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  • Title: Comparative effect of dietary sitosterol on plasma sterols and cholesterol and bile acid synthesis in a sitosterolemic homozygote and heterozygote subject.
    Author: Cobb MM, Salen G, Tint GS.
    Journal: J Am Coll Nutr; 1997 Dec; 16(6):605-13. PubMed ID: 9430090.
    Abstract:
    OBJECTIVE: Sitosterolemia is a genetic disorder characterized by an increased plasma plant sterol concentration due to enhanced sterol absorption coupled with reduced steroid excretion. The purpose of the present investigation was two-fold; first to assess the effects of a "basal" low sitosterol metabolic diet on plasma sterols and sterol balance, and, secondly, to quantify the relative influence of graduated increase in dietary sitosterol intake on a metabolic diet in a sitosterolemic homozygote, obligate heterozygote, and controls. METHODS: Patients were studied under strict metabolic conditions and fed a "basal" 30% fat, low-sitosterol (33 mg per 2000 kcal) diet. The level of dietary sitosterol was increased by addition of oils and resulted in final dietary sitosterol intakes of 1.8 mg/kg, 2.6 mg/kg and 3.5 mg/kg/day intakes of dietary sitosterol in the homozygote. These sitosterol dosages were selected based on sitosterol intakes equivalent to 2.6 mg/kg/day in the average American diet. Plasma cholesterol, sitosterol, and apolipoprotein A were measured, and stool collections assayed for sterol balance. RESULTS: Fecal sterol excretion and cholesterol synthesis were depressed markedly by 50% in the homozygote compared to the heterozygous parent, whereas plasma sitosterol levels were increased over 50-fold. When the sitosterol content of the diet was increased three-fold and dietary cholesterol was maintained in the homozygous and hypercholesterolemic control, plasma levels did not increase in the homozygote. Plasma cholesterol and sitosterol levels were unaffected in the hypercholesterolemic control. CONCLUSIONS: Plasma sterol levels remained elevated with the dietary sitosterol changes in the sitosterolemic homozygote. These findings were associated with a low fecal sterol excretion rate and depressed endogenous cholesterol synthesis. In this sitosterolemic patient, a very low sitosterol diet to curtail sterol input was of minimal therapeutic benefit. These results have important implications regarding the selection of therapy for this patient under these experimental conditions, but cannot be generalized to other homozygotes.
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