UC Davis study suggests that excess folic acid may pose health risks for the elderly


A new UC Davis study found that elevated levels of folic acid may aggravate metabolic complications associated with vitamin B-12 deficiency, a serious health concern that can lead to anemia and neurological damage. The results, which were published in the December issue of the American Journal of Clinical Nutrition, suggest that it is wise to avoid taking folic-acid supplements unless specifically advised by a physician.

woman looking at pharmacy shelves

"There have been concerns that some people may be getting too much folic acid through a combination of sources, and we wanted to determine if there were reasons for those concerns," said Ralph Green, UC Davis professor of pathology and laboratory medicine and senior author of the study. "Our results show that higher levels of folic acid could set in motion a metabolic imbalance that leads to more serious B-12 deficiency."

Green has had a long-standing interest in folic acid and vitamin B-12, particularly since the mid-1990s, when the government began discussing fortifying grain products with folic acid to reduce the incidence of certain birth defects of the brain and spine. He participated in several expert and advisory committees for the National Institutes of Health, Centers for Disease Control and Prevention and Food and Drug Administration. Today, in addition to mandated fortification of cereals and grains, many foods like breakfast cereals can be further enriched with folic acid. In some instances, those foods contain 100 percent of the recommended daily allowance. Knowing that many people also take vitamin supplements, especially as they get older, he thought it might be possible for some elderly to get too much folic acid.

Green and his colleagues conducted the study, in part, to determine if folic-acid fortification could increase cognitive impairment or depression, as a previous study had suggested. To find out, they evaluated folic-acid and B-12 levels in blood samples from 1,535 participants in the Sacramento Area Latino Study on Aging (SALSA), an ongoing, community-based study of health behaviors and outcomes for Latinos aged 60 and older living in the Sacramento region. Those results were compared with evaluations of the participants' cognitive functions and depressive symptoms.

The researchers did not find brain or mental-health changes for study participants with low B-12 and higher levels of folic acid. That same group, however, was more likely to take vitamin supplements and had the highest blood levels of methylmalonic acid and homocysteine — two metabolites that are early and highly sensitive indicators of B-12 deficiency.

Green thinks higher levels of these metabolites could indicate adverse shifts in metabolic health due to too much folic acid, and that a larger-scale, longitudinal study that includes participants from additional racial and ethnic groups is warranted.

"We are at an early stage in determining the effects of this biochemical change," said Green. "But we're well on our way now to establishing the facts about how these vitamins can interact and alter body systems."

In the meantime, since fortification of the food supply has almost eliminated folic acid deficiency in the United States, Green suggests avoiding supplements that contain folic acid, especially since the most significant and potentially irreversible outcome of B-12 deficiency neurological damage can be difficult to detect before it is very serious.

Ralph Green
We do have to worry about folic-acid supplementation. The fact is that a lot of people are getting more of it than is good for them."Ralph Green

"We do have to worry about folic-acid supplementation," said Green. "The fact is that a lot of people are getting more of it than is good for them. If they happen to be B-12 deficient, more folic acid may actually harm them."

Additional study researchers included lead author Joshua W. Miller and Marjorie G. Garrod of UC Davis; Lindsay H. Allen of UC Davis and the U.S. Department of Agriculture; and Mary N. Haan of UC San Francisco and principal investigator of the SALSA project.

The research was sponsored with grants from the National Institutes of Health and U.S. Department of Agriculture.

UC Davis School of Medicine is among the nation's leading medical schools, recognized for its specialty- and primary-care programs. The school offers combined medical and master's degree programs in public health, business administration and rural health, as well as a combined medical and doctoral degree for physician scientists interested in addressing specific scientific, social, ethical and political challenges of health care. Along with being a leader in health-care research, the school is known for its commitment to people from underserved communities and a passion for clinical care. For more information, visit https://health.ucdavis.edu/medical-school/.