Effects of dietary cholesterol and simvastatin on cholesterol synthesis in smith-lemli-opitz syndrome

Yen Ming Chan, Louise S. Merkens, William E. Connor, Jean-Baptiste Roullet, Jennifer A. Penfield, Julia M. Jordan, Robert D. Steiner, Peter J H Jones

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Deficient cholesterol and/or excessive 7-dehydrocho-lesterol (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.

Original languageEnglish (US)
Pages (from-to)681-685
Number of pages5
JournalPediatric Research
Volume65
Issue number6
DOIs
StatePublished - Jun 2009

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Smith-Lemli-Opitz Syndrome
Dietary Cholesterol
Simvastatin
Cholesterol
Diet
Deuterium Oxide
Deuterium
Therapeutic Uses
Sterols
Dietary Supplements
Isotopes
Gas Chromatography
Oral Administration

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Chan, Y. M., Merkens, L. S., Connor, W. E., Roullet, J-B., Penfield, J. A., Jordan, J. M., ... Jones, P. J. H. (2009). Effects of dietary cholesterol and simvastatin on cholesterol synthesis in smith-lemli-opitz syndrome. Pediatric Research, 65(6), 681-685. https://doi.org/10.1203/PDR.0b013e31819ea4eb

Effects of dietary cholesterol and simvastatin on cholesterol synthesis in smith-lemli-opitz syndrome. / Chan, Yen Ming; Merkens, Louise S.; Connor, William E.; Roullet, Jean-Baptiste; Penfield, Jennifer A.; Jordan, Julia M.; Steiner, Robert D.; Jones, Peter J H.

In: Pediatric Research, Vol. 65, No. 6, 06.2009, p. 681-685.

Research output: Contribution to journalArticle

Chan, YM, Merkens, LS, Connor, WE, Roullet, J-B, Penfield, JA, Jordan, JM, Steiner, RD & Jones, PJH 2009, 'Effects of dietary cholesterol and simvastatin on cholesterol synthesis in smith-lemli-opitz syndrome', Pediatric Research, vol. 65, no. 6, pp. 681-685. https://doi.org/10.1203/PDR.0b013e31819ea4eb
Chan, Yen Ming ; Merkens, Louise S. ; Connor, William E. ; Roullet, Jean-Baptiste ; Penfield, Jennifer A. ; Jordan, Julia M. ; Steiner, Robert D. ; Jones, Peter J H. / Effects of dietary cholesterol and simvastatin on cholesterol synthesis in smith-lemli-opitz syndrome. In: Pediatric Research. 2009 ; Vol. 65, No. 6. pp. 681-685.
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