Antioxidant pills and mortality

Overview

Bjelakovic G et al.. JAMA 2007 · PMID 17327526 · DOI 10.1001/jama.297.8.842

In low-bias trials, beta-carotene, vitamin A and vitamin E were linked to slightly more deaths.

Does the study support the specific claim? Partly · Methodological quality: moderate

Original publication

Plain-language summary

Scientific in-depth review

1. Full reference

Authors

Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C

Journal

JAMA

Year

2007

Identifier

PMID 17327526 DOI 10.1001/jama.297.8.842

Verification

verified – PubMed E-utilities efetch, 2026-10-25

Retracted

no

Corrections

PubMed lists: ErratumIn (JAMA. 2008 Feb 20;299(7):765-6)

Extent checked

abstract only

Conflicts of interest and funding

not stated in abstract

2. Research question

Effect of antioxidant supplements on mortality

3. Study design and population

Study design

Meta-analysis – Systematic review and meta-analysis of randomised antioxidant trials

Population

Adults in 68 RCTs

Country

Multinational

Period

to Oct 2005

Sample size

68 trials, 232,606

Inclusion and exclusion criteria

see abstract

4. Methods and endpoints

Exposure / intervention

Beta-carotene, vitamin A, C, E, selenium

Comparator

Placebo/no intervention

Endpoints

All-cause mortality

Statistical methods

Random effects; meta-regression; bias stratification

5. Actual results

Results

All trials RR 1.02 (0.98–1.06, n.s.); 47 low-bias trials RR 1.05 (1.02–1.08); beta-carotene RR 1.07, vitamin A 1.16, vitamin E 1.04; vitamin C and selenium n.s.

Absolute risks

not reported in abstract

Authors' conclusion

Beta-carotene, vitamin A and vitamin E may increase mortality.

6. Strengths

• Large
• Bias stratification

7. Weaknesses

• Exclusion of zero-death trials and methods were debated
• Heterogeneous populations
• Erratum

8. Risk of bias

Orienting tool

AMSTAR 2

Type of assessment

simplified assessment (abstract only)

Full formal assessment

no

Overall risk of bias

some concerns

Rationale

Methodological choices debated.

9. Assessment of the statistical interpretation

See results.

10. Relevance to the specific claim

C-SUP-02; C-SUP-03.

11. Independent contrary findings

USPSTF 2022: vitamin E OR 1.02 mortality.

12. Transferability to Germany and Europe

High: biology and trial populations comparable to European adults.

13. Overall methodological judgement

Supports harm for beta-carotene; vitamin E less certain.

14. Open questions

15. Linked fact checks

• Beta-carotene supplements (with or without vitamin A) increased lung cancer and mortality in smokers and asbestos-exposed workers (CARET, ATBC), and the USPSTF recommends against them. – Studies supporting the claim
• High-dose vitamin E (400 IU/day) increases prostate cancer (SELECT, +17%) and may increase all-cause mortality (Miller 2005: +39 per 10,000). – Studies supporting the claim

Use by the Tayebat archive

Note: according to the archive, the studies were compiled by the archive operators. Whether Dr. Elawady himself cited this study is not established.

What the archive says about the study

In 47 low-bias trials, antioxidant supplements increased mortality (RR 1.05); beta-carotene 1.07, vitamin A 1.16, vitamin E 1.04.

A. What was actually studied?

Antioxidant RCTs and mortality.

B. What did the authors find?

RR 1.05 in low-bias trials; overall RR 1.02 n.s.

C. What conclusions do the authors themselves draw?

May increase mortality.

D. What does the archive derive from it?

Used as evidence of harm.

E. Is this derivation scientifically justified?

Essentially correct; omits that pooled all trials showed no significant effect.

Adequacy of the interpretation (by the archive)

essentially correct but incomplete