Serum unconjugated bile acids in patients with small bowel bacterial overgrowth

Concentrations of total and unconjugated bile acids in serum were measured fasting and 2 h postprandially in 9 patients with a positive [14C]glycocholate breath test consistent with small bowel bacterial overgrowth and in 13 controls. Gas-liquid chromatography-mass spectrometry (GLC-MS) and enzymatic-fluorometric assays were both used. In contrast to previous work, total serum bile acids were only occasionally elevated in patients with bacterial overgrowth. Total 2 h postprandial unconjugated bile acids, however, were elevated in 7/9 patients when measured by GLC-MS and in 6/9 when measured by the enzymatic-fluorometric method. The best separation between patients and controls was achieved by GLC-MS determinations of 2 h postprandial unconjugated cholic acid or primary bile acids, which were abnormal in 8/9 patients. This study indicates that measurement of serum bile acids may be a useful approach to the diagnosis of bacterial overgrowth, but would require accessible methods for separating and measuring cholic acid or unconjugated primary bile acids in post-prandial sera.     

Serum concentrations of unconjugated and conjugated cholic acid in portal venous and systemic venous blood of fasting man

The fasting concentrations of unconjugated and conjugated cholic acid were determined in the peripheral venous serum of 15 healthy subjects, eight patients with ileal resection and six patients with known bacterial overgrowth of the upper small intestine. In addition, the estimated hepatic uptake of unconjugated and conjugated cholic acid was determined in 15 gallstone patients undergoing cholecystectomy. A highly accurate and specific mass-fragmentographic technique with high sensitivity was used. The proportion of unconjugated cholic acid averaged 34% in the healthy subjects. The estimated fractional hepatic uptake of unconjugated cholic acid was lower than that of conjugated cholic acid, 71% and 87%, respectively (means). Patients with ileal resection had an increased proportion of unconjugated cholic acid in their peripheral venous serum, 49% (mean). The patients with bacterial overgrowth of the upper small intestine also displayed a high proportion of unconjugated cholic acid, 63% (mean). It is suggested that determination of the proportion of unconjugated cholic acid in peripheral venous blood may possibly be used for detection of bacterial contamination of the upper small intestine.     

Unconjugated serum bile acids as a marker of small intestinal bacterial overgrowth

Non-invasive methods to detect small intestinal bacterial overgrowth often lack specificity in patients who have undergone an ileal resection or have an accelerated intestinal transit. Since elevated serum unconjugated bile acid levels have been found in patients with clinical signs of bacterial overgrowth, we studied the clinical value of unconjugated serum bile acids as a marker of small intestinal bacterial overgrowth. Patients with culture-proven bacterial overgrowth had significantly elevated fasting unconjugated serum bile acid levels (median and range: 4.5; 1.4-21.5 mumol l-1) as compared to healthy subjects (0.9; 0.3-1.7 mumol l-1, P less than 0.005), to persons with an accelerated intestinal transit (1.0; 0.3-1.9 mumol l-1, P less than 0.005) and to persons who have undergone an ileal resection (2.1; 0.7-3.6 mumol l-1, P less than 0.005). The same was true 30 and 60 min after ingestion of a Lundh meal. Serum unconjugated bile acid levels above 4 mumol l-1 were found in eight of 10 patients with culture-proven small intestinal bacterial overgrowth whereas serum levels above 4 mumol l-1 were found in none of the patients from the three control groups. These results suggest that determination of unconjugated serum bile acids is of clinical value in the evaluation of patients suspected of small intestine bacterial overgrowth.     

IIeal dysfunction and bacterial overgrowth in patients with Crohn''s disease

The intestinal bile acid metabolism was studied in sixty-one patients with non-operated Crohn's disease (twenty-seven ileitis and thirty-four ileocolitis patients) by means of the 14C-glycocholate breath test with marker-corrected faecal analysis before and after a short course of antibiotics. The results of the combined breath and faecal analysis were compared with the data of other tests detecting bacterial overgrowth and ileal dysfunction. Fifteen of the sixty-one patients (25%) presented with a 14C excretion pattern consistent with bacterial overgrowth of the small bowel. Repetition of the combined breath and faecal analysis after antibiotic treatment revealed that concurrent ileal dysfunction was present in at least six of these fifteen patients. In twenty other patients elevated marker-corrected 14C faecal excretion indicated ileal dysfunction. Thus, the overall incidence of ileal dysfunction amounted to 26/61 (44%). The sensitivity of the bile acid breath test with marker-corrected stool analysis was comparable to that of aerobic and anaerobic jejunal cultures in twenty non-selected patients for the detection of bacterial overgrowth, and to that of chemical bile acid measurement in stools for the detection of ileal dysfunction. The bile acid breath test with faecal analysis was more sensitive than measurement of glycine-taurine ratio in bile (twenty patients) and the Schilling test.     

