Impact of massive dose of vitamin A given to preschool children with acute diarrhoea on subsequent respiratory and diarrhoeal morbidity Vitamin A supplements and diarrheal and respiratory tract infections among children in Dar es Salaam, Tanzania. Serum 25-Hydroxyvitamin D and the Incidence of Acute Viral Respiratory Tract Infections in Healthy Adults Effect of daily vitamin E and multivitamin-mineral supplementation on acute respiratory tract infections in elderly persons: a randomized controlled trial. Zinc combined with vitamin A reduces upper respiratory tract infection morbidity in a randomised trial in preschool children in Indonesia. Effect of High-Dose vs Standard-Dose Wintertime Vitamin D Supplementation on Viral Upper Respiratory Tract Infections in Young Healthy Children Effect of vitamin A supplementation on diarrhoea and acute lower-respiratory-tract infections in young children in Brazil Vitamin supplements, socioeconomic status, and morbidity events as predictors of wasting in HIV-infected women from Tanzania. Risk factors for acute respiratory tract infections in young Greenlandic children. Maternal vitamin D supplementation during pregnancy and lactation to prevent acute respiratory infections in infancy in Dhaka, Bangladesh (MDARI trial): protocol for a prospective cohort study nested within a randomized controlled trial Vitamin E and respiratory tract infections in elderly nursing home residents: a randomized controlled trial. A double-blind, randomized, clinical trial of the effect of vitamin A and zinc supplementation on diarrheal disease and respiratory tract infections in children in Mexico City, Mexico. Effect of vitamin A supplementation on morbidity of low-birth-weight neonates. Vitamin C supplementation reduces the incidence of postrace symptoms of upper-respiratory-tract infection in ultramarathon runners. Vitamin D supplementation and upper respiratory tract infections in adolescent swimmers: a randomized controlled trial. Vitamin D3 supplementation in patients with chronic obstructive pulmonary disease (ViDiCO): a multicentre, double-blind, randomised controlled trial. Effect of vitamin A supplementation on diarrhoea and acute respiratory tract infection in children Zinc and vitamin A supplementation in Indigenous Australian children hospitalised with lower respiratory tract infection: a randomised controlled trial. Effect of routine zinc supplementation on pneumonia in children aged 6 months to 3 years: randomised controlled trial in an urban slum Clinical trial of vitamin A as adjuvant treatment for lower respiratory tract infections. Vitamin D3 supplementation in patients with frequent respiratory tract infections: a randomised and double-blind intervention study Prevention of urinary tract infections with vitamin D supplementation 20,000 IU per week for five years. Results from an RCT including 511 subjects Respiratory infections reduce the growth response to vitamin A supplementation in a randomized controlled trial.
Abstract Objective : To assess the impact of vitamin A supplementation on  morbidity from acute respiratory tract infections and diarrhoea .  Design : Double blind r and omised placebo controlled field trial . Setting : An urban slum area in New Delhi , India . Subjects—900 children aged 12 - 60 months attending a local health facility for acute diarrhoea of less than seven days ' duration r and omly allocated to receive vitamin A 200000 IU or placebo . Main outcome measures : Incidence and prevalence of acute lower respiratory tract infections and diarrhoea during the 90 days after termination of the enrolment diarrhoeal episode measured by twice weekly household surveillance . Results : The incidence ( relative risk 1.07 ; 95 % confidence interval 0.92 to 1.26 ) and average number of days spent with acute lower respiratory tract infections were similar in the vitamin A supplementation and placebo groups . Among children aged 23 months or less there was a significant reduction in the incidence of measles ( relative risk 0.06 ; 95 % confidence interval 0.01 to 0.48 ) . The incidence of diarrhoea was also similar ( relative risk 0.95 ; 0.86 to 1.05 ) in the two groups . There was a 36 % reduction in the mean daily prevalence of diarrhoea associated with fever in the vitamin A supplemented children older than 23 months . Conclusions : Results were consistent with a lack of impact on acute lower respiratory tract related mortality after vitamin A supplementation noted in other trials and a possible reduction in the severity of diarrhoea OBJECTIVE To determine the effect of vitamin A supplementation on the  risk of diarrhea and of acute respiratory infection .  DESIGN Double-blind , r and omized , placebo-controlled trial . SETTING Dar-es-Salaam , Tanzania . SUBJECTS Six hundred eighty-seven children , 6 to 60 months old , hospitalized with pneumonia , who received vitamin A or placebo at baseline and at 4 and 8 months after discharge from hospital . MAIN OUTCOME VARIABLES Incidence and duration of episodes of diarrhea and respiratory tract infections during the year after discharge from the hospital . RESULTS Relative to those receiving placebo , children receiving vitamin A had a significantly smaller risk of severe watery diarrhea ( multivariate odds ratio = 0.56 , 95 % CI = 0.32 - 0.99 , P = .04 ) but a higher risk of cough and rapid respiratory rate ( multivariate odds ratio = 1.67 , 95 % CI = 1.17 - 2.36 , P = .004 ) . Vitamin A supplementation was also associated with increased risk of acute diarrhea among normally nourished children or children with stunted growth but was relatively protective among children with wasting disease ( P value for interaction = .01 ) . The apparently