By Merritt McKinney
NEW YORK (Reuters Health) – New research suggests that vitamin D may protect against colon cancer by helping to get rid of a toxic acid that promotes the disease.
The discovery could point the way to the development of therapies that provide the cancer protection of vitamin D without the side effects caused by consuming too much of the vitamin, the study’s lead author told Reuters Health in an interview.
“Now we believe that we have discovered the potential mechanism of how vitamin D can be protective of colon cancer,” said Dr. David J. Mangelsdorf, of the Howard Hughes Medical Institute at the University of Texas Southwestern Medical Center in Dallas. If it is not the only mechanism, it is “at least one of them,” he said.
Mangelsdorf explained that vitamin D is known to protect against colon cancer, but exactly how has been uncertain. The high-fat “Western” diet has been linked to an increased risk of the disease, although this connection is controversial, according to Mangelsdorf.
The new research, which is reported in the May 17th issue of the journal Science, provides a possible explanation for the protection of vitamin D as well as the increased risk of a high-fat diet. Mangelsdorf and his colleagues found that vitamin D and a type of bile acid called lithocholic acid (LCA) both activate the vitamin D receptor in cells.
In the interview, Mangelsdorf explained that when a person eats fatty foods, the liver empties bile acids into the intestine, making it possible for the body to absorb fatty substances. After doing their job in the intestine, most bile acids are taken back into the liver, he said.
But LCA does something unusual, Mangelsdorf said. It is not recirculated into the liver. Instead, an enzyme called CYP3A degrades LCA in the intestine, he said. If LCA is not detoxified by the enzyme, it passes into the colon where it can promote cancer, according to the Texas researcher.
LCA is “very toxic,” Mangelsdorf said.
Since vitamin D has been shown to prevent colon cancer in animals, Mangelsdorf and his colleagues decided to see whether its receptor had any effect on the detoxification of LCA.
In fact, the vitamin D receptor seems to act as a sensor for high levels of LCA, according to Mangelsdorf. The vitamin D receptor binds to LCA, triggering an increase in the expression of the gene for CYP3A, the acid-neutralizing enzyme. This seems to be the body’s way of protecting itself from colon cancer, Mangelsdorf said.
If a person does not get enough vitamin D, this balance may be interrupted, increasing the risk of colon cancer, according to Mangelsdorf.
The research also provides a possible explanation of how high-fat diets may increase the risk of colon cancer, the Dallas researcher said. Since LCA is released from the liver when a person eats fatty food, a high-fat diet that keeps LCA levels high may “overwhelm the system,” Mangelsdorf said. He speculated that the body may stop producing enough CYP3A to keep LCA under control. He added that a high-fat diet is “something our bodies were never, never meant to have to deal with.”
The study does not prove that a high-fat diet increases the risk of colon cancer, according to Mangelsdorf, but “it gives us a testable hypothesis for testing the effects of a high-fat diet.”
The discovery may also help researchers develop drugs to prevent colon cancer, Mangelsdorf suggested. Too much vitamin D can have harmful effects, but it may be possible to develop a drug that would provide the vitamin’s cancer-protective effects without its harmful side effects.
Source: Science 2002;296:1313-1316