Supplements for Mental Health, Part 1: Folic Acid

The nutritional supplement industry has a global market size of over 300 billion US Dollars annually.   This is comparable to all the money spent in the world on fresh fruit and vegetables.  

People generally take supplements with the idea that they will improve health or vitality, or prevent disease.  

What is the current evidence that supplements could help improve mental health?  I'll start by looking at vitamin and mineral supplements.  

The vitamin with the most recent attention in the literature is folic acid.  This is a B vitamin found in leafy green vegetables, oranges, and other healthy foods.  It has been established for many years as an essential supplement for pregnant women, to help reduce the risk of birth defects.  

Supplementation of folic acid during pregnancy may modestly reduce the risk of post-partum depression, but there is a lack of rigorous randomized controlled trials (RCTs) to prove this.   

The most compelling recent study was published in JAMA Psychiatry in 2022, finding a strong association between folic acid supplementation at doses at 1 mg daily, and a substantially reduced risk of suicide.   

But a major negative study was published in 2018: this was an RCT showing no reduction in depression risk with high-dose folic acid supplementation over an amazing 7 years of follow-up.  But this study did not specifically look at using folic acid as an augmentation in the treatment of people who already have depression or other mental health problems.  

A 2015 meta-analysis found no significant benefit for short-term use of folic acid as an augmentation for treating depression.  

So in conclusion, there is some evidence of folic acid being useful in treating depression or reducing suicidal ideation, but the findings are by no means definitive, and there are negative studies in RCTs.  As with many of these issues, there should be better RCTs with standardized doses (probably 1 or 2 mg daily) and longer durations, looking at using folic acid as an augmentation in people with established mental health symptoms.  In the meantime, there is negligible risk to supplementing with folic acid 1 mg daily, so it is ok to do so.  

References:

Nutritional Supplements Market Size Report, 2030. (n.d.). Retrieved 28 December 2022, from https://www.grandviewresearch.com/industry-analysis/nutritional-supplements-market

Global Marketing Associates (2021, March 8). Global fruit and vegetable market: Export opportunity analysis. Global Marketing Associates. http://www.globalmarketing1.com/food-beverage/global-fruit-and-vegetable-market-export-opportunity-analysis/

Jin, X., Cheng, Z., Yu, X., Tao, Q., Huang, R., & Wang, S. (2022). Continuous supplementation of folic acid in pregnancy and the risk of perinatal depression–A meta-analysis. Journal of Affective Disorders, 302, 258–272. https://doi.org/10.1016/j.jad.2022.01.080

Gibbons, R. D., Hur, K., Lavigne, J. E., & Mann, J. J. (2022). Association Between Folic Acid Prescription Fills and Suicide Attempts and Intentional Self-harm Among Privately Insured US Adults. JAMA Psychiatry, 79(11), 1118–1123. https://doi.org/10.1001/jamapsychiatry.2022.2990

Okereke, O. I., Cook, N. R., Albert, C. M., Denburgh, M. V., Buring, J. E., & Manson, J. E. (2015). Effect of long-term supplementation with folic acid and B vitamins on risk of depression in older women. The British Journal of Psychiatry, 206(4), 324–331. https://doi.org/10.1192/bjp.bp.114.148361

Almeida, O. P., Ford, A. H., & Flicker, L. (2015). Systematic review and meta-analysis of randomized placebo-controlled trials of folate and vitamin B12 for depression. International Psychogeriatrics, 27(5), 727–737. https://doi.org/10.1017/S1041610215000046