High-Dose Vitamin D Helps Malnourished Kids Make Health Gains

Pam Harrison

May 09, 2018

Administration of two doses of vitamin D3 given along with standardized ready-to-use therapeutic food significantly and safely enhances both weight gain and developmental milestones in severely malnourished children compared with ready-to-use therapeutic food alone, results from the first study of its kind indicate.

"High-dose vitamin D significantly boosted weight gain in malnourished children," lead author Javeria Saleem, MD, Punjab University, Lahore, Pakistan, and Queen Mary University, London, UK, said in a statement.

"This could be a game-changer in the management of severe acute malnutrition, which affects 20 million children worldwide," he added. The study was published May 2 in the American Journal of Clinical Nutrition.

Extra Vitamin D Affected Weight

Saleem and colleagues explain that vitamin D deficiency is common in children with severe acute malnutrition, in whom it is associated with severe wasting. "Ready-to-use therapeutic food (the standard treatment) contains modest amounts of vitamin D that do not reliably correct deficiency," they observe.

So they set out to determine whether high-dose oral vitamin D3 enhances weight gain and development in children with uncomplicated severe acute malnutrition.

A total of 185 severely malnourished children, mean age 15.4 months, were randomized to 8 weeks of energy-dense, micronutrient-enriched paste given in separate food sachets. Mean weight at baseline was 5.5 kg and mean weight-for-height z score was -3.9.

Ninety-two of the children assigned to the intervention also received two, 200,000 IU doses of vitamin D3 administrated via a plastic syringe at 2 and 4 weeks following initiation of the ready-to-use therapeutic food intervention. The remainder received placebo.

"High-dose vitamin D3 did not influence the proportion of children gaining > 15% of baseline weight at the end of the study," the primary endpoint.

But the mean weight-for-height z score, along with mean weight at 8 weeks following initiation of the therapeutic food intervention strategy, were both significantly higher in children assigned to additional vitamin D3, they add.

Adjusted for baseline differences, the mean difference in the weight-for-height z score for children in the additional vitamin D3 arm at 8 weeks was 7% higher than it was for children in the therapeutic food alone arm, at a hazard ratio (HR) of 1.07 (P < .001).

Similarly, the mean difference in weight, again adjusted for baseline differences, was 0.26 kg in favor of the additional vitamin D3 arm compared with the therapeutic food alone arm (P = .001), investigators add.

First Study to Show Vitamin D Impacts Brain Development

Importantly, high-dose vitamin D3 also reduced the proportion of children with delayed global development at 8 weeks by 51% (HR, 0.49; P = .002); delayed gross motor development by 71% (HR, 0.29; P = .002); delayed fine motor development by 41% (HR, 0.59; P = .018), and delayed language development by 43% (HR, 0.57; P = .036) compared with the therapeutic food alone arm.

As noted by senior author Adrian Martineau, MD, also of Queen Mary University, this is the first trial to demonstrate that vitamin D3 can affect brain development, "lending weight to the idea that vitamin D has important effects on the central nervous system," he pointed out in the statement.

No adverse reactions were reported in the supplemental vitamin arm.

Not surprisingly, mean serum 25-hydroxyvitamin D [25(OH)D] concentrations were significantly higher, at 99.4 nmol/L, in children who received additional vitamin D3 compared with 46.6 nmol/L in children who did not (P < 0.001), the researchers add.

They reiterate that while ready-to-use therapeutic food does contain some vitamin D, at a dose of 600 IU per sachet, this is not enough to lead to consistently elevated circulating 25(OH)D concentrations and offset the high prevalence of vitamin D deficiency seen in severely malnourished children.

"Taken together, our findings suggest that the vitamin D content of current ready-to-use therapeutic food is not optimal for supporting weight gain and development in children with severe acute malnutrition, at least in the population that we studied," they indicate.

"Further trials in other settings are now needed to see whether our findings can be reproduced elsewhere," they note.

They are also planning a larger trial in Pakistan to see whether the same high-dose vitamin D3 approach might reduce mortality in severely malnourished children.

The study was funded by the Higher Education Commission of Pakistan. The authors have reported no relevant financial relationships.

Am J Clin Nutr. 2018;107:725-733. Abstract

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