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THE WALL STREET JOURNAL, MARCH 2, 2004
Folic Acid's Benefits Go Beyond Birth

Raising Vitamin's Intake may Cut Risk of Cancer, Heart Attacks in Adults
By Amy Dockser Marcus

It's long been clear that one of the best things women of child-bearing age can do to prevent certain birth defects is to take folic acid supplements. Now, new research indicates that increasing folic acid intake may reduce the risk of heart attacks, strokes and cancer in adults as well.
"I think that ultimately we will see that folic acid will prevent 10 times as many cardiovascular deaths a year as birth defects," says Godfrey P. Oakley Jr., visiting professor of epidemiology at Rollins School of Public Health of Emory University, Atlanta, and a leading advocate of increasing folic acid intake.
Folic acid is part of the B-complex group of vitamins, which help the body break down carbohydrates into simple sugars to be used for energy. It is found naturally in a number of foods, including leafy green vegetables, spinach and bananas. Since 1998, the federal Food and Drug Administration has required food manufacturers to add synthetic folic acid to enriched bread and grain products as well. Still, it is very difficult to get the recommended daily allowance of 400 micrograms only through diet.
Folic acid is essential for the growth and development of a fetus and the prevention of neural-tube defects such as spina bifida, a condition when the spine fails to close properly, and anencephaly, a usually fatal defect that leads to a baby born with an underdeveloped brain or incomplete skull. Four hundred micrograms of folic acid a day, taken a few months before conception through the first several months of pregnancy, can reduce the risk of these defects by more than 50%. Since 1998, the number of babies born with neural-tube defects in the US has declined approximately 25%.
But there is mounting evidence that folic acid's benefits may extend far beyond the realm of birth defects. A 2002 study suggested that folic acid can help prevent the recurrence of blocked arteries in patients who underwent heart-bypass surgery. A randomized trial whose results were published in the British Medical Journal indicated that increasing folic acid levels to twice the daily recommended level, or 800 micrograms, significantly reduces risk of heart disease, stroke and deep vein thrombosis.
Low folic acid levels are associated with chromosome breaks and a higher incidence of certain cancers, such as colon cancer, acute lymphocytic leukemia and pancreatic cancer, according to some recent studies. Three studies published last year found that folic acid has a role in protecting against oral and pharyngeal cancer, that it may decrease a person's risk for colorectal cancer and may also reduce the risk of developing breast cancer.
It also appears from a growing number of studies that folic acid reduces the risk of additional birth defects, including congenital heart disease, some limb defects, and cleft lip and cleft palate.
Still, the exact role of folic acid in preventing disease remains controversial and open to debate. Joseph Mulinare, a medical epidemiologist at the Centers for Disease Control and Prevention, says there aren't enough randomized clinical trials yet that conclusively prove that increasing folic acid intake will lower the incidence of these additional risks. The data are there for neutral-tube defects, he says. But in the case of other birth defects, such as cleft lip and palate, he says "it looks like folic acid reduces these risks, but there are not enough randomized clinical trials done for these conditions, so we can't come out with a statement saying they prevent those other defects."
Earlier this month, a study was published in the Journal of the American Medical Association looking at whether high doses of folic acid - 2.5 milligrams a day, or more than six times the recommended daily allowance - given to people who have had a stroke would reduce the risk of recurrence. It concluded that the higher dose of folic acid didn't appear to make a different.
Still, James F. Toole, director of the Stroke Research center at Wake Forest University in Winston-Salem, N.C., and a co-author of the study, said he believes that starting to take high doses of folic acid when you are in your 30s, rather than in your 60s, will offer better protection against stroke. Data analysis of this question along with others is continuing.
Even in the area where the evidence is strongest of a link between folic acid and disease prevention - preventing neutral-tube defects - doctors say more still needs to be done. Despite educational efforts since the late 1990s to alert women to the benefits of folic acid, the percentage of women of reproductive age who take a daily multivitamin containing folic acid, now at 31%, has increased only slightly, says Nancy Green, the medical director of the March of Dimes.
Dr. Green says the foundation is also worried about the growing popularity of low-carbohydrate diets and the potential that women may not be getting as much folic acid as they need if they give up enriched cereal and bread. "It's hard to know what the effect of these low-carb diets is going to be, but we're very nervous about this", she says.
There are some efforts to find other ways to boost women's intake of folic acid. In December, Johnson & Johnson testified before the FDA about its plans to develop a folic-acid-enriched oral contraceptive. One million women every year get pregnant while on the pill or within three months of coming off it. By adding folic acid to the pill, the company argues that these women will have a much lower risk of having a child with a birth defect. The company and the FDA are discussing the next steps in the drug's development.