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Original Research

Effects of Vitamin D3 and Marine Omega-3 Fatty Acids Supplementation on Indicated and Selective Prevention of Depression in Older Adults: Results From the Clinical Center Sub-Cohort of the VITamin D and OmegA-3 TriaL (VITAL)

Chirag M. Vyas, MBBS, MPH; David Mischoulon, MD, PhD; Grace Chang, MD, MPH; Nancy R. Cook, ScD; Alison Weinberg, MA; Trisha Copeland, MS, RD; Jae H. Kang, ScD; Vadim Bubes, PhD; Georgina Friedenberg, MPH; Meryl S. LeBoff, MD; I-Min Lee, MBBS, ScD; Julie E. Buring, ScD; JoAnn E. Manson, MD, DrPH; Charles F. Reynolds III, MD; and Olivia I. Okereke, MD, SM

Published: June 26, 2023


Objective: To test vitamin D3 and omega-3 fatty acids (omega-3s) for late-life depression prevention under the National Academy of Medicine framework for indicated (targeting subthreshold depression) and selective (targeting presence of high-risk factors) prevention.

Methods: The VITamin D and OmegA-3 TriaL (VITAL) is a 2 í 2 factorial trial of vitamin D3 (2,000 IU/d) and/or omega-3s (1 g/d) for cardiovascular and cancer prevention (enrollment: November 2011–March 2014; end date: December 31, 2017). In this targeted prevention study, we included 720 VITAL clinical sub-cohort participants who completed neurobehavioral assessments at baseline and 2 years (91.9% retention). High-risk factors were subthreshold or clinical anxiety, impaired activities of daily living, physical/functional limitation, medical comorbidity, cognitive impairment, caregiving burden, problem drinking, and low psychosocial support. Coprimary outcomes were incident major depressive disorder (MDD), adjudicated using DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition), and change in mood (Patient Health Questionnaire-9 [PHQ-9]). We used exact tests to determine treatment effects on MDD incidence and repeated-measures models to determine treatment effects on PHQ-9.

Results: A total of 11.1% had subthreshold depression, 60.8% had ≥ 1 high-risk factor, MDD incidence was 4.7% (5.1% among completers), and mean PHQ-9 score change was 0.02 points. Among those with subthreshold depression, the MDD risk ratio (95% confidence interval) was 0.36 (0.06 to 1.28) for vitamin D3 and 0.85 (0.25 to 2.92) for omega-3s, compared to placebo; results were also null among those with ≥ 1 high-risk factor (vitamin D3 vs placebo: 0.63 [0.25 to 1.53]; omega-3s vs placebo: 1.08 [0.46 to 2.71]). There were no significant differences in PHQ-9 score change comparing either supplement with placebo.

Conclusions: Neither vitamin D3 nor omega-3s showed benefits for indicated and selective prevention of late-life depression; statistical power was limited.

Trial Registration: identifier: NCT01696435

J Clin Psychiatry 2023;84(4):22m14629

Author affiliations are listed at the end of this article.

Volume: 84

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