Vitamin C intake and susceptibility to pneumonia.

Feeding guinea pigs a diet deficient in vitamin C increases their susceptibility to infections, which may be caused by the effects of the vitamin on T lymphocytes and phagocytes (1). A few studies suggest that vitamin C intake affects human susceptibility to infections to some as yet unknown extent (1). In particular four trials involving British males showed an average 30% decrease in common cold incidence in groups given vitamin C, suggesting effects in certain population groups (2). Controlled trials have consistently found that large dose vitamin C supplementation alleviates the symptoms of the common cold, but the mechanism of this effect is poorly understood (1-3). Here we assess the relation of vitamin C intake to the incidence of pneumonia by analyzing findings from three controlled trials. The literature on vitamin C and infectious diseases has already been explored thoroughly (1,2) and all controlled trials that reported the number of pneumonia cases in the study groups were selected for this analysis (Table 1). Fisher's exact test was used to calculate the one-tailed mid-P values (4) for each set of data separately. Exact hypothesis test for several 2×2 contingency tables (4) was used to calculate a one-tailed mid-P value for the combined data of two or three studies. Three controlled trials have reported the number of pneumonia cases in a vitamin C group and a control group, each trial finding a considerably lower incidence of pneumonia in the group given vitamin C (Table 1). Glazebrook and Thomson (5) studied schoolboys (15 to 20 years old) in an institution in the UK. No cases of pneumonia occurred in the vitamin C group. Placebo was not used, but because the vitamin was added to the food in the kitchen the placebo effect does not seem relevant. For practical reasons the subjects were not randomly allocated to the study groups, but certain administrative divisions were served vitamin-supplemented food and others remained as controls. A tonsillitis epidemic that affected all divisions uniformly the year before had shown that they could not be considered discrete units (5). Kimbarowski and Mokrow (6) in the former Soviet Union investigated military recruits who had acquired influenza A infection. The number of pneumonia cases was significantly smaller in the vitamin C group. Placebo was not used and the allocation method was not described. Nevertheless the distribution of influenza severity was similar in both study groups. Pitt and Costrini (7), primarily interested in whether vitamin C affects the common cold, carried out a randomized double blind placebo-controlled trial with military recruits in a training camp in the United States. Pneumonia incidence was substantially lower in the vitamin C group. Each of these three trials found a 80% lower incidence of pneumonia in the vitamin C group. It is highly unlikely that the differences reported between the study groups in favor of the vitamin C groups would have occurred purely by chance (P = 0.00002). The study of Pitt and Costrini (7) is the most carefully conducted of the three, but the size of the effect is similar to the others. Thus there is no obvious tendency for the technically superior trial to show a smaller effect. If the Kimbarowski-Mokrow study is excluded from the analysis because it is technically the least satisfactory, there is still a highly significant difference in the pneumonia incidence between the vitamin C and control groups in the remaining two trials (P = 0.0004). The notion that vitamin C intake may effect various infections is an old one (1,5,8,9). In 1917 Hess (10) concluded from his clinical experience with children that one of the important consequences of vitamin C deficiency was a markedly increased susceptibility to infection, pneumonia being a particular danger. In 1939 Sabin (11) reported about 5 cases of pneumonia in 25 rhesus monkeys deficient in