A new review suggests that vitamin D does more than support bones in early life, but says stronger human evidence is still needed for the strongest non-skeletal benefits.
key takeaways
Vitamin D is clearly important during the first 1,000 days for skeletal health, especially for preventing rickets and aiding early bone development.
The review suggests that vitamin D may also influence immunity, metabolism, and selected neurodevelopmental pathways, providing biological plausibility as an early life programming factor.
Evidence for most non-skeletal benefits in humans remains mixed, limited, and context-dependent, with stronger signals often seen in people or populations with vitamin D deficiency.
The authors argue that future research should move toward more personalized supplement strategies, including consideration of genetics, baseline vitamin D status, and timing of exposure during pregnancy and early life.
Major maternal, infant, and environmental factors influencing nutritional programming during pregnancy, infancy, and infancy.
In a recent review published in the journal NutrientsResearchers took advantage of the evolutionary origins of health and disease (dahod) Framework for evaluating the physiological role of vitamin D (VITD) during the first 1,000 days of human life.
The review showed that early life VITD is essential for nutritional prevention of skeletal diseases such as rickets. More importantly, the review highlights emerging data indicating that vitamin D affects more than 1,000 genes through the nuclear vitamin D receptor (VDR), with potential relevance to immunity, metabolism and selected neurodevelopmental health.
The review concludes that while vitamin D demonstrates biological plausibility as a programming factor, current human clinical evidence for non-skeletal outcomes is nascent and incomplete, leading to heterogeneous, context-dependent findings.
background
The first 1,000 days of a newborn’s life are now considered a “window of opportunity” as well as a “window of susceptibility” in pediatric practice, during which environmental stimuli significantly shape long-term health trajectories. Vitamin D, often called the “sunshine vitamin”, has historically been studied for its role in calcium-phosphate homeostasis.
Recent research has shown that vitamin D has important extraskeletal effects. Despite its important role, vitamin D deficiency remains a global health concern, with estimates suggesting that approximately 28% of the population is affected.
Meta-analyses of pregnant populations (n > 54,000) have found this group to be particularly susceptible to vitamin D deficiency, with 54% having serum 25(OH)D levels below 20 ng/mL (50 nmol/L). Because the stock of newborns is largely dependent on maternal transfer, maternal depletion can have adverse consequences for infants.
About review
The present narrative review aims to address this knowledge gap by synthesizing recent literature examining the effects of vitamin D in pregnancy, early life, infancy, and infancy. Studies were identified from PubMed, Scopus and Cochrane databases and included systematic reviews, meta-analyses, randomized controlled trials (RCT), and high quality observational studies.
Key outcomes examined included biomarkers such as serum 25(OH)D concentrations, skeletal outcomes including bone mineral content (BMC) and bone mineral density (BMD), immune and metabolic indicators such as acute respiratory tract infections (Artis) and body mass index (bmi), and molecular pathways including transcriptomics and epigenetics.
The analyzes also examined different vitamin D dosage regimens, ranging from standard 400 IU/day supplementation to high-dose maternal intervention of 6,400 IU/day during breastfeeding.
review findings
The findings revealed that VITD is involved in multiple physiological functions across developmental domains.
For skeletal development, supplementation of 1,000 IU/day during pregnancy increased whole-body BMC of the newborn, with some persistence through mid-childhood, although long-term clinical relevance remains uncertain.
For immune regulation, meta-analyses involving over 48,000 participants showed a small reduction in ARTI risk with vitamin D supplementation, particularly at doses of 400–1,000 IU daily. However, the effects were not significant in infants younger than 1 year of age, indicating age-dependent responses.
For metabolism and birth outcomes, observational studies involving more than 35,000 mother-offspring pairs linked low maternal 25(OH)D levels to higher risks of small for gestational age (SGA) infant and low birth weight, although randomized trial data remain inconsistent.
For molecular programming, maternal supplementation was associated with less epigenetic gestational age acceleration and altered placental gene expression, although the clinical implications remain uncertain.
conclusion
The review supports the biological plausibility of vitamin D as an early-life nutritional programming factor. Its role extends beyond skeletal health to immune tolerance and potential neurodevelopmental effects, although evidence for these outcomes remains emerging and heterogeneous.
The 2024 Endocrine Society guidelines suggest empirical supplementation during pregnancy at approximately 2,500 IU/day, while emphasizing that non-skeletal benefits are not yet certain.
Future research should adopt a precision nutrition approach that considers genetic variation, including polymorphisms in vitamin D-binding proteins (DBP), which may influence individual responses to supplementation.
