Does Folic Acid Supplementation Decrease Suicide Attempt Risk?

Study finds a beneficial association between folic acid supplementation and lower rates of suicide attempts.

A large-scale study found evidence that folic acid supplementation associated with a lower suicide attempt rate. These findings were published in JAMA Psychiatry.

Investigators from the University of Chicago sourced data for this study from the MarketScan Commercial Claims and Encounters databases. Suicide attempts were evaluated between 2010 and 2018 and compared with whether the individual filled a folic acid prescription between 2012 and 2017 using a within-person exposure-only cohort design. Suicide attempts during cyanocobalamin and vitamin B12 supplementation were used as the comparator.

The entire study cohort comprised 866,586 individuals who were mostly women (81.30%) and few were aged 60 years or older (10.42%).

A total of 261 suicide attempts occurred during folic acid use (incidence rate [IR], 4.73 per 100,000 person-months [pm]) and 895 attempts occurred without folic acid supplementation (IR, 10.61 per 100,000 pm).

These results warrant the conduct of a randomized clinical trial with suicidal ideation and behavior as outcomes of interest.

Folic acid use decreased risk for suicide events (adjusted hazard ratio [aHR], 0.56; 95% CI, 0.48-0.65) and a duration-response was observed for each additional month of 1 mg/d folic acid supplementation (hazard ratio [HR], 0.95; 95% CI, 0.93-0.97).

No significant moderation effects were observed for folate-reducing medications and no interactions between age, gender, and folic acid were observed.

For cyanocobalamin, there were 128 suicide attempts during use (IR, 8.76 per 100,000 pm) compared with 206 attempts with no use (IR, 8.44 per 100,000 pm). Cyanocobalamin was not associated with suicide attempt risk (aHR, 1.01; 95% CI, 0.80-1.27).

The results of this study may have included healthy user bias among supplement users.

Study authors concluded, “This large-scale well-controlled pharmacoepidemiologic study of folic acid found a beneficial association in terms of lowering rates of suicide attempts. These results warrant the conduct of a randomized clinical trial with suicidal ideation and behavior as outcomes of interest. If confirmed, folic acid may be a safe, inexpensive, and widely available treatment for suicidal ideation and behavior.”

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Gibbons RD, Hur K, Lavigne JE, Mann JJ. Association between folic acid prescription fills and suicide attempts and intentional self-harm among privately insured US adults. JAMA Psychiatry. 2022;79(11):1118-1123. doi:10.1001/jamapsychiatry.2022.2990