Clinical value of the bile acid breath test. Evaluation of the Mayo Clinic experience

The Mayo Clinic experience with more than 200 bile acid breath tests was analyzed retrospectively to assess its clinical value. In patients with suspected bacterial overgrowth, the result of the bile acid breath test was compared with that of culture of aspirates of small bowel, and the test was found to have a sensitivity of 0.70 and a specificity of 0.90 (1.0 highest possible value). Although in one-third of the patients with a positive small-bowel culture the bile acid breath test failed to demonstrate the presence of bacterial overgrowth, analysis of the data according to the Bayes theorem showed that, compared with a routine evaluation without a small-bowel culture, the availability of breath test results will double the probability with which the clinician can be certain about the presence or absence of bacterial overgrowth. The test result appeared to influence the diagnosis in 83% and the management in 74% of the 163 patients in whom it was performed because of suspected bacterial overgrowth. In patients with suspected malabsorption of bile acids, on the other hand, the test that was performed without determination of fecal bile acid excretion appeared to be rather insensitive, and only rarely was information gained that was not already known from a routine workup of the patient.     

The Interdigestive Motor Complex of Normal Subjects and Patients with Bacterial Overgrowth of the Small Intestine

Intraluminal pressures were measured in the gastric antrum and at different levels of the upper small intestine in 18 normal subjects to investigate whether or not the interdigestive motor complex, identified in several animal species, occurs in man and, if so, to determine its characteristics. In all normal subjects, the activity front of the interdigestive motor complex was readily identified as an uninterrupted burst of rhythmic contraction waves that progressed down the intestine and that was followed by a period of quiescence. Quantitative analysis of various parameters of the complex and simultaneous radiological and manometrical observations revealed that it resembled closely the canine interdigestive motor complex. To test the hypothesis that disorders of this motor complex may lead to bacterial overgrowth in the small intestine, similar studies were performed in 18 patients with a positive ¹⁴CO₂ bile acid breath test and in an additional control group of 9 patients with a normal ¹⁴CO₂ breath test. All but five patients had normal interdigestive motor complexes. The five patients in whom the motor complex was absent or greatly disordered had bacterial overgrowth as evidenced by ¹⁴CO₂ bile acid breath tests before and after antibiotics. These studies establish the presence and define the characteristics of the normal interdigestive motor complex in man. They also suggest that bacterial overgrowth may be due to a specific motility disorder i.e., complete or almost complete absence of the interdigestive motor complex.     

Rate of synthesis of albumin in relation to serum levels of essential amino acids in patients with bacterial overgrowth in the small bowel

Summary. Bacterial overgrowth in the small bowel has been recognised in 11 patients with the aid of the breath-test with [glyco-1-¹⁴C] cholic acid and by the determination of the amount of bacteria in the jejunal juice. In all but one patient hypoalbuminaemia, from 21.9 to 42.9 g/1, was observed. This low level of serum albumin can be due to an excessive intestinal protein-loss or to a decreased rate of synthesis of albumin as the result of an insufficient delivery of amino acids to the liver. In 11 patients with bacterial overgrowth the rate of synthesis of albumin has been determined by the ¹⁴C-carbonate method. Compared to a control group the rate of albumin synthesis and the serum level of valine, leucine, lysine and tryptophan were significantly decreased in the patients with bacterial overgrowth. A positive correlation was found between the rate of albumin synthesis and the serum levels of valine, isoleucine, leucine and tryptophan. When the serum levels of these 4 essential amino acids were low, the rate of albumin synthesis was depressed.     