increased risk of respiratory tract infection was limited to children who were seronegative for human immunodeficiency virus ( HIV ) ( P value for interaction = .07 ) . CONCLUSIONS Vitamin A supplements provide a low-cost intervention against morbidity in HIV-infected and undernourished children . Supplements may also have serious non-lethal adverse outcomes in well-nourished individuals . Whether these apparent detrimental effects of vitamin A are transient or long-term needs to be examined Background Declining serum concentrations of 25-hydroxyvitamin D seen in the fall and winter as distance increases from the equator may be a factor in the seasonal increased prevalence of influenza and other viral infections . This study was done to determine if serum 25-hydroxyvitamin D concentrations correlated with the incidence of acute viral respiratory tract infections . Methodology / Findings In this prospect i ve cohort study serial monthly concentrations of 25-hydroxyvitamin D were measured over the fall and winter 2009–2010 in 198 healthy adults , blinded to the nature of the substance being measured . The participants were evaluated for the development of any acute respiratory tract infections by investigators blinded to the 25-hydroxyvitamin D concentrations . The incidence of infection in participants with different concentrations of vitamin D was determined . One hundred ninety-five ( 98.5 % ) of the enrolled participants completed the study . Light skin pigmentation , lean body mass , and supplementation with vitamin D were found to correlate with higher concentrations of 25-hydroxyvitamin D. Concentrations of 38 ng/ml or more were associated with a significant ( p<0.0001 ) two-fold reduction in the risk of developing acute respiratory tract infections and with a marked reduction in the percentages of days ill . Conclusions / Significance Maintenance of a 25-hydroxyvitamin D serum concentration of 38 ng/ml or higher should significantly reduce the incidence of acute viral respiratory tract infections and the burden of illness caused thereby , at least during the fall and winter in temperate zones . The findings of the present study provide direction for and call for future interventional studies examining the efficacy of vitamin D supplementation in reducing the incidence and severity of specific viral infections , including influenza , in the general population and in sub population s with lower 25-hydroxyvitamin D concentrations , such as pregnant women , dark skinned individuals , and the obese CONTEXT Immune response in elderly individuals has been reported to improve after micronutrient supplementation . However , efficacy trials evaluating infectious diseases as outcomes are scarce and inconclusive . OBJECTIVE To investigate the effect of daily multivitamin-mineral and vitamin E supplementation on incidence and severity of acute respiratory tract infections in elderly individuals . DESIGN A r and omized , double blind , placebo-controlled , 2 x 2 factorial trial . SETTING AND PARTICIPANTS A total of 652 noninstitutionalized individuals aged 60 years or older enrolled from 2 community-based sampling strategies in the Wageningen area of the Netherl and s , conducted from 1998 to 2000 . At baseline , 6 % of participants had suboptimal ascorbic acid and 1.3 % had suboptimal alpha-tocopherol plasma concentration . INTERVENTION Physiological doses of multivitamin-minerals , 200 mg of vitamin E , both , or placebo . MAIN OUTCOME MEASURES Incidence and severity of self-reported acute respiratory tract infections at 15 months , as assessed by a nurse ( telephone contact ) , home visits , and microbiological and serological testing in subsets of patients . RESULTS During a median observation period of 441 days , 443 ( 68 % ) of 652 participants recorded 1024 respiratory tract infection episodes . The incidence rate ratio of acute respiratory tract infection for multivitamin-mineral supplementation was 0.95 ( 95 % confidence interval , 0.75 - 1.15 ; P = .58 ) and for vitamin E supplementation , 1.12 ( 95 % confidence interval , 0.88 - 1.25 ; P = .21 ) . Severity of infections was not influenced by multivitamin-mineral supplementation . For vitamin E vs no vitamin E , severity was worse : median ( interquartile range ) for illness- duration was 19 ( 9 - 37 ) vs 14 ( 6 - 29 ) days , P = .02 ; number of symptoms , 6 ( 3 - 8 ) vs 4 ( 3 - 8 ) , P = .03 ; presence of fever , 36.7 % vs 25.2 % , P = .009 ; and restriction of activity , 52.3 % vs 41.1 % , P = .02 . CONCLUSIONS Neither daily multivitamin-mineral supplementation at physiological dose nor 200 mg of vitamin E showed a favorable effect on incidence and severity of acute respiratory tract infections in well-nourished noninstitutionalized elderly individuals . Instead we observed adverse effects of vitamin E on illness severity Zn supplementation has shown inconsistent effects on  respiratory morbidity in young children in developing countries . Few studies have focused on upper respiratory tract infection ( URTI ) , a frequent cause of morbidity in this group , and potential benefit from Zn supplementation or factors that influence its efficacy . We investigated the effects of Zn supplementation on URTI before and after vitamin A supplementation . This r and omised double-blinded controlled Zn supplementation study was conducted on 826 children aged 2 - 5 years .  