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Pediatric trials of high dose vitamin D -163 are in a single online database – Feb 2016

A systematic review of pediatric clinical trials of high dose vitamin D

PeerJ February 25, 2016, DOI: 10.7717/peerj.1701
Nassr Nama 1,2, Kusum Menon 2, Klevis Iliriani 3, Supichaya Pojsupap 2, Margaret Sampson 4, Katie O’Hearn 2, Linghong (Linda) Zhou 1, Lauralyn McIntyre 5, Dean Fergusson 6, James D. McNally​1,2 dmcnally at cheo.on.ca
1 Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
2 Department of Pediatrics, Children’s Hospital of Eastern Ontario, Ottawa, Ontario, Canada
3 School of Medicine, Trinity College, Dublin, Ireland
4 Department of Volunteers, Communication and Information Resources, Children’s Hospital of Eastern Ontario, Ottawa, Ontario, Canada
5 Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
6 Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada

Background. Due to inadequate UV exposure, intake of small quantities of vitamin D is recommended to prevent musculoskeletal disease. Both basic science and observational literature strongly suggest that higher doses may benefit specific populations and have non-musculoskeletal roles. Evaluating the evidence surrounding high dose supplementation can be challenging given a relatively large and growing body of clinical trial evidence spanning time, geography, populations and dosing regimens. Study objectives were to identify and summarize the clinical trial literature, recognize areas with high quality evidence, and develop a resource database that makes the literature more immediately accessible to end users.

Methods. Medline (1946 to January 2015), Embase (1974 to January 2015), and Cochrane databases (January 2015), were searched for trials. All pediatric (0–18 years) trials administering doses higher than 400 IU (<1 year) or 600 IU (≥1 year) were included. Data was extracted independently by two of the authors. An online searchable database of trials was developed containing relevant extracted information (http://www.cheori.org/en/pedvitaminddatabaseOverview). Sensitivity and utility were assessed by comparing the trials in the database with those from systematic reviews of vitamin D supplementation including children.

Results. A total of 2,579 candidate papers were identified, yielding 169 trials having one or more arms meeting eligibility criteria. The publication rate has increased significantly from 1 per year (1970–1979) to 14 per year (2010–2015). Although 84% of the total trials focused on healthy children or known high risk populations (e.g., renal, prematurity), this proportion has declined in recent years due to the rise in trials evaluating populations and outcomes not directly related to the musculoskeletal actions of vitamin D (27% in 2010s). Beyond healthy children, the only pediatric populations with more than 50 participants from low risk of bias trials evaluating a clinically relevant outcome were prematurity and respiratory illness. Finally, we created and validated the online searchable database using 13 recent systematic reviews. Of the 38 high dose trials identified by the systematic review, 36 (94.7%) could be found within the database. When compared with the search strategy reported in each systematic review, use of the database reduced the number of full papers to assess for eligibility by 85.2% (±13.4%).

Conclusion. The pediatric vitamin D field is highly active, with a significant increase in trials evaluating non-classical diseases and outcomes. Despite the large overall number there are few high quality trials of sufficient size to provide answers on clinical efficacy of high-dose vitamin D. An open access online searchable data should assist end users in the rapid and comprehensive identification and evaluation of trials relevant to their population or question of interest.

Big increase in Vitamin D3 trials


Large dose trials are often outside of North America and Europe


Snips from the PDF

Dosing groups

RDA/AI–999 19.0%
1,000–3,999 27.8%
4,000–39,999 12.6%
≥40,000 40.7%


Daily 52.1%
Intermittent/single dose 36.5 %
Weekly/biweekly 11.4%
  • “The decline in publications on high-dose vitamin D may relate to a late 1980’s publication reporting high hypercalcemia rates (34%) in young infants receiving 600,000 IU (Markestad et al., 1987).”
  • . . “if the current rate is maintained there will have been more trials published between 2010 and 2019 then in the preceding 5 decades combined.”
  • “ Our analysis demonstrated that 90% of trials used a constant dose, with no evidence of a recent shift towards age or weight based practise.”
  • “Considering all low-risk of bias studies, regardless of size, there were only two areas (respiratory infection/asthma, n = 2,166 and prematurity/low birth weight, n = 2,127) with more than 100 total children enrolled in the high-dose arms”
  • “ Our goal is to update this list yearly, and provide a data entry page for research groups to provide relevant information on their study.”

Database https://vitamind.knackhq.com/pediatrics/

A few of the selection parameters for the database



Dosing Frequency

 Download the PDF from VitaminDWiki

 Download the list of trials from VitaminDWiki

Attached files

ID Name Comment Uploaded Size Downloads
6954 Arms vs dose size.jpg admin 07 Aug, 2016 18:19 21.13 Kb 327
6953 Arms D3 D2.jpg admin 07 Aug, 2016 18:19 13.79 Kb 329
6459 Database frequency.jpg admin 08 Mar, 2016 17:01 3.71 Kb 439
6458 Database condition.jpg admin 08 Mar, 2016 17:01 10.16 Kb 518
6457 database age.jpg admin 08 Mar, 2016 17:00 3.89 Kb 472
6456 names of 169 trials.docx admin 08 Mar, 2016 16:01 177.43 Kb 372
6455 Pediatric trials online.pdf PDF 2016 admin 08 Mar, 2016 16:00 498.07 Kb 395
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