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, I² = 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.