Increased Folate Level Appears to Lower Colon Cancer Risk

BETHESDA, Md--When it comes to avoiding colon cancer, Grandma was right: Eat your vegetables, take vitamins, and forget that burger, for goodness sakes. Edward Giovannucci, MD, conveyed this basic message at a workshop on preventing colon cancer, held in conjunction with the American Society of Preventive Oncology (ASPO) annual meeting.

Dietary factors--red meat, fiber, and folate--are under increasing scrutiny for their effects on the development of colon cancer, said Dr. Giovannucci, assistant professor of medicine, Harvard Medical School. "Daily red meat consumption is associated with increased risk of colon cancer," he said, "while fiber intake and folate levels are inversely associated."

Essential in Remethylation

Numerous studies suggest that increased blood levels of folate may cut the risk of colorectal cancer, he said. Folate (or folic acid) is essential in remethylation processes involving 5-methyl tetrahydro-folate and 5,10 methylene tetrahydrofo-late (5,10 MTHF). Both substances are needed by cells, and low levels of 5,10 MTHF may lead to DNA hypomethyl-ation, which could be carcinogenic in a variety of ways, possibly by increasing spontaneous mutations.

Another hint in this direction is that people with specific polymorphisms in the methyltetrahydrofolate reductase (MTHFR) gene have shown a higher colon cancer risk.

Two other dietary factors--alcohol and methionine--may complicate the action of folate in the body. Alcohol can cut serum folate levels "dramatically" in a matter of days, Dr. Giovannucci said. People at highest risk are those with high alcohol intake and low folate or low methionine levels. Two drinks a day will raise the risk by 50%, and a heavy drinker with a poor diet will have an even greater risk, he said.

Methionine represents a contradiction. On the one hand, it is a constituent of red meat. On the other, it appears to be protective against colon cancer. He said that chicken and fish, which are also good sources of methionine, seem protective, while red meat is not.

Folate is no magic bullet, he said. The substance appears to exert its protective effects over time. Citing unpublished studies of multivitamin use (a marker for folate intake), he said that 1 to 4 years of taking vitamins did not reduce colon cancer risk at all; 5 to 14 years cut the relative risk to 0.8; and only after 15 or more years was risk reduced to 0.2. This suggests that folate may have some early role in carcinogenesis.

Folate does prevent colon cancer, he said, but at very high levels it also seems to promote tumor growth once cancer is present. But one would need a much higher intake of folate than 200 µg/day to influence tumor growth. Some treatments for colon cancer, he added, are designed to interfere with the folate cascade. "We might look at people with higher folate intake to see if they are diagnosed at a later stage or have lower survival rates."

Folate has other positive effects as well. It prevents neural tube defects in growing fetuses and may have a role in blocking heart disease by cutting homocysteine levels in the blood. Its only possible drawback, some have suggested, is that higher folate levels would mask vitamin B12 deficiency. "But that’s more theoretical than real," Dr. Giovannucci said. "There’s no epidemic of pernicious anemia in this country."

How can we increase the folate intake in the population? he asked. Because of the differences in folate availability in different foods, and individual differences in absorption, simply boosting dietary consumption is not enough. Dr. Giovannucci recommends a combination of increasing consumption of fruits and vegetables, fortification of foods, and use of vitamin supplements.