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December 4, 2007

A Growing Debate Over Folic Acid in Flour


Every year, an estimated 200,000 children around the world are born with crippling defects of the spinal column. Many are paralyzed or permanently impaired by spina bifida; some, with a condition called anencephaly (literally, “no brain”), survive in a vegetative state.

It is a stubborn and terrible problem, in the developed and developing worlds alike. But many experts believe it could be greatly eased by a simple government measure: requiring that flour be fortified with the dietary supplement folic acid, which has been shown to prevent these neural tube defects if taken by expectant mothers from before conception through the first trimester.

The debate over folic acid is a familiar one, and Americans could be excused for thinking it was over. Since 1998, the federal government has required that almost all flour be fortified with the supplement.

But in fact, the requirement has meant women receive an average extra dose of just 100 micrograms of folic acid a day — far below the levels that have been shown in studies to prevent spina bifida and other neural tube defects. For more than a decade, the Food and Drug Administration has resisted calls to require that the amount be doubled.

To Dr. Godfrey Oakley, the former director of birth defects research for the Centers for Disease Control and Prevention, it is a baffling situation. “Until this day the F.D.A. still obstructs folic acid supplementation,” he said. “It’s like making a vaccine against polio with only one strain instead of four.”

The debate is intensifying. In the past two years, the American Medical Association, the March of Dimes and several pediatric societies have called on the food and drug agency to reconsider. The only country now adding the amount recommended by experts like Dr. Michael Katz, the medical director of the March of Dimes, is Chile.

Folic acid’s promise emerged 40 years ago, when British obstetricians realized that spina bifida often occurred when mothers had a form of anemia caused by folic acid deficiency. Then, in a 1991 British study of mothers of children with spina bifida, Dr. Nicholas Wald, the lead investigator, found such extraordinary results that he stopped the trial prematurely. When the women took folic acid daily before their next conception and through the first trimester of pregnancy, spina bifida recurrences fell 72 percent.

“That was the most important scientific data I’d heard in my career,” Dr. Oakley said.

In 1992, the Public Health Service called for all menstruating women to take a daily folic acid pill. (Folic acid helps only if taken before the fetus’s nervous system forms, which is before women realize they’re pregnant.)

But when few women followed that advice, the C.D.C. prevailed on the food and drug agency to hold hearings on folic acid fortification. That led to the federal requirement in effect today, though the food and drug agency was never enthusiastic about it. Dr. David A. Kessler, the food and drug commissioner at the time, told me recently that the issue “was probably the hardest decision I had on my tenure on the commission.”

“Adding a biologically active ingredient to the food supply of 300 million people is a very weighty issue,” Dr. Kessler said. “You can’t experiment on the American people.”

For critics of the idea, the first problem was that the recommended doses of folic acid were large, dwarfing the amount found in the average person’s diet. The second worry was that too much folic acid could mask symptoms of vitamin B12 deficiency and perhaps lead to irreversible brain damage in older people.

More recently, some researchers have pointed out that the rate of colon cancer rose slightly in the late 1990s, after the folic acid requirement took effect. But colon cancer rates have since fallen, suggesting the increase was a statistical anomaly.

Skeptics remain. Dr. James Mills, a foe of increased fortification at the National Institutes of Health, concludes that most women’s folate levels are already high enough to avoid preventable neural tube defects. He says there is no way the population’s safety can be guaranteed with higher fortification levels, and asks, “How would you design a study to determine if this is safe?”

Yet the folic acid requirement has had clear benefits. Within a year of the limited fortification, the C.D.C. reported, neural tube defect rates fell 20 percent, and no reports of widespread toxic effects emerged.

And there is good reason to think that requiring more fortification may prevent more birth defects. Blood levels of folate among women have been declining, according to a C.D.C. study released last January, perhaps because of worsening obesity and the popularity of low-carbohydrate diets.

The United States has a long history of accepting food fortification for public health. Iodine in salt has been shown to prevent many cases of mental retardation; while almost one-third of the world’s population has no access to iodized salt, Americans have been ingesting it since 1924. Similarly, additives like vitamin D in milk to prevent rickets, iron in flour to prevent anemia and fluoride in water to prevent cavities have been widespread in the developed world for half a century. Ultimately every public health intervention, including fortification, widespread vaccination and banning trans fats, involves a leap of faith, since no study can ever prove safety beyond the shadow of a doubt. One can show only that unintended harm is very unlikely.

From this perspective, the fact that 300 million Americans have already been exposed to folic acid in flour constitutes one of the world’s largest medical trials — one that suggests fortification is safe. And new benefits have emerged: in June, the American Heart Association reported that folic acid prevented common birth defects of the heart, and the journal Lancet reported that more folic acid might reduce strokes in adults by 18 percent.

Ideally, the authorities would address every concern before any intervention. But this approach causes public health paralysis.

Dr. Oakley bemoans the lack of incentives to prevent birth defects. For example, efforts to include package inserts in tampons or oral contraceptives to educate women about folic acid have not been adopted.

By comparison, he pointed to the introduction of a new vaccine two decades ago that led to the near eradication of Hemophilus meningitis in children.

“The vaccine-industrial complex works like a charm,” Dr. Oakley said. But with folic acid, things are slow: “Nobody’s making any money off this.”

Darshak Sanghavi is a pediatric cardiologist at the University of Massachusetts Medical School and the author of “A Map of the Child: A Pediatrician’s Tour of the Body.”