Dynamics of vitamin A uptake, storage, and utilization in vocal fold mucosa.

Abstract Objective Extrahepatic vitamin A is housed within organ-specific stellate cells that support local tissue function. Such cells have been reported in the vocal fold mucosa (VFM) of the larynx; however, it is unknown how vitamin A reaches and is disseminated amongst VFM target cells, how VFM storage and utilization vary as a function of total body stores, and how these parameters change in the context of pathology. Therefore, in this study, we investigated fundamental VFM vitamin A uptake and metabolism. Methods Using cadaveric tissue and serum from human donors representing the full continuum of clinical vitamin A status, we established a concentration range and analyzed the impact of biologic and clinical covariates on VFM vitamin A. We additionally conducted immunodetection of vitamin A-associated markers and pharmacokinetic profiling of orally dosed α-retinyl ester (a chylomicron tracer) in rats. Results Serum vitamin A was a significant predictor of human VFM concentration, suggesting that VFM stores may be rapidly metabolized in situ and replenished from the circulatory pool. On a vitamin A-sufficient background, dosed α-vitamin A was detected in rat VFM in both ester and alcohol forms, showing that – in addition to plasma retinol and local stellate cell stores – VFM can access and process postprandial retinyl esters from circulating chylomicra. Both α-forms were rapidly depleted, confirming high metabolic demand for vitamin A within VFM. Conclusion This deep physiologic analysis validates VFM as an extrahepatic vitamin A repository and characterizes its unique uptake, storage, and utilization phenotype.