NIHR Signal Vitamin D supplements can reduce risk of asthma attacks

Published on 6 December 2016

People with mild to moderate asthma experience fewer severe asthma attacks if they take vitamin D supplements.

This review found that the average number of asthma attacks was equivalent to about one every four years in those taking vitamin D, compared to nearly one every two years in those taking a placebo. Half as many people attended hospital for asthma treatment each year when taking vitamin D (3%) compared with those not taking vitamin D (6%). These reductions were clinically and statistically significant.

There are a few unknowns still. It’s not clear if these results apply to everyone or just those with low levels of vitamin D. Also, these results apply to adults with mild to moderate asthma when taken alongside their usual asthma medication. The effects are less clear for children and those with severe asthma. As the trials used widely varying dosages of vitamin D, the optimum dose is not known.

There is currently no specific guidance for people with asthma on whether to take vitamin D, however they seem to offer the potential for reducing treatment costs.

Vitamin D supplements can reduce risk of asthma attacks

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Why was this study needed?

In the UK, 5.4 million people have asthma. This long-term condition affects children and adults and costs the NHS about £1 billion each year. Asthma attacks can be life-threatening and many people end up being admitted to hospital for treatment.

Vitamin D is an essential nutrient that keeps muscles and bones healthy. It can be obtained from food and made in the skin from exposure to sunlight. About 22% of children over 11 years and adults of all ages have low levels of vitamin D in their blood. This is not the same as having a deficiency, with symptoms, but signifies people at greater risk of developing a deficiency. Public Health England report that low levels of vitamin D are common  and recommends that everyone in the UK (including those without asthma) considers taking a 10microgram dose of vitamin D daily, especially in winter.

This review aimed to get a clearer picture of how vitamin D supplements could help manage asthma symptoms by reviewing the strongest evidence available.

What did this study do?

This was a Cochrane systematic review of nine double-blind, randomised, placebo-controlled trials of 1093 people that measured the effects of vitamin D on asthma. Vitamin D was taken alongside normal asthma treatment for between four and 12 months.

The reviewers pooled the results of similar trials for each outcome.

This was a high quality review and the trials had a low risk of bias. However, there were several differences between the trials, which limit direct applicability. The majority of participants had mild to moderate asthma, with variable regular use of inhaled steroids. Vitamin D doses also varied between trials with some using daily regimes and others monthly injections. Baseline vitamin D levels were not recorded in most trials so we do not know how many people had a deficiency or whether there was a stronger effect for those that did.

What did it find?

  • Vitamin D supplements reduced the average number of asthma attacks requiring oral steroids from 0.44 per year to 0.28 per year (three trials, 22 children and 658 adults). This equates to a reduction from nearly one every two years to about one every four years (rate ratio [RR] 0.63, 95% confidence interval [CI] 0.45 to 0.88).
  • Fewer people taking vitamin D supplements had an asthma attack severe enough that they visited an emergency department or were admitted to hospital or both (odds ratio 0.39, 95% CI 0.19 to 0.78, seven trials, 307 children, 658 adults). Over a period of eight months, vitamin D reduced the rate from 6 in 100 people to 3 in 100 people (95% CI 1 to 5). Results were mostly based on adults as there were few events in the child trials.
  • Lung function and daily symptoms were unchanged by vitamin D supplements.
  • Vitamin D did not cause any increase in serious adverse events.

What does current guidance say on this issue?

The British Thoracic Society 2016 guideline on the management of asthma does not include advice on vitamin D.

NICE advises health professionals to recommend vitamin D supplements for people at risk of deficiency. This includes children under the age of five, pregnant and breastfeeding women, people with low skin exposure to the sun and those with darker skin.

From July this year (2016) Public Health England advise that everyone needs vitamin D equivalent to an average daily intake of 10 micrograms to protect bone and muscle health. This, they say can come from, natural food sources, fortified foods (including infant formula milk) or supplements.

What are the implications?

Preventing asthma attacks not only improves quality of life but reduces the risk of serious consequences, including death. This review of the best available evidence suggests taking a vitamin D supplement alongside usual medication can reduce the number of exacerbations or attacks.

However before clinical recommendations can be made, it would be nice to know the optimum dosage of vitamin D supplements and who is likely to benefit most, taking into consideration age, severity of asthma, and baseline vitamin D levels.

Citation and Funding

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

Cochrane UK and the Cochrane Airways Group are supported by NIHR infrastructure funding.

Bibliography

Bibliography

Asthma UK. Asthma facts and statistics. London: Asthma UK; 2016.

BTS. British guideline on the management of asthma: A national clinical guideline. London. British Thoracic Society and Scottish Intercollegiate Guidelines Network; 2016.

