The results, published in the BMJ, are based on a new analysis of raw data from around 11,000 participants in 25 clinical trials conducted in 14 countries including the UK, USA, Japan, India, Afghanistan, Belgium, Italy, Australia and Canada. Individually, these trials yielded conflicting results, with some reporting that vitamin D protected against respiratory infections, and others showing no effect.
Lead researcher Professor Adrian Martineau from QMUL said: "This major collaborative research effort has yielded the first definitive evidence that vitamin D really does protect against respiratory infections. Our analysis of pooled raw data from each of the 10,933 trial participants allowed us to address the thorny question of why vitamin D 'worked' in some trials, but not in others.
"The bottom line is that the protective effects of vitamin D supplementation are strongest in those who have the lowest vitamin D levels, and when supplementation is given daily or weekly rather than in more widely spaced doses.
"Vitamin D fortification of foods provides a steady, low-level intake of vitamin D that has virtually eliminated profound vitamin D deficiency in several countries. By demonstrating this new benefit of vitamin D, our study strengthens the case for introducing food fortification to improve vitamin D levels in countries such as the UK where profound vitamin D deficiency is common."
Vitamin D - the 'sunshine vitamin' - is thought to protect against respiratory infections by boosting levels of antimicrobial peptides - natural antibiotic-like substances - in the lungs. Results of the 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.
Daily or weekly supplementation halved the risk of acute respiratory infection in people with the lowest baseline vitamin D levels, below 25 nanomoles per litre (nmol/L). However, people with higher baseline vitamin D levels also benefited, although the effect was more modest (10 per cent risk reduction). Overall, the reduction in risk of acute respiratory infection induced by vitamin D was on a par with the protective effect of injectable 'flu vaccine against 'flu-like illnesses.
Acute respiratory infections are a major cause of global morbidity and mortality. Upper respiratory infections such as colds and 'flu are the commonest reason for GP consultations and days off work. Acute lower respiratory infections such as pneumonia are less common, but caused an estimated 2.65 million deaths worldwide in 2013. Vitamin D supplementation is safe and inexpensive, so reductions in acute respiratory infections brought about by vitamin D supplementation could be highly cost-effective.
The study was conducted by a consortium of 25 investigators from 21 institutions worldwide and funded by the National Institute for Health Research.
Institutions involved in the research: Edmond and Lily Safra Children's Hospital (Tel Hashomer, Israel), Geisel School of Medicine at Dartmouth (NH, USA), Harvard School of Public Health (Boston, MA, USA), Jikei University School of Medicine (Tokyo, Japan), Karolinska Institutet (Stockholm, Sweden), Massachusetts General Hospital (Boston, MA, USA), McMaster University (Hamilton, Ontario, Canada), Medical University of Lodz (Poland), QIMR Berghofer Medical Research Institute (Queensland, Australia), Queen Mary University of London (UK), The Pennsylvania State University (Hershey, PA, USA), Università degli Studi di Milano (Milan, Italy), Universitair ziekenhuis Leuven (Belgium), University of Auckland (New Zealand), University of Birmingham (UK), University of Colorado School of Medicine (Aurora, CO, USA), University of Delhi (India), University of Otago (Christchurch, New Zealand), University of Tampere (Finland), University of Tasmania (Australia), Winthrop University Hospital (Mineola, NY, USA).
Martineau AR, Jolliffe DA, Hooper RL, Greenberg L, Aloia JF, Bergman P, Dubnov-Raz G, Esposito S, Ganmaa D, Ginde AA, Goodall EC, Grant CC, Griffiths CJ, Janssens W, Laaksi I, Manaseki-Holland S, Mauger D, Murdoch DR, Neale R, Rees JR, Simpson S Jr, Stelmach I, Kumar GT, Urashima M, Camargo CA Jr.
Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data.
BMJ. 2017 Feb 15;356:i6583. doi: 10.1136/bmj.i6583.