Serum lathosterol concentration is an indicator of whole-body cholesterol synthesis in humans

The power of serum lathosterol concentration as an indicator of whole-body cholesterol synthesis was investigated in 47 human volunteers consuming two diets differing in fatty acid composition. The cholesterol balance (fecal excretion of neutral and acid steroids minus cholesterol intake) was strongly correlated with the serum level of total (free plus esterified) lathosterol and also with the ratio of serum lathosterol over serum cholesterol, both on a diet rich in polyunsaturated fatty acids (r = 0.74 for the ratio) and one containing mainly saturated fatty acids (r = 0.70 for the ratio). In a subgroup for which the serum levels of free lanosterol and other free methylsterols were also quantitated, the correlations of these levels (expressed relative to serum free cholesterol) with the cholesterol balance were lower than that found for total lathosterol (expressed relative to serum total cholesterol). A further corroboration was obtained by measuring the lathosterol/cholesterol ratio in 20 patients with familial hypercholesterolemia before and during treatment with the hydroxymethylglutaryl coenzyme A reductase inhibitor Mk-733. The ratio was lowered by 47% during drug treatment, suggesting a significant decrease of the cholesterol balance in these patients. We conclude, from the various indicators proposed to monitor whole-body cholesterol synthesis, that the lathosterol/cholesterol ratio in serum appears preferable with respect to indicative power and ease of quantitation.     

Evaluation of the use of serum lathosterol concentration to assess whole-body cholesterol synthesis in rabbits.

Serum lathosterol concentration in rabbits was assessed as a possible indicator of whole-body cholesterol synthesis. In random-bred New Zealand White (NZW) rabbits fed a control diet or a diet containing either cholesterol, simvastatin, or cholestyramine, neither serum lathosterol concentration nor the serum lathosterol:total cholesterol ratio systematically corresponded with the anticipated rate of cholesterol synthesis. In control rabbits and those fed simvastatin or cholestyramine, whole-body cholesterol synthesis, which was calculated from the sterol balance, was correlated with serum lathosterol concentration when expressed relative to cholesterol in very low, intermediate, and low density lipoproteins (VLDL + IDL + LDL) (r = 0.61; n = 23; P = 0.002). The low correlation coefficient indicates that the predictive value of the lathosterol: (VLDL + IDL + LDL) cholesterol ratio is limited when applied to individual rabbits. Cholesterol and simvastatin feeding reduced the group mean serum lathosterol:(VLDL + IDL + LDL) cholesterol ratio, whereas cholestyramine in the diet raised the group mean ratio in the NZW rabbits. We conclude that the serum lathosterol:(VLDL + IDL + LDL) cholesterol ratio may be an indicator of group mean rates of whole-body cholesterol synthesis in rabbits but may not yield reliable information on individual rabbits. The lathosterol:(VLDL + IDL + LDL) cholesterol ratio predicted that in hyperresponsive inbred rabbits, showing an excessive hypercholesterolemia after cholesterol feeding, baseline whole-body cholesterol synthesis is lower than in hyporesponsive rabbits. Addition of cholesterol to the diet caused a reduction of predicted cholesterol synthesis in hypo- but not in hyper-responsive rabbits.     

Quantification of acetylcholine, choline, betaine, and dimethylglycine in human plasma and urine using stable-isotope dilution ultra performance liquid chromatography-tandem mass spectrometry

Disorders in choline metabolism are related to disease conditions. We developed a stable-isotope dilution ultra performance liquid chromatography-mass spectrometry (UPLC-MS/MS) method for the simultaneous quantification of acetylcholine (ACh), betaine, choline, and dimethylglycine (DMG). We used this method to measure concentrations of the analytes in plasma and urine in addition to other biological fluids after a protein precipitation by acetonitrile. The detection limits were between 0.35 nmol/L (for ACh in urine) and 0.34 μmol/L (for betaine in urine). ACh concentrations were not detectable in plasma. Intraassay and interassay coefficient of variation (CVs) were all <10.0% in biological fluids, except for DMG in cerebrospinal fluid (CV=12.44%). Mean recoveries in urine pool samples were between 99.2% and 103.9%. The urinary excretion of betaine, choline, and DMG was low, with approximately 50.0% higher excretion of choline in females compared to males. Median urinary excretion of ACh were 3.44 and 3.92 μmol/mol creatinine in males and females, respectively (p=0.689). Plasma betaine concentrations correlated significantly with urinary excretions of betaine (r=0.495, p=0.027) and choline (r=0.502, p=0.024) in females. Plasma choline concentrations correlated significantly with urinary excretion of ACh in males (r=0.419, p=0.041) and females (r=0.621, p=0.003). The new method for the simultaneous determination of ACh, betaine, choline, and DMG is sensitive, precise, and fast enough to be used in clinical investigations related to the methylation pathway.     