Rate of Synthesis of Albumin in Relation to Serum Levels of Essential Amino Acids in Patients with Bacterial Overgrowth in the Small Bowel

Summary. Bacterial overgrowth in the small bowel has been recognised in 11 patients with the aid of the breath-test with [glyco-l-"C] cholic acid and by the determination of the amount of bacteria in the jejunal juice. In all but one patient hypoalbuminaemia, from 21.9 to 42.9 g/1, was observed. This low level of serum albumin can be due to an excessive intestinal protein-loss or to a decreased rate of synthesis of albumin as the result of an insufficient delivery of amino acids to the liver. In 11 patients with bacterial overgrowth the rate of synthesis of albumin has been determined by the ¹⁴C-carbonate method. Compared to a control group the rate of albumin synthesis and the serum level of valine, leucine, lysine and tryptophan were significantly decreased in the patients with bacterial overgrowth. A positive correlation was found between the rate of albumin synthesis and the serum levels of valine, isoleucine, leucine and tryptophan. When the serum levels of these 4 essential amino acids were low, the rate of albumin synthesis was depressed.     

Breath tests in the diagnosis of small intestine bacterial overgrowth

Analysis of breath specimens for volatile metabolites of orally administered substrates offers a simplified detection method for the presence of an abnormal small-intestinal flora. This technique is not only simpler and more acceptable to patients than jejunal aspiration, but also gives quicker information to the clinician than microbiologic culture of the jejunal aspirate. Experience with a probe which is usually completely absorbed before the colon is reached (1 g 14C-xylose) has demonstrated better test sensitivity (separating normal from abnormal) and test specificity (separating bacterial overgrowth from small-bowel malabsorption) than that seen with a probe which normally has substantial passage of substrate to the colonic bacteria (as seen with the 14C-bile acid breath test). Ongoing evaluation of nonradioactive probes (H2 generation from fermentable carbohydrate, 13CO2 generation from 13C-labeled substrate similar to the principle of the 14C-xylose breath test) offers promise for use of bacterial overgrowth breath tests in children and reproductive-age females.     

Serum unconjugated bile acids: qualitative and quantitative profiles in ileal resection and bacterial overgrowth

Qualitative and quantitative profiles of unconjugated bile acids in the serum obtained over a 24-h period from three patients with ileal resections and one with a bacterial overgrowth are described. Unconjugated serum bile acids were determined using the high sensitivity and resolution of capillary column gas liquid chromatography after their rapid extraction and isolation using reverse phase octadecylsilane bonded silica cartridges and the lipophilic gel Lipidex 1000. Unconjugated serum bile acid concentrations were elevated throughout the day in both ileum resected patients and in conditions involving bacterial overgrowth when compared to healthy subjects. Total conjugated cholic acid concentrations were expectedly low in both intestinal disorders and were without the postprandial increases generally observed in healthy subjects. Qualitative gas chromatographic profiles of serum unconjugated bile acids in bacterial overgrowth distinctly revealed a predominance of deoxycholic acid and other secondary bile acids in all samples, while, in conditions of an impaired enterohepatic circulation, deoxycholic acid was absent or present in only trace amounts. The potential significance of measuring serum unconjugated bile acids in intestinal disorders is discussed.     

Quantitative studies of the delivery of hepatic-synthesized bilirubin to plasma utilizing δ-aminolevulinic acid-4-14C and bilirubin-3H in man

After the simultaneous intravenous administration of unconjugated bilirubin-(3)H and delta-aminolevulinic acid-4-(14)C, the plasma disappearance curves of unconjugated bilirubin-(3)H and the plasma appearance curves of biosynthesized unconjugated bilirubin-(14)C have been defined in seven patients, three of whom had acute intermittent porphyria (AIP). The incorporation of (14)C into plasma unconjugated bilirubin, derived by an analysis which involves deconvolution of the two plasma curves, varied between 13.1 and 23.5% (mean 19.3%) of the injected dose in the nonporphyric patients and between 5.4 and 13.6% (mean 8.3%) of the injected dose in the porphyric patients. In five of the patients, the stercobilin-(14)C specific activity in a pooled specimen of feces was measured, enabling the following further values to be calculated: (a) the total (14)C radioactivity incorporated into bilirubin (21.0 and 25.3% [mean 23.2%] of the injected dose in two of the nonporphyric patients and between 8.5 and 25.3% [mean 14.2%] of the injected dose in the porphyric patients), and (b) the proportion of hepatic synthesized bilirubin delivered directly to plasma in the unconjugated form (between 0.520 and 0.904; mean for nonporphyric patients 0.712; mean for porphyric patients 0.614). The results demonstrate that a large proportion of bilirubin derived from hepatic hemes passes through the plasma in the unconjugated form before conjugation and secretion into bile.     

