High folic acid supplementation linked to increased Covid infections, mortality: UK study

PTI

London, September 2

People in the UK with folic acid prescriptions were 1.5 times more likely to get COVID-19 and 2.6 times more likely to die from the viral disease compared to the control group, according to a study.

The research, published in the journal BMJ Open, also found that having a prescription for the antifolate drug methotrexate mitigated the negative impact of folic acid on COVID-19 when the two were given together.

The researchers from University of California (UC) Davis and the University of Alabama, US studied a large cohort of patients enrolled in the UK BioBank, a major biomedical database containing health information from half a million people.

“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 Ralph Green, professor at UC Davis.

“We found that the risk of becoming infected and dying from COVID-19 was significantly greater in the group treated with folic acid,” said Green, co-senior author of the study.

Folic acid is a synthetic form of vitamin B9, also known as folate. Low levels of B9 are associated with health conditions such as an increased risk of heart disease, stroke and birth defects.

Folic acid is prescribed for several conditions, including sickle cell disease, high-risk pregnancies, and people receiving anti-seizure medications, the researchers said.

It is also prescribed to help offset some side effects for patients taking methotrexate which is used to treat certain types of cancer and some autoimmune diseases. The drug is an “antifolate,” meaning it interferes with folate, which cancer cells require for proliferation.

The researchers looked at folic acid and methotrexate prescription data from 2019 to 2021 in 380,380 participants in the UK Biobank.

They identified 26,033 individuals with COVID-19, of whom 820 died from COVID-19. People with a methotrexate prescription were diagnosed with COVID-19 at a similar rate to the general study population.

However, people with a folic acid prescription were diagnosed with COVID-19 infections at a higher rate (5.99 per cent) and had a much higher COVID-19 mortality rate (15.97 per cent) than the control group.

“Our findings could have implications for patients who take supplementary folate to prevent complications of other pharmacological therapies,” said Angelo L. Gaffo, co-senior author and an associate professor at the University of Alabama.

“Although taking folate in these cases is clearly indicated, clinicians should be cautious about excessive folate intake. Of course, our results will require replication,” Gaffo said.

The researchers note that due to the makeup of the UK BioBank data, the current findings are limited to people 45 years of age and older who are predominantly from White European ethnicities of the UK population. The study did not look at the serum folate levels of the participants.

They note that further investigations are needed to explore the impact of folate status and folic acid intake on susceptibility to SARS-CoV-2 infection and its fatal complications.

“The defined safe upper limit of folic acid is one milligram. Until we have more information, it would be prudent to avoid extremely high doses of folic acid unless it is medically indicated. High folic acid would be of greater concern in unvaccinated individuals,” Green added.