Dataset Information

The Effects of Four Doses of Vitamin D Supplements on Falls in Older Adults : A Response-Adaptive, Randomized Clinical Trial.

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.

SUBMITTER: Appel LJ

PROVIDER: S-EPMC8240534 | biostudies-literature |

REPOSITORIES: biostudies-literature

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