“There are no real side effects, it doesn’t cost a lot of money, and you can get it without a prescription,” said the lead study author, Robert Gibbons, PhD, a professor of biostatistics and medicine at the University of Chicago. “This could potentially save tens of thousands of lives.” Suicide is the 12th leading cause of death in the United States, according to the American Foundation for Suicide Prevention. In 2020, 45,979 Americans died by suicide, and there were an estimated 1.2 million suicide attempts.

Folic Acid: An Unlikely Candidate for Suicide Prevention

Folic acid is a B vitamin that helps the body make healthy new cells. Although everyone needs folic acid, it’s especially important for women who may get pregnant, because the recommended amount of the vitamin before and during pregnancy has been shown to prevent major birth defects in the baby’s brain or spine, according to MedlinePlus. On the surface, the vitamin may appear to have little connection to suicide prevention, which typically includes screening, access to ongoing and crisis support, therapy, and medications such as antidepressants. How did the authors decide to look at the relationship between folic acid and suicide attempts in the first place? The identification of folic acid as a way to reduce suicide attempts was discovered with the application of a new statistical screening methodology called iDEAS (High Dimensional Empirical Bayes Screening), to a database that included health and prescription records from 160 million people in the United States over a 10-year period, explains Dr. Gibbons.

Certain Medications and Conditions May Decrease Folate Levels

That prior research looked at associations between suicide attempts and more than 900 different drugs (including supplements) and found that 10 drugs were associated with increased suicide risk and 44 with decreased risk. Unexpectedly, folic acid was one of the 5 drugs most strongly associated with fewer suicide attempts. Further analysis revealed that more than half the people who had a folic acid prescription (which is available over the counter and is more commonly purchased that way) had a pain diagnosis, and 31 percent who were prescribed the supplement had also filled a prescription for methotrexate, which is often prescribed to people with rheumatoid arthritis (RA). Methotrexate can deplete folate, which is why folic acid supplements are often prescribed to people taking the drug. Researchers believed that the low levels of folate caused by methotrexate may increase suicide risk, and that folic acid supplementation then decreased that risk.

Folic Acid Supplements Were Associated With Reduced Risk of Suicide Attempts in All Populations

To test this association, investigators used databases of inpatient, outpatient, and prescription claims from more than 100 insurers to identify about 866,000 adults who filled a folic acid prescription between 2012 and 2017. The data allowed researchers to see which months the prescriptions were filled and cross-reference that with suicide attempts. Researchers were also able to pinpoint individuals who had been diagnosed with conditions, such as depression and anxiety, that could increase suicide risk, as well as those taking drugs like methotrexate that reduce folate. In the group that was prescribed folic acid over the five-year period, there were 261 suicidal events (suicide attempts and intentional self-harm) specifically during times when folic acid was being taken, and there were 895 events recorded when folic acid was not being taken by the same individuals. After adjusting for age, sex, mental health diagnoses, and other central nervous system drugs that might affect the results, researchers found a 44 percent lower rate of suicidal events while folic acid was being taken, typically at a dosage of 1 milligram (mg) daily. “In all of our sensitivity analyses, we found similar reductions in suicide attempt rates, suggesting that the association is present in all of the populations that we have studied,” says Gibbons. The longer people were on the supplement, the lower the risk. Each month of taking folic acid was associated with an additional 5 percent decrease in the risk of attempted suicide during the two-year follow-up period. The authors’ theory that the association between folic acid and suicide attempt was produced by folate-reducing drugs like methotrexate was not confirmed in the study, says Gibbons. Could it be that people who take any type of prescription vitamin supplements to improve their health may be less likely to attempt suicide? To further validate the findings and make sure that was not the reason for the reduced risk, the same analysis was repeated with people who took another vitamin supplement, vitamin B12, with no known relationship to suicidality. In that “control” trial, researchers found no association between vitamin B12 and suicidal events.

This isn’t the first study to find a connection between folate levels, folic acid supplementation, depression, and suicidality. In a meta-analysis of 43 studies published in the December 2017 Journal of Psychiatric Research, investigators found that people with depression had lower folate levels than those without depression. A study published in Frontiers in Psychiatry in December 2021 found an association between folate levels and fatal and nonfatal suicide attempts in people with depressive disorder.

Because this study was observational, it doesn’t prove that the folic acid supplements reduced the risk of suicide attempts, the authors noted. Plans for a large-scale randomized clinical trial of folic acid are underway, and if these findings are confirmed, folic acid supplementation might save thousands of lives, says Gibbons. The authors plan to use the same methodology to identify other associations. “The possibility of discovering drugs or supplements that could potentially reduce life-threatening conditions such as suicidal behavior is a huge advantage of the iDEAS methodology relative to traditional drug safety screening, and the most rewarding part of this program of research,” he says.

People Who Have Suicidal Thoughts Should Seek Professional Help

The American Foundation for Suicide Prevention offers resources for people who are grieving from a loss, thinking of suicide, have survived a suicide attempt, or who are worried about someone who may be at risk for suicide. People who are in crisis can call 911 or call or text 988 or text TALK to 741741.