Placebo or Zn ( 10 mg/d ) was given in syrup daily for 4 months , with 200 000 IU vitamin A ( 60 mg retinol ) given to all children at 2 months . Health workers visited children every 3 d for compliance and morbidity information . We found that 84 % of children experienced URTI during the study . Zn supplementation reduced the percentage of days with URTI ( 12 % reduction ; P = 0·09 ) , with greater impact following vitamin A supplementation ( 20 % reduction ; P = 0·01 ) . Vitamin A supplementation was associated with a decreased number but an increased duration of URTI episodes . We conclude that Zn combined with vitamin A supplementation significantly reduced the percentage of days with URTI in a population of preschool Indonesian children with marginal nutritional status . The results suggest that vitamin A status modifies the efficacy of Zn supplementation  on URTI Importance Epidemiological studies support a link between low 25-hydroxyvitamin D levels and a higher risk of viral upper respiratory tract infections . However , whether winter supplementation of vitamin D reduces the risk among children is unknown . Objective To determine whether high-dose vs st and ard-dose vitamin D supplementation reduces the incidence of wintertime upper respiratory tract infections in young children . Design , Setting , and Participants A r and omized clinical trial was conducted during the winter months between September 13 , 2011 , and June 30 , 2015 , among children aged 1 through 5 years enrolled in TARGet Kids ! , a multisite primary care practice –based research network in Toronto , Ontario , Canada . Interventions Three hundred forty-nine participants were r and omized to receive 2000 IU/d of vitamin D oral supplementation ( high-dose group ) vs 354 participants who were r and omized to receive 400 IU/d ( st and ard-dose group ) for a minimum of 4 months between September and May. Main Outcome Measures The primary outcome was the number of laboratory-confirmed viral upper respiratory tract infections based on parent-collected nasal swabs over the winter months . Secondary outcomes included the number of influenza infections , noninfluenza infections , parent-reported upper respiratory tract illnesses , time to first upper respiratory tract infection , and serum 25-hydroxyvitamin D levels at study termination . Results Among 703 participants who were r and omized ( mean age , 2.7 years , 57.7 % boys ) , 699 ( 99.4 % ) completed the trial . The mean number of laboratory-confirmed upper respiratory tract infections per child was 1.05 ( 95 % CI , 0.91 - 1.19 ) for the high-dose group and 1.03 ( 95 % CI , 0.90 - 1.16 ) for the st and ard-dose group , for a between-group difference of 0.02 ( 95 % CI , −0.17 to 0.21 ) per child . There was no statistically significant difference in number of laboratory-confirmed infections between groups ( incidence rate ratio [ RR ] , 0.97 ; 95 % CI , 0.80 - 1.16 ) . There was also no significant difference in the median time to the first laboratory-confirmed infection : 3.95 months ( 95 % CI , 3.02 - 5.95 months ) for the high-dose group vs 3.29 months ( 95 % CI , 2.66 - 4.14 months ) for the st and ard-dose group , or number of parent-reported upper respiratory tract illnesses between groups ( 625 for high-dose vs 600 for st and ard-dose groups , incidence RR , 1.01 ; 95 % CI , 0.88 - 1.16 ) . At study termination , serum 25-hydroxyvitamin D levels were 48.7 ng/mL ( 95 % CI , 46.9 - 50.5 ng/mL ) in the high-dose group and 36.8 ng/mL ( 95 % CI , 35.4 - 38.2 ng/mL ) in the st and ard-dose group . Conclusions and Relevance Among healthy children aged 1 to 5 years , daily administration of 2000 IU compared with 400 IU of vitamin D supplementation did not reduce overall wintertime upper respiratory tract infections . These findings do not support the routine use of high-dose vitamin D supplementation in children for the prevention of viral upper respiratory tract infections . Trial Registration clinical trials.gov Identifier : A beneficial effect of periodic vitamin A supplementation on  childhood mortality  has been demonstrated , but the effect on morbidity is less clear . We investigated the effect of vitamin A supplementation on  diarrhoea and acute lower-respiratory-tract infections ( ALRI ) in children from northeastern Brazil in a r and omised , double-blind , placebo-controlled community trial . 1240 children aged 6 - 48 months were assigned vitamin A or placebo every 4 months for 1 year . They were followed up at home three times a week , and data about the occurrence and severity of diarrhoea and ALRI were collected . Any child with cough and respiratory rate above 40 breaths per min was visited by a paediatrician . The overall incidence of diarrhoea episodes was significantly lower in the vitamin-A-supplemented group than in the placebo group ( 18.42 vs 19.58 x 10(-3 ) child-days ; rate ratio 0.94 [ 95 % Cl 0.90 - 0.98 ] ) . The benefit of supplementation was greater as regards severe episodes of diarrhoea ; the incidence was 20 % lower in the vitamin A group than in the placebo group ( rate ratio 0.80 [ 0.65 - 0.98 ] ) . With the st and ard definition of diarrhoea ( > or = 3 liquid or semi-liquid stools in 24 h ) the effect of vitamin A on mean daily prevalence did not reach significance , but as the definition of diarrhoea was made more stringent ( increasing number of stools per day ) , a significant benefit became apparent , reaching for diarrhoea with 6 or more liquid or semi-liquid stools in 24 h a 23 % lower prevalence . We found no effect of vitamin A supplementation on the incidence of ALRI . The reduction in severity of diarrhoea may be the most important factor in the lowering of mortality by vitamin A supplementation BACKGROUND Wasting is a strong independent predictor of mortality in HIV-infected persons .  