Vitamin D supplementation fails to improve asthma control, reduce asthma exacerbations
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Vitamin D supplements did not reduce asthma exacerbations or improve asthma control among adults or children, according to an updated Cochrane review, contradicting an earlier review showing benefits of supplementation.
But the review did not find any harm in taking vitamin D either, nor did it address any other possible health benefits, according to Adrian R. Martineau, DTM&H, PhD, clinical professor of respiratory infection and immunity at Barts and the London School of Medicine and Dentistry, Queen Mary University of London, and colleagues.
A previous Cochrane review on the topic reported a protective effect, but since its publication several trials reported null findings, indicating the need for an updated review, Martineau told Healio.
“The original review was prompted by positive findings of several randomized controlled trials of vitamin D to reduce asthma exacerbation risk,” Martineau said, “which were in turn prompted by lab data suggesting favorable immunomodulatory activities of vitamin D supporting innate antiviral responses and regulating inflammation and observational studies reporting associations between lower vitamin D status and increased exacerbation risk in people with asthma.”
The 2016 review included nine trials and 1,093 patients, whereas the update included 15 trials of 1,155 children and five trials of 1,070 adults (age range, 1-84 years). Most of these individuals had mild to moderate asthma.
At baseline, profound vitamin D deficiency defined as less than 25 nmol/L of 25-hydroxyvitamin D (25(OH)D) was rare, with mean/median serum concentrations ranging from 28 nmol/L to 89 nmol/L across studies.
Review findings
High-quality evidence from 14 studies (n = 1,778) showed that the proportion of patients who experienced one or more asthma exacerbations treated with systemic corticosteroids did not increase or decrease with administration of vitamin D or its hydroxylated metabolites (OR = 1.04; 95% CI, 0.81-1.34; I2 = 0%).
These findings correspond with an absolute risk of 226 per 1,000 individuals (95% CI, 185-273) in the pooled vitamin D group from a baseline risk of 219 per 1,000 individuals in the pooled placebo group.
Vitamin D supplementation also did not have any effect on the rate of exacerbations that required systemic corticosteroids in 10 studies (n =1,599; RR = 0.86; 95% CI, 0.62-1.19; I2 = 60%), nor did it have any effect on time to first exacerbation in three studies ( n = 850; HR = 0.82; 95% CI, 0.59-1.15; I2 = 22%), with both of these findings based on high-quality evidence.
Researchers found no evidence of any effect modification by baseline vitamin D status, vitamin D dose, frequency of dosing regimen or age.
Most of the individuals in the trials took cholecalciferol, which is the form used in most vitamin D supplements. But one trial (n = 112) that used calcidiol, which is a compound that the body makes from vitamin D, showed a reduced rate of exacerbations with supplementation (RR = 0.43; 95% CI, 0.22-0.82; I2 = 77%), although with low-quality evidence.
Vitamin D supplementation also had no effect on the incidence of serious adverse events in 12 studies with high-quality evidence (n = 1,556; OR = 0.89; 95% CI, 0.56-1.41; I2 = 0%), with its effect on fatal asthma exacerbations not estimable, with no such events reported in any trial.
Adverse reactions potentially attributable to vitamin D including hypercalciuria, hypervitaminosis D, kidney stones, gastrointestinal symptoms and mild itch happened across treatment and control arms.
Conclusions, next steps
“Key findings were null results across the board, contrasting with protective effects against severe exacerbation shown in the previous review,” Martineau said.
The studies in the review did not include many people with severe asthma or people with very low levels of vitamin D in their blood, however, so more research is needed in these areas, according to the researchers.
The positive results from the single study involving calcidiol suggest another area deserving study, the researchers continued.
The researchers suggested that people with asthma may be getting better treatment now than they were in the earlier review, or that vitamin D deficiency rates have fallen with increases in supplements and fortified foods, both of which could obscure the potential benefits that supplements offer.
Still, the findings have implications for care, Martineau said.
“Technically, doctors who had been prescribing vitamin D solely to reduce asthma exacerbations could stop doing so on basis of these null results. However, vitamin D is also often given to patients with asthma who are taking inhaled or systemic corticosteroids in order to preserve bone mineral density,” Martineau said.
Martineau noted that the review did not address the effects of vitamin D on bone.
“If this is the indication for vitamin D, then it should not be discontinued,” Martineau said. “We showed that vitamin D was safe in asthma patients, so there is no question of supplementation causing harm here.”
References:
Cochrane Review finds that vitamin D does not reduce risk of asthma attacks. https://www.cochrane.org/news/cochrane-review-finds-vitamin-d-does-not-reduce-risk-asthma-attacks#:~:text=Taking%20vitamin%20D%20supplements%20does,in%20people%20taking%20vitamin%20D. Published Feb. 5, 2023. Accessed Feb. 6, 2023.
Martineau AR, et al. Cochrane Database Syst Rev. 2016;doi:10.1002/14651858.CD011511.pub2.
For more information:
Adrian R. Martineau, DTM&H, PhD, can be reached at a.martineau@qmul.ac.uk.
Perspective
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The findings are significant, as they represent a well-conducted meta-analysis of previously conducted trials on vitamin D for asthma. The findings indicate no benefit of vitamin D on a variety of asthma outcomes. This is important as vitamin D treatment in asthmatic patients with and without vitamin D deficiency has been debated as a viable therapy.
We generally have not seen any strong effect of vitamin D treatment on asthmatic patients, although we have not formally studied it. We have recently reported a role for vitamin D in eosinophilic esophagitis, primarily preclinical murine modeling.
Importantly, we found that vitamin D deficiency contributed to the severity of EoE-like responses and that vitamin D supplementation was therapeutic only in the setting of vitamin D deficiency. As such, the current studies are limited in that they did not focus on vitamin D-deficient patients.
Doctors can use these findings to improve care by not placing patients on vitamin D supplementation as a routine measure for asthma management.
Next steps would be to do a prospective study on asthmatic patients with severe vitamin D deficiency at baseline. Also, additional prospective trials with the vitamin D metabolite calcidiol, which seemed promising in one article reviewed, could be conducted.
Reference:
Brusilovsky M, et al. Gut. 2022;doi:10.1136/gutjnl-2022-327276.
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