NHS Choices. Vitamin D ‘protects against severe asthma attacks’. London: Department of Health; 2016.

NHS Choices. Vitamins and minerals – vitamin D. London: Department of Health; 2015.

NICE. Vitamin D: Increasing supplement use in at risk groups. PH56. London. National Institute for Health and Care Excellence; 2014.

NICE. NICE support for commissioners and others using the quality standard for asthma. QS25. London: National Institute for Health and Care Excellence; 2013.

SACN. Vitamin D and health. London: Public Health England, Scientific Advisory Committee on Nutrition; 2016.

Why was this study needed?

In the UK, 5.4 million people have asthma. This long-term condition affects children and adults and costs the NHS about £1 billion each year. Asthma attacks can be life-threatening and many people end up being admitted to hospital for treatment.

Vitamin D is an essential nutrient that keeps muscles and bones healthy. It can be obtained from food and made in the skin from exposure to sunlight. About 22% of children over 11 years and adults of all ages have low levels of vitamin D in their blood. This is not the same as having a deficiency, with symptoms, but signifies people at greater risk of developing a deficiency. Public Health England report that low levels of vitamin D are common  and recommends that everyone in the UK (including those without asthma) considers taking a 10microgram dose of vitamin D daily, especially in winter.

This review aimed to get a clearer picture of how vitamin D supplements could help manage asthma symptoms by reviewing the strongest evidence available.

What did this study do?

This was a Cochrane systematic review of nine double-blind, randomised, placebo-controlled trials of 1093 people that measured the effects of vitamin D on asthma. Vitamin D was taken alongside normal asthma treatment for between four and 12 months.

The reviewers pooled the results of similar trials for each outcome.

This was a high quality review and the trials had a low risk of bias. However, there were several differences between the trials, which limit direct applicability. The majority of participants had mild to moderate asthma, with variable regular use of inhaled steroids. Vitamin D doses also varied between trials with some using daily regimes and others monthly injections. Baseline vitamin D levels were not recorded in most trials so we do not know how many people had a deficiency or whether there was a stronger effect for those that did.

What did it find?

  • Vitamin D supplements reduced the average number of asthma attacks requiring oral steroids from 0.44 per year to 0.28 per year (three trials, 22 children and 658 adults). This equates to a reduction from nearly one every two years to about one every four years (rate ratio [RR] 0.63, 95% confidence interval [CI] 0.45 to 0.88).
  • Fewer people taking vitamin D supplements had an asthma attack severe enough that they visited an emergency department or were admitted to hospital or both (odds ratio 0.39, 95% CI 0.19 to 0.78, seven trials, 307 children, 658 adults). Over a period of eight months, vitamin D reduced the rate from 6 in 100 people to 3 in 100 people (95% CI 1 to 5). Results were mostly based on adults as there were few events in the child trials.
  • Lung function and daily symptoms were unchanged by vitamin D supplements.
  • Vitamin D did not cause any increase in serious adverse events.

What does current guidance say on this issue?

The British Thoracic Society 2016 guideline on the management of asthma does not include advice on vitamin D.

NICE advises health professionals to recommend vitamin D supplements for people at risk of deficiency. This includes children under the age of five, pregnant and breastfeeding women, people with low skin exposure to the sun and those with darker skin.

From July this year (2016) Public Health England advise that everyone needs vitamin D equivalent to an average daily intake of 10 micrograms to protect bone and muscle health. This, they say can come from, natural food sources, fortified foods (including infant formula milk) or supplements.

What are the implications?

Preventing asthma attacks not only improves quality of life but reduces the risk of serious consequences, including death. This review of the best available evidence suggests taking a vitamin D supplement alongside usual medication can reduce the number of exacerbations or attacks.

However before clinical recommendations can be made, it would be nice to know the optimum dosage of vitamin D supplements and who is likely to benefit most, taking into consideration age, severity of asthma, and baseline vitamin D levels.

Citation and Funding

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

Cochrane UK and the Cochrane Airways Group are supported by NIHR infrastructure funding.

Bibliography

Bibliography

Asthma UK. Asthma facts and statistics. London: Asthma UK; 2016.

BTS. British guideline on the management of asthma: A national clinical guideline. London. British Thoracic Society and Scottish Intercollegiate Guidelines Network; 2016.

NHS Choices. Vitamin D ‘protects against severe asthma attacks’. London: Department of Health; 2016.

NHS Choices. Vitamins and minerals – vitamin D. London: Department of Health; 2015.

NICE. Vitamin D: Increasing supplement use in at risk groups. PH56. London. National Institute for Health and Care Excellence; 2014.

NICE. NICE support for commissioners and others using the quality standard for asthma. QS25. London: National Institute for Health and Care Excellence; 2013.

