Does vitamin D supplementation reduce asthma exacerbations?

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Clinical Inquiries

Does vitamin D supplementation reduce asthma exacerbations?

J Fam Pract. 2020 May;69(4):E4-E6

By

Jaspreet Jaura, MD

Gary Kelsberg, MD

Sarah Safranek, MLIS

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EVIDENCE-BASED ANSWER:

Yes, to some extent it does, and primarily in patients with low vitamin D levels. Supplementation reduces asthma exacerbations requiring systemic steroids by 30% overall in adults and children with mild-to-moderate asthma (number needed to treat [NNT] = 7.7). The outcome is driven by the effect in patients with vitamin D levels < 25 nmol/L (NNT = 4.3), however; supplementation doesn’t decrease exacerbations in patients with higher levels. Supplementation also reduces, by a smaller amount (NNT = 26.3), the odds of exacerbations requiring emergency department care or hospitalization (strength of recommendation [SOR]: A, meta-analysis of randomized controlled trials [RCTs]).

In children, vitamin D supplementation may also reduce exacerbations and improve symptom scores (SOR: C, low-quality RCTs).

Vitamin D doesn’t improve forced expiratory volume in 1 second (FEV₁) or standardized asthma control test scores. Also, it isn’t associated with serious adverse effects (SOR: A, meta-analysis of RCTs).

References

1. Martineau AR, Cates CJ, Urashima M, et al. Vitamin D for the management of asthma. Cochrane Database Syst Rev. 2016;9:CD011511.

2. Jensen M, Mailhot G, Alos N, et al. Vitamin D intervention in preschoolers with viral-induced asthma (DIVA): a pilot randomised controlled trial. Trials. 2016;26:17:353.

3. Majak P, Jerzyiska J, Smejda K, et al. Correlation of vitamin D with Foxp3 induction and steroid-sparing effect of immunotherapy in asthmatic children. Ann Allergy Asthma Immunol. 2012;109:329-335.

4. Majak P, Olszowiec-Chlebna M, Smejda K, et al. Vitamin D supplementation in children may prevent asthma exacerbation triggered by acute respiratory infection. J Allergy Clin Immunol. 2011;127:1294-1296.

5. Tachimoto H, Mezawa H, Segawa T, et al. Improved control of childhood asthma with low-dose, short-term vitamin D supplementation: a randomized, double-blind, placebo-controlled trial. Allergy. 2016;71:1001-1009.

6. Urashima M, Segawa T, Okazaki M, et al. Randomized trial of vitamin D supplementation to prevent seasonal influenza A in school children. Am J Clin Nutr. 2010;91:1255-1260.

7. Joliffe DA, Greenberg L, Hooper RL, et al. Vitamin D supplementation to prevent asthma exacerbations: a systematic review and meta-analysis of individual participant data. Lancet 2017;5:881-890.

8. Kerley CP, Hutchinson K, Cormical L, et al. Vitamin D3 for uncontrolled childhood asthma: a pilot study. Pediatr Allergy Immunol. 2016;27:404-412.

9. Castro M, King TS, Kunselman SJ, et al. Effect of vitamin D3 on asthma treatment failures in adults with symptomatic asthma and lower vitamin D levels: the VIDA randomized clinical trial. JAMA. 2014;311:2083-2091.

10. Martineau AR, MacLaughlin BD, Hooper RL, et al. Double-blind multi-centre randomised controlled trial of vitamin D3 supplementation in adults with inhaled corticosteroid-treated asthma (ViDiAs). Thorax. 2015:70:451-457.

11. Riverin B, Maguire J, Li P. Vitamin D supplementation for childhood asthma: a systematic review and meta-analysis. PLOS One. 2015;10:e0136841.

12. Qiu J. Vitamin D for the management of asthma. Am Fam Phys . 2017;96:290-293.

EVIDENCE SUMMARY

A Cochrane systematic review of vitamin D for managing asthma performed meta-analyses on RCTs that evaluated several outcomes.¹ The review found improvement in the primary outcome of asthma exacerbations requiring systemic steroids, mainly in adult patients, and in the secondary outcomes of emergency department visits or hospitalization, in a mix of adults and children (TABLE^1-6).

Most participants had mild-to-moderate asthma; trials lasted 4 to 12 months. Vitamin D dosage regimens varied, with a median daily dose of 900 IU/d (range, 400-4000 IU/d). Six RCTs were rated high-quality, and 1 had unclear risk of bias.

Supplementation reduced exacerbations in patients with low vitamin D levels

A subsequent (2017) systematic review and meta-analysis evaluating the primary outcome of exacerbations requiring steroids⁷included another study⁸ (in addition to the 6 RCTs in the Cochrane review).

When researchers reanalyzed individual participant data from the trials in the Cochrane review, plus the additional RCT, to include baseline vitamin D levels, they found that vitamin D supplementation reduced exacerbations overall (NNT = 7.7) and in patients with low baseline vitamin D levels (25[OH] vitamin D < 25 nmol/L; 92 participants in 3 RCTs; NNT = 4.3) but not in patients with higher baseline levels (764 participants in 6 RCTs). Vitamin D supplementation reduced the asthma exacerbation rate in patients with low baseline vitamin D levels (0.19 vs 0.42 events per participant-year; P = .046).

Smaller benefit found on ED visits and hospitalizations

The Cochrane review, with 2 RCTs with adults (n = 658)¹ and 5 RCTs with children (n = 305),^2-6 evaluated whether Vitamin D reduced the need for emergency department visits and hospitalization with asthma exacerbations; they found a smaller benefit (NNT = 26.3).

Effects on FEV₁, daily asthma symptoms, and serious adverse effects

Several RCTs included in the 2017 meta-analysis found no effect of vitamin D supplementation on FEV₁, daily asthma symptoms (evaluated with the standardized Asthma Control Test Score), or reported serious adverse events.^2-6,9,10 No deaths occurred in any trial.

Additional findings in children from lower-quality studies

A 2015 systematic review and meta-analysis of RCTs evaluating vitamin D supplementation for children with asthma found¹¹:

moderate-quality evidence for decreased emergency department visits (1 RCT from India, 100 children ages 3 to 14 years, decrease not specified; P = .015);
low-quality evidence for reduced exacerbations (6 RCTs [3 RCTs also in Cochrane review], 507 children ages 3 to 17 years; risk ratio = 0.41; 95% confidence interval, 0.27-0.63); and
low-quality evidence for reduced standardized asthma symptom scores (6 RCTs [2 RCTs also in Cochrane review], 231 children ages 3 to 17 years; amount of reduction not listed; P = .01).

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Evidence-based answers from the Family Physicians Inquiries Network

Does vitamin D supplementation reduce asthma exacerbations?

EVIDENCE-BASED ANSWER:

References

EVIDENCE SUMMARY

Supplementation reduced exacerbations in patients with low vitamin D levels

Smaller benefit found on ED visits and hospitalizations

Effects on FEV1, daily asthma symptoms, and serious adverse effects

Additional findings in children from lower-quality studies

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Effects on FEV₁, daily asthma symptoms, and serious adverse effects