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The New England Journal of Medicine Nov 1995Dietary plant sterols, especially sitostanol, reduce serum cholesterol by inhibiting cholesterol absorption. Soluble sitostanol may be more effective than a less soluble... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
BACKGROUND
Dietary plant sterols, especially sitostanol, reduce serum cholesterol by inhibiting cholesterol absorption. Soluble sitostanol may be more effective than a less soluble preparation. We tested the tolerability and cholesterol-lowering effect of margarine containing sitostanol ester in a population with mild hypercholesterolemia.
METHODS
We conducted a one-year, randomized, double-blind study in 153 randomly selected subjects with mild hypercholesterolemia. Fifty-one consumed margarine without sitostanol ester (the control group), and 102 consumed margarine containing sitostanol ester (1.8 or 2.6 g of sitostanol per day).
RESULTS
The margarine containing sitostanol ester was well tolerated. The mean one-year reduction in serum cholesterol was 10.2 percent in the sitostanol group, as compared with an increase of 0.1 percent in the control group. The difference in the change in serum cholesterol concentration between the two groups was -24 mg per deciliter (95 percent confidence interval, -17 to -32; P < 0.001). The respective reductions in low-density lipoprotein (LDL) cholesterol were 14.1 percent in the sitostanol group and 1.1 percent in the control group. The difference in the change in LDL cholesterol concentration between the two groups was -21 mg per deciliter (95 percent confidence interval, -14 to -29; P < 0.001). Neither serum triglyceride nor high-density lipoprotein cholesterol concentrations were affected by sitostanol. Serum campesterol, a dietary plant sterol whose levels reflect cholesterol absorption, was decreased by 36 percent in the sitostanol group, and the reduction was directly correlated with the reduction in total cholesterol (r = 0.57, P < 0.001).
CONCLUSIONS
Substituting sitostanol-ester margarine for part of the daily fat intake in subjects with mild hypercholesterolemia was effective in lowering serum total cholesterol and LDL cholesterol.
Topics: Adult; Anticholesteremic Agents; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Dietary Fats; Double-Blind Method; Female; Humans; Hypercholesterolemia; Male; Margarine; Middle Aged; Phytosterols; Sitosterols; Triglycerides
PubMed: 7566021
DOI: 10.1056/NEJM199511163332002 -
Journal of Lipid Research Oct 1995For over a decade investigators have quantified cholesterol absorption by comparison of dietary intake and fecal excretion of isotopic cholesterol with that of...
For over a decade investigators have quantified cholesterol absorption by comparison of dietary intake and fecal excretion of isotopic cholesterol with that of beta-sitosterol as a "nonabsorbable" marker. However, beta-sitosterol might not be ideal due to its potential for absorption. We therefore carried out two studies to evaluate a new marker with less potential for absorption, [3H]beta-sitostanol. In the first study (Study I, n = 22), we compared absorption of [3H]beta-sitostanol and [14C]beta-sitosterol in a simultaneous dual-label continuous feeding ("phytosterol absorption") experiment. We observed a consistently higher ratio of [3H]beta-sitostanol/[14C]beta-sitosterol in the stool relative to diet on the first day of fecal collection (6.1% +/- 3.2% loss of [3H]beta-sitosterol, range 3-12%), but thereafter, the ratio in stool was similar to that in diet. In Study II (n = 23), we compared cholesterol absorption directly using [3H]beta-sitosterol and [14C]cholesterol, and, separately, [3H]beta-sitostanol and [14C]cholesterol. We found that mean absorption between the two methods was similar (45% +/- 11% versus 44% +/- 10%, respectively, P difference = 0.40), and the two methods correlated well with one another (r = 0.83) when samples from all available days were used. Variability between the two methods was greater in individuals who absorbed more than 40% of cholesterol. Cholesterol loss on day 2 estimated from use of beta-sitostanol as a nonabsorbable marker was predictive of absorption using ratios from days 4-6 (r = 0.80). These results suggest that, for the majority of subjects, beta-sitosterol is a valid nonabsorbable marker for cholesterol absorption.
Topics: Adult; Aged; Biomarkers; Cholesterol; Evaluation Studies as Topic; Female; Humans; Intestinal Absorption; Male; Middle Aged; Reference Values; Sitosterols
PubMed: 8576653
DOI: No ID Found -
Journal of Lipid Research Aug 1995In familial hypercholesterolemia (FH) the lowering of serum cholesterol levels should be started in childhood in order to prevent coronary artery disease later in life.... (Clinical Trial)
Clinical Trial
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.
