title: Comprehensive Safety Monitoring of 12-Month Daily 7000-IU Vitamin D3 Supplementation in Human Immunodeficiency Virus-Infected Children and Young Adults.
abstract: There is uncertainty whether long-term daily dosing with vitamin D3 (cholecalciferol) supplementation (vitD3) above the 4000-IU/d dietary reference intake upper tolerable limit in children and adults is safe. As part of a randomized placebo-controlled trial, we determined if supplementation with 7000-IU/d vitD3 for 12 months in human immunodeficiency virus (HIV)-Infected subjects was safe and/or associated with metabolic outcomes.
  
  
  
  A total of 58 HIV-infected subjects-aged 9-24.9 years and stratified by mode of HIV acquisition (perinatal or behavioral)-were recruited, randomized to 7000-IU/d vitD3 or placebo, and followed at 3, 6, and 12 months with physical examinations, blood and urine sampling for measures of 25(OH)D (serum 25-hydroxyvitamin D), metabolic status, safety measures, and HIV immune status. Safety was defined by a low incidence (<5%) of the study-defined serious adverse events-that is, elevated serum calcium plus 25(OH)D >160 ng/mL-and no changes in hematologic, liver, renal, metabolic, lipid, or inflammatory status.
  
  
  
  Randomization groups did not differ in demographic characteristics, vitamin D status, or HIV disease status at baseline. Over the 12 months, serum 25(OH)D increased with supplementation. No subject experienced a serious adverse safety event; none had 25(OH)D >80 ng/mL at any time. There were no clinically significant changes in hematologic, liver, renal, metabolic, lipid, or inflammatory status.
  
  
  
  Safety of daily 7000-IU vitD3 supplementation in children and young adults with HIV was comprehensively monitored over 12 months. High-dose daily vitD3 supplementation was efficacious in improving vitamin D status, and there were no safety events.
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA schall@email.chop.edu.
authors.forename: Joan I
authors.initials: JI
authors.lastname: Schall
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
authors.forename: Mary L
authors.initials: ML
authors.lastname: Hediger
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Babette S
authors.initials: BS
authors.lastname: Zemel
authors.affiliation: Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA General Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Rutstein
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Virginia A
authors.initials: VA
authors.lastname: Stallings
mesh_terms: D000293:Adolescent; D001786:Blood Glucose / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D002118:Calcium / Q000097:blood; D002648:Child; D002762:Cholecalciferol / Q000008:administration & dosage* / Q000097:blood; D002784:Cholesterol / Q000097:blood; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D005260:Female; D015658:HIV Infections / Q000097:blood*; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D014280:Triglycerides / Q000097:blood; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007328:Insulin; D014280:Triglycerides; D002762:Cholecalciferol; D002097:C-Reactive Protein; D002784:Cholesterol; D002118:Calcium
keywords: HIV infection; children; metabolic outcomes; safety; vitamin D; young adults