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Indole-3-Carbinol

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Principal Proposed UsesOther Proposed Uses


Supplement Forms/Alternate Names :

  • I3C

Uses

Principal Proposed Uses

Other Proposed Uses

Indole-3-carbinol (I3C), a chemical found in vegetables of the broccoli family, is thought to possess cancer preventive properties.
Indole-3-carbinol appears to work in several ways:
  • Facilitating the conversion of estrogen to a less cancer-promoting form 1-3,6
  • Partially blocking the effects of estrogen on cells 4,6,30
  • Directly killing or inhibiting cancer cells 6
  • Reducing levels of free radicals, which can promote cancer by damaging DNA 5

Sources

I3C is found in cruciferous vegetables ( Brassica plants), such as cabbage, broccoli, brussels sprouts, cauliflower, kale, kohlrabi, and turnips. A typical Japanese diet provides the equivalent of about 112 mg of I3C daily; intake in Western diets is lower. 7,8

Therapeutic Dosages

A 4-week, double-blind, placebo-controlled trial of 57 women found that a minimum dose of 300 mg of I3C daily may be necessary to reduce risk of estrogen-promoted cancers. 9 Another study found benefits with 400 mg of I3C per day. 10 However, until the overall effects of I3C are better understood, we recommend obtaining this substance through consumption of broccoli family vegetables rather than taking it as a supplement. (See Safety Issues .)

Therapeutic Uses

I3C is being studied as a chemopreventive agent: a substance that helps prevent cancer . Numerous animal studies suggest that I3C might help reduce the risk of estrogen-sensitive cancers, as well as other types of cancer. 16-19,31-33 One double-blind, placebo-controlled study in humans suggests that it can help reverse cervical dysplasia , a precancerous condition. 20 Weaker evidence hints at benefits for vulvar intraepithelial neoplasia, a precancerous condition of the vulva. 37Note : Do not attempt to treat cervical dysplasia, or any other precancerous or cancerous condition, without physician supervision.
Some evidence indicates that I3C might also help prevent recurrences of a rare condition called respiratory papillomatosis. 21,34 This disease involves benign tumors in the lungs, mouth, and vocal chords.
I3C has additionally been investigated as a liver protectant . 22
Further evidence suggests that I3C must be exposed to stomach acid to exert its full effects. 11-15 For this reason, individuals with low stomach acid, such as those taking H 2 blockers (eg, ranitidine [Zantac]) or proton pump inhibitors (eg, omeprazole [Prilosec]), may not benefit as much from I3C.

What Is the Scientific Evidence for Indole-3-Carbinol?

A 12-week, placebo-controlled trial of 30 women with stage II or III cervical dysplasia found that treatment with I3C at a daily dose of 200 or 400 mg significantly improved the rate at which the cervix spontaneously returned to normal. 23

Safety Issues

Studies in rats, chickens, guinea pigs, mice, and dogs suggest that I3C is safe at recommended doses. 24 Human trials have found no significant side effects with I3C. 25,26,27
However, one study in rats found increased abnormalities in male offspring, specifically related to their fertility. 35 For this reason, I3C supplements should not be used by pregnant women.
There are other concerns with I3C, as well. For example, despite its overall anticancer effects, there is some evidence that I3C has tumor-promoting properties under certain circumstances. 28,29,36 For this reason, long-term use of concentrated I3C supplements may not be safe. In addition, individuals who have already had cancer shouldn’t use I3C (or any other supplement) except under physician supervision. (But you don’t need physician supervision to increase your broccoli intake!)
In addition, because it facilitates the inactivation of estrogen, it is possible that I3C might tend to promote osteoporosis in postmenopausal women and could interfere with estrogen therapies (such as birth control pills and hormone replacement therapy). However, this concern is purely theoretical at this time.

Interactions You Should Know About

If you are taking:

References

1 Michnovicz JJ. Increased estrogen 2-hydroxylation in obese women using oral indole-3-carbinol. Int J Obes Relat Metab Disord . 1998;22:227-229.