RP-HPLC测定红丝线中香豆素的含量

采用反相高效液相色谱法,测定红丝线中香豆素的含量。色谱柱为ZORBAXXDB-C18(4.6mm×150mm,5μm);流动相:V(甲醇)∶V(0.01mol/L磷酸二氢钠溶液(pH5.4))=45∶55;流速:1mL/min;检测波长278nm。香豆素的线性范围为2.5~30mg/L(r=0.9998),回收率97.5%~101%。该法简便、准确,重复性好,适用于测定红丝线中香豆素的含量。     

Plasma non-cholesterol sterols in patients with non-insulin dependent diabetes mellitus.

Plasma plant sterol concentrations (an index of cholesterol absorption efficiency) and plasma lathosterol concentration (an index of cholesterol synthesis rate) were measured in 52 patients with non-insulin dependent diabetes mellitus (NIDDM) and 36 non-diabetic controls. Plasma plant sterol concentrations were significantly (P less than 0.01) lower in diabetic patients (campesterol: men -36%, women -48%; betasitosterol: men -35%, women -42%). Fasting serum insulin levels were inversely correlated with plasma plant sterol concentrations in diabetic patients (campesterol: r = -0.347, P = 0.012; betasitosterol: r = -0.345, P = 0.012) and in non-diabetic men (campesterol: r = -0.578, P = 0.039; betasitosterol: r = -0.702, P = 0.008). Serum insulin levels were also correlated significantly with plasma lathosterol concentration in diabetic patients (r = 0.295, P = 0.034). The results of this study suggest that absorption of plant sterols and possibly cholesterol from the diet may be reduced in hyperinsulinemic diabetics.     

胶束电动毛细管色谱法测定红丝线提取物中紫蓝素的含量

建立了胶束电动毛细管电泳色谱法(MECC)测定红丝线提取物中紫蓝素的含量的方法。毛细管柱内径75μm,长50.2cm;运行电压25kV,检测波长585nm,温度25℃;缓冲液为25mmol/L,β-CD10mmol/L,硼酸盐-20%乙腈(pH值8.0);进样方式:压力进样,进样时间5s。结果表明紫蓝素在10～100μmol/L浓度范围内具有良好的线性关系(r=0.9995),回收率为95.3%～103.2%。该方法快速、简便、并且较为准确,适用于测定红丝线提取物中紫蓝素的含量。     

The determination of ascorbic acid and uric acid in human seminal plasma using an HPLC with UV detection

Oxidative stress has been proposed as one of the potential causes for infertility in men. Ascorbic acid and uric acid play important role in protection of spermatozoa against free radicals. A method for the simultaneous determination of ascorbic acid and uric acid in human seminal plasma using HPLC with UV detection and investigation their clinical significance as antioxidants protecting male germ cells against oxidative damage are described. Semen samples were obtained from consecutive male partners of couples presenting for a fertility evaluation. After liquefaction, the samples were centrifuged and the supernatants were diluted with dithiothreitol solution and after a filtration injected onto an analytical column. For the separation, a reverse-phase column MAG 1, 250 mm × 4.6 mm, Labiospher PSI 100 C18, 5 μm, was used. The mixture of ethanol and 25 mmol/L sodium dihydrogenphosphate (2.5:97.5, v/v), pH 4.70 was used as a mobile phase. Analytical performance of this method is satisfactory for both ascorbic acid and uric acid: the intra-assay and inter-assay coefficients of variation were below 10%. Quantitative recoveries from spiked seminal plasma were between 92.1 and 102.1%. We have found no significant differences in both ascorbic acid and uric acid concentration between the smokers and non-smokers (351.0 ± 237.9 μmol/L and 323.7 ± 99.5 μmol/L vs. 444.8 ± 245.5 μmol/L and 316.6 ± 108.9 μmol/L, p>0.05). This assay is a simple and reproducible HPLC method for the simultaneous measurement of ascorbic acid and uric acid in human seminal plasma.     

