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 < 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 (< 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. 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.