Randomised controlled trialindependent cross-checkabstract checked I-SUP-121 standard review
Beta-carotene harm persisted after stopping (CARET)
The Beta-Carotene and Retinol Efficacy Trial: incidence of lung cancer and cardiovascular disease mortality during 6-year follow-up after stopping beta-carotene and retinol supplements.
Overview
Goodman GE et al.. J Natl Cancer Inst 2004 · PMID 15572756 · DOI 10.1093/jnci/djh320
Six years after stopping the pills, lung cancer and deaths were still somewhat higher in the beta-carotene group.
Does the study support the specific claim? Yes · Methodological quality: high
Plain-language summary
Study explained simply
- What did the researchers want to find out?
To follow CARET participants after the trial stopped.
- How was the study done?
Follow-up of a randomised trial.
- How many people, animals or samples were studied?
18,314 high-risk adults.
- What was actually found?
Lung cancer RR 1.12 and death RR 1.08 after stopping.
- How large was the observed effect?
RR 1.12 (0.97-1.31).
- What do the results mean in everyday life?
Smokers should not take beta-carotene pills.
- What are the study's limitations?
Not statistically significant after stopping.
- What does it say about Elawady's specific claim?
Supports C-SUP-02.
- Do the results apply to Germany and Europe?
Applicable.
- What can explicitly not be concluded from this study?
Not about carotenoids in food.
Scientific in-depth review
1. Full reference
- Authors
- Goodman GE et al.
- Journal
- J Natl Cancer Inst
- Year
- 2004
- Identifier
- PMID 15572756 DOI 10.1093/jnci/djh320
- Verification
- verified – PubMed efetch 2026-10-26; Crossref works API 2026-10-26
- Retracted
- no
- Corrections
- none
- Extent checked
- abstract only
- Conflicts of interest and funding
No COI statement in PubMed record; funding listed: NCI NIH HHS
2. Research question
Do adverse effects of beta-carotene plus retinyl palmitate persist after stopping?
3. Study design and population
- Study design
- Randomised controlled trial – Post-intervention follow-up of a randomised placebo-controlled trial (CARET)
- Population
Smokers, former smokers and asbestos-exposed workers
- Country
USA
- Period
Intervention stopped January 1996; follow-up to 31 December 2001
- Sample size
18,314
- Inclusion and exclusion criteria
CARET participants
4. Methods and endpoints
- Exposure / intervention
30 mg beta-carotene + 25,000 IU retinyl palmitate daily (stopped)
- Comparator
Placebo
- Endpoints
Lung cancer, all-cause and CVD mortality
- Statistical methods
Relative risks with 95% CI; smoothed RR curves
5. Actual results
- Results
Post-intervention RR lung cancer 1.12 (0.97-1.31); all-cause mortality 1.08 (0.99-1.17); RRs remained above 1.0; CVD mortality RR returned to 1.0. Females had larger RRs (lung cancer mortality 1.33 vs 1.14; all-cause mortality 1.37 vs 0.98, P=0.001).
- Absolute risks
not reported in abstract
- Authors' conclusion
Adverse effects on lung cancer and all-cause mortality persisted after stopping, though no longer statistically significant.
6. Strengths
- Randomised
- Long follow-up
7. Weaknesses
- Post-intervention phase; self-reported endpoints confirmed by records
- Subgroup findings by sex
8. Risk of bias
- Orienting tool
- RoB 2
- Type of assessment
- simplified assessment (abstract only)
- Full formal assessment
- no
- Overall risk of bias
- low
- Rationale
Follow-up of randomised groups.
9. Assessment of the statistical interpretation
Point estimates above 1 with CIs including 1.
10. Relevance to the specific claim
Confirms the CARET harm signal persisted after stopping.
11. Independent contrary findings
Not significant post-intervention.
12. Transferability to Germany and Europe
Applicable.
13. Overall methodological judgement
Supports C-SUP-02.
| Multidimensional assessment | |
|---|---|
| Authenticity of the source | verified |
| Methodological quality | high |
| Risk of bias | low |
| Precision of results | moderate |
| Directness | direct |
| Reproducibility | replicated |
| Consistency with the overall evidence | consistent |
| Regional transferability | high |
| Adequacy of the interpretation (by the archive) | not applicable |
14. Open questions
Mechanism.