A new model to assess deoxycholic acid metabolism in health using stable isotope dilution technique

A model has been developed that permits calculation of the absorption rates of newly formed and deconjugated deoxycholic acid (DCA) from the intestine, the fractional absorption rate of deconjugated DCA and the daily rate of formation of DCA. The model is based on steady state conditions and isotopic equalities of conjugated DCA in blood and in the enterohepatic circulation, as well as between unconjugated DCA in blood and in the intestinal content. The model requires measurement of isotopic enrichment in the conjugated and unconjugated fractions of DCA in serum after administration of an isotopic label. The measurements were carried out in seven healthy volunteers using capillary gas chromatography/mass spectrometry after oral administration of 24-13C-DCA. Intestinal absorption of deconjugated DCA exceeded that of newly formed DCA: (mean +/- SD) 7.4 +/- 5.6 vs. 4.5 +/- 2.1 mumol kg-1 d-1. Total absorption of unconjugated DCA (11.9 +/- 6.9 mumol kg-1 d-1) accounted for approximately 6% of estimated total intestinal DCA absorption. The fractional absorption rate of unconjugated DCA in the intestine averaged 55.5 +/- 15.1%; 8.2 +/- 3.3 mumol kg-1 d-1 DCA were formed daily by 7 alpha-dehydroxylation of cholic acid. This rate of DCA formation compares well with values for fecal DCA excretion (15 mumol kg-1 d-1) and cholic acid synthesis rate (11.9 mumol kg-1 d-1) obtained in comparable controls by the same laboratory.(ABSTRACT TRUNCATED AT 250 WORDS)     

The [14C]-triolein breath test is not valid as a test of fat absorption.

The [14C]-triolein breath test is used as a test of fat absorption. However, its validity has not been established. The aim of this study was to investigate, whether the absorption of [14C]-triolein could be estimated from the breath test, and whether the breath test could be useful as a clinical test. The [14C]-triolein absorption was estimated from faecal measurements, using 51CrCl3 as non-absorbable marker. The breath test was done according to the standard technique with hourly estimations of the 14CO2 expiration. Fifty-one patients participated. A nearly perpendicular, curvilinear relation between the 6-h cumulative 14CO2 expiration and the [14C]-triolein absorption was found, and no obvious cut-off level for normal 14CO2 expiration could be identified. Accordingly, the diagnostic sensitivity of the breath test was 80% at the expense of a specificity of 45%. In 19 patients duplicate measurements were done. A high intra- and inter-individual variation in the fraction of absorbed [14C]-triolein, expired within 6 h, was found. It is concluded that expiration of 14CO2 is influenced by factors other than the absorption of [14C]-triolein, and that the [14C]-triolein breath test is not useful as test of fat absorption.     

肝硬化失代偿期患者病因及分级与小肠细菌过度生长的关系研究

目的研究肝硬化失代偿期患者肝硬化病因及肝硬化分级与小肠细菌过度生长的关系。方法选取2018年1月至2019年1月洪湖市中医医院收治的178例肝硬化失代偿期患者(Child-Pugh分级B级98例,C级80例)作为观察组,120例肝纤维化患者作为肝纤维化组,另选择同期50例体检健康者作为对照组。将观察组分为小肠细菌过度生长阳性组与阴性组。采用乳果糖氢呼气试验(LHBT)检测被研究者小肠细菌过度生长情况,分析肝硬化失代偿期患者肝硬化病因及肝硬化分级与小肠细菌过度生长的关系。结果观察组小肠细菌过度生长阳性率及LHBT集值均高于肝纤维化组,差异有统计学意义(P<0.05);肝纤维化组小肠细菌过度生长阳性率及LHBT集值均高于对照组,差异有统计学意义(P<0.05)。Child-Pugh分级C级肝硬化患者小肠细菌过度生长阳性率及LHBT集值均高于B级患者,差异有统计学意义(P<0.05)。K-M生存曲线结果显示,小肠细菌过度生长阳性组患者3年生存率为40.5%,小肠细菌过度生长阴性组患者3年生存率为79.8%,两组生存情况差异有统计意义(χ2=3.146,P=0.016)。受试者工作特征曲线分析结果显示,LHBT集值超过101 ppm时,其诊断肝硬化失代偿期的价值最高,曲线下面积为0.76(95%CI=0.704~0.826),诊断灵敏度、特异度分别为89.9%和65.8%。结论肝硬化失代偿期患者小肠细菌过度生长发生率高,且随着肝功能分级的升高,小肠细菌过度生长发生风险升高。小肠细菌过度生长可能促进肝硬化失代偿期病情发展。     

