EAL

FNOA: Antioxidants (2011-2012)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To assess the effect of antioxidant supplements (beta carotene, vitamin A, vitamin C and vitamin E, and selenium) on overall mortality in primary or secondary prevention randomized clinical trials.

Inclusion Criteria:

The present review is based on studies that took place in Europe, North and South America, Asia and Australia.

Inclusion details:

Adults ranging in age from 18 to 103 years
Cancer and mortality were the main outcome measures
Antioxidants, administered alone or in combination with minerals or other interventions
Healthy participants were in the primary prevention trials
Unhealthy participants with a disease were included in the secondary prevention trials.

Exclusion Criteria:

Less than 18 years of age
Children or pregnant women
Tertiary prevention trials
Studies that violated the purpose or outcome of the mortality study.

Description of Study Protocol:

Recruitment: All primary and secondary prevention randomized clinical trials on antioxidant supplements (beta carotene, vitamin A, vitamin C and vitamin E, and selenium) vs. placebo or no intervention
Design: Three authors extracted data. Trials with adequate randomization, blinding and follow-up were classified as having a low risk of bias. Disagreement was resolved by discussion or in consultation with the article authors. Trial authors were contacted if there was missing information.
Blinding used: Yes
Interventions: Antioxidant supplements (beta carotene, vitamins A, C and E, and selenium) vs. placebo or no intervention
Statistical analysis: Random effects and fixed effects meta analysis were performed. Random effects meta regression analysis were performed to assess sources of intertrial heterogeneity.

Data Collection Summary:

Timing of Measurements

The dates used for search in various data banks were 1945 to 2006.

Dependent Variable

Mortality data in healthy participants and patients with various diseases.

Independent Variables

Antioxidant supplements (beta carotene, vitamins A, C and E, and selenium) vs. placebo or no intervention
Antioxidant supplements were administered orally and included doses of 1.2mg to 50mg (mean, 18mg) beta-carotene, 1,333 IU to 200,000 IU (mean, 20,219 IU) vitamin A, 60mg to 2,000mg (mean, 497mg) vitamin C, 10 IU to 5,000 IU (mean, 70 IU) vitamin E and 20mcg to 200mcg (mean, 99mcg) selenium daily or on alternate days for durations lasting 28 days to 12 years.
Mean duration of follow-up in all trials was 3.4 years.

Description of Actual Data Sample:

Number of articles identified: 16,111
Number of studies reviewed: 386
Number included: 67 RCTs
Sample size in studies: Between 24 and 39,876 participants
Age: 18 to 103 years; average age was 60 years or older
Ethnicity: Chinese, US citizens and European citizens
Location: China, US, Switzerland and Germany.

Summary of Results:

Findings

There was no effect on mortality in a random-effects meta-analysis (RR, 1.02; 95% CI, 0.99 to 1.06). However, in a fixed-effect meta-analysis, antioxidant supplements significantly increased mortality (RR, 1.04; 95% CI, 1.02 to 1.06).
Antioxidants significantly increased mortality (RR, 1.05; 95% CI, 1.02 to 1.08) in trials with low risk of bias. Antioxidants were assessed separately.
The fat-soluble supplements significantly increased mortality. RR and 95% CI were as follows
- Vitamin A: RR, 1.16; 95% CI, 1.10 to 1.24)
- Beta-carotene: RR, 1.07; 95% CI, 1.02 to 1.11)
- Vitamin E: RR, 1.04; 95% CI, 1.01 to 1.07)
- There was no significant effect for vitamin C (RR, 1.06; 95% CI, 0.94 to 1.20) or selenium (RR, 0.90; 95% CI, 0.80 to 1.01).

Author Conclusion:

No evidence was found to support antioxidant supplements for primary or secondary prevention
Vitamin A, beta carotene and vitamin E may increase mortality
Antioxidants supplements should be considered medicinal products and should undergo more evaluation before marketing occurs.

Funding Source:

University/Hospital:	Copenhagen University Hospital
Other:

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?	No

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