Vitamin D3 (Cholecalciferol) for Alzheimer's Disease
Also known as: Cholecalciferol, Calcitriol, 25-hydroxyvitamin D
Vitamin D deficiency is strongly associated with dementia risk, with low levels doubling Alzheimer's incidence.
Mechanism of Action
VDR is widely expressed in hippocampal and cortical neurons. Calcitriol upregulates nerve growth factor, enhances amyloid-beta phagocytic clearance by macrophages, reduces tau phosphorylation, and modulates calcium signaling essential for synaptic plasticity and LTP.
General mechanism: Secosteroid hormone. VDR-mediated gene transcription affecting calcium, immunity, neurotrophic factors, cell differentiation, and apoptosis.
Current Evidence
Meta-analyses of observational studies show 2x dementia risk with vitamin D deficiency. The DO-HEALTH trial showed cognitive benefit in supplemented elderly. Mendelian randomization supports causal relationship.
Clinical Status: Strong observational and genetic evidence. Supplementation trials ongoing for AD prevention.
Safety Profile
Safe at recommended doses (1000-4000 IU/day). Hypercalcemia at very high doses. Monitor 25(OH)D levels. Rare: kidney stones.
Key Research Questions
- Can correcting vitamin D deficiency prevent AD in high-risk populations?
- Does vitamin D3 enhance amyloid clearance in established AD?