This single-centre, double-blind Canadian study randomised 132 healthy, term, breastfed infants who were 1 month of age to 400, 800, 1200, or 1600 IU/d of oral cholecalciferol (vitamin D3) for 11 months.
The primary outcome was to establish a dosage of oral vitamin D supplementation that would support 25(OH)D concentrations of 75 nmol/L or greater in 97.5% of breastfed infants by 3 months of age. This higher target of 75 to 150 nmol/L (30-60 ng/mL) is the recommended range set by paediatric societies in the United States and Canada . However the Institute of Medicine's health policy recommends a lower range of 40 and 50 nmol/L (16-20 ng/mL) to support bone health.
By 3 months, the following results were reported:
• 55% (95% CI, 38%-72%) of infants in the 400-IU/d group achieved a 25(OH)D concentration of 75 nmol/L or greater vs 81%(95% CI, 65%-91%) in the 800-IU/d group, 92% (95% CI, 77%-98%) in the 1200-IU/d group, and 100% in the 1600-IU/d group.
• The 1600-IU/d dosage was discontinued prematurely because of elevated plasma 25(OH)D concentrations.
• The percentage of infants at 6, 9, and 12 months who met or exceeded the target cutoff of 75 nmol/L of 25(OH)D declined with time.
• Growth and bone mineral content did not differ by dosage.The authors concluded that only the 1600-IU/d dosage of vitamin D met the 25(OH)D concentration target of 75 nmol/L or greater. However, it also led to plasma 25(OH)D concentrations that exceeded the healthy population target range of 50 to 125 nmol/L. Furthermore, dosages of vitamin D exceeding 400 IU/d did not provide additional benefits for bone mineral accretion up to 1 year of age.
The authors note that the study was not representative of the general population because the sample mainly consisted of well-educated, high-income mothers, and baseline plasma 25(OH)D concentrations at 1 month of age were robust (average of 59 nmol/L). Furthermore the sample was underrepresented in participants with darker skin pigmentation, who are at higher risk of deficiency and the study was too short to assess for bone health benefit.
Despite these limitations, the study provides important dose-response information and noted that higher doses of vitamin D are toxic and do not lead to improved bone outcomes. Pending further clinical trial data, the author of a related editorial concludes that these study findings provide reassurance that a “daily vitamin D intake of 400 IU/d in infants, as currently recommended, leads to adequate plasma 25(OH)D concentration for identified physiological functioning related to bone health.”
In the UK, the Department of Health recommends vitamin D supplementation in the following paediatric groups:
• all infants and young children aged 6 months to 5 years to help them meet the set requirement of 7-8.5 micrograms (280-340 IU) of vitamin D per day.
• Formula fed infants who are receiving less than 500ml of infant formula a day
• Breastfed infants from one month of age if their mother has not taken vitamin D supplements throughout pregnancy.