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We investigated the changes of cholesterol and non-cholesterol sterol metabolism during plant stanol ester margarine feeding in 153 hypercholesterolemic subjects. Rapeseed oil (canola oil) margarine without (n = 51) and with (n = 102) stanol (2 or 3 g/day) ester was used for 1 year. Serum sterols were analyzed with gas–liquid chromatography. The latter showed a small increase in sitostanol peak during stanol ester margarine eating. Cholestanol, campesterol, and sitosterol proportions to cholesterol were significantly reduced by 5–39% (P < 0.05 or less for all) by stanol esters; the higher their baseline proportions the higher were their reductions. The precursor sterol proportions were significantly increased by 10–46%, and their high baseline levels predicted low reduction of serum cholesterol. The decrease of the scheduled stanol dose from 3 to 2 g/day after 6-month feeding increased serum cholesterol by 5% (P < 0.001) and serum plant sterol proportions by 8–13% (P < 0.001), but had no consistent effect on precursor sterols. In twelve subjects, the 12-month level of LDL cholesterol exceeded that of baseline; the non-cholesterol sterol proportions suggested that stimulated synthesis with relatively weak absorption inhibition contributed to the non-responsiveness of these subjects. In conclusion, plant stanol ester feeding lowers serum cholesterol in about 88% of subjects, decreases the non-cholesterol sterols that reflect cholesterol absorption, increases the sterols that reflect cholesterol synthesis, but also slightly increases serum plant stanols. Low synthesis and high absorption efficiency of cholesterol results in the greatest benefit from stanol ester consumption.—Gylling, H., P. Puska, E. Vartiainen, and T. A. Miettinen. Serum sterols during stanol ester feeding in a mildly hypercholesterolemic population. J. Lipid Res. 1999. 40: 593–600.

In familial hypercholesterolemia (FH) the lowering of serum cholesterol levels should be started in childhood in order to prevent coronary artery disease later in life. However, treatment of children is problematic. We studied the effects of sitostanol (3 g/day) ester dissolved in rapeseed oil margarine as a hypocholesterolemic agent in one homozygous and 14 heterozygous children with FH maintained on a low cholesterol diet for 6 weeks, using a double-blind crossover design. Absorption and synthesis of cholesterol were evaluated by measuring serum plant sterol and cholesterol precursor proportions to cholesterol by gas-liquid chromatography. The compliance was good, and the children could not distinguish by taste the two margarines without and with sitostanol ester. Sitostanol margarine significantly reduced serum total, intermediate density (IDL), and low density lipoprotein (LDL) cholesterol by 11, 26, and 15%, respectively, and increased HDL/LDL cholesterol ratio by 27%. The proportions of serum delta 8-cholestenol, lathosterol, and desmosterol were significantly increased by 36, 19, and 18%, and those of serum cholestanol, campesterol, and sitosterol were significantly decreased by 9, 42 and 29%, respectively, suggesting that cholesterol absorption was decreased and synthesis was compensatorily increased. High basal precursor sterol proportions predicted a high decrease in LDL cholesterol levels. In conclusion, partial replacement of normal dietary fat consumption by sitostanol ester margarine appears to be an effective and safe hypocholesterolemic treatment in children with FH.

The fat cells of rat epididymal adipose tissue contain an average of 0.5 mg of cholesterol per gram of triglyceride. Of this cholesterol, 90% is nonesterified and 80% is located in the lipid storage compartment. The fat cell cholesterol content correlated positively with cell size. During fasting the free cholesterol of the adipocyte decreased in parallel with triglyceride, whereas the amount of esterified cholesterol did not change. The fat cell cholesterol content is independent of the amount of dietary cholesterol. On in vitro incubation of rat fat cells with radiolabeled acetate, mevalonate, glucose, leucine, or water, labeled cholesterol was synthesized. The rate of cholesterol synthesis increased with fat cell size. Fasting suppressed cholesterol synthesis by 90%, whereas refeeding stimulated the synthesis above values found in normally fed rats. Stimulation of lipolysis with theophylline or with dibutyryl cyclic AMP markedly inhibited cholesterol synthesis in fat cells. Insulin increased the incorporation of glucose and leucine into fat cell cholesterol. The cholesterol synthesis in fat cells was not suppressed by a high cholesterol diet. Addition of very low or low density lipoprotein into the incubation medium suppressed fat cell cholesterol synthesis whereas high density lipoprotein did not. The lipoprotein-free serum stimulated cholesterol synthesis compared with serum-free medium. The rate of cholesterol synthesis in total adipose tissue of rat was estimated to be 4% of that in the liver. It seems unlikely that the increased body cholesterol turnover present in obesity is accounted for by the enhanced cholesterol formation in the enlarged adipose tissue.