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Effects of dietary cholesterol and simvastatin on cholesterol synthesis in Smith-Lemli-Opitz syndrome.

Authors :
Chan YM
Merkens LS
Connor WE
Roullet JB
Penfield JA
Jordan JM
Steiner RD
Jones PJ
Source :
Pediatric research [Pediatr Res] 2009 Jun; Vol. 65 (6), pp. 681-5.
Publication Year :
2009

Abstract

Deficient cholesterol and/or excessive 7-dehydrocholesterol (7-DHC) may be responsible for the pathology of Smith-Lemli-Opitz syndrome (SLOS). Both high-cholesterol diets given to ameliorate cholesterol deficiency while decreasing 7-DHC and cholesterol-enriched diets plus simvastatin to further decrease sterol synthesis have been used as potential therapies. However, the effect of dietary cholesterol and simvastatin on cholesterol synthesis in SLOS has not been reported. Twelve subjects with SLOS enrolled in the study: Nine had received a high cholesterol diet (HI) for 3 y and three were studied after 4 wk on a low cholesterol diet (LO). Cholesterol fractional synthesis rate (FSR) was measured after oral administration of deuterium oxide, using gas chromatography isotope ratio mass spectrometry. FSR was lower in HI compared with LO (HI: 1.46 +/- 0.62%/d; LO: 4.77 +/- 0.95%/d; p < 0.001). Three HI subjects were retested after 0.8 y taking simvastatin (HI + ST). Simvastatin tended to reduce FSR and significantly decreased (p < 0.01) plasma 7-DHC compared with cholesterol supplementation alone. The study demonstrates the utility of the deuterium incorporation method to understand the effect of therapeutic interventions in SLOS. The data suggest that dietary cholesterol supplementation reduces cholesterol synthesis in SLOS and further support the rationale for the combined treatment of SLOS with a cholesterol-enriched diet and simvastatin.

Details

Language :
English
ISSN :
1530-0447
Volume :
65
Issue :
6
Database :
MEDLINE
Journal :
Pediatric research
Publication Type :
Academic Journal
Accession number :
19430384
Full Text :
https://doi.org/10.1203/PDR.0b013e31819ea4eb