Vitamin D3 supplements improve symptoms in patients with asthma
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Key takeaways:
- Vitamin D3 supplementation was associated with less severe asthma, fewer symptoms, better symptom control and less steroid use.
- Immune responses shift from pro-inflammatory to anti-inflammatory with vitamin D3.
Patients with asthma who used vitamin D3 supplements experienced less severe disease, fewer daytime symptoms and better symptom control, according to research published in The Journal of Allergy and Clinical Immunology: Global.
These patients also needed fewer steroid medications, Janina C. Grund, doctoral candidate in the department of molecular pneumology at University Hospital Erlangen, and colleagues wrote.
“Vitamin D3 has been controversially discussed in the context of asthma. Previous studies already showed correlations between asthma severity and vitamin D3 blood levels, but the exact immunomodulatory mechanisms remained unclear,” Grund told Healio.
The researchers began by investigating the effects of vitamin D3 among children with asthma.
“Based on these previous findings, we aimed to understand exact effects of vitamin D3 on the inflammatory immune response in asthma to set the foundation for further, more specific studies and clear, clinical therapeutical recommendations,” Grund said.
Pediatric results
The European PreDicta study comprised two cohorts including 24 children with asthma and 22 controls aged 4 to 6 years. Participants with asthma were divided into subgroups who did or did not receive vitamin D3 supplements.
“Our adult and pediatric asthma studies are non-prospective cohort-studies,” Grund said. “The exact dose and duration of regular vitamin D3 intake varied within the groups from at least 1,000 IU daily up to 20,000 IU weekly for several months.”
While 80% of the pediatric patients who used supplements reported restraints in their activities and 20% did not, 36.8% of the patients who did not use supplements reported restraints and 63.2% did not.
The researchers expected children on the supplement to have fewer restraints. However, Grund cautioned that these results are based on answers that these children, supported by their parents, provided in the questionnaire, making them difficult to objectify.
“Additionally, this was a yes/no question, so we do not know to what extent they were restricted in their activities,” Grund said. “Also, usual activities among the children cohort might vary. Here, more detailed questions on specific activities and exactly in what way they are restricted will be interesting for further studies.”
The researchers also assessed asthma symptom control via the Global Initiative for Asthma (GINA) 2005 guidelines. Levels of asthma control ranged from uncontrolled (10.53%) to partly controlled (36.84%) and controlled (52.63%) among the children who did not use supplements and from partly controlled (20%) to controlled (80%) among those who did use supplements.
None of the children in the supplement group reported any daily symptoms, although 80% experienced them less than once a week and 20% had them once a week or more. Among the group that did not use supplements, 15.79% reported daily symptoms, 52.63% had symptoms less than once a week and 31.58% had symptoms once a week or more.
Similarly, 60% of the supplement group reported nighttime symptoms less than twice a month, and 40% reported symptoms more than once a week. The group that did not use supplements reported them more than once a week (26.32%), less than twice a month (52.63%) and more than twice a month (21.05%).
Daily steroid use was reported by 84.2% of those who did not use supplements and 60% of those who did.
Additionally, the researchers said they found positive significant correlations between 1.25-OH-vitamin D3 serum levels and higher levels of IL-7 in the supernatants of cultured, unstimulated peripheral blood mononuclear cells (PBMCs). There was an association between high levels of vitamin D3 serum and higher IL-10 mRNA expression in the blood of the children with asthma but not in the control group as well.
In the control group, there was an association between higher vitamin D3 serum levels and higher expression of B lymphocyte-induced maturation protein 1 (Blimp-1), which controls the immune response of T helper cells, in untouched PBMCs as well. Together, the researchers said, these findings indicate an asthma-resolving role for vitamin D3 in this population.
Adult results
Results were similar for the 26 adults with asthma, which included patients who did and did not receive vitamin D3 supplementation, and the 19 controls in the AZCRA study.
For example, 64.3% of the patients who did not use supplements reported restraints in their activities, compared with 45.5% of the patients who used supplements.
Also, GINA 2009 guidelines indicated partly controlled asthma among 63.64% and controlled asthma for 36.36% of the patients on supplements as well as uncontrolled asthma among 21.43%, partly controlled asthma among 57.14% and controlled asthma among 21.43% of the group that did not use supplements.