2 Bradlow HL, Michnovicz JJ, Halper M, et al. Long-term responses of women to indole-3-carbinol or a high fiber diet. Cancer Epidemiol Biomarkers Prev . 1994;3:591-595.

3 Wong GY, Bradlow L, Sepkovic D, et al. Dose-ranging study of indole-3-carbinol for breast cancer prevention. J Cell Biochem Suppl . 1997;28-29:111-116.

4 Yuan F, Chen DZ, Liu K, et al. Anti-estrogenic activities of indole-3-carbinol in cervical cells: implication for prevention of cervical cancer. Anticancer Res . 1999;19:1673-1680.

5 Arnao MB, Sanchez-Bravo J, Acosta M. Indole-3-carbinol as a scavenger of free radicals. Biochem Mol Biol Int . 1996;39:1125-1134.

6 Bradlow HL, Sepkovic DW, Telang NT, et al. Multifunctional aspects of the action of indole-3-carbinol as an antitumor agent. Ann N Y Acad Sci . 1999;889:204-213.

7 Heaney RK, Fenwick GR. Natural toxins and protective factors in brassica species, including rapeseed. Nat Toxins . 1995;3:233-237,242.

8 McDanell R, McLean AE, Hanley AB, et al. Chemical and biological properties of indole glucosinolates (glucobrassicins): a review. Food Chem Toxicol . 1988;26:59-70.

9 Wong GY, Bradlow L, Sepkovic D, et al. Dose-ranging study of indole-3-carbinol for breast cancer prevention. J Cell Biochem Suppl . 1997;28-29:111-116.

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;78:123-129.

11 Bradfield CA, Bjeldanes LF. Modification of carcinogen metabolism by indolylic autolysis products of Brassica oleraceae . Adv Exp Med Biol . 1991;289:153-163.

12 Bjeldanes LF, Kim JY, Grose KR, et al. Aromatic hydrocarbon responsiveness-receptor agonists generated from indole-3-carbinol in vitro and in vivo: comparisons with 2,3,7,8-tetrachlorodibenzo-p-dioxin. Proc Natl Acad Sci U S A . 1991;88:9543-9547.

13 Jellinck PH, Forkert PG, Riddick DS, et al. Ah receptor binding properties of indole carbinols and induction of hepatic estradiol hydroxylation. Biochem Pharmacol . 1993;45:1129-1136.

14 Arnao MB, Sanchez-Bravo J, Acosta M. Indole-3-carbinol as a scavenger of free radicals. Biochem Mol Biol Int . 1996;39:1125-1134.

15 Kelloff GJ, Boone CW, Crowell JA, et al. New agents for cancer chemoprevention. J Cell Biochem Suppl . 1996;26:1-28.

16 Broadbent TA, Broadbent HS. The chemistry and pharmacology of indole-3-carbinol (indole-3-methanol) and 3-(methoxymethyl)indole. [Part II]. Curr Med Chem . 1998;5:469-491.

17 Background information. Indole-3-carbinol (I3C). 700-06-1, June 28, 2000. National Institute of Environmental Health Sciences web site. Available at: http://ntp-server.niehs.nih.gov/htdocs/Chem%5FBackground/ExecSumm/Indolecarbinoll . Accessed September 19, 2000.

18 Heaney RK, Fenwick GR. Natural toxins and protective factors in brassica species, including rapeseed. Nat Toxins . 1995;3:233-237,242.

19 McDanell R, McLean AE, Hanley AB, et al. Chemical and biological properties of indole glucosinolates (glucobrassicins): a review. Food Chem Toxicol . 1988;26:59-70.

20 Bell MC, Crowley-Nowick P, Bradlow HL, et al. Placebo-controlled trial of indole-3-carbinol in the treatment of CIN. Gynecol Oncol . 2000;78:123-129.

