On 2014 Nov 30, Harri Hemila commented:

Morens DM, 2008 examined pieces of lung tissues from 1918-19 flu pandemic victims and perused contemporary autopsy reports, concluding that the high mortality associated with influenza was caused by secondary bacterial pneumonia. They suggested that antibiotics and bacterial vaccines should be stockpiled for the next flu pandemic.

I would like to propose that as part of pandemic-related research activities, the effect of vitamin C on bacterial pneumonia should be investigated.

In mice, influenza A infection decreases the level of vitamin C in the lungs Hennet T, 1992, and vitamin C deficiency leads to more severe pathological changes in these organs Li W, 2006. In dozens of animal studies, vitamin C protected against infections by various viruses and bacteria Hemilä 2006, pp. 5-9,105-21. In the early 20th century, Alfred Hess carried out extensive studies of scurvy and summarized a large series of autopsy findings as follows: “pneumonia, lobular or lobar, is one of the most frequent complications [of scurvy] and causes of death” and “secondary pneumonias, usually broncho-pneumonic in type, are of common occurrence, and in many [scurvy] epidemics constitute the prevailing cause of death”, see Hemilä H, 2007. Furthermore, in about two dozen placebo-controlled trials, vitamin C reduced the duration and severity of the common cold suggesting that the vitamin may have effects on the respiratory system of humans even in the absence of frank deficiency Hemilä H, 2013.

Because of the evidence suggesting that vitamin C may have an effect on pneumonia, Hemilä H, 2013 carried out a Cochrane review and found three controlled trials that looked at whether vitamin C prevents pneumonia and two that looked at whether it might help in curing pneumonia. Each of the five trials found that vitamin C supplementation was beneficial. Two of the studies were double-blind placebo-controlled RCTs, one was prophylactic and the other therapeutic.

Pitt HA, 1979 administered vitamin C to US marine recruits and reported 7 cases of pneumonia in the placebo-group compared with 1 case in the vitamin C group. Hunt C, 1994 administered vitamin C to elderly people who were admitted to hospital in the UK because of bronchopneumonia or acute exacerbation of chronic bronchitis. They reported a significant decrease in the “total respiratory score” by vitamin C administration, and 5 deaths in the placebo group compared with 1 death in the vitamin C group. Hunt et al. tested the effect of vitamin C “over and above those of normal medication (mainly antibiotics and cough medicines) to which all participants were exposed” so that all their patients received antibiotics and vitamin C was not an alternative to them.

As to bacterial pneumonia caused by influenza A infection, Kimbarowski JA, 1967 is particularly interesting as they administered vitamin C to soldiers of the former USSR who were hospitalized because of influenza A. Their main purpose was to examine an investigational laboratory test; however, as a secondary issue, they reported the number of bronchopneumonia cases in the study groups after hospitalization. The reason for diagnosing pneumonia was that the authors excluded those cases from their further study of the laboratory test. Thus, the pneumonia cases occurred after vitamin C supplementation was initiated for the influenza A patients. The two arms were balanced for the severity of influenza. The allocation method was not described but the study arms were of very similar size (112 versus 114 in the control and vitamin C arms) so it is possible that allocation occurred sequentially in the two trial arms. A placebo was not mentioned in the paper and apparently not used. Blinding of outcome assessment was not described; however, since pneumonia was a nuisance issue in their study, it seems improbable that the trial authors had substantial bias in their diagnosis of pneumonia. There were 10 cases of bronchopneumonia in the control group compared with 2 cases in the vitamin C group (P = .02, Fisher’s exact test).

Even though Kimbarowski and Mokrow’s trial is methodologically unsatisfactory in comparison with current standards, the difference in the occurrence of pneumonia in the study groups cannot be dismissed because of obvious biases Hemilä H, 2013. Furthermore, the finding is consistent with other evidence suggesting that under some conditions vitamin C may affect respiratory infections. Methodologically satisfactory trials are needed to corroborate or refute the possibility that vitamin C has an effect on bacterial pneumonia caused by influenza.

