Assessing the risk of excess folic acid intake
It is well established that folic acid supplementation can significantly reduce the risk of birth defects, including neural tube defects like spina bifida, the most common birth defect of the central nervous system and the second most common of all structural birth defects. More than 80 nations, including the U.S. 25 years ago, have established mandated folic acid food fortification programs, which have been successful.
“However, there is a lack of research on whether excessive folic acid intake has the potential to harm human beings,” said co-corresponding author, , William T. Butler, M.D., Distinguished Chair Professor in the and the departments of , and at Baylor College of Medicine.

There are reports of adverse effects associated with high folate intake in humans. In this study published in the journal , Finnell and his colleagues investigated in an animal model the potential effect of folic acid supplementation on DNA mutation rates and other genetic modifications such as whole genome methylation, which can change how much of any given gene product gets expressed in cells.
The animals received one of three folic-acid-supplemented diets: folic acid low, folic acid control and folic acid high. “Compared to the mutation frequency of the folic acid-control diet group, that of the folic acid-low diet group increased two-fold and the folic acid-high diet group increased 1.8 fold,” Finnell said.
The researchers found that DNA repair genes were significantly hypermethylated in the folic acid-high diet, suggesting that excess folic acid supplementation may affect the mutation rate by reducing the expression of DNA repair genes and consequently impairing DNA repair activity. Understanding these mechanisms requires further investigation.
“The effects of high- or low-folic acid diets should be confirmed in human population in future studies,” Finnell said. “Our data supports that folic acid supplementation should be restricted to an ideal benefit range. What we have here is a “Goldilocks Effect”: Too little or too much of a good thing (folic acid) may not be such a good thing.”
This article first appeared on the Baylor College of Medicine news site.
Enjoy reading ASBMB Today?
Become a member to receive the print edition four times a year and the digital edition monthly.
Learn moreGet the latest from ASBMB Today
Enter your email address, and we’ll send you a weekly email with recent articles, interviews and more.
Latest in Science
Science highlights or most popular articles

What’s in a diagnosis?
When Jessica Foglio’s son Ben was first diagnosed with cerebral palsy, the label didn’t feel right. Whole exome sequencing revealed a rare disorder called Salla disease. Now Jessica is building community and driving research for answers.

Peer through a window to the future of science
Aaron Hoskins of the University of Wisconsin–Madison and Sandra Gabelli of Merck, co-chairs of the 2026 ASBMB annual meeting, to be held March 7–10, explain how this gathering will inspire new ideas and drive progress in molecular life sciences.

Glow-based assay sheds light on disease-causing mutations
University of Michigan researchers create a way to screen protein structure changes caused by mutations that may lead to new rare disease therapeutics.

How signals shape DNA via gene regulation
A new chromatin isolation technique reveals how signaling pathways reshape DNA-bound proteins, offering insight into potential targets for precision therapies. Read more about this recent ɬÀï·¬ paper.

A game changer in cancer kinase target profiling
A new phosphonate-tagging method improves kinase inhibitor profiling, revealing off-target effects and paving the way for safer, more precise cancer therapies tailored to individual patients. Read more about this recent ɬÀï·¬ paper.

How scientists identified a new neuromuscular disease
NIH researchers discover Morimoto–Ryu–Malicdan syndrome, after finding shared symptoms and RFC4 gene variants in nine patients, offering hope for faster diagnosis and future treatments.