d-Alpha-tocopheryl polyethylene glycol-1000 succinate enhances the absorption of vitamin D in chronic cholestatic liver disease of infancy and childhood.
Rickets and osteopenia, common problems in chronic childhood cholestasis, have been attributed to vitamin D malabsorption leading to reduced serum levels of 25(OH)-vitamin D. d-alpha-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 D3 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 +/- 83.1 nmol x h/L (155.6 +/- 32.1 ng x h/mL), with a mean rise above baseline of 13.5 +/- 1.8 nmol/L (5.2 +/- 0.7 ng/mL) with vitamin D/TPGS compared with no rise when vitamin D was given alone (both p less than 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 (less than 37.5 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Argao
E A
EA
Division of Gastroenterology and Nutrition, Children's Hospital Research Foundation, Cincinnati, Ohio 45229.
Heubi
J E
JE
Hollis
B W
BW
Tsang
R C
RC
D000328:Adult; D016738:Alagille Syndrome / Q000188:drug therapy / Q000378:metabolism; D001656:Biliary Atresia / Q000188:drug therapy / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D002779:Cholestasis / Q000188:drug therapy* / Q000378:metabolism; D002780:Cholestasis, Intrahepatic / Q000188:drug therapy / Q000378:metabolism; D002908:Chronic Disease; D005260:Female; D006801:Humans; D007223:Infant; D007408:Intestinal Absorption / Q000187:drug effects; D008297:Male; D008823:Micelles; D011092:Polyethylene Glycols; D014807:Vitamin D / Q000493:pharmacokinetics*; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000627:therapeutic use
D008823:Micelles; D014807:Vitamin D; D014810:Vitamin E; D011092:Polyethylene Glycols; C014225:tocophersolan