Guest guest Posted February 23, 2005 Report Share Posted February 23, 2005 Hi All, Does taking vitamin E reduce the incidence of respiratory tract infections? It seems that the supplement in this placebo/ control random trial given a standard alpha form of vitamin E not statistically significantly reduced the overall rate of respiratory tract infections. For those completing the one-year trial, the numbers shown below in the pdf-available paper's Table 4 are compelling. Lower respiratory tract infections were very slightly more and so was the corresponding use of antibiotics. The number of days with infections resembled the incidence of infections and thus the infections were prevented but not treated with the vitamin. Alternative medicines have been suggested to reduce infections such as these if taken early in the course of the infection, but this apparently does not apply for vitamin E. The routinely used of the alpha form of the vitamin was taken by the subjects of the trial. Also observed was that " Post hoc analysis found no significant effect of vitamin E on other URIs (0.035 vs 0.050 for influenzalike infections, 0.082 vs 0.073 for pharyngitis, 0.013 vs 0.009 for otitis media, and 0.030 vs 0.009 for sinusitis per person-year in the vitamin E and placebo groups, respectively) " . Many more had colds, as would be expected. JAMA. 2004 Aug 18;292(7):828-36. Vitamin E and respiratory tract infections in elderly nursing home residents: a randomized controlled trial. Meydani SN, Leka LS, Fine BC, Dallal GE, Keusch GT, Singh MF, Hamer DH. 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 randomized, 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 randomized 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. Publication Types: Clinical Trial Multicenter Study Randomized Controlled Trial PMID: 15315997 [PubMed - indexed for MEDLINE] Infections, particularly respiratory tract infections, are common in elderly individuals, resulting in decreased daily activity, prolonged recovery times, increased health care service use, and more frequent complications, including death.1-11 In the United States, an estimated 43% of elderly persons will be admitted to a nursing home, with more than 85% of them admitted to long-term (>1 year) care facilities.12 Infections occur more frequently in nursing home residents than among independent-living elderly,2-10,13 and respiratory tract infections are a major cause of morbidity and mortality.9, 14-15 Contributing to the increased incidence of infection with age is the well-described decline in immune response.16 For example, those who have diminished delayed-type hypersensitivity skin test responses have higher morbidity and mortality from cancer, pneumonia, and postoperative complications.17- 19 Nutritional status is an important determinant of immune function.20-21 Nutritional supplementation has been shown to enhance the immune response in older persons.22-23 In our earlier placebo- controlled, double-blind trials in elderly persons, vitamin E supplementation improved immune response, including delayed-type hypersensitivity and response to vaccines.24-25 Furthermore, participants receiving vitamin E in the 6-month trial25 had a 30% lower incidence of infectious diseases (primarily respiratory tract infections) compared with those receiving placebo, but this result was not significant, perhaps because of insufficient power, and infections were self-reported. To overcome these limitations, the current study determined the effect of 1 year of supplementation with vitamin E on objectively recorded respiratory tract infections in elderly nursing home residents. Study Design ... The vitamin E group received a daily capsule containing 200 IU of vitamin E (DL--tocopherol) ... RESULTS Participant Characteristics The mean (SD) follow-up time was 317 (104) days for the vitamin E group and 321 (97) days for the placebo group. Of the 617 randomized persons, 231 (37%) and 220 (36%) in the vitamin E and placebo groups, respectively, completed the 1-year study period (Figure 1). The 2 groups did not differ statistically in the proportion or causes of discontinuation (Figure 1) or in mortality rates (12.5% [39/311] and 14.4% [44/306] for the vitamin E and placebo groups, respectively). Table 1 shows participant characteristics for all who were enrolled in the study (all) and for those who completed 1 year (completers). The groups were well balanced with regard to baseline characteristics. One exception was a lower percentage of completers with diabetes mellitus in the vitamin E group compared with placebo (P = .04) (Table 1). All participants received influenza vaccine, and the 2 groups did not differ statistically in the percentage of participants receiving pneumococcal vaccine (30/311 [9.6%] vitamin E vs 23/306 [7.5%] placebo, P = .53 for all; 29/231 [12.6%] vitamin E vs 19/220 [8.6%] placebo, P = .18 for completers). The mean number of days during which completers took immune-related medications during the study period did not differ significantly (nonsteroidal anti-inflammatory drugs [131 vs 110], antihistamines [4.5 vs 7.9], steroids [16.3 vs 9.2], or nutrient supplements [84 vs 92] for vitamin E and placebo groups, respectively). Biochemical and hematological measurements before and after vitamin E supplementation indicated