Topics: Adolescent; Child; Child, Preschool; Dietary Fats; Esters; Female; Humans; Hyperlipoproteinemia Type II; Lipids; Male; Margarine; Sitosterols
PubMed: 7595101
DOI: No ID Found -
Journal of Lipid Research Aug 1995Absorption of dietary cholesterol, campesterol, and sitosterol, cholesterol balance, and fecal excretion of plant sterols were determined in three unrelated patients...
Absorption of dietary cholesterol, campesterol, and sitosterol, cholesterol balance, and fecal excretion of plant sterols were determined in three unrelated patients with phytosterolemia and three healthy volunteers during constant intake of cholesterol and plant sterols using accurate gas-liquid chromatography-mass spectrometry techniques. Each subject received a mixture of [26,26,26,27,27,27-2H6]cholesterol, [6,7,7-2H3]sitostanol, and [6,7,7-2H3]campesterol together with two non-absorbable markers, [5,6,22,23-2H4]sitostanol and chromic oxide. Feces were collected from days 5 to 7 and absorption of different sterols was calculated from the intestinal disappearance of the different sterols relative to [5,6,22,23-2H4]sitostanol and chromic oxide. The results obtained by the two markers were not different and the absorption of cholesterol averaged 53 +/- 4% for the patients (mean +/- SD) and 43 +/- 3% for the volunteers. Campesterol absorption averaged 24 +/- 4% in patients and 16 +/- 3% in healthy volunteers, whereas sitosterol absorption averaged 16 +/- 1% and 5 +/- 1%, respectively. Cholesterol synthesis expressed by body weight varied considerably in the two groups but appeared to be about 5 times lower in patients than in controls. Administration of a high dose of sitostanol (0.5 g t.i.d.) to two patients was followed by a reduction in cholesterol absorption by 24% and 44%, an increase in fecal output of cholesterol and steroids derived from cholesterol and plant steroids, and a marked reduction of serum cholesterol, campesterol, and sitosterol. Under the conditions used, inhibition of cholesterol absorption by sitostanol was not followed by a significant rise in cholesterol synthesis. The time of observation was, however, too short to allow final conclusion on this. The results show that the absolute difference in absorption rate of different sterols between the patients and healthy volunteers was about the same. As a consequence, increasing hydrophobicity causes a relative decrease of absorption rates. Thus, patients with phytosterolemia seem to have a generally increased absorption of sterols rather than a loss of a specific discriminatory mechanism, and oral administration of sitostanol seems to be an interesting new approach for treatment of phytosterolemia.
Topics: Absorption; Adult; Anticholesteremic Agents; Bile Acids and Salts; Cholesterol; Cholesterol, Dietary; Deuterium; Dietary Fats; Feces; Female; Humans; Intestinal Mucosa; Lipid Metabolism, Inborn Errors; Lipoproteins; Male; Middle Aged; Phytosterols; Sitosterols; Steroids; Sterols
PubMed: 7595097
DOI: No ID Found -
Journal of Lipid Research Jun 1993The continuous isotope feeding method of Crouse and Grundy (1978. J. Lipid Res. 19: 967-971) for measurement of dietary cholesterol absorption has been modified by using...
The continuous isotope feeding method of Crouse and Grundy (1978. J. Lipid Res. 19: 967-971) for measurement of dietary cholesterol absorption has been modified by using markers labeled with stable isotopes ([2,2,4,4,6-2H5]cholesterol or [25,26,26,26,27,27,27-2H4]cholesterol or [26,26,26,27,27,27-2H6] cholesterol and [5,6,22,23-2H4]sitostanol) quantified by gas-liquid chromatography-selected ion monitoring. Tracing of the isotope distribution of the authentic markers and after their intestinal passage, including the microbiological products (coprostanol and coprostanone) revealed stability of the labels. The new method was evaluated in six monkeys on two occasions by comparison with the original method using radioactively labeled cholesterol and sitosterol. The results obtained by the two different methods were in excellent agreement, and absorption ranged from 49% to 73% (mean 60%) for the stable isotope method and from 51% to 69% (mean 62%) for the radioactive method. The coefficient of variation of cholesterol absorption in animals ranged from 3.9% to 15.1% (mean 7.1%) for stable isotopes and 1.9% to 13.6% (mean 5.7%) for radioactive isotopes. In twelve subjects cholesterol absorption was measured by the new method from total fecal samples frozen immediately and compared to results obtained from small fecal aliquots (approximately 1 g) sent by ordinary mail to the laboratory. A significant correlation of cholesterol absorption between the two different sample handlings was obtained (r = 0.981, P < 0.001). In addition, measurement of cholesterol absorption twice in seven volunteers 2 weeks apart revealed identical results. Thus, the new method is extremely safe and reproducible without radioactive exposure to the subjects and labortory staff and can be used on women of child-bearing age.
