Treatment of severe familial hypercholesterolemia in childhood with sitosterol and sitostanol

doi:10.1016/S0022-3476(06)80136-8

The Journal of Pediatrics

Volume 122, Issue 2, February 1993, Pages 292-296

https://doi.org/10.1016/S0022-3476(06)80136-8 Get rights and content

This study was undertaken to compare the ability of two plant sterols to reduceserum levels of lipids and to compare their mechanism of action in nine children with severe familial hypercholesterolemia (total and low-density lipoprotein cholesterol concentrations averaged 9.57 mmol/L (370 mg/dl) and 7.87 mmol/L (301 mg/di)). After a 3-month strict diet, the children were given sitosterol, pastils (2 gm three times a day) for 3 months, followed by a 7-month course of sitostanol (0.5 gm three times a day). Serum lipoprotein levels and serum concentrations of campesterol and sitosterol were determined in all nine children, and the fecal excretion of neutral and acidic sterols were determined in seven children at the end of each therapeutic regimen. Sitosterol reduced low-density lipoprotein cholesterol levels by 20% (p<0.01); sitostanol reduced low-density liloprotein cholesterol levels by 33% after 3 months and 29% after 7 months (p<0.01 compared with diet; p<0.05 compared with sitosterol). Although sitosterol did not alter serum concentrations of campesterol and sitosterol, a significant reduction did occur during sitostanol therapy (−47% and −51%, respectively; p<0.01). Fecal excretion of neutral sterols increased from 6.7 mg/kg per day during the control period to 9.7 mg/kg per day during sitosterol administration (p<0.05), and to 12.6 mg/kg per day during sitostanol administration (p<0.05 compared with diet and sitosterol periods), indicating an increase in the inhibition of intestinal cholesterol absorption. All children completed the study and no obvious side effects occurred. The data indicate that sitostanol, even with a dose four-fold lower than that of sitosterol, was significantly more effective in reducing elevated levels of low-density lipoprotein cholesterol, and the reduction in serum lipid levels was of the same magnitude as that observed with systemic lipid-lowering drugs. These results suggest that sitostanol, a nonabsorbable plant sterol, could be the drug of choice for treating familial hypercholesterolemia in childhood.

References (29)

WestRJ et al.
Long-term follow-up of children with familial hypercholesterolaemia treated with cholestyramine
Lancet
(1980)
LeesAM et al.
Results of colestipol therapy in type II hyperlipoproteinemia
Atherosclerosis
(1976)
SchlierfG et al.
Sitosterol in juvenile type II hyperlipoproteinemia
Atherosclerosis
(1978)
HeinemannT et al.
Effect of low-dose sitostanol on serum cholesterol in patients with hypercholesterolemia
Atherosclerosis
(1986)
CzubaykoF et al.
A simplified method for quantitation of fecal excretion of neutral and acidic sterols for outpatient studies in man
J Lipid Res
(1991)
GrundySM et al.
Quantitative isolation and gas-liquid chromatographic analysis of total fecal bile acids
J Lipid Res
(1965)
CalvertRJ et al.
An improved method for oxidation of chromium (III) oxide-containing fecal samples by using sodium peroxide fusion
Am J Clin Nutr
(1989)
TilvisRS et al.
Serum plant sterols and their relation to cholesterol absorption
Am J Clin Nutr
(1986)
WidhalmK
Pediatric guidelines for lipid reduction
Eur Heart J
(1987)
WestRJ et al.
Use of cholestyramine in treatment of children with familial hypercholesterolemia
Arch Dis Child
(1973)

WestRJ

Problems of long-term treatment in children with familial hypercholesterolemia

Prog Clin Biol Res

(1985)

GlueckCJ et al.

Pediatric familial type II hyperlipoproteinemia: therapy with diet and cholestyramine resin

Pediatrics

(1973)

GlueckCJ et al.

Therapy of familial hypercholesterolemia in childhood: diet and cholestyramine resin for 24 to 36 months

Pediatrics

(1977)

GlueckCJ et al.

Safety and efficacy of long-term diet and diet plus bile acid-binding resin cholesterol-lowering therapy in 73 children heterozygous for familialhypercholesterolemia

Pediatrics

(1986)

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Treatment of severe familial hypercholesterolemia in childhood with sitosterol and sitostanol+

Lancet

Atherosclerosis

Atherosclerosis

Atherosclerosis

J Lipid Res

J Lipid Res

Am J Clin Nutr

Am J Clin Nutr

Pediatric guidelines for lipid reduction

Eur Heart J

Use of cholestyramine in treatment of children with familial hypercholesterolemia

Arch Dis Child

Problems of long-term treatment in children with familial hypercholesterolemia

Prog Clin Biol Res

Pediatric familial type II hyperlipoproteinemia: therapy with diet and cholestyramine resin

Pediatrics

Therapy of familial hypercholesterolemia in childhood: diet and cholestyramine resin for 24 to 36 months

Pediatrics

Safety and efficacy of long-term diet and diet plus bile acid-binding resin cholesterol-lowering therapy in 73 children heterozygous for familialhypercholesterolemia

Pediatrics