Vitamin C for preventing and treating the common cold

Harri Hemilä; Elizabeth Chalker; Bob Douglas

doi:10.1002/14651858.CD000980.pub3

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Figure 1

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

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Figure 2

Forest plot of comparison: 1 Development of colds while on vitamin C prophylaxis, outcome: 1.1 Proportions developing one or more cold episodes during prophylaxis.

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Figure 3

Forest plot of comparison: 2 Duration of colds developing on vitamin C prophylaxis, outcome: 2.1 Duration of common cold symptoms (placebo group duration set as 100%).

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Analysis 1.1

Comparison 1 Development of colds while on vitamin C prophylaxis, Outcome 1 Proportions developing one or more cold episodes during prophylaxis.

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Analysis 2.1

Comparison 2 Duration of colds developing on vitamin C prophylaxis, Outcome 1 Duration of common cold symptoms (placebo group duration set as 100%).

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Analysis 3.1

Comparison 3 Severity of colds developing on vitamin C prophylaxis, Outcome 1 Indicators of severity of episodes experienced while on prophylaxis.

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Analysis 4.1

Comparison 4 Duration of colds treated with vitamin C, Outcome 1 Mean symptom days per episode standardised against control group.

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Analysis 5.1

Comparison 5 Severity of colds treated with vitamin C, Outcome 1 Indicators of severity of episodes for which vitamin C was used as therapy.

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Table 1. Three volunteer transmission studies

Study characteristics	Walker 1967	Schwartz 1973	Dick 1990
Number of participants	91 healthy volunteers; 47 vitamin C and 44 placebo	21 healthy male volunteers	Altogether 48 participants. Three separate transmission experiments each involving 16 healthy volunteers (8 vitamin C; 8 placebo) housed closely for one week with 8 volunteers actively infected with rhinovirus
Viruses used	Rhinovirus (3 strains); 29 vitamin C and 26 placebo Influenza B (8 / 8) B814 virus (10 / 10)	Rhinovirus 44; 11 vitamin C and 10 placebo	Rhinovirus 16; 24 vitamin C and 24 placebo
Transmission method	Nasal instillation	Nasal instillation	Close contact with infected volunteers over a period of a week
Intervention	1 g/d vitamin C for 3 days before and 6 days after inoculation	3 g/d vitamin C or placebo for 2 weeks before and 1 week after inoculation	2 g/d vitamin C for 3.5 weeks before exposure to infected volunteers
Incidence outcome	18 colds developed in each group	All in both groups developed colds	19/24 in vitamin C group and 22/24 in placebo group became infected
Duration outcome	Mean duration in each group 5 days	Both groups resolved by 6 to 7 days	Not provided
Severity outcome	Mean severity score 8 for vitamin C and 7 for placebo	Severity peaked earlier for vitamin C group and resolution more advanced by day 4 (P = 0.02). Overall mean severity scores not significantly different in the 2 groups	Mean cumulative severity score and mucus weights reduced in the vitamin C recipients (P = 0.03). Severity of colds reduced by 50% (P = 0.02; Dick 1990)
Comments	Not double‐blind	Double‐blind. Nasal virus shedding similar in the two groups	Double‐blind. Viral shedding similar in these 2 groups. The studies are briefly described in a series of conference abstracts but no full published paper is available

Table 1. Three volunteer transmission studies

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Comparison 1. Development of colds while on vitamin C prophylaxis

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Proportions developing one or more cold episodes during prophylaxis Show forest plot	29	11306	Risk Ratio (M‐H, Fixed, 95% CI)	0.95 [0.92, 0.98]

1.1 All eligible trials with exception of subgroup removed below	24	10708	Risk Ratio (M‐H, Fixed, 95% CI)	0.97 [0.94, 1.00]
1.2 Short‐term exposure to cold and/or severe physical stress	5	598	Risk Ratio (M‐H, Fixed, 95% CI)	0.48 [0.35, 0.64]

Comparison 1. Development of colds while on vitamin C prophylaxis

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Comparison 2. Duration of colds developing on vitamin C prophylaxis

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Duration of common cold symptoms (placebo group duration set as 100%) Show forest plot	29	9649	Mean Difference (IV, Fixed, 95% CI)	‐9.07 [‐12.58, ‐5.57]

1.1 Prophylaxis 200 mg or more daily plus or minus loading dose at cold onset in adults	17	7215	Mean Difference (IV, Fixed, 95% CI)	‐7.72 [‐11.76, ‐3.69]
1.2 Prophylaxis 200 mg or more daily plus or minus loading dose at cold onset in children	12	2434	Mean Difference (IV, Fixed, 95% CI)	‐13.24 [‐20.32, ‐6.16]

Comparison 2. Duration of colds developing on vitamin C prophylaxis

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Comparison 3. Severity of colds developing on vitamin C prophylaxis

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Indicators of severity of episodes experienced while on prophylaxis Show forest plot	14	7018	Std. Mean Difference (IV, Fixed, 95% CI)	‐0.12 [‐0.17, ‐0.07]

1.1 Mean days indoors or off work or school per episode	7	5066	Std. Mean Difference (IV, Fixed, 95% CI)	‐0.11 [‐0.17, ‐0.05]
1.2 Mean symptom severity score per episode	7	1952	Std. Mean Difference (IV, Fixed, 95% CI)	‐0.14 [‐0.22, ‐0.05]

Comparison 3. Severity of colds developing on vitamin C prophylaxis

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Comparison 4. Duration of colds treated with vitamin C

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mean symptom days per episode standardised against control group Show forest plot	7	3249	Mean Difference (IV, Fixed, 95% CI)	‐2.90 [‐8.20, 2.39]

Comparison 4. Duration of colds treated with vitamin C

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Comparison 5. Severity of colds treated with vitamin C

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Indicators of severity of episodes for which vitamin C was used as therapy Show forest plot	4	2708	Std. Mean Difference (IV, Fixed, 95% CI)	‐0.07 [‐0.15, 0.01]

1.1 Mean days indoors or off work or school	3	2569	Std. Mean Difference (IV, Fixed, 95% CI)	‐0.08 [‐0.16, ‐0.00]
1.2 Mean symptom severity score per episode	1	139	Std. Mean Difference (IV, Fixed, 95% CI)	0.15 [‐0.21, 0.51]

Comparison 5. Severity of colds treated with vitamin C

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