gamma-sitosterol and Hyperlipoproteinemia-Type-II

Topics: Apolipoprotein B-100; Apolipoproteins B; Coronary Artery Disease; Genes, Dominant; Genes, Recessive; History, 20th Century; Humans; Hyperlipoproteinemia Type II; Lipoproteins, LDL; Sitosterols

Topics: Adaptor Proteins, Signal Transducing; Adaptor Proteins, Vesicular Transport; ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; ATP-Binding Cassette Transporters; Bile; Chromosomes, Human, Pair 1; Endocytosis; Genes, Recessive; Humans; Hyperlipoproteinemia Type II; Lipoproteins; Mutation; Receptors, LDL; Sitosterols; Sterols

This mini-review deals with a new appraisal of cerebrotendinous xanthomatosis. In addition to neurologic symptoms, patients with cerebrotendinous xanthomatosis develop cataracts, diarrhea, Achilles tendon xanthoma, atherosclerotic vascular disease, and many other abnormalities. Although the pathophysiology of the disease is not completely understood, excess production and consequent accumulation of cholestanol in tissues may play a crucial role. Chenodeoxycholic acid is the most effective therapy. The causative role and detrimental effects (at a low plasma level) of cholestanol merit further investigation.

Topics: Brain Diseases; Chenodeoxycholic Acid; Cholestanol; Diagnosis, Differential; Humans; Hyperlipoproteinemia Type II; Musculoskeletal Diseases; Sitosterols; Tendons; Xanthomatosis

Topics: Cholesterol, Dietary; Cholestyramine Resin; Clofibrate; Colestipol; Dietary Fats; Drug Therapy, Combination; Humans; Hyperlipidemias; Hyperlipoproteinemia Type II; Hyperlipoproteinemia Type IV; Lipoproteins, LDL; Lipoproteins, VLDL; Niacin; Nicotinic Acids; Sitosterols

Subjects with increased cholesterol absorption might benefit more from statin therapy combined with a cholesterol absorption inhibitor. We assessed whether baseline cholesterol absorption markers were associated with response to ezetimibe/simvastatin therapy, in terms of LDL-cholesterol (LDL-C) lowering and cholesterol absorption inhibition, in patients with familial hypercholesterolemia (FH). In a posthoc analysis of the two-year ENHANCE trial, we assessed baseline cholesterol-adjusted campesterol (campesterol/TC) and sitosterol/TC ratios in 591 FH patients. Associations with LDL-C changes and changes in cholesterol absorption markers were evaluated by multiple regression analysis. No association was observed between baseline markers of cholesterol absorption and the extent of LDL-C response to ezetimibe/simvastatin therapy (beta = 0.020, P = 0.587 for campesterol/TC and beta<0.001, P = 0.992 for sitosterol/TC). Ezetimibe/simvastatin treatment reduced campesterol levels by 68% and sitosterol levels by 62%; reductions were most pronounced in subjects with the highest cholesterol absorption markers at baseline, the so-called high absorbers (P < 0.001). Baseline cholesterol absorption status does not determine LDL-C lowering response to ezetimibe/simvastatin therapy in FH, despite more pronounced cholesterol absorption inhibition in high absorbers. Hence, these data do not support the use of baseline absorption markers as a tool to determine optimal cholesterol lowering strategy in FH patients. However, due to the exploratory nature of any posthoc analysis, these results warrant further prospective evaluation in different populations.

Topics: Adult; Aged; Anticholesteremic Agents; Azetidines; Biomarkers; Cholesterol; Cholesterol, LDL; Double-Blind Method; Drug Therapy, Combination; Ezetimibe; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipoproteinemia Type II; Intestinal Absorption; Male; Middle Aged; Phytosterols; Simvastatin; Sitosterols; Statistics as Topic

