Efficacy of High‐Dose Vitamin D Supplementation as an Adjuvant Treatment on Pneumonia: Systematic Review and a Meta‐Analysis of Randomized Controlled Studies

Abstract

The purpose of this meta-analysis was to summarize randomized controlled trial (RCT) evidence and evaluate the efficacy and safety of vitamin D (VD) supplementation as an adjunct to antibiotics for the treatment of pneumonia. Data sources published from the inception dates up to January 2020 were searched. RCTs of VD supplementation of any duration, age, and dosing regimen type were eligible for inclusion if data on pneumonia were collected. Thirteen studies (4786 randomized participants) fulfilled eligibility criteria. VD supplementation significantly increased levels of serum 25(OH)D (mean difference = 15.97; 95% CI, 7.49-24.44; P = .002) and reduced incidence of repeat episodes of pneumonia (risk ratio [RR] = 0.68; 95% CI, 0.50-0.93; P = .02). Subgroup analysis revealed VD supplementation had more reducing effects on repeat episodes of pneumonia among participants in trials in which the population were children (RR = 0.66; 95% CI, 0.48-0.90), duration <3 months (RR = 0.55; 95% CI, 0.33-0.91), or dose of VD <300,000 IU (RR = 0.51; 95% CI, 0.29-0.89). Although our results suggested that VD supplementation had a positive effect on recovery rate of pneumonia (RR = 1.28; 95% CI, 0.94-1.74; I 2 = 13%), there was no statistical difference (P = .12). High-dose VD intervention may have an effect on reducing the incidence rate of repeat episodes of pneumonia by enhancing immune efficacy, although more population studies are needed to support that VD supplementation has therapeutic effects on pneumonia itself.

Post-discharge pneumonia after hip arthroplasty. A population-based study of 55,842 patients in Poland

“…There are reports that treatment of osteoporosis reduces the risk of death [17]. Moreover, vitamin D supplementation significantly reduced the incidence of recurrent episodes of pneumonia in a study by Yang et al [18].…”

Efficacy of Vitamin D Supplements in Treatment of Acute Respiratory Infection: A Meta-Analysis for Randomized Controlled Trials

“…Regarding pulmonary TB, two meta-analyses [ 39 , 40 ] reported that a significant accelerated sputum conversion was observed, three [ 33 , 34 , 35 ] reported that there was no significant benefit because the time to sputum conversion was not shortened or the proportion of sputum smear and culture conversion was not increased, and one [ 32 ] reported that the time to sputum smear and culture conversion did not improve, whereas the proportion of sputum smear and culture conversion increased. Among the three meta-analyses [ 36 , 37 , 38 ] about the treatment of pneumonia, two of them [ 36 , 38 ] reported that vitamin D supplementation had no marked efficacy in the treatment of pneumonia, and the remaining one [ 37 ] reported that it was uncertain whether vitamin D supplementation was effective because the results were imprecise. Among the two meta-analyses [ 41 , 42 ] about the treatment of COVID-19, one [ 41 ] reported a statistically lower ICU requirement in patients with vitamin D supplementation, while the other one [ 42 ] reported no significant efficacy on major health-related outcomes in patients with COVID-19.…”

“…Several RCTs reported that vitamin D supplements had a beneficial effect [ 14 , 19 , 21 , 28 , 29 , 30 ], while others reported no effect [ 15 , 16 , 17 , 18 , 20 , 22 , 23 , 24 , 25 , 26 , 27 , 31 ]. Several meta-analyses have been published on the efficacy of vitamin D supplements in the treatment of pulmonary tuberculosis (TB), pneumonia, and COVID-19 [ 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ]. However, no meta-analysis has been published for the efficacy of vitamin D supplements in the treatment of comprehensive ARIs.…”

Exclusive Breastfeeding and Vitamin D Supplementation: A Positive Synergistic Effect on Prevention of Childhood Infections?

“…In Table 4 we reported the meta-analyses that evaluated the association between vitamin D status or vitamin D supplementation with infections risk or severity in children [ 127 , 128 , 134 , 135 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 , 152 , 153 , 154 , 155 , 156 ]. Most of meta-analyses confirmed a significant protective role of vitamin D supplementation against respiratory infections; particularly, major benefits were observed in children and adolescents, asthmatic subjects, individuals with severe vitamin D deficiency, and those receiving a daily dosing regimen (400–1000 IU/day) for a duration of 12 months or less.…”

“…A systematic review of observational studies and randomized controlled trials (RCTs) focusing on extra-skeletal actions of vitamin D confirmed that vitamin D supplementation plays a significant role in the primary prevention of acute respiratory infections [ 157 ]. Preventive efficacy of vitamin D supplementation was particularly evident in subjects with severe deficiency [25(OH)D < 10 ng/mL], while vitamin D administration was not effective as adjunctive treatment of acute respiratory infections [ 155 , 156 , 157 ]. An expert consensus statement from the World Association of Infectious Diseases and Immunological Disorders confirmed that vitamin D could play a role in children with recurrent respiratory infections.…”