Beta-carotene and the application of transcriptomics in risk-benefit evaluation of natural dietary components

Our plain-English summary of Beta-carotene and the application of transcriptomics in risk-benefit evaluation of natural dietary components, by J. Keijer, A. Bunschoten, A. Palou, et al (Biochimica et Biophysica Acta, 2005).

The study

• Authors: J. Keijer, A. Bunschoten, A. Palou, N.L. Franssen-van Hal
• Journal: Biochimica et Biophysica Acta
• Published: 2005;1740(2):139-46
• Type of article: Review
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Beta-carotene is a natural food component that is present in fruits and vegetables and is also used as a food colorant and a supplement. Beta-carotene is an anti-oxidant and a source of vitamin A. It is endowed with health beneficial properties, but a number of studies showed that with high intakes it may increase the risk for lung cancer in at risk individuals (heavy smokers, asbestos workers and alcohol users). To establish the window of benefit, it is necessary to identify early markers of effect and to obtain insight in the mechanism of action of beta-carotene, in the absence and presence of environmental risk factors. Genomics technologies are well suited to dissect the mechanisms of action and identify the markers of effect. Human cell lines can be used to analyse the effects of beta-carotene, but exposure studies with beta-carotene show that cell lines display a widely variant behaviour, which hampers translation to the in vivo situation in humans. Alternatively, animal studies can be used. Especially the ferret seems to be a good model, but little sequence information of this species is available. However, heterologous hybridization on human cDNA seems possible and provides and a new tool for molecular analysis of health effects of beta-carotene.

In plain English

This article was a review, not a study of asbestos-exposed people. The authors summarised evidence on the health benefits and possible harms of beta-carotene and described how gene-expression (transcriptomics) methods might show how it acts. Among the trials reviewed, the CARET trial included 4060 asbestos-exposed males among its participants, who were given beta-carotene and vitamin A. It reported higher lung cancer incidence in the supplemented group than in the placebo group (RR 1.28, 95% CI 1.07 to 1.57). The article gave no separate result for the asbestos-exposed men. The authors also reported their own laboratory work. Human intestinal and lung cell lines differed in how fast and how much beta-carotene they took up. In two lung cell lines, gene-expression changes after beta-carotene exposure were small. Ferret RNA gave signal at an average of 32% of positions on a human array and 23% on a mouse array. The authors concluded that a human array seems usable for ferret studies, though some information may be lost. They also cautioned against drawing health conclusions from single cell lines.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Review of published evidence on beta-carotene, with preliminary laboratory data from the authors (human cell-line experiments and a pilot test of ferret tissue on human and mouse gene arrays)
• Who was studied: In the authors' own work: human intestinal cell lines (the text says four but names five: CaCo-2, HT-29, HT29D4, CCD841CoTr, HuTu 80) and four human lung cell lines (NCI-H292, NCI-H460, NCI-H661, BEAS-2B), plus 3 ferret tissue samples. No human participants were studied by the authors.
• Exposure: Beta-carotene. In the authors' cell experiments, lung cells were exposed to 1 micromolar beta-carotene (delivered with linoleic acid and 0.02% THF) for 76 hours. Asbestos was not studied by the authors. It appears only as a risk group in the reviewed trials.
• Main results:
  • Reviewed trial, not the authors' own data: CARET included 4060 asbestos-exposed males among its participants, who received 30 mg beta-carotene and 25,000 IU vitamin A daily. Lung cancer incidence was higher in the supplemented group than in the placebo group (RR 1.28, 95% CI 1.07 to 1.57). No separate figure was given for the asbestos-exposed men.
  • Authors' data: both the speed and the level of beta-carotene uptake differed for each human cell line tested, and no specific lung or intestinal pattern was found.
  • Authors' data: in lung cell lines H661 and BEAS-2B, gene-expression differences between the two cell lines were larger than the changes caused by beta-carotene. The changes were small: at most 2.4-fold (H661) and 2.1-fold (BEAS-2B).
  • Authors' data: 3 ferret samples on arrays showed signal at an average of 32% of positions on the human array and 23% on the mouse array. Human lung RNA showed 56% on a human array.
  • Authors' data: of the 250 most highly expressed ferret lung genes, 61 (24.4%) were also among the 250 most highly expressed genes in the human lung sample.
• The authors' conclusion: The authors concluded that a human gene array seems usable to study the molecular effects of beta-carotene in ferrets, although some information may be lost.
• Limitations the authors state:
  • It was not possible to say which cell line best represents what happens in the human body.
  • Results from a single cell line should not be read as an effect on human health without confirmation in intact humans.
  • The small gene-expression changes may reflect measurement at steady state (76 hours) rather than truly mild effects.
  • Using ferret RNA on human arrays calls for caution about the reliability of the data and needs confirmation by other methods.

Topics

Medical terms in this study, explained in our Lexicon: Lung Cancer.

Related studies

• Risk factors for lung cancer and for intervention effects in CARET, the Beta-Carotene and Retinol Efficacy Trial — G.S. Omenn, G.E. Goodman, et al. (1996)
• Beta-carotene and other carotenoids as antioxidants — S.A. Paiva, R.M. Russell (1999)
• Chemoprevention of cancer: lessons to be learned from beta-carotene trials — H. Vainio (2000)
• No dose-dependent increase in fracture risk after long-term exposure to high doses of retinol or beta-carotene — G.L. Ambrosini, A.P. Bremner, et al. (2013)
• Role of Beta-Carotene in Lung Cancer Primary Chemoprevention: A Systematic Review with Meta-Analysis and Meta-Regression — J. Kordiak, F. Bielec, et al. (2022)
• Beta carotene: from biochemistry to clinical trials — W.A. Pryor, W. Stahl, et al. (2000)

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