Determination of β-blockers in pharmaceutical and human urine by capillary electrophoresis with electrochemiluminescence detection and studies on the pharmacokinetics

A novel method for simultaneous determination of atenolol, metoprolol and esmolol was proposed by capillary electrophoresis (CE) separation and electrochemiluminescence (ECL) detection. Poly-β-cyclodextrin (Poly-β-CD) was used as an additive in the running buffer to improve the separation of three analytes. The conditions for CE separation, ECL detection and effect of Poly-β-CD were investigated in detail. The three β-blockers with very similar structures were well separated and detected under the optimum conditions. The linear ranges of the standard solution for atenolol and esmolol were 2.5-125 μmol/L with a detection limit (S/N=3) of 0.5 μmol/L, and for metoprolol was 0.5-25 μmol/L with a detection limit of 0.1 μmol/L. For three β-blockers from spiked aqueous and urine samples, the accuracy and precision including intraday and interday experiments were performed by calculating the recovery, the relative standard deviations of the ECL intensity and the migration time, respectively. The developed method was applied to the determination of metoprolol content in commercial pharmaceutical, and the analytical results are in good agreement with the nominal value with recoveries in the range of 98.7-105%. The proposed method was also applied to the monitoring of pharmacokinetics for metoprolol in human body.     

Simultaneous determination of urinary tryptophan, tryptophan-related metabolites and creatinine by high performance liquid chromatography with ultraviolet and fluorimetric detection

A high performance liquid chromatography method with ultraviolet and fluorimetric detection has been developed for the simultaneous determination of urinary creatinine (Cr), tryptophan (Trp) and three Trp-related metabolites including kynurenine (Kyn), kynurenic acid (Kyna) and 5-hydroxyindole-3-acetic acid (5-HIAA). Samples were pretreated by centrifugation after a freeze-thaw cycle to remove protein and other precipitates. Separation was achieved by an Agilent HC-C18 (2) analytical column and a gradient elution program with a constant flow rate 1mL/min at an ambient temperature. Total run time was 30 min. Cr, Kyn and Kyna were measured by a variable wavelength detector at wavelengths 258 nm, 365 nm and 344 nm respectively. Trp and 5-HIAA were measured by a fluorescence detector with an excitation wavelength of 295 nm and an emission wavelength of 340 nm. This allowed the determination of Kyn/Cr, Kyna/Cr, Trp/Cr and 5-HIAA/Cr concentration ratios in a single run on the same urine sample. Good linear responses were found with correlation coefficient (r)>0.999 for all analytes within the concentration range of physiological level. The limit of detection of the developed method was: Cr, 0.0002 g/L; Kyn, 0.1 μmol/L; Kyna, 0.04 μmol/L; Trp, 0.02 μmol/L and 5-HIAA, 0.01 μmol/L. Recoveries from spiked human urine were: Cr, 93.0-106.4%; Kyn, 97.9-106.9%; Kyna, 98.5-105.6%; Trp, 96.7-105.2% and 5-HIAA, 96.1-99.7%. CVs of repeatability and intermediate precision of all analytes were less than 5%. This method has been applied to the analysis of urine samples from normal subjects.     

高效液相色谱串联质谱法同时检测粪便中三种抗抑郁药物*

目的:建立同时检测粪便中度洛西汀、氟西汀、艾斯西酞普兰三种抗抑郁药物的高效液相色谱串联质谱(HPLC-MS)方法。方法:样品经正己烷-异丙醇(95:5,v/v)预处理后,以超纯水和乙腈混合液作为流动相进行梯度洗脱,在Agilent ZORBAX SB-C18液相色谱柱(2.1 mm×100 mm,3.5 μm)上分离后用电喷雾串联质谱法检测,内标法定量。结果:粪便样品中度洛西汀、氟西汀、艾斯西酞普兰的加标回收率为61.6%～116.5%,精密度为 2.80%～12.9%(n=5),线性方程相关系数(r)均大于0.995,检出限分别为0.1 μg/g、1 μg/g、0.001 μg/g,定量限分别为0.5 μg/g、2 μg/g、0.005 μg/g,符合高效液相色谱串联质谱的分析要求。结论:该方法能够简单、准确检测出粪便中度洛西汀、氟西汀、艾斯西酞普兰这三种抗抑郁药的含量。     

Determination of free cholesterol based on a novel flow‐injection chemiluminescence method by immobilizing enzyme

