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.


CONCLUSIONS
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.
Division of Endocrinology, Metabolism and Lipids, Emory University School of Medicine, Atlanta, Georgia.
Malcolm D
MD
Kearns
Division of Endocrinology, Metabolism and Lipids, Emory University School of Medicine, Atlanta, Georgia.
Jessica A
JA
Alvarez
Division of Endocrinology, Metabolism and Lipids, Emory University School of Medicine, Atlanta, Georgia Atlanta Veterans Affairs Medical Center, Section of Endocrinology, Atlanta, Georgia.
Vin
V
Tangpricha
D000284:Administration, Oral; D000328:Adult; D019587:Dietary Supplements; D006801:Humans; D010281:Parathyroid Hormone / Q000097:blood; D014807:Vitamin D / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives / Q000097:blood
D010281:Parathyroid Hormone; D014807:Vitamin D; C104450:25-hydroxyvitamin D