In industrialized countries, it is well known that the water and soils are contaminated with Dioxin or Dioxin-like compounds, also called persistent organic pollutants, meaning that they take a long time to break down in nature. Dioxins are by-products of industrial processes, including incineration of vinyl, plastics, other petroleum-based products. Consequently, most of our foods, including grains, seafoods, vegetables and meats, are already contaminated with Dioxin and once they enter our body, it typically takes more than 10 years to eliminate them from our system. In addition, Dioxin can be also introduced into our foods during cooking, such as grilling and frying.
Once inside our blood stream and cells, Dioxin is known to be highly toxic and work through the action of a xenobiotic receptor called “Aryl Hydrocarbon Receptor” (AhR), typically found in the cytoplasm of thymic epithelial cells, reproductive organs, liver, lung, skin epithelial cells, etc. Dioxin causes reproductive, developmental defects, disruption in immune system and also cancer. Dioxin suppress the immune system by impairing the maturation of thymocytes by binding to AhR in thymocytes, leading to reduced output of matured T cells from the thymus. Reduced output of matured T cells results in greatly reduced immune-surveillance for cells with DNA damages and cancerous cells, which in the long term may increase the chance of cancer.
For instance, Agent Orange, the herbicide used during Vietnam war, contained significant amount of TCDD, a Dioxin, resulting in severe consequences for US veterans’ and their offspring’s’ health following the war.
Surprisingly, the cellular receptor for Dioxin, AhR, also binds Indole-3-Carbinol (I3C) (as well as its dimeric and trimeric condensates, DIM and ICZ that form in the acidic environment of the stomach), the endogenous ligands typically found in Cruciferous vegetables, such as Broccoli, Cauliflower and Cabbages, with very high affinity.
By competing with Dioxin for AhR, I3C is known to create a different, beneficial signaling inside cells. Importantly, dietary uptake of I3C is necessary for sufficient AhR signaling levels and critical for health. Indeed, scientists have shown that the removal of AhR ligands (such as I3C) from the diet in mice results in chronic inflammation, increased viral/bacterial infection and greatly increased cancers. These findings led to the now famous quote “Eat your veggies” in 1990s.
I3C uptake can greatly influence the skin, as lack of AhR-ligands, such as I3C, in the diet disrupt skin barrier functions. For skin, activation of AhR-signaling by I3C dictates the decision of whether a UV-damaged skin epithelial cell is to repair DNA-damage or go into apoptosis (cell death), influencing skin barrier integrity and chance of skin cancer.
AhR-signaling activity has also been shown to regulate gut bacteria abundance and composition. A healthy AhR-signaling activity in the gut is affected not only by I3C, but also by gut bacterial metabolites. Therefore, it is best to eat diets that are fiber-rich, fresh vegetables for optimal health.
In this way, there is a strong link between our daily uptake of Indole-3-Carbinol as a diet (or as a dietary supplement) and our overall health.