EAL

DLM: Vitamin E, C, B-carotene Supplements and All-Cause Mortality (2007-2010)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

The purpose of the present paper is to re-analyze the association of vitamin E supplementation and mortality as presented by Miller et al, 2005
By means of augmented data sources as well as additional methodological approaches, the results of the meta analysis is to be either confirmed or called into question.

Inclusion Criteria:

This is a statistical paper designed to re-analyze data from Miller, 2005. The author included the 22 studies from the Miller paper, seven studies that Miller excluded due to fewer than 10 deaths, plus three studies published since Miller, 2005.

Human clinical trials related to vitamin E supplementation and mortality
Vitamin E doses: 16.5 IU to 5,000 IU per day
Studies with information on number of deaths due to vitamin E supplementation.

Exclusion Criteria:

Not applicable.

Description of Study Protocol:

Design

Meta-analysis.

Intervention

Reported studies includes vitamin E supplementation
Details are not discussed.

Statistical Analysis

It includes fixed effects models, random effects models and methods of meta regression of univariate effect measures. Binary outcome variables hierarchical logistic regression models also used.
The outcome is modeled by means of a bivariate approach
Categorical model or by a continuous model is used for the dose response relationship of vitamin E supplementation
All statistical analyses are intended to be exploratory
P-values are not interpreted in confirmatory sense
No adjustment for multiplicity is performed.

Data Collection Summary:

The data was analyzed using fixed effects models, random effects models, methods of meta regression of univariate effect measures and binary outcomes variable hierarchical logistic regression models.

In order to analyse the dose-response relationship of vitamin E supplementation and mortality, basic approaches can either be formulated by means of a categorical model or by a continuous model.

Timing of measurements: Studies included in the meta-analysis (from 1994 to 2005) to study the effects of Vitamin E at different doses on mortality
Dependent variable: Mortality
Independent variable: Dose of vitamin E (low and high dose; range, 16.5 IU to 5,000 IU per day).

Description of Actual Data Sample:

Initial N

29 clinical trials
- 19 clinical trials comprising a total of 135,967 participants were included (same as Miller et al, 2005, paper)
- 10 additional trials were included (2,495 additional participants receiving vitamin E doses from 136 IU to 5,000 IU per day). These included seven trials excluded by Miller, 2005, due to fewer than 10 deaths, plus three papers published after that of Miller et al, 2005.
Vitamin E supplementation used by the subjects were included.

Age

Mean age range: 47 to 85 years.

Location

Meta-analysis is reported from Germany (studies included from different countries).

Summary of Results:

Hierarchical regression analysis confirmed the results of Miller et al, 2005, that supplementing vitamin E resulted in increased mortality in 19 trials. However, further results from two trials were available. Gerss et al added this data plus 10 additional trials and applied traditional meta-analysis techniques to reveal that the increased mortality was not due to the vitamin E, but rather to the higher proportion of males in the trials.

Author Conclusion:

High dose supplemental vitamin E does not increase mortality.

Funding Source:

University/Hospital:

University of Münster, Department of Medical Informatics and Biomathematics, Münster, Germany

Reviewer Comments:

Quality Criteria Checklist: Review Articles
Relevance Questions
	1.	Will the answer if true, have a direct bearing on the health of patients?	Yes
	2.	Is the outcome or topic something that patients/clients/population groups would care about?	Yes
	3.	Is the problem addressed in the review one that is relevant to dietetics practice?	Yes
	4.	Will the information, if true, require a change in practice?	Yes

Validity Questions
	1.	Was the question for the review clearly focused and appropriate?	Yes
	2.	Was the search strategy used to locate relevant studies comprehensive? Were the databases searched and the search termsused described?	Yes
	3.	Were explicit methods used to select studies to include in the review? Were inclusion/exclusion criteria specified andappropriate? Wereselectionmethods unbiased?	Yes
	4.	Was there an appraisal of the quality and validity of studies included in the review? Were appraisal methodsspecified,appropriate, andreproducible?	Yes
	5.	Were specific treatments/interventions/exposures described? Were treatments similar enough to be combined?	Yes
	6.	Was the outcome of interest clearly indicated? Were other potential harms and benefits considered?	Yes
	7.	Were processes for data abstraction, synthesis, and analysis described? Were they applied consistently acrossstudies and groups? Was thereappropriate use of qualitative and/or quantitative synthesis? Was variation in findings among studies analyzed? Were heterogeneity issued considered? If data from studies were aggregated for meta-analysis, was the procedure described?	Yes
	8.	Are the results clearly presented in narrative and/or quantitative terms? If summary statistics are used, are levels ofsignificance and/or confidence intervals included?	Yes
	9.	Are conclusions supported by results with biases and limitations taken into consideration? Are limitations ofthe review identified anddiscussed?	Yes
	10.	Was bias due to the review's funding or sponsorship unlikely?	Yes