Indole-3-Carbinol (I3C) and DIM
As usual, Mom was right – you need to eat your veggies! Especially cruciferous vegetables like Brussels sprouts, cabbage, cauliflower and kale. And here are a few reasons why.
Cruciferous vegetables are a special class of veggies, in that they are rich sources of sulfur-containing compounds called glucosinolates, five of which contribute most to total glucosinolate intake in our diet: glucobrassicin, sinigrin, glucoraphasatin (dehydroerucin), glucoraphanin, and glucoiberin. The health benefits of cruciferous vegetables have been extensively studied, and attributed in large part to the compounds derived from the digestion and enzymatic breakdown of these glucosinolates.
The breakdown of one type of glucosinolate, called glucobrassicin, yields indole-3-carbinol, or I3C, which is further broken down in the gut to various active metabolites. This metabolism is pH dependent, requiring the normal acid environment of the stomach. The most predominant metabolite seems to be DIM (3,3′-diindolylmethane), and it seems to be the most stable, hence, the most measurable.
Research on I3C began in the 1960s, and has been extensively studied in both animal and human clinical trials and found to support breast, uterine and cervical health as well as stomach, colon, lung, prostate and liver health.*
As far as supporting healthy hormone metabolism, research concludes both I3C and DIM may interfere with CYP activities involved in estrogen metabolism, and both have been found to modulate the expression and activity of biotransformation enzymes that are involved in the metabolism and elimination of many biologically active compounds, including hormones and drugs.* Both compounds upregulate the phase I enzyme, CYP1A1, and the phase II enzymes, glutathione S-transferase theta-1 (GST q1) and aldo-keto reductase.*
It’s interesting to note, that research measuring the glucobrassicin content of various cruciferous vegetables, points to Brussels sprouts consistently containing the absolute highest levels, followed by kale and cabbage. Broccoli and cauliflower rank next. However, glucobrassicin content is determined by the vegetables’ growing environment, the soil and the weather. So vegetables vary in content quite significantly. Americans have a lower intake of these vegetables than in some other countries, especially Asian countries. This makes the availability of supplementation attractive.
Clinical trials on investigating I3C supplementation for various conditions used doses of 200 to 400 mg/day. There aren’t enough human clinical trials on DIM itself, to sufficiently determine dosage recommendations. But there has been increasing research activity on DIM in the past five years.
Evidence that I3C and DIM can increase the activity of CYP1A2 suggests the potential for I3C or DIM supplementation to decrease serum concentrations of medications metabolized by CYP1A2.* Both I3C and DIM modestly increase the activity of CYP3A4 in rats. This suggests the potential for drug interactions in humans since CYP3A4 is involved in the metabolism of a majority of drugs.
In summary, we have known for a long time that I3C is partially responsible for many of the beneficial effects of consuming cruciferous vegetables. I3C breaks down to many different active metabolites, but DIM appears to be the most stable, and the most measurable, making it easier to isolate. To obtain the highest beneficial levels of I3C and DIM from glucobraccisin in the diet, it’s advisable to eat Brussels sprouts every day. Fortunately, there are high quality dietary supplements containing both I3C and DIM as an alternative!
Selected References:
Oregon State University. Linus Pauling Institute. Micronutrient Information Center. Indole-3-Carbinol. First published 2005, updated 2008, 2017. Copyright 2005-2019 Linus Pauling Institute. https://lpi.oregonstate.edu/mic/dietary-factors/phytochemicals/indole-3-carbinol#references
Licznerska B1, Baer-Dubowska. Indole-3-Carbinol and Its Role in Chronic Diseases. Adv Exp Med Biol. 2016;928:131-154.
Fujioka N, Ainslie-Waldman CE et al. Urinary 3,3′-diindolylmethane: a biomarker of glucobrassicin exposure and indole-3-carbinol uptake in humans. Cancer Epidemiol Biomarkers Prev. 2014 Feb;23(2):282-7. doi: 10.1158/1055-9965.EPI-13-0645. Epub 2013 Dec 19.
Minich DM, Bland JS. A review of the clinical efficacy and safety of cruciferous vegetable phytochemicals. Nutr Rev. 2007 Jun;65(6 Pt 1):259-67.
Kapusta-Duch J1, Kopeć A, Piatkowska E, Borczak B, Leszczyńska T.The beneficial effects of Brassica vegetables on human health. Rocz Panstw Zakl Hig. 2012;63(4):389-95.
