Can folic acid fight cancer?

If you're not a smoker and your breasts or prostate stay healthy, the biggest cancer risk is to your large bowel - that's your colon and rectum. Fortunately, scientists have learned enough to tell us what may lower that risk.

"It's very clear that people who eat a lot of fruits and vegetables and don't eat a lot of fat, especially animal fat, have a lower risk of colon cancer," says physician John Baron of Dartmouth Medical School in Hanover, New Hampshire.

But for researchers that's just the beginning. "Are those people at lower risk because of what they eat or because of something else they do?" he asks. "And if it is diet, is it the beta-carotene, the folate, the vitamin C, or something else in fruits and vegetables?"

The evidence that it's folic acid - which occurs in food as folate - is one of the most exciting.

First, there's the "epidemiological" evidence. For example, among women in the Nurses' Health Study or men in the Health Professionals Follow-Up Study, those who reported eating more folate-rich foods were less likely to develop colon cancer over the next few years.[1]

And there are the animal studies.[2] "If we mildly deplete animals of folic acid, it increases their risk of colorectal tumors three- or four-fold," says Joel Mason of the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University in Boston.

But what's compelling about the evidence on folic acid, says Edward Giovannucci of Harvard Medical School, is that "it has a direct effect on DNA." And errors in DNA are thought to trigger cancer.

PEOPLE AT RISK

Like many cancers, colon cancer often has no symptoms until it has spread. But in some people, the doctor first finds a kind of benign tumor called an adenomatous polyp.

"Adenomas are very common," says Baron. "They're found in a third or more of autopsies of older men and women, no matter what they died of."

Most people don't know they have polyps, he adds. "And only a very small percent turn into cancer." But sometimes bleeding or a sigmoidoscopy (examination of the lower bowel) brings them out of hiding ... and out of the bowel.

Doctors remove polyps because "almost all colon cancers develop out of adenomas," says Baron. That lowers their cancer risk, but even people who've had polyps removed have a higher risk of more tumors.

"If you take people with colon cancer or adenomatous polyps and remove the cancer or polyp, their colons are still abnormal," says Mason. "There's something about their colons that makes them a fertile field for tumors."

One abnormality involves something called a "methyl group" - a carbon atom surrounded by three hydrogen atoms. "One of folate's major functions is to transfer methyl groups to DNA," explains Mason. But in people who've had polyps or tumors removed, even the healthy tissue left in their bowel shows evidence of fewer methyl groups than normal.

In a small pilot study, Mason and his colleagues gave those people a whopping dose of 10,000 micrograms of folic acid a day.[3] "After six months, their methylation rates increased markedly," he says.

How might methyl groups stop cancer? "If DNA is methylated, it might keep a cancer-causing gene from being switched on," says Giovannucci. When methyl groups aren't plentiful, he adds, it "seems to cause the same mutation that occurs in most colon tumors."

And, adds Mason, "any tissue that reproduces more quickly requires a lot of folic acid. The whole intestinal lining turns over every three to five days."

He's found lower folate levels in the colons of people who've had precancerous polyps, even though the amount of folate in their blood is normal.

So if you've had polyps, says Mason, "you may be getting the Recommended Dietary Allowance for folate and still have a higher risk of colon cancer than someone next door who gets half as much."

Fascinating. But proof that folic acid prevents tumors? Not by a long shot.

TRIALS UNDER WAY

That proof could come in another five years or so. Three clinical trials are just getting under way to test high doses of folic acid (1,000 to 5,000 micrograms a day) on people who've had polyps removed.

In the meantime, load up on fruits and vegetables and watch the animal fats. Oh, and don't forget your annual tests for hidden blood in the stool and your sigmoidoscopy.

"You may not have a great afternoon," says Baron. But you may be lucky enough to find a large polyp that's just turning into cancer. "If they're found early," says Giovannucci, "they're fairly curable."

[1] Journal of the National Cancer Institute 85: 875, 1993. [2] Cancer Research 52: 5002, 1992. [3] European Journal of Cancer Prevention 3: 473, 1994.