title: High-dose vitamin D3 in adults with pulmonary tuberculosis: a double-blind randomized controlled trial.
abstract: BACKGROUND
  Tuberculosis, including multidrug-resistant tuberculosis (MDR-TB), is a major global health problem. Individuals with tuberculosis disease commonly exhibit vitamin D deficiency, which may adversely affect immunity and the response to therapy.
  
  
  OBJECTIVE
  We determined whether adjunctive high-dose vitamin D3 supplementation improves outcomes in individuals with pulmonary tuberculosis disease.
  
  
  METHODS
  The study was a double-blind, randomized, placebo-controlled, intent-to-treat trial in 199 individuals with pulmonary tuberculosis disease in Tbilisi, Georgia. Subjects were randomly assigned to receive oral vitamin D3 [50,000 IUs (1.25 mg) thrice weekly for 8 wk and 50,000 IU every other week for 8 wk] or a placebo concomitant with standard first-line antituberculosis drugs. The primary outcome was the time for the conversion of a Mycobacterium tuberculosis (Mtb) sputum culture to negative.
  
  
  RESULTS
  Baseline characteristics between groups were similar. Most subjects (74%) were vitamin D deficient (plasma 25-hydroxyvitamin D [25(OH)D] concentration <50 nmol/L). With vitamin D3, plasma 25(OH)D concentrations peaked at ∼250 nmol/L by 8 wk and decreased to ∼125 nmol/L at week 16. Adverse events and plasma calcium concentrations were similar between groups. In 192 subjects with culture-confirmed tuberculosis, an adjusted efficacy analysis showed similar median culture-conversion times between vitamin D3 and placebo groups [29 and 27 d, respectively; HR: 0.86; 95% CI: 0.63, 1.18; P = 0.33). Eight-week culture-conversion rates were also similar (84.0% and 82.1% for vitamin D3 and placebo, respectively; P = 0.99).
  
  
  CONCLUSIONS
  A high-dose vitamin D3 regimen safely corrected vitamin D deficiency but did not improve the rate of sputum Mtb clearance over 16 wk in this pulmonary tuberculosis cohort. This trial was registered at clinicaltrials.gov at NCT00918086.
authors.affiliation: National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia;
authors.forename: Nestan
authors.initials: N
authors.lastname: Tukvadze
authors.affiliation: National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia;
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Sanikidze
authors.affiliation: National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia;
authors.forename: Maia
authors.initials: M
authors.lastname: Kipiani
authors.affiliation: Divisions of Endocrinology, Metabolism and Lipids and.
authors.forename: Gautam
authors.initials: G
authors.lastname: Hebbar
authors.affiliation: Biostatistics and Bioinformatics and.
authors.forename: Kirk A
authors.initials: KA
authors.lastname: Easley
authors.affiliation: Biostatistics and Bioinformatics and.
authors.forename: Neeta
authors.initials: N
authors.lastname: Shenvi
authors.affiliation: Divisions of Endocrinology, Metabolism and Lipids and Infectious Diseases and.
authors.forename: Russell R
authors.initials: RR
authors.lastname: Kempker
authors.affiliation: Divisions of Endocrinology, Metabolism and Lipids and Center for Clinical and Molecular Nutrition, Department of Medicine, Emory University School of Medicine, Atlanta, GA; Departments of.
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Frediani
authors.affiliation: National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia; Divisions of Endocrinology, Metabolism and Lipids and.
authors.forename: Veriko
authors.initials: V
authors.lastname: Mirtskhulava
authors.affiliation: Divisions of Endocrinology, Metabolism and Lipids and Center for Clinical and Molecular Nutrition, Department of Medicine, Emory University School of Medicine, Atlanta, GA; Departments of.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Alvarez
authors.affiliation: National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia;
authors.forename: Nino
authors.initials: N
authors.lastname: Lomtadze
authors.affiliation: National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia;
authors.forename: Lamara
authors.initials: L
authors.lastname: Vashakidze
authors.affiliation: Divisions of Endocrinology, Metabolism and Lipids and.
authors.forename: Li
authors.initials: L
authors.lastname: Hao
authors.affiliation: Infectious Diseases and Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA; and.
authors.forename: Carlos
authors.initials: C
authors.lastname: Del Rio
authors.affiliation: Divisions of Endocrinology, Metabolism and Lipids and Center for Clinical and Molecular Nutrition, Department of Medicine, Emory University School of Medicine, Atlanta, GA; Departments of Atlanta Veterans Affairs Medical Center, Decatur, GA.
authors.forename: Vin
authors.initials: V
authors.lastname: Tangpricha
authors.affiliation: Infectious Diseases and Epidemiology and.
authors.forename: Henry M
authors.initials: HM
authors.lastname: Blumberg
authors.affiliation: Divisions of Endocrinology, Metabolism and Lipids and Center for Clinical and Molecular Nutrition, Department of Medicine, Emory University School of Medicine, Atlanta, GA; Departments of tzieg01@emory.edu.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Ziegler
mesh_terms: D000293:Adolescent; D000328:Adult; D000995:Antitubercular Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002112:Calcifediol / Q000097:blood; D002762:Cholecalciferol / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use; D015331:Cohort Studies; D019587:Dietary Supplements / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D005846:Georgia (Republic); D006801:Humans; D057194:Intention to Treat Analysis; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000276:immunology* / Q000302:isolation & purification; D010352:Patient Dropouts; D013183:Sputum / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D014808:Vitamin D Deficiency / Q000097:blood / Q000150:complications / Q000178:diet therapy* / Q000276:immunology; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D002762:Cholecalciferol; D002112:Calcifediol
keywords: Mycobacterium tuberculosis; multidrug-resistant tuberculosis; randomized controlled trial; tuberculosis; vitamin D