The supplemental group experienced daytime symptoms daily (27.27%), less than once a week (27.27%) or once a week or more (45.45%). The group that did not use supplements also had daily (28.57%), less than once weekly (21.43%) and once weekly or more (50%) symptoms.
Additionally, 18.18% of the supplemental group never experienced nighttime symptoms, 54.55% had them less than twice a month, 18,18% had them more than once a week and 9.1% had them more than twice a month. Among the group that did not use supplements, 21.43% had them more than once a week, 7.14% had them more than twice a month and 71.42% had them less than twice a month.
Daily steroid use was reported by 92.9% of those who did not use supplements and 54.5% of those who did.
Also, like the PreDicta study, the researchers said the AZCRA study found significant induction of IL-10 in the supernatant of cultured PBMCs among the adults with asthma with 1.25-OH-vitamin D3 stimulation compared with the unstimulated cells of the respective group.
There was a significant correlation between vitamin D receptors and Blimp-1 expression in freshly isolated PBMCs of controls as well, the researchers continued, but not in those of the patients with asthma, supporting he findings of the PreDicta group.
Based on these findings, the researchers said, vitamin D3 supplementation may have an immunosuppressive and resolving function in asthma that may involve the regulation of immune cells via Blimp-1.
Mouse models, conclusions
Additional research involving mice with and without asthma who were fed diets rich or deficient in vitamin D3 found that the vitamin led to less severe cases of asthma in these mice as well. Also, the mice who had diets enriched with vitamin D3 had less IgE.
Higher doses of vitamin D3 triggered anti-inflammatory reactions in the immune system in these mice, the researchers continued, specifically with IL-10 and cells that create Blimp-1. These supplements impacted long-lived memory T cells, which are part of the long-term immune response in asthma, as well.
“We would like to spotlight the regulation of the transcription factor Blimp-1 via vitamin D3 as a key transcription factor in T-lymphocyte and ILC2 fate,” Grund said. “These findings will set the foundation for the reevaluation of potential therapeutical effects also in other inflammatory diseases.”
Considering these human and murine results, the researchers concluded that diets supplemented with vitamin D3 resulted in less severe clinical manifestations of asthma, as the vitamin shifts proinflammatory immune responses to anti-inflammatory ones via the upregulation of Blimp-1.
Also, Grund noted that researchers are still in the beginnings of more detailed studies about vitamin D3 immunomodulatory mechanisms in allergic asthma.
“We now have made a great progress in understanding mechanisms, but we will have to figure out exact dose-related and individual advantages of supplementation,” Grund said.
Doctors should pay attention to adequate vitamin D3 blood levels to prevent any deficiencies, she said.
“To give clear recommendations for doses/duration/regular/temporary supplementation of vitamin D3, we need to enlarge our further studies in study population size to be able to investigate the effect of supplementation,” Grund said. “For example, in different age groups, asthma severity, patients with combined asthma medications, etc.”
Further studies with larger cohorts also could determine if these effects can be found across the spectrum of asthma severity and to clarify which pathways are involved to inform potential therapeutic recommendations, the researchers said.
For more information:
Janina C. Grund can be reached at janina.grund@fau.de.
Perspective
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Adrian R. Martineau, DTM&H, PhD
The essential problem with the findings relating to asthma phenotypes in adults and children relates to the fact that this is an observational study, not a clinical trial. Thus, the authors are comparing people who choose to take vitamin D vs. those who do not, as opposed to comparing outcomes in people who have been randomly assigned to receive vitamin D vs. placebo.
Decisions to take nutritional supplements are tied in with numerous socioeconomic and behavioral factors that can also influence asthma control. As far as I can see, these have not been adjusted for in the analysis, and the socioeconomic/behavioral characteristics of patients who do vs. those who do not take supplements are not presented or compared.
In my view, it is therefore inappropriate to conclude from the data presented that taking vitamin D supplements resulted in improved asthma outcomes in humans, eg, in statements such as “Supplementing VitD3 resulted in amelioration of clinical asthma manifestations in human studies.” The conclusion drawn in the “Clinical Implication” bottom line, “Patients with asthma benefit from VitD3 supplementation,” is also inappropriate. The authors may have demonstrated an association, but this is not necessarily due to causation.
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