retinol-palmitate and Chronic-Disease

This study was designed to determine whether oral retinol palmitate (vitamin A) can reduce the symptoms of radiation proctopathy.. A randomized, double-blind trial comparing retinol palmitate (10,000 IU by mouth for 90 days) to placebo was conducted. Eligible patients were more than six months postpelvic radiotherapy and had significant symptoms as measured with the Radiation Proctopathy System Assessments Scale. Nineteen patients were randomized in total: ten to retinol palmitate and nine to placebo. The Radiation Proctopathy System Assessments Scale scores before and every 30 days for 90 days were measured. Five placebo nonresponders were crossed over to the retinol palmitate for another 90 days. Response was defined as a reduction in two or more symptoms by at least two Radiation Proctopathy System Assessments Scale points.. Seven of ten retinol palmitate patients responded, whereas two of nine responded to placebo (P = 0.057). Mean pre-post-treatment change in Radiation Proctopathy System Assessments Scale (delta Radiation Proctopathy System Assessments Scale) in the retinol palmitate group was 11 +/- 5, whereas delta Radiation Proctopathy System Assessments Scale in the placebo group was 2.5 +/- 3.6 (P = 0.013, Mann-Whitney U test). Additionally, all five placebo nonresponders who were crossed over to treatment with retinal palmitate responded to treatment.. In our trial, retinol palmitate significantly reduced rectal symptoms of radiation proctopathy, perhaps because of wound-healing effects. The current results can serve as the foundation for future trials examining retinol palmitate in the multi-institutional setting.

Topics: Aged; Aged, 80 and over; Antioxidants; Chronic Disease; Diterpenes; Double-Blind Method; Humans; Male; Middle Aged; Placebos; Prospective Studies; Prostatic Diseases; Radiation Injuries; Retinyl Esters; Severity of Illness Index; Treatment Outcome; Vitamin A

Malabsorption of fat-soluble vitamins is a major complication of chronic cholestatic liver disease. The most accurate way to assess vitamin A status in children who have cholestasis is unknown. The goal of this study was to assess the accuracy of noninvasive tests to detect vitamin A deficiency. Children with chronic cholestatic liver disease (n = 23) and noncholestatic liver disease (n = 10) were studied. Ten cholestatic patients were identified as vitamin A-deficient based on the relative dose response (RDR). Compared with the RDR, the sensitivity and specificity to detect vitamin A deficiency for each test was, respectively: serum retinol, 90% and 78%; retinol-binding protein (RBP), 40% and 91%; retinol/RBP molar ratio, 60% and 74%; conjunctival impression cytology, 44% and 48%; slit-lamp examination, 20% and 66%; tear film break-up time, 40% and 69%; and Schirmer's test, 20% and 78%. We developed a modified oral RDR via oral coadministration of d-alpha tocopheryl polyethylene glycol-1000 succinate and retinyl palmitate. This test had a sensitivity of 80% and a specificity of 100% to detect vitamin A deficiency. In conclusion, vitamin A deficiency is relatively common in children who have chronic cholestatic liver disease. Our data suggest that serum retinol level as an initial screen followed by confirmation with a modified oral RDR test is the most effective means of identifying vitamin A deficiency in these subjects.

Topics: Administration, Oral; Adolescent; Adult; Child; Child, Preschool; Cholestasis; Chronic Disease; Diterpenes; Dry Eye Syndromes; Female; Humans; Infant; Liver Diseases; Male; Polyethylene Glycols; Retinol-Binding Proteins; Retinyl Esters; Sensitivity and Specificity; Vitamin A; Vitamin A Deficiency; Vitamin E

Several clinical trials have revealed that individuals who were given beta-carotene and vitamin A did not have a reduced risk of cancer compared to those given placebo; rather, vitamin A could actually have caused an adverse effect in the lungs of smokers [Omenn, G.S., Goodman, G.E., Thornquist, M.D., Balmes, J., Cullen, M.R., Glass, A., Keogh, J.P., Meyskens, F.L., Valanis, B., Williams, J.H., Barnhart, S. & Hammar, S. N. Engl. J. Med (1996) 334, 1150-1155; Hennekens, C.H., Buring, J.E., Manson, J.E., Stampfer, M., Rosner, B., Cook, N.R., Belanger, C., LaMotte, F., Gaziano, J.M., Ridker, P.M., Willet, W. & Peto, R. (1996) N. Engl. J. Med. 334, 1145-1149]. Using differential display techniques, an initial survey using rats showed that liver RNA expression of c-H-Ras was decreased and p53 increased in rats with chronic vitamin A deficiency. These findings prompted us to evaluate the expression of c-Jun, p53 and p21WAF1/CIF1 (by RT-PCR) in liver and lung of rats. This study showed that c-Jun levels were lower and that p53 and p21WAF1/CIF1 levels were higher in chronic vitamin A deficiency. Vitamin A supplementation increased expression of c-Jun, while decreasing the expression of p53 and p21WAF1/CIF1. Western-blot analysis demonstrated that c-Jun and p53 showed a similar pattern to that found in the RT-PCR analyses. Binding of retinoic acid receptors (RAR) to the c-Jun promoter was decreased in chronic vitamin A deficiency when compared to control hepatocytes, but contrasting results were found with acute vitamin A supplementated cells. DNA fragmentation and cytochrome c release from mitochondria were analyzed and no changes were found. In lung, an increase in the expression of c-Jun produced a significant increase in cyclin D1 expression. These results may explain, at least in part, the conflicting results found in patients supplemented with vitamin A and illustrate that the changes are not restricted to lung. Furthermore, these results suggest that pharmacological vitamin A supplementation may increase the risk of adverse effects including the risk of oncogenesis.

Topics: Animals; Blotting, Western; Cell Division; Chronic Disease; Cyclin-Dependent Kinase Inhibitor p21; Cyclins; Diterpenes; DNA; Gene Expression Profiling; Gene Expression Regulation; Hypervitaminosis A; Liver; Lung; Macromolecular Substances; Precipitin Tests; Proto-Oncogene Proteins c-jun; Rats; Rats, Wistar; Receptors, Retinoic Acid; Retinyl Esters; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tumor Suppressor Protein p53; Vitamin A; Vitamin A Deficiency

Post-mortem concentrations of hepatic retinol and retinyl esters were determined in 40 subjects aged over 65 years to assess the effects of disease and malnutrition on vitamin A reserves. Three groups of patients (mean age 79.6 years) were studied: (1) previously healthy, (2) chronically ill, (3) chronically ill and wasted. There was no significant difference in height or age between the groups, but group 3 was lighter than both group 1 (P less than 0.001) and group 2 (P less than 0.05). Free retinol and retinyl esters were measured by high pressure liquid chromatography, and the total hepatic retinol calculated. Analysis of variance showed that the three groups differed significantly (P less than 0.02) with regard to total retinol, retinyl palmitate and total retinyl ester content.

Topics: Aged; Aged, 80 and over; Animals; Autopsy; Chromatography, High Pressure Liquid; Chronic Disease; Diterpenes; Female; Humans; Liver; Male; Nutrition Disorders; Retinoids; Retinyl Esters; Vitamin A; Vitamin A Deficiency