# VITAL-DEP (VITamin D and OmegA 3 TriaL-Depression Endpoint Prevention)

> **NIH NIH R56** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $1,297,413

## Abstract

VITAL-DEP (VITamin D and OmegA-3 TriaL-Depression Endpoint Prevention; NCT01696435) began as a first-
of-its-kind factorial randomized controlled trial of two plausible agents – vitamin D3 (cholecalciferol 2000 IU/d)
and omega-3 fatty acids (EPA and DHA in 1:1 ratio, 1000 mg/d) – for the prevention of late-life depression (LLD)
and promotion of long-term healthier mood among older adults. VITAL-DEP, an ancillary of the VITAL trial of
cardiovascular disease and cancer prevention, enrolled over 18,000 men and women, aged 50+ years (mean
age=67 years) and at risk for depression, who were followed for a median of 5.3 years of randomized treatment.
Detailed phenotypic assessments were completed at baseline and follow-up in a subset of over 1,000
participants in the local Clinical and Translational Science Center for: psychiatric diagnostic interviews;
neuropsychological testing; self-reports on dimensional measures of depression, anxiety, daily functioning, and
social, health and behavioral risk factors. VITAL-DEP achieved substantial racial/ethnic diversity: 20% of
participants are Black/African American adults and 30% are racial/ethnic minorities. This competing renewal
leverages the rich resources of the assembled cohort and builds on the findings regarding randomized treatment
effects in the prior funding period. We observed: 1) evidence that vitamin D3 significantly reduces decline in
global cognition and executive function among Black adults; 2) modest differences in effects of omega-3 on LLD
risk and sex differences in effects. Inflammatory, structural and functional MRI, and plasma and PET tau markers
selected for this proposal show evidence in the literature and preliminary data for relevance to LLD and cognition.
Also, given evidence of higher burden of LLD and cognitive decline for women, Black adults, APOE4 carriers
and those with higher systemic inflammation, we will determine moderation in outcomes by these risk groups.
Specific Aims: 1) We will test causal effects of long-term vitamin D3 on serial measures of plasma tau (NT1),
which is associated with neuropsychiatric symptoms in preclinical dementia and has high long-term predictive
validity for cognitive decline, independent of other preclinical cognitive markers. 2) We will measure associations
of baseline plasma tau with long-term cognitive change, mood symptoms and differences in MRI and PET-tau
markers at follow-up. Secondarily, we will examine biological mechanisms for observed sex differences for
omega-3 and LLD risk and race differences for vitamin D3 and cognitive decline. In exploratory aims, we
hypothesize: study associations will be moderated by baseline inflammation, vascular risk, age, hormone status
(in women), and APOE4. Findings from prior funding periods already have implications for public health
regarding use of both supplements for prevention in late-life mental health. This renewal proposal will similarly
impact the field by clarifying mechanisms for treatment eff...

## Key facts

- **NIH application ID:** 10512847
- **Project number:** 2R56MH091448-11A1
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Olivia Ifeoma Okereke
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,297,413
- **Award type:** 2
- **Project period:** 2010-09-29 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10512847

## Citation

> US National Institutes of Health, RePORTER application 10512847, VITAL-DEP (VITamin D and OmegA 3 TriaL-Depression Endpoint Prevention) (2R56MH091448-11A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10512847. Licensed CC0.

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