Meydani 2004Low.

Methods	Randomised, double‐blind placebo‐controlled trial with parallel group design (two intervention groups).
Participants	Country: United States. Number of participants randomised: 617, 169 men and 448 women, mean age 84 years. Inclusion criteria: aged 65 years or older; life expectancy greater than 6 months; no anticipated discharge within 3 months; not room‐bound for the past 3 months; absence of active neoplastic disease; no tube feeding, no kidney dialysis; no intravenous or urethral catheters for the last 30 days; no tracheostomy or chronic ventilator; antibiotic‐free for more than 2 weeks; no long‐term steroid treatment greater than 10 mg/d, no use of immunosuppressive drugs, or greater than the recommended daily allowance (RDA) level of supplements of vitamins E, C, or B6, selenium, zinc, beta‐carotene, or fish oil; body mass index of at least 18; serum albumin at least 3.0 g/dL; able to swallow pills; willing to receive influenza vaccine; and willing to provide informed consent (for patients with dementia, family members provided informed consent).
Interventions	Participants were randomly assigned to receive: group 1: 200 IU of vitamin E (dl‐alpha‐tocopherol) (n = 311); group 2: placebo 4 IU of vitamin E (n = 306); both in soybean oil, one capsule daily for a period of one year. All participants received a capsule containing half the recommended daily allowance of essential vitamins and minerals. All participants received influenza vaccine.
Outcomes	Primary outcomes of the trial were: incidence of, number of persons with, and number of days with respiratory tract infections (upper and lower), and number of new antibiotic prescriptions for respiratory tract infection. Secondary outcomes included emergency department visits, hospitalisation, and death. A post hoc subgroup analysis was performed to determine the effect of vitamin E on common colds.
Notes	Adherence to trial protocol was verified by nursing home medication records, returned pill count, and quarterly measurement of plasma vitamin E levels. Ninety‐eight percent of those completing the trial 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. Of the 617 randomised persons, 37% in the vitamin E and 36% in the placebo groups, respectively, completed the 1‐year trial period. Forty‐one participants in the vitamin group and 42 participants in the placebo group were lost to follow‐up. The losses to follow‐up were equal in both groups. Capsules were manufactured by Tishcon Corporation (Westbury, NY). The capsules were packed by Pharmasource Healthcare Inc (Marlboro, Mass).
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Sequence generation was achieved using computer random number generation.
Allocation concealment (selection bias)	Low risk	Allocation was controlled by a central and independent randomisation unit, so that intervention allocations could not have been foreseen in advance of, or during, enrolment.
Blinding (performance bias and detection bias) All outcomes	Low risk	The trial was described as blinded, the parties that were blinded, and the method of blinding was described, so that knowledge of allocation was adequately prevented during the trial.
Incomplete outcome data (attrition bias) All outcomes	Low risk	The numbers and reasons for dropouts and withdrawals in all intervention groups were described.
Selective reporting (reporting bias)	Low risk	Pre‐defined, or clinically relevant and reasonably expected outcomes are reported on.
Other bias	Low risk	The trial appears to be free of other components that could put it at risk of bias.