DENVER – Mandatory food fortification with folic acid not only prevents neural tube defects, it also prevents an estimated 10 million cases of folate-deficiency anemia annually in the United States, James L. Mills, MD, reported at the annual meeting of the Teratology Society.

“We should have people be thinking about the fact that we’re preventing millions of cases of folate-deficiency anemia, not just thousands of cases of neural tube defects. That point does not seem to have reached the public health community. We need to correct the erroneous assumption that a small group are the only ones benefiting by exposing the entire population to folic acid,” said Dr. Mills, senior investigator at the Eunice Kennedy Shriver National Institute of Child Health and Human Development in Bethesda, Md.

He highlighted an analysis of National Health and Nutrition Examination Survey (NHANES) data led by Christine M. Pfeiffer, PhD, chief of the nutritional biomarkers branch at the Centers for Disease Control and Prevention in Atlanta. The investigators determined that NHANES participants’ prevalence of folate-deficiency anemia as defined by an RBC folate level below 340 nmol/L dropped from 3.5% during the premandated food fortification years of 1988-1994 to 0.1% or less in the fortification era of 1999-2010 (J Nutr. 2012 May;142[5]:886-93).

Extrapolating from the nationally representative survey to the full U.S. population, Dr. Mills estimated that translates to roughly 10 million cases of folate-deficiency anemia prevented per year as a result of the mandatory fortification of grain introduced in 1998. That represents an enormous financial savings in avoided costs of diagnosis and treatment of this disorder.

The Food Fortification Initiative reports that 86 countries have embraced mandatory food fortification of wheat, maize, and/or rice. More than two dozen reports from around the world describe 40%-60% reductions in neural tube defect rates as a consequence. However, some of the world’s most populous nations are not on board. These include China, India, Russia, and the entire European Union.

Among the arguments raised by opponents of mandatory food fortification is the notion that it exposes the entire population to folic acid while benefiting only a small group of individuals who are spared having a neural tube defect. But the findings regarding prevention of folate-deficiency anemia demonstrate that argument is incorrect, Dr. Mills said.

Increased risks of asthma, cancer, and twinning as a consequence of mandatory food fortification have been proposed but are not supported by evidence. The only well-established adverse event is masking of vitamin B₁₂ deficiency by correction of the anemia. But most reported cases have occurred after exposure to folic acid in milligram per day amounts, whereas the average U.S. exposure in women of childbearing age is just 163 mcg per day, less than half the recommended daily intake for that group. Also, no increase in cases of newly diagnosed vitamin B₁₂ deficiency without anemia occurred in the U.S. after mandatory fortification was introduced, according to Dr. Mills.

Audience member Godfrey P. Oakley Jr., MD, noted that there is randomized trial evidence to indicate that folic acid supplementation has another important benefit: primary prevention of stroke in hypertensive adults. He cited the randomized, double-blind China Stroke Primary Prevention Trial, in which almost 21,000 hypertensive Chinese adults without a history of myocardial infarction or stroke were randomized to a single-pill combination of 10 mg of enalapril and 0.8 mg of folic acid daily or to a tablet containing 10 mg of enalapril alone.

During a median 4.5 years of follow-up, the enalapril/folic acid group had a 24% reduction in the risk of ischemic stroke and a 20% reduction in the composite of cardiovascular death, MI, and stroke (JAMA. 2015 Apr 7;313[13]:1325-35).

This is a potential game-changing finding which cries out for a confirmatory trial, he said. “There’s a lot going for that paper. I don’t know of a research agenda item that’s more important than trying to find out the relationship between folic acid fortification and stroke. I wish somebody would put some money into it,” said Dr. Oakley, research professor of epidemiology at Emory University in Atlanta.

Dr. Mills responded that he has reservations about the quality of the Chinese study, particularly in light of a Chinese government analysis that concluded that 80% of Chinese clinical trials were fraudulent (BMJ. 2016 Oct 5;355:i5396).

“That makes me want to see more data from a source I have a little bit more confidence in,” he added.

Another possible benefit of folic acid supplementation worthy of investigation is its theoretic potential for cancer prevention. “Folic acid provides one-carbon atoms for DNA repair,” Dr. Mills noted.

Dr. Mills reported having no relevant financial disclosures.

bjancin@frontlinemedcom.com

Folic acid fortification prevents millions of cases of anemia