Vitamin C and Infections
"> Figure 1
<p>The numbers of participants in the placebo-controlled trials for which ≥1 g/day of vitamin C was administered. The numbers of participants in studies published over two consecutive years are combined and plotted for the first of the two years. This figure is based on data collected by Hemilä and Chalker (2013) [<a href="#B68-nutrients-09-00339" class="html-bibr">68</a>,<a href="#B69-nutrients-09-00339" class="html-bibr">69</a>]. See <a href="#app1-nutrients-09-00339" class="html-app">Supplementary file 1</a> of this review for the list of the studies. RCT, randomized controlled trial.</p> "> Figure 2
<p>(<b>A</b>) Dose–response relationship in the Karlowski (1975) trial. The placebo arm is located at 0 g/day, the 3 g/day regular vitamin C and the 3 g/day treatment vitamin C arms are in the middle and the regular + treatment arm is at 6 g/day [<a href="#B72-nutrients-09-00339" class="html-bibr">72</a>]. The 95% CIs are shown for the comparison against the placebo arm. With inverse-variance weighing, test for trend in a linear model gives <span class="html-italic">p</span>(2-tail) = 0.018. The addition of the linear vitamin C effect to the statistical model containing a uniform vitamin C effect improved the regression model by <span class="html-italic">p</span> = 0.002. Previously, analysis of variance for trend calculated <span class="html-italic">p</span> = 0.040 for the linear trend [<a href="#B83-nutrients-09-00339" class="html-bibr">83</a>]; (<b>B</b>) Dose–response relationship in the Anderson (1974) trial. The placebo arm #4 is located at 0 g/day, vitamin C treatment arm #7 at 4 g/day and vitamin C treatment arm #8 at 8 g/day [<a href="#B84-nutrients-09-00339" class="html-bibr">84</a>]. In the Anderson (1974) trial, vitamin C was administered only on the first day of the common cold. The 95% CIs are shown for the comparison against the placebo arm. With inverse-variance weighing, test for trend in a linear model gives <span class="html-italic">p</span>(2-tail) = 0.013. See <a href="#app1-nutrients-09-00339" class="html-app">Supplementary file 2</a> for the calculation of the trend for both studies.</p> ">
Abstract
:1. Early History on Vitamin C and Infections
2. Biology Relevant to the Effects of Vitamin C on Infections
2.1. Dose–Concentration Relationship
2.2. Infections Increase Oxidative Stress
2.3. Vigorous Physical Activity Increases Oxidative Stress
2.4. Vitamin C May Protect against Stress Caused by Cold and Hot Environments
2.5. Marginally Low Vitamin C Status Might Lead to Benefits of Supplementation
2.6. Vitamin C Has Effects on the Immune System
2.7. The Diverse Biochemical, Physiological, and Psychological Effects of Vitamin C
2.8. The Effects of Antioxidants against Infections May Be Heterogeneous
3. Infections in Animals
3.1. Studies with Diets Containing Vitamin C
3.2. Studies with Pure Vitamin C
3.3. Implications of the Animal Studies
4. The Common Cold
4.1. Vitamin C and the Common Cold
4.2. Vitamin C Does Not Decrease the Average Incidence of Colds in the General Community
4.3. Vitamin C May Decrease Common Cold Incidence in Special Conditions
4.4. Vitamin C Might Protect against the Common Cold in a Restricted Subgroup of the General Community
4.5. Vitamin C Shortens and Alleviates the Common Cold
4.6. Possible Differences in the Effects of Vitamin C between Subgroups
4.7. Dose Dependency of Vitamin C Supplementation Effect
4.8. Vitamin C and Complications of the Common Cold
5. Problems in the Interpretation: Non-Comparability of the Vitamin C and Common Cold Trials
5.1. Vitamin C Doses in Vitamin C and Control Groups
5.2. Non-Compliance of Participants
5.3. Implications of the Common Cold Studies
6. Evaporation of Interest in Vitamin C and the Common Cold after 1975
7. Pneumonia
7.1. Vitamin C and the Incidence of Pneumonia
7.2. Vitamin C in the Treatment of Pneumonia
8. Tetanus
9. Other Infections
10. Observational Studies on Vitamin C and Infections
11. Potentially Harmful Interactions between Vitamins C and E
12. Misconceptions and Prejudices about Vitamin C and Infections
13. Conclusions
Supplementary Materials
Acknowledgments
Conflicts of Interest
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Infection | No. of Studies | No. of Studies with Benefit in Any Infectious Disease Outcome with p ≤ 0.01 |
---|---|---|
All | 28 | 20 |
Tuberculosis (TB) | 11 | 7 |
Bacterial infection (non-TB) a | 15 | 11 |
Diphtheria toxin | 2 | 2 |