SACN. Vitamin D and health. London: Public Health England, Scientific Advisory Committee on Nutrition; 2016.

Vitamin D for the management of asthma

Published on 5 September 2016

A Martineau, C Cates, M Urashima, M Jensen, A Griffiths, U Nurmatov, A Sheikh, C Griffiths

Cochrane Library , 2016

Background Several clinical trials of vitamin D to prevent asthma exacerbation and improve asthma control have been conducted in children and adults, but a meta-analysis restricted to double-blind, randomised, placebo-controlled trials of this intervention is lacking. Objectives To evaluate the efficacy of administration of vitamin D and its hydroxylated metabolites in reducing the risk of severe asthma exacerbations (defined as those requiring treatment with systemic corticosteroids) and improving asthma symptom control. Search methods We searched the Cochrane Airways Group Trial Register and reference lists of articles. We contacted the authors of studies in order to identify additional trials. Date of last search: January 2016. Selection criteria Double-blind, randomised, placebo-controlled trials of vitamin D in children and adults with asthma evaluating exacerbation risk or asthma symptom control or both. Data collection and analysis Two review authors independently applied study inclusion criteria, extracted the data, and assessed risk of bias. We obtained missing data from the authors where possible. We reported results with 95% confidence intervals (CIs). Main results We included seven trials involving a total of 435 children and two trials involving a total of 658 adults in the primary analysis. Of these, one trial involving 22 children and two trials involving 658 adults contributed to the analysis of the rate of exacerbations requiring systemic corticosteroids. Duration of trials ranged from four to 12 months, and the majority of participants had mild to moderate asthma. Administration of vitamin D reduced the rate of exacerbations requiring systemic corticosteroids (rate ratio 0.63, 95% CI 0.45 to 0.88; 680 participants; 3 studies; high-quality evidence), and decreased the risk of having at least one exacerbation requiring an emergency department visit or hospitalisation or both (odds ratio (OR) 0.39, 95% CI 0.19 to 0.78; number needed to treat for an additional beneficial outcome, 27; 963 participants; 7 studies; high-quality evidence). There was no effect of vitamin D on % predicted forced expiratory volume in one second (mean difference (MD) 0.48, 95% CI -0.93 to 1.89; 387 participants; 4 studies; high-quality evidence) or Asthma Control Test scores (MD -0.08, 95% CI -0.70 to 0.54; 713 participants; 3 studies; high-quality evidence). Administration of vitamin D did not influence the risk of serious adverse events (OR 1.01, 95% CI 0.54 to 1.89; 879 participants; 5 studies; moderate-quality evidence). One trial comparing low-dose versus high-dose vitamin D reported two episodes of hypercalciuria, one in each study arm. No other study reported any adverse event potentially attributable to administration of vitamin D. No participant in any included trial suffered a fatal asthma exacerbation. We did not perform a subgroup analysis to determine whether the effect of vitamin D on risk of severe exacerbation was modified by baseline vitamin D status, due to unavailability of suitably disaggregated data. We assessed two trials as being at high risk of bias in at least one domain; neither trial contributed data to the analysis of the outcomes reported above. Authors' conclusions Meta-analysis of a modest number of trials in people with predominantly mild to moderate asthma suggests that vitamin D is likely to reduce both the risk of severe asthma exacerbation and healthcare use. It is as yet unclear whether these effects are confined to people with lower baseline vitamin D status; further research, including individual patient data meta-analysis of existing datasets, is needed to clarify this issue. Children and people with frequent severe asthma exacerbations were under-represented; additional primary trials are needed to establish whether vitamin D can reduce the risk of severe asthma exacerbation in these groups.

All studies in this review administered oral vitamin D3 (cholecalciferol) to participants in the intervention arm. The vitamin D dosage regimens differed between trials:

  • Four studies used exclusively daily dosing regimens ranging from 500 IU/day to 1200 IU/day.
  • One study used weekly dosing
  • One study used monthly dosing
  • One study used two-monthly dosing
  • Two studies gave a bolus dose at the start of the study, followed by daily dosing

Ten micrograms is equivalent to 400 IU vitamin D3 (international Units), so these trials used supplementation that was more than the current reference nutrient intake (RNI).

Expert commentary

Vitamin D is all the rage. It keeps cropping up in all sorts of new areas. Why should asthma miss out? This expertly conducted Cochrane review demonstrates a reduction in attack frequency in adults and children given supplementation though there is some uncertainty in those with severe asthma. What isn’t clear is if this helps across the board or just in those with low levels to start with. More work is required here. With few if any adverse reactions in the intervention groups we should now consider this as part of the management strategy for those suffering repeated attacks.

Dr John White, Consultant Physician, York Teaching Hospital, NHS Foundation Trust