Treatment of vitamin E deficiency during chronic childhood cholestasis with oral d-α-tocopheryl polyethylene glycol-1000 succinate

Sokol, Ronald J.; Heubi, James E.; Butler–Simon, Nancy; McClung, H J; Lilly, John R.; Silverman, Arnold

doi:10.1016/0016-5085(87)90559-2

Cited by 86 publications

(48 citation statements)

References 31 publications

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“…Oral d-alpha tocopheryl polyethylene glycol-1000 succinate (TPGS), a water-soluble form of vitamin E, is absorbed well in vitamin E-deficient children with chronic cholestasis who fail to absorb other forms of vitamin E. 19,20 Additionally, TPGS, when given concurrently with other lipid-soluble compounds (such as cyclosporine 21 ), increases their absorption. This effect of TPGS is related to its amphipathic structure, resulting in the formation of micelles in the absence of bile acids.…”

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“…This effect of TPGS is related to its amphipathic structure, resulting in the formation of micelles in the absence of bile acids. 19 Based on these observations, we postulated that the oral RDR method to assess vitamin A status during cholestasis could be modified by the oral coadministration of TPGS and retinyl palmitate; with the TPGS promoting solubilization and absorption of oral vitamin A. If this modified oral RDR accurately reflected vitamin A status in cholestatic children, it would mitigate against the need for parenteral (intravenously or intramuscularly) RDR to assess vitamin A status.…”

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Comparison of indices of vitamin A status in children with chronic liver disease

et al. 2005

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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%; retinolbinding 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. (HEPATOLOGY 2005;42:782-792.)

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Comparison of indices of vitamin A status in children with chronic liver disease

et al. 2005

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“…[3][4][5] Although vitamin E plasma Toc/TL ratio would predict hepatic vitamin E status. therapy is used to prevent neurological injury caused byTo test these hypotheses, we measured a-tocopherol concenvitamin E deficiency in patients with serious liver distrations in liver biopsy specimens, RBCs, and plasma and eases, 1,6,7 it is controversial whether vitamin E therapy clinisimultaneously determined concentrations of the three major lipid fractions in sera and liver tissues.Abbreviations: RBC, red blood cell; FL, fatty liver; CPH, chronic persistent hepatitis; …”

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“…To test these hypotheses, we measured a-tocopherol concenvitamin E deficiency in patients with serious liver distrations in liver biopsy specimens, RBCs, and plasma and eases, 1,6,7 it is controversial whether vitamin E therapy clinisimultaneously determined concentrations of the three major lipid fractions in sera and liver tissues.…”

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Assessment of hepatic vitamin E status in adult patients with liver disease

Nagita

Ando

1997

Hepatology

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cally prevents liver injury from this or other causes. This No published reports compare hepatic a-tocopherol (adcontroversy is the result of many factors, including use of justed for hepatic lipid content) with indicators of blood different dosages of vitamin E, differences in the mechanisms a-tocopherol in adult patients with various liver diseases.of liver injury between experimental animals and clinical a-Tocopherol was simultaneously measured in liver biopsy subjects, and the lack of a reliable indicator of hepatic vitamin tissues and blood from 66 subjects (9 comparison patients E status. Because vitamin E-deficient red blood cells (RBCs) hospitalized for biliary tract surgery, 13 with chronic persisare fragile (as a result of hydrogen peroxidation), 7 RBCs are tent hepatitis, 9 with chronic aggressive hepatitis, 10 with considered a peripheral target tissue for vitamin E. RBC aacute hepatitis, 10 with cirrhosis, 7 with both cirrhosis and tocopherol has been assumed to be a reliable indicator of hepatic cell carcinoma, and 8 with fatty liver). Hepatic, erythvitamin E status in biomembranes. 8,9 The ratio of plasma arocyte, and plasma a-tocopherol concentrations were meatocopherol to total serum lipid concentration (plasma Toc/ sured, as were hepatic and serum lipids. The ratios of a-TL ratio) has also been used as a clinical index of plasma tocopherol to total lipid concentrations (Toc/TL ratios) in vitamin E status. 7,10-12 However, to our knowledge, no pubplasma and liver were calculated. In both comparison patients lished reports compare hepatic a-tocopherol concentrations and patients with chronic persistent hepatitis and fatty liver, with RBC a-tocopherol concentrations or plasma Toc/TL rahepatic a-tocopherol concentrations were strongly correlated tios in adult patients with liver disease. with hepatic triglyceride and total lipid concentrations (r Å Previous reports have shown diminished hepatic a-to-.72, P õ .001; and r Å .75, P õ .001, respectively); the copherol concentrations in alcoholic patients with cirrhorelationships (slopes) when hepatic a-tocopherol concentrasis, 13,14 but another report showed no correlation between tions were compared with hepatic triglyceride and total lipid the ratios of hepatic a-tocopherol to total hepatic lipid conconcentrations were similar in these patients and in all subcentrations (hepatic Toc/TL ratios) and inflammatory histojects. No strong correlations were found between hepatic and logical changes in alcoholic patients. 15 In our study (Nagita blood a-tocopherol parameters in all subjects. These results A, et al., unpublished observations, January 1997), hepatic suggest that hepatic a-tocopherol is present at similar concena-tocopherol concentrations were higher in pediatric patrations in triglycerides as well as total cholesterol and phostients with fatty liver (FL) than in comparison subjects and pholipids and that neither plasma Toc/TL ratios nor erythrowere strongly correlated with hepatic areas occupied by fat cyte a-tocopherol concentrations are usefu...

