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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.
Now we believe that we have
discovered the potential mechanism of how vitamin D can be protective
of colon cancer. If it is not the only mechanism, it is at least one of
them.
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.
The new research provides a
possible explanation for the protection of vitamin D as well as the increased
risk of a high-fat diet. Researchers found that vitamin D and a type of
bile acid called lithocholic acid (LCA) both activate the vitamin D receptor
in cells.
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.
But LCA does something unusual.
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.
LCA
Is Very Toxic
Since vitamin D has been shown
to prevent colon cancer in animals, the researchers 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. 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.
If a person does not get enough
vitamin D, this balance may be interrupted, increasing the risk of colon
cancer.
The research also provides
a possible explanation of how high-fat diets may increase the risk of
colon cancer. 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." The body may stop producing enough CYP3A to keep LCA
under control.
Science
May 17, 2002;296:1313-1316
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