The Effects of Four Doses of Vitamin D Supplements on Falls in Older Adults
What this study found
Vitamin D3 supplementation at 1000 IU/d or higher did not reduce falls compared with 200 IU/d in this older, fall-prone population. In the primary comparison, time to first fall or death was not improved with 1000 IU/d versus 200 IU/d: HR = 0.94 (CI 0.76-1.15), P = 0.54. Higher-dose regimens raised safety concerns, with more first serious falls (HR = 1.87 [1.03-3.41]) and more first falls with hospitalization (HR = 2.48 [1.13-5.46]) versus 200 IU/d. Mean total 25-(OH)D at 3 months increased across dose groups to 67.1, 80.3, 87.3, and 119.2 nmol/L, but this biochemical response did not…
- Study & population
- Randomized, two-stage dose-finding and confirmatory study in community-dwelling adults aged 70 years and older at elevated fall risk with low serum 25-(OH)D.
- Intervention
- Oral vitamin D3 (cholecalciferol) was tested at 200, 1000, 2000, and 4000 IU daily for up to 2 years.
- Key limitation
- The trial used a complex two-stage design with dose switching, which makes long-term dose comparisons less straightforward.
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Open PDFOriginal abstract
BACKGROUND Vitamin D supplementation may prevent falls in older persons, but evidence is inconsistent, possibly because of dosage differences. OBJECTIVE To compare the effects of 4 doses of vitamin D3 supplements on falls. DESIGN 2-stage Bayesian, response-adaptive, randomized trial. (ClinicalTrials.gov: NCT02166333). SETTING 2 community-based research units. PARTICIPANTS 688 participants, aged 70 years and older, with elevated fall risk and a serum 25-hydroxyvitamin D [25-(OH)D] level of 25 to 72.5 nmol/L. INTERVENTION 200 (control), 1000, 2000, or 4000 IU of vitamin D3 per day. During the dose-finding stage, participants were randomly assigned to 1 of the 4 vitamin D3 doses, and the best noncontrol dose for preventing falls was determined. After dose finding, participants previously assigned to receive noncontrol doses received the best dose, and new enrollees were randomly assigned to receive 200 IU/d or the best dose. MEASUREMENTS Time to first fall or death over 2 years (primary outcome). RESULTS During the dose-finding stage, the primary outcome rates were higher for the 2000- and 4000-IU/d doses than for the 1000-IU/d dose, which was selected as the best dose (posterior probability of being best, 0.90). In the confirmatory stage, event rates were not significantly different between participants with experience receiving the best dose (events and observation time limited to the period they were receiving 1000 IU/d; n = 308) and those randomly assigned to receive 200 IU/d (n = 339) (hazard ratio [HR], 0.94 [95% CI, 0.76 to 1.15]; P = 0.54). Analysis of falls with adverse outcomes suggested greater risk in the experience-with-best-dose group versus the 200-IU/d group (serious fall: HR, 1.87 [CI, 1.03 to 3.41]; fall with hospitalization: HR, 2.48 [CI, 1.13 to 5.46]). LIMITATIONS The control group received 200 IU of vitamin D3 per day, not a placebo. Dose finding ended before the prespecified thresholds for dose suspension and dose selection were reached. CONCLUSION In older persons with elevated fall risk and low serum 25-(OH)D levels, vitamin D3 supplementation at doses of 1000 IU/d or higher did not prevent falls compared with 200 IU/d. Several analyses raised safety concerns about vitamin D3 doses of 1000 IU/d or higher. PRIMARY FUNDING SOURCE National Institute on Aging.