The VITamin D and OmegA-3 TriaL-Depression Endpoint Prevention (VITAL-DEP): Rationale and design of a large-scale ancillary study evaluating vitamin D and marine omega-3 fatty acid supplements for prevention of late-life depression

Abstract

Rationale: Depression is a leading cause of disease burden and disability for older adults; thus, prevention is a priority. Biologic and observational data support potential mental health benefits of vitamin D and omega-3 fatty acids; however, it is unclear whether these supplements can prevent late-life depression.

Design: We describe the novel methodology of a large-scale study: VITAL-DEP (VITamin D and OmegA-3 TriaL-Depression Endpoint Prevention), an ancillary to the VITAL trial. Primary Aims of VITAL-DEP are to determine effects on prevention of depression and on trajectory of mood symptoms of long-term (mean=5years) supplementation with vitamin D (vitamin D3 [cholecalciferol], 2000IU/day) and marine omega-3 fatty-acids (eicosapentaenoic acid + docosahexaenoic acid, 1g/day), in a 2×2 factorial design, among 25,874 older adults. Secondary Aims will evaluate: vitamin D's effects among African-Americans (an at-risk group for vitamin D deficiency); both agents' effects among those with high-risk factors or sub-syndromal depression in a sub-set of ~1000 participants with detailed examinations at baseline and 2-year follow-up; whether baseline nutrient levels influence depression risk and/or modify agents' effects. Additional planned analyses will use pre-randomization blood samples available in ~17,000 participants to address whether key biomarkers and factors influence long-term mood and depression risk and/or the agents' effects.

Conclusion: VITAL-DEP applies all modalities of state-of-the-art prevention research - universal, selective and indicated. VITAL-DEP will clarify effects of supplemental vitamin D and/or omega-3 on mood, and inform clinical care and public health guidelines on the use of these agents for prevention of depression in mid-life and older adults.

Trial registration: ClinicalTrials.gov NCT01169259 NCT01696435.

Keywords: Cholecalciferol; Depression; Fish oil; Geriatric; Mood; Omega-3; Prevention.

Copyright © 2018 Elsevier Inc. All rights reserved.

Figures

Figure 1. Mechanisms by which vitamin D and/or fish oil may lower depression risk

Four hypothesized mechanistic areas are illustrated: inflammation, oxidative stress, vascular/metabolic health and neuroprotection. Vitamin D may lower depression risk through: more favorable profiles of inflammatory indicators, vascular (renin-angiotensin-aldosterone system) and metabolic (improved insulin sensitivity and glucose tolerance) factors, and increased expression and levels of brain-derived neurotrophic factor (BDNF). Marine omega-3 fatty acids (fish oil) may lower depression risk through: more favorable profiles of inflammatory indicators, lower levels of free radicals and reactive oxygen species formation, improved protection against cardiovascular disease (CVD), and increased expression and levels of BDNF.

Figure 2

Sources of study participants for assessments and analyses in VITAL-DEP.