Fenretinide inhibits vitamin A formation from β-carotene and regulates carotenoid levels in mice

Anthony P. Miller, Molly Black, Jaume Amengual

Research output: Contribution to journalArticlepeer-review


N-[4-hydroxyphenyl]retinamide, commonly known as fenretinide, a synthetic retinoid with pleiotropic benefits for human health, is currently utilized in clinical trials for cancer, cystic fibrosis, and COVID-19. However, fenretinide reduces plasma vitamin A levels by interacting with retinol-binding protein 4 (RBP4), which often results in reversible night blindness in patients. Cell culture and in vitro studies show that fenretinide binds and inhibits the activity of β-carotene oxygenase 1 (BCO1), the enzyme responsible for endogenous vitamin A formation. Whether fenretinide inhibits vitamin A synthesis in mammals, however, remains unknown. The goal of this study was to determine if the inhibition of BCO1 by fenretinide affects vitamin A formation in mice fed β-carotene. Our results show that wild-type mice treated with fenretinide for ten days had a reduction in tissue vitamin A stores accompanied by a two-fold increase in β-carotene in plasma (P < 0.01) and several tissues. These effects persisted in RBP4-deficient mice and were independent of changes in intestinal β-carotene absorption, suggesting that fenretinide inhibits vitamin A synthesis in mice. Using Bco1−/− and Bco2−/− mice we also show that fenretinide regulates intestinal carotenoid and vitamin E uptake by activating vitamin A signaling during short-term vitamin A deficiency. This study provides a deeper understanding of the impact of fenretinide on vitamin A, carotenoid, and vitamin E homeostasis, which is crucial for the pharmacological utilization of this retinoid.

Original languageEnglish (US)
Article number159070
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Issue number2
StatePublished - Feb 2022


  • Alpha-tocopherol
  • Bioavailability
  • Lutein
  • Retinoic acid
  • beta-carotene

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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