Vitamin supplements delay the disease progression , but their effect on wasting is not known . Data are lacking on the risk factors for wasting in African HIV-infected persons . OBJECTIVES The objectives were to examine the effect of vitamin supplements on wasting in HIV-infected women and to assess the effects of sociodemographic characteristics , morbidity events , and immunologic progression on the risk of wasting . DESIGN HIV-infected women ( n = 1078 ) from Tanzania were r and omly assigned to receive 1 of 4 daily oral regimens : multivitamins ( B complex , C , and E ) , vitamin A plus beta-carotene , multivitamins that included vitamin A plus beta-carotene , or placebo . The endpoints of the study included first episodes of a midupper arm circumference < 22 cm or a body mass index ( BMI ; in kg/m2 ) < 18 and the incidence of weight loss episodes during a median 5.3 y of follow-up . RESULTS Multivitamins alone significantly reduced the risk of a first episode of a midupper arm circumference < 22 cm ( relative risk : 0.66 ; 95 % CI : 0.47 , 0.94 ; P = 0.02 ) . In multivariate-adjusted Cox models , the woman 's age , education level , and height were inversely related to the incidence of wasting . Episodes of diarrhea , nausea or vomiting , lower respiratory tract infections , oral ulcers , thrush , severe anemia , and low CD4 + cell counts were each significantly related to an increased risk of wasting . CONCLUSIONS Vitamins C and E and the vitamin B complex have a protective effect on wasting in HIV-infected women . Prevention of diarrhea , severe respiratory tract infections , and anemia are likely to decrease the burden of wasting Acute respiratory infections cause considerable morbidity among Inuit children , but there is very little information on the risk factors for these infections in this population . To identify such factors , the authors performed a prospect i ve community-based study of acute respiratory infections in an open cohort of 288 children aged 0 - 2 years in the town of Sisimiut , Greenl and . Between July 1996 and August 1998 , children were monitored weekly , and episodes of upper and lower respiratory tract infections were registered . Risk factor analyses were carried out using a multivariate Poisson regression model adjusted for age . Risk factors for upper respiratory tract infections included attending a child-care center ( relative risk = 1.7 compared with home care ) and sharing a bedroom with adults ( relative risk = 2.5 for one adult and 3.1 for two adults ) . Risk factors for lower respiratory tract infections included being a boy ( relative risk = 1.5 ) , attending a child-care center ( relative risk = 3.3 ) , exposure to passive smoking ( relative risk = 2.1 ) , and sharing a bedroom with children aged 0 - 5 years ( relative risk = 2.0 for two other children ) . Breastfeeding tended to be protective for lower respiratory tract infections . The population -attributable risk of lower respiratory tract infections associated with passive smoking and child-care centers was 47 % and 48 % , respectively . The incidence of acute respiratory infections among Inuit children may be reduced substantially through public health measures Background Early infancy is a high-risk period for severe acute respiratory infection ( ARI ) , particularly in low-income countries with re source -limited health systems . Lower respiratory tract infection ( LRTI ) is commonly preceded by upper respiratory infection ( URTI ) , and often caused by respiratory syncytial virus ( RSV ) , influenza and other common community-acquired viral pathogens . Vitamin D status is a c and i date modifiable early-life determinant of the host antiviral immune response and thus may influence the risk of ARI-associated morbidity in high-risk population s. Methods / Design In the Maternal Vitamin D for Infant Growth ( MDIG ) study in Dhaka , Bangladesh ( NCT01924013 ) , 1300 pregnant women are r and omized to one of five groups : placebo , 4200 IU/week , 16,800 IU/week , or 28,000 IU/week from 2nd trimester to delivery plus placebo from 0–6 months postpartum ; or , 28,000 IU/week prenatal and until 6-months postpartum . In the Maternal Vitamin D for ARI in Infancy ( MDARI ) sub- study nested within the MDIG trial , trained personnel conduct weekly postnatal home visits to inquire about ARI symptoms and conduct a st and ardized clinical assessment . Supplementary home visits between surveillance visits are conducted when caregivers make phone notifications of new infant symptoms . Mid-turbinate nasal swab sample s are obtained from infants who meet st and ardized clinical ARI criteria . Specimens are tested by polymerase chain reaction ( PCR ) for 8 viruses ( influenza A/B , parainfluenza 1/2/3 , RSV , adenovirus , and human metapneumovirus ) , and nasal carriage density of Streptococcus pneumoniae . The primary outcome is the incidence rate of microbiologically-positive viral ARI , using incidence rate ratios to estimate between-group differences . We hypothesize that among infants 0–6 months of age , the incidence of microbiologically-confirmed viral ARI will be significantly lower in infants whose mothers received high-dose prenatal/postpartum vitamin D supplements versus placebo . Secondary outcomes include incidence of ARI associated with specific pathogens ( influenza A or B , RSV ) , clinical ARI , and density of pneumococcal carriage . Discussion If shown to reduce the risk of viral ARI in infancy , integration of maternal prenatal/postpartum vitamin D supplementation into antenatal care programs in South Asia may be a feasible primary preventive strategy to reduce the burden of ARI-associated morbidity and mortality in young infants . Trial registration NCT02388516 , registered March 9 , 2015 CONTEXT Respiratory tract infections are prevalent in elderly individuals , result ing in increased morbidity , mortality , and use of