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

Abstract

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-α-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 non-syndromic 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 lU/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 ± h/L (155.6 ± 32.1 ng ± 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.