A B S T R A C T Although the usual diet may contain 150-250 mg of plant sterols, chiefly f8-sitosterol, only trace amounts of these sterols have heretofore been found in human or animal blood and tissues. We now report elevated plant sterol levels in the blood and tissues of two sisters with extensive tendon xanthomas but normal plasma cholesterol levels. Besides. P-sitosterolemia and xanthomatosis, no other physical, mental, or biochemical abnormalities were detected.Repeatedly, the plasmas of the two sisters have contained 27.1 and 17.7 mg/100 ml of p-sitosterol, 9.7 and 8.2 mg/100 ml of campesterol, and 0.5 and 0.5 mg/100 ml of stigmasterol, respectively. These plant sterols constituted 15.6 and 11.3% of the total plasma sterols. Some 60% of the plasma f-sitosterol and campesterol was esterified; the measurable stigmasterol was entirely unesterified. The transport of the plasma P-sitosterol and campesterol was largely in low density lipoproteins (76 and 83%, respectively). High density lipoproteins carried the remainder. Plant sterols were barely detectable in the very low density lipoprotein fraction. Only trace amounts of stigmasterol could be detected in the low density and high density lipoprotein fractions. The plant sterol content of the red blood cells averaged 12-13 mg/100 ml packed cells or about 13% of the total sterols. Two tendon xanthoma biopsies with the usual high concentration of cholesterol had 36.7 and 4.0 mg of plant sterols/g dry wt, of which 25.7 and 2.9 mg were fi-sitosterol, entirely in the free form. Plant sterols were also found in adipose tissue This work was presented in part at the 65th Annual

We compared the fatty acid composition of adipose tissue from three different sites, one deep-seated site (perirenal) and two subcutaneous sites (abdominal and buttock), in 143 autopsied adult humans aged 24-61 y. The proportion of saturated fatty acids was highest in the perirenal adipose tissue and lowest in buttock adipose tissue. The proportions of monounsaturated fatty acids in the three sites were in the reverse order. Linoleic and linolenic acids were similar in the three adipose-tissue sites, an important finding for those concerned about the essential fatty acids, which are solely derived from the diet. The results clearly show that the fatty acid composition of the two subcutaneous fat depots differ significantly. We conclude that abdominal fat is more saturated than buttock fat.

Sitosterolemia and xanthomatosis are characterized by the development of tendon and tuberous xanthomas at an early age and premature atherosclerosis despite normal plasma cholesterol concentrations. The reason(s) for the xanthoma formation and premature atherosclerosis are not clearly understood. The accumulation of sitosterol in the tissues of these patients could be due to increased uptake of low density lipoprotein (LDL) via LDL receptors because of an expanded sitosterol pool caused by sluggish turnover and decreased excretion of sitosterol into bile and feces coupled with the hyperabsorption of sitosterol. We have studied sitosterol and cholesterol turnovers, the biliary and fecal excretion of neutral and acidic steroids, and the response of plasma sterol (sitosterol and cholesterol) levels to either a sterol-free formula or low plant sterol diet in three patients. The average half-life of the first exponential (t A l/2) for sitosterol was 9.2 ±3.3 (mean±SD) days, which was more than twice that in normal humans. The second exponential (t B l/2) was 156±108 days, which was nearly 10 times longer than that for normal humans. The average cholesterol production rate in pool A was 0.87 g/day, which is about 40% of that in normal humans. Cholesterol synthesis measured by the sterol balance technique was also found to be about 70% lower than that for normal humans. In two patients fed a sterol-free formula diet, by 25 days their plasma sitosterol and cholesterol levels had decreased by 42% and 36%, respectively. However, in one patient plasma sitosterol and cholesterol concentrations remained unchanged while on the low plant sterolmixed food diet. The sitosterol to cholesterol ratio in bile (0.05) was extremely low compared with that found in plasma (0.14), indicating low excretion of sitosterol into the bile. Thus, patients with sitosterolemia have a slow turnover of sitosterol, low excretion of sitosterol into the duodenal bile and feces, and low cholesterol synthesis. These metabolic defects have implications in the formation of xanthomas and the development of premature atherosclerosis in these patients. (Arteriosclerosis and Thrombosis 1991;11:1287-1294)