Serum retinol is typically low in measles infection and is inversely related to the severity of the disease. Supplementation with large doses of vitamin A for two days is therefore recommended in severe cases to reduce complications and mortality rates [1]. Infants under 6 months receive 50,000 IU, those ages 6 months to 1 year receive 100,000 IU, and those over 1 year receive 200,000 IU of vitamin A [2]. However, the notion that measles is due to a deficiency of vitamin A is contradicted by the fact that the common presenting symptoms– poor appetite, nausea, vomiting, diarrhea, sensitivity to light, and dry rough skin– are also common symptoms of vitamin A toxicity1 (p 9). This fact calls for a fresh look at the role of vitamin A in the pathogenesis and treatment of measles.
Here the case is made that low serum retinol in measles, rather than indicating deficiency, results from the inflammation-induced accumulation of vitamin A in the liver and an impairment in the mobilization and secretion of the transporter, retinol-binding protein (RBP), due to cholestatic liver function, which can be severe in measles [3]. Furthermore, it is proposed that all of the signs and symptoms of measles and its complications represent an endogenous form of hypervitaminosis A due to the hepatic spillage of stored retinyl esters into the circulation in toxic concentrations. Retinyl esters have not been measured in patients with measles.
These considerations suggest the hypothesis that high-dose vitamin A supplementation, rather than correcting a deficiency, serves to inhibit vitamin A metabolism, thereby reducing both vitamin A toxicity and the signs and symptoms of measles. This hypothesis receives preliminary support from the observation that a single oral dose of retinoic acid (0.167 mM) in corn oil given to six healthy human subjects was associated with a mean decline in serum retinol levels of approximately 20% within one hour, which lasted for 24 h [4]. In another study, the oral administration of micromolar concentrations of retinoic acid to rats produced significant transient depressions of both serum retinol and RBP [5].
It is hoped that this letter will lead to testing these hypotheses and to alternative methods for managing the disease, in view of the toxicity of vitamin A in the form of retinyl esters unbound to protein.
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Anthony R. Mawson confirms the sole responsibility for the conception of the study, presented results, and manuscript preparation.
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References
- 1.Call to Action: Vitamin A for the Management of Measles in the United States. National Foundation for Infectious Diseases. March 2020 https://www.nfid.org/wp-content/uploads/2023/04/Call-to-Action-Vitamin-A-for-the-Management-of-Measles-in-the-US-FINAL.pdf
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