Update of the tolerable upper intake level for vitamin D for infants

Abstract

Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to revise the tolerable upper intake level (UL) for vitamin D for infants (≤ 1 year) set in 2012. From its literature review, the Panel concluded that the available evidence on daily vitamin D intake and the risk of adverse health outcomes (hypercalciuria, hypercalcaemia, nephrocalcinosis and abnormal growth patterns) cannot be used alone for deriving the UL for infants. The Panel conducted a meta-regression analysis of collected data, to derive a dose-response relationship between daily supplemental intake of vitamin D and mean achieved serum 25(OH)D concentrations. Considering that a serum 25(OH)D concentration of 200 nmol/L or below is unlikely to pose a risk of adverse health outcomes in infants, the Panel estimated the percentage of infants reaching a concentration above this value at different intakes of vitamin D. Based on the overall evidence, the Panel kept the UL of 25 μg/day for infants aged up to 6 months and set a UL of 35 μg/day for infants 6-12 months. The Panel was also asked to advise on the safety of the consumption of infant formulae with an increased maximum vitamin D content of 3 μg/100 kcal (Commission Delegated Regulation (EU) 2016/127 repealing Directive 2006/141/EC in 2020). For infants aged up to 4 months, the intake assessment showed that the use of infant formulae containing vitamin D at 3 μg/100 kcal may lead some infants to receive an intake above the UL of 25 μg/day from formulae alone without considering vitamin D supplemental intake. For infants aged 4-12 months, the 95th percentile of vitamin D intake (high consumers) estimated from formulae and foods fortified or not with vitamin D does not exceed the ULs, without considering vitamin D supplemental intake.

Keywords: 25(OH)D; UL; adverse health outcomes; infants; intake; vitamin D.

Figure 1

Confounders and modifiers

Figure 2

Forest plot of total calcium in serum for studies from tiers 1 and 2 for the RoB

1. *Vitamin D₃ **Vitamin D₂

   CI: confidence interval; D: vitamin D dose (μg/day).

   Values for trials (NRCT: non‐randomised controlled trial; NRNCT: non‐randomised non‐controlled trial; RCT: randomised controlled trial; RNCT: randomised non‐controlled trial) and prospective studies (PROSP) are indicated separately.

   Age: age of the infants in weeks (rounded). Calcium concentrations at baseline are not shown. Measurements before 6 months of age (blue) or after 6 months of age (green).

Figure 3

Figure 4