Familial hypercholesterolemia (FH) is associated with a high risk of coronary heart disease. Pharmacological treatment and diet are both essential for the management of FH. Foods rich in plant sterols (PS) may play an important role in the treatment of patients with these disorders.. To test the effect of the intake of PS on low-density lipoprotein (LDL) concentration, endothelial function (EF) and LDL particle size in 30 patients with FH.. Randomized and crossover dietary intervention study.. Tertiary outpatient care.. Thirty-eight were recruited, but only 30 were subjected to four low-fat dietary intervention periods, each of 4 weeks.. Each intervention had a different content of cholesterol (<150 or 300 mg/day) and sitosterol (<1 or 2 g/day). Lipid response, EF and LDL particle size were analysed after the intervention.. Plasma sitosterol/cholesterol ratio was higher during both plant sterol-rich periods than during the low plant sterols periods. Basal sitosterol concentrations predicted the LDL-cholesterol response during the intake of plant sterol-enriched diets. The change in LDL-cholesterol was significantly greater in subjects in the upper and intermediate tertiles of basal plasma sitosterol concentrations (-21+/-8 mg/dl, P=0.03; -19+/-7 mg/dl, P=0.04, respectively) than in subjects in the lower tertile (8+/-5 mg/dl) when they changed from a low cholesterol diet to a low cholesterol plus plant sterol diet.. Our study demonstrates that basal sitosterol values can predict hypolipidemic response in patients with FH.

Topics: Adult; Cholesterol, LDL; Combined Modality Therapy; Cross-Over Studies; Diet, Fat-Restricted; Endothelium, Vascular; Female; Humans; Hyperlipoproteinemia Type II; Hypolipidemic Agents; Male; Particle Size; Phytosterols; Predictive Value of Tests; Sitosterols; Treatment Outcome

To assess causes for insufficient cholesterol-lowering response to pravastatin and plant stanol esters in children with heterozygous familial hypercholesterolemia (HeFH).. Nine of 16 children with HeFH who had not reached normocholesterolemia (< or =194 mg/dL [< or =5 mmol/L]) by 1 year after treatment (40 mg pravastatin and plant stanol ester) were called nonresponders. The 7 remaining children were responders. Serum noncholesterol sterol ratios (10(2) x mmol/mol of cholesterol), surrogate estimates of cholesterol absorption (cholestanol, campesterol, sitosterol) and synthesis (desmosterol and lathosterol), were studied at study baseline (on plant stanol esters) and during combination therapy with pravastatin and plant stanol esters.. Pravastatin decreased the serum levels of cholesterol and cholesterol synthesis markers, and increased the ratios of cholesterol absorption markers. Compared with the responders, the nonresponders had higher study baseline (on plant stanol esters) serum cholesterol concentrations (299 +/- 39 vs 251 +/- 35 mg/dL [7.7 +/- 1.0 vs 6.5 +/- 0.9 mmol/L]; P <.001) and higher respective ratios of campesterol (371 +/- 99 vs 277 +/- 67 10(2) x mmol/mol of cholesterol; P = .049) and sitosterol (176 +/- 37 vs 126 +/- 24 10(2) x mmol/mol of cholesterol; P = .008). The higher the ratio of cholestanol at study baseline, the smaller the 1-year percent reduction in cholesterol (r = .556; P = .025).. Pravastatin treatment increases the markers of cholesterol absorption and decreases those of cholesterol synthesis in HeFH during simultaneous inhibition of cholesterol absorption. Combined inhibition of cholesterol absorption and synthesis may not normalize serum lipids in those patients with the highest cholesterol levels, especially if signs of enhanced cholesterol absorption are detectable.

Topics: Adolescent; Anticholesteremic Agents; Child; Cholestanol; Cholesterol; Desmosterol; Female; Heterozygote; Humans; Hyperlipoproteinemia Type II; Male; Phytosterols; Pravastatin; Sitosterols; Triglycerides

