Zahra Ali Padhani1, Zorays Moazzam2, Alina Ashraf2, Hasana Bilal3, Rehana A Salam3, Jai K Das3, Zulfiqar A Bhutta4. 1. Department of Women's and Children's Health, Aga Khan University Hospital, Karachi, Pakistan. 2. Aga Khan University, Karachi, Pakistan. 3. Division of Women and Child Health, Aga Khan University Hospital, Karachi, Pakistan. 4. Centre for Global Child Health, The Hospital for Sick Children, Toronto, Canada.
Abstract
BACKGROUND: According to the Global Burden of Disease Study 2015, lower respiratory tract infection is the leading cause of infectious disease death, and the fifth most common cause of death overall. Vitamin C has a role in modulating resistance to infectious agents, therefore vitamin C supplementation may be important in preventing and treating pneumonia. OBJECTIVES: To assess the impact of vitamin C supplementation to prevent and treat pneumonia in children and adults. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, PubMed, CINAHL, LILACS, Web of Science, and two trials registers to 4 March 2020. We also checked references to identify additional studies. We did not apply any publication status or language filters. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs (studies using allocation methods that are not random, e.g. date of birth, medical record number) assessing the role of vitamin C supplementation in the prevention and treatment of pneumonia in children and adults compared to control or placebo. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included seven studies in the review and identified two ongoing studies. The seven included studies involved a total of 2774 participants; five studies were RCTs and two were quasi-RCTs. The included studies were conducted in high-income countries (UK, USA and Chile) and lower-middle-income countries (Bangladesh and Pakistan). Four studies were conducted in hospital inpatient settings, two in schools, and one in a military training centre. Three studies included children under five years of age, two school-aged children, one adult participants, and one older participants aged 60 to 90 years. Two studies assessed the effect of vitamin C supplementation for pneumonia prevention; four studies assessed the effect of vitamin C supplementation as an adjunct to pneumonia treatment; and one study assessed the role of vitamin C for both prevention and treatment of pneumonia. For pneumonia prevention, the included studies provided supplementation in doses of 500 mg daily for 14 weeks, 2 g daily for 8 weeks, and 2 g daily for 12 weeks. For pneumonia treatment, the included studies provided vitamin C supplementation in doses of 125 mg daily (until discharge), 200 mg for 4 weeks, and 200 mg until discharge, as an adjunct to the pneumonia treatment. We assessed the included studies as at overall either high or unclear risk of bias for random sequence generation, allocation concealment, and blinding. We judged the quality of the evidence as very low. Three studies assessed the effect of vitamin C supplementation for pneumonia prevention; we judged the quality of the evidence as very low. We are uncertain about the effect of vitamin C supplementation on pneumonia incidence (risk ratio (RR) 0.46, 95% confidence interval (CI) 0.06 to 3.61; 2 studies, 736 participants; I² = 75%; very low-quality evidence) and adverse events (urticaria) (RR 3.11, 95% CI 0.13 to 76.03; 1 study, 674 participants; very low-quality evidence). No included studies reported our other primary outcomes (pneumonia prevalence and mortality) or any of our secondary outcomes. Five studies assessed the effect of vitamin C supplementation as an adjunct to pneumonia treatment; we judged the quality of the evidence as very low. One study reported a decrease in the duration of illness in the vitamin C supplementation group (3.4 days ± 2.54) compared to the control group (4.5 days ± 2.35), and one study reported a decrease in number of days required for improvement in oxygen saturation (1.03 days ± 0.16 versus 1.14 days ± 1.0) and respiratory rate (3.61 days ± 1.50 versus 4.04 days ± 1.62) in the vitamin C supplementation group compared to the control group. We are uncertain of the effect of vitamin C supplementation on mortality due to pneumonia (RR 0.21, 95% CI 0.03 to 1.66; 1 study, 57 participants; very low-quality evidence). One study reported that the mean duration of hospital stay was 6.75 days amongst children in the vitamin C supplementation group and 7.75 days in the control group; another study reported a lower mean duration of hospital stay in the vitamin C supplementation group compared to the control group (109.55 hours ± 27.89 versus 130.64 hours ± 41.76). AUTHORS' CONCLUSIONS: Due to the small number of included studies and very low quality of the existing evidence, we are uncertain of the effect of vitamin C supplementation for the prevention and treatment of pneumonia. Further good-quality studies are required to assess the role of vitamin C supplementation in the prevention and treatment of pneumonia.
