High‐Dose Monthly Vitamin D for Prevention of Acute Respiratory Infection in Older Long‐Term Care Residents: A Randomized Clinical Trial

Double-blind, parallel-group randomized controlled phase II trial. Participants: older long-term care residents (≥60 years) at 25 Colorado facilities; 107 randomized (55 high-dose, 52 standard-dose); informed consent from participants or legally authorized representatives; randomization 1:1, stratified by site and baseline vitamin D supplementation; safety oversight by DSMB; IRB approval; NCT01102374.

Monthly oral vitamin D3 for 12 months. High-dose: 100,000 IU per month (total daily intake ≈ 3,000–4,000 IU/day when combined with usual supplementation). Standard-dose: 12,000 IU per month for those starting <400 IU/day, or matched placebo monthly for those starting 400–1,000 IU/day, with continuation of usual vitamin D intake to ensure at least 400 IU/day.

High-dose vitamin D3 reduced ARI incidence over 12 months by 40% (IRR 0.60; 95% CI 0.38–0.94; P=0.02). 31% vs 46% experienced at least one ARI. Upper ARIs decreased (IRR 0.52; P=0.02) and skin/soft tissue infections decreased (IRR 0.32; P=0.02). No differences in lower ARIs, ARI-related hospitalizations, urinary tract infections, or other infections. No vitamin D–related safety events observed. Falls were higher in the high-dose group (IRR 2.33; P<0.001); fractures did not differ. Subgroups with greater ARI reduction included baseline <400 IU/day, baseline 25OHD ≥20 ng/mL, completion of ≥11 doses, age ≥80, dementia, and eGFR ≥60. Conclusion: Monthly high-dose vitamin D3 may reduce ARI incidence in older LTC residents but increases falls; daily dosing could mitigate fall risk; larger confirmatory trials are needed.

Small sample size (107 randomized; planned 200); early trial termination; no true placebo group across all strata; intermittent bolus dosing (not daily) may affect safety/efficacy; potential baseline imbalances; no data on baseline fall history; some missed doses; limited generalizability to daily dosing or non-LTC populations.