health care services . Vitamin E supplementation has been shown to improve immune response in elderly persons . However , the clinical importance of these findings has not been determined . OBJECTIVE To determine the effect of 1 year of vitamin E supplementation on respiratory tract infections in elderly nursing home residents . DESIGN , SETTING , AND PARTICIPANTS A r and omized , double-blind , placebo-controlled trial was conducted from April 1998 to August 2001 at 33 long-term care facilities in the Boston , Mass , area . A total of 617 persons aged at least 65 years and who met the study 's eligibility criteria were enrolled ; 451 ( 73 % ) completed the study . INTERVENTION Vitamin E ( 200 IU ) or placebo capsule administered daily ; all participants received a capsule containing half the recommended daily allowance of essential vitamins and minerals . MAIN OUTCOME MEASURES Incidence of respiratory tract infections , number of persons and number of days with respiratory tract infections ( upper and lower ) , and number of new antibiotic prescriptions for respiratory tract infections among all participants r and omized and those who completed the study . RESULTS Vitamin E had no significant effect on incidence or number of days with infection for all , upper , or lower respiratory tract infections . However , fewer participants receiving vitamin E acquired 1 or more respiratory tract infections ( 60 % vs 68 % ; risk ratio [ RR ] , 0.88 ; 95 % confidence interval [ CI ] , 0.76 - 1.00 ; P = .048 for all participants ; and 65 % vs 74 % ; RR , 0.88 ; 95 % CI , 0.75 - 0.99 ; P = .04 for completing participants ) , or upper respiratory tract infections ( 44 % vs 52 % ; RR , 0.84 ; 95 % CI , 0.69 - 1.00 ; P = .05 for all participants ; and 50 % vs 62 % ; RR , 0.81 ; 95 % CI , 0.66 - 0.96 ; P = .01 for completing participants ) . When common colds were analyzed in a post hoc subgroup analysis , the vitamin E group had a lower incidence of common cold ( 0.67 vs 0.81 per person-year ; RR , 0.83 ; 95 % CI , 0.68 - 1.01 ; P = .06 for all participants ; and 0.66 vs 0.83 per person-year ; RR , 0.80 ; 95 % CI , 0.64 - 0.98 ; P = .04 for completing participants ) and fewer participants in the vitamin E group acquired 1 or more colds ( 40 % vs 48 % ; RR , 0.83 ; 95 % CI , 0.67 - 1.00 ; P = .05 for all participants ; and 46 % vs 57 % ; RR , 0.80 ; 95 % CI , 0.64 - 0.96 ; P = .02 for completing participants ) . Vitamin E had no significant effect on antibiotic use . CONCLUSIONS Supplementation with 200 IU per day of vitamin E did not have a statistically significant effect on lower respiratory tract infections in elderly nursing home residents . However , we observed a protective effect of vitamin E supplementation on upper respiratory tract infections , particularly the common cold , that merits further investigation BACKGROUND The efficacy of micronutrient supplementation in improving childhood health and survival in developing countries may be specific to the micronutrient used and health outcome measured . OBJECTIVE We evaluated the effect of vitamin A and zinc supplementation on overall rates of childhood diarrheal disease and respiratory tract infections  and rates stratified by household and personal characteristics . DESIGN A double-blind , r and omized , placebo-controlled trial was carried out in which 736 children aged 6 - 15 mo living in a periurban area of Mexico City were assigned to receive vitamin A every 2 mo , zinc daily , vitamin A and zinc together , or placebo . Children were followed for 12 mo to determine overall counts of diarrheal episodes and respiratory tract infections . RESULTS Vitamin A supplementation was associated with a 27 % increase in diarrheal disease [ risk ratio ( RR ) : 1.27 ; 95 % CI : 1.10 , 1.45 ; P < 0.001 ] and a 23 % increase in cough with fever ( RR : 1.23 ; 95 % CI : 1.02 , 1.47 ; P = 0.02 ) , whereas zinc had no effect on these outcomes . Vitamin A supplementation decreased diarrhea in children from households with dirt floors but increased diarrhea in children from households with nondirt floors , piped water , and indoor bathrooms . Zinc supplementation decreased diarrhea in children from households with dirt floors and whose mothers were more educated . Vitamin A supplementation increased cough with fever in children from less-crowded households that lacked indoor bathrooms and in children of less-educated mothers . CONCLUSIONS Vitamin A increases diarrheal disease and respiratory tract infections in young children in periurban areas of Mexico City .  Vitamin A and zinc have more heterogeneous effects in different subgroups of children BACKGROUND Low-birth-weight ( LBW ) infants ( < 2,500 g ) are at increased risk of respiratory infection in the first few months of life and have low liver stores of vitamin A. As retinol is essential for respiratory epithelial cell differentiation , deficiency could result in pathological changes in the respiratory epithelium , with respiratory problems . OBJECTIVE A r and omised , double-blind , placebo-controlled trial to investigate the effect of vitamin A supplementation on the incidence and severity of respiratory infections in LBW infants during their first year of life . METHOD One hundred and thirty LBW infants ( gestational age < 36 weeks and birth weight 950 - 1,700 g ) were enrolled in the study . The infants were r and omly allocated to a vitamin A or placebo group . Infants in the vitamin A group received 25,000 IU of vitamin A ( retinyl palmitate , Arovit drops , Roche , Basle , Switzerl and ) on study days 1 , 4 and 8 . Study day 1 was between 36 and 60 hours after delivery . Infants in the placebo group received a placebo ( formulated by Roche ) with a similar appearance and packed in the same dropper bottles as the vitamin A drops . RESULTS Vitamin A supplementation markedly improved serum retinol levels . After the last vitamin A dose , the vitamin A group had higher mean serum retinol concentrations than the placebo group ( 45.77 + /- 17.07 micrograms/dl v. 12.88 + /- 6.48 micrograms/dl , P = 0.0001 ) . There was no evidence of improvement in neonatal or post-neonatal respiratory problems associated with vitamin A supplementation . Vitamin A and placebo groups did not differ in the occurrence or duration of respiratory distress or the need for head-box oxygen . There were also no significant differences in the cumulative probability of developing lower or upper respiratory tract infection through the first year of life . There was a slight suggestion of an increase in the risk of hospitalisation with pneumonia associated with vitamin A supplementation . The cumulative probability of being hospitalised with pneumonia by 6 months of age was 24.6 % ( 7 hospitalisations ) in the vitamin A group compared with 7.4 % ( 2 hospitalisations ) in the placebo group ( log rank test P = 0.04 ) . After adjusting for risk factors this difference was no longer significant . CONCLUSION Vitamin A supplementation in LBW neonates may not reduce incidence or severity of respiratory infections . These results do not negate the importance of improving vitamin A status in children as an important public health measure to reduce morbidity and mortality from other childhood infections This study determined whether daily supplementation with 600 mg vitamin C would reduce the incidence of symptoms of  upper-respiratory-tract ( URT ) infections after participation in a competitive ultramarathon race ( > 42 km ) . Ultramarathon runners with age-matched controls were r and omly divided into placebo and experimental ( vitamin C-supplemented ) groups . Symptoms of URT infections were monitored for 14 d after the race . Sixty-eight percent of the runners in the placebo group reported the development of symptoms of URT infection after the race ; this was significantly more ( P < 0.01 ) than that reported by the vitamin C-supplemented group ( 33 % ) . The duration and severity of symptoms of URT infections reported in the vitamin C-supplemented nonrunning control group was also significantly less than in the nonrunning control group receiving the placebo ( P < 0.05 ) . This study provides evidence that vitamin C supplementation may enhance resistance to the postrace URT infections that occur commonly in competitive ultramarathon runners and may reduce the severity of such infections in those who are sedentary Observational studies identified associations between vitamin D insufficiency ( serum 25(OH)D < 30ng·ml-1 ) and risk of upper respiratory infection ( URI ) .  Swimmers are highly prone to URIs , which might hinder their performance . The aim of this study was to examine if vitamin D3 supplementation reduces URI burden in vitamin D-insufficient swimmers . Fifty-five competitive adolescent swimmers with vitamin D insufficiency were r and omized to receive vitamin D3 ( 2,000IU·d-1 ) or placebo for 12 winter weeks . A URI symptom question naire was completed weekly . Serum 25(OH)D concentrations were measured by radio-immunoassay before and after supplementation . We used linear regression to examine the relation between the change in 25(OH)D concentrations during the trial , and the duration and severity of URIs . There were no between-group differences in the frequency , severity , or duration of URIs . Exploratory analyses revealed that in the placebo group only , the change in 25(OH)D concentrations during the trial was highly associated with the duration of URIs ( r = -0.90,p < .001 ) , and moderately associated with the severity of URIs ( r = -0.65,p = .043 ) . The between-group differences for duration  were highly significant . Vitamin D3 supplementation in adolescent swimmers with vitamin D insufficiency did not reduce URI burden . However , larger decreases in serum 25(OH)D concentrations were associated with significantly longer and more severe URI episodes BACKGROUND Patients with chronic obstructive pulmonary disease ( COPD ) often have vitamin D deficiency , which is associated with increased susceptibility to upper respiratory infection-a major precipitant of exacerbation . Multicentre trials of vitamin D supplementation for prevention of exacerbation and upper respiratory infection in patients with COPD are lacking . We therefore investigated whether vitamin D3 ( colecalciferol ) supplementation would reduce the incidence of moderate or severe COPD exacerbations and upper respiratory infections . METHODS We did a r and omised , double-blind , placebo-controlled trial of vitamin D3 supplementation in adults with COPD in 60 general practice s and four Acute National Health Service Trust clinics in London , UK . Patients were allocated to receive six 2-monthly oral doses of 3 mg vitamin D3 or placebo over 1 year in a 1:1 ratio using computer-generated permuted block r and omisation . Participants and study staff were masked to treatment assignment . Co primary outcomes were time to first moderate or severe exacerbation and first upper respiratory infection . Analysis was by intention to treat . A prespecified subgroup analysis was done to assess whether effects of the intervention on the co primary outcomes were modified by baseline vitamin D status . This trial is registered with Clinical Trials.gov , number NCT00977873 . FINDINGS 240 patients were r and omly allocated to the vitamin D3 group ( n=122 ) and placebo group ( n=118 ) . Vitamin D3 compared with placebo did not affect time to