Denmark: In children aged 0 to 6 years, high-dose vitamin D supplementation was not linked with an increased risk of severe adverse events (SAEs), and clinical adverse events probably due to the supplementation were infrequent, says an article published in the Journal of American Medical Association.
Several health advantages of vitamin D have been proposed; yet, the safety of high-dose administration in early development is unknown. As a result, Nicklas Brustad and colleagues undertook this investigation to comprehensively examine the likelihood of adverse events after high-dose vitamin D supplementation described in published randomized clinical trials.

ClinicalTrials.gov and PubMed were searched for this study until August 24, 2021. The study required randomized trials of high-dose vitamin D administration in children aged 0 to 6 years, defined as higher than 1000 IU/d for babies (aged 0-1 year) and greater than 2000 IU/d for children aged 1 to 6 years. Serious adverse events (SAEs), adverse events, and/or levels of 25-hydroxyvitamin D, alkaline phosphatase, calcium, parathyroid hormone, phosphate, and/or urine calcium-to-creatinine ratio.
The key findings of this study were as follows:
1. A total of 32 randomized clinical trials with a total of 8400 unique individuals were included in the study.
2. The clinical effects of children who received high-dose vitamin D supplements ranging from 1200 to 10 000 IU/d and bolus doses ranging from 30 000 IU/week to a single dose of 600 000 IU were studied.
3. When assessing the risk of SAEs such as hospitalization or death, eight trials involving 4612 individuals were qualified for meta-analysis, with a control group receiving either low-dose vitamin D supplementation (400 IU/d) or placebo.
4. There was no overall higher risk of SAEs in the high-dose vitamin D groups compared to the control groups.
5. Furthermore, the risk of hypercalcemia (n = 726) was not raised. Clinical side effects possibly related to vitamin D administration were seldom documented in the trials.
In conclusion, these findings imply that high-dose vitamin D supplementation for children between the ages of 0 to 6 years may be a safe supplement method for a variety of health outcomes.
Reference: Brustad N, Yousef S, Stokholm J, Bønnelykke K, Bisgaard H, Chawes BL. Safety of High-Dose Vitamin D Supplementation Among Children Aged 0 to 6 Years: A Systematic Review and Meta-analysis. JAMA Netw Open. 2022;5(4):e227410. doi:10.1001/jamanetworkopen.2022.7410