The aminopyrine breath test, an inadequate early indicator of methotrexate-induced liver disease in patients with psoriasis

The aminopyrine breath test has been shown to be a sensitive noninvasive indicator of liver cell dysfunction. In a search for a noninvasive method of monitoring the effects of methotrexate therapy, we have investigated the use of the aminopyrine breath test in patients receiving methotrexate for the treatment of severe psoriasis. The [14C]-aminopyrine breath test was performed in 20 normal control subjects, 32 patients with psoriasis receiving methotrexate therapy, and 8 patients with histologically confirmed cirrhosis of differing etiology. Eighteen patients on methotrexate had liver biopsies classified as grade I changes, 6 patients as grade II, and 8 patients as grade III. The normal value for the breath test was 11.0 +/- 1.6% (mean +/- 1 SD). The mean [14C]-CO2 excretion (8.3 +/- 4.4%) of the 8 patients with grade III liver disease was significantly different from the control subjects (p less than 0.02), and those with grade I liver changes (p less than 0.04). The aminopyrine breath test was only able to detect the later severe stages of methotrexate hepatotoxicity, grade III, when fibrosis occurs, before established cirrhosis was present. Our data suggests that the aminopyrine breath test is not a sensitive indicator for the detection of early methotrexate-induced hepatotoxicity, (stages I and II), but will detect the precirrhotic stage III change. Consequently, we recommend that a liver biopsy should be performed annually in all psoriatic patients receiving methotrexate, to detect histological damage, especially when the aminopyrine breath test score falls below the 95% confidence limits of normal.     

Metabolism of steroid and amino acid moieties of conjugated bile acids in man: II. Glycine-conjugated dihydroxy bile acids

Chenodeoxycholyl-2,4-(3)H-glycine-1-(14)C and deoxycholyl-2,4-(3)H-glycine-1-(14)C were synthesized and administered orally to 10 healthy subjects. Distribution of radioactivity among bile acids and specific activity of steroid and amino acid moieties were determined in bile samples. (3)H and (14)C were measured in feces. (14)C in breath was calculated from interval (14)CO(2) specific activity determinations.The daily fractional turnover of the glycine moiety of chenodeoxycholyl and deoxycholylglycines was more than three times that of the steroid moiety. Pool size of chenodeoxycholylglycine was about twice that of deoxycholylglycine, but similar fractional turnover rates of steroid and amino acid moieties suggested that intestinal absorption of the two conjugated bile acids was equally efficient (about 95%). The amount of unlabeled deoxycholic acid (newly formed by bacterial 7alpha-dehydroxylation) absorbed from the intestine approximated 30% of the cholic acid that was lost. (3)H radioactivity remained predominantly in administered bile acid implying that, normally, secondary bile acids derived from chenodeoxycholic acid are not appreciably absorbed from the intestine and that deoxycholic acid is not hydroxylated by the liver.Approximately 25% of administered (14)C was recovered in the breath in the first 24 hr and less than 8% in the feces in 8 days; (14)CO(2) excretion correlated highly with fractional turnover of the glycine moiety. (3)H appeared predominantly in feces, and the rate of excretion correlated highly with the fractional turnover of the steroid moiety of bile acids. From the results in this paper plus previous measurements on the metabolism of cholylglycine, we calculated that about 6 mmoles/day of glycine is used for bile acid conjugation in health.     

Effects of cholecystectomy on the kinetics of primary and secondary bile acids.

