Vitamin D supplementation can help protect against acute respiratory infections including colds and flu, particularly among very deficient individuals, according to a new study published in the journal BMJ.

Acute respiratory tract infections are a major cause of global morbidity and mortality and are responsible for 10% of ambulatory and emergency department visits in the United States.

They can include anything from the common cold to bronchitis and pneumonia and have been linked with low blood levels of vitamin D.

Some studies have shown that vitamin D can trigger immune responses to certain bacteria and viruses, but randomized trials of vitamin D supplements to prevent acute respiratory tract infection have led to conflicting results.

To resolve these discrepancies, an international team of researchers — led by Queen Mary University of London Professor Adrian Martineau — set out to assess the overall effect of vitamin D supplements on risk of acute respiratory tract infection, and to identify factors modifying this effect.

They conducted a systematic review and meta-analysis of raw data from 11,321 participants in 25 randomized controlled trials of vitamin D supplementation conducted in 14 countries including the UK, the United States, Japan, India, Afghanistan, Belgium, Italy, Australia and Canada.

While traditional meta-analyses compare average data from all participants in each study, individual participant data meta-analysis separates out the data from each individual participant, producing what could be considered a higher resolution analysis of the data from all studies.

All but two trials were assessed as being at low risk of bias (problems with study design that can influence results).

“25 eligible randomized controlled trials (total 11,321 participants, aged 0 to 95 years) were identified. Individual participant data were obtained for 10,933 (96.6%) participants,” the authors explained.

After adjusting for other potentially influential factors such as age, sex and study duration, they found that vitamin D supplementation resulted in a 12% reduction in the proportion of participants experiencing at least one acute respiratory tract infection.

Prof. Martineau and co-authors calculate that 33 people would need to take vitamin D supplements to prevent one acute respiratory tract infection.

Further analyses among specific groups showed benefit was greater in those receiving daily or weekly vitamin D without additional large (bolus) doses.

And the protective effects in this group were strongest in those with severe vitamin D deficiency (less than 25 nmol/L baseline blood levels).

The scientists calculate that only four people in this group would need to take supplements to prevent one acute respiratory tract infection.

“Use of vitamin D was safe. Potential adverse reactions were rare, and the risk of such events was the same between participants randomized to intervention and control arms,” they said.

“Most people understand that vitamin D is critical for bone and muscle health,” said study’s senior author Dr. Carlos Camargo, of Massachusetts General Hospital.

“Our analysis has also found that it helps the body fight acute respiratory infection.”

Vitamin D is thought to protect against respiratory infections by boosting levels of antimicrobial peptides in the lungs.

The results of this study fit with the observation that colds and flu are commonest in winter and spring, when levels of vitamin D are at their lowest.

They may also explain why vitamin D protects against asthma attacks, which are commonly triggered by respiratory viruses.

“Our results add to the body of evidence supporting the introduction of public health measures such as food fortification to improve vitamin D status, particularly in settings where profound vitamin D deficiency is common,” the researchers said.

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Adrian R. Martineau et al. 2017. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ 356: i6583; doi: 10.1136/bmj.i6583