To study the compliance and changes in plasma lipids, plant sterols, fat-soluble vitamins and carotenoids in children and parents with familial hypercholesterolemia (FH) consuming a plant sterol ester-enriched (PSE) spread.. A 26-week open-label follow-up of children who had previously been studied in a controlled cross-over design. The parents were also included in the open-label arm of the study.. Outpatient clinic for treatment of hyperlipidemia.. A total of 37 children (7-13 y) and 20 parents (32-51 y) diagnosed with 'definite' or 'possible' heterozygous FH. In all, 19 of the parents, but no children, used statins. All were patients at the Lipid Clinic, National Hospital in Oslo.. Subjects were recommended to eat 20 g/day of PSE spread as part of their lipid-lowering diet.. The mean intake of PSE spread was 13.7 and 16.5 g/days in the children and parents, respectively, corresponding to 1.2 and 1.5 g of plant sterols. Plasma total cholesterol decreased by 9.1% in both children (P<0.001) and parents (P=0.002). The corresponding decreases in LDL cholesterol were 11.4% (P<0.001) and 11.0% (P=0.012). Increases in serum lathosterol, campesterol and sitosterol, adjusted for total cholesterol, were observed in the children (31, 96, 48%, respectively, P<0.001) at the end of the controlled cross-over period. In the parents, serum campesterol and sitosterol, adjusted for total cholesterol, increased by 92 and 39%, respectively (P< 0.001). Lipid-adjusted serum alpha- and beta-carotene decreased by 17.4% (P=0.008) and 10.9% (P=0.018), respectively, in the children at the end of the controlled PSE period, but increased again during the follow-up. In the parents, serum alpha- and beta-carotene concentrations were unchanged, while serum lutein and lycopene decreased by 7.3% (P=0.037) and 14.6% (P=0.044), respectively.. Sustained efficacy of cholesterol reduction and long-term compliance of PSE intake were demonstrated in this study.

Topics: Adolescent; Adult; Carotenoids; Child; Cholesterol; Cross-Over Studies; Female; Humans; Hyperlipoproteinemia Type II; Lipids; Male; Margarine; Middle Aged; Patient Compliance; Phytosterols; Sitosterols; Treatment Outcome

The nonabsorbable bile acid sequestrant resin, colestipol, was administered to 16 patients with primary hypercholesterolemia, and its effect on serum lipids, lipoprotein fractions, and circulating platelet aggregate ratio and platelet aggregation in response to adenosine diphosphate (ADP) was compared with that of sitosterol. Cholesterol absorption and sterol balance studies were done in four of the subjects during the following treatment periods: diet alone, colestipol, and sitosterol. Total serum cholesterol was significantly reduced by colestipol but only slightly decreased by sitosterol. Combination treatment with colestipol and sitosterol was associated with a smaller decrease in serum cholesterol than was demonstrated with colestipol alone. Serum triglycerides tended to increase during colestipol therapy (this increase was not clinically significant) but showed a minimal nonsignificant decrease with sitosterol treatment. Colestipol decreased cholesterol absorption, whereas sitosterol slightly increased it. Fecal sterol excretion was increased with colestipol treatment but was minimally affected by administration of sitosterol. Low-density lipoprotein and high-density lipoprotein cholesterol significantly decreased with colestipol treatment. The circulating platelet aggregate ratio was significantly lower in the group of patients with hypercholesterolemia who received colestipol initially than in control subjects, but platelet aggregation in response to ADP was not significantly different between these two groups. No significant change in platelet aggregation was noted during colestipol or sitosterol treatment despite a significant decrease in total serum cholesterol with colestipol therapy, a suggestion that the platelet and lipid abnormalities are not interrelated.

Topics: Adenosine Diphosphate; Adult; Aged; Cholesterol; Colestipol; Female; Humans; Hyperlipoproteinemia Type II; Lipids; Lipoproteins; Male; Middle Aged; Platelet Aggregation; Polyamines; Sitosterols; Sterols

Sitosterolemia is caused by homozygous or compound heterozygous gene mutations in either ATP-binding cassette subfamily G member 5 (ABCG5) or 8 (ABCG8). Since ABCG5 and ABCG8 play pivotal roles in the excretion of neutral sterols into feces and bile, patients with sitosterolemia present elevated levels of serum plant sterols and in some cases also hypercholesterolemia. A 48-year-old woman was referred to our hospital for hypercholesterolemia. She had been misdiagnosed with familial hypercholesterolemia at the age of 20 and her serum low-density lipoprotein cholesterol (LDL-C) levels had remained about 200-300 mg/dL at the former clinic. Although the treatment of hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors was ineffective, her serum LDL-C levels were normalized by ezetimibe, a cholesterol transporter inhibitor. We noticed that her serum sitosterol and campesterol levels were relatively high. Targeted analysis sequencing identified a novel heterozygous ABCG5 variant (c.203A>T; p.Ile68Asn) in the patient, whereas no mutations were found in low-density lipoprotein receptor (LDLR), proprotein convertase subtilisin/kexin type 9 (PCSK9), or Niemann-Pick C1-like intracellular cholesterol transporter 1 (NPC1L1). While sitosterolemia is a rare disease, a recent study has reported that the incidence of loss-of-function mutation in the ABCG5 or ABCG8 gene is higher than we thought at 1 in 220 individuals. The present case suggests that serum plant sterol levels should be examined and ezetimibe treatment should be considered in patients with hypercholesterolemia who are resistant to HMG-CoA reductase inhibitors.