no difference between the 2 groups, except as otherwise specified (complete data available on request). Adherence Ninety-eight percent (442/451) of those completing the study consumed the capsules for at least 330 days (>90% of the 1-year supplementation period). The number of missed supplements did not differ statistically between the vitamin E and placebo groups (data available on request). Adherence was confirmed by plasma vitamin E measurement every 3 months. Nutritional Status Vitamin E and placebo groups did not differ statistically in body mass index or serum levels of vitamins and minerals before or after supplementation (data available on request). The vitamin E group had small but significantly higher hemoglobin levels than the placebo group before and after supplementation (mean [sD], 12.4 [1.4] vs 12.2 [1.3] g/dL before and 12.4 [1.3] vs 12.1 [1.5] g/dL after in the vitamin E and placebo groups, respectively; P = .02). Significantly fewer participants had low serum albumin levels in the vitamin E group compared with placebo at baseline and after supplementation (Table 2). The percentage of participants with low albumin levels increased significantly during the 1-year period for both groups, but the change over time in serum albumin between the 2 groups did not differ significantly. Except for vitamin E, the level of micronutrients did not change significantly during the study period in either group. Plasma vitamin E levels increased significantly in the vitamin E group, which doubled after 3 months of supplementation with no further change (mean [sD], 1141 [391] vs 2119 [689] µg/dL before and after supplementation, respectively; P<.001). No significant change in serum vitamin E levels was observed in the placebo group (1148 [429] vs 1209 [408] µg/dL before and after supplementation, respectively). The fraction of participants with low serum vitamin A levels increased slightly but significantly, whereas the fraction of participants with low vitamin D and B6 levels decreased in both groups (Table 2), with no significant difference between treatments in change over time. Significantly fewer participants had low hemoglobin levels in the vitamin E group before and after supplementation (Table 2). The fraction of participants with low hemoglobin levels in each group did not change significantly over time. Low serum zinc levels were equally prevalent in both groups (Table 2). Respiratory Tract Infections Results generally were similar whether the data from all participants (Table 3) or completing participants (Table 4) were compared. Adjustment for obstructive lung diseases, current smoking status, diabetes mellitus, dementia, year of enrollment, and baseline albumin and hemoglobin levels did not affect the outcomes, with a few exceptions, as noted in the text. Further adjustment for nursing home gave essentially the same results. Thus, only the unadjusted data are shown (Table 3 and Table 4), except as noted in the text. Table 4. Respiratory Tract Infection Among Participants Completing the Study* ------------------------------------------------------ Vitamin E (n = 231) Placebo (n = 220) Rate Ratio (95% CI) P Value ---------------------------------------- Incidence of infection All respiratory tract infections Infections, No. 304 320 Infections per person per year 1.30 1.44 0.91 (0.77 to 1.06) .22 Lower respiratory tract infection** Infections, No. 115 105 Infections per person per year 0.49 0.47 1.05 (0.80 to 1.36) .74 Upper respiratory tract infection*** Infections, No. 189 215 Infections per person per year 0.81 0.96 0.84 (0.69 to 1.02) .08 Colds Infections, No. 155 186 Infections per person per year 0.66 0.83 0.80 (0.64 to 0.98) .04 ------------------------------------- Antibiotic prescriptions for all respiratory tract infections Prescriptions, No. 153 125 Prescriptions per person per year 0.655 0.561 1.17 (0.92 to 1.47) .20 ------------------------------------ -----------------------------------Risk Ratio Participants with =/>1 infection, No. All respiratory tract infections 150 163 0.88 (0.75 to 0.99) .04 Lower respiratory tract infection 76 71 1.02 (0.77 to 1.31) .89 Upper respiratory tract infection 116 136 0.81 (0.66 to 0.96) .01 Colds 106 126 0.80 (0.64 to 0.96) .02 ------------------------------------ -----------------------Difference (Vitamin E & #8722;Placebo) No. of days with infection per person per year All respiratory tract infections 15.36 17.32 & #8722;1.97 ( & #8722;5.55 to 1.62) ..28 Lower respiratory tract infection 6.69 6.45 0.24 ( & #8722;2.11 to 2.59) .84 Upper respiratory tract infection 8.66 10.87 & #8722;2.21 ( & #8722;4.95 to 0.54) ..12 Colds 7.37 9.42 & #8722;2.05 ( & #8722;4.57 to 0.47) .11 ------------------------------------------- Abbreviation: CI, confidence interval. *Total days in study: 85 342 vitamin E, 81 436 placebo. **Bronchitis, pneumonia. ***Common cold, influenzalike infection, pharyngitis, otitis media, sinusitis. The highest incidence of respiratory tract infection occurred in the winter and the lowest in the summer (0.41 and 0.24 episodes per placebo participant, respectively). For all study participants, the rate of respiratory tract infection for vitamin E and placebo groups was 1.35 and 1.47 per person per year, respectively (Table 3), and for completers, 1.30 and 1.44 respiratory tract