first moderate or severe exacerbation ( adjusted hazard ratio 0·86 , 95 % CI 0·60 - 1·24 , p=0·42 ) or time to first upper respiratory infection ( 0·95 , 0·69 - 1·31 , p=0·75 ) . Prespecified subgroup analysis showed that vitamin D3 was protective against moderate or severe exacerbation in participants with baseline serum 25-hydroxyvitamin D concentrations of less than 50 nmol/L ( 0·57 , 0·35 - 0·92 , p=0·021 ) , but not in those with baseline 25-hydroxyvitamin D levels of at least 50 nmol/L ( 1·45 , 0·81 - 2·62 , p=0·21 ; p=0·021 for interaction between allocation and baseline serum 25-hydroxyvitamin D status ) . Baseline vitamin D status did not modify the effect of the intervention on risk of upper respiratory infection ( pinteraction=0·41 ) . INTERPRETATION Vitamin D3 supplementation protected against moderate or severe exacerbation , but not upper respiratory infection , in patients with COPD with baseline 25-hydroxyvitamin D levels of less than 50 nmol/L. Our findings suggest that correction of vitamin D deficiency in patients with COPD reduces the risk of moderate or severe exacerbation . FUNDING UK National Institute for Health Research To determine the effect of a massive single oral dose of Vitamin A ( 200,000 IU ) supplementation on  diarrhoea and acute respiratory infection ( ARI )  , a double blind placebo controlled trial involving 174 children under six years of age ( excluding infants ) was carried out in a Calcutta slum community . Ninety-one children received vitamin A supplementation ( experimental group ) and 83 children received a placebo ( control group ) . All the children were followed up for six months by active fortnightly surveillance for occurrence of diarrhoea or ARI and their duration . There was no statistically significant difference in the incidence of diarrhoeal episodes or ARI . However , there was a significant difference ( p<0.05 ) in the average duration of diarrhoea per episode ( 2.1 vs. 3 days ) between the experimental and control groups . Possible beneficial effects of a single oral dose of vitamin A supplementation on the incidence of diarrhoea and ARI could not be demonstrated in the present study OBJECTIVE To evaluate the efficacy of supplementation with zinc and vitamin A in Indigenous children hospitalised with acute lower respiratory infection ( ALRI ) . DESIGN R and omised controlled , 2-by-2 factorial trial of supplementation with zinc and vitamin A. SETTING AND PARTICIPANTS 187 Indigenous children aged < 11 years hospitalised with 215 ALRI episodes at Alice Springs Hospital ( April 2001 to July 2002 ) . INTERVENTIONS Vitamin A was administered on Days 1 and 5 of admission at a dose of 50 000 IU ( infants under 12 months ) , or 100 000 IU ; and zinc sulfate was administered daily for 5 days at a daily dose of 20 mg ( infants under 12 months ) or 40 mg . MAIN OUTCOME MEASURE Time to clinical recovery from fever and tachypnoea , duration of hospitalisation , and readmission for ALRI within 120 days . RESULTS There was no clinical benefit of supplementation with vitamin A , zinc or the two combined , with no significant difference between zinc and no-zinc , vitamin A and no-vitamin A or zinc + vitamin A and placebo groups in time to resolution of fever or tachypnoea , or duration of hospitalisation . Instead , we found increased morbidity ; children given zinc had increased risk of readmission for ALRI within 120 days ( relative risk , 2.4 ; 95 % CI , 1.003 - 6.1 ) . CONCLUSION This study does not support the use of vitamin A or zinc supplementation in the management of ALRI requiring hospitalisation in Indigenous children living in remote areas . Even in population s with high rates of ALRI and poor living conditions , vitamin A and zinc therapy may not be useful . The effect of supplementation may depend on the prevalence of deficiency of these micronutrients in the population Abstract Objectives : To evaluate the effect of daily zinc supplementation  in children on the incidence of acute lower respiratory tract infections and pneumonia . Design : Double masked , r and omised placebo controlled trial . Setting : A slum community in New Delhi , India . Participants : 2482 children aged 6 to 30 months . Interventions : 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 enrolment . Main outcome measures : 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 . Results : At four months the mean plasma zinc concentration was higher in the zinc group ( 19.8 ( SD 10.1 ) v 9.3 ( 2.1 ) μmol/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 result ed 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 . Conclusions : Zinc supplementation substantially reduced the incidence of pneumonia in children who had received vitamin OBJECTIVE To test the efficacy of a high dose of vitamin A as adjuvant treatment for radiographically confirmed cases of acute lower respiratory tract infection ( ALRI ) . DESIGN R and omized , double-masked , placebo-controlled clinical trial . SETTING Two large urban hospitals in Guatemala City . PATIENTS Sequential sample of 263 children aged 3 to 48 months , identified in the emergency departments and admitted to the hospital . INTERVENTIONS Vitamin A ( 100,000 IU for children less than 1 year of age , and 200,000 IU for older children ) or placebo in addition to st and ard treatment for ALRI which included antibiotics , oxygen , bronchodilators , and intravenously administered solutions . MEASUREMENTS AND MAIN RESULTS The children were assessed every 8 hours . There were neither statistically nor clinical ly significant differences by treatment group in the rate of normalization in respiratory rate , oxygen saturation , temperature , or clinical score . Duration