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Americans' penchant for fatty foods is thought to be one of the reasons the rate of colorectal cancer is so high in the U.S. (as a killer, it is second only to lung cancer in industrialized countries). Vitamin D has been shown to offer protection against the disease in rats, but the mechanism behind its beneficial effects was unclear. Now a report published in the current issue of the journal Science reveals that the vitamin helps to detoxify cancer-triggering chemicals that the body releases during the digestion of high-fat foods. The findings suggest that drugs capable of mimicking this beneficial action of vitamin D could help combat colon cancer.
The liver produces a number of acids to digest dietary fat. One of these, lithocholic acid (LCA), is a known carcinogen and is the focus of the new work. David J. Mangelsdorf of the Howard Hughes Medical Institute at the University of Texas Southwestern Medical Center and his colleagues determined that LCA activates the receptor for vitamin D. Using cultures of human cells, the researchers further demonstrated that the gene known as CYP3A, which triggers a cell's detoxification machinery, is switched on when LCA binds to the receptor. "Other investigators had published data showing that the vitamin D could switch on this gene," Mangelsdorf says, "but it was a big surprise that LCA could do it also."
The results indicate that the vitamin D receptor acts as a sensor to detect high levels of the toxic LCA, according to the report. Thus, in theory, compounds that switch the receptor on could help prevent colon cancer by clearing LCA from the body. Simply administering vitamin D as a protective drug to ward off the disease is problematic because it can produce dangerous levels of calcium in the blood, a condition known as hypercalcemia. "But now we know that there's another endogenous compound, LCA, that can also attach to the receptor," Mangelsdorf notes. "This suggests that we can develop protective drugs that don't produce hypercalcemia but do activate the detoxification pathway."
