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

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 = 5 years) supplementation with vitamin D (vitamin D3 [cholecalciferol], 2000 IU/day) and marine omega-3 fatty-acids (eicosapentaenoic acid + docosahexaenoic acid, 1 g/day), in a 2 x 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 similar to 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 similar to 17,000 participants to address whether key blomarkers 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.