Study shows treatment associated with folic acid

Suicide is one of the leading causes of death in the United States, with more than 45,000 suicidal deaths in 2020. Experts recommend many strategies and treatments to reduce the risk of suicide, including psychotherapy, peer support, economic support, and medications such as antidepressants. Few would likely put folic acid supplements on that list, but a recent study from the University of Chicago could change that.

The study, Published in JAMA Psychiatry on September 28th, 2019 data from the health insurance applications of 866,586 patients and examined the connection between folic acid treatment and suicide attempts over a period of two years. They found that patients prescribed folic acid, also known as vitamin B9, experienced a 44 percent reduction in suicidal events (suicide attempts and intentional self-harm). Robert Gibbons, Ph.DThe Blum-Riese Professor of Biostatistics and Medicine at the University of Chicago, the study’s lead author, hopes these findings could improve suicide prevention efforts, particularly given the ready availability of folic acid.

“There aren’t any real side effects, it doesn’t cost a lot of money, you can get it without a prescription,” Gibbons said. “This could potentially save tens of thousands of lives.”

Gibbons was initially interested in folic acid in connection with suicide because of a previous study in which his group looked for associations between the risk of attempting suicide and 922 different prescribed drugs. The study looked at each drug simultaneously for associations with increases and decreases in suicide attempts. Surprisingly, folic acid has been linked to a reduced risk of suicide attempts, along with drugs thought to be associated with suicide risk, such as antidepressants, anxiolytics, and antipsychotics.

One of the challenges of this earlier study was analyzing the effects of many drugs on a large dataset, which is difficult. Many people take more than one medication, and medications can have different effects when taken together than when taken alone. It can also be difficult to get meaningful results from studies like these that look for associations in large data sets because of confounding factors that can cause two variables in a study, such as suicide and a drug, to appear to be directly causally related stand each other. In fact, sometimes these are both related to a confounding factor, such as socioeconomic status or health-conscious attitudes, or because they are being prescribed for a condition associated with suicide (e.g., depression). But Gibbons and his group were able to partially eliminate these complications by comparing subjects before and after a drug was prescribed to themselves, rather than subjects who took the drug and those who didn’t take the drug to compare.

In fact, they initially thought folic acid appeared in their study simply because of a simple explanation, but that turned out not to be the case. “When we first saw this result, we thought it was pregnancy. Pregnant women take folic acid and pregnant women tend to have low suicide rates, so it’s just a false association. So we just did a quick analysis to narrow it down to men. But we’ve seen exactly the same effect in men,” Gibbons said.

To examine and further confirm the relationship between folic acid and suicide risk, Gibbons and his co-authors conducted this new study, focusing specifically on folic acid and taking into account many possible confounding factors, including age, gender, mental health diagnoses and other key medications the nervous system, disorders affecting folic acid metabolism, and more. Even after accounting for all of these factors, taking a prescription for folic acid was still associated with a reduced risk of attempting suicide.

They even found that the risk of attempting suicide tended to be lower the longer a person was taking folic acid. Each month of folic acid prescription was associated with an additional 5% reduction in suicide attempt risk during the 24-month follow-up of their study.

It also occurred to the authors that people who take vitamin supplements in general might want to improve their health and therefore would be less likely to attempt suicide. To address this possibility, they performed a similar analysis using another dietary supplement, vitamin B12, as a negative control. But unlike folic acid, there appeared to be no link between vitamin B12 and suicide risk.

Although Gibbons and his co-authors have been careful to account for confounding factors, they cannot yet say with certainty that the association between folic acid and suicidal events is causal; That said, they don’t yet know if taking folic acid directly reduces a person’s risk of suicide. To know for sure, the authors are following up this study with a large-scale randomized controlled trial (RCT) to test whether folic acid directly reduces the risk of suicidal events, including idea, attempt, and completion. To do this, the subjects are randomly divided into two groups, one given a placebo and the other given folic acid, and the rate of suicidal events is compared over time.

If their findings are confirmed in the new research, folic acid would be a safe, inexpensive, and widely used suicide prevention strategy, and could potentially help save thousands of lives.

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