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“…As early as 1970, evidence was available suggesting that vitamin E as TPGS was absorbed in infants with extrahepatic biliary atresia and cystic fibrosis (12). More recently, TPGS was shown to be an effective form of therapy for vitamin E deficiency in children with severe chronic cholestasis (13). The present study was designed to evaluate the potential role of TPGS in enhancing the absorption of vitamin D3 from the gastrointestinal tract in infants and children with chronic cholestatic disease.…”

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d-α-Tocopheryl Polyethylene Glycol-1000 Succinate Enhances the Absorption of Vitamin D in Chronic Cholestatic Liver Disease of Infancy and Childhood

et al. 1992

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ABSTRACT. Rickets and osteopenia, common problems in chronic childhood cholestasis, have been attributed to vitamin D malabsorption leading to reduced serum levels of 25(0H)-vitamin D. d-a-Tocopheryl polyethylene glycol-1000 succinate (TPGS), a water-soluble form of vitamin E, forms micelles at low concentration. We evaluated the potential role of TPGS in enhancing vitamin D absorption in eight children (aged 5 mo to 19 y) with severe chronic cholestasis (three extrahepatic biliary atresia, three nonsyndromic intrahepatic cholestasis, and two Alagille syndrome). To evaluate vitamin D absorption, the subjects received vitamin D3 1000 IU/kg (maximum dose of 50 000 IU); they then received the same dose of vitamin Dg mixed with TPGS (25 IU/kg). Serial serum vitamin D3 levels and areas under the curve were measured. All patients had enhanced absorption of vitamin D when it was administered in a mixture with TPGS. Mean area under the curve for serum vitamin D3 was 403.0 -C 83.1 nmol x h/L (155.6 f 32.1 ng x h/mL), with a mean rise above baseline of 13.5 f 1.8 nmol/L (5.2 f 0.7 ng/mL) with vitamin D/TPGS compared with no rise when vitamin D was given alone (both p < 0.001). Seven patients have been followed for at least 3 mo while receiving the vitamin D/TPGS combination. Those with initially low serum 25(OH)-vitamin D levels (C37.5 nmol/L or 15 ng/mL) had normalization (range 37.5-146 nmol/L) within 1 mo, whereas those with initially normal levels remained normal. While the patients were receiving vitamin D/TPGS, serum vitamin E to total lipid ratio either normalized or remained normal. In conclusion, 1 ) TPGS enhances vitamin D absorption in infants and children with severe chronic cholestasis and 2) the enhanced absorption of both vitamins is sufficient to normalize or maintain adequate levels of serum 25(OH)-vitamin D and vitamin E to total lipid ratio. (Pediatr Res 31: 146-150,1992) Abbreviations 25(OH)D, 25-hydroxy-vitamin D TPGS, d-a-tocopheryl polyethylene glycol-1000 succinate

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Treatment of vitamin E deficiency during chronic childhood cholestasis with oral d-α-tocopheryl polyethylene glycol-1000 succinate

Cited by 86 publications

References 31 publications

Comparison of indices of vitamin A status in children with chronic liver disease

Comparison of indices of vitamin A status in children with chronic liver disease

Assessment of hepatic vitamin E status in adult patients with liver disease

d-α-Tocopheryl Polyethylene Glycol-1000 Succinate Enhances the Absorption of Vitamin D in Chronic Cholestatic Liver Disease of Infancy and Childhood

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