Meta-analysis of 64,086 participants shows no significant overall reduction in acute respiratory infections with vitamin D supplementation, though children and those on daily low doses may see protective effects.

Study: Vitamin D supplementation to prevent acute respiratory infections: systematic review and meta-analysis of stratified aggregate data. Image Credit: Aria Armoko/Shutterstock.com

Vitamin D supplement sales exceed USD 1 billion worldwide, with market growth projected at nearly 8%, reaching USD 2.4 billion by 2030. This vitamin is widely promoted for various health benefits, though robust evidence is still needed for many of its claimed effects.

Prior research suggests vitamin D supplementation provides modest protection against acute respiratory infections (ARIs), reducing incidence by about 8%. A recent report in The Lancet updates this analysis by incorporating more recent trials.

Introduction

Vitamin D is a fat-soluble vitamin essential for calcium and phosphorus absorption, supporting bone health and innate immunity.

Deficiency has been linked to an increased risk of cardiovascular conditions, including ischemic heart disease, strokes, heart failure, and heart attacks. It has also been associated with improvements in depression symptoms and exercise capacity.

An acute respiratory infection (ARI) is any respiratory tract infection resolving within 21 days. Vitamin D plays a role in innate immune responses to respiratory viruses, and low vitamin D levels have been linked to higher ARI risk.

Randomized controlled trials (RCTs) examining vitamin D supplementation for ARI prevention have shown mixed results, with some indicating a protective effect while others show no benefit.

A previous meta-analysis of 43 RCTs reported a small overall protective effect, particularly in children aged 1 to 15 years receiving daily doses of 400-1,000 IU. The current study aimed to update this meta-analysis by incorporating six additional RCTs.

Study findings

Researchers conducted a systematic review and meta-analysis of RCTs meeting the inclusion criteria. The study analyzed data from 16,085 participants in three new RCTs alongside 48,888 participants from 43 prior RCTs, totaling 64,086 participants.

The trials spanned 24 countries across five continents and included participants from infancy to 100 years old. Baseline active vitamin D levels in 38 trials ranged from 18.9 nmol/L to 90.9 nmol/L.

Dosage regimens varied from daily to monthly, with one study combining a single bolus dose with continued daily supplementation. Trial durations ranged from seven weeks to five years. Most trials were methodologically sound and unbiased.

Overall, vitamin D supplementation did not significantly reduce ARI risk compared to a placebo. However, subgroup analyses revealed some protective effects.

• Age: A 26% reduction in ARI risk was observed in participants aged 1-15 years.
• Dosing frequency: Daily dosing was associated with a 16% reduction in ARI risk.
• Dosage: Supplementation with 400-1,000 IU/day correlated with a 30% lower ARI risk.
• Duration: Trials lasting up to a year showed a 15% reduction in ARI risk, though this benefit disappeared with longer interventions.
• Preexisting conditions: No significant benefit was observed for individuals with asthma or chronic obstructive pulmonary disease (COPD).

Despite these subgroup findings, further statistical analysis did not confirm that vitamin D’s effects were significantly modified by dosage, frequency, age, or intervention duration. The overall evidence quality was considered moderate.

Conclusions

This updated meta-analysis, incorporating data from 46 RCTs and 64,086 participants, found no significant overall effect of vitamin D supplementation on ARI risk. However, some trends suggested potential benefits in specific groups.

Larger trials are needed to determine whether vitamin D provides meaningful protection against ARIs in certain populations.