Cruciferous Vegetables, Indole-3-Carbinol, and Colon Cancer Risk
Decreasing Cancer Risk
Scientists have long suspected that eating cruciferous vegetables lowers our risk of colorectal cancer. Observational studies have shown a link between the inclusion of the vegetables in our diet and a reduced risk of cancer in the large intestine. An explanation for this link has been hard to obtain, however.
Some new research shows how a chemical called indole-3-carbinol that's made when we eat cruciferous vegetables helps mice. The chemical reduces inflammation and the risk of uncontrolled cell division in the gut of lab mice. The discoveries may be applicable to humans.
What Are Cruciferous Vegetables?
Cruciferous vegetable include broccoli, Brussels sprouts, cabbage, and other examples. Today the vegetables are often classified in the family Brassicaceae. Until quite recently, the family was known as the Cruciferae. The word “Cruciferae” was transformed into an adjective to describe the vegetables and is still used for this purpose. The flowers of the plants are shaped like a cross.
Some commonly available cruciferous vegetables include the following:
- Brussels sprouts
- bok choy
- rutabagas (or swedes)
There are many more examples. The family is large and provides lots of options for someone who wants to eat the vegetables.
Glucosinolates and the Myrosinase Enzyme
Cruciferous plants contain chemicals called glucosinolates. When their tissue is damaged by actions such as cutting, chopping, and chewing, an enzyme called myrosinase is released from cells or cell organelles and comes into contact with the glucosinolate molecules. The enzyme reacts with the glucosinolates to produce new chemicals, including isothiocyanates and indole-3-carbinol. These substances are also produced by the action of bacteria living in the colon when they break down the cooked vegetables. Both substances are believed to be responsible for the reduction in colon cancer risk. The latest research relates specifically to indole-3-carbinol, or I3C, however.
A Plant Scientist Discusses Glucosinolates
Glucosinolates contain sulphur. They are responsible for the somewhat pungent taste of cruciferous vegetables that develops when we chew them, as the scientist in the video above mentions.
The Large Intestine
The small intestine is continuous with the large one. The colon is the first and longest part of the large intestine. It ends in the shorter rectum, where feces is stored before it’s released through the anus. The surface of the intestinal lining is made of epithelial cells. These absorb nutrients and produce a protective layer of mucus. I3C appears to play a role in keeping the epithelial cells healthy.
The colon is active even when it doesn’t contain undigested food that has reached it from the small intestine. The lining of both the small and the large intestine is continually being renewed. The complete replacement of the lining takes approximately four to six days. The reported times vary considerably. In addition, the large intestine contains a large and active population of living bacteria. Many of these bacteria help us in some way. Some species are harmful, but they are usually much less numerous than the helpful ones.
Though most bacteria in our intestine appear to be helpful for us, even “good” bacteria can produce irritating chemicals as well as beneficial ones. It’s important that the intestine has a way to monitor and neutralize these chemicals. Fortunately, it does. One method is via the action of a protein known as AHR.
The Aryl Hydrocarbon Receptor or AHR
The presence of indole-3-carbinol in the digestive tract stimulates the activity of the aryl hydrocarbon receptor, or AHR (sometimes abbreviated as AhR). The protein is found in the cytoplasm of both intestinal epithelial cells and cells from the immune system in the intestine. It’s also found in the cells of other barriers between the body and the outside environment, including those in the skin and the lungs.
AHR binds to a range of chemicals, including ones produced by intestinal bacteria as well as a derivative of indole-3-carbinol. This derivative is formed when I3C reacts with hydrochloric acid from the stomach. The binding is required in order to activate the protein and is a reversible process. The "ligand", or the atom or molecule that joins to the receptor, later separates.
AHR in the intestine can be thought of as a type of environmental sensor. When it’s activated by an appropriate ligand, it stimulates processes that help to prevent intestinal inflammation. Chronic inflammation in the intestine sometimes leads to cancer in the organ. Activated AHR can also stop inappropriate and excessive division of specific cells in the intestine. Excessive cell division can be a sign of cancer.
Indole-3-carbinol has other effects in the cell that are unrelated to the AHR receptor and that may reduce the risk of cancer. It appears to be a very helpful chemical.
Some of the strongest endogenous AHR ligands are derived from phytochemicals such as indole-3-carbinol (I3C) that is converted to the high-affinity AHR ligand ICZ by exposure to stomach acid.— Amina Matidji et al, Immunity journal from Cell Press
I3C and Intestinal Inflammation in Mice
Researchers from the Francis Crick Institute in the UK recently studied genetically-modified mice. The animals had been "programmed" to have insufficient AHR activation due to a variety of factors. As a result of the deficiency, the intestinal lining of the mice became inflamed and they eventually developed colon cancer. If these mice were fed a diet enriched with I3C, however, they didn’t develop inflammation or cancer. In addition, if the genetically-defective mice in whom inflammation had already begun were fed the I3C-enriched diet, they developed “significantly fewer tumours which were more benign”.