Topics: Anticholesteremic Agents; ATP Binding Cassette Transporter, Subfamily G, Member 5; Cholesterol; Cholesterol, LDL; Diagnostic Errors; Ezetimibe; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hyperlipoproteinemia Type II; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipoproteins; Loss of Function Mutation; Middle Aged; Phytosterols; Sitosterols; Treatment Failure

Cholesterol analogs have been used to treat hypercholesterolemia. The present study was to examine the effect of dihydrocholesterol (DC) on plasma total cholesterol (TC) compared with that of β-sitosterol (SI) in hamsters fed a high cholesterol diet.. Forty-five male hamsters were randomly divided into 6 groups, fed either a non-cholesterol diet (NCD) or one of five high-cholesterol diets without addition of DC and SI (HCD) or with addition of 0.2% DC (DA), 0.3% DC (DB), 0.2% SI (SA), and 0.3% SI (SB), respectively, for 6 weeks. Results showed that DC added into diet at a dose of 0.2% could reduce plasma TC by 21%, comparable to that of SI (19%). At a higher dose of 0.3%, DC reduced plasma TC by 15%, less effective than SI (32%). Both DC and SI could increase the excretion of fecal sterols, however, DC was more effective in increasing the excretion of neutral sterols but it was less effective in increasing the excretion of acidic sterols compared with SI. Results on the incorporation of sterols in micellar solutions clearly demonstrated both DC and SI could displace the cholesterol from micelles with the former being more effective than the latter.. DC was equally effective in reducing plasma cholesterol as SI at a low dose. Plasma TC-lowering activity of DC was mediated by inhibiting the cholesterol absorption and increasing the fecal sterol excretion.

Topics: Adipose Tissue; Animal Feed; Animals; Anticholesteremic Agents; Aortic Diseases; Atherosclerosis; Bile Acids and Salts; Cholestanol; Cholesterol; Cholesterol, Dietary; Cricetinae; Drug Evaluation, Preclinical; Feces; Gene Expression Profiling; Hyperlipoproteinemia Type II; Intestinal Absorption; Lipids; Lipoproteins; Liver; Male; Mesocricetus; Metabolic Networks and Pathways; Micelles; Molecular Structure; Organ Size; Plaque, Atherosclerotic; Random Allocation; RNA, Messenger; Sitosterols; Sterols; Viscera

Current guidelines strongly recommend the identification of genetic forms of hypercholesterolemia (HC) during childhood.The usefulness of non-cholesterol sterols (NCS) in the diagnosis of genetic HC has not been fully explored. Plasma NCS were measured by gas chromatography/mass spectrometry (GC/MS) in 113 children with hypercholesterolemia affected by: autosomal dominant hypercholesterolemia (ADH), familial combined hyperlipidemia(FCHL), polygenic hypercholesterolemia (PHC), and in 79 controls to evaluate: i) plasma NCS profile in different genetic HC and ii) the usefulness of NCS for the diagnosis of HC beyond current clinical criteria. ADH was characterized by raised lathosterol/total cholesterol (TC) and reduced phytosterols/TC ratios, indicative of increased cholesterol synthesis. FCHL showed a slight increase of lathosterol/TC ratio, whereas PHC showed increased phytosterols/TC ratios, indicative of increased cholesterol absorption. In a post hoc discriminant analysis of patients with HC, lipid values correctly classified the 73% (14 of 19) of ADH, whereas the inclusion of plasma sterols allowed the correct identification of all 19 patients with ADH. FCHL was not differentiated from PHC (62 versus 69%).In conclusion, NCS measurement showed that cholesterol plasma levels are related to the cholesterol synthesis in ADH and to cholesterol absorption in PHC. NCS improve the detection of ADH in pediatric patients, whereas FCHL diagnosis is not improved.