infections per person per year, respectively (Table 4). Rates of respiratory tract infections and number of days with respiratory tract infections per person-year (Table 3 and Table 4), although lower in the vitamin E group, did not differ significantly in either group. However, significantly fewer persons in the vitamin E group contracted 1 or more respiratory tract infections (60% [186/311] vs 68% [207/306] for all participants, 65% [150/231] vs 74% [163/220] for completing participants in the vitamin E and placebo groups, respectively). The incidence, proportion, or number of sick days of lower respiratory tract infection (includes acute bronchitis and pneumonia) did not differ significantly between the 2 treatment groups (Table 3, Table 4). The number of upper respiratory tract infections (URIs) per person- year and days with URI, although lower in the vitamin E group, were not significantly different between groups (Table 3 and Table 4). However, significantly fewer participants in the vitamin E–treated group contracted 1 or more URIs compared with the placebo group (44% [137/311] vs 52% [159/306], respectively, for all participants [Table 3]; 50% [116/231] vs 62% [136/220], respectively, for completers [Table 4]). After adjusting for obstructive lung disease, current smoking status, diabetes mellitus, dementia, year of enrollment, and baseline albumin and hemoglobin levels, the RR for having at least 1 URI was 0.82 (95% CI, 0.66-0.98, P = .03) among all persons randomized to receive vitamin E. Among the URIs, 84% [397/470] were common colds. Post hoc subgroup analysis indicated that vitamin E–supplemented participants who completed the study had a significantly lower incidence of common colds (Table 4). In addition, significantly in the vitamin E group acquired at least 1 cold (for all participants: 40% [125/311] vs 48% [147/306] in the placebo group [Table 3]; for completers: 46% [106/231] vs 57% [126/220] in the placebo group [Table 4]). After adjustment for obstructive lung disease, current smoking status, diabetes mellitus, dementia, year of enrollment, and baseline albumin and hemoglobin levels, the risk ratio for all persons randomized to vitamin E having at least 1 cold was 0.81 (95% CI, 0.64-0.98; P = .03). The vitamin E group had fewer days with common cold per person-year, but the result did not reach statistical significance (20% for all randomized in the vitamin E group [difference of 1.59 days compared with 7.82 days in the placebo group; P = .11] and 22% for completers [difference of 2.05 days compared with 9.42 days in the placebo group; P = .11; Table 3 and Table 4]). Post hoc analysis found no significant effect of vitamin E on other URIs (0.035 vs 0.050 for influenzalike infections, 0.082 vs 0.073 for pharyngitis, 0.013 vs 0.009 for otitis media, and 0.030 vs 0.009 for sinusitis per person-year in the vitamin E and placebo groups, respectively), although incidence was low and the study was not powered to detect differences. Vitamin E had no significant effect on antibiotic use for all respiratory tract infections (Table 3 and Table 4), number of emergency department visits (0.086 for vitamin E vs 0.058 for placebo per person-year; RR, 1.66; 95% CI, 0.80-3.43; P = .17) or hospitalizations for respiratory tract infection (0.060 for vitamin E vs 0.067 for placebo per person-year; RR, 0.91; 95% CI, 0.43-1.95; P = .81). COMMENT We found that vitamin E had no statistically demonstrable effect on the incidence or duration of all respiratory tract infections, as well as upper and lower (after adjustment for confounding factors). However, fewer persons in the vitamin E group acquired 1 or more respiratory tract infections or URIs. Common colds were the most frequent URIs, and in a post hoc subgroup analysis, participants in the vitamin E group who completed the study had significantly fewer common colds and a 20% lower risk of acquiring a cold than those in the placebo group. Further clinical trials of vitamin E supplementation in elderly persons, with common cold as the primary outcome, are warranted. Although our data suggest that vitamin E may protect against the common cold, the most frequently encountered form of URI in this study, vitamin E had no effect on the incidence or duration of other URIs or of lower respiratory tract infections, which may have been due to the small number of such episodes or differences in the types of pathogens responsible. Most URIs, especially the common cold, are caused by viruses. Animal studies suggest that vitamin E protects against viral but not bacterial infection in aged mice.42 We have found that although vitamin E supplementation did not protect old mice against primary pulmonary Staphylococcus aureus infection, it was protective against secondary S aureus infection after influenza infection.43 The respiratory tract infection definitions applied in our study were derived by using commonly accepted criteria from the medical literature.13, 32-37 These criteria do not allow the differentiation of viral from bacterial etiology. Future studies should include detailed microbiologic methods to determine whether vitamin E has an effect on respiratory tract infections of viral vs bacterial etiology. Vitamin E did not affect antibiotic use. If the effects of vitamin E were on URIs of viral etiology, this