Efficacy of Weekly Versus Daily Cholecalciferol for Repleting Serum Vitamin D (25(OH)D) Deficiency: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Background/rationale: Weekly cholecalciferol can replace daily supplementation to reduce pill burden in patients with complex medication regimens and hypovitaminosis D, but evidence supporting this switch is unclear.

Objective: We aimed to determine whether weekly cholecalciferol was superior to daily cholecalciferol to replete patients with hypovitaminosis D.

Methods: We conducted a systematic review of randomized controlled trials involving participants with baseline hypovitaminosis D (<30 ng/ml) comparing weekly versus daily cholecalciferol dosing and where serum cholecalciferol was measured within 120 days of starting treatment. We searched MEDLINE, CINAHL and EMBASE from inception to 7 May 2024. A random-effects meta-analysis evaluated the odds ratio for repletion of serum vitamin D levels.

Findings: Eight trials involving 542 patients were included in the analysis. Weekly and daily cholecalciferol were not significantly different in correcting hypovitaminosis D (OR = 1.5, 95% CI = 0.3-6.9, p = 0.6, favouring weekly dosing, I = 85.3%). A sensitivity analysis excluding otherwise healthy patients had similar findings (OR = 0.8, 95% CI = 0.3-2.1, p = 0.6). Most studies were at risk of bias; the different doses being compared increased the heterogeneity.

Conclusions: Limited direct evidence supports a switch from daily to weekly cholecalciferol dosing; however, weekly supplementation was not demonstrably worse at repleting levels and decreased a patient's daily pill burden.