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No Significant Protective Effect of Vitamin D Supplements Against Respiratory Infections: Lancet

A recent meta-analysis found the effectiveness of vitamin D supplements in preventing acute respiratory infections (ARIs), revealing that the previously observed modest protective effect may not be statistically significant after all. The findings were published in The Lancet Diabetes & Endocrinology.
This study updates a 2021 meta-analysis which had shown a statistically significant, albeit modest, reduction in ARI risk from vitamin D supplementation (odds ratio [OR] 0.92, 95% CI 0.86–0.99). At the time, the results were based on 37 randomized controlled trials (RCTs).
Now, this meta-analysis has included data from six newly completed RCTs, incorporating a large-scale trial involving over 15,800 participants. The new systematic review examined data from a total of 49 RCTs, including 61,589 participants. Of these, data from three of the new trials (involving 16,085 participants) were successfully obtained and integrated with previous data.
The primary outcome assessed whether any dose of vitamin D versus placebo could prevent ARIs, where the updated analysis showed an odds ratio of 0.94 (95% CI 0.88–1.00) with a p-value of 0.057. Subgroup analyses were conducted to explore whether the effect of vitamin D varied depending on participants' age, baseline vitamin D levels, dosing frequency (daily, weekly, or monthly), or dosage size. No significant differences were found in any of these categories. This suggests that vitamin D’s potential protective effect against respiratory infections is consistent, or consistently limited, across various population groups and dosing regimens.
The proportion of participants experiencing serious adverse events did not differ significantly between the vitamin D and placebo groups (OR 0.96, 95% CI 0.90–1.04). Heterogeneity across studies was relatively low (I²=26.4%), indicating that the results were fairly consistent. However, asymmetry in the funnel plot (p=0.0020, Egger's test) suggests possible publication bias, with smaller studies showing positive results potentially overrepresented in the literature.
While the updated analysis arrives at a similar point estimate to that of the 2021 review, the newer confidence interval now includes the null value of 1.00, weakening the statistical evidence for a protective effect of vitamin D supplements against ARIs. Overall, this study suggest that vitamin D supplementation does not significantly reduce the risk of developing respiratory infections, calling into question its utility as a broad public health measure for this purpose.
Source:
Jolliffe, D. A., Camargo, C. A., Jr, Sluyter, J. D., Aglipay, M., Aloia, J. F., Bergman, P., Bischoff-Ferrari, H. A., Borzutzky, A., Bubes, V. Y., Damsgaard, C. T., Ducharme, F. M., Dubnov-Raz, G., Esposito, S., Ganmaa, D., Gilham, C., Ginde, A. A., Golan-Tripto, I., Goodall, E. C., Grant, C. C., … Martineau, A. R. (2025). Vitamin D supplementation to prevent acute respiratory infections: systematic review and meta-analysis of stratified aggregate data. The Lancet. Diabetes & Endocrinology, 13(4), 307–320. https://doi.org/10.1016/S2213-8587(24)00348-6
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Dr Kamal Kant Kohli-MBBS, DTCD- a chest specialist with more than 30 years of practice and a flair for writing clinical articles, Dr Kamal Kant Kohli joined Medical Dialogues as a Chief Editor of Medical News. Besides writing articles, as an editor, he proofreads and verifies all the medical content published on Medical Dialogues including those coming from journals, studies,medical conferences,guidelines etc. Email: drkohli@medicaldialogues.in. Contact no. 011-43720751