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

Abstract

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

Efficacy of Fat-Soluble Vitamin Supplementation in Infants With Biliary Atresia

“…24 When TPGS is coadministered with other FSV, enhanced absorption of the unmodified vitamins has been observed in the setting of significant cholestasis. 7 This property formed the basis for the commercially available liquid preparations of multiple FSV (with larger doses of FSV than standard multivitamin preparations) suspended in TPGS that were used in this study. Although initially formulated for use in cystic fibrosis, these preparations had the potential for relatively simplified administration of all FSV to infants with cholestasis and were thus chosen as the standard form of vitamin supplementation for infants with BA in this prospective study.…”

“…The TPGS (an amphipathic molecule) potentially serves to enhance absorption of FSV that are comixed in these preparations. 7 The vitamin composition of the 2 preparations differed in that AquADEKs contained more vitamin A as b carotene, 25% more vitamin E, and 4 …”

“…A liquid multiple FSV preparation made with d-a tocopheryl polyethylene glycol-1000 succinate (TPGS; a micelle forming water-soluble form of vitamin E), FSV/ TPGS, is frequently used in the management of infants with BA because of ease of administration and presumed efficacy due to the inclusion of TPGS, which enhances absorption of FSV independent of luminal bile acids. 7 The efficacy of these preparations in preventing vitamin deficiencies in cholestasis in general, and BA in particular, has not been evaluated, despite their widespread clinical use.…”

Bioavailability of a Novel, Water-Soluble Vitamin E Formulation in Malabsorbing Patients

“…TPGS has been used to enhance absorption of poorly soluble drugs, such as cyclosporine or amprenavir (Agenerase r capsules). Argao et al [25] showed that co-administration of TPGS and vitamin D 3 increased serum 25(OH)D in cholestatic patients. The role of TPGS, however, in normalizing the vitamin E status in malabsorption may be greatly enhanced by utilizing its ability to achieve micellar solubilization and increase absorption of the natural tocols.…”

Endocrine and Metabolic Complications in Alagille’s Syndrome

“…Befunde bei Patienten mit chronischer Cholestase sprechen zudem fª eine Steigerung der Vitamin-D-Absorption nach Applikation von Vitamin-E-Analoga [3]. Molekularbiologische Untersuchungen aus jª Zeit unterstreichen zudem die Bedeutung von c~-TocopherolTransferprotein (c~-TTP) als wesentlichem Faktor fª einen ausreichenden antioxidativen Schutz ron Neuronen [24].…”