Water-miscible, emulsified, and solid forms of retinol supplements are more toxic than oil-based preparations.

BACKGROUND: It is well established that an excessive intake of retinol (vitamin A) is toxic; however, it has been > 25 y since the last extensive treatise of case reports on this subject. OBJECTIVE: The objectives were to identify and evaluate all individual cases of retinol toxicity published in the scientific literature that assessed the thresholds and symptoms induced by high intakes of retinol and to compare the toxicity of different physical forms of retinol preparations. DESIGN: We performed a meta-analysis of case reports on toxicity claimed to be induced by intakes of excessive amounts of dietary retinol (ie, retinol and retinyl esters in foods or supplements). Using free text and MESH (medical subheading) strategies in PubMed, we identified 248 articles in the scientific literature. From these initial articles we identified other relevant citations. The final database consisted of 259 cases in which individual data on dose, sex, age, time of exposure, and symptoms are reported. RESULTS: Chronic hypervitaminosis A is induced after daily doses of 2 mg retinol/kg in oil-based preparations for many months or years. In contrast, doses as low as 0.2 mg retinol. kg(-1). d(-1) in water-miscible, emulsified, and solid preparations for only a few weeks caused chronic hypervitaminosis A. Thus, water-miscible, emulsified, and solid preparations of retinol are approximately 10 times as toxic as are oil-based retinol preparations. The safe upper single dose of retinol in oil or liver seems to be approximately 4-6 mg/kg body wt. These thresholds do not vary considerably with age. CONCLUSIONS: The results of the present study indicate that the physical form of retinol supplements is a major determinant of toxicity. The use of water-miscible, emulsified, and solid preparations of retinol should therefore be carefully considered before being used in supplements and fortifications.

Intralobular Distribution of Vitamin A-Storing Lipid Droplets in Hepatic Stellate Cells with Special Reference to Polar Bear and Arctic Fox.

We examined the liver of adult polar bears, arctic foxes, and rats by gold chloride staining, fluorescence microscopy for the detection of autofluorescence of vitamin A, hematoxylin-eosin staining, staining with Masson's trichrome, Ishii and Ishii's silver impregnation, and transmission electron microscopical morphometry. The liver lobules of the arctic animals showed a zonal gradient in the storage of vitamin A. The density (i.e., cell number per area) of hepatic stellate cells was essentially the same among the zones. These results indicate that the hepatic stellate cells of the polar bears and arctic foxes possess heterogeneity of vitamin A-storing capacity in their liver lobules.

Vitamin A distribution and content in tissues of the lamprey, Lampetra japonica.

Vitamin A (retinol and retinyl ester) distribution and content in tissues of a lamprey (Lampetra japonica) were analyzed by morphological methods, namely, gold chloride staining, fluorescence microscopy to detect specific vitamin A autofluorescence, and electron microscopy, as well as high-performance liquid chromatography (HPLC). Hepatic stellate cells showed an abundance of vitamin A stored in lipid droplets in their cytoplasm. Similar cells storing vitamin A were present in the intestine, kidney, gill, and heart in both female and male lampreys. Morphological data obtained by gold chloride staining method, fluorescence microscopy, transmission electron microscopy, and HPLC quantification of retinol were consistent. The highest level of total retinol measured by HPLC was found in the intestine. The second and third highest concentrations of vitamin A were found in the liver and the kidney, respectively. These vitamin A-storing cells were not epithelial cells, but mesoderm-derived cells. We propose as a hypothesis that these cells belong to the stellate cell system (family) that stores vitamin A and regulates homeostasis of the vitamin in the whole body in the lamprey. Fibroblastic cells in the skin and somatic muscle stored little vitamin A. These results indicate that there is difference in the vitamin A-storing capacity between the splanchnic and intermediate mesoderm-derived cells (stellate cells) and somatic and dorsal mesoderm-derived cells (fibroblasts) in the lamprey. Stellate cells derived from the splanchnic and intermediate mesoderm have high capacity and fibroblasts derived from the somatic and dorsal mesoderm have low capacity for the storage of vitamin A in the lamprey.