Several observational studies have linked low serum 25-hydroxyvitamin D (vitamin D) levels to severe asthma exacerbations, lower lung function, and reduced response to corticosteroids. A meta-analysis of clinical trials showed that vitamin D3 supplementation was associated with lower risk of asthma, but the pooled estimate was not significant among children younger than 16. More recently, a comprehensive review of vitamin D3 for the prevention of wheeze attacks found insufficient evidence to recommend vitamin D3 supplementation in children.
Previous paediatric randomised clinical trials have not focused on children with low vitamin D levels or who are at high risk for severe asthma exacerbation. Therefore a team of researchers from the US carried out a trial to test whether supplementation with vitamin D3 would improve the time to a severe exacerbation in high-risk children. They also aimed to discover whether the protective effect would result from reduced viral-induced exacerbations or enhanced response to corticosteroids.
For three years, the Vitamin-D-Kids Asthma (VDKA) Study followed nearly 200 children ages 6 to 16 across seven different U.S. hospital systems. All had at least one asthma attack during the year before the study began.
Half of the participants were randomised to receive 4,000 IU of vitamin D per day, and the other half got placebo pills. No one involved in the study knew which type of pill each participant was getting.
All of the children had vitamin D levels low enough that supplements should have an effect - if vitamin D truly is beneficial for reducing severe asthma attacks - but the study excluded children with severe vitamin D deficiency because it would be unethical to withhold it in those cases.
Their findings, published in JAMA, reveal that, compared to placebo, vitamin D did not reduce the number of asthma attacks participants experienced or their reliance on inhaled steroids.
"The reason that's important is there are colleagues around this country and worldwide who are testing vitamin D levels for kids with asthma and giving them vitamin D," said study lead author Juan C. Celedón, M.D., Dr.P.H., chief of pediatric pulmonary medicine at UPMC Children's Hospital of Pittsburgh. "As a system, it costs a lot of money to run all these tests and give the supplements. We've shown no benefit for children with moderately low vitamin D levels."
The report explains why its findings are different from what was seen in the past with observational studies where children with naturally low vitamin D levels seemed to have worse asthma.
It states: "While observational studies have reported associations between low vitamin D levels and childhood asthma outcomes, randomised clinical trials have provided less encouraging evidence of a protective effect of vitamin D3 supplementation against morbidity from asthma.
"Moreover, both the VDAART (Vitamin D Antenatal Asthma Reduction Trial) and the COPSAC 2010 (Copenhagen Prospective Studies on Asthma in Childhood 2010 cohort) trials have recently reported no significant effect of vitamin D3 supplementation during pregnancy on asthma in the offspring by age 6 years, strongly suggesting that there is no role for such supplementation in the primary prevention of asthma."
Celedón adds: "With observational studies, you never know - is vitamin D causing asthma to be worse or do kids with worse asthma end up having lower vitamin D?"
He acknowledges that he can't draw conclusions about whether very low vitamin D levels contribute to asthma attacks, but he argues that those children would be supplemented either way because of known effects on bone health.
Vitamin D and Asthma severity
Previously observed links between high vitamin D levels and lower asthma exacerbation have been explained by immune-modulatory and anti-inflammatory effects of vitamin D, including regulatory T-cell induction, attenuation of Th2 and Th17 responses, enhancement of IL-10 production, and inhibition of airway smooth muscle hypertrophy and collagen deposition.
Vitamin D may attenuate viral-induced asthma attacks by reducing rhinovirus replication in bronchial epithelium, promoting interferon-mediated antiviral pathways and inducing production of antimicrobial peptides.
Forno, E., et al.
"Effect of Vitamin D3 Supplementation on Severe Asthma Exacerbations in Children With Asthma and Low Vitamin D Levels."