Efficacy of Vitamin C Supplementation on Chronic Obstructive Pulmonary Disease (COPD): A Systematic Review and Meta-Analysis

Figures & data

Figure 1 PRISMA 2009 Flow Diagram.

Notes: PRISMA figure adapted from Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009). Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med 6(7): e1000097. 72.

Table 1 Characteristics of Included Studies

Study	Design	Country	Group	Sample Size	Average Age	Sex (Male/Female)	Intervention	Primary Outcome	Secondary Outcome	Mean Follow-Up (Weeks)
Wu et al 2007^Citation6	RCT	China, Taiwan	Vitamin C	9	14.05±12.12	7:2	Vitamin C 250mg/d	ab	ef	12
			Placebo	8	9.41±7.87	7:1	Placebo
Ansari et al 2010^Citation26	RCT, Single blind	Pakistan	Vitamin C	22	55.33±2.19	Male	Vitamin C 1000mg/d	ab	NA	36 (9months)
			Placebo	23	53.46±1.94	Male	salbutamol 100µg and beclomethasone 50µg
Liu, L.C. et al 2010^Citation13	RCT, Double blind	China, Taiwan	Vitamin C	12	68–72	Male	Vitamin C 500mg/d+Vitamin E 400IU/d	ab	efh	13
			Placebo	9	68–72	Male	Vitamin E 400IU/d
Kanani et al 2012^Citation14	RCT	India	Vitamin C	18	71.24+0.56	Male	Vitamin C 500mg/d+Vitamin E 200mg/d	ab	g	12 (3months)
			Placebo	16	71.24+0.56	Male	Vitamin E 200mg/d
Long et al 2013^Citation24	RCT	China	Vitamin C	25	45.5±13.2	15:1	Conventional therapy+exercise+vc400–800mg/d+ve8–10iu/d	a	ef	NA
			Placebo	20	46.4±3.6	12:8	Conventional therapy+exercise
Zou et al 2015^Citation25	RCT	China	Vitamin C	58	NA	NA	Vitamin C 300–600mg/d	ab	NA	24 (6months)
			Placebo	59	NA	NA	Nothing
Pirabbasi et al 2016^Citation27	RCT, Single blind	Malaysia	Vitamin C	13	64.5±10.2	Male	Vitamin C 500mg/d	NA	cfefg	24 (6months)
			Placebo	18	64.17±8.3	Male	NA
Chen et al 2016^Citation22	RCT	China	Vitamin C	30	71. 27±3.32	14:16	Conventional therapy+Vitamin C 500mg/d	a	gh	20d
			Placebo	30	71. 57 ± 2. 69	13:17	Conventional therapy
Jia et al 2017^Citation23	RCT	China	Vitamin C	30	64.17±8.3	Male	Vitamin C 1500mg/d	NA	cdefg	24 (6months)
			Placebo	30	64.17±8.3	Male	Blank control group
Gouzi et al 2019^Citation15	RCT, Double blind	France	Vitamin C	31	40–78	13:13	Vitamin C 180mg/d	NA	cdefh	28d
			Placebo	26	40–78	15:16	Placebo

Notes: Conventional therapy: anti-infection; oxygen therapy: antiasthmatic routine treatment. ^aFEV1%; ^bFEV1/FVC; ^cBMI; ^dFFMI; ^eVitamin C; ^fVitamin E; ^gGSH; ^hSOD.

Abbreviations: FEV1%, forced expiratory volume in 1 second; RCT, Randomized Clinical Trial; GSH, glutathione; SOD, Superoxide Dismutase.

Table 2 GRADE Evaluation Results

Outcome	No of Participants (Studies)	Risk of Bias	Inconsistency	Indirectness	Imprecision	Publication Bias	Relative Effect (95% CI)	GRADE
FEV1%	256 (6)	Not serious	Serious^a	Not serious	Serious^b	Not serious	SMD:1.34, (0.01, 2.67)	⊕⊕〇〇
FEV1/FVC	234 (5)	Not serious	Serious^a	Not serious	Serious^b	Not serious	SMD:0.66, (0.26, 1.06)	⊕⊕〇〇
Serum vitamin C levels	231 (6)	Not serious	Serious^a	Not serious	Serious^b	Not serious	SMD:0.63, (0.02, 1.24)	⊕⊕〇〇
Serum vitamin E levels	231 (6)	Not serious	Serious^a	Not serious	Serious^b	Not serious	SMD: 0.83, (−0.08, 1.74)	⊕⊕〇〇
Serum GSH levels	185 (4)	Not serious	Serious^a	Not serious	Serious^b	Not serious	SMD:2.47, (1.06, 3.89)	⊕⊕〇〇
Serum SOD levels	138 (3)	Not serious	Serious^a	Not serious	Serious^b	Not serious	SMD: 0.42, (−1.31, 2.15)	⊕⊕〇〇
BMI	148 (3)	Not serious	Not serious	Not serious	Serious^b	Not serious	WMD: −0.17, (−1.5, 1.16)	⊕⊕⊕〇
FFMI	148 (3)	Not serious	Not serious	Not serious	Serious^b	Not serious	WMD: −0.17, (−1.06, 0.72)	⊕⊕⊕〇

Notes: ^aI²>50%; ^bThe sample size is less than 300.

Abbreviation: GRADE, Grading of Recommendations Assessment Development and Evaluation.

Figure 2 (A) Summary of risk of bias for each included study. (B) bar graph of the risk of bias showing the percentage of risk level for each characterized risk. Each color represents a different level of bias: red for high risk, green for low risk, and yellow for unclear risk of bias.

Figure 3 FEV1% in lung function.

Figure 4 Sensitivity Analysis FEV1%.

Figure 5 FEV1/FVC in lung function.

Figure 6 Vitamin C level in serum.

Figure 7 Serum vitamin E level.

Figure 8 GSH level in serum in COPD patients.

Figure 9 Enzymatic antioxidants of lungs.

Figure 10 Nutrition levels (A, B).

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