Rebuttal: Folic Acid Exposure a Fair Price to Pay for Healthy Babies

Editors’ Note: Last week, The Doctor’s Tablet published a post by Paul Marantz, M.D., M.P.H., in which he asserted that adding folic acid to the food supply may be helping babies at the expense of harming adults. The widely accepted practice of adding this B vitamin to our food supply is credited with preventing devastating neural tube defects. Dr. Marantz argued that this condition is relatively rare and that folate supplementation might be harmful to millions of adults, because taking folic acid can mask the serious effects of vitamin B-12 deficiency. This week, we present an opposing view by Einstein pediatrician Robert Marion, M.D. Drs. Marantz and Marion are featured contributors to this blog.

I hate to disagree with my distinguished and learned colleague, but to my eye, the fortification of the food supply with folic acid in 1998 represented one of the most significant advances in public health in the 20th century. Because of the outcome, I believe that adding folic acid to the food supply ranks up there with the development of the polio vaccine, fluoridation of the water supply and the introduction of chemotherapy for tuberculosis.

The ability to engineer a way to get folic acid to women before conception has saved thousands of lives, preventing children and their families from the grief of a life lived with the painful, expensive and debilitating disabilities that are part and parcel of spina bifida.

For the past 26 years, I have been fortunate enough to serve as medical director of the Montefiore/Einstein Spina Bifida Clinic. During those years, I have cared for more than 250 infants, children and adults with this condition. Most of my patients live their lives in wheelchairs and wear heavy braces; they have orthopedic abnormalities, including joint contractures, dislocated hips and scoliosis; most have hydrocephalus, for which ventriculoperitoneal shunts have been placed and need to be closely monitored; they have neurogenic bowels and bladders, preventing them from ever becoming continent, requiring that they catheterize themselves four or more times a day and wear diapers, in case of the not-uncommon “accidents.”

Many are stigmatized by their condition and marginalized by society, forced after graduating from high school to live their lives in isolation, becoming prisoners to poorly engineered elevators in apartment buildings, unable to leave their homes, unable to find employment, unable to integrate themselves into society.

And the costs are not only social: providing medical services to a child with spina bifida is not insubstantial. According to the Spina Bifida Association, in 2006, the average total lifetime cost to society for each infant born with spina bifida was $532,000. Over the past few years, the cost of medical care for these patients has been skyrocketing; it is likely that this total will soon approach $1 million per person.

To me, it is amazing that the fortification of the food supply has worked. Each year prior to 1998, our clinic welcomed an average of 9.3 newborns, babies with spina bifida who had been born at hospitals in the Bronx. After 1998, the year folic acid was added to bread, cereals and other foods, that average dropped to 2.6 newborns per year. This means that in the Bronx alone, over the course of the past 15 years, spina bifida was prevented in more than 100 infants, a savings to society of more than $50 million.

The numbers in the Bronx closely reflect those published in prospective studies done in the 1980s and 1990s, which showed that periconceptual treatment with folic acid decreased the prevalence of neural tube defects by 70 percent. Now that’s a wonder drug!

Dr. Marantz is concerned that in addition to masking the signs of megaloblastic anemia, which led to the 56 year-old man he describes presenting with a wobbly gait, this man, and others like him, are not benefiting from being forced to ingest folic acid, as they are not likely to become pregnant. However, folic acid is useful not only for its teratophobic effects; it has multiple health benefits for men and women alike. In addition to its role in preventing neural tube defects, there is evidence that folic acid supplementation may improve heart health, prevent Alzheimer’s disease, reduce the risk of colon cancer and improve response to antidepressant medications in people who are depressed. In short, if we keep in mind that we may have masked symptoms and signs of megaloblastic anemia when we approach patients, everyone comes out a winner.

So, yes, all of this is being done, as Dr. Marantz notes, in the name of preventing “rare birth defects.” But if Dr. Marantz had the ability to ask the 56 year-old man with the wobbly gait whether he thought fortifying the food supply to prevent spina bifida in his grandchild was worth the delay that occurred in having his diagnosis made, I bet dollars to donuts that the patient would reply that it was well worth it!

Response by Dr. Paul Marantz:

Dr. Marion, of course, “wins” this argument. After all, my respected colleague is defending disfigured and suffering babies, and I’m heartlessly and coldly calculating societal risks and benefits. He’s a practicing doctor, caring for (and about) these human beings, while I’m a lapsed doctor, caring about societal issues writ large rather than allowing my heartstrings to be pulled by anecdotal human misery. Alas, that’s the fate that any public health argument—no matter how rational and evidence-based—must suffer when compared with moving and heartfelt stories of pain and torment, no matter how rare they may be.

So while I concede defeat, I must at least respond to some inaccuracies, like the old saw that folate will prevent heart disease (which Dr. Marion kindly softened to “may improve heart health”). But even this qualified statement simply is not true; the trials have been unequivocal on this, yet the idea that folate will prevent heart disease persists as a belief (or hope?). As for reducing the risk of colon cancer (or other cancers)—while long ago this was suggested from observational studies, it turned out that it was just because people who take vitamins take better care of themselves (in other ways) than those who don’t. When evaluated in a meta-analysis of clinical trials, folic acid not only did not reduce the risk of colon cancer or many of the other cancers it was tested in; it appeared to increase the incidence of prostate cancer. Sound familiar? (Think of beta-carotene to prevent lung cancer, or estrogen to prevent heart disease.) As for Alzheimer’s disease: I found a few epidemiological suggestions (like the one above) and some mouse studies, but no clinical trials in this arena. Maybe they are out there, but I couldn’t find them.

And while I always prefer cold, hard statistics over anecdotes, I don’t want to leave the impression that masked B-12 deficiency is just some wobbly walking that can be easily fixed with a little vitamin. The gait disturbance can be quite dramatic and debilitating, and B-12 deficiency can lead to a range of neurological insults, some severe, some irreversible. Given the numbers I provided in my blog post, there are almost certainly more people harmed by folate supplementation than babies saved by it. That’s just the underlying math, not a value judgment. Public health policymaking always involves a balancing of potential benefits with potential harms; I just think we need to acknowledge those potential harms.

To me, the bottom line is that we have two irresistible forces that support (and keep supporting) the ongoing mandatory supplementation of our food supply with folic acid: the significant sympathy we feel for these diminishingly rare but heartbreaking birth defects, and the strong underlying belief that taking vitamin supplements has got to be “good for you” (and certainly could never be harmful). These two facts conspire to make us support this supplementation; I just wanted to make my pitiful (but evidence-based) case for the rest of us.