Kids internalized fewer problems when given high doses of Vitamin D3 as babies, a secondary analysis of a randomized trial suggested.

Compared with infants given 400 IU of daily vitamin D3, those given a dose of 1,200 IU had a 60% lower chance of Internalizing Problems like depression by ages 6 to 8 (OR 0.40, 95% CI 0.17-0.94, P=0.04), reported Samuel Sandboge, MD, PhD, of the University of Tampere in Finland, and colleagues.

The model was adjusted for several factors including sex, birth season, maternal depressive symptoms at birth, and parental single status at follow-up.

In total, 11.8% of infants on the 400 IU dose — the standard recommended daily dose — experienced clinically significant internalizing problems versus 5.6% of the higher-dose group, the researchers wrote in JAMA Network Open.

There was no significant difference between the groups when it came to externalizing problems, as well as total clinically significant psychiatric problems.

Internalizing problems often manifest in the form of depression, anxiety, or social withdrawal, while externalizing behaviors can manifest in the form of verbal or physical aggression.

High-dose vitamin D3 appeared more protective against internalizing problems when taking maternal 25(OH)D concentrations into account. For example, odds for internalizing problems were significantly lower among kids in the 1,200 IU group who had maternal 25(OH)D levels of 30 ng/mL or greater compared with kids in the 400 IU group with maternal 25(OH)D levels less than 30 ng/mL (adjusted OR 0.21, 95% CI 0.06-0.78, P=0.02).

The mean difference of internalizing problems score was significantly lower among kids in the 1,200 IU group regardless of whether their mothers had concentrations above or below the 30 ng/mL cutoff versus kids in the 400 IU group with maternal concentrations falling below 30 ng/mL.

“Results from previous studies, which were primarily observational, suggested that lower childhood vitamin D levels, measured as serum 25-hydroxyvitamin D (25[OH]D), were associated with autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD),” Sandboge’s group pointed out. “Lower childhood vitamin D levels have also been associated with increased levels of depressive symptoms and internalizing and externalizing problems later in childhood.”

To delve deeper into this, the researchers recruited infants to the Vitamin D Intervention in Infants (VIDI) study, which was initially aimed at testing the different levels of vitamin D3 supplementation on bone strength and infection.

In this sub-analysis of mental health outcomes, 169 infants were on the 400 IU dose and 177 were on the 1,200 IU dose from ages 2 weeks to 2 years via oral dropper. All infants were of Northern European ancestry and recruited at a single center in Helsinki, Finland, located at 60 degrees north latitude.

Psychiatric symptoms were measured around age 7 using the 113-item, parent-reported Child Behavior Checklist (CBCL) questionnaire.

While these findings need to be repeated and reassessed for safety, Sandboge’s group also said the results “need to be interpreted in context with outcomes related to children’s somatic health (e.g., growth and allergies), for which lower doses were found to be more beneficial during infancy.” Whether the findings generalize to children living at other geographical latitudes also needs to be investigated.