Folic acid, a B vitamin that's used widely to fortify foods and lower the risk of birth defects, may carry a hidden risk for those who have to take huge quantities of it: A new study shows those folks were more likely to get COVID-19 and to die from it.
“We examined whether COVID-19 diagnosis and death were related to the large doses of folic acid -- five times the safe upper limit -- prescribed to patients for a variety of medically approved indications," said study co-author Dr. Ralph Green, an expert on B vitamins from the University of California, Davis. "We found that the risk of becoming infected and dying from COVID-19 was significantly greater in the group treated with folic acid.”
In general, low levels of folic acid are linked to an increased risk of birth defects, heart disease and stroke. Also known as vitamin B9, it is prescribed for a number conditions, including sickle cell disease, high-risk pregnancies and also to people taking anti-seizure medications. Some patients taking methotrexate, a drug used to treat some cancers and autoimmune diseases, also take folic acid to help reduce side effects from the folate-inhibiting drug. Interestingly, the study found that methotrexate countered any increased COVID risk for those patients.
Green said he was first motivated to investigate the link between folic acid supplementation and COVID by studies published last year in Nature Communications.
That research suggested that SARS-CoV-2 uses a host's folate to replicate. That means the virus may be sensitive to both folate and folate inhibitors like methotrexate.
For the latest study, Green examined prescription data for more than 380,000 people in the UK Biobank.
His team wanted to determine whether folic acid was linked to an increased risk of COVID and methotrexate to a lower one.
Of more than 26,000 people with COVID, 820 died. Those with folic acid prescriptions were 1.5 times more likely to get COVID and 2.6 times more likely to die from it, compared to a control group.
Meanwhile, people prescribed methotrexate had a similar rate of COVID diagnoses as the rest of the study population.
“Our findings could have implications for patients who take supplementary folate to prevent complications of other pharmacological therapies,” said study co-author Dr. Angelo Gaffo, an associate professor of medicine at the University of Alabama at Birmingham. “Although taking folate in these cases is clearly indicated, clinicians should be cautious about excessive folate intake.”
Due to the makeup of the study population, the researchers said the findings only apply to people 45 or older who are predominately of white European ancestry.
Gaffo said the new results need to be replicated, and the team noted that more study is needed to fully understand how folic acid intake and folate levels affect susceptibility to COVID infection. Levels of folate in participants' blood were not examined in this study.
“The defined safe upper limit of folic acid is 1 milligram. Until we have more information, it would be prudent to avoid extremely high doses of folic acid unless it is medically indicated," Green said, adding that "high folic acid would be of greater concern in unvaccinated individuals.”
The findings were recently published in the journal BMJ Open.
The U.S. Centers for Disease Control and Prevention offers more on folic acid.
SOURCE: University of California - Davis Health, news release, Aug. 31, 2022