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However, for vitamin E, a higher dose, such as 200 mg/d, has been needed to prove effective. Until now, the effect of multivitamin-mineral supplementation at physiological doses or of 200 mg of vitamin E on respiratory tract infections has not been investigated in non-institutionalized elderly persons. And, results in institutionalized elderly individuals have been inconsistent. A group of researchers set out to determine whether long-term daily supplementation with multivitamins and minerals at the RDA level or with 200 mg of vitamin E reduced incidence and severity of acute respiratory tract infections in non-institutionalized elderly individuals. A total of 652 men and women, above 60 years of age, were enrolled in the randomized, double-blind, placebo-controlled trial. Subjects were excluded if they used immunosuppressive treatment, anticoagulants interfering with vitamin K metabolism, or dietary supplements in the previous two months, or if they had a history of cancer, liver disease, or fat malabsorption during the five years prior to randomization. The following treatments were applied in a 2 X 2 factorial design: multivitamins and minerals, vitamin E, multivitamins and minerals plus vitamin E, and placebo. The multivitamin included dosages at RDA levels for vitamins and 25% to 50% of RDA levels for minerals. The vitamin E capsule contained 200 mg/dl of alpha-tocopheryl acetate because this dose was suggested to be optimal for improving immune response. Each participant received two capsules per day to be taken with dinner for a maximum of 15 months. Subjects filled out a questionnaire regarding relevant population characteristics and supplement use at baseline and yearly influenza vaccination after treatment. The main outcomes were incidence and severity of acute respiratory tract infections assessed using a diary in which participants recorded all acute symptoms. Participants were instructed to report symptoms of a possible acute respiratory tract infection by telephone to the study nurse who checked whether the symptoms met the definition. As a more specific diagnostic test, microbiology tests by polymerase chain reaction and serology tests were performed in a random subsample of 97 symptomatic patients. The median observation period was 441 days. A total of 443 of 652 subjects recorded 1024 respiratory tract infection episodes. The incidence rate ratio of acute respiratory tract infection for multivitamin-mineral supplementation was (95% DI, .15; P = .58) and for vitamin E supplementation, (95% CI, .25; P=.21). Severity of infections was not influenced by multivitamin-mineral supplementation. For vitamin E versus no vitamin E, severity was found to be worse; median for illness-duration was 19 versus 14 days, P=.02; number of symptoms, 6 versus 4, P=.03, presence of fever, % versus %, P=.009,; and restriction of activity, % versus %, P=.02. It appears that neither daily multivitamin-mineral supplementation at physiological doses nor 200 mg of vitamin E improved the incidence and severity of acute respiratory tract infection in non-institutionalized elderly individuals. Investigators actually observed the opposite of what was expected; they observed adverse effects of vitamin E on illness severity in this population. J. Graat, E. Schouten, F. Kok. Effect of daily vitamin E and multivitamin-mineral supplementation on acute respiratory tract infections in elderly persons. JAMA; 288:715-720 (August 14, 2002). [Correspondence: Judith M. Graat, MSc, Division of Human Nutrition and Epidemiology, Wageningen University, PO Box 8129, 6700 EV Wageningen, Netherlands. E-mail: .]
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