Response of Vitamin D Concentration to Vitamin D3 Administration in Older Adults without Sun Exposure: A Randomized Double-Blind Trial

OBJECTIVES: To determine the dose-response relationship between 25-hydroxyvitamin D (25(OH) D) and supplemental vitamin D3 in elderly nursing home residents. DESIGN: Randomized double-blind investigation. SETTING: Nursing home. PARTICIPANTS: Of 81 women (n = 51) and men (n = 30) (mean age 87.4 +/- 8) enrolled, 72 completed the study. INTERVENTION: Sixteen weeks of oral vitamin D3 at 800, 2,000, or 4,000 IU/d or 50,000 IU/wk. MEASUREMENTS: The main outcome was 25(OH) D concentrations (tandem mass spectrometry) after 16 weeks. Free 25(OH) D and intact parathyroid hormone (iPTH) were also analyzed. Safety monitoring of calcium and estimated glomerular filtration rate was performed, and adherence and clinical status were measured. RESULTS: 25(OH) D concentrations increased with dose (P<.001) and were higher with 50,000 IU/wk (P<.001) than other doses and with 4,000 IU/d than 800 or 2,000 IU/d, but 800 IU and 2,000 IU/d did not differ. One subject receiving 800 IU/d had concentrations less than 20 ng/mL. All subjects receiving more than 2000 IU/d had concentrations of 20 ng/mL and greater. Free 25(OH) D concentrations rose with total 25(OH) vitamin D. Total and free 25(OH) D were related to calcium concentrations; only free 25(OH) D was related to iPTH. CONCLUSION: 25(OH) D increased linearly with 800 to 4,000 IU/d and 50,000 IU/wk of vitamin D3, without a ceiling effect. Data suggest that some elderly adults will require more than 800 IU/d of vitamin D3 to ensure adequate vitamin D levels. Changes in 25(OH) D with vitamin D3 were related to starting concentrations (greatest with the lowest concentrations and unchanged with 800 and 2,000 IU/d if 20-40 ng/mL). Relationships between serum calcium and iPTH and free 25(OH) D suggest the potential for free 25(OH) D in defining optimal 25(OH) D concentrations.