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• Posted September 30, 2022

Could a Folic Acid Prescription Help Prevent Suicide?

More than 1 million Americans attempted suicide in 2020, and a new study is hinting at a potential way to reduce that risk: prescription folic acid.

The study, of more than 800,000 Americans in a health care database, found that when people were on prescription folic acid, their likelihood of being treated for self-harm or suicide attempt dropped by 44%.

Folic acid is a synthetic form of folate, or vitamin B9, that is used in supplements and added to some foods.

Experts stressed that the new findings do not prove that folic acid, itself, reduces suicide risk.

"I would not rush out to the drugstore to get folic acid," said lead researcher Robert Gibbons, a professor at the University of Chicago. "And I certainly wouldn't replace any medical evaluation, or ongoing care, with a supplement."

To prove that folic acid has a direct effect on suicidal behavior, Gibbons said, it will take a clinical trial where people are randomly assigned to take the vitamin or not.

But the study, published Sept. 28 in JAMA Psychiatry, does add to evidence tying vitamin B9 to mental health.

Past research has linked low folate levels in the blood to depression. And when evaluating patients for depression, some mental health professionals order blood tests to measure folate, as well as vitamins D and B12 (as deficiencies in those nutrients have been tied to depression symptoms, too).

"I do that all the time," said Dr. Christine Crawford, a psychiatrist and associate medical director of the nonprofit National Alliance on Mental Illness.

Crawford, who was not involved in the new study, agreed the evidence supports doing a clinical trial.

But given that folic acid is low-risk, she said patients already in treatment for depression could talk to their provider about adding the vitamin.

"This is not something that should replace standard treatment for mental health conditions," Crawford said. "But it could be used in conjunction with it."

Plus, she said, if talking about folic acid helps "normalize conversations around suicide," that would be an important impact, too.

The current study stems from another one Gibbons and his colleagues conducted in 2019, where they looked at the relationship between all available prescription medications and suicide risk.

It turned out 44 drugs were linked to a reduced risk, and -- surprisingly -- prescription folic acid was among them.

At first, Gibbons said, the researchers thought that might be because of who was taking folic acid: Pregnant women often do, to reduce the risk of certain birth defects. So they ran another analysis of male patients only.

"And we saw the same association in men," Gibbons said.

For the new analysis, the researchers turned to an insurance claims database with information on more than 866,000 Americans who filled a folic acid prescription between 2012 and 2017.

Since there may be many differences between people who use folic acid and those who do not, the researchers looked at the question a different way: What was the risk of self-harm or suicide attempt during a period when patients were on folic acid, versus when they were not? So each person served as their own "control."

Overall, the study found, the rate of self-harm/suicide attempt was roughly halved when people were using folic acid. There were just under five such incidents per 100,000 people each month. That compared with a rate of over 10 per 100,000 people during months when there was no folic acid use.

When the researchers weighed other factors -- like age, sex and history of mental health diagnoses -- folic acid use was still linked to a 44% reduction in the risk of suicide attempt/self-harm.

There was still another possibility, Gibbons said: Maybe people who use prescription supplements are particularly interested in enhancing their health, and that explains the link.

So the researchers looked at whether prescription vitamin B12 was tied to a lower risk of suicide attempt. It was not.

The researchers also considered the possibility that folic acid specifically helps people who are taking prescriptions that deplete folate in the blood.

Certain medications -- such as methotrexate, prescribed for rheumatoid arthritis -- "wipe out" users' folate levels, Gibbons said. So doctors commonly prescribe folic acid to patients on those drugs.

In fact, in the 2019 study, many people using prescription folic acid had been diagnosed with pain conditions -- 52% overall -- and almost one-third were on methotrexate.

But in the new analysis, there was no clear evidence that folic acid helps by countering the effects of folate-depleting medications.

The researchers now plan to put folic acid to the test in a clinical trial, looking at whether the supplement can reduce suicidal thoughts and behaviors.

"Folic acid is inexpensive, widely available and doesn't really have side effects," Gibbons said. "If this relationship is causal, think of all the lives that could be saved."

More information

The American Foundation for Suicide Prevention has resources for people at risk.

SOURCES: Robert Gibbons, PhD, professor, biostatistics and medicine, University of Chicago; Christine Crawford, MD, MPH, associate medical director, National Alliance on Mental Illness, Arlington, Va., and assistant professor, psychiatry, Boston University School of Medicine; JAMA Psychiatry, Sept. 28, 2022, online