Topics: Adolescent; Biomarkers; Case-Control Studies; Child; Cholesterol; Discriminant Analysis; Female; Gas Chromatography-Mass Spectrometry; Genetic Predisposition to Disease; Humans; Hyperlipidemia, Familial Combined; Hyperlipoproteinemia Type II; Italy; Male; Multifactorial Inheritance; Phytosterols; Predictive Value of Tests; Sitosterols; Sterols

We studied the concentrations and ratios to cholesterol of noncholesterol sterols reflecting absorption (eg, campesterol) or synthesis (eg, lathosterol) of cholesterol off and on plant sterol and stanol ester spreads in serum and in different lipoproteins of a family with familial hypercholesterolemia, including heterozygous parents receiving no treatment and their homozygous offspring undergoing long-term treatment with statins and apheresis. Serum cholesterol levels were similar in the homozygous and heterozygous individuals, but the concentrations of sterols reflecting cholesterol absorption were as much as 10 times greater in the homozygous child than in the heterozygous parents, whereas the respective markers of cholesterol synthesis only tended to be higher. About 70% of squalene in the homozygous individual (60% in the heterozygous family members) and 85% to 90% of noncholesterol sterols (60%-80% in the heterozygous subjects) were transported by low-density lipoprotein. The ratios of absorption sterols to cholesterol were higher in high-density lipoprotein (HDL) than in very low-density lipoprotein (VLDL), whereas those of synthesis markers and plant stanols were highest in VLDL. The ratios of absorption sterols in serum were mostly lower than those in HDL but higher than in VLDL, whereas the ratios of synthesis sterols in serum were lower than they were in VLDL. Both spreads reduced serum total cholesterol by about 14% in the heterozygous family members and 9% in the homozygous individual. The sterol ester spread increased serum plant sterol concentrations (eg, campesterol in the homozygous family member increased from 5 to 9 mg/dL) and the ratios to cholesterol, but the stanol ester spread decreased them. Plant sterol esters seemed to similarly decrease serum cholesterol in this family with familial hypercholesterolemia, but the clinical role of increased plant sterol concentrations, almost doubled in the LDL of homozygous individuals, is not known.

Topics: Adult; Blood Component Removal; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Dietary Fats; Double-Blind Method; Female; Heterozygote; Homozygote; Humans; Hyperlipoproteinemia Type II; Hypolipidemic Agents; Male; Margarine; Middle Aged; Phytosterols; Sitosterols; Squalene; Triglycerides

Topics: Aged; Cholesterol; Female; Humans; Hyperlipoproteinemia Type II; Myocardial Infarction; Sitosterols

This study was undertaken to compare the ability of two plant sterols to reduce serum levels of lipids and to compare their mechanism of action in nine children with severe familial hypercholesterolemia (total and low-density lipoprotein cholesterol concentrations averaged 9.57 mmol/L (370 mg/dl) and 7.87 mmol/L (301 mg/dl)). After a 3-month strict diet, the children were given sitosterol pastils (2 gm three times a day) for 3 months, followed by a 7-month course of sitostanol (0.5 gm three times a day). Serum lipoprotein levels and serum concentrations of campesterol and sitosterol were determined in all nine children, and the fecal excretion of neutral and acidic sterols were determined in seven children at the end of each therapeutic regimen. Sitosterol reduced low-density lipoprotein cholesterol levels by 20% (p < 0.01); sitostanol reduced low-density lipoprotein cholesterol levels by 33% after 3 months and 29% after 7 months (p < 0.01 compared with diet; p < 0.05 compared with sitosterol). Although sitosterol did not alter serum concentrations of campesterol and sitosterol, a significant reduction did occur during sitostanol therapy (-47% and -51%, respectively; p < 0.01). Fecal excretion of neutral sterols increased from 6.7 mg/kg per day during the control period to 9.7 mg/kg per day during sitosterol administration (p < 0.05), and to 12.6 mg/kg per day during sitostanol administration (p < 0.05 compared with diet and sitosterol periods), indicating an increase in the inhibition of intestinal cholesterol absorption. All children completed the study and no obvious side effects occurred. The data indicate that sitostanol, even with a dose four-fold lower than that of sitosterol, was significantly more effective in reducing elevated levels of low-density lipoprotein cholesterol, and the reduction in serum lipid levels was of the same magnitude as that observed with systemic lipid-lowering drugs. These results suggest that sitostanol, a nonabsorbable plant sterol, could be the drug of choice for treating familial hypercholesterolemia in childhood.

