Indole-3-carbinol as a dietary supplement
Indole-3-carbinol (I3C) is a naturally occurring compound found in cruciferous vegetables like broccoli, cabbage, and Brussels sprouts, and is often promoted as a dietary supplement for its potential health benefits. It is primarily recognized for its proposed role in cancer prevention, particularly concerning estrogen-sensitive cancers, as it may help convert estrogen into a less harmful form and inhibit cancer cell growth. Research indicates that a daily intake of around 300 to 400 mg of I3C could be beneficial, although many experts recommend obtaining it through food rather than supplements for safety and effectiveness.
In addition to cancer-related uses, I3C has been studied for its potential effects on conditions such as cervical dysplasia and respiratory papillomatosis. Some evidence suggests it may also offer liver protection and enhance immune function. However, the safety of I3C supplements is a concern, particularly for pregnant women and cancer survivors, as they might have adverse effects, including gastrointestinal issues and interactions with certain medications. Overall, while I3C shows promise for various health applications, further research is necessary to fully understand its benefits and safety profile.
Indole-3-carbinol as a dietary supplement
DEFINITION: Natural substance promoted as a dietary supplement for specific health benefits. It has several common names, including Indolylmethanol, 3-Indolylcarbinol, 3-(Hydroxymethyl)indole, Indole-3-methanol, and I3C.
PRINCIPAL PROPOSED USE: Cancer prevention
OTHER PROPOSED USES: Liver protection, respiratory papillomatosis
Overview
Indole-3-carbinol (I3C), a tumor chemopreventive substance found in vegetables of the broccoli family, is thought to possess properties against cancer and appears to work in several ways, including facilitating the conversion of estrogen to a less cancer-promoting form, partially blocking the effects of estrogen on cells; directly killing or inhibiting cancer cells; and reducing levels of free radicals, which can promote cancer by damaging deoxyribonucleic acid (DNA).
Sources
I3C is found in cruciferous vegetables (Brassica plants), such as cabbage, broccoli, Brussels sprouts, cauliflower, kale, kohlrabi, mustard greens, and turnips. A typical Japanese diet provides the equivalent of about 112 milligrams (mg) of I3C daily; intake in Western diets is lower.
Therapeutic Dosages
A four-week, double-blind, placebo-controlled trial of fifty-seven women found that a minimum dose of 300 mg of I3C daily may be necessary to reduce the risk of estrogen-promoted cancers. Another study found benefits with 400 mg of I3C per day. However, until the overall effects of I3C are better understood, it is recommended that one obtain this substance through the consumption of broccoli family vegetables rather than by taking it as a supplement.
Therapeutic Uses
I3C is proposed as a chemopreventive agenta substance that helps prevent cancer. Numerous animal studies suggest that I3C might help reduce the risk of estrogen-sensitive cancers and other types of cancer. One double-blind, placebo-controlled study in humans suggests that it can help reverse cervical dysplasia, a precancerous condition. Weaker evidence hints at benefits for vulvar intraepithelial neoplasia, a precancerous condition of the vulva. (Note that one should not attempt to treat cervical dysplasia or any other precancerous or cancerous condition without physician supervision.) Early clinical studies suggest supplementing with IC3 may decrease the risk of breast cancer, but more study is needed.
Some evidence indicates that I3C might also help prevent recurrences of a rare condition called respiratory papillomatosis. This disease involves benign tumors in the lungs, mouth, and vocal cords. I3C has additionally been investigated as a liver protectant. Finally, lab studies suggest IC3 may boost immune function and have antiviral effects.
Further evidence suggests that I3C must be exposed to stomach acid to exert its full effects. For this reason, persons with low stomach acid, such as those taking H2 blockers (such as ranitidine, or Zantac) or proton pump inhibitors (such as omeprazole, or Prilosec), may not benefit as much from I3C.
I3C maintains Interleukin-22 (IL-22) levels and reduces the number of pro-inflammatory cytokines, which combine to reduce the total inflammation in the body. It acts as an antiviral against SARS-CoV-2. Some animal studies indicate that I3C improves neurological function after certain brain injuries.
Other proposed uses include systemic lupus erythematosus (SLE), viral infections, fibromyalgia, and liver disease.
Scientific Evidence
A twelve-week, placebo-controlled trial of thirty women with stage two or three 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.
Further research found that I3C significantly impacts the proliferation, invasion, and migration of cancer cells in the liver, breast, and cervix. However, additional research is needed to confirm these results. Other researchers found that I3C may have enhanced the chemotherapy treatment of some cancers, but the findings were not robust.
Animal studies of I3C's impact on SLE showed positive potential results in slowing SLE's progression into kidney disease, resulting in longer life spans. However, a small human trial did not replicate these results.
Safety Issues
Studies in rats, chickens, guinea pigs, mice, and dogs suggest that I3C is safe at recommended doses. Human trials have found no significant side effects with I3C. However, one study in rats found increased abnormalities in male offspring, specifically related to their fertility. For this reason, I3C supplements should not be used by pregnant women.
There are other concerns with I3C, too. For example, despite its overall anticancer effects, there is some evidence that I3C has tumor-promoting properties under certain circumstances. For this reason, the long-term use of concentrated I3C supplements may not be safe. In addition, persons who have already had cancer should not use I3C (or any other supplement) except under physician supervision.
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. Finally, high doses of IC3 have been shown to cause gastrointestinal issues and tremors, and healthcare providers urge patients to consume IC3 from food sources rather than supplements until more studies confirm their effectiveness and safety.
Important Interactions
Persons who are taking any medication that contains estrogen (including birth control pills) should be aware that I3C might interfere with the action of this type of medication. Other studies found interactions with the antipsychotic Clozaril (clozapine) and the selective serotonin reuptake inhibitor Cymbalta (duloxetine).
Bibliography
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Centofanti, Federica, et al. “Synthetic Methodologies and Therapeutic Potential of Indole-3-Carbinol (I3C) and Its Derivatives.” Pharmaceuticals (Basel, Switzerland), vol. 16, no. 2, Feb. 2023, p. 240, doi:10.3390/ph16020240.
Coelho, Steph. “Indole-3-Carbinol: Benefits, Side Effects, Dosage.” Verywell Health, 28 June 2024, www.verywellhealth.com/indole-3-carbinol-5096349. Accessed 20 Sept. 2024.
Hong, C., G. L. Firestone, and L. F. Bjeldanes. “Bcl-2 Family-Mediated Apoptotic Effects of 3,3’-Diindolylmethane (DIM) in Human Breast Cancer Cells.” Biochemical Pharmacology 63 (2002): 1085-97.
“Indole-3-Carbinol.” Memorial Sloan Kettering Cancer Center, 2 Aug. 2023, www.mskcc.org/cancer-care/integrative-medicine/herbs/indole-3-carbinol. Accessed 20 Sept. 2024.
Naik, R., et al. “A Randomized Phase II Trial of Indole-3-Carbinol in the Treatment of Vulvar Intraepithelial Neoplasia.” International Journal of Gynecological Cancer 16 (2006): 786-90.
Peng, L., et al. "Indole-3-carbinol (I3C) Reduces Apoptosis and Improves Neurological Function after Cerebral Ischemia–reperfusion Injury by Modulating Microglia Inflammation." ScientificReports, vol. 14, 2024, doi.org/10.1038/s41598-024-53636-6.