title: Vitamin D₃supplementation and childhood diarrhea: a randomized controlled trial.
abstract: OBJECTIVE
  To investigate the effect of vitamin D3 supplementation on the incidence and risk for first and recurrent diarrheal illnesses among children in Kabul, Afghanistan.
  
  
  METHODS
  This double-blind placebo-controlled trial randomized 3046 high-risk 1- to 11-month-old infants to receive 6 quarterly doses of oral vitamin D3 (cholecalciferol 100000 IU) or placebo in inner city Kabul. Data on diarrheal episodes (≥ 3 loose/liquid stools in 24 hours) was gathered through active and passive surveillance over 18 months of follow-up. Time to first diarrheal illness was analyzed by using Kaplan-Meier plots. Incidence rates and hazard ratios (HRs) were calculated by using recurrent event Poisson regression models.
  
  
  RESULTS
  No significant difference existed in survival time to first diarrheal illness (log rank P = .55). The incidences of diarrheal episodes were 3.43 (95% confidence interval [CI], 3.28-3.59) and 3.59 per child-year (95% CI, 3.44-3.76) in the placebo and intervention arms, respectively. Vitamin D3 supplementation was found to have no effect on the risk for recurrent diarrheal disease in either intention-to-treat (HR, 1.05; 95% CI, 0.98-1.17; P = .15) or per protocol (HR, 1.05; 95% CI, 0.98-1.12; P = .14) analyses. The lack of preventive benefit remained when the randomized population was stratified by age groups, nutritional status, and seasons.
  
  
  CONCLUSIONS
  Quarterly supplementation with vitamin D3 conferred no reduction on time to first illness or on the risk for recurrent diarrheal disease in this study. Similar supplementation to comparable populations is not recommended. Additional research in alternative settings may be helpful in elucidating the role of vitamin D3 supplementation for prevention of diarrheal diseases.
authors.affiliation: MSc, SUNY Downstate Medical Center, Department of Emergency Medicine, 450 Clarkson Ave, Brooklyn, NY 11203. adam.aluisio@gmail.com.
authors.forename: Adam R
authors.initials: AR
authors.lastname: Aluisio
authors.forename: Zabihullah
authors.initials: Z
authors.lastname: Maroof
authors.forename: Daniel
authors.initials: D
authors.lastname: Chandramohan
authors.forename: Jane
authors.initials: J
authors.lastname: Bruce
authors.forename: M Zulf
authors.initials: MZ
authors.lastname: Mughal
authors.forename: Zulfiqar
authors.initials: Z
authors.lastname: Bhutta
authors.forename: Gijs
authors.initials: G
authors.lastname: Walraven
authors.forename: Mohammad I
authors.initials: MI
authors.lastname: Masher
authors.forename: Jeroen H J
authors.initials: JH
authors.lastname: Ensink
authors.forename: Semira
authors.initials: S
authors.lastname: Manaseki-Holland
mesh_terms: D000346:Afghanistan / Q000453:epidemiology; D002675:Child, Preschool; D002762:Cholecalciferol / Q000627:therapeutic use*; D003967:Diarrhea / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology; D003968:Diarrhea, Infantile / Q000175:diagnosis* / Q000188:drug therapy* / Q000453:epidemiology; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008297:Male; D012306:Risk
chemical_list: D002762:Cholecalciferol
keywords: Afghanistan; children; diarrhea prevention; vitamin D supplementation
references.citation: Nutr Rev. 2008 Sep;66(9):487-505
references.pmid: 18752473
references.citation: Pediatrics. 2008 Aug;122(2):398-417
references.pmid: 18676559
references.citation: BMC Public Health. 2012 Mar 21;12:220
references.pmid: 22436130
references.citation: Trans R Soc Trop Med Hyg. 2005 Jun;99(6):407-16
references.pmid: 15837352
references.citation: Eur J Clin Nutr. 2004 Apr;58(4):563-7
references.pmid: 15042122
references.citation: P N G Med J. 1995 Dec;38(4):272-7
references.pmid: 9522867
references.citation: Lancet. 2000 Feb 5;355(9202):451-5
references.pmid: 10841125
references.citation: Int J Epidemiol. 1989 Sep;18(3):697-700
references.pmid: 2807676
references.citation: Bull World Health Organ. 2008 Sep;86(9):710-7
references.pmid: 18797647
references.citation: Arch Pediatr Adolesc Med. 2008 Jun;162(6):583-4
references.pmid: 18524751
references.citation: Indian J Public Health. 1998 Jan-Mar;42(1):3-6
references.pmid: 10389497
references.citation: PLoS One. 2012;7(6):e38321
references.pmid: 22675542
references.citation: Indian Pediatr. 2006 Mar;43(3):247-51
references.pmid: 16585820
references.citation: J Immunol. 2004 Sep 15;173(6):3668-75
references.pmid: 15356112
references.citation: BMJ. 2011 Aug 25;343:d5094
references.pmid: 21868478
references.citation: Arch Pediatr Adolesc Med. 2008 Jun;162(6):513-9
references.pmid: 18524740
references.citation: Braz J Infect Dis. 2008 Feb;12(1):89-93
references.pmid: 18553022
references.citation: Lancet. 2000 Feb 19;355(9204):618-21
references.pmid: 10696983
references.citation: Am J Clin Nutr. 2007 Sep;86(3):714-7
references.pmid: 17823437
references.citation: Ann Epidemiol. 2010 Feb;20(2):151-8
references.pmid: 20123166
references.citation: Int J Epidemiol. 2008 Aug;37(4):816-30
references.pmid: 18567626
references.citation: J Immunol. 2004 Sep 1;173(5):2909-12
references.pmid: 15322146
references.citation: Anticancer Res. 2009 Sep;29(9):3675-84
references.pmid: 19667164
references.citation: J Clin Endocrinol Metab. 2010 Feb;95(2):471-8
references.pmid: 20133466
references.citation: Pediatr Infect Dis J. 2013 Jun;32(6):585-93
references.pmid: 23340562
references.citation: Rev Endocr Metab Disord. 2008 Sep;9(3):181-92
references.pmid: 18604643
references.citation: Indian J Med Res. 1986 Jul;84:53-8
references.pmid: 3770836
references.citation: Annu Rev Public Health. 2007;28:127-43
references.pmid: 17222079
references.citation: Science. 2006 Mar 24;311(5768):1770-3
references.pmid: 16497887
references.citation: Int J Vitam Nutr Res. 2008 Jan;78(1):16-20
references.pmid: 18654949
references.citation: Lancet. 2012 Apr 14;379(9824):1419-27
references.pmid: 22494826
references.citation: Am J Epidemiol. 1977 May;105(5):488-95
references.pmid: 871121
references.citation: Curr Opin Gastroenterol. 2007 Jan;23(1):32-8
references.pmid: 17133082
references.citation: Pediatrics. 2007 Jun;119(6):1120-30
references.pmid: 17545379
references.citation: Am J Public Health. 2004 Mar;94(3):400-5
references.pmid: 14998803
references.citation: Int J Environ Res Public Health. 2011 Apr;8(4):1174-205
references.pmid: 21695035
references.citation: Pediatrics. 2013 Apr;131(4):634-6
references.pmid: 23509166
references.citation: J Immunol. 2008 Mar 1;180(5):2786-95
references.pmid: 18292499
references.citation: Bull World Health Organ. 2003;81(3):197-204
references.pmid: 12764516
references.citation: Endocr Pract. 2009 Jul-Aug;15(5):438-49
references.pmid: 19491064