Does I3C (from broccoli) or DIM (a related chemical) reduce the risk of cancer?

Answer:

Studies have shown that high consumption of broccoli and other cabbage-family vegetables is associated with reduced risk of a variety of cancers. This has spurred research into potential anticancer effects of compounds that occur in these vegetables, such as indole-3-carbinol (I3C) and its derivative diindolylmethane (DIM), both of which are sold as supplements.

I3C

Some studies in animals indicate that I3C may help reduce the risk of estrogen-sensitive cancers (Auborn, J Nutr 2003), and a study in women with cervical dysplasia found 200 mg to 400 mg of I3C daily improved the rate at which the cervix spontaneously returned to normal (Bell, Gynecol Oncol 2000). In addition, a preliminary study found that adding 400 mg of I3C daily to standard therapy for ovarian cancer (surgery and chemotherapy) resulted in better outcomes than standard therapy alone. However, in an experimental model of breast cancer in rats, I3C treatment resulted in more tumors than when it was not given, suggesting that I3C may have the potential to increase cancer risk in some situations.

Potential health effects of I3C

Laboratory research has shown that I3C can inhibit an enzyme that deactivates a tumor-suppressive protein called PTEN, and applying I3C to prostate tumor cells suppressed their growth (Lee, Science 2019). Consequently, I3C is being considered as a treatment for people with a rare genetic mutation affecting PTEN that predisposes them to higher rates of cancers; however, this has yet to be tested clinically, so it is too early to say if it will work.

Safety of I3C

Although short-term studies with I3C indicate that doses as high as 800 mg daily are safe, longer-term and larger studies are needed to assess its benefits and risks. It should not be given to women who are pregnant or people already diagnosed with cancer (Indole-3-carbinol Altern Med Rev 2005; Licznerska, Adv Exp Med Biol 2016).

DIM (Diindolylmethane)

DIM is a chemical formed in the body upon ingestion of I3C. If taken by itself, DIM has poor absorption. However, a proprietary DIM ingredient called BioReponse-DIM® (other trade names include Indolplex®, BioDIM®, DIM-PRO® and DIM®), which is microencapsulated, has been shown to have improved absorption (Reed, Cancer Epidemil Biomarkers Prev 2008).

Potential health effects of DIM

Laboratory studies have shown that DIM can cause the death of hormone-sensitive cancer cells, suggesting that DIM may be more potent than I3C (Chen, J Nutr 2001). However, most clinical studies have shown limited to no benefit of microencapsulated DIM for people with cancer or pre-cancerous conditions.

Breast cancer
A study among women taking tamoxifen for breast cancer found that also taking 150 mg of DIM as BioResponse-DIM twice daily for 12 months promoted favorable changes in estrogen metabolism, including an increase in the ratio of urinary 2-hydroxyestrone (an anticancer estrogen metabolite) to 16-alpha-hydroxyestrone (a cancer-promoting estrogen metabolite) compared to placebo. However, DIM treatment also caused significant reductions in blood levels of all three tamoxifen metabolites, which raised concerns that DIM may reduce tamoxifen's effects, although those given DIM in this study did not show unfavorable changes in breast density compared to placebo (Thomson, Breast Cancer Res Treat 2017).

Prostate cancer
A study among 45 men with prostate cancer awaiting radical prostatectomy found that taking 400 mg of DIM daily for 3 to 4 weeks improved the ratio of the estrogen metabolites (as also occurred in the breast cancer study above) in comparison to placebo, although total prostate-specific antigen, testosterone or other biomarker levels did not improve (Gee, Eur J Cancer Prev 2016).

Cervical dysplasia
A pilot study among women (average age 27) with biopsy-confirmed cervical dysplasia (abnormal cervical cell growth that can lead to cancer) found that those given 2 mg/kg of body weight of DIM as BioResponse-DIM daily for 12 weeks did not have improvements in Pap smear, human papillomavirus (HPV) status, lesion number, or the rate at which the cervix spontaneously returned to normal compared to placebo (Del Priore, Gynecol Oncol 2010). Similarly, a larger, double-blind trial among women (average age 37) with low-grade cervical abnormalities found that taking 150 mg of the same DIM product daily for 6 months did not improve HPV status or increase the number of women in whom the cervix returned to normal compared to placebo (Castañon, Br J Cancer 2012).

Safety of DIM

Microencapsulated DIM has generally been well-tolerated in clinical studies, with only minor side effects, although there have been rare reports of stroke associated with use.

The most commonly reported side effect is darkening of the urine (Castañon, Br J Cancer 2012; Thomson, Breast Cancer Res Treat 2017). In one study, two people reported feeling nauseas when taking DIM at 2 mg/kg of body weight. This side effect resolved in one person when the daily dose was divided into morning and nighttime doses (Del Priore, Gynecol Oncol 2010).

DIM has been linked to a few cases of clot-related events, including a case of basilar artery stroke (which interrupts blood flow to the brain) and a case of recurrent deep vein thrombosis causing pulmonary embolism (clots in the lungs) (Rhodes, Cureus 2020; Bui, Case Rep Med 2016). More recently, a case of ischemic stroke was reported in a 38-year-old healthy woman in the U.S. military who had been taking 200 mg of DIM for several months, although she had also been taking taking vitamin D, vitamin K2, elderberry gummies and a caffeine supplement in an effort to increase her energy and sex drive, and she had other risk factors for stroke — including a small structural heart abnormality and a history of traumatic subdural hematoma. Nevertheless, her physicians speculated that DIM may have contributed to her increased tendency to develop blood clots due to its effects on estrogen. The patient was started on antiplatelet therapy for 30 days and advised to discontinue supplement use (Pence, Mil Med 2022).