of hospitalization was not different by treatment group . Adverse outcomes ( mechanical ventilation , prolonged hospitalization , readmission or transfer , and death ) were equally distributed between the two groups . CONCLUSIONS Treatment with high doses of vitamin A over and above st and ard care for infants and children with non-measles-related ALRI is not efficacious for the current episode . Additional trials among population s in which vitamin A deficiency is more prevalent and severe should be considered Background Low serum levels of 25-hydroxyvitamin D3 are associated with an increased risk of respiratory tract infections ( RTIs ) . Clinical trials with vitamin D3 against various infections have been carried out but data are so far not conclusive . Thus , there is a need for additional r and omised controlled trials of effects of vitamin D3 on infections . Objective To investigate if supplementation with vitamin D3 could reduce infectious symptoms and antibiotic consumption among patients with antibody deficiency or frequent RTIs . Design A double-blind r and omised controlled trial . Setting Karolinska University Hospital , Huddinge . Participants 140 patients with antibody deficiency ( selective IgA subclass deficiency , IgG subclass deficiency , common variable immune disorder ) and patients with increased susceptibility to RTIs ( > 4 bacterial RTIs/year ) but without immunological diagnosis . Intervention Vitamin D3 ( 4000 IU ) or placebo was given daily for 1 year . Primary and secondary outcome measures The primary endpoint was an infectious score based on five parameters : symptoms from respiratory tract , ears and sinuses , malaise and antibiotic consumption . Secondary endpoints were serum levels of 25-hydroxyvitamin D3 , microbiological findings and levels of antimicrobial peptides ( LL-37 , HNP1–3 ) in nasal fluid . Results The overall infectious score was significantly reduced for patients allocated to the vitamin D group ( 202 points ) compared with the placebo group ( 249 points ; adjusted relative score 0.771 , 95 % CI 0.604 to 0.985 , p=0.04 ) . Limitations A single study centre , small sample size and a selected group of patients . The sample size calculation was performed using p=0.02 as the significance level whereas the primary and secondary endpoints were analysed using the conventional p=0.05 as the significance level . Conclusions Supplementation with vitamin D3 may reduce disease burden in patients with frequent RTIs Abstract Background : In observational studies vitamin D deficiency is associated with increased risk of infections , whereas the effect of vitamin D supplementation in r and omized controlled trials is non-conclusive . Methods : Five hundred and eleven subjects with prediabetes were r and omized to vitamin D3 ( 20,000 IU per week ) versus placebo for five years . Every sixth month , a question naire on respiratory tract infections ( RTI ) ( common cold , bronchitis , influenza ) and urinary tract infection ( UTI ) was filled in . Results : Mean baseline serum 25-hydroxyvitamin D ( 25(OH)D ) level was 60 nmol/L. Two hundred and fifty-six subjects received vitamin D and 255 placebo . One hundred and sixteen subjects in the vitamin D and 111 in the placebo  group completed the five-year study . Eighteen subjects in the vitamin D group and 34 subjects in the placebo group reported UTI during the study ( p < 0.02 ) , whereas no significant differences were seen for RTI . The effect on UTI was most pronounced in males . The effect of vitamin D on UTI was unrelated to baseline serum 25(OH)D level . Conclusion : Supplementation with vitamin D might prevent UTI , but confirmatory studies are needed BACKGROUND Studies on the effect of vitamin A supplementation on growth have yielded various results . It is possible that such growth is dependent on the burden of infectious diseases in the population . METHODS We analysed data from a r and omized , double-masked , placebo-controled trial to examine the role of respiratory infections and diarrhoea in modifying the growth response to vitamin A supplementation . A single high dose of vitamin A or placebo was given every 4 months to 1405 children aged 6 - 48 months , and 4430 child treatment cycles were used in this analysis . RESULTS Vitamin A supplementation modestly improved linear but not ponderal growth of children who experienced little respiratory infection and especially of those who had vitamin A intake below the normative requirement ( < 400 RE/day ) . Children who received vitamin A and were free of respiratory infection grew 0.22 cm/4 months ( 95 % CI : 0.08 , 0.37 ) more in height than the placebo group , but those with > or = 21.5 % of days of respiratory infection did not show a significant growth response to vitamin A supplementation . Children who experienced no respiratory infection and had vitamin A intake < 400 RE/day benefited most , gaining 0.31 cm/4 months ( 95 % CI : 0.10 , 0.52 ) more in height compared to the placebo group . Diarrhoea was associated with poorer growth , but did not significantly modify the effect of  vitamin A supplementation  on growth . CONCLUSIONS Vitamin A supplementation improves the linear growth of children who have a low intake of vitamin A but this impact is muted with increasing levels of respiratory infections
Conclusions Vitamin D supplementation  was safe and it protected against acute respiratory tract infection overall .
Patients who were very vitamin D deficient and those not receiving bolus doses experienced the most benefit .
Objectives To assess the overall effect of vitamin D supplementation on  risk of acute respiratory tract infection  , and to identify factors modifying this effect .