Meta-analysis authors
say 'yes,' but other experts are skeptical
Vitamin
D supplementation appeared to have a modest protective effect against acute
respiratory tract infections, especially among people who were very deficient,
according to a meta-analysis.
After
adjusting for potential confounders such as age, sex, and study duration,
vitamin D supplementation was associated with a 12% reduction in the proportion
of participants experiencing at least one acute respiratory tract infection,
reported Adrian Martineau, PhD, of
Queen Mary University of London, and colleagues.
Among
participants with baseline vitamin D deficiency (less than 25 nmol/L) a strong
protective effect was seen (adjusted odds ratio 0.58, 95% CI 0.40-0.82, number
needed to treat =8) in 538 participants in 14 studies (P=0.002),
they wrote in BMJ.
The
researchers concluded that the meta-analysis findings,"support the
introduction of public health measures to improve vitamin D status,
particularly in settings where profound vitamin D deficiency is common."
But
in an accompanying editorial, Mark Bolland, PhD, of
the University of Auckland New
Zealand University of Aberdeen Scotland
"In
absolute terms, the primary result is a reduction from 42% to 40% in the
proportion of participants experiencing at least one acute respiratory tract
infection," they wrote. "It seems unlikely that the general
population would consider a 2% absolute risk reduction sufficient justification
to take supplements."
Martineau's
group searched various databases for randomized, double-blind, placebo
controlled trials of supplementation with vitamin D3 or
vitamin D2 which included prospectively
collected data on incidence of acute respiratory tract infection. Twenty-five
eligible studies, totalling 11,321 participants, were included in the analysis,
and individual participant data were available for 10,933 participants (96.6%).
They
reported that vitamin D supplementation reduced the risk of acute respiratory
tract infection among all participants (adjusted OR 0.88, 95% CI 0.81-0.96, P<0.001
for heterogeneity).
In
subgroup analysis, protective effects were seen in those receiving daily or
weekly vitamin D without additional bolus doses (adjusted OR 0.81, 95% CI
0.72-0.91) but not in those receiving one or more bolus doses (adjusted OR
0.97, 95% CI 0.86-1.10; P=0.05
for interaction).
Also,
among those receiving daily or weekly vitamin D, protective effects were
stronger in those with baseline 25-hydroxyvitamin D levels <25 nmol/L than
in those with baseline 25-hydroxyvitamin D levels ≥25 nmol/L.
Finally,
vitamin D did not influence the proportion of participants who experienced at
least one serious adverse event (adjusted OR 0.98, 9% CI 0.80-1.20, P=0.83).
The
authors noted that patients who did not receive bolus doses experienced the
most benefit. "Why might use of bolus dose vitamin D be ineffective for
prevention of acute respiratory tract infection?," they wrote. "One explanation relates
to the potentially adverse effects of wide fluctuations in circulating
25-hydroxyvitamin D concentrations, which are seen after use of bolus doses but
not with daily or weekly supplementation."
Overall,
the body of evidence contributing to the analysis was assessed to be of high
quality.
Study
limitations were limited power to detect effects of vitamin D supplementation
for certain subgroups, including those with very low 25-hydroxyvitamin D serum
levels receiving bolus dosing regimens, and inadequate data on adherence to
study drugs.
Nonetheless,
the researchers concluded that their analysis suggests "a major new
indication for vitamin D supplementation: the prevention of acute respiratory
tract infection."
But
Bolland and Avenell stated that the findings "probably not change clinical
practice. The results are heterogeneous and not sufficiently applicable to the
general population. We think that they should be viewed as hypothesis
generating only, requiring confirmation in well-designed, adequately powered
controlled trials."
They
noted that several such trials are currently underway, and results from these
trials are expected within the next few years.
"We
consider that current evidence does not support the use of vitamin D
supplementation to prevent disease, except for those at high risk of
osteomalacia, currently defined as 25-hydroxyvitamin D levels less than 25
nmol/L," they wrote.
This study was funded by the
National Health Service's National Institute for Health Research.
Martineau and co-authors disclosed
no relevant relationships with industry.
Bolland and Avenell disclosed
support from the Health Research Council of New Zealand.
·
Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine,University of California San Francisco
Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine,
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