{"entity":{"id":"paper-caret-beta-carotene-retinol-lung-cancer-nejm-1996","kind":"paper","name":"Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease","aka":[],"tldr":"A vitamin trial in 18,314 smokers and asbestos workers was stopped early because the people taking the supplements were getting more lung cancer, not less.","summary":"The Beta Carotene and Retinol Efficacy Trial (CARET): a multicentre, randomised, double-blind, placebo-controlled primary prevention trial of 30 mg of beta carotene plus 25,000 IU of retinol daily against placebo in 18,314 smokers, former smokers and workers exposed to asbestos, reported by Omenn, Goodman, Thornquist and colleagues.\n\nObservational data had linked high dietary carotenoid intake to lower lung cancer risk, and the trial was built to convert that correlation into a preventive intervention. It did the opposite, and it did so at the same time as the Finnish ATBC trial found the same direction of harm. CARET is the standing answer to any proposal to move a nutritional association into a supplement without randomising it.","asOf":"2026-09-25","links":[{"label":"N Engl J Med 1996","url":"https://doi.org/10.1056/NEJM199605023341802"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/8602180/"}],"tags":["lung-evidence"],"related":["nutrition-lifestyle-roadmap","prevention-roadmap"],"cancers":["lung-cancer","nsclc"],"sections":["prevention"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption","b-misinformation","b-negative-results"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":1996,"doi":"10.1056/NEJM199605023341802","pmid":"8602180","authors":"Omenn GS, Goodman GE, Thornquist MD, et al.","paperType":"rct","findings":["388 new cases of lung cancer during 73,135 person-years of follow-up, with a mean follow-up of 4.0 years.","Relative risk of lung cancer in the active-treatment group 1.28 (95 percent confidence interval 1.04 to 1.57; P equals 0.02).","Relative risk of death from any cause 1.17 (1.03 to 1.33), from lung cancer 1.46 (1.07 to 2.00) and from cardiovascular disease 1.26 (0.99 to 1.61).","The trial was stopped 21 months earlier than planned on these findings.","No statistically significant differences in the risks of other types of cancer."],"whatItMeans":"Supplements are drugs, and drugs have to be tested. A plausible mechanism, a consistent observational signal and a safe-sounding intervention still produced measurable harm in the people it was meant to protect.","caveats":["High-risk population (heavy smokers and asbestos-exposed workers) at a high supplement dose; it does not say what dietary carotenoids do at dietary levels.","The mechanism of the excess risk was never settled.","Four years of mean follow-up for an exposure whose latency is measured in decades."],"changedPractice":true,"participants":18314},"route":"/key-papers/paper-caret-beta-carotene-retinol-lung-cancer-nejm-1996/","neighbours":{"roadmap":[{"id":"prevention-roadmap","kind":"roadmap","name":"Cancer prevention roadmap: tobacco control and vaccines → biomarker-guided chemoprevention → interception in carriers","route":"/roadmaps/prevention-roadmap/"},{"id":"nutrition-lifestyle-roadmap","kind":"roadmap","name":"Diet, exercise and lifestyle roadmap: causes established → interventions that disappointed → exercise proven as treatment","route":"/roadmaps/nutrition-lifestyle-roadmap/"}],"cancer":[{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"section":[{"id":"prevention","kind":"section","name":"Prevention & Risk","route":"/fronts/prevention/"}],"bottleneck":[{"id":"b-negative-results","kind":"bottleneck","name":"Failures are hidden","route":"/bottlenecks/b-negative-results/"},{"id":"b-misinformation","kind":"bottleneck","name":"Misinformation and unproven therapies","route":"/bottlenecks/b-misinformation/"},{"id":"b-prevention-adoption","kind":"bottleneck","name":"Prevention we already have is not deployed","route":"/bottlenecks/b-prevention-adoption/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}]}}