Removal of the gallbladder is thought to increase formation and pool size of secondary bile acids, mainly deoxycholic acid (DCA), by increased exposure of primary bile acids (cholic acid [CA], chenodeoxycholic acid [CDCA]) to bacterial dehydroxylation in the intestine. We have tested this hypothesis by simultaneous determination of pool size and turnover of DCA, CA, and CDCA in nine women before and at various intervals after removal of a functioning gallbladder. An isotope dilution technique using marker bile acids labeled with stable isotopes (2H4-DCA, 13C-CA, 13C-CDCA) was used. After cholecystectomy, concentration and output of bile acids relative to bilirubin increased (P less than 0.02) in fasting duodenal bile and cholesterol saturation decreased by 27% (P less than 0.05) consistent with enhanced enterohepatic cycling of bile acids. Three months after removal of the gallbladder bile acid kinetics were in a new steady state: pool size and turnover of CDCA were unchanged. Synthesis of CA, the precursor of DCA, was diminished by 37% (P = 0.05), probably resulting from feedback inhibition by continuous transhepatic flux of bile acids. The fraction of CA transferred after 7 alpha-dehydroxylation to the DCA pool increased from 46 +/- 16 to 66 +/- 32% (P less than 0.05). However, this enhanced transfer did not lead to increased input or size of the DCA pool, because synthesis of the precursor CA had decreased.     

Absorption of 13C-labeled stearic, oleic, and linoleic acids in humans: application to breath tests

Intestinal absorption of ingested [1-13C]stearic, [1-13C]oleic, and [1-13C]linoleic acid was compared in six healthy men. A bolus of each [1-13C]-labeled fatty acid was ingested in random order at 72-hour intervals with the breakfast meal. Subjects consumed fixed diets during a 9-day fecal collection period. Pooled 9-day fecal samples were homogenized and total fat extracted. Fat extracts were saponified and methylated, and individual fatty acids were quantitated by gas-liquid chromatography. Preparative high-performance liquid chromatography was used to obtain fractions containing stearic, oleic, and linoleic acid for combustion to CO2 and assay of 13C enrichment over background. Prelabel period 24-hour samples were treated similarly to measure background 13C abundance. Total fatty acid and stearic, oleic, and linoleic acid excretion (+/- SEM) in the six volunteers over the 9-day period was 41.5 +/- 7.3, 10.0 +/- 1.3, 8.8 +/- 2.9, and 0.8 +/- 0.1 mg/day/kg body weight, respectively. The absorption efficiency for [1-13C]stearic, [1-13C]oleic, and [1-13C]linoleic acid was 78.0% +/- 4.5%, 97.2% +/- 1.7%, and 99.9% +/- 0.1%, respectively. The reduced absorption of [1-13C]stearic acid observed emphasizes the importance of correcting breath test oxidation data for fecal loss of 13C substrate. The potential application of our method to other areas of intermediary metabolism is discussed.     

Effect of cholestyramine on bile acid metabolism in normal man

The effect of cholestyramine administration on the enterohepatic circulation of bile acids was studied in eight normal volunteers. In six subjects the metabolism of sodium taurocholate-(14)C was determined after its intravenous injection before and during the 6th wk of cholestyramine administration, 16 g/day. In two subjects, the metabolism of cholic acid-(14)C was observed before and during the 2nd wk of cholestyramine, 16 g/day. Bile acid sequestration resulted in a more rapid disappearance of the injected primary bile acid and its metabolic products. The composition of fasting bile acids was promptly altered by cholestyramine to predominantly glycine-conjugated trihydroxy bile acid. In four subjects, unconjugated bile acid-(14)C was administered during cholestyramine administration; the relative proportion of glycine-conjugated bile acid-(14)C before enterohepatic circulation was similar to the relative proportion of unlabeled glycine-conjugated bile acid present in duodenal contents after an overnight fast, indicating that a hepatic mechanism was responsible for the elevated ratios of glycine- to taurine-conjugated bile acid (G: T ratios) observed. The relative proportions of both dihydroxy bile acids, chenodeoxycholic and deoxycholic, were significantly reduced. Steatorrhea did not occur, and the total bile acid pool size determined after an overnight fast was unaltered by cholestyramine. These findings suggest that in normal man bile acid sequestered from the enterohepatic circulation by cholestyramine is replaced by an increase in hepatic synthesis primarily via the pathway leading to production of glycocholic acid.     

Bile Acid Kinetics in Relation to Sex, Serum Lipids, Body Weights, and