Folate is an essential B-vitamin that is needed for DNA synthesis and cell division. Folate deficiency can lead to anemia, and deficiency early in pregnancy can lead to neural tube defects – birth defects of the brain, spine and spinal cord, including spina bifida.

A Cochrane systematic review on the benefits and safety of fortifying wheat or maize flour with folic acid and population health outcomes, led by scientists in the Division of Nutritional Sciences at Cornell, found that fortification with folic acid (the synthetic form of folate) may improve folate status and reduce the occurrence of neural tube defects. However, the review found limited evidence for an effect of fortifying wheat or maize flour with folic acid on hemoglobin levels or risk of anemia, and no studies reported on the occurrence of adverse side effects.

The researchers’ findings, published in the Cochrane Database of Systematic Reviews, will help to inform World Health Organization (WHO) guidelines and recommendations for the national policies and public health programs of its 194 member states.

Cochrane systematic reviews are recognized internationally as representing a gold standard for high-quality evidence for medicine and public health.

This is the first Cochrane systematic review to examine the efficacy of wheat and maize flour fortified with this essential vitamin that is widely known to help prevent neural tube defects.

“The links between maternal folate status early in pregnancy and risk of neural tube defects, a type of severe pregnancy outcome, has been known for over 50 years – and the benefits of periconceptional folic acid supplementation were established with two landmark randomized trials in the early ‘90s,” said Julia Finkelstein, assistant professor in Cornell’s Division of Nutritional Sciences.

“Based on this evidence, flour has been fortified with folic acid in over 60 countries and is one of the most important public health success stories worldwide to prevent neural tube defects,” she said. “However, a systematic review was needed to evaluate the efficacy and safety of folic acid fortification interventions of these two staple flours – and to inform the development of World Health Organization guidelines,” she said.

“This review complements the existing evidence from observational studies and programmatic experience from public health programs, and the findings lead to a better understanding of the benefits and safety of folic acid-fortified wheat and maize flour on population health outcomes,” said Elizabeth Centeno-Tablante, doctoral student in the Division of Nutritional Sciences.

Fortification is one of the main approaches to improve vitamin and mineral intake in populations – to reach at-risk populations without requiring behavior change. “Fortification of staple foods with folic acid is an important strategy to improve folate status in women of childbearing age – since neural tube defects develop in the first four weeks of pregnancy when most women do not yet know they are pregnant,” said Finkelstein.

“In a public health framework, if you can shift the population distribution of folate, you can improve folate nutrition in women during a vulnerable period and help reduce the risk of a very serious health outcome – without changing behavior, in an inexpensive way, to the most vulnerable populations,” Finkelstein said.

No previous systematic reviews evaluated the efficacy of folic acid fortified flour on other health outcomes in the general population. For example, what are its impacts on folate status, anemia or other pregnancy outcomes? What might the benefits or harms be for those with no chance of becoming pregnant – such as children, men or the elderly?

“This Cochrane review includes benefits and safety and any health outcome in any population – for a holistic view of the scientific evidence available to date on this topic,” Finkelstein said.

Evidence from this review has been incorporated into the World Health Organization guideline titled, “Fortification of Maize Flour and Corn Meal With Vitamins and Minerals” and will be incorporated into the upcoming WHO guideline for wheat flour fortification.

The Division of Nutritional Sciences at Cornell University has been a PAHO/World Health Organization Collaborating Centre since 2015, and this year was named an Affiliate Centre for Nutrition in the new Cochrane US Network.

The Cochrane protocol and review were developed as part of the annual WHO/Cochrane/Cornell University Summer Institute for Systematic Reviews in Nutrition for Global Policy Making, hosted by the Division of Nutritional Sciences.

Helena Pachon ’93, M.S. ’96, Ph.D. ’06, of the Food Fortification Initiative and Hubert Department of Global Health at Emory University, contributed to the study.

Stephen D’Angelo is assistant director for communications for the College of Human Ecology.