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

In 2017, a team led by Dr. Adrian Martineau at Queen Mary University of London published the definitive analysis of vitamin D supplementation for preventing respiratory infections. This landmark meta-analysis used individual participant data from 25 randomized controlled trials involving nearly 11,000 people.

Why Individual Participant Data Matters

Unlike typical meta-analyses that combine published summary statistics, Martineau's team obtained raw data from each trial. This allowed them to examine effects across subgroups that couldn't be analyzed from published papers alone—a much more powerful approach.

Key Findings

The overall results showed vitamin D supplementation reduced the risk of acute respiratory tract infections by 12% (adjusted odds ratio 0.88). But the benefits varied dramatically by baseline vitamin D status:

• •Severely deficient (<25 nmol/L): 70% reduction in infections
• •Moderately deficient (25-50 nmol/L): 25% reduction
• •Sufficient (>50 nmol/L): No significant benefit

Dosing Matters

Perhaps the most clinically important finding: how you take vitamin D matters as much as how much:

• •Daily or weekly dosing: Protective (19% reduction)
• •Monthly or less frequent boluses: Not protective

This suggests that maintaining steady vitamin D levels is more important than periodic high doses.

Biological Mechanism

Vitamin D enhances the innate immune response by stimulating production of antimicrobial peptides like cathelicidin and defensins. These peptides help destroy pathogens in the respiratory tract before they can cause infection.

Clinical Impact

This study provided the strongest evidence to date that correcting vitamin D deficiency can meaningfully reduce respiratory infections. During the COVID-19 pandemic, this research received renewed attention as scientists investigated potential protective effects against SARS-CoV-2.

The findings support routine vitamin D testing and supplementation, particularly for those at high risk of deficiency or frequent respiratory infections.