Topics: Adolescent; Alanine Transaminase; Alkaline Phosphatase; Apolipoproteins B; Carotenoids; Child; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Feces; Female; Heterozygote; Humans; Hyperlipoproteinemia Type II; Male; Phytosterols; Sitosterols; Sterols

The hypocholesterolaemic effect of pravastatin 40 mg and lovastatin 40 mg daily has been compared in patients with familial hypercholesterolaemia (FH). Administration of the two drugs was separated by a three-month washout period. The reduction in total serum cholesterol after 1,2 and 4 weeks of treatment was similar after pravastatin (-23%, -32% and -32%) and lovastatin (-23%, -30% and -31%). The serum concentrations of LDL cholesterol were similarly reduced, whilst triglycerides, other lipoproteins, cholestanol and squalene were not altered. The reductions in the serum levels of the cholesterol precursor sterols, delta 8-cholesterol, desmosterol and lathosterol were not significantly different after either drug. The lack of difference suggests that cholesterol synthesis was equally inhibited by the two agents. In addition, the serum content of the plant sterols campesterol and sitosterol tended to be equally increased. The comparability of the increases suggests that the absorption and biliary elimination of the two sterols were equally affected by the two statins. Thus, no difference was found between the effects of pravastatin and lovastatin on the serum levels and metabolic precursors of cholesterol in FH during four weeks of treatment.

Topics: Adult; Aged; Cholesterol; Cholesterol, LDL; Desmosterol; Female; Humans; Hyperlipoproteinemia Type II; Isomerism; Lovastatin; Male; Middle Aged; Phytosterols; Pravastatin; Sitosterols; Triglycerides

Seven prepubertal children (age range 5.3 to 10.8 years) with severe heterozygous familial hypercholesterolemia (serum cholesterol concentration 416 +/- 85 mg/dL and low-density lipoprotein [LDL] cholesterol concentration 360 +/- 90 mg/dL) were first treated by dietary intervention, second by sitosterol (3 x 2 g/d), and third by bezafibrate (2 x 200 mg/d). Each treatment period lasted 3 months. Subsequently, a treatment combining half the dose of sitosterol and bezafibrate was administered for the following 24 months. Diet alone reduced total and LDL cholesterol values by 4.5% (not significant) and 6.6% (P less than .05), respectively. Sitosterol lowered total and LDL cholesterol values by 17% (P less than .05) when compared with diet alone. Compared with sitosterol, bezafibrate produced a more pronounced effect on total and LDL cholesterol values (-18% and -28%, P less than .05), and high-density lipoprotein cholesterol concentration increased significantly from 48 mg/dL to 55 mg/dL. Combined treatment with half the dose each of sitosterol and bezafibrate was as effective as the higher dose of bezafibrate, and reduction averaged almost 40% and 50% for total and LDL cholesterol values; this lipid-lowering effect persisted for the next 24 months. Laboratory safety parameters and physical examination revealed no obvious side effects. This study indicates that the combination of sitosterol (3 x 1 g/d) plus bezafibrate (1 x 200 mg/d) is an alternate, acceptable, safe, and effective therapeutic approach for treatment of severe hypercholesterolemia in children with high-risk familial hypercholesterolemia.

