Free Vitamin D3 Inferior to Total Concentrations in Predicting Asthma Response

blood sample in gloved hand
blood sample in gloved hand
No associations were found between free concentration vitamin D3 levels and treatment failure or exacerbation rates in adults with asthma

The results of an analysis of data from the VIDA trial (Study of the Effect of Vitamin D as an Add-on Therapy to Corticosteroids in Asthma; Identifier: NCT01248065) published in the Annals of Allergy, Asthma, & Immunology found no associations between free concentration (Cf ) vitamin D3 levels and rates of treatment failure or exacerbations in adults with asthma. 

John J. Lima, PharmD, of Nemours Children’s Health System in Jacksonville, Florida, and colleagues explored the relationship between vitamin D and the outcomes of the VIDA trial to determine the associations between Cf vitamin D3 and treatment failure during a reduction of inhaled corticosteroids (ICS) in VIDA participants.

Vitamin D status (vitamins D2 and D3) is determined by circulating total concentrations (Ctot) of vitamin D3 but not concentrations of active 1,25-dihydroxyvitamin D3. Serum concentrations of vitamin D3 ≥30 ng/mL are required for the skeletal actions of vitamin D and concentrations ≥50 ng/mL are necessary for the extraskeletal pleiotropic effects of vitamin D. However, serum concentrations of vitamin D3 may not be an accurate measure of vitamin D status because of uncertainties concerning the methods of measuring Ctot concentrations of vitamin D3. Genetic variations have shown significant differences in Ctot vitamin D3 concentrations in certain ethnic populations, including individuals with substantial African ancestry, such as African Americans and some Hispanic groups, compared with individuals of European descent.

Determining the relationship between this vitamin and asthma is important, however, because hypovitaminosis D has been associated with an increased risk for asthma, reduced lung function, increased airway responsiveness, asthma exacerbations, and a reduced response to glucocorticoids in individuals with asthma.

The primary finding of this analysis demonstrated that there is no association between Cf or changes in Cf and the outcomes following vitamin D3 supplementation. However, the investigators noted that this is not consistent with the previous VIDA finding that vitamin D supplementation improved the efficacy of inhaled corticosteroids when participants achieved levels ≥30 ng/mL. The researchers did not anticipate the inconsistency between Cf and Ctot level associations with response outcomes, particularly in view of the strong relationship between Cf and Ctot and the predictions of the Cf  hormone hypothesis that only Cf  concentrations of vitamin D3 diffuse across the cell membrane and undergo metabolism to 1,25-dihydroxyvitamin D3, which activates the vitamin D receptor.

In addition, the investigators noted that this observation is not congruent with others that reported that Cf levels are more closely associated with skeletal markers, atopy, and lung function in children with asthma than Ctot levels. Cf concentrations of vitamin D3 were in fact inferior to Ctot concentrations in predicting responsiveness to vitamin D supplementation in the VIDA trial, the researchers concluded.

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The investigators argued that their results justify further studies to investigate the relationship between Cf  and Ctot vitamin D concentrations as biomarkers of skeletal and extraskeletal actions of vitamin D supplementation in patients with asthma. They also suggested that future studies of vitamin D supplementation in patients with asthma measure both Cf and Ctot levels of vitamin D3.


Lima JJ, Castro M, King TS, et al. Association of free vitamin D3 concentrations and asthma treatment failures in the VIDA trial [published online June 13, 2018]. Ann Allergy Asthma Immunol. doi:10.1016/j.anai.2018.06.001