The researchers also performed a dietary experiment with genetically-normal mice. Some of the mice were fed a highly-controlled and purified diet which was low in AHR-stimulating chemicals. Other mice were fed standard rat chow, which contained a higher level of AHR-stimulating chemicals than the purified diet. Yet another group of mice was fed an I3C-enriched diet. The mice in the first group developed colon cancer within ten weeks; the mice in the other two groups didn't develop colon cancer.
"Gut” is another word for the digestive tract. It's most often used to refer to the stomach or the intestine. In the experiment described below, it refers to the intestine.
I3C and Cell Division in the Mouse Gut
The researchers also explored the effects of AHR activation on cell division in gut organoids. An organoid is a miniature organ produced from stem cells. Stem cells are unspecialized but have the ability to produce specialized cells as well as additional stem cells when they are stimulated correctly. An organoid has many of the cell types found in the real organ due to the activity of its stem cells. The cell types are also arranged correctly. Organoids are especially interesting to some people because they may reduce the need for animals in research.
The researchers found that activated AHR was essential in order for a new layer of epithelial cells to form in the mouse gut organoids. Without activated AHR, the stem cells in the organoid failed to differentiate into epithelial cells and instead kept on dividing to produce more stem cells.
The scientists made the same observation in the gut of mice without activated AHR. They also found that AHR-stimulating chemicals in the diet (including I3C) restored stem cell differentiation into epithelial cells in the gut of the affected mice.
Applicability to Human Biology
The mouse research is interesting and worth thinking about. It may apply to humans. If so, some questions need to be answered. One is whether the concentration and total amount of IC3 in the enriched diet followed by the mice is relevant to what a person might obtain when eating cruciferous vegetables. Others include:
- What quantity of cruciferous vegetables might a person need to eat in order to experience similar benefits to the mice?
- How often should the vegetables be eaten?
- What factors affect the quantity of I3C in the vegetables?
- Are they best eaten raw or cooked?
- What is the best cooking method with respect to providing I3C availability?
It's already known that vegetables have a range of health benefits, so it's important to eat them even though we don't have all the answers with respect to cancer prevention yet. Nutritionists say that some of the vegetables in our diet should be cruciferous.
A Precaution: Diet and Supplements
I have never read or heard any concerns about obtaining indole-3-carbinol by eating moderate amounts of cruciferous vegetables. The Linus Pauling Institute has a warning about taking the chemical in the form of a supplement, however. Supplements contain concentrated and isolated forms of chemicals which may produce different effects from eating them in food.
Some experts have cautioned against the widespread use of I3C ... supplements for cancer prevention in humans until their potential risks and benefits are better understood.— Linus Pauling Institute, Oregon State University
Purple forms of normally white vegetables may offer extra health benefits due to their anthocyanin content.
Vegetables in the Diet
The Office of Disease Prevention and Health Promotion (a government organization in the United States) recommends that adults eat two servings of fruit and three servings of vegetables a day. Health Canada (also a government organization) recommends a combined total of seven to ten servings of fruits and vegetables every day for an adult, depending on their age and gender.
In 2017, scientists from Imperial College London presented a report based on their analysis of ninety-five studies of the health effects of fruit and vegetable consumption. The researchers said that although five servings of produce a day was helpful for disease reduction, ten servings a day was linked to an even better reduction in disease.
Many nutrition and medical sources say that cruciferous vegetables should be included in vegetable servings, Different sources make different recommendations about the frequency of eating this type of vegetable, however. I've seen recommendations of once a day, three times a week, and once a week.
Consumption of the vegetables might reduce the risk of other types of cancer besides cancer of the colon. Some research suggests that different types of cancer require a different frequency of vegetable consumption in order to reduce the risk of disease. It's probably best to eat cruciferous vegetables at least several times a week.
Some sources say that when fruits and vegetables are grouped together in a serving recommendation, more vegetables should be eaten than fruits.
Benefits of Cruciferous Vegetables
Now that significant results have been discovered in mice, the researchers at the Francis Crick Institute plan to examine the effects of indole-3-carbinol in humans. They plan to experiment with organoids made from human gut biopsies first of all and then conduct clinical trials in people. As they say, though, there’s no need to wait for the results of their investigations before eating cruciferous vegetables. We already know that the vegetables contain valuable nutrients, including vitamins, minerals, and fibre. It would be a good idea to eat them even if they had no effect on cancer. If they do reduce the risk of colon cancer, as seems likely, that’s another great reason for including them in the diet.
Information about cruciferous vegetables from the Linus Pauling Institute at Oregon State University
Indole-3-carbinol facts from Oregon State University
Chemicals in vegetables and colon cancer in mice from the Francis Crick Institute
The environmental sensor AHR protects the colon from inflammatory damage and maintains stem cell homeostasis from the Immunity journal
Food pyramid guidelines from health.gov
Food serving guidelines from the Government of Canada
Up to ten servings of fruits and vegetables a day may prevent premature deaths from the Eurekalert news service
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© 2018 Linda Crampton