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Cancer Resources > Cancer News > Cancer News from Reuters > Reuters Cancer News > 2002 > May
Vitamin D protects against colon cancer by inducing bile acid breakdown
Last Updated: 2002-05-16 14:47:49 -0400 (Reuters Health)
NEW YORK (Reuters Health) - Vitamin D may mitigate the increased risk of colon cancer associated with a high fat diet, according to a report in the May 17th issue of Science.
The link between Vitamin D and colon cancer appears to be the vitamin D receptor's (VDR) response to levels of lithocholic acid, a toxic bile acid produced in fat breakdown, according to Dr. David J. Mangelsdorf, of the University of Texas Southwestern Medical Center in Dallas, and colleagues.
To investigate the potential protective effects of vitamin D, Dr. Mangelsdorf and his associates used a model of human embryonic kidney cells to which vitamin D receptor (VDR) was fused. VDR is a nuclear receptor found primarily in the intestine. "We normally think of VDR as responding to vitamin D and mediating the actions of calcium homeostasis, but it also binds to the secondary bile acid lithocholic acid," Dr. Mangelsdorf told Reuters Health.
The investigators found that receptor activation results in expression of a cytochrome P450 enzyme, CYP3A, which is responsible for the breakdown of lithocholic acid.
"The question becomes, if this sensor causes [lithocholic acid] to be detoxified, why does anyone develop colon cancer?" Dr. Mangelsdorf asked.
According to his team's research, under normal conditions, the concentration of lithocholic acid slightly induces VDR, he said. When vitamin D levels are adequate, the receptor remains saturated and the concentration of lithocholic acid tends not to fluctuate.
"If you lower the vitamin D levels, however, the receptor's action goes down and it loses its protective effect," Dr. Mangelsdorf said, "so that [lithocholic acid] builds up to toxic levels." Or, in the case of high-fat diets, the production of lithocholic acid is stimulated and it simply "overwhelms" the system's ability for detoxification.
These results suggest that the popular low-carbohydrate, high-fat diet many individuals use for weight loss could still put them at substantial risk for colon cancer, he added.
The protective powers of vitamin D could come at a cost, however. High intake of the vitamin can lead to hypercalcemia.
"The other thing our research suggests is that two different compounds activate the same receptor," Dr. Mangelsdorf said. "So this provides the proof of principle that we can make a drug" with action similar to that of vitamin D in protecting the colon but that will not stimulate hypercalcemia, he said.
Such a drug could be protect individuals at elevated genetic risk for colon cancer. However, this approach would be ill-advised in people with normal risk who simply wish to maintain their high-fat diet, he added.
"The best way for normal individuals to lower their cancer risk is to modify their diet," Dr. Mangelsdorf emphasized.
Science 2002;296:1313-1316.
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