Barbara A. Underwood

Blood and Liver Concentrations of Vitamins A and E in Children with Cystic Fibrosis of the Pancreas

Extract: The median vitamin A level in plasma of patients with cystic fibrosis of the pancreas (CFP) (18 μg/100 ml) was less than half that of a control group (39 μg/100 ml), whereas the median vitamin A level in liver (57 μg/g) was nearly 3.5 times higher (Table II.). Concentrations of vitamin E in both the plasma and the liver of the patients were less than one-third those of the control group. The data suggest that vitamin A-supplemented children with CFP are unable to maintain normal circulating levels of vitamin A because of a defect in mobilization or transport from storage tissue, rather than because of tissue depletion. Low blood levels of vitamin E, however, reflect tissue depletion and not defective transport.Speculation: The cause of the apparent defect in ability to mobilize or transport vitamin A from the liver in children with CFP may be due to a limited ability to synthesize transport proteins or to a reduced activity of hepatic retinyl ester hydrolase enzymes These alternatives are under investigation.

Solubilization of β-carotene and retinol into aqueous solutions of mixed micelles

Abstract 1. 1. The solubility of β-carotene (non-polar solute) and retinol (polar solute) into aqueous solutions containing mixed micelles has been studied in vitro using experimental conditions simulating those present in the lumen of the human small intestine during fat digestion with respect to bile salts, lipids, Na+, pH and temperature. 2. 2. Altering the glycine to taurine conjugated bile salt ratio had no effect on the solubility of either β-carotene or retinol. Altering the ratio of tri- to dihydroxy bile salts changed the solubility of both solutes; the higher the ratio the lower the solubility. The solubility of retinol in the systems studied was approximately 7–9-fold greater than that of β-carotene. 3. 3. Increasing the concentration of Na+ greatly increased the solubility of β-carotene but only slightly increased the solubility of retinol. 4. 4. In a mixture containing both solutes, no competition for solubilization occurred. 5. 5. pH values between 4.5 and 7 had no effect on the solubility of either solute but at pH values below 4.5, the solubility of both solutes markedly decreased.

Depressed plasma retinol-binding protein (RBP) in cystic fibrosis (CF)

Decreased plasma levels with normal or increased liver stores of vitamin A were reported previously in CF patients orally supplemented with water-miscible vitamin A. These findings suggested a defect in the mechanism by which vitamin A is transported from the liver in patients with CF. Plasma levels of RBP, the specific carrier protein for vitamin A, have been measured by radioimmunoassay in 69 samples from 49 CF patients and in 96 normal age-matched controls. Mean RBP levels (± SEM) in CF, 24.4 ± 1.3 μg/ml, were significantly (p < .001) lower than in normal controls, 37.3 ± 1.3 μg/ml. In normal children 14 years and under, plasma RBP and vitamin A levels showed a signification (p < .001) correlation with age; in contrast no age-related rise was observed in CF children of comparable age. Saturation of RBO with vitamin A was less than normal (p < .004), and the levels of plasma prealbumin (the protein normally complexed with RBP) were decreased (p < .001) in the CF group 15 years and older compared with controls. Depressed plasma RBP levels were not correlated with plasma G.O.T. or albumin levels. These results suggest that a defect in the hepatic production and/or secretion of RBP occurs in CF.

Correlation Between Plasma and Liver Concentrations of Vitamins A and E in Patients with Cystic Fibrosis (CF)

This study was designed to determine if the low plasma concentrations of vitamins A and E often seen in children with CF are a reflection of tissue depletion or of a defect in transport mechanisms. Ten patients with CF, ranging in age from 9 to 23 years, were studied. Plasma concentrations of vitamins A and E and carotene were measured in 7 of the 10 patients during the 18 months prior to death. At autopsy all 10 subjects had repeat measurements of these parameters plus an assessment of liver concentrations of vitamin A and α-tocopherol. All patients had received regular supplementation with vitamin A at twice the recommended daily allowance for several years; however, plasma levels of this vitamin were consistently below normal and carotene values were remarkably low in all subjects. Nine of the 10 CF patients had normal or increased vitamin A concentrations in the liver. Eight of the 10 patients received no supplemental vitamin E and had plasma vitamin E levels than 0.4 mg/100 ml and liver concentrations of α-tocopherol less than half that of the control group. This study has shown that the low plasma concentrations of vitamin E do correlate with decreased liver stores of α-tocopherol. (Supported by grants from the National Cystic Fibrosis Research Foundation and the Nutrition Foundation.)