Record ID: MS-N087 · Family: Nutrients and supplements / harmful prevention claim · Clinical question: Do beta-carotene and retinyl palmitate prevent lung cancer in people who smoke or have asbestos exposure?

Evidence label: Harmful in randomized evidence: the CARET combination increased lung-cancer incidence and mortality and was stopped early.

Evidence at a glance

• Benefit: No chemoprevention benefit.
• Certainty: High for harm in the high-risk population and doses tested.
• Risk: More lung cancers and deaths; the intervention was stopped 21 months early.
• Cancer control: The supplement combination did not prevent or treat cancer.

What was studied

CARET randomized 18,314 current or former smokers and people with occupational asbestos exposure to beta-carotene 30 mg/day plus retinyl palmitate 25,000 IU/day or placebo. It was double-blind and placebo-controlled.

The active intervention was stopped 21 months early after the monitoring evidence showed no benefit and possible harm.

What the results show

In the prespecified weighted analysis, the active combination increased lung-cancer incidence: RR 1.36 (95% CI 1.07–1.73), and lung-cancer mortality: RR 1.59 (95% CI 1.13–2.23). The early report described 28% more lung cancers and 17% more deaths overall in the active group.

During six years after supplements stopped, relative risks remained above 1 but were no longer statistically significant: lung cancer RR 1.12 (95% CI 0.97–1.31) and all-cause mortality RR 1.08 (95% CI 0.99–1.17).

Important limits

• The findings concern high-dose supplements, not beta-carotene in vegetables.
• The trial tested a combination, so the exact contribution of retinyl palmitate cannot be completely separated.
• Results are most directly applicable to smokers, former smokers and asbestos-exposed people.
• Subgroup findings by sex or alcohol intake are exploratory and should not distract from the overall harm.

Safety and practical context

People who smoke or have smoked should avoid high-dose beta-carotene supplements for lung-cancer prevention. Retinoid toxicity can include liver injury, bone effects and birth defects. A “natural antioxidant” label does not make this combination safe.

Questions for the care team

• Does my multivitamin contain beta-carotene or preformed vitamin A?
• Am I in a high-risk group because of smoking or asbestos exposure?
• Is the dose far above food-level intake?
• What evidence-based smoking cessation and lung-cancer screening steps apply to me?

Sources checked

• CARET prespecified intervention analysis, JNCI 1996 (PMID 8901853)
• CARET six-year post-intervention follow-up, JNCI 2004 (PMID 15572756)

Funding and conflicts: CARET was a US National Cancer Institute–supported multicenter prevention trial; detailed supplement supply and author disclosures are reported in the original publications.

Last literature search: October 20, 2026 · Record appraisal: October 20, 2026

Educational information only. This record is not a prescription and does not replace advice from the oncology team, registered dietitian or oncology pharmacist.