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Does vitamin D supplementation reduce asthma exacerbations?
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 (TABLE1-6).
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 steroids7 included 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).
Continue to: RECOMMENDATIONS
RECOMMENDATIONS
No published guidelines discuss using vitamin D in managing asthma. An American Academy of Family Physicians (AAFP) summary of the Cochrane systematic review recommends that family physicians await further studies and updated guidelines before recommending vitamin D for patients with asthma.12 The AAFP also points out that the Endocrine Society has recommended vitamin D supplementation for adults (1500-2000 IU/d) and children (at least 1000 IU/d) at risk for deficiency.
Editor's takeaway
In the meta-analyses highlighted here, researchers evaluated asthma patients with a wide range of ages, baseline vitamin D levels, and vitamin D supplementation protocols. Although vitamin D reduced asthma exacerbations requiring steroids overall, the effect was driven by 3 studies of patients with low baseline vitamin D levels. As a result, disentangling who might benefit the most remains a challenge. The conservative course for now is to manage asthma according to current guidelines and supplement vitamin D in patients at risk for, or with known, deficiency.
, , , . 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.
, , , 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.
, , , et al. Vitamin D supplementation in children may prevent asthma exacerbation triggered by acute respiratory infection. J Allergy Clin Immunol. 2011;127:1294-1296.
, , , 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.
, , , 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.
, , , 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.
, , , 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.
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 (TABLE1-6).
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 steroids7 included 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).
Continue to: RECOMMENDATIONS
RECOMMENDATIONS
No published guidelines discuss using vitamin D in managing asthma. An American Academy of Family Physicians (AAFP) summary of the Cochrane systematic review recommends that family physicians await further studies and updated guidelines before recommending vitamin D for patients with asthma.12 The AAFP also points out that the Endocrine Society has recommended vitamin D supplementation for adults (1500-2000 IU/d) and children (at least 1000 IU/d) at risk for deficiency.
Editor's takeaway
In the meta-analyses highlighted here, researchers evaluated asthma patients with a wide range of ages, baseline vitamin D levels, and vitamin D supplementation protocols. Although vitamin D reduced asthma exacerbations requiring steroids overall, the effect was driven by 3 studies of patients with low baseline vitamin D levels. As a result, disentangling who might benefit the most remains a challenge. The conservative course for now is to manage asthma according to current guidelines and supplement vitamin D in patients at risk for, or with known, deficiency.
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 (TABLE1-6).
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 steroids7 included 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).
Continue to: RECOMMENDATIONS
RECOMMENDATIONS
No published guidelines discuss using vitamin D in managing asthma. An American Academy of Family Physicians (AAFP) summary of the Cochrane systematic review recommends that family physicians await further studies and updated guidelines before recommending vitamin D for patients with asthma.12 The AAFP also points out that the Endocrine Society has recommended vitamin D supplementation for adults (1500-2000 IU/d) and children (at least 1000 IU/d) at risk for deficiency.
Editor's takeaway
In the meta-analyses highlighted here, researchers evaluated asthma patients with a wide range of ages, baseline vitamin D levels, and vitamin D supplementation protocols. Although vitamin D reduced asthma exacerbations requiring steroids overall, the effect was driven by 3 studies of patients with low baseline vitamin D levels. As a result, disentangling who might benefit the most remains a challenge. The conservative course for now is to manage asthma according to current guidelines and supplement vitamin D in patients at risk for, or with known, deficiency.
, , , . 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.
, , , 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.
, , , et al. Vitamin D supplementation in children may prevent asthma exacerbation triggered by acute respiratory infection. J Allergy Clin Immunol. 2011;127:1294-1296.
, , , 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.
, , , 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.
, , , 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.
, , , 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.
, , , . 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.
, , , 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.
, , , et al. Vitamin D supplementation in children may prevent asthma exacerbation triggered by acute respiratory infection. J Allergy Clin Immunol. 2011;127:1294-1296.
, , , 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.
, , , 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.
, , , 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.
, , , 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.
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).
