Effects of moderate doses of vitamin A as an adjunct to the treatment of pneumonia in underweight and normal-weight children: a randomized, double-blind, placebo-controlled trial. The clinical effects of vitamin C supplementation in elderly hospitalised patients with acute respiratory infections. Vitamin A supplementation and severity of pneumonia in children admitted to the hospital in Dar es Salaam, Tanzania. Vitamin C and acute illness in Navajo school children. Randomised, double blind, placebo controlled clinical trial of efficacy of vitamin A treatment in non-measles childhood pneumonia. Vitamin C prophylaxis in marine recruits. A randomized controlled trial of the effect of zinc as adjuvant therapy in children 2-35 mo of age with severe or nonsevere pneumonia in Bhaktapur, Nepal. Effect of routine zinc supplementation on pneumonia in children aged 6 months to 3 years: randomised controlled trial in an urban slum. Vitamin C as a preventive medicine against common colds in children.
Randomized controlled trials have shown inconsistent responses of childhood pneumonia to the use of vitamin A as an adjunct to the standard treatment of pneumonia.
                We evaluated the effect of a moderate dose of vitamin A as an adjunct to standard antimicrobial treatment on the duration of respiratory signs in children with pneumonia.
                Children, aged 2-59 mo, with pneumonia and weight-for-age <50th percentile who had been admitted to the Baca Ortíz Children's Hospital in Quito, Ecuador, were randomly assigned to receive 50,000 IU (aged 2-12 mo) or 100,000 IU (aged >12-59 mo) vitamin A or a placebo.
                Of the 287 children enrolled, 145 received vitamin A and 142 received placebo. No overall differences were observed between the 2 groups in the duration of signs of pneumonia. Multiple linear regression showed a significant interaction between basal serum retinol concentration and vitamin A group for the time (in h) to remission of respiratory signs (beta = -3.57, SE = 1.09, P = 0.001). Duration of clinical signs was less in children with basal serum retinol concentrations >200 microg/L who received vitamin A supplements than in children with similar concentrations who received placebo (69.9 +/- 49.9 h compared with 131.3 +/- 143.9 h; P = 0.049).
                Overall, we found no effect of a moderate dose of vitamin A supplementation on the duration of uncomplicated pneumonia in underweight or normal-weight children aged <5 y. However, a beneficial effect was seen in children with high basal serum retinol concentrations. A randomised double-blind trial involving vitamin C/placebo supplementation was conducted on 57 elderly patients admitted to hospital with acute respiratory infections (bronchitis and bronchopneumonia). Patients were assessed clinically and biochemically on admission and again at 2 and 4 weeks after admission having received either 200 mg vitamin C per day, or placebo. This relatively modest oral dose led to a significant increase in plasma and white cell vitamin C concentration even in the presence of acute respiratory infection. Using a clinical scoring system based on major symptoms of the respiratory condition, patients supplemented with the vitamin fared significantly better than those on placebo. This was particularly the case for those commencing the trial most severely ill, many of whom had very low plasma and white cell vitamin C concentrations on admission. Various mechanisms by which vitamin C could assist this type of patient are discussed. Vitamin A deficiency and acute lower respiratory tract infections coexist as important public health problems in many developing countries. We carried out a randomized, double-blind, placebo-controlled trial to examine whether large doses of vitamin A given to Tanzanian children who are admitted to the hospital with nonmeasles pneumonia would reduce the severity of respiratory disease. Six hundred eighty-seven children were randomly assigned to receive either placebo or vitamin A [200 000 IU (60 mg retinol equivalents) for children > 1 y of age and 100000 IU (30 mg retinol equivalents) for infants] on the day of admission and another dose on the following day. Of the 346 children in the vitamin A group, 13 died in the hospital, compared with 8 of 341 children in the placebo group; the relative mortality was 1.63 (95% CI: 0.67, 3.97; P = 0.28). The mean number of days of hospitalization was the same in both groups (4.2 d). There were no differences between the vitamin A and placebo groups in the duration of hospital stay when examined within categories of children stratified by age, sex, breast-feeding status, nutritional status at baseline, or quartile of dietary vitamin A intake in the 4 mo before admission to the hospital. There were also no differences in the mean number of days of fever, rapid respiratory rate, or hypoxia, whether these endpoints were examined in the total number of subjects or in a subset with more severe clinical conditions at baseline. Large doses of vitamin A had no protective effect on the course of pneumonia in hospitalized Tanzanian children. To evaluate earlier observations, including our own, showing usefulness of vitamin C for managing the common cold, we performed a double-blind trial of vitamin C versus placebo in 868 children. There was no difference in number becoming ill (133 versus 129), number of episodes (166 versus 159) or mean illness duration (5.5 versus 5.8 days) between the groups. Children receiving vitamin C had fewer throat cultures yielding beta-hemolytic streptococcus (six versus 13, P less than 0.10), but no difference in overall complicated illness rate (24 versus 25). Plasma ascorbic acid levels were higher in the vitamin group 24 to 26 hours after supplementation (1.28 versus 1.04 mg per 100 ml, P less than 0.01). Children with high plasma ascorbic acid concentrations had longer mean illness (6.8 versus 4.0 days, P less than 0.05) than those with low levels. Vitamin C does not seem to be an effective prophylactic or therapeutic agent for upper respiratory illness. To evaluate the impact on clinical recovery and severity of the addition of large doses of vitamin A to the standard treatment for childhood pneumonia.
                A randomised, double blind, placebo controlled trial.
                Study children were recruited at a public hospital in Recife, north east Brazil, an area of marginal vitamin A deficiency.
