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A randomized controlled trial of high-dose vitamin D2 followed by intranasal insulin in Alzheimer’s disease


Stein, Mark S., Scherer, Samuel C., Ladd, Kylie S., Harrison, Leonard C.


Journal Of Alzheimer's Disease: JAD, Volume: 26, No.: 3, Pages.: 477-484

Year of Publication



Poor vitamin D nutrition is linked with dementia, but vitamin D has not been tested in a randomized controlled trial (RCT) in Alzheimer’s disease (AD). Nasal insulin acutely improves cognition and vitamin D upregulates insulin receptor expression and enhances insulin action. In an RCT we examined the effect of high-dose vitamin D followed by nasal insulin on memory and disability in mild-moderate AD. 63 community-dwelling individuals aged > 60 were recruited; 32 with mild-moderate disease (Folstein Mini-Mental State Examination [MMSE] score 12-24) met entry criteria and were randomized. All took low-dose vitamin D (1000 IU/day) throughout. After run-in (8 weeks), they were randomized to additional high-dose D/placebo for 8 weeks, followed immediately by randomization to nasal insulin (60 IU qid)/placebo for 48 h. Primary outcome measures were Alzheimer’s disease assessment scale-cognitive subscale (ADAS-cog) and Disability Assessment in Dementia (after high-dose D) and ADAS-cog and Wechsler Memory Scale-Revised Logical memory (WMS-R LM) for immediate and delayed recall (after nasal insulin). Baseline median (interquartile range, IR) age, MMSE, and ADAS-cog were 77.5 (69-80), 19.5 (17-22), and 25.5 (20-31), respectively. Median 25OHD increased from 49 to 60 nM (p < 0.01) after run-in and was 187 nM after high-dose vitamin D and 72 nM after placebo (p < 0.001). Neither cognition nor disability changed significantly after high-dose D. ADAS-cog improved by a median (IR) of 9 (1-11) with nasal insulin after placebo high-dose vitamin D (p = 0.02), but may represent regression to the mean as WLS-R LM did not change. We conclude that high-dose vitamin D provides no benefit for cognition or disability over low-dose vitamin D in mild-moderate AD.;


administration & dosage, administration intranasal, aged, 80 and over, alzheimer disease, cognition, complications, d, depression, dietary supplements, double-blind method, drug effects, drug therapy, ergocalciferols, etiology, feasibility studies, female, humans, hypoglycemic agents, insulin, linear models, male, middle aged, nasal, neuropsychological tests, pilot projects, psychology, therapeutic use, treatment outcome, vitamin, vitamin d deficiency, vitamins, wechsler scales

Countries of Study


Types of Dementia

Alzheimer’s Disease

Types of Study

Randomised Controlled Trial

Type of Outcomes

ADLs/IADLs, Cognition



Type of Interventions

Pharmaceutical Interventions

Pharmaceutical Interventions

Herbal remedies, vitamins, dietary supplements, Other