NIHR Signal Vitamin D supplements may reduce the chance of developing a chest infection

Published on 27 June 2017

Vitamin D supplements may reduce the chances of contracting an acute respiratory tract infection, particularly for those with low existing levels of vitamin D.

This NIHR-funded study pooled patient data from 25 randomised controlled trials and found that daily or weekly supplements reduced respiratory tract infections compared with placebo. About 20 people would need to take regular supplements in order to prevent one infection. One-off monthly dosing gave no benefit.

Public Health England (PHE) currently recommends that 10µg vitamin D is needed each day to maintain bone, teeth and muscle health. Supplements are advised for all in the winter months, and throughout the year for those who are at risk of being deficient. This review adds evidence in support of vitamin D supplementation in reducing the chance of an acute respiratory tract infection, an additional health outcome.

Vitamin D supplements may reduce the chance of developing a chest infection

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Why was this study needed?

Acute respiratory tract infections are said to account for one in 10 emergency department visits in the US. Upper respiratory tract infections are limited to the nose, throat and sinuses while lower infections affect the airways and lungs, both can be caused by viruses, though some infections due to bacteria can require antibiotics.

In 2016 the Scientific Advisory Committee on Nutrition (SACN) review on vitamin D and health recommended adults take 10µg vitamin D per day throughout the year based on the benefits for musculoskeletal health. The SACN at the time, found conflicting evidence on whether vitamin D supplements reduce risk of respiratory tract infection or other non-musculoskeletal outcomes and recommended more research into these areas.

This systematic review, including trials published since the SACN review, aimed to gather the evidence looking at the effect of vitamin D on risk of acute upper, lower or undefined respiratory tract infections.

What did this study do?

The review identified 25 randomised controlled trials including 11,321 people of all ages from 14 countries, including the UK, assigned to vitamin D3 supplements or placebo. Trials were included if double blind, with neither participant nor assessors aware of the treatment given, and looked at the effect on respiratory tract infections.

Vitamin D3 dose varied from daily dosing to bolus doses given every three months. Study duration ranged from seven weeks to 18 months. Nearly all trials were assessed to be at low risk of bias.

Individual patient data was pooled in meta-analysis. Researchers carried out subgroup analyses to see if any factors could explain differences in the results, such as whether people were vitamin D deficient, dose and duration of supplementation, age, body mass index and existing asthma.

What did it find?

  • When pooling results from all 25 trials, people talking vitamin D supplementation by any route were less likely to develop at least one acute respiratory tract infection adjusting for age, sex, and study duration. Forty percent experienced one or more infections while taking supplements, compared with 42% in the control group, (adjusted odds ratio [aOR] 0.88, 95% confidence interval [CI] 0.81 to 0.96).
  • Subgroup analysis found that those taking daily or weekly supplements (excluding trials of large one-off bolus doses) were also less likely to develop at least one infection (aOR 0.81, 95% CI 0.72 to 0.91; 15 studies, 5133 people), 45% experienced one of more infections while taking supplements, compared with 50% in the control group. Bolus dose had no effect (aOR 0.97, 95% CI 0.86 to 1.10; 10 studies, 5800 people).
  • For participants taking these daily or weekly doses without a bolus, vitamin D supplementation was most beneficial for people with low vitamin D levels (less than 25nmol/L) reducing risks of at least one infection for these people from 60% to 31%. aOR 0.30 (95% CI 0.17 to 0.53; six studies, 234 participants). It was still effective for participants with normal levels (aOR 0.75, 95% CI 0.60 to 0.95; six studies, 1603 participants).
  • There was no difference in the rate of serious adverse effects between vitamin D and placebo groups. High calcium or kidney stones were rare.

The effects of Vitamin D supplementation on chance of developing acute respiratory infections

What does current guidance say on this issue?

PHE advise that everyone needs 10 µg of vitamin D daily to protect bones, teeth and muscles.

Most people get enough vitamin D in spring and summer, but PHE recommend a daily 10µg supplement in autumn and winter as it is unclear how much vitamin D is gained from sunlight in these months.

People whose skin has little or no sun exposure should take a supplement throughout the year.

PHE recommend children aged one to four years take a 10µg vitamin D supplement daily. Babies under one should take 8.5 to 10µg, unless they have more than 500ml infant formula a day.

What are the implications?

Daily or weekly vitamin D supplements could reduce risk of acute respiratory tract infection particularly among people who are deficient, alongside known musculoskeletal benefits. People at risk of being deficient might include those belonging to a minority ethnic group, people in care homes or those who are housebound.