Topics: Apolipoprotein A-I; Bezafibrate; Child; Cholesterol, HDL; Cholesterol, LDL; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Hyperlipoproteinemia Type II; Male; Sitosterols; Triglycerides

We measured the serum lathosterol level, a reflection of the rate of whole body cholesterol synthesis, in 15 patients with manifest type III hyperlipoproteinemia (HLP), in 20 subjects with apolipoprotein (apo) E2/2 phenotype, but without type III HLP, in 21 patients with type IIA and 10 patients with type IIB HLP. A group of 100 subjects with apo E3/3 phenotype served as reference. Using ANCOVA, lathosterol was adjusted for serum cholesterol and triglyceride concentrations, since these parameters were found to independently correlate with lathosterol. The adjusted means (+/- SEM), in mumol/L, in these groups were 12.9 +/- 1.1, 8.2 +/- 1.1, 4.8 +/- 0.9, 9.8 +/- 1.4, and 7.8 +/- 0.4, respectively. Type III HLP patients had significantly higher lathosterol levels than all other groups except type IIB HLP. In addition, lathosterol was significantly lower in type IIA patients than in all other groups. The serum levels of plant sterols, used as a reflection of cholesterol absorption, did not differ among the various groups after adjustment for serum cholesterol. These findings suggest that an overproduction of cholesterol is one factor discriminating E2/2 homozygotes with type III HLP from those without the disease.

Topics: Analysis of Variance; Apolipoprotein E2; Apolipoproteins E; Cholesterol; Humans; Hyperlipoproteinemia Type II; Hyperlipoproteinemia Type III; Isomerism; Phenotype; Phytosterols; Sitosterols

A case of a 3 1/2 year old female child is described in which symptomless cutaneous xanthomatosis led to the diagnosis of sitosterolaemia in the presence of a defect of low-density lipoprotein uptake by cultured fibroblasts. The condition responded to treatment by cholestyramine with normalisation of the blood lipid levels. Normal growth and development continued for three years of observation.

Topics: Child, Preschool; Female; Heterozygote; Humans; Hyperlipoproteinemia Type II; Lipoproteins; Sitosterols

We studied the effect on the serum LCAT activity and apolipoproteins in ten subjects with primary hypercholesterolemia after treatment with beta-sitosterol. The 2-month administration of beta-sitosterol resulted in an increase of the fractional as well as of the molar esterification rate of the LCAT. These alterations were associated with a decrease of the levels of total, esterified, and unesterified cholesterol, whereas the levels of HDL-cholesterol and the apolipoproteins A-I and B were not affected. We conclude that beta-sitosterol primarily lowers cholesterol-rich lipoproteins with a lower density range than LDL via an accelerated esterification rate of the LCAT enzyme.

Topics: Adult; Aged; Apolipoproteins; Cholesterol; Cholesterol, HDL; Esterification; Female; Humans; Hyperlipoproteinemia Type II; Lipoproteins; Lipoproteins, HDL; Male; Middle Aged; Phosphatidylcholine-Sterol O-Acyltransferase; Sitosterols; Triglycerides

The fecal steroid elimination profile was studied in 7 type II hyperlipoproteinemic patients given a low-lipid diet with textured soybean proteins, in order to define the mechanism of the hypocholesterolemic activity of this new dietary regimen. Four of the patients followed a 3- + 3-week cross-over protocol, comparing the soybean diet with a reference low-lipid diet with animal proteins. In these, fecal neutral steroids and bile acids were analyzed by chromatography during the two dietary periods. In spite of the clear hypocholesterolemic effect, no significant differences in steroid output were noted between the two dietary periods. In the 3 remaining patients, a chromatographic + isotopic method (by injecting 14C-labelled cholesterol i.v. 4-6 weeks prior to the dietary study) was employed. Again, no marked changes were noted in the fecal neutral steroid and bile acid outputs and the slope of the decay curve of the plasma cholesterol-specific activity was not changed by the experimental diet, in spite of the remarkable decrease in plasma cholesterol. The reported results do not provide a definitive contribution to the mode of action of the soybean protein diet. They suggest, however, that it is not an effect mediated by undigestible dietary components. The possibility of a cholesterol redistribution from plasma to tissue pools should be considered.

Topics: Bile Acids and Salts; Cholesterol; Cholesterol, Dietary; Dietary Fats; Feces; Female; Glycine max; Humans; Hyperlipoproteinemia Type II; Male; Plant Proteins, Dietary; Sitosterols

Topics: Adolescent; Adult; Cholesterol; Female; Humans; Hyperlipoproteinemia Type II; Sitosterols