title: Rapid normalization of vitamin D levels: a meta-analysis.
abstract: BACKGROUND
  Vitamin D deficiency may represent a modifiable risk factor to improve outcome in severe illness. The efficacy of high-dose regimens in rapid normalization of vitamin D levels is uncertain.
  
  
  METHODS
  We conducted a systematic review of pediatric clinical trials administering high-dose vitamin D to evaluate 25-hydroxyvitamin D (25[OH]D) response and characteristics associated with final 25(OH)D levels by using Medline, Embase, and the Cochrane Central Register of Controlled Trials, including reference lists of systematic reviews and eligible publications. Uncontrolled and controlled trials reporting 25(OH)D levels after high-dose (≥1000 IU) ergocalciferol or cholecalciferol were selected. Two reviewers independently extracted and verified predefined data fields.
  
  
  RESULTS
  We identified 88 eligible full-text articles. Two of 6 studies that administered daily doses approximating the Institute of Medicine's Tolerable Upper Intake Level (1000-4000 IU) to vitamin D-deficient populations achieved group 25(OH)D levels >75 nmol/L within 1 month. Nine of 10 studies evaluating loading therapy (>50 000 IU) achieved group 25(OH)D levels >75 nmol/L. In meta-regression, baseline 25(OH)D, regimen type, dose, age, and time factors were associated with final 25(OH)D levels. Adverse event analysis identified increased hypercalcemia risk with doses >400 000 IU, but no increased hypercalcemia or hypercalciuria with loading doses <400 000 IU (or 10 000 IU/kg). Few studies in adolescents evaluated loading dose regimens >300 000 IU.
  
  
  CONCLUSIONS
  Rapid normalization of vitamin D levels is best achieved by using loading therapy that considers disease status, baseline 25(OH)D, and age (or weight). Loading doses >300 000 IU should be avoided until trials are conducted to better evaluate risk and benefit.
authors.affiliation: Department of Pediatrics, Faculty of Medicine, University of Ottawa, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada; Research Institute, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada; dmcnally@cheo.on.ca.
authors.forename: J Dayre
authors.initials: JD
authors.lastname: McNally
authors.affiliation: Research Institute, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada; School of Medicine, Trinity College, Dublin, Ireland;
authors.forename: Klevis
authors.initials: K
authors.lastname: Iliriani
authors.affiliation: Department of Pediatrics, Faculty of Medicine, University of Ottawa, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada; Division of Critical Care, Department of Pediatrics, Phramonghutklao Hospital, Bangkok, Thailand; and.
authors.forename: Supichaya
authors.initials: S
authors.lastname: Pojsupap
authors.affiliation: Department of Pediatrics, Faculty of Medicine, University of Ottawa, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada;
authors.forename: Margaret
authors.initials: M
authors.lastname: Sampson
authors.affiliation: Department of Pediatrics, Faculty of Medicine, University of Ottawa, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada; Research Institute, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada;
authors.forename: Katie
authors.initials: K
authors.lastname: O'Hearn
authors.affiliation: Division of Critical Care, Department of Medicine, and.
authors.forename: Lauralyn
authors.initials: L
authors.lastname: McIntyre
authors.affiliation: Department of Epidemiology and Community Medicine, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Dean
authors.initials: D
authors.lastname: Fergusson
authors.affiliation: Department of Pediatrics, Faculty of Medicine, University of Ottawa, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada; Research Institute, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada;
authors.forename: Kusum
authors.initials: K
authors.lastname: Menon
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D012016:Reference Values; D012074:Remission Induction; D013997:Time Factors; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood / Q000627:therapeutic use*; D014808:Vitamin D Deficiency / Q000097:blood / Q000188:drug therapy*; D014815:Vitamins / Q000627:therapeutic use*
chemical_list: D014815:Vitamins; D014807:Vitamin D; C104450:25-hydroxyvitamin D
keywords: meta-regression; pediatrics; risk factors; systematic review; vitamin D