A novel flow injection chemiluminescence method is proposed for determination of cholesterol in this paper. The cholesterol oxidase was immobilized onto sol–gel and prepared as an enzymatic reaction column. The determination of cholesterol was performed by quantitative determination of hydrogen peroxide produced from an enzymatic reaction. The luminol–H₂O₂–metal chelate diperiodatocuprate(III) system ensured that the method was highly sensitive and selective. Free cholesterol was determined over the range 5.0 × 10^–8 mol/L–5.0 × 10^–7 mol/L, with a limit of detection (3σ) of 1.9 × 10^–8 mol/L. The relative standard deviation (RSD) for 2.5 × 10^–7 mol/L was 2.7% (n = 7). The proposed method offered the advantages of sensitivity, selectivity, simplicity and rapidity for free cholesterol determination, and was successfully applied to the direct determination of free cholesterol in serum. Copyright © 2008 John Wiley & Sons, Ltd.     

Effects of pravastatin and cholestyramine on products of the mevalonate pathway in familial hypercholesterolemia

Patients with heterozygous familial hypercholesterolemia (n = 12) were treated either with pravastatin, a specific inhibitor of HMG-CoA reductase, or cholestyramine, followed by a period of combined treatment with both drugs. Initially, these patients had increased serum levels of low density lipoprotein (LDL) cholesterol (8.77 +/- 0.48 mmol/l; SEM), lathosterol (5.32 +/- 0.60 mg/l), and ubiquinone (0.76 +/- 0.09 mg/l), while the serum dolichol concentration was in the normal range. Cholestyramine treatment (n = 6) decreased the levels of LDL cholesterol (-32%) and increased lathosterol (+125%), but did not change dolichol or ubiquinone levels in a significant manner. Pravastatin treatment (n = 6) decreased LDL cholesterol (-27%), lathosterol (-46%), and ubiquinone (-29%). In this case, the amount of dolichol in serum also showed a small but statistically insignificant decrease (-16%) after 12 weeks of treatment. Combined treatment with cholestyramine and pravastatin (n = 6) resulted in changes that were similar to, but less pronounced than, those observed during pravastatin treatment alone. In no case was the ratio between ubiquinone and LDL cholesterol reduced. Possible effects on hepatic cholesterol, ubiquinone, and dolichol concentrations were studied in untreated (n = 2), cholestyramine-treated (n = 2), and pravastatin-treated (n = 4) gallstone patients and no consistent changes could be observed. The results indicate that treatment with pravastatin in familial hypercholesterolemia decreases serum ubiquinone levels in proportion to the reduction in LDL cholesterol.     

Insulin sensitivity regulates cholesterol metabolism to a greater extent than obesity: lessons from the METSIM Study

Cholesterol synthesis is upregulated and absorption downregulated in insulin resistance and in type 2 dia-betes. We investigated whether alterations in cholesterol metabolism are observed across the glucose tolerance status, from normoglycemia through impaired glucose tolerance to type 2 diabetes, in 781 randomly selected men 45 to 70 years of age from a population-based Metabolic Syndrome in Men Study. Cholesterol metabolism was assayed using surrogate serum markers, squalene, and noncholesterol sterols. The study population was classified into subgroups according to glucose tolerance as follows: normoglycemia, impaired fasting glucose, impaired glucose tolerance, and type 2 diabetes. LDL cholesterol did not differ between the groups. Cholesterol synthesis markers were lowest and absorption markers highest in normoglycemia. Sitosterol was lower in subjects with impaired fasting glucose compared with normoglycemic subjects (113 ± 7 vs. 136 ± 3 10² μmol/mmol of cholesterol, P < 0.05). LDL cholesterol was not associated with lathosterol/sitosterol ratio, a marker of cholesterol metabolism. Peripheral insulin sensitivity evaluated by the Matsuda index was associated with the lathosterol/sitosterol ratio in the entire population (r = −0.457, P < 0.001) and with that of lathosterol/cholestanol independently of obesity. In conclusion, cholesterol metabolism was altered already from subjects with impaired fasting glucose. Upregulated cholesterol synthesis was associated with peripheral insulin resistance independent of obesity.     