                472 children aged 6 to 59 months with clinical diagnosis of pneumonia.
                200,000 IU (infants) or 400,000 IU (1-4 year olds) of vitamin A in oil or similar capsules of placebo divided into two daily oral doses, in addition to the standard treatment.
                Duration of the episode and incidence of adverse outcomes.
                The groups were similar with respect to overall duration of pneumonia and incidence of adverse outcomes. Children who received vitamin A, however, were less likely to have fever by day 3 (P = 0.008) and were 29% less likely to fail to respond to the first line antibiotic (P = 0.054).
                There was little evidence for an effect of vitamin A treatment on the immediate outcome of the pneumonia episode. A prospective, randomized, double-blind study was carried out to determine whether vitamin C prophylaxis, 2.0 g/day, vs placebo prophylaxis would reduce the incidence or morbidity of the common cold and other respiratory illnesses in 674 marine recruits during an eight-week period. Whole-blood ascorbic acid levels measured six weeks after initiation of the study were significantly higher in the vitamin C group. There was no difference between the two groups in the incidence or duration of colds. The vitamin C group rated their colds as being less severe, but this was not reflected in different symptom complexes or in fewer sick-call visits or training days lost. This study and the literature do not support the prophylactic use of vitamin C to prevent the common cold. Pneumonia is a leading cause of illness and death in young children. Interventions to improve case management of pneumonia are needed.
                Our objective was to measure the effect of zinc supplementation in children with pneumonia in a population in which zinc deficiency is common.
                In a double-blind, placebo-controlled clinical trial, children aged 2-35 mo with severe (n = 149) or nonsevere (n = 2479) pneumonia defined according to criteria established by the World Health Organization were randomly assigned to receive zinc (10 mg for children aged 2-11 mo, 20 mg for children aged > or =12 mo) or placebo daily for 14 d as an adjuvant to antibiotics. The primary outcomes were treatment failure, defined as a need for change in antibiotics or hospitalization, and time to recovery from pneumonia.
                One of 5 children did not respond adequately to antibiotic treatment; the odds ratios between zinc and placebo groups for treatment failure were 0.95 (95% CI: 0.78, 1.2) for nonsevere pneumonia and 0.97 (95% CI: 0.42, 2.2) for severe pneumonia. There was no difference in time to recovery between zinc and placebo groups for nonsevere (median: 2 d; hazard ratio: 1.0; 95% CI: 0.96, 1.1) or severe (median: 4 d; hazard ratio: 1.1; 95% CI: 0.79, 1.5) pneumonia. Regurgitation or vomiting < or =15 min after supplementation was observed more frequently among children in the zinc group than among those in the placebo group during the supplementation period (37% compared with 13%; odds ratio: 0.25; 95% CI: 0.20, 0.30).
                Adjuvant treatment with zinc neither reduced the risk of treatment failure nor accelerated recovery in episodes of nonsevere or severe pneumonia. This trial was registered at clinicaltrials.gov as NCT00148733. To evaluate the effect of daily zinc supplementation in children on the incidence of acute lower respiratory tract infections and pneumonia.
                Double masked, randomised placebo controlled trial.
                A slum community in New Delhi, India.
                2482 children aged 6 to 30 months.
                Daily elemental zinc, 10 mg to infants and 20 mg to older children or placebo for four months. Both groups received single massive dose of vitamin A (100 000 IU for infants and 200 000 IU for older children) at enrollment.
                All households were visited weekly. Any children with cough and lower chest indrawing or respiratory rate 5 breaths per minute less than the World Health Organization criteria for fast breathing were brought to study physicians.
                At four months the mean plasma zinc concentration was higher in the zinc group (19.8 (SD 10.1) v 9.3 (2.1) micromol/l, P<0.001). The proportion of children who had acute lower respiratory tract infection during follow up was no different in the two groups (absolute risk reduction -0.2%, 95% confidence interval -3.9% to 3.6%). Zinc supplementation resulted in a lower incidence of pneumonia than placebo (absolute risk reduction 2.5%, 95% confidence interval 0.4% to 4.6%). After correction for multiple episodes in the same child by generalised estimating equations analysis the odds ratio was 0.74, 95% confidence interval 0.56 to 0.99.
                Zinc supplementation substantially reduced the incidence of pneumonia in children who had received vitamin A. During 7 weeks in the spring of 1973 a double-blind pilot study on 172 children in the age group 8-9 was carried out to test the possible effect of 1000 mg vitamin C daily as a prophylactic agent against common colds. During the autumn of 1973, a main study was carried out on 642 children of the same age. The investigations had the same pattern and lasted for 3 months. Both studies have been processed on the same principles. The results were somewhat divergent but, like previously published studies on children, seemed to indicate that the duration and severity of the cold were reduced while, on the other hand, the incidence remained unaltered or indeed increased. The total number of days of upper respiratory tract infection was smaller for the vitamin C group only in the pilot study (not in the main study). No proven biochemical effects were obtained. Preventive treatment of healthy children with vitamin C in large doses this had no definitely proved effect against colds.
The prophylactic use of vitamin C to prevent pneumonia should be further investigated in populations who have high incidence of pneumonia, especially if dietary vitamin C intake is low. Similarly, the therapeutic effects of vitamin C should be studied, especially in patients with low plasma vitamin C levels. The current evidence is too weak to advocate widespread prophylactic use of vitamin C to prevent pneumonia in the general population. However, therapeutic vitamin C supplementation may be reasonable for pneumonia patients who have low vitamin C plasma levels because its cost and risks are low.