BACKGROUND: According to the Global Burden of Disease Study 2015, lower respiratory tract infection is the leading cause of infectious disease death, and the fifth most common cause of death overall. Vitamin C has a role in modulating resistance to infectious agents, therefore vitamin C supplementation may be important in preventing and treating pneumonia. OBJECTIVES: To assess the impact of vitamin C supplementation to prevent and treat pneumonia in children and adults. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, PubMed, CINAHL, LILACS, Web of Science, and two trials registers to 4 March 2020. We also checked references to identify additional studies. We did not apply any publication status or language filters. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs (studies using allocation methods that are not random, e.g. date of birth, medical record number) assessing the role of vitamin C supplementation in the prevention and treatment of pneumonia in children and adults compared to control or placebo. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included seven studies in the review and identified two ongoing studies. The seven included studies involved a total of 2774 participants; five studies were RCTs and two were quasi-RCTs. The included studies were conducted in high-income countries (UK, USA and Chile) and lower-middle-income countries (Bangladesh and Pakistan). Four studies were conducted in hospital inpatient settings, two in schools, and one in a military training centre. Three studies included children under five years of age, two school-aged children, one adult participants, and one older participants aged 60 to 90 years. Two studies assessed the effect of vitamin C supplementation for pneumonia prevention; four studies assessed the effect of vitamin C supplementation as an adjunct to pneumonia treatment; and one study assessed the role of vitamin C for both prevention and treatment of pneumonia. For pneumonia prevention, the included studies provided supplementation in doses of 500 mg daily for 14 weeks, 2 g daily for 8 weeks, and 2 g daily for 12 weeks. For pneumonia treatment, the included studies provided vitamin C supplementation in doses of 125 mg daily (until discharge), 200 mg for 4 weeks, and 200 mg until discharge, as an adjunct to the pneumonia treatment. We assessed the included studies as at overall either high or unclear risk of bias for random sequence generation, allocation concealment, and blinding. We judged the quality of the evidence as very low. Three studies assessed the effect of vitamin C supplementation for pneumonia prevention; we judged the quality of the evidence as very low. We are uncertain about the effect of vitamin C supplementation on pneumonia incidence (risk ratio (RR) 0.46, 95% confidence interval (CI) 0.06 to 3.61; 2 studies, 736 participants; I² = 75%; very low-quality evidence) and adverse events (urticaria) (RR 3.11, 95% CI 0.13 to 76.03; 1 study, 674 participants; very low-quality evidence). No included studies reported our other primary outcomes (pneumonia prevalence and mortality) or any of our secondary outcomes. Five studies assessed the effect of vitamin C supplementation as an adjunct to pneumonia treatment; we judged the quality of the evidence as very low. One study reported a decrease in the duration of illness in the vitamin C supplementation group (3.4 days ± 2.54) compared to the control group (4.5 days ± 2.35), and one study reported a decrease in number of days required for improvement in oxygen saturation (1.03 days ± 0.16 versus 1.14 days ± 1.0) and respiratory rate (3.61 days ± 1.50 versus 4.04 days ± 1.62) in the vitamin C supplementation group compared to the control group. We are uncertain of the effect of vitamin C supplementation on mortality due to pneumonia (RR 0.21, 95% CI 0.03 to 1.66; 1 study, 57 participants; very low-quality evidence). One study reported that the mean duration of hospital stay was 6.75 days amongst children in the vitamin C supplementation group and 7.75 days in the control group; another study reported a lower mean duration of hospital stay in the vitamin C supplementation group compared to the control group (109.55 hours ± 27.89 versus 130.64 hours ± 41.76). AUTHORS' CONCLUSIONS: Due to the small number of included studies and very low quality of the existing evidence, we are uncertain of the effect of vitamin C supplementation for the prevention and treatment of pneumonia. Further good-quality studies are required to assess the role of vitamin C supplementation in the prevention and treatment of pneumonia.
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