21 Rosen CA, Woodson GE, Thompson JW, et al. Preliminary results of the use of indole-3-carbinol for recurrent respiratory papillomatosis. Otolaryngol Head Neck Surg . 1998;118:810-815.

22 Shertzer HG, Berger ML, Tabor MW. Intervention in free radical mediated hepatotoxicity and lipid peroxidation by indole-3-carbinol. Biochem Pharmacol . 1988;37:333-338.

23 Bell MC, Crowley-Nowick P, Bradlow HL, et al. Placebo-controlled trial of indole-3-carbinol in the treatment of CIN. Gynecol Oncol . 2000;78:123-129.

24 Background information. Indole-3-carbinol (I3C). 700-06-1, June 28, 2000. National Institute of Environmental Health Sciences web site. Available at: http://ntp-server.niehs.nih.gov/htdocs/Chem%5FBackground/ExecSumm/Indolecarbinoll . Accessed September 19, 2000.

25 Bell MC, Crowley-Nowick P, Bradlow HL, et al. Placebo-controlled trial of indole-3-carbinol in the treatment of CIN. Gynecol Oncol . 2000;78:123-129.

26 Rosen CA, Woodson GE, Thompson JW, et al. Preliminary results of the use of indole-3-carbinol for recurrent respiratory papillomatosis. Otolaryngol Head Neck Surg . 1998;118:810-815.

27 Wong GY, Bradlow L, Sepkovic D, et al. Dose-ranging study of indole-3-carbinol for breast cancer prevention. J Cell Biochem Suppl . 1997;28-29:111-116.

28 Dashwood RH. Indole-3-carbinol: anticarcinogen or tumor promoter in brassica vegetables? Chem Biol Interact . 1998;110:1-5.

29 Bailey GS, Hendricks JD, Shelton DW, et al. Enhancement of carcinogenesis by the natural anticarcinogen indole-3-carbinol. J Natl Cancer Inst . 1987;78:931-934.

30 Meng Q, Yuan F, Goldberg ID, et al. Indole-3-carbinol is a negative regulator of estrogen receptor-alpha signaling in human tumor cells. J Nutr. 2000;130:2927-293l .

31 Chinni SR, Sarkar FH. Akt inactivation is a key event in indole-3-carbinol-induced apoptosis in PC-3 cells. Clin Cancer Res. 2002;8:1228-1236.

32 Hong C, Firestone GL, Bjeldanes LF. Bcl-2 family-mediated apoptotic effects of 3,3'-diindolylmethane (DIM) in human breast cancer cells. Biochem Pharmacol. 2002;63:1085-1097.

33 Rahman KM, Sarkar FH. Steroid hormone mimics: molecular mechanisms of cell growth and apoptosis in normal and malignant mammary epithelial cells. J Steroid Biochem Mol Biol. 2002;80:191-201.

34 Auborn KJ. Therapy for recurrent respiratory papillomatosis. Antivir Ther. 2002;7:1-9.

35 Wilker C, Johnson L, Safe S. Effects of developmental exposure to indole-3-carbinol or 2,3,7,8-tetrachlorodibenzo-p-dioxin on reproductive potential of male rat offspring. Toxicol Appl Pharmacol . 1996; 141:68-75.

36 Stoner G, Casto B, Ralston S, et al. Development of a multi-organ rat model for evaluating chemopreventive agents: efficacy of indole-3-carbinol. Carcinogenesis. 2002;23:265-272.

37 Naik R, Nixon S, Lopes A, et al. A randomized phase II trial of indole-3-carbinol in the treatment of vulvar intraepithelial neoplasia. Int J Gynecol Cancer. 2006;16:786-90.

Revision Information

This content is reviewed regularly and is updated when new and relevant evidence is made available. This information is neither intended nor implied to be a substitute for professional medical advice. Always seek the advice of your physician or other qualified health provider prior to starting any new treatment or with questions regarding a medical condition.

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