Beta-Carotene: From Carrot to Provitamin A, and the Smoker Trials
Beta-carotene is a carrot pigment the body turns into vitamin A. Karrer shared the 1937 Nobel Prize for work on carotenoids. Two 1990s trials in smokers then found that high-dose beta-carotene raised lung cancer risk, and the NIH fact sheet ties the warning to smokers and asbestos workers.
Beta-carotene is a carrot pigment that the body can turn into vitamin A, which makes it a provitamin A. The high-dose supplement, though, raised lung cancer risk in two large trials that both enrolled smokers. In the 1994 Finnish trial, men who took 20 mg of beta-carotene a day had 18 percent more lung cancers than men who did not take it. ## Karrer's Nobel covered the carotenoids Paul Karrer shared half of the 1937 Nobel Prize in Chemistry for his investigations on carotenoids, flavins and vitamins A and B2, according to the [Nobel Prize site](https://www.nobelprize.org/prizes/chemistry/1937/karrer/facts/). In 1931 he extracted vitamin A from cod-liver oil and determined its composition. Cod liver oil has a long record of its own, which our [omega-3 history](/blog/history/history-of-omega-3-from-cod-liver-oil-to-epa-and-dha) covers. The Nobel site also says vitamin A was the first vitamin whose structure was mapped. The same citation covers vitamin B2, whose structure he worked out in 1933, which made artificial production possible. We could not find a primary or institutional record that dates the first isolation of the carrot pigment, so this post does not name a discoverer. Curcumin, one of turmeric's compound groups, has its own isolation story in our [turmeric and curcumin history](/blog/history/history-of-turmeric-and-curcumin-from-ayurveda-to-isolation). ## Retinol counts one to one, beta-carotene does not The NIH Office of Dietary Supplements expresses vitamin A in retinol activity equivalents, or RAE. One microgram RAE equals one microgram of retinol, two micrograms of supplemental beta-carotene, or 12 micrograms of dietary beta-carotene. The fact sheet says these provitamin A carotenoids are all converted by the body into retinol, so the gap is how much of the pigment it takes to make the same amount of vitamin A ([NIH ODS](https://ods.od.nih.gov/factsheets/VitaminA-HealthProfessional/)). The trials reported doses in milligrams and IU, while the fact sheet reports vitamin A in RAE, so comparing them takes that conversion. Vitamin A is a group of fat-soluble retinoids, primarily retinol and retinyl esters. Our [vitamin D guide](/health/vitamin-d-complete-guide) covers the wider fat-soluble picture. The same fact sheet says orlistat, a weight-loss treatment, can decrease absorption of vitamin A and beta-carotene in some patients. ## The 1994 trial found more lung cancers The trials came nearly six decades after Karrer's Nobel. According to [PubMed](https://pubmed.ncbi.nlm.nih.gov/8127329/), the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC) enrolled 29,133 male smokers aged 50 to 69 in southwestern Finland. Participants were assigned to vitamin E, beta-carotene at 20 mg a day, both, or placebo, and followed for five to eight years. The trial was built to test whether those supplements would lower lung cancer, and it recorded 876 new lung cancer cases. Lung cancer incidence was 18 percent higher in the beta-carotene group (95 percent confidence interval, 3 to 36 percent). Total mortality was 8 percent higher, mostly from lung cancer and ischemic heart disease deaths. The vitamin E arm showed no reduction in lung cancer and more deaths from hemorrhagic stroke ([DOI](https://doi.org/10.1056/NEJM199404143301501)). ## CARET added vitamin A and saw the same pattern The Beta-Carotene and Retinol Efficacy Trial (CARET) enrolled 18,314 smokers, former smokers and workers exposed to asbestos. Its active group took 30 mg of beta-carotene and 25,000 IU of vitamin A, as retinyl palmitate, each day. According to [PubMed](https://pubmed.ncbi.nlm.nih.gov/8602180/), the trial recorded 388 lung cancers over 73,135 person-years of follow-up, and the relative risk was 1.28 against placebo (95 percent confidence interval, 1.04 to 1.57). The trial also measured cardiovascular death, with a relative risk of 1.26 that did not reach statistical significance. The authors wrote that the combination "had no benefit and may have had an adverse effect" after an average of four years of supplementation ([DOI](https://doi.org/10.1056/NEJM199605023341802)). The two trials side by side: | Trial | Who was enrolled | Beta-carotene dose | Follow-up | Lung cancer result | |---|---|---|---|---| | ATBC (1994) | 29,133 male smokers, ages 50 to 69, Finland | 20 mg a day | 5 to 8 years | 18% higher incidence in the beta-carotene group (95% CI 3 to 36) | | CARET (1996) | 18,314 smokers, former smokers and asbestos-exposed workers | 30 mg a day, plus 25,000 IU vitamin A as retinyl palmitate | Mean 4.0 years | Relative risk 1.28 against placebo (95% CI 1.04 to 1.57) | ## Carotenemia is the benign yellow story The other beta-carotene story is a yellow one. A 2003 paper in *Cutis* describes carotenemia as a common, benign pediatric condition in which blood beta-carotene rises and the skin turns yellow. It is usually caused by excessive intake, and the paper says the diet-driven kind does not have serious sequelae. Rarely, it is linked to a serious metabolic disorder ([According to PubMed](https://pubmed.ncbi.nlm.nih.gov/12839253/)). A 2017 review in *Clinical Nutrition ESPEN* says high intake of carotenoid-rich foods, or beta-carotene supplements above 30 mg a day for months, can produce the yellowing, which shows especially on the palms and soles ([DOI](https://doi.org/10.1016/j.clnesp.2017.12.002)). The same review notes that some studies found no major link between intake and the yellowing, which the authors read as a sign that genetics plays a part. ## The fact sheet ties the warning to smokers and asbestos workers The NIH fact sheet says the CARET and ATBC results "suggest that large supplemental doses of beta-carotene with or without retinyl palmitate have detrimental effects in current or former smokers and workers exposed to asbestos." It adds that among nonsmokers, beta-carotene and vitamin A supplements do not appear to affect the risk of cancer ([NIH ODS](https://ods.od.nih.gov/factsheets/VitaminA-HealthProfessional/)). That is a narrow warning, and it should be read narrowly. The trials gave daily supplement doses of 20 or 30 mg of beta-carotene to smokers and asbestos-exposed workers. None of the sources we read tested food that way, so the history teaches a lesson about dose and population, not about carrots. The CARET investigators stopped the trial 21 months early, on the basis of what they had found, and still planned five more years of follow-up. **Next reads** - [Vitamin D complete guide](/health/vitamin-d-complete-guide): the wider fat-soluble vitamin reference, next to vitamin A. - [Vitamin C history, from scurvy to ascorbic acid](/blog/history/history-of-vitamin-c-from-scurvy-to-ascorbic-acid): another vitamin story where a deficiency disease came before the compound. ### Related reading - [how a fertility factor became vitamin E](/blog/history/history-of-vitamin-e-from-fertility-factor-to-tocopherol) - [how night blindness became a vitamin A story](/blog/history/history-of-vitamin-a-from-night-blindness-to-retinol) - [lutein's research history, from marigold petals to eye trials](/blog/history/history-of-lutein-from-marigold-to-eye-supplements)