could explain the finding. In addition, overuse of antimicrobial agents in nursing homes44 may have impaired our ability to demonstrate an effect of vitamin E on antibiotic use. Previous studies of vitamin E and infection in the elderly have demonstrated mixed results. A retrospective study showed that persons with plasma vitamin E levels above 1670 µg/dL had significantly fewer infections compared with those with plasma vitamin E levels below 1200 µg/dL (mean, 1.0 vs 2.3, respectively; 95% CI for difference, 0.12-2.48).45 A recent double-blind trial of Dutch elderly46 persons living in the community reported no difference for all respiratory tract infections among those receiving vs not receiving vitamin E (RR, 1.12; 95% CI, 0.88-1.25). Our population and diagnostic method differed from those of the Dutch study. In the Dutch study,46 participants self-reported their infections by telephone, and then the infections were confirmed by nurse visits. Lack of infection was not confirmed. In our study, the presence and type of respiratory tract infection, or absence, was documented by infectious disease specialists according to review of data gathered by trained research nurses during weekly participant interviews, review of medical records, and physical examination focused on respiratory tract infection according to standardized case definitions.13, 32-35 Our results indicate that vitamin E may reduce URIs, particularly common colds, with no effect on lower respiratory tract infections or seasonal allergies. Graat et al46 did not differentiate between types of infections or between respiratory tract infections and allergies, and thus might have overlooked any effect of vitamin E on URI. Furthermore, in our study adherence was checked by nursing home medication records and by periodic plasma vitamin E measurements, whereas the study by Graat et al46 measured plasma vitamin E levels only at baseline. Several potential limitations of our study merit comment. First, of the originally planned sample size of 640, 617 were enrolled. However, this limitation should not influence the reported results because the change in power to detect statistical significance was from 80% to 78.5%. Second, 27% (166/617) of the enrolled persons did not complete the study because of withdrawal or death. This level of loss to follow-up was anticipated in our original study design. It demonstrates the challenges inherent in a 1-year study of a frail nursing home population. Because there were minimal differences in the characteristics of those who did and did not complete the study, this loss to follow-up did not have an impact on our overall results. Results among completers only were more likely to show an effect of vitamin E because attaining plasma and tissue saturation levels of vitamin E requires several months.25 However, the analysis of all patients randomized is the most conservative analysis and showed fewer significant effects. Third, the use of a half RDA multivitamin28 capsule for all participants might have lessened the impact of vitamin E on respiratory tract infection by improving the micronutrient status of the placebo group. However, we found no statistically significant differences between the vitamin E and placebo groups with change over time in the status of any nutrients other than vitamin E. Although our vitamin E group had a lower proportion of persons with low albumin and hemoglobin levels at baseline and follow-up, statistical adjustment for these potentially confounding factors did not change our conclusion. A high percentage of participants had low plasma zinc levels, but the 2 groups did not differ in the fraction of zinc- deficient participants before or after treatment and thus did not influence the reported results. Fourth, the significant reduction in URIs with vitamin E supplementation was not consistent in all analyses, and the common cold analysis was post hoc. However, these results suggest that future randomized trials of vitamin E should concentrate on these end points. The common cold is generally less severe than influenza. However, its much higher incidence and its recognized morbidity in the elderly33 make it an important public health problem in this age group. This is particularly relevant because no clinically useful vaccine or antiviral therapy is available to combat colds. In conclusion, we found no effect of vitamin E supplementation on the incidence or duration of respiratory tract infections. However, significantly fewer vitamin E participants acquired 1 or more respiratory tract infections, which was most evident in URIs. Post hoc subgroup analysis among individuals completing the study revealed a significantly lower incidence of common cold and fewer participants acquiring a cold. Common colds are frequent36 and associated with increased morbidity33 in this age group, and if confirmed, these findings suggest important implications for the well- being of the elderly. Future studies in elderly individuals should assess the effect of vitamin E supplementation on the common cold and incorporate microbiologic methods to allow for assessment of the impact of vitamin E on specific types of respiratory pathogens. Al Pater. Quote Link to comment Share on other sites More sharing options...
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