Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data
et al., BMJ 2017, 356, doi:10.1136/bmj.i6583, Feb 2017
Vitamin D for COVID-19
8th treatment shown to reduce risk in
October 2020, now with p < 0.00000000001 from 126 studies, recognized in 18 countries.
No treatment is 100% effective. Protocols
combine treatments.
6,200+ studies for
200+ treatments. c19early.org
|
Meta analysis of 25 RCTs showing vitamin D supplementation was safe and it protected against acute respiratory tract infection overall. Patients who were very vitamin D deficient and those not receiving bolus doses experienced the most benefit.
Vitamin D supplementation reduced the risk of acute respiratory tract infection among all participants (adjusted odds ratio aOR 0.88 [0.81-0.96], p=0.003).
In subgroup analysis, protective effects were seen in those receiving daily or weekly vitamin D without additional bolus doses (aOR 0.81 [0.72-0.91]) but not in those receiving one or more bolus doses (aOR 0.97 [0.86-1.10]). Among those receiving daily or weekly vitamin D, protective effects were stronger in those with baseline 25-hydroxyvitamin D levels <25 nmol/L (aOR 0.30 [0.17-0.53]) than in those with baseline 25-hydroxyvitamin D levels ≥25 nmol/L (aOR 0.75 [0.60-0.95]).
19 meta analyses show significant improvements with vitamin D treatment for mortality1-13,
mechanical ventilation1,5,6,11,14-16 ,
ICU admission1,3,5,6,9,11,13-18 ,
hospitalization11,
severity2,4,5,10,19 , and
cases7,18,19 .
Currently there are 126 vitamin D treatment for COVID-19 studies, showing 38% lower mortality [31‑45%], 19% lower ventilation [-3‑36%], 45% lower ICU admission [28‑58%], 19% lower hospitalization [9‑29%], and 17% fewer cases [9‑24%].
|
risk of case, 7.3% lower, RR 0.93, p = 0.003, odds ratio converted to relative risk.
|
| Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates |
1.
Shah et al., Does vitamin D supplementation reduce COVID-19 severity? - a systematic review, QJM: An International Journal of Medicine, doi:10.1093/qjmed/hcac040.
2.
Nikniaz et al., The impact of vitamin D supplementation on mortality rate and clinical outcomes of COVID-19 patients: A systematic review and meta-analysis, Pharmaceutical Sciences, doi:10.34172/PS.2021.13.
3.
Hosseini et al., Effects of Vitamin D Supplementation on COVID-19 Related Outcomes: A Systematic Review and Meta-Analysis, Nutrients, doi:10.3390/nu14102134.
4.
D’Ecclesiis et al., Vitamin D and SARS-CoV2 infection, severity and mortality: A systematic review and meta-analysis, PLOS ONE, doi:10.1371/journal.pone.0268396.
5.
Xie et al., Micronutrient perspective on COVID-19: Umbrella review and reanalysis of meta-analyses, Critical Reviews in Food Science and Nutrition, doi:10.1080/10408398.2023.2174948.
6.
Hariyanto et al., Vitamin D supplementation and Covid‐19 outcomes: A systematic review, meta‐analysis and meta‐regression, Reviews in Medical Virology, doi:10.1002/rmv.2269.
7.
Begum et al., The Role of Vitamin D in COVID-19 Survival and Prevention: A Meta-analysis, Sudan Journal of Medical Sciences, doi:10.18502/sjms.v19i1.15776.
8.
Jamilian et al., The role of vitamin D in outcomes of critical care in COVID-19 patients: Evidence from an umbrella meta-analysis of interventional and observational studies, Public Health Nutrition, doi:10.1017/S1368980024000934.
9.
Sobczak et al., Effect of Vitamin D3 Supplementation on Severe COVID-19: A Meta-Analysis of Randomized Clinical Trials, Nutrients, doi:10.3390/nu16101402.
10.
Petrelli et al., Therapeutic and prognostic role of vitamin D for COVID-19 infection: A systematic review and meta-analysis of 43 observational studies, The Journal of Steroid Biochemistry and Molecular Biology, doi:10.1016/j.jsbmb.2021.105883.
11.
Asla et al., Vitamin D on COVID-19 Patients During the Pandemic, 2022. A Systematic Review and Meta-Analysis, Current Research in Nutrition and Food Science Journal, doi:10.12944/CRNFSJ.11.1.3.
