Large, Single-dose, Oral Vitamin D Supplementation in Adult Populations: a Systematic Review

Objective: Daily vitamin D supplementation is often inadequate in treating vitamin D deficiency due to poor compliance. A single, large dose of vitamin D given at timed intervals may be an alternative strategy.

Methods: We conducted a systematic literature review to investigate the efficacy of a single large bolus dose to treat vitamin D deficiency. We identified 2,243 articles in PubMed using the terms "high dose vitamin D," "single dose vitamin D," "bolus vitamin D," or "annual dose vitamin D." Review articles, cross-sectional studies, non-human studies, responses to other articles, and non-English articles were excluded. Manuscripts were also excluded if the study: (1) did not use oral cholecalciferol or ergocalciferol, (2) used vitamin D analogs, (3) enrolled participants under age 18 years, (4) administered doses <100,000 international units (IU) (2.5 mg), or (5) administered >1 dose per year. References of eligible manuscripts and the Cochrane databases were also searched. Two independent reviewers identified eligible manuscripts, and a third reviewer evaluated disagreements. Thirty manuscripts were selected using these criteria.

Results: Large, single doses of vitamin D consistently increased serum/plasma 25-hydroxyvitamin D (25[OH]D) concentrations in several vitamin D-sufficient and -deficient populations. Vitamin D3 doses ≥300,000 IU provided optimal changes in serum/plasma 25(OH)D and parathyroid hormone (PTH) concentrations. Vitamin D supplementation also impacted bone health and extraskeletal endpoints.

Conclusion: This review recommends that vitamin D3 be used for supplementation over vitamin D2 and concludes that single vitamin D3 doses ≥300,000 IU are most effective at improving vitamin D status and suppressing PTH concentrations for up to 3 months. Lower doses, however, may be sufficient in certain populations. Vitamin D doses >500,000 IU should be used judiciously in order to minimize adverse events.