dietary supplements.

Indole-3-carbinol – Negative Regulator of Estrogen

In certain situations where estrogens are contributing to unwanted effects (such as gynecomastia and certain forms of breast cancer) inducing a state of hypoestrogenism may be beneficial.

Indole-3-carbinol predictably alters endogenous estrogen metabolism which leads to enhanced formation of the inactive catechol estrogens and may thereby provide a novel dietary supplement for reducing cancer risk [1]. Studies in animals [2,3] and humans [1,4,5] as well as in vitro [6] studies are showing increased 2-hydroxlation by indole-3-carbinol supplementation. 2-hydroxylation leads to the formation of 2-hydroxyestrone and 2-methoxyestrone, which not only are devoid of estrogenic activity, but may also have some anti-estrogenic activity [6,7,8].

A study by Yuan et al. [6] concluded that indole-3-carbinol has anti-estrogenic activities which should prevent cancer in cervical cells (the second most common cancer in women). When 500 mg/day of indole-3-carbinol was administered to humans for 1 week by Jon J. Michnovicz and colleagues [5], a significantly increased (mean ± SEM) estradiol 2-hydroxylation was noted [29.3% ± 2.1% to 45.6% ± 2.1% (P <.001)]. Also, in rat osteoblasts, I3C abolished the E2-mediated stimulation of cell activities and increases the 2-hydroxylation of E1, resulting in formation of inactive and anti-estrogenic metabolites [11].

Indole-3-carbinol is also a potent inducer of cytochrome P450 enzymes in many species [1], including humans [2]. Cytochrome P450 group of enzymes increase 2-hydroxilation activity [9].

Why is I3C added to Sport Supplements?

Indole-3-carbinol and its dimer diindolylmethane (DIM) are often found in testosterone boosters in belief that they will decrease excess estrogen which may result if testosterone is increased above normal levels.

Side Effects

According to [10], Indole-3-carbinol is likely safe and it seems to be safe for most people when used in medicinal amounts under proper medical supervision. Common side effects include skin rashes and small increases in liver enzymes.


Overuse of I3C for cancer prevention may be unwise. Hormone balance should be tested before using indole-3-carbinol in the hope of preventing cancer.

I3C may greatly reducee the formation of blood clots and decrease platelet aggregation [12].

(Other Common names: 3-Hydroxymethyl Indole, 3-Indolylcarbinol, Indole-3-methanol)


  1. Michnovicz, Jon J., and H. Leon Bradlow. “Altered estrogen metabolism and excretion in humans following consumption of I3C.” (1991): 59-66.
  2. Bradlow, H. Leon, et al. “Effects of dietary indole-3-carbinol on estradiol metabolism and spontaneous mammary tumors in mice.” Carcinogenesis 12.9 (1991): 1571-1574.
  3. Newfield, L., et al. “Estrogen metabolism and human papillomavirus-induced tumors of the larynx: chemo-prophylaxis with indole-3-carbinol.” Anticancer research 13.2 (1992): 337-341.
  4. Michnovicz, Jon J. “Increased estrogen 2-hydroxylation in obese women using oral I3C.” International journal of obesity and related metabolic disorders: journal of the International Association for the Study of Obesity 22.3 (1998): 227.
  5. Michnovicz, Jon J., and H. Leon Bradlow. “Induction of estradiol metabolism by dietary indole-3-carbinol in humans.” Journal of the National Cancer Institute 82.11 (1990): 947-949.
  6. Yuan, F., et al. “Anti-estrogenic activities of indole-3-carbinol in cervical cells: implication for prevention of cervical cancer.” Anticancer research 19.3A (1999): 1673-1680.
  7. Bradlow, H. L., et al. “2-hydroxyestrone: the ‘good’ estrogen.” Journal of Endocrinology 150.3 Suppl (1996): S259-S265.
  8. Schneider, Jill, et al. “Antiestrogen action of 2-hydroxyestrone on MCF-7 human breast cancer cells.” Journal of Biological Chemistry 259.8 (1984): 4840-4845.
  9. Badawi, Alaa F., Ercole L. Cavalieri, and Eleanor G. Rogan. “Role of human cytochrome P450 1A1, 1A2, 1B1, and 3A4 in the 2-, 4-, and 16 [alpha]-hydroxylation of 17 [beta]-estradiol.” Metabolism 50.9 (2001): 1001-1003.
  10. “Find a Vitamin or Supplement – I-3-c”. Retrieved 11. July 2013
  11. Enríquez, J., et al. “The anti-estrogenic activity of i-3-c in neonatal rat osteoblasts is associated with the estrogen receptor antagonist 2-hydroxyestradiol.” Journal of Endocrinological Investigation 39.10 (2016): 1149-1158.
  12. Park, Min‐Kyu, et al. “Antiplatelet and antithrombotic activity of indole‐3‐carbinol in vitro and in vivo.” Phytotherapy Research 22.1 (2008): 58-64.

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