12.
Kow et al., The impact of vitamin D administration on mortality in COVID-19 patients: a systematic review and meta-analysis of randomized controlled trials, Inflammopharmacology, doi:10.1007/s10787-024-01564-2.
13.
Zhang et al., The impact of supplementing vitamin D through different methods on the prognosis of COVID-19 patients: a systematic review and meta-analysis, Frontiers in Nutrition, doi:10.3389/fnut.2024.1441847.
14.
Meng et al., The role of vitamin D in the prevention and treatment of SARS-CoV-2 infection: A meta-analysis of randomized controlled trials, Clinical Nutrition, doi:10.1016/j.clnu.2023.09.008.
15.
Yang et al., Therapeutic effects of vitamin D supplementation on COVID-19 aggravation: a systematic review and meta-analysis of randomized controlled trials, Frontiers in Pharmacology, doi:10.3389/fphar.2024.1367686.
16.
Szarpak et al., Vitamin D supplementation to treat SARS-CoV-2 positive patients. Evidence from meta-analysis, Cardiology Journal, doi:10.5603/CJ.a2021.0122.
17.
Tentolouris et al., The effect of vitamin D supplementation on mortality and intensive care unit admission of COVID-19 patients. A systematic review, meta-analysis and meta-regression, Diabetes/Metabolism Research and Reviews, doi:10.1002/dmrr.3517.
Martineau et al., 15 Feb 2017, peer-reviewed, 25 authors.
Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data
BMJ, doi:10.1136/bmj.i6583
Objectives To assess the overall effect of vitamin D supplementation on risk of acute respiratory tract infection, and to identify factors modifying this effect.
Design Systematic review and meta-analysis of individual participant data (IPD) from randomised controlled trials.
Data sOurces Medline, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, ClinicalTrials.gov, and the International Standard Randomised Controlled Trials Number registry from inception to December 2015. eligibility criteria fOr stuDy selectiOn Randomised, double blind, placebo controlled trials of supplementation with vitamin D 3 or vitamin D 2 of any duration were eligible for inclusion if they had been approved by a research ethics committee and if data on incidence of acute respiratory tract infection were collected prospectively and prespecified as an efficacy outcome. results 25 eligible randomised controlled trials (total 11 321 participants, aged 0 to 95 years) were identified. IPD were obtained for 10 933 (96.6%) participants. Vitamin D supplementation reduced the risk of acute respiratory tract infection among all participants (adjusted odds ratio 0.88, 95% confidence interval 0.81 to 0.96; P for heterogeneity <0.001). In subgroup analysis, protective effects were seen in those receiving daily or weekly vitamin D without additional bolus doses (adjusted odds ratio 0.81, 0.72 to 0.91) but not in those receiving one or more bolus doses (adjusted odds ratio 0.97, 0.86 to 1.10; P for interaction=0.05). Among those receiving daily or weekly vitamin D, protective effects were stronger in those with baseline 25-hydroxyvitamin D levels <25 nmol/L (adjusted odds ratio 0.30, 0.17 to 0.53) than in those with baseline 25-hydroxyvitamin D levels ≥25 nmol/L (adjusted odds ratio 0.75, 0.60 to 0.95; P for interaction=0.006). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (adjusted odds ratio 0.98, 0.80 to 1.20, P=0.83). The body of evidence contributing to these analyses was assessed as being of high quality. cOnclusiOns Vitamin D supplementation was safe and it protected against acute respiratory tract infection overall. Patients who were very vitamin D deficient and those not receiving bolus doses experienced the most benefit. systematic review registratiOn PROSPERO CRD42014013953.
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare financial support for this work from the National Institute for Health Research under its Health Technology Assessment programme. No author has had any financial relationship with any organisations that might have an interest in the submitted work in the previous three years. No author has had any other relationship, or undertaken any activity, that could appear to have influenced the submitted work. Ethical approval: Not required. Data sharing: A partial dataset, incorporating patient level data from trials for which the relevant permissions for data sharing have been obtained, is available from the corresponding author at a.martineau@ qmul.ac.uk. Transparency: The manuscript's guarantor (ARM) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported and that no important aspects of the study have been omitted. All analyses were prespecified in the study protocol, other than those presented in tables 3 and 5, which were conducted in response to a reviewer's request. This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 3.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/3.0/.
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