On 2014 Nov 30, Harri Hemila commented:

Morens DM, 2008 examined pieces of lung tissues from 1918-19 flu pandemic victims and perused contemporary autopsy reports, concluding that the high mortality associated with influenza was caused by secondary bacterial pneumonia. They suggested that antibiotics and bacterial vaccines should be stockpiled for the next flu pandemic.

I would like to propose that as part of pandemic-related research activities, the effect of vitamin C on bacterial pneumonia should be investigated.

In mice, influenza A infection decreases the level of vitamin C in the lungs Hennet T, 1992, and vitamin C deficiency leads to more severe pathological changes in these organs Li W, 2006. In dozens of animal studies, vitamin C protected against infections by various viruses and bacteria Hemilä 2006, pp. 5-9,105-21. In the early 20th century, Alfred Hess carried out extensive studies of scurvy and summarized a large series of autopsy findings as follows: “pneumonia, lobular or lobar, is one of the most frequent complications [of scurvy] and causes of death” and “secondary pneumonias, usually broncho-pneumonic in type, are of common occurrence, and in many [scurvy] epidemics constitute the prevailing cause of death”, see Hemilä H, 2007. Furthermore, in about two dozen placebo-controlled trials, vitamin C reduced the duration and severity of the common cold suggesting that the vitamin may have effects on the respiratory system of humans even in the absence of frank deficiency Hemilä H, 2013.

Because of the evidence suggesting that vitamin C may have an effect on pneumonia, Hemilä H, 2013 carried out a Cochrane review and found three controlled trials that looked at whether vitamin C prevents pneumonia and two that looked at whether it might help in curing pneumonia. Each of the five trials found that vitamin C supplementation was beneficial. Two of the studies were double-blind placebo-controlled RCTs, one was prophylactic and the other therapeutic.

Pitt HA, 1979 administered vitamin C to US marine recruits and reported 7 cases of pneumonia in the placebo-group compared with 1 case in the vitamin C group. Hunt C, 1994 administered vitamin C to elderly people who were admitted to hospital in the UK because of bronchopneumonia or acute exacerbation of chronic bronchitis. They reported a significant decrease in the “total respiratory score” by vitamin C administration, and 5 deaths in the placebo group compared with 1 death in the vitamin C group. Hunt et al. tested the effect of vitamin C “over and above those of normal medication (mainly antibiotics and cough medicines) to which all participants were exposed” so that all their patients received antibiotics and vitamin C was not an alternative to them.

As to bacterial pneumonia caused by influenza A infection, Kimbarowski JA, 1967 is particularly interesting as they administered vitamin C to soldiers of the former USSR who were hospitalized because of influenza A. Their main purpose was to examine an investigational laboratory test; however, as a secondary issue, they reported the number of bronchopneumonia cases in the study groups after hospitalization. The reason for diagnosing pneumonia was that the authors excluded those cases from their further study of the laboratory test. Thus, the pneumonia cases occurred after vitamin C supplementation was initiated for the influenza A patients. The two arms were balanced for the severity of influenza. The allocation method was not described but the study arms were of very similar size (112 versus 114 in the control and vitamin C arms) so it is possible that allocation occurred sequentially in the two trial arms. A placebo was not mentioned in the paper and apparently not used. Blinding of outcome assessment was not described; however, since pneumonia was a nuisance issue in their study, it seems improbable that the trial authors had substantial bias in their diagnosis of pneumonia. There were 10 cases of bronchopneumonia in the control group compared with 2 cases in the vitamin C group (P = .02, Fisher’s exact test).

Even though Kimbarowski and Mokrow’s trial is methodologically unsatisfactory in comparison with current standards, the difference in the occurrence of pneumonia in the study groups cannot be dismissed because of obvious biases Hemilä H, 2013. Furthermore, the finding is consistent with other evidence suggesting that under some conditions vitamin C may affect respiratory infections. Methodologically satisfactory trials are needed to corroborate or refute the possibility that vitamin C has an effect on bacterial pneumonia caused by influenza.