Antioxidant supplements vitamin E and selenium – taken alone or in combination – did not prevent dementia in asymptomatic older men, according to the results of a clinical trial.
Antioxidants as potential treatment for cognitive impairment or dementia have been of interest for years because oxidative stress has been implicated as a dementia pathway.
The Prevention of Alzheimer’s Disease by Vitamin E and Selenium (PREADViSE) clinical trial initially enrolled 7,540 older men who used the supplements for an average of about five years and a subset of 3,786 men who agreed to be observed longer. The men received either vitamin E, selenium, both or a placebo.
The incidence of dementia (325 of 7,338 men (4.4%)) was not different among the four study groups, according to the results in the article by Dr Richard J Kryscio, of the University of Kentucky, Lexington, and co-authors.
Limitations of the study include losing about half of the participants to long-term follow-up during the transition from a randomised clinical trial to a cohort study. Publicity about the negative effect of supplements also may have played a role, according to the authors.
“The supplemental use of vitamin E and selenium did not forestall dementia and are not recommended as preventive agents. This conclusion is tempered by the underpowered study, inclusion of only men, a short supplement exposure time, dosage considerations and methodologic limitations in relying on real-world reporting of incident cases,” the article concludes.
Abstract
Importance: Oxidative stress is an established dementia pathway, but it is unknown if the use of antioxidant supplements can prevent dementia.
Objective: To determine if antioxidant supplements (vitamin E or selenium) used alone or in combination can prevent dementia in asymptomatic older men.
Design, Setting, and Participants: The Prevention of Alzheimer’s Disease by Vitamin E and Selenium (PREADViSE) trial began as a double-blind randomized clinical trial in May 2002, which transformed into a cohort study from September 2009 to May 2015. The PREADViSE trial was ancillary to the Selenium and Vitamin E Cancer Prevention Trial (SELECT), a randomized clinical trial of the same antioxidant supplements for preventing prostate cancer, which closed in 2009 owing to findings from a futility analysis. The PREADViSE trial recruited 7540 men, of whom 3786 continued into the cohort study. Participants were at least 60 years old at study entry and were enrolled at 130 SELECT sites, and Cox proportional hazards models were used in a modified intent-to-treat analysis to compare hazard rates among the study arms.
Interventions: Participants were randomized to vitamin E, selenium, vitamin E and selenium, or placebo. While taking study supplements, enrolled men visited their SELECT site and were evaluated for dementia using a 2-stage screen. During the cohort study, men were contacted by telephone and assessed using an enhanced 2-stage cognitive screen. In both phases, men were encouraged to visit their physician if the screen results indicated possible cognitive impairment.
Main Outcomes and Measures: Dementia case ascertainment relied on a consensus review of the cognitive screens and medical records for men with suspected dementia who visited their physician for an evaluation or by review of all available information, including a functional assessment screen.
Results: The mean (SD) baseline age of the 7540 participants was 67.5 (5.3) years, with 3936 (52.2%) reporting a college education or better, 754 (10.0%) reporting black race, and 505 (6.7%) reporting Hispanic ethnicity. Dementia incidence (325 of 7338 men [4.4%]) was not different among the 4 study arms. A Cox model, which adjusted incidence for participant demographic information and baseline self-reported comorbidities, yielded hazard ratios of 0.88 (95% CI, 0.64-1.20) for vitamin E, 0.83 (0.60-1.13) for selenium, and 1.00 (0.75-1.35) for the combination compared with placebo.
Conclusions and Relevance: Neither supplement prevented dementia. To our knowledge, this is the first study to investigate the long-term association of antioxidant supplement use and dementia incidence among asymptomatic men.
Authors
Richard J Kryscio; Erin L Abner; Allison Caban-Holt; Mark Lovell; Phyllis Goodman; Amy K Darke; Monica Yee; John Crowley; Frederick A Schmitt
[link url="http://media.jamanetwork.com/news-item/vitamin-e-selenium-supplements-did-not-prevent-dementia/"]JAMA material[/link]
[link url="http://jamanetwork.com/journals/jamaneurology/fullarticle/2612477"]JAMA Neurology abstract[/link]
[link url="http://jamanetwork.com/journals/jamaneurology/fullarticle/2612473"]JAMA Neurology editorial[/link]