Researchers in Canada suggest that vitamin D supplementation of 1,600 IU per day increased plasma 25-hydroxyvitamin D concentrations to at least 75 nmol/L among 97.5% of infants aged 3 months. However, this dosage also increased concentrations associated with hypocalcemia, according to data.

The literature has established that vitamin D supplementation for infants is required to support healthy bone mineral accretion. However, conflicting recommendations for this patient population have led to further research.

“We have generated strong support using evidence-based dose response studies that the 400 IU dosage is quite satisfactory and that this is recommended now by the Institute of Medicine, Health Canada, Canadian Pediatric Society and the American Academy of Pediatrics,” researcher Hope Weiler, RD, PhD, of the School of Dietetics and Human Nutrition at McGill University in Quebec, said during a media telebriefing. “We also know that the higher dose recommended by the Canadian Pediatrics Society was well received by our infants and did generate a nice response in 25-hydroxyvitamin D, and the upper limits of 1,000 IU and 1,200 IU would be suitable as safety markers across the first year of life.”

According to data from a double blind, randomized study published in JAMA, Weiler and colleagues investigated the efficacy of various dosages of vitamin D supplements in supporting plasma 25-(OH)D concentrations in healthy, breast-fed infants (n=132) aged 1 month. The patients were randomly assigned to oral cholecalciferol (vitamin D3) supplements of 400 IU per day (n=39), 800 IU per day (n=39), 1,200 IU per day (n=38) or 1,600 IU per day (n=16), and they were followed for 11 months.

According to 3-month data, 55% (95% CI, 38-72) of infants in the 400-IU group demonstrated a 25-(OH)D concentration of at least 75 nmol/L vs. 81% (95% CI, 65-91) in the 800-IU group, 92% (95% CI, 77-98) in the 1,200-IU group and 100% in the 1,600-IU group. Due to elevations in 25-(OH)D concentrations, the 1,600 IU dosage was discontinued, researchers wrote. Moreover, the concentration did not continue in 97.5% of the infants at age 12 months in any of the groups.

Further data indicate that all dosages established 25-(OH)D concentrations of at least 50 nmol/L among 97% (95% CI, 94-100) of the infants at 3 months. This continued in 98% (95% CI, 94-100) at 12 months, the researchers wrote.

“Future studies should be larger and, hopefully, be able to detect early, as well as [determine], long-term benefits to bone. We may also consider other health benefits such as the immune system. Our future studies should consider other populations,” Weiler said. “We should also consider those at higher risk for deficiency, whether it’s due to geographic location where a mother’s exposure to sunshine is limited or the infant is born with vitamin D deficiency.”

In an accompanying editorial, Steven A. Abrams, MD, of the department of pediatrics at the US Department of Agriculture/Agricultural Research Service Children’s Nutrition Research Center at Baylor College of Medicine and Texas Children’s Hospital in Houston, said the study did not answer the question of what the target should be for plasma 25-(OH)D concentrations.

“Of importance, higher vitamin D dosages in this study did not lead to improved bone outcomes as reflected by DXA results for bone mineral content,” Abrams wrote.

He suggested that higher vitamin D intake and target plasma 25-(OH)D concentrations should be tested in clinical trials with markedly defined outcomes and precise safety monitoring.

Weiler H. JAMA. Theme Issue on Child Health: New research on the optimal dosing and possible adverse effects of different levels of vitamin D supplementation, important for bone health, for infants. Presented at: the JAMA Network 2013 Media Briefing; April 30, 2013; New York.

Disclosure: Abrams reports payment for lectures’/speakers’ bureaus from Mead-Johnson Nutrition and Abbott Nutrition and grants to his institution from Mead-Johnson Nutrition. Gallo reports travel support from CIHR Human Development Child and Youth Health and the American Society for Bone and Mineral Research. Sharma reports consulting fees for analyses prepared for Rodd and Weiler. Jones reports being cofounder and scientific advisory board member for Cytochroma Inc., and for receiving payment for speakers’ bureaus from Genzyme/Sanofi.

PERSPECTIVE

• I  think it’s a helpful study in terms of the fact that they had different groups of newborn children treated with vitamin D with 400 IU being the recommended dose up to 12 months according to the Institute of Medicine and Endocrine Society guidelines. It was a well-designed study and relevant because vitamin D is a very hot topic right now due to the deficiencies in children and adults.

I agree with the editorial. This group of patients was a mostly white group with relatively high socioeconomic status. In the group that was administered 400 IU per day, researchers found that those infants reached 25(OH)D level of at least 20 ng/mL. That is a big debate. The IOM thinks 25(OH)D levels of 20 ng/mL are adequate for most, and I think a lot of endocrinologists and the Endocrine Society says most people need a level of 30 ng/mL.

This study shows that infants who were administered up to 400 IU per day reached a level of at least 20 ng/mL by 3 months. The whole group did not attain the level of 30 ng/mL, which again is what some endocrinologists think is an optimal level. To achieve a level of 30 ng/mL, perhaps 400 IU is not enough per day for some infants (especially those with darker skin pigmentation or at higher risk for deficiencies).

In addition to looking at the levels or how much vitamin D is needed to achieve a level of 20 ng/mL or 30 ng/mL, they also looked at the bone mineral content but found no significant difference in the groups. I think the editorial comment summed up this point. In treating infants with higher doses of vitamin D corresponding to higher serum levels above 30 ng/mL; does that confer other benefits? There are many early studies now looking at the relationship between vitamin D and asthma, food allergies, incidence of type 1 diabetes and autoimmune disease.

The important point Abrams raises is that we need more long-term studies to see if there is a skeletal benefit in terms of having a higher vitamin D level which would correspond to having a higher dose of vitamin D administered.

• Dominique Noё Long, MD
• Instructor of pediatric endocrinology
  The Johns Hopkins Children’s Center
  Baltimore, Md.

PERSPECTIVE

• The strengths and usefulness of the study are the quantification of serum 25-OH vitamin D levels with various doses of vitamin D supplementation. The currently recommended dose of vitamin D, 400 IU daily, was chosen because historically this dose has proven to prevent rickets, which as pediatric endocrinologists, is our main objective. Therefore this study helps provide information in the ongoing debate regarding the optimal serum level of 25(OH) D. Interestingly, all doses of cholecalciferol increased serum levels of 25(OH) D to >50 nmol/L. Higher doses of cholecalciferol correlated with higher levels of 25(OH) D, however no group sustained >97.5% of infants to vitamin D levels >75 nmol/L. No one truly knows the ideal serum level of vitamin D, but this study suggests that >50 nmol/L was sufficient in this patient population. This study also provides information on the safety of higher doses of vitamin D supplementation. It may be harder to extrapolate in the darker-skin pigmented population who may need more vs. the white population. It’s just another piece to the puzzle of the debate on vitamin D.
• Janet Crane, MD
• Clinical research fellow in pediatric endocrinology
  The Johns Hopkins Children’s Center
  Baltimore, Md.