Accumulation of cholesterol precursors and plant sterols in human stenotic aortic valves

The pathogenesis of aortic valve stenosis (AS) is characterized by the accumulation of LDL-derived cholesterol in the diseased valves. Since LDL particles also contain plant sterols, we investigated whether plant sterols accumulate in aortic valve lesions. Serum samples were collected from 82 patients with severe AS and from 12 control subjects. Aortic valves were obtained from a subpopulation of 21 AS patients undergoing valve surgery and from 10 controls. Serum and valvular total cholesterol and noncholesterol sterols were measured by gas-liquid chromatography. Noncholesterol sterols, including both cholesterol precursors and sterols reflecting cholesterol absorption, were detected in serum samples and aortic valves. The higher the ratios to cholesterol of the cholesterol precursors and absorption markers in serum, the higher their ratios in the stenotic aortic valves (r=0.74, P<0.001 for lathosterol and r=0.88, P<0.001 for campesterol). The valvular ratio to cholesterol of lathosterol correlated negatively with the aortic valve area (r= -0.47, P=0.045), suggesting attenuation of cholesterol synthesis with increasing severity of AS. The higher the absorption of cholesterol, the higher the plant sterol contents in stenotic aortic valves. These findings suggest that local accumulation of plant sterols and cholesterol precursors may participate in the pathobiology of aortic valve disease.     

A new on-line dual enzymatic method for simultaneous quantification of cholesterol and triglycerides in lipoproteins by HPLC

We describe an on-line dual detection method using HPLC for lipoprotein analysis that allows simultaneous determination of cholesterol and triglyceride profiles from a single injection of sample. Two different gel permeation columns, TSKgel LipopropakXL and Superose 6HR, were applied to the dual detection system, evaluating analytical performance of the proposed method and the columns by analyzing serum samples from human and nonhuman subjects. Both TSK and Superose columns produced good within-day imprecision values less than 4.7% for cholesterol and 4.2% for triglyceride determination. Linear regression analysis showed the results from the Superose column (y) correlated well with those from the TSK column (x): y = 0.969x + 5.44 (r = 0.990) for total cholesterol (mg/dl), y = 1.08x - 11.14 (r = 0.985) for total triglycerides (mg/dl), and y = 1.093x - 0.06 (r = 0.978) for the ratios of triglycerides to cholesterol (mg/mg). Furthermore, the cholesterol and triglyceride profiles elucidated the differences in the resolution ability of the columns, which have not been apparent from a single lipid profile. We conclude that the dual detection concept with proper choice of column and enzymic reagents specific to the objectives of the particular study can facilitate studies of lipoprotein metabolism.     

Determination of picropodophyllin and its isomer podophyllotoxin in human serum samples with electrospray ionization of hexylamine adducts by liquid chromatography-tandem mass spectrometry

A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for determination of the new anticancer agent picropodophyllin (AXL1717) and its isomer podophyllotoxin levels in human serum has been developed. Monitoring of hexylamine adducts rather than proton adducts was used to optimize sensitivity. The chromatography system was an Acquity BEH C18, 2.1 mm × 50 mm 1.7 μm column with gradient elution (mobile phase A: 2.5 mM hexylamine and 5 mM formic acid in Milli-Q water and mobile phase B: methanol). The retention times were 1.4 min for picropodophyllin, 1.5 min for podophyllotoxin and 1.9 min for internal standard deoxypodophyllotoxin. The isomers were base-line separated. The analytes were detected after electrospray ionization in positive mode with selected reaction monitoring (SRM) with ion transitions m/z 516→102 for picropodophyllin and podophyllotoxin and m/z 500→102 for internal standard. The sample preparation was protein precipitation with acetonitrile (1:3) containing internal standard followed by dilution of the supernatant with mobile phase A (1:1). The limit of quantification (LOQ) was 0.01 μmol/L for picropodophyllin and podophyllotoxin. The limit of detection (LOD) at 3 times the signal to noise (S/N) was estimated below 0.001 μmol/L for picropodophyllin and podophyllotoxin. The quantification range of the method was between 0.01 μmol/L and 5 μmol/L for both isomers. The accuracy was within ±15% of the theoretical value for both picropodophyllin and podophyllotoxin and inter-assay precision did not exceed ±15%, except for the 0.016 μmol/L level of podophyllotoxin, which was 18%. The selectivity of the method was verified by analysis of two different product ions for each analyte and by analysis for interference of seven different batches of blank human serum. The combined recovery and matrix effects were about 83% for picropodophyllin and podophyllotoxin. The new LC-MS/MS method showed sufficient sensitivity and selectivity for determination of picropodophyllin and its isomer podophyllotoxin levels in human serum from subjects receiving therapeutic doses of AXL1717.     

