title: Dose response to vitamin D supplementation in postmenopausal women: a randomized trial.
abstract: BACKGROUND
  Serum 25-hydroxyvitamin D (25-[OH]D) is considered the best biomarker of clinical vitamin D status.
  
  
  OBJECTIVE
  To determine the effect of increasing oral doses of vitamin D(3) on serum 25-(OH)D and serum parathyroid hormone (PTH) levels in postmenopausal white women with vitamin D insufficiency (defined as a 25-[OH]D level ≤50 nmol/L) in the presence of adequate calcium intake. These results can be used as a guide to estimate the Recommended Dietary Allowance (RDA) (defined as meeting the needs of 97.5% of the population) for vitamin D(3).
  
  
  METHODS
  Randomized, placebo-controlled trial. (ClinicalTrials.gov registration number: NCT00472823)
  
  
  METHODS
  Creighton University Medical Center, Omaha, Nebraska.
  
  
  METHODS
  163 healthy postmenopausal white women with vitamin D insufficiency enrolled in the winter or spring of 2007 to 2008 and followed for 1 year.
  
  
  METHODS
  Participants were randomly assigned to receive placebo or vitamin D(3), 400, 800, 1600, 2400, 3200, 4000, or 4800 IU once daily. Daily calcium supplements were provided to increase the total daily calcium intake to 1200 to 1400 mg.
  
  
  METHODS
  The primary outcomes were 25-(OH)D and PTH levels at 6 and 12 months.
  
  
  RESULTS
  The mean baseline 25-(OH)D level was 39 nmol/L. The dose response was curvilinear and tended to plateau at approximately 112 nmol/L in patients receiving more than 3200 IU/d of vitamin D(3). The RDA of vitamin D(3) to achieve a 25-(OH)D level greater than 50 nmol/L was 800 IU/d. A mixed-effects model predicted that 600 IU of vitamin D(3) daily could also meet this goal. Compared with participants with a normal body mass index (<25 kg/m(2)), obese women (≥30 kg/m(2)) had a 25-(OH)D level that was 17.8 nmol/L lower. Parathyroid hormone levels at 12 months decreased with an increasing dose of vitamin D(3) (P = 0.012). Depending on the criteria used, hypercalcemia occurred in 2.8% to 9.0% and hypercalciuria in 12.0% to 33.0% of participants; events were unrelated to dose.
  
  
  CONCLUSIONS
  Findings may not be generalizable to other age groups or persons with substantial comorbid conditions.
  
  
  CONCLUSIONS
  A vitamin D(3) dosage of 800 IU/d increased serum 25-(OH)D levels to greater than 50 nmol/L in 97.5% of women; however, a model predicted the same response with a vitamin D(3) dosage of 600 IU/d. These results can be used as a guide for the RDA of vitamin D(3), but prospective trials are needed to confirm the clinical significance of these results.
  
  
  BACKGROUND
  National Institute on Aging.
authors.affiliation: Bone Metabolism Unit, Creighton University School of Medicine, Omaha, Nebraska 68131, USA. jcg@creighton.edu
authors.forename: J Christopher
authors.initials: JC
authors.lastname: Gallagher
authors.forename: Adarsh
authors.initials: A
authors.lastname: Sai
authors.forename: Thomas
authors.initials: T
authors.lastname: Templin
authors.forename: Lynette
authors.initials: L
authors.lastname: Smith
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D002136:Calcium, Dietary / Q000008:administration & dosage; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000139:chemically induced; D053565:Hypercalciuria / Q000139:chemically induced; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000150:complications; D010281:Parathyroid Hormone / Q000097:blood; D017698:Postmenopause / Q000097:blood*; D011446:Prospective Studies; D014807:Vitamin D / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives / Q000097:blood; D014808:Vitamin D Deficiency / Q000097:blood* / Q000150:complications / Q000188:drug therapy*
chemical_list: D015415:Biomarkers; D002136:Calcium, Dietary; D010281:Parathyroid Hormone; D014807:Vitamin D; C104450:25-hydroxyvitamin D