The vitamin D in milk and other foods can help protect against the disease by neutralizing a cancer-causing acid the liver produces to help digest fatty foods, a new study says. A high-fat diet is a known risk factor for colon cancer.
The research has established the exact mechanism by which vitamin D acts to prevent colon cancer. A report in tomorrow's issue of Science by two scientists sponsored by the Howard Hughes Medical Institute shows just how vitamin D does the job. It also sets a course toward finding drugs that can do an even better job.The background to the work is "a long history of epidemiological and experimental data, sometimes confusing and controversial, about the role of the Western high-fat diet in colon cancer and the protective effects of vitamin D," says David J. Mangelsdorf, a Howard Hughes researcher who is professor of pharmacology at the University of Texas Southwestern Medical Center.
Working first in cell cultures and then in mice, Mangelsdorf and Ronald M. Evans, a Hughes researcher at the Salk Institute, have outlined just what happens when you eat a hamburger-and-fries meal.
"You increase the metabolism of bile acids, one of which is lithocholic acid (LCA)," Mangelsdorf says. "LCA is extremely toxic, one of the more toxic substances in the body. Most bile acids are made in the liver, go into the intestine where they help absorb fatty foods, and then go back to the liver, where they are stored. LCA cannot go back to the liver. It stays in the colon, where it can damage DNA and induce colon cancer."
It's been known that vitamin D can prevent that genetic damage. The Hughes researchers find this protective effect is due to the fact that LCA binds to the same receptor on cell surfaces as does vitamin D. When vitamin D binds to the receptor, it sets off a chain of events by which LCA is rendered harmless. However, if there is not enough vitamin D or too much LCA, "you overwhelm the system, and so you get colon cancer," Mangelsdorf says.
"This suggests a new therapeutic mechanism that we have not yet tapped," he says. "We can develop potent drugs that activate the vitamin D receptor."
Such drugs would be welcome because they could avoid the side effects of excess vitamin D, which include nausea, weight loss and weakness. Too much vitamin D also raises blood levels of calcium excessively, which can cause other adverse effects.
"That is one of the goals of our research," Mangelsdorf says. "Our next step is to identify compounds that do not have the side effects of vitamin D but do have its protective properties."
Evans, a professor of gene expression at the Salk Institute, is involved in the same effort. In addition to the vitamin D receptor, he says, there are two other receptors for LCA and other bile acids. "Each of these provides an opportunity for potential pharmaceutical and therapeutic intervention," he says.
Until such compounds come along, an obvious protective measure is to get an adequate amount of vitamin D in the diet. Milk has long been fortified with vitamin D to prevent rickets; one cup of milk provides a quarter of the daily recommended dietary allowance. Sunlight makes the body produce vitamin D; rickets was prevalent in yesterday's crowded, sunless slums. Other dietary sources of vitamin D are egg yolks, cod liver oil, prepared cereals (which are fortified with it), margarine (also fortified), and fish such as salmon, mackerel and sardines.
Guidelines say an adequate intake is 200 international units (IU) a day for ages 19 to 50, 400 IU daily for ages 51 to 69 and 600 IU daily for 70 and over.
There's an equally effective dietary strategy that carries other benefits, Mangelsdorf says: eat less fat.
"Our bodies never evolved the ability to sustain a high-fat diet that is a property of modern society," he says. "Our bodies were never intended to see that much fat. The pathological consequences of a high-fat diet include not only colon cancer, but also diabetes and cardiovascular disease. The best drug is to modify your diet."
Vitamin D also helps prevent osteoporosis, and studies have shown it can cut the risk of diabetes in children.
What To Do: You can learn all about the benefits and risks of vitamin D and how to get enough of it from the National Institutes of Health. Learn more about colon cancer from the National Cancer Institute.