A daily vitamin D dose of 400 IU was enough for breast-fed infants to reach the plasma concentration recommended by several clinical associations.

Very nearly 100% of the infants in a randomized trial who took 400 IU attained the 50-nmol/L target for 25-hydroxyvitamin D (25(OH)D). All infants who took a daily dose of 800 IU or 1,200 IU also met that goal, although those babies didn’t gain any additional bone health benefits over the 400-IU group, Hope Weiler, Ph.D., and her colleagues wrote in the May 1 issue of JAMA (JAMA 2013;309:1785-92).

In a press briefing, Dr. Weiler, of the McGill University School of Dietetics and Human Nutrition, Montreal, said she and her coinvestigators undertook the study for two reasons: Six different clinical associations each recommend a different daily dose of the vitamin, and there are no clear data on what plasma level confers maximum health benefits while posing the smallest risk to infants.

"What we were lacking is an understanding of that relationship between how much is consumed and how much is in the blood, and whether that is enough to help them grow in a healthy manner," she said. "We know that very low levels [of 25(OH)D] are associated with rickets, and we have good evidence that you don’t want levels to go below 30 nmol/L."

Some studies, however, had found rickets associated with 25(OH)D levels as high as 50 nmol/L. This evidence spread has led to the divergent dosing recommendations, calling for as little as 200 IU/day to as much as 1,600 IU/day.

The American Academy of Pediatrics recommends a level of 200 IU/day. Health Canada recommends 400 IU/day, and the Canadian Paediatric Society recommends 400-800 IU/day. The AAP and CPS also recommend aiming for a plasma concentration of 75 nmol/L, "but this is based on findings in adults and older children," Dr. Weiler said. "We wanted to find out if this was a good fit for infants, too."

The study’s primary goal was to find the vitamin D dosage that would achieve a 75-nmol/L level in more than 97% of infants. A secondary goal was to find a dosage that would result in a level of at least 50 nmol/L.

The trial randomized 132 breast-fed, 1-month-old infants to a vitamin D supplement of 400, 800, 1,200 or 1,600 IU/day. The babies were assessed at 2, 3, 6, 9, and 12 months.

The mothers were an average of 33 years; 85% were white. Most of the babies (58%) were born between October and April, months when sunlight is limited in Canada.

At 3 and 6 months, nearly 100% of infants taking the 1,600-IU dose fulfilled the primary endpoint of a 97% response rate for 75 nmol/L. By 6 and 12 months, however, the response rates were about 90%. In fact, all of the response rates declined over the study period.

There was a clear dose-dependent response in the other groups. At 3 months, compared with infants taking 400 IU/day, those taking 800 IU were 3.5 times as likely to hit the target of 75 nmol/L, and those taking 1,200 IU were almost 10 times as likely to hit the target.

Nearly 100% of all groups, however, hit the 50-nmol/L target, and the response was sustained at each assessment throughout the study.

The 25(OH)D concentrations peaked at 3 months in every group. At that time, the mean concentrations were 78 nmol/L in the 400-IU group, 102 nmol/L in the 800-IU group, 134 nmol/L in the 1,200-IU group, and 180 nmol/L in the 1,600-IU group. Several infants had levels of more than 200 nmol/L – a level generally considered to increase the risk of hypercalcemia.

The 1,600-IU dosage "was discontinued because most infants in that group developed elevated plasma 25(OH)D concentrations that have been associated with hypercalcemia," Dr. Weiler and her coauthors noted in the paper. However, additional safety testing on these infants showed no signs of the disorder, she added. Dual-energy x-ray absorptiometry scans at each assessment showed that infants in each group were growing well, with no significant between-group differences in bone mineral content or bone density.

"The 400-IU dose was quite satisfactory to meet the plasma concentration recommended by the Institute of Medicine, Canadian Paediatric Association, and the American Academy of Pediatrics," Dr. Weiler said during the briefing. But there are still unanswered questions, she added.

"We’ve been able to link up how much vitamin D gets us the response we want in vitamin D stores in the body, but how high should those stores be, not only for bone health, but for other processes, like immune regulation? We also had a mostly white, well-educated group, so we need to focus now on mothers and infants with darker skin who are at a higher risk of deficiency."

The Canadian Institutes of Health Research funded the study. Dr. Weiler declared no financial relationships.

msullivan@frontlinemedcom.com

Small vitamin D dose hits the plasma target