To the Editor: Based on their meta-analysis of antioxidant supplementation trials, Dr Bjelakovic and colleagues1 conclude that some of the intervention nutrients appeared to be associated with increased mortality. Particular aspects of their approach, analysis, and reported findings may have led to incomplete or biased determinations of the real effect of such nutrients in various populations.
Although vitamin A is related to beta carotene (and other provitamin A carotenoids) by virtue of its in vivo formation through oxidative cleavage of the latter, it is not considered an antioxidant nutrient.2 Its primary inclusion in the meta-analysis, except as an eligible trial cosupplement, is therefore surprising, with specific implications for the 2 trials that tested vitamin A only. Controlled trials of several other nonantioxidant vitamins could have been similarly included in the analysis along with those testing vitamin A.
Nearly half of the studies originally identified from the literature (405 of 815) were excluded because no deaths occurred, and most of the 68 trials that were analyzed were small, with few deaths (12 trials had only 1 death). This would yield findings heavily weighted by a few large studies. Also, it would be useful to know what hypotheses formed the basis for the “preconceived” subgroup analyses that excluded selenium and high-bias risk trials, which showed essentially protective effects and whose exclusion would certainly shift the risk estimates higher.
The findings from this analysis have implications primarily for supplementation in high-risk populations. Sixty-nine percent of the studies involved secondary prevention and tested efficacy for recurrence or advancement of preexisting cardiovascular, neoplastic, neurological, ocular, and other diseases. Even of the 21 primary prevention trials, many encompassed elevated baseline population risks from smoking,3 asbestos exposure,4 or multinutritional deficiencies,5 for example. The population risk-antioxidant-mortality interaction might be more clearly elucidated if the respective summary relative risk (RR) estimates for the primary and secondary prevention trials were provided. Also, is it possible that primary vs secondary prevention trials did not significantly differ with respect to mortality in the models, as stated on page 847, when according to the article's Figures 2 and 3 and Tables 1 and 2, these studies had median crude mortality rates of 2.1 and 6.0 deaths per 100 participants (or median crude annual rates of 0.9 and 3.3 deaths per 100 person-years), respectively?
Financial Disclosures: None reported.
Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature
Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
Instructions
Comments are moderated and will appear on the site at the discretion of the Journal of American Medical Association editors. Comments should not exceed 500 words of text and 10 references.
Do not submit personal medical questions or information that could identify a specific patient, questions about a particular case, or general inquiries to an author. Only content that has not been published, posted, or submitted elsewhere should be submitted. By submitting this Comment, you and any coauthors transfer copyright to the journal if your Comment is posted.
* = Required Field
Disclosure of Any Conflicts of Interest* Indicate all relevant conflicts of interest of each author below, including all relevant financial interests, activities, and relationships within the past 3 years including, but not limited to, employment, affiliation, grants or funding, consultancies, honoraria or payment, speakers’ bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued. If all authors have none, check "No potential conflicts or relevant financial interests" in the box below. Please also indicate any funding received in support of this work. The information will be posted with your response.
Register and get free email Table of Contents alerts, saved searches, PowerPoint downloads, CME quizzes, and more
Subscribe for full-text access to content from 1998 forward and a host of useful features
Activate your current subscription (AMA members and current subscribers)
Some tools below are only available to our subscribers or users with an online account.
Download citation file:
Customize your page view by dragging & repositioning the boxes below.
and access these and other features:
Register Now
Enter your username and email address. We'll send you a reminder to the email address on record.
Athens and Shibboleth are access management services that provide single sign-on to protected resources. They replace the multiple user names and passwords necessary to access subscription-based content with a single user name and password that can be entered once per session. It operates independently of a user's location or IP address. If your institution uses Athens or Shibboleth authentication, please contact your site administrator to receive your user name and password.