The effect of alcohol on zinc absorption

Two methods of intestinal perfusion are described and used to study the effecs of alcohol on zinc absorption in the rat small intestine. The first method used perfusion of the lumen of the rat small intestinein situ without interruption of the vascular supply. During perfusion with a zinc-containing medium (with and without alcohol), alcohol was found to have no effect on net zinc uptake from the lumen of the intestine. However, there were significantly higher serum zinc concentrations recorded in the rats perfused wih the zinc and alcohol, 28.8 μmol/L, when compared with a group perfused without alcohol, 19.1 μmol/L (P < 0.01). The second method used simultaneous perfusion of the lumen of the rat small intestine, with constant-rate perfusion of the vascular bed with an artificial blood supply. In this experiment with a zinc-containing medium, with and without alcohol, there was no difference noted in zinc absorption from the lumen of the intestine, or release into the artificial blood supply. Therefore, in conclusion, alcohol does not appear to directly influence zinc absorption by the mucosal cells of the small intestine.     

Chemiluminescent measurement of oxalate in serum by detection of hydrogen peroxide generated through oxalate oxidase

Today, chemiluminescence detection reactions have become popular in analytical biochemistry essentially due to their high sensitivity. A chemiluminescent synthetic system (luminol/porphyrin) was successfully used to measure serum oxalate by determination of hydrogen peroxide generated through oxalate oxidase (EC 1.2.3.4.). This new method is efficient and simple, highly sensitive and the results obtained in normal adult subjects are in good agreement with those of approved methods. This original application of such a chemiluminescent system allowed us to achieve a sensitive serum oxalate assay (detection limit of 0.2 μmol/L) characterized by a low serum volume (200 μL) required for analysis. © 1997 John Wiley & Sons, Ltd.     

Insulin resistance is associated with increased cholesterol synthesis and decreased cholesterol absorption in normoglycemic men

Type 2 diabetes has been associated with high synthesis and low absorption of cholesterol independent of weight, indicating that insulin resistance may be a link between glucose and cholesterol metabolism. Therefore, we investigated the relationship of serum cholesterol precursors, reflecting cholesterol synthesis, and serum plant sterols and cholestanol, reflecting cholesterol absorption efficiency, with insulin sensitivity measured with the hyperinsulinemic euglycemic clamp in 72 healthy normoglycemic men. Men in the most insulin-resistant tertile had higher serum cholesterol precursor ratios (P < 0.05), whereas no significant differences in serum absorption sterols were observed. In bivariate analysis, cholesterol synthesis markers correlated with fasting insulin (r = 0.36-0.46, P < 0.01) and the rates of insulin-stimulated whole-body glucose uptake (WBGU; r = -0.37-0.40, P < 0.01). Also, cholesterol absorption markers correlated with fasting insulin and WBGU (P < 0.05). Fasting insulin correlated with desmosterol (r = 0.286, P = 0.015) and lathosterol (r = 0.248, P = 0.037) even when the rates of WBGU and body mass index (BMI) were controlled for. We conclude that insulin resistance is linked to high cholesterol synthesis and decreased cholesterol absorption. Because fasting insulin correlated with cholesterol synthesis independent of the rates of BMI and WBGU, it is possible that regulation of cholesterol synthesis by hyperinsulinemia may be a link between insulin resistance and cholesterol metabolism.     

High levels of plant sterols and cholesterol precursors in cerebrotendinous xanthomatosis

We measured the cholestanol, cholesterol precursor (lathosterol), and plant sterol (campesterol and sitosterol) concentrations of serum and bile in 11 patients with cerebrotendinous xanthomatosis. The mean values of serum cholestanol, lathosterol, campesterol, and sitosterol were, respectively, 8.4-, 2.5-, 2.7-, and 1.4-times higher in the patients than in normal control subjects (n = 26). Cholestanol (6.7-fold) and campesterol (3.7-fold) levels in bile (n = 4) were also elevated in the patients. There was no significant difference of serum sterol levels between patients with coronary artery disease and those without it. Chenodeoxycholic acid treatment for periods ranging from 6 months to 3 years and 4 months lowered serum lathosterol (57.7% reduction) and campesterol (57.8%) levels in parallel with cholestanol (70.8%) level, but the sitosterol level (19.7%) decreased less. Thus, increased levels of cholesterol precursor (lathosterol), plant sterols (campesterol and sitosterol), and cholestanol were found in the serum and bile in cerebrotendinous xanthomatosis. Chenodeoxycholic acid treatment effectively reduced the levels of these sterols, except for sitosterol.