The new study suggests excess folic acid intake could reduce the immune system's ability to fight off infections.
The study, published in the Journal of Nutritional Biochemistry, was conducted by researchers at the Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA) at Tufts University in Boston, MA.
Because low folic acid levels in pregnancy are a major risk factor for neural tube defects in babies, the US government has set the Recommended Daily Allowance (RDA) for pregnant women at 600 µg; the normal RDA is 400 µg.
Folate is found naturally in many foods, including green and leafy vegetables, beans, eggs, grains and fish. Additionally, many cereals are fortified with folic acid, which is the synthetic form of folate.
The body uses folic acid every day to make new, healthy cells, and as such, everyone needs folic acid.
According to the National Institutes of Health (NIH), around 35% of people in the US consume folic acid through dietary supplements. However, some population groups are at risk of acquiring excess folic acid.
The NIH report that people over the age of 50 have the highest folic acid intakes, and around 5% have intakes that exceed the established tolerable upper intake, which is 1,000 µg per day.
Although previous studies have demonstrated a link between high folic acid intake and reduced immune system defenses, the researchers from this latest study wanted to assess whether excess folic acid intake can cause negative changes in the immune system.
Immune system diminishes with age
To conduct their investigation, the researchers - led by Hathairat Sawaengsri, doctoral student at Tufts University - used aged mice to confirm that the links previously observed in women over 60 years of age did not "occur by chance."
The team looked specifically at natural killer (NK) cells, which are a particular type of immune cell vital in defending against viral infections and cancer by identifying and attacking infected cells.
Impairing the function of NK cells could lead to increased vulnerability to disease. In the elderly, these cells are particularly important, because the immune system diminishes with age, leaving them more open to infections and cancer.
As an index of immune function in the aged mice, the researchers used NK cell cytotoxicity, which is the ability of NK cells to destroy other cells.
Their study design involved giving a control group of mice a level of folic acid that was equivalent to the human RDA. Meanwhile, they gave a treatment group of mice an intake of folic acid 20 times greater than the human RDA.
They note that although the amount of folic acid consumed by most adults is lower and taken over a longer time period, they used a higher dose in their study to account for the fact that mice are more efficient at metabolizing folic acid than humans are.
Causal relationship between excess folic acid and lowered NK cell activity
Results showed that the mice that were fed high amounts of folic acid in the treatment group had higher concentrations of unmetabolized folic acid in their blood plasma and higher concentrations of folate in their spleens, compared with mice in the control group.
What is more, the mice in the treatment group had lowered NK cell activity, compared with those in the control group; the researchers say these results establish a causal relationship between excess folic acid intake and lowered NK cell activity in aged mice.
"Our aim was to look at excess folic acid and its impact on immune function," says Sawaengsri. "Taking what we have found in this study, the next step is to determine if excess folic acid actually increases our susceptibility to infections."
Commenting further, study author Ligi Paul, PhD, from the HNRCA, says:
"If we want to optimize the efforts of NK cells to increase resistance to infections, the use of folic acid in some contexts may need to be reassessed. Among older adults, additional research might show that it is important to take supplements only if one has been documented to be folate-deficient."
Their results build on the findings of a study from 2005 conducted by the same lab, which found that 78% of healthy postmenopausal women had unmetabolized folic acid in their blood plasma, indicating excess folic acid. They, too, had lower NK cell activity.
In 2015, Medical News Today reported on a study that suggested folic acid may reduce the risk of stroke in people with hypertension.