# Phase II RCT of High-dose Vitamin D Supplements in Older Adults without Dementia

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2021 · $955,397

## Abstract

Project Summary/Abstract
There is mounting evidence that low vitamin D blood levels are associated with increased risk of dementia and Alzheimer's disease (AD). There are several mechanisms by which low vitamin D status may promote AD
pathology, including reduced β-amyloid (Aβ) clearance, dysregulation of calcium influx and glutamate-
mediated neurotoxicity. Vitamin D interacts with receptors in the hippocampus and many other brain regions,
and has established antioxidant and anti-inflammatory effects. Recent neuroimaging studies have found that
low vitamin D levels are associated with increased periventricular white matter disease, reduced white matter
volume and larger ventricles. Vitamin D deficiency may also have a toxic effect on brain function independent
of Aβ metabolism. Preliminary studies of serum vitamin D levels in a diverse multi-ethnic cohort (n=382) of the
UC Davis Alzheimer's Disease Center found a high prevalence of low vitamin D status (61% with levels <20
ng/ml), which was associated with faster rates of decline on executive function and episodic memory.
This Phase II randomized clinical trial aims to test if supplementation with high dose oral vitamin D will
successfully correct vitamin D insufficiency, compared to treatment with standard (RDA) dose vitamin D in a
diverse community-based elderly cohort. The effect of high-dose vs. standard-dose vitamin D on altering
cognitive trajectories will also be assessed and data will be expected to be used in designing a potential
definitive Phase III trial in elderly groups at risk for dementia. A total of 180 elderly persons with longitudinal
biomarkers, neuropsychological testing and brain MRI scans will be enrolled, with 152 (~50 with MCI, 50 with
mild AD and 50 with no cognitive impairment) expected to complete the 3½-year study. One-half of each
diagnostic group will be randomized to treatment with high-dose vitamin D3 (4,000 IU daily) or to standard
dose Vitamin D (600 IU capsule daily + ~200 IU dietary = ~800 IU total/day). Longitudinal MRI analyses will
provide an estimate of the treatment effect size on brain atrophy rate. Vitamin D receptor genotype
polymorphisms and their impact on response to oral supplementation will also be examined. If vitamin D
supplementation improves cognitive outcome, this could have a large impact on the public health, since low
vitamin D status is a common, readably treatable condition which may provide a novel window to prevent
dementia and AD. Furthermore, the higher prevalence of AD and dementia in African Americans and Latinos
could be partially attributable to vitamin D insufficiency.

## Key facts

- **NIH application ID:** 10134978
- **Project number:** 5R01AG051618-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** John M Olichney
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $955,397
- **Award type:** 5
- **Project period:** 2017-09-15 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10134978

## Citation

> US National Institutes of Health, RePORTER application 10134978, Phase II RCT of High-dose Vitamin D Supplements in Older Adults without Dementia (5R01AG051618-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10134978. Licensed CC0.

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