Vitamin D deficiency is highly prevalent in older people in the absence of vitamin D supplementation. The limited data available show marked inter-individual variability in response to vitamin D supplementation in very old, frail elderly wih almost 25% remaining vitamin D deficient (25-OH D <20 ng/mL) when receiving the currently recommended 800 IU/day vitamin D. This proposal is for exploratory research on the use of a wide range of oral vitamin D3 doses in frail elderly living in controlled living environments. We will determine the dose response relationship of total and unbound 25- OH vitamin D3 to supplemental vitamin D3 at daily doses of 800 (currently recommended for the elderly), 2000, and 4000 IU or 50,000 IU/weekly in a randomized blinded investigation We will also compare the efficacy of each dosing regimen in achieving 25-OH vitamin D levels >20 ng/mL (50 nmol/L) and identify covariates that contribute to inter-individual variation in the dose response relationship. In patients with osteoporosis, relationships between unbound vs. total 25-OH on intact parathyroid hormone and a marker of bone resorption (beta-Ctx) will be analyzed. We will also examine responses of inflammatory cytokines. A long-term goal is to develop algorithms for estimation of D3 dosages to achieve target 25-OH vitamin D doses for very elderly and frail individuals.

Public Health Relevance

Vitamin D deficiency is very common in the elderly but the dose required to normalize vitamin D levels has not been determined for very old or frail people. This proposal will evaluate responses to a wide range of daily oral vitamin D3 doses and a higher weekly dose of oral vitamin D3 in old, very old, frail, and nursing home patients to determine the best dose to correct vitamin D deficiency in the almost 2 million elderly Americans living in nursing homes. It will also explore what doses of vitamin D decrease inflammation and bone resorption.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Exploratory/Developmental Grants (R21)
Project #
3R21AG041660-02S1
Application #
8726675
Study Section
Special Emphasis Panel (ZRG1-EMNR-H (02))
Program Officer
Hannah, Judy S
Project Start
2012-08-15
Project End
2014-07-31
Budget Start
2013-09-01
Budget End
2014-07-31
Support Year
2
Fiscal Year
2013
Total Cost
$69,141
Indirect Cost
$25,125
Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Schwartz, Janice B; Gallagher, J Christopher; Jorde, Rolf et al. (2018) Determination of Free 25(OH)D Concentrations and Their Relationships to Total 25(OH)D in Multiple Clinical Populations. J Clin Endocrinol Metab 103:3278-3288
Bikle, Daniel D; Malmstroem, Sofie; Schwartz, Janice (2017) Current Controversies: Are Free Vitamin Metabolite Levels a More Accurate Assessment of Vitamin D Status than Total Levels? Endocrinol Metab Clin North Am 46:901-918
Schwartz, Janice B; Kane, Lynn; Bikle, Daniel (2016) Response of Vitamin D Concentration to Vitamin D3 Administration in Older Adults without Sun Exposure: A Randomized Double-Blind Trial. J Am Geriatr Soc 64:65-72
Lai, Jennifer C; Bikle, Daniel D; Lizaola, Blanca et al. (2015) Total 25(OH) vitamin D, free 25(OH) vitamin D and markers of bone turnover in cirrhotics with and without synthetic dysfunction. Liver Int 35:2294-300
Schwartz, Janice B (2015) Primary prevention: do the very elderly require a different approach? Trends Cardiovasc Med 25:228-39