Supplements for Mental Health, Part 3: Omega-3 Fatty Acids & Vitamin D

Omega-3 supplements and Vitamin D have seemed very promising for years, to help with general health, depressive symptoms, cognition, or bipolar symptoms.  

But there was a very large randomized controlled trial, of over 18 000 people,  with an incredible treatment duration of 5 years.  Amazing study!  Recipients received a typical good dose of omega-3 (about 1 gram total of EPA+DHA), plus 2000 IU daily of vitamin D.   

The study showed no effect of the supplement compared to placebo.  There were no significant differences in depression rating scales, suicides, overall death rate, cancer rates, or heart disease rates.  Other findings from this study suggested some possible benefits from Omega-3 for cardiovascular health particularly for people with low dietary fish intake.  

A limitation would be that the study population comprised healthy adults.  It may be that using omega-3 supplementation in the treatment of people with established illnesses such as major depressive disorder or bipolar disorder would be more useful.  

One recent study suggested that omega-3 supplementation may have small but significant benefit in postpartum depression.  Another recent small meta-analysis suggested some benefit in treating residual depressive symptoms in bipolar disorder.   Yet, another good year-long RCT in bipolar patients showed no benefit.  

In ADHD, recent research also showed no benefit from omega-3 in a year-long study.  

In terms of other general health issues, though, there may be benefits from omega-3 and vitamin D supplementation.   The same large RCT mentioned initially (the VITAL study) showed about a 15-20% reduction in autoimmune diseases in the omega-3 or vitamin-D supplemented groups.  There is other evidence that omega-3 supplements could help in other diseases such as macular degeneration.  

So, in conclusion, omega-3 and vitamin D appear to be quite underwhelming in terms of potential mental health benefits.   But there may be some small general health benefits, for particular categories of disease such as autoimmune conditions, for people who may be at risk for deficiencies, such as those of us without much sun exposure, or for those of us who don't eat very much fish.  

Addendum: another study, published by Lavigne & Gibbons in February 2023, showed strong associations between vitamin D supplementation and a lower risk of suicide, in male U.S. veterans, with a stronger association among those with lower vitamin D levels to begin with.  But this is a retrospective cohort study, always much weaker than an RCT, and subject to potential non-causal associations.   Once again, supplementation with a standard daily dose of vitamin D is reasonable and safe; there is negligible risk of harm, with some suggestive data implying potential benefit in autoimmune conditions and mood symptoms, particularly in those who might have been deficient.   

References:

Okereke, O. I., Vyas, C. M., Mischoulon, D., Chang, G., Cook, N. R., Weinberg, A., Bubes, V., Copeland, T., Friedenberg, G., Lee, I.-M., Buring, J. E., Reynolds, C. F., III, & Manson, J. E. (2021). Effect of Long-term Supplementation With Marine Omega-3 Fatty Acids vs Placebo on Risk of Depression or Clinically Relevant Depressive Symptoms and on Change in Mood Scores: A Randomized Clinical Trial. JAMA, 326(23), 2385–2394. https://doi.org/10.1001/jama.2021.21187

Mocking, R. J. T., Steijn, K., Roos, C., Assies, J., Bergink, V., Ruhé, H. G., & Schene, A. H. (2020). Omega-3 Fatty Acid Supplementation for Perinatal Depression: A Meta-Analysis. The Journal of Clinical Psychiatry, 81(5), 13281. https://doi.org/10.4088/JCP.19r13106

Kishi, T., Sakuma, K., Okuya, M., Ikeda, M., & Iwata, N. (2021). Omega-3 fatty acids for treating residual depressive symptoms in adult patients with bipolar disorder: A systematic review and meta-analysis of double-blind randomized, placebo-controlled trials. Bipolar Disorders, 23(7), 730–731. https://doi.org/10.1111/bdi.13115

McPhilemy, G., Byrne, F., Waldron, M., Hibbeln, J. R., Davis, J., McDonald, C., & Hallahan, B. (2021). A 52-week prophylactic randomised control trial of omega-3 polyunsaturated fatty acids in bipolar disorder. Bipolar Disorders, 23(7), 697–706. https://doi.org/10.1111/bdi.13037

Abdullah, M., Jowett, B., Whittaker, P. J., & Patterson, L. (2019). The effectiveness of omega-3 supplementation in reducing ADHD associated symptoms in children as measured by the Conners’ rating scales: A systematic review of randomized controlled trials. Journal of Psychiatric Research, 110, 64–73. https://doi.org/10.1016/j.jpsychires.2018.12.002

Prokopiou, K., Kolovos, P., Tsangari, H., Bandello, F., Rossetti, L. M., Mastropasqua, L., Mohand-Said, S., & Georgiou, T. (2022). A prospective, multicentre, randomised, double-blind study designed to assess the potential effects of omega-3 fatty acids supplementation in dry age-related macular degeneration or Stargardt disease. Investigative Ophthalmology & Visual Science, 63(7), 377-F0208.

Lavigne, J. E., & Gibbons, J. B. (2023). The association between vitamin D serum levels, supplementation, and suicide attempts and intentional self-harm. PLOS ONE, 18(2), e0279166. https://doi.org/10.1371/journal.pone.0279166