Topics: Animals; Cholesterol; Cryopreservation; Deuterium; Feces; Gas Chromatography-Mass Spectrometry; Humans; Hypercholesterolemia; Intestinal Absorption; Macaca fascicularis; Male; Sitosterols
PubMed: 8354951
DOI: No ID Found -
Journal of Lipid Research Nov 1991A simple and precise micro-method for measurement of daily fecal excretion of neutral and acidic sterols has been developed which utilizes sitostanol (24-ethyl-5...
A simple and precise micro-method for measurement of daily fecal excretion of neutral and acidic sterols has been developed which utilizes sitostanol (24-ethyl-5 alpha-cholestane-3 beta-ol) as fecal flow and recovery marker. Extractions of sterols were performed from 50 microliters of fecal homogenate (feces-water 1:1), and analyses of neutral and acidic sterols were carried out by gas-liquid chromatography. The method is sensitive, precise, and easy to perform; the intra-assay variability yielded coefficients of variations of 1.9% and 3.5% (n = 6) for neutral and acidic sterols, respectively. The results from this method were compared with those obtained with the standard fecal flow marker chromic oxide. The correlation coefficients between the two markers were compared in 16 subjects and were 0.938 and 0.998 for excretion of neutral sterols and acidic sterols, respectively. Comparison of the fecal excretion of neutral and acidic sterols in 12 subjects determined from frozen samples and aliquots (approximately 1 g) sent by ordinary mail to the laboratory (transport time 1 to 5 days) gave identical results using sitostanol as fecal flow marker (818 +/- (SEM) 85 mg/day vs. 838 +/- 89 mg/day for neutral sterols and 417 +/- 59 mg/day vs. 414 +/- 60 mg/day for acidic sterols). The new micro-method is ideally suited for research laboratories in need of a simple, accurate, inexpensive, and high through-put method for measuring daily fecal excretion of neutral and acidic sterols, as well as total cholesterol synthesis, and can be performed on an outpatient basis.
Topics: Adult; Chromatography, Gas; Chromium; Chromium Compounds; Feces; Female; Humans; Hydrogen-Ion Concentration; Male; Outpatients; Sitosterols; Sterols
PubMed: 1770305
DOI: No ID Found -
Journal of Nematology Jan 1986Current knowledge of steroid nutrition, metabolism, and function in free-living, plant-parasitic and animal-parasitic nematodes is reviewed, with emphasis upon recent...
Current knowledge of steroid nutrition, metabolism, and function in free-living, plant-parasitic and animal-parasitic nematodes is reviewed, with emphasis upon recent investigation of Caenorhabditis elegans. A number of 4-desmethylsterols with a trans-A/B ring configuration can satisfy the steroid nutritional requirement in C. elegans, but sterols with a cis-A/B ring configuration or trans-A/B sterols with a 4-methyl group cannot. C. elegans removes methyl or ethyl substituents at C-24 of the plant sterols sitosterol, campesterol, stigmasterol, stigmastanol, and 24-methylene-cholesterol to produce various sterols with structures partially dependent upon that of the dietary sterol. Additional metabolic steps in C. elegans include reduction of Delta(2)(2)- and Delta-bonds, C-7 dehydrogenation, isomerization of a Delta-bond to a Delta(1)-bond, and 4alpha-methylation. An azasteroid and several long-chain alkyl amines interfere with the dealkylation pathway in C. elegans by inhibiting the Delta(2)-sterol reductase; these compounds also inhibit growth and reproduction in various plant-parasitic and animal-parasitic nematodes. A possible hormonal role for various steroids identified in nematodes is discussed.
