Abstract
We measured the percent absorption, turnover, and distribution of campestanol (24-methyl-5α-cholestan-3β-ol) in a sitosterolemic homozygote, her obligate heterozygous mother, and three healthy human control subjects. For reasons relating to sterol hyperabsorption, the homozygote consumed a diet low in plant sterols that contained campestanol at about 2 mg/day. The heterozygote and three control subjects were fed a diet supplemented with a spread that contained campestanol at 540 mg/day and sitostanol (24-ethyl-5α-cholestan-3β-ol) at 1.9 g/day as fatty acid esters. Plasma campestanol concentrations determined by capillary gasliquid chromatography were 0.72 ± 0.03 mg/dl in the homozygote, 0.09 ± 0.04 mg/dl in the heterozygote, and 0.05 ± 0.03 mg/dl for the control mean. After simultaneous pulse labeling with [3α-3H]campestanol intravenously and [23-14C]campestanol orally, the maximum percent absorption measured by the plasma dual-isotope ratio method as a single time point was 80% in the homozygote, 14.3% in the heterozygote, and 5.5 ± 4.3% as the mean for three control subjects. Turnover (pool size) values estimated by mathematical analysis of the specific activity versus time [3α-3H]campestanol decay curves were as follows: 261 mg in the homozygote, 27.3 mg in the heterozygote, and 12.8 ± 7.6 mg in the three control subjects (homogygote vs. controls, P < 0.001). The calculated production rate (mg/24 h) equivalent to actual absorption in the presence of dietary sterols and stanols was 0.67 mg/day or 31% of intake in the homozygote, 2.1 mg/day or 0.3% of intake in the heterozygote, and 0.7 ± 0.3 mg/day or 0.1% of intake in the three control subjects. However, the excretion constant from pool A (KA) was prolonged markedly in the homozygote, but was 100 times more rapid in the heterozygote and three control subjects. Thus, campestanol, like other noncholesterol sterols, is hyperabsorbed and retained in sitosterolemic homozygotes. However, campestanol absorption was only slightly increased in the sitosterolemic heterozygote and removal was as rapid as in control subjects.—Salen, G., G. Xu, G. S. Tint, A. K. Batta, and S. Shefer. Hyperabsorption and retention of campestanol in a sitosterolemic homozygote: comparison with her mother and three control subjects. J. Lipid Res. 2000. 41: 1883–1889.
Highlights
We measured the percent absorption, turnover, and distribution of campestanol (24-methyl-5␣-cholestan-3ol) in a sitosterolemic homozygote, her obligate heterozygous mother, and three healthy human control subjects
The 5␣-dihydro derivatives of the most common plant sterols have been prepared by catalytic hydrogenation of the respective ⌬5-unsaturated precursors, campesterol and sitosterol (Fig. 1)
Sive tissue accumulation, the homozygote was fed a diet low in plant sterols and stanols, whereas the heterozygote and controls consumed a spread enriched with campestanol (540 mg/day) and sitostanol (1.9 g/day)
Summary
We measured the percent absorption, turnover, and distribution of campestanol (24-methyl-5␣-cholestan-3ol) in a sitosterolemic homozygote, her obligate heterozygous mother, and three healthy human control subjects. The heterozygote and three control subjects were fed a diet supplemented with a spread that contained campestanol at 540 mg/day and sitostanol (24-ethyl5␣-cholestan-3-ol) at 1.9 g/day as fatty acid esters. Because plant sterols contain extra methyl and ethyl substituents at the C-24 position of the cholesterol side chain, absorption is limited, hepatic removal is rapid, and plasma concentrations in most humans are low (1 –3). The 5␣-dihydro derivatives of the most common plant sterols have been prepared by catalytic hydrogenation of the respective ⌬5-unsaturated precursors, campesterol and sitosterol (Fig. 1) These 5␣-stanol derivatives are more resistant to autooxidation and when esterified with fatty acids and incorporated into foods such as margarine and mayonnaise, allow the released free stanols easier entry into the micellar phase of intestinal contents after enzymatic hydrolysis [4]. Sive tissue accumulation, the homozygote was fed a diet low in plant sterols and stanols, whereas the heterozygote and controls consumed a spread enriched with campestanol (540 mg/day) and sitostanol (1.9 g/day). In contrast to the three controls and heterozygote, who absorbed little campestanol, and excreted what was absorbed rapidly, substantial absorption and retention of campestanol occurred in the homozygote
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