Category | No. of Studies in the Category | No. of Studies with Benefit in Any Infectious Disease Outcome with p ≤ 0.01 |
---|---|---|
All studies | 148 | 86 |
Time of publication | ||
Published in 1935–1949 | 40 | 20 |
Published in 1950–1989 | 48 | 32 |
Published in 1990–2005 | 60 | 34 |
Animal species | ||
Monkey | 13 | 4 |
Guinea pig | 36 | 21 |
Cow, sheep, rabbit | 10 | 8 |
Cat | 1 | 1 |
Rat | 15 | 10 |
Gerbil, hamster | 7 | 5 |
Mouse | 18 | 9 |
Mammals a | 100 | 58 |
Birds | 13 | 8 |
Fish | 35 | 20 |
Etiological agent | ||
Tuberculosis (TB) | 8 | 3 |
Bacteria (non-TB) | 70 | 36 |
Bacterial toxins | 19 | 16 |
Virus | 22 | 12 |
Candida albicans | 6 | 4 |
Protozoa | 23 | 15 |
All Studies | 29 |
---|---|
Tuberculosis (TB) | 6 |
Bacteria (non-TB) a | 7 |
Bacterial toxin b | 6 |
Virus (rabies) | 1 |
Candida albicans | 2 |
Protozoa c | 7 |
Outcome Participants | No. of Studies | No. of Participants | Effect of Vitamin C (95% CI) | p |
---|---|---|---|---|
Incidence of colds b | ||||
General population | 24 | 10,708 | −3% (−6% to 0%) | |
People under heavy short-term physical stress | 5 | 598 | −52% (−65% to −36%) | 10−6 |
Duration of colds | No. of colds | |||
All studies (≥0.2 g/day) | 31 | 9745 | −9.4% (−13% to −6%) | 10−7 |
Adults (≥1 g/day) | 13 | 7095 | −8% (−12% to −4%) | 10−4 |
Children (≥1 g/day) | 10 | 1532 | −18% (−27% to −9%) | 10−5 |
Severity of colds | No. of colds | |||
All studies | 16 | 7209 | −0.12 (−0.17 to −0.07) c | 10−6 |
Study | Subgroup | Effect of Vitamin C | Outcome | Test of Subgroup Differences (p) |
---|---|---|---|---|
Anderson (1972) [80] | Contact with young children | −46% | total days confined to house | 0.036 |
No contact with young children | −17% | |||
Anderson (1972) [80] | Usually ≥2 colds per winter | −43% | total days confined to house | 0.033 |
Usually 0–1 colds per winter | −13% | |||
Constantini (2011) [86] | Male adolescent competitive swimmers | −47% | duration of colds | 0.003 |
Female adolescent competitive swimmers | +16% | |||
Baird (1979) [78] | Male students in UK | −37% | incidence of colds | 0.0001 |
Female students in UK | +24% | |||
Carr (1981) [87] | Twins living separately | −35% | duration of colds | 0.035 |
Twins living together | +1% |
Vitamin C Level (g/Day) | |||
---|---|---|---|
Trial Country, Participants | Dietary Intake Level in the Control Group | Supplement to the Control Group a | Supplement to the Vitamin C Group |
Cowan (1942) [100] USA, schoolchildren | ? | 0.025–0.05 | |
Baird (1979) [78] UK, students | 0.05 | 0.08 | |
Glazebrook (1942) [97] UK, boarding school boys | 0.015 | 0.05–0.3 | |
Peters (1993) [99] South Africa, marathon runners | 0.5 | 0.6 | |
Sabiston (1974) [98] Canada, military recruits | 0.04 | 1 | |
Carr (1981) [87] Australia, twins | ? | 0.07 | 1 |
Karlowski (1975) [72] USA, NIH employees | b | 3 6 |
Study | Pneumonia Cases/Total | p a | Incidence of Pneumonia in the Control Group (1/1000 Person-Years) | |
---|---|---|---|---|
Vitamin C | Control | |||
Glazebrook (1942) [97] | 0/335 | 17/1100 | 0.006 | 30 |
Kimbarowski (1967) [121] | 2/114 | 10/112 | 0.022 | 9% b |
Pitt (1979) [122] | 1/331 | 7/343 | 0.009 | 120 |
Incidence of pneumonia in selected populations: | ||||
Merchant (2004) [124] | Middle-aged males in the USA | 3 | ||
Hemilä (2004) [125] | Middle-aged males in Finland | 5 | ||
Pazzaglia (1983) [126] | Military recruits in the USA | 60 | ||
Paynter (2010) [127] | Children in developing countries, up to | 400 |
Infection, ATBC Study Subgroup | No. of Participants | Effect of Vitamin E RR (95% CI) | Test of Interaction p | NNH |
---|---|---|---|---|
Pneumonia | ||||
Body weight < 60 kg who started smoking at ≤20 years | ||||
Dietary vitamin C | ||||
<median | 467 | 0.98 (0.48 to 2.0) | 0.026 | |
≥median (75 mg/day) | 468 | 3.48 (1.61 to 7.5) | 13 | |
Pneumonia | ||||
Body weight ≥ 100 kg who started smoking at ≤20 years | ||||
Dietary vitamin C | ||||
<median | 613 | 1.37 (0.46 to 4.0) | 0.019 | |
≥median (95 mg/day) | 613 | 14.5 (1.84 to 114) | 28 | |
Tuberculosis | ||||
Smoking ≥ 20 cigarettes/day | ||||
Dietary vitamin C | ||||
<median | 9073 | 0.82 (0.50 to 1.33) | 0.011 a | |
≥median (90 mg/day) | 8172 | 2.25 (1.19 to 4.23) | 240 |
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Hemilä, H. Vitamin C and Infections. Nutrients 2017, 9, 339. https://doi.org/10.3390/nu9040339
Hemilä H. Vitamin C and Infections. Nutrients. 2017; 9(4):339. https://doi.org/10.3390/nu9040339
Chicago/Turabian StyleHemilä, Harri. 2017. "Vitamin C and Infections" Nutrients 9, no. 4: 339. https://doi.org/10.3390/nu9040339