PubMed: 19294131
DOI: No ID Found -
The Journal of Biological Chemistry Nov 19824-14C-labeled-5 beta-cholestan-3 alpha-ol and 24 alpha-ethyl-5 beta-cholestan-3 alpha-ol were incubated with rat liver 18,000 X g supernatant fractions fortified with...
4-14C-labeled-5 beta-cholestan-3 alpha-ol and 24 alpha-ethyl-5 beta-cholestan-3 alpha-ol were incubated with rat liver 18,000 X g supernatant fractions fortified with NADPH. Among the metabolites formed were the 15 alpha- and 15 beta-hydroxy derivatives of the two substrates. The identification of these metabolites with liquid chromatography, thin layer chromatography, and gas-liquid chromatography-mass spectrometry is described. The formation of 15 beta-hydroxylated metabolites exceeded that of 15 alpha-hydroxylated ones. The total yields of 15-hydroxylated compounds formed was of the order 0.5-1.0%. The 15-hydroxylated metabolites could not be detected after incubations with rat liver mitochondria or a soluble liver fraction or after incubations of 5 beta-cholestan-3 alpha-ol with soybean lipoxygenase and linoleic acid.
Topics: Animals; Carbon Radioisotopes; Cholestyramine Resin; Chromatography, Thin Layer; Cytosol; Gas Chromatography-Mass Spectrometry; Hydroxylation; Liver; Rats; Sitosterols
PubMed: 7142175
DOI: No ID Found -
Journal of Lipid Research Jul 1979The intestinal absorption of cholesterol and beta-sitostanol (the saturated analogue of beta-sitosterol) were measured and their absorptions compared in the presence and...
The intestinal absorption of cholesterol and beta-sitostanol (the saturated analogue of beta-sitosterol) were measured and their absorptions compared in the presence and absence of cholestyramine. After test meals containing [(3)H]cholesterol and [(14)C]beta-sitostanol without added cholestyramine, 4-day fecal collections yielded an average of 51% of the fed cholesterol and 83% of the fed beta-sitostanol. In separate lymph transport studies without cholestyramine, 36% of the fed cholesterol was recovered in lymph in 24 hours compared to only 2% of the fed beta-sitostanol. Thus, while total recoveries of the two labeled compounds in feces plus lymph were nearly identical (51% + 36% = 87% for cholesterol and 83% + 2% = 85% for beta-sitostanol) their distribution in the two compartments was markedly different, reflecting the relative nonabsorbability of beta-sitostanol. Adding cholestyramine to the test meal caused fecal excretion of cholesterol to increase to 73%, independent of the dose of cholestyramine used. Cholestyramine had no effect on the fecal excretion of beta-sitostanol (average excretion after cholestyramine, 85%). The relative non-absorbability of beta-sitostanol compared to cholesterol is clearly evident in this study and leads us to suggest its possible use as a lipid-soluble, nonabsorbable reference compound for measurement of the absorption of cholesterol and other lipids. Further data are presented to justify its use for this purpose.-Hassan, A. S., and A. J. Rampone. Intestinal absorption and lymphatic transport of cholesterol and beta-sitostanol in the rat.
Topics: Animals; Biological Transport; Cholesterol; Cholestyramine Resin; Feces; Intestinal Absorption; Lymph; Male; Rats; Sitosterols
PubMed: 490042
DOI: No ID Found -
Journal of Nematology Jul 1978Globodera solanacearum females were found to have less than 0.01% of dry wt as sterols. Seven sterols were detected in the nematode, with stanols (campestanol and...
Globodera solanacearum females were found to have less than 0.01% of dry wt as sterols. Seven sterols were detected in the nematode, with stanols (campestanol and stigmastanol) making tip more than 50% of the total sterols present. Lipid amounted to 29.4% of the dry weight of the nematode. Triglyceride, free fatty acid, and phospholipid classes were composed predominantly of 20:4, 20:1, and 18:1 fatty acids. Of the total weight of fatty acids found in G. solanacearum females, the greatest portion occurred in the triglyceride fraction, followed by the free fatty acid fraction then the phospholipid fraction. Several unidentified hydrocarbons were detected in the nematode. Paraffinic hydrocarbons detected ranged in carbon length from C15 to C29. Total concentration of hydrocarbon composed 0.20% of the dry wt.
PubMed: 19305854
DOI: No ID Found