title: Effect of different dosages of oral vitamin D supplementation on vitamin D status in healthy, breastfed infants: a randomized trial.
abstract: OBJECTIVE
  Vitamin D supplementation in infancy is required to support healthy bone mineral accretion. A supplement of 400 IU of vitamin D per day is thought to support plasma 25-hydroxyvitamin D (25[OH]D) concentrations between 40 and 50 nmol/L; some advocate 75 to 150 nmol/L for bone health.
  
  
  OBJECTIVE
  To investigate the efficacy of different dosages of vitamin D in supporting 25(OH)D concentrations in infants.
  
  
  METHODS
  Double-blind randomized clinical trial conducted among 132 one-month-old healthy, term, breastfed infants from Montréal, Québec, Canada, between March 2007 and August 2010. Infants were followed up for 11 months ending August 2011 (74% completed study).
  
  
  METHODS
  Participants were randomly assigned to receive oral cholecalciferol (vitamin D3) supplements of 400 IU/d (n=39), 800 IU/d (n=39), 1200 IU/d (n=38), or 1600 IU/d (n=16).
  
  
  METHODS
  The primary outcome was a plasma 25(OH)D concentration of 75 nmol/L or greater in 97.5% of infants at 3 months. Secondary outcomes included 25(OH)D concentrations of 75 nmol/L or greater in 97.5% of infants at 6, 9, and 12 months; 25(OH)D concentrations of 50 nmol/L or greater across all times; growth; and whole body and regional bone mineral content. Data were analyzed by intention to treat using available data, logistic regression, and mixed-model analysis of variance.
  
  
  RESULTS
  By 3 months, 55% (95% CI, 38%-72%) of infants in the 400-IU/d group achieved a 25(OH)D concentration of 75 nmol/L or greater vs 81%(95% CI, 65%-91%) in the 800-IU/d group, 92% (95% CI, 77%-98%) in the 1200-IU/d group, and 100% in the 1600-IU/d group. This concentration was not sustained in 97.5% of infants at 12 months in any of the groups. The 1600-IU/d dosage was discontinued prematurely because of elevated plasma 25(OH)D concentrations. All dosages established 25(OH)D concentrations of 50 nmol/L or greater in 97% (95% CI, 94%-100%) of infants at 3 months and sustained this in 98% (95% CI, 94%-100%) to 12 months. Growth and bone mineral content did not differ by dosage.
  
  
  CONCLUSIONS
  Among healthy, term, breastfed infants, only a vitamin D supplement dosage of 1600 IU/d (but not dosages of 400, 800, or 1200 IU/d) increased plasma 25(OH)D concentration to 75 nmol/L or greater in 97.5% of infants at 3 months. However, this dosage increased 25(OH)D concentrations to levels that have been associated with hypercalcemia.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00381914.
authors: School of Dietetics and Human Nutrition, McGill University, Montréal, Québec, Canada.
authors: Sina
authors: S
authors: Gallo
authors: Kathryn
authors: K
authors: Comeau
authors: Catherine
authors: C
authors: Vanstone
authors: Sherry
authors: S
authors: Agellon
authors: Atul
authors: A
authors: Sharma
authors: Glenville
authors: G
authors: Jones
authors: Mary
authors: M
authors: L'Abbé
authors: Ali
authors: A
authors: Khamessan
authors: Celia
authors: C
authors: Rodd
authors: Hope
authors: H
authors: Weiler
mesh_terms: D000284:Administration, Oral; D001846:Bone Development; D001942:Breast Feeding; D002762:Cholecalciferol / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000139:chemically induced; D007223:Infant; D007227:Infant Nutritional Physiological Phenomena; D007231:Infant, Newborn; D008297:Male; D016896:Treatment Outcome; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D014815:Vitamins / Q000008:administration & dosage*
chemical_list: D014815:Vitamins; D014807:Vitamin D; D002762:Cholecalciferol; C104450:25-hydroxyvitamin D