Several supplement manufacturers are now selling a product called indole-3-carbinol (I3C), a compound that has gained attention in scientific circles as a powerful anticancer agent.
But what exactly is I3C and who can benefit from this strange-sounding substance?
Plant power
I3C is a chemical compound found in high concentrations in cruciferous vegetables such as broccoli, cabbage, cauliflower and Brussels sprouts. Diets high in these vegetables have an anticancer effect in both animals and humans, and scientists suspect that I3C is one of the main reasons why.
Laboratory research has shown I3C to be a powerful stimulator of detoxification enzymes in the body (known as ‘phase-I and phase-II enzymes’), which play a crucial role in neutral-izing and eliminating various toxins and cancer-causing agents. I3C has also been found to regulate many genes that are important in the control of the cell cycle, cell proliferation and other cellular processes, as well as in enhancing DNA repair by affecting several of the proteins involved in the process (J Nutr, 2004; 134 [12 Suppl]: 3493S-8S; In Vivo, 2006; 20: 221-8). All of these activities point to a cancer-fighting capacity.
Indeed, in human cell-culture studies, I3C has been found to inhibit the growth of breast, prostate, colon and cervical cancer cells (J Nutr, 2004; 134 [12 Suppl]: 3493S-8S). And in mice, I3C prevented the growth of tobacco-induced lung cancer (Cancer Lett, 2011; 311: 57-65).
The real question, however, is how does I3C perform in clinical trials-in other words, in studies of actual human beings?
Reversing ‘precancer’
Not many clinical trials been carried out yet, but the results so far are promising.
One of I3C’s key actions is its ability to beneficially alter the metabolism (breakdown) of oestrogen, a family of hormones that can cause cancer if the body can’t deal with them effectively. For this reason, much of the scientific focus has been on I3C’s potential in oestrogen-dependent cancers such as breast and cervical cancer.
In a placebo-controlled study of 60 women judged to be at an increased risk for breast cancer, scientists from the Strang Cancer Prevention Center in New York City investigated the effects of various doses of I3C on the urinary 2:16 hydroxyestrone ratio, a measurement of oestrogen metabolism that is related to breast cancer risk. Ideally, the ratio should be greater than 2; and if it’s less than 1, it’s a danger sign.
The scientists discovered that an oral dose of 300 or 400 mg/day of I3C for just four weeks
was enough to significantly increase the 2:16 hydroxyestrone ratio, suggesting a reduction in breast cancer risk (J Cell Biochem Suppl, 1997; 28-29: 111-6).
Another small trial had similar results. A group of premenopausal women at high risk for breast cancer were split into three groups: the first received 400 mg/day of I3C; the second took a high-fibre supplement; and the third got a placebo. Compared with the other two groups after three months, the women taking I3C showed a statistically significant increase in urinary 2:16 hydroxyestrone ratios. Only three of the 20 women taking I3C failed to have a clinical response, and no adverse effects were reported (Cancer Epidemiol Biomarkers Prev, 1994; 3: 591-5).
More recently, a trial of 17 women (who, again, were considered at high risk for breast cancer) reported that 400 mg/day of I3C not only improved their 2:16 hydroxyestrone ratios, but also produced significant changes in the activities of at least two crucial detoxifying enzymes. The researchers concluded that this might indicate a cancer-protective effect (Cancer Epidemiol Biomarkers Prev, 2005; 14: 1953-60).
Other studies have looked at I3C’s effect on the abnormal cell changes associated with the future develop-ment of cancer-the so-called ‘precancerous’ conditions. In a UK trial conducted at Queen Elizabeth Hospital in Gateshead, women with severe vulvar intraepithelial neo-plasia (VIN)-which is characterized by changes in the skin covering the vulva-were given either I3C (200 or 400 mg/day) or a placebo for six months.
By the end of that time, both I3C groups showed significant improvements in symptoms such as itching and pain, as well as a significant reduction in terms of lesion size and severity. However, tissue biopsies from the worst-affected vulval areas revealed no improvement in the grade of VIN during the six-month period (Int J Gynecol Cancer, 2006; 16: 786-90).
Nevertheless, more dramatic results were seen in a US study of 30 women with moderate-to-severe cervical intraepithelial neoplasia (CIN)-abnormal cellular changes in the cervix that are associated with the development of cervical cancer. Using a similar study design, one group received 200 mg/day of I3C, another group received 400 mg/day of I3C, while a third group received a placebo. After 12 weeks, a biopsy was done to see if there were any changes.
Remarkably, four out of eight patients in the 200 mg/day arm and four out of nine patients in the 400 mg/day arm showed complete regression of their CIN, whereas none of the 10 patients in the placebo group enjoyed such an outcome (Gynecol Oncol, 2000; 78: 123-9).
I3C has also been tested in recurrent respiratory papillomatosis (RRP), a rare disease in which benign tumours grow in the respiratory tract. In some cases, the growths may become cancerous.
In a trial of 18 patients with RRP by the University of Pittsburgh School of Medicine, six patients saw a reduced papilloma growth rate while, in another six, the growth stopped completely (Otolaryngol Head Neck Surg, 1998; 118: 810-5). A follow-up trial reported similar results, leading the researchers to conclude that “I3C has been found to be a successful treatment option for RRP” (J Voice, 2004; 18: 248-53).
Too good to be true?
These clinical trials suggest that I3C may be a useful cancer preventative-especially for people at high risk of the disease. And laboratory studies suggest that it may have a role to play in cancer treatment, too.
However, evidence from animals suggests that, under certain circumstances, I3C could actually promote or enhance the development of cancer (Carcinogenesis, 2002; 23: 265-72).
Such an effect hasn’t been reported in human trials-and the long-term studies looking at cruciferous vegetable intakes certainly don’t appear to suggest it-but the contradictory results in animals have led some experts to caution against the widespread use of I3C supplements until their potential risks and benefits have been better clarified.
In the meantime, though, we may still be able to reap some of the benefits of 13C with generous helpings of broccoli, cabbage, cauliflower and Brussels sprouts. So, when your mum told you to eat your vegetables, she knew best after all.
Joanna Evans
Factfile: Food sources of 13C
To get the most I3C, eating these vegetables raw is best.
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