High-Dose Vitamin D Well Tolerated in Pediatric Patients

Nicklas Brustad, MD, PhD

A new systematic review on vitamin D supplements found that daily doses of 10,000 IU/d or bolus doses to 600,000 IU were well tolerated in children 0-6 years.

Previous research thoroughly confirmed the influence of vitamin D on skeletal health, as well as other biological non-skeletal effects.

However, evidence from systematic reviews and meta-analyses regarding the safety of high-dose vitamin D supplementation in early childhood has been lacking.

As such, an investigative team led by Nicklas Brustad, MD, PhD, of the University of Copenhagen, investigated the safety of high-dose vitamin D in children 0-6 years and examined the potential clinical adverse events and biochemical changes reported in previous trials.

The team conducted a systematic review using the PubMed database to identify relevant studies published up until August 24, 2021.

Search terms included "randomized controlled trials", "child/infant", and "vitamin D".

Study selection was based on inclusion criteria that focused on original RCT, intervention with vitamin D2 or D3 supplementation greater than 1000 IU/d or bolus therapy, children aged 0 to 6 years, and clinical adverse events and/or biochemical levels of 25(OH)D, calcium, alkaline phosphatase (ALP), phosphate, parathyroid hormone (PTH), and/or ratio of urine calcium to creatinine levels (Ca:Cr ratio).

Investigators extracted data on age, race and ethnicity, study participants, and intervention details from relevant studies.

Safety outcome data included the number of children with 25(OH)D levels greater than 100 ng/mL, hypercalcemia, abnormal levels of ALP, phosphate, PTH, or Ca:Cr ratio, and clinical and serious adverse events (SAEs).

Finally, reference ranges and comments featured in eligible studies were used in the categorization of biochemical values as abnormal or within reference ranges.

In total, 32 randomized clinical trials with 8400 total participants were included in the study.

A total of 8 studies featuring 4612 participants were deemed eligible for a meta-analysis and featured a control group receiving either low-dose vitamin D supplementation (≤400 IU/d) or placebo when investigating the risk of SAEs.

Investigators did not observe an overall increased risk of SAEs in pediatric patients who received high-dose vitamin D compared to control groups (P = .89).

Additionally, the risk of hypercalcemia observed in 726 pediatric patients was not increased (P=.51) and clinical adverse events related to vitamin D supplementation were rare.

“The safety outcomes assessed in this study are clinically relevant and should be investigated further because high-dose vitamin D administered to children seems to have beneficial effects on different health outcomes, such as preventing pneumonia and influenza,” the team wrote.

The study, "Safety of High-Dose Vitamin D Supplementation Among Children Aged 0 to 6 Years," was published online in JAMA Open Network.