Treatment of cholestatic children with water-soluble vitamin E (alpha-tocopheryl polyethylene glycol succinate): effects on serum vitamin E, lipid peroxides, and polyunsaturated fatty acids.
BACKGROUND
Treatment of vitamin E-deficient cholestatic children with water-soluble alpha-tocopherol polyethylene glycol succinate (TPGS) was previously shown to normalize vitamin E status and to improve neurological outcome.


METHODS
Because vitamin E plays an important role as a free-radical scavenger, we studied the effects of long-term TPGS supplementation on lipid peroxidation and polyunsaturated fatty acid status in 15 children ages 9 months-3.4 years (median, 1.3 years) with chronic cholestasis with low serum vitamin E concentrations [1.95 (0.8-3.7) mg/L; median (1st-3rd quartile)]. The previous supplementation of alpha-tocopherol was replaced by a 20% solution of TPGS in one daily dose of 20 IU/kg. Serum alpha-tocopherol, plasma lipid peroxides expressed as thiobarbiturate reactive substance concentration (TBARS) and plasma phospholipid fatty acid profile were estimated at baseline and again after 1 month in all 15 patients, and after 1 year of TPGS therapy in 11 patients.


RESULTS
alpha-Tocopherol was significantly increased after 1 month [6.9 (4.4-8.4) mg/L; p = 0.008] and rose further after 1 year [9.7 (7.2-14.9) mg/L]; similar results were obtained for the ratio vitamin E/total lipids. TBARS concentrations were significantly higher in cholestatic children at baseline [2.9 (1.5-3.32) nmol/ml] than in a control group [1.2 (1.1-1.3) nmol/ml; p = 0.0006], but were not changed significantly during TPGS therapy [after 1 year 2.34 (1.9-3.0) nmol/ml]. Compared with controls, the contributions of polyunsaturated fatty acids to total phospholipid fatty acids were markedly decreased in cholestatic patients at baseline [27.7 (22.4-31.5)% versus 36.9 (34.5-39.0)%; p = 0.001] and did not show major changes after 1 year of TPGS supplementation.


CONCLUSIONS
We conclude that oral TPGS supplementation of cholestatic children can quickly normalize serum vitamin E levels but does not improve the increased lipid peroxidation and poor polyunsaturated fatty acid status.
Socha
P
P
Kinderpoliklinik, Ludwig-Maximilians-University, Munich, Germany.
Koletzko
B
B
Pawlowska
J
J
Proszynska
K
K
Socha
J
J
D002675:Child, Preschool; D002779:Cholestasis / Q000097:blood / Q000188:drug therapy*; D005227:Fatty Acids / Q000097:blood* / Q000378:metabolism; D006801:Humans; D007223:Infant; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology*; D010743:Phospholipids / Q000737:chemistry* / Q000378:metabolism; D011092:Polyethylene Glycols; D012995:Solubility; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis* / Q000378:metabolism; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000097:blood* / Q000378:metabolism / Q000627:therapeutic use; D014867:Water
D005227:Fatty Acids; D010743:Phospholipids; D017392:Thiobarbituric Acid Reactive Substances; D014867:Water; D014810:Vitamin E; D011092:Polyethylene Glycols; C014225:tocophersolan