This review does not supply evidence for a differential effect on upper or lower respiratory tract infections analysed separately, or for other outcomes of interest, like hospital admissions, school or work absence.  

It’s uncertain whether the findings could lead to a modification to the general population recommendations on vitamin D supplementation, as many following PHE advice will be already taking supplements. Another potential avenue the authors suggest considering for population health is fortification of foods with vitamin D. This is not something that is currently recommended or covered by this research.

Citation and Funding

Martineau AR, Jolliffe DA, Hooper RL, et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ. 2017;356:i6583.

This project was funded by the National Institute for Health Research (NIHR) under its Health Technology Assessment programme (reference No 13/03/25, to ARM).

Bibliography

NHS Choices. Respiratory Tract Infections. London: Department of Health; 2015.

Public Health England. PHE publishes new advice on vitamin D. London: Department of Health; 2016.

Scientific Advisory Committee on Nutrition. Vitamin D and Health. London: Department of Health; 2016. 

Why was this study needed?

Acute respiratory tract infections are said to account for one in 10 emergency department visits in the US. Upper respiratory tract infections are limited to the nose, throat and sinuses while lower infections affect the airways and lungs, both can be caused by viruses, though some infections due to bacteria can require antibiotics.

In 2016 the Scientific Advisory Committee on Nutrition (SACN) review on vitamin D and health recommended adults take 10µg vitamin D per day throughout the year based on the benefits for musculoskeletal health. The SACN at the time, found conflicting evidence on whether vitamin D supplements reduce risk of respiratory tract infection or other non-musculoskeletal outcomes and recommended more research into these areas.

This systematic review, including trials published since the SACN review, aimed to gather the evidence looking at the effect of vitamin D on risk of acute upper, lower or undefined respiratory tract infections.

What did this study do?

The review identified 25 randomised controlled trials including 11,321 people of all ages from 14 countries, including the UK, assigned to vitamin D3 supplements or placebo. Trials were included if double blind, with neither participant nor assessors aware of the treatment given, and looked at the effect on respiratory tract infections.

Vitamin D3 dose varied from daily dosing to bolus doses given every three months. Study duration ranged from seven weeks to 18 months. Nearly all trials were assessed to be at low risk of bias.

Individual patient data was pooled in meta-analysis. Researchers carried out subgroup analyses to see if any factors could explain differences in the results, such as whether people were vitamin D deficient, dose and duration of supplementation, age, body mass index and existing asthma.

What did it find?

  • When pooling results from all 25 trials, people talking vitamin D supplementation by any route were less likely to develop at least one acute respiratory tract infection adjusting for age, sex, and study duration. Forty percent experienced one or more infections while taking supplements, compared with 42% in the control group, (adjusted odds ratio [aOR] 0.88, 95% confidence interval [CI] 0.81 to 0.96).
  • Subgroup analysis found that those taking daily or weekly supplements (excluding trials of large one-off bolus doses) were also less likely to develop at least one infection (aOR 0.81, 95% CI 0.72 to 0.91; 15 studies, 5133 people), 45% experienced one of more infections while taking supplements, compared with 50% in the control group. Bolus dose had no effect (aOR 0.97, 95% CI 0.86 to 1.10; 10 studies, 5800 people).
  • For participants taking these daily or weekly doses without a bolus, vitamin D supplementation was most beneficial for people with low vitamin D levels (less than 25nmol/L) reducing risks of at least one infection for these people from 60% to 31%. aOR 0.30 (95% CI 0.17 to 0.53; six studies, 234 participants). It was still effective for participants with normal levels (aOR 0.75, 95% CI 0.60 to 0.95; six studies, 1603 participants).
  • There was no difference in the rate of serious adverse effects between vitamin D and placebo groups. High calcium or kidney stones were rare.

The effects of Vitamin D supplementation on chance of developing acute respiratory infections

What does current guidance say on this issue?

PHE advise that everyone needs 10 µg of vitamin D daily to protect bones, teeth and muscles.

Most people get enough vitamin D in spring and summer, but PHE recommend a daily 10µg supplement in autumn and winter as it is unclear how much vitamin D is gained from sunlight in these months.

People whose skin has little or no sun exposure should take a supplement throughout the year.

PHE recommend children aged one to four years take a 10µg vitamin D supplement daily. Babies under one should take 8.5 to 10µg, unless they have more than 500ml infant formula a day.

What are the implications?

Daily or weekly vitamin D supplements could reduce risk of acute respiratory tract infection particularly among people who are deficient, alongside known musculoskeletal benefits. People at risk of being deficient might include those belonging to a minority ethnic group, people in care homes or those who are housebound.

This review does not supply evidence for a differential effect on upper or lower respiratory tract infections analysed separately, or for other outcomes of interest, like hospital admissions, school or work absence.  

It’s uncertain whether the findings could lead to a modification to the general population recommendations on vitamin D supplementation, as many following PHE advice will be already taking supplements. Another potential avenue the authors suggest considering for population health is fortification of foods with vitamin D. This is not something that is currently recommended or covered by this research.

Citation and Funding

Martineau AR, Jolliffe DA, Hooper RL, et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ. 2017;356:i6583.

This project was funded by the National Institute for Health Research (NIHR) under its Health Technology Assessment programme (reference No 13/03/25, to ARM).

Bibliography

NHS Choices. Respiratory Tract Infections. London: Department of Health; 2015.

Public Health England. PHE publishes new advice on vitamin D. London: Department of Health; 2016.

Scientific Advisory Committee on Nutrition. Vitamin D and Health. London: Department of Health; 2016. 

Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data

Published on 17 February 2017

Martineau, A. R.,Jolliffe, D. A.,Hooper, R. L.,Greenberg, L.,Aloia, J. F.,Bergman, P.,Dubnov-Raz, G.,Esposito, S.,Ganmaa, D.,Ginde, A. A.,Goodall, E. C.,Grant, C. C.,Griffiths, C. J.,Janssens, W.,Laaksi, I.,Manaseki-Holland, S.,Mauger, D.,Murdoch, D. R.,Neale, R.,Rees, J. R.,Simpson, S., Jr.,Stelmach, I.,Kumar, G. T.,Urashima, M.,Camargo, C. A., Jr.

Bmj Volume 356 , 2017

Objectives To assess the overall effect of vitamin D supplementation on risk of acute respiratory tract infection, and to identify factors modifying this effect.Design Systematic review and meta-analysis of individual participant data (IPD) from randomised controlled trials.Data sources Medline, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, ClinicalTrials.gov, and the International Standard Randomised Controlled Trials Number registry from inception to December 2015.Eligibility criteria for study selection Randomised, double blind, placebo controlled trials of supplementation with vitamin D3 or vitamin D2 of any duration were eligible for inclusion if they had been approved by a research ethics committee and if data on incidence of acute respiratory tract infection were collected prospectively and prespecified as an efficacy outcome.Results 25 eligible randomised controlled trials (total 11 321 participants, aged 0 to 95 years) were identified. IPD were obtained for 10 933 (96.6%) participants. Vitamin D supplementation reduced the risk of acute respiratory tract infection among all participants (adjusted odds ratio 0.88, 95% confidence interval 0.81 to 0.96; P for heterogeneity <0.001). In subgroup analysis, protective effects were seen in those receiving daily or weekly vitamin D without additional bolus doses (adjusted odds ratio 0.81, 0.72 to 0.91) but not in those receiving one or more bolus doses (adjusted odds ratio 0.97, 0.86 to 1.10; P for interaction=0.05). Among those receiving daily or weekly vitamin D, protective effects were stronger in those with baseline 25-hydroxyvitamin D levels <25 nmol/L (adjusted odds ratio 0.30, 0.17 to 0.53) than in those with baseline 25-hydroxyvitamin D levels >/=25 nmol/L (adjusted odds ratio 0.75, 0.60 to 0.95; P for interaction=0.006). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (adjusted odds ratio 0.98, 0.80 to 1.20, P=0.83). The body of evidence contributing to these analyses was assessed as being of high quality.Conclusions Vitamin D supplementation was safe and it protected against acute respiratory tract infection overall. Patients who were very vitamin D deficient and those not receiving bolus doses experienced the most benefit.Systematic review registration PROSPERO CRD42014013953.

Expert commentary

This new review of vitamin D supplementation to prevent respiratory tract infections uses individual patient data to provide a clear message; that vitamin D supplementation when given regularly reduces the risk of infection in those receiving it, particularly those with low serum levels of 25-hydroxyvitamin D.

The diagnosis of respiratory infection is a broad one from the common cold to pneumonia and further clarity on this is required. However, given the intervention had no clear adverse effects it is likely we will see a rise prescription of supplements, particularly for those with low levels for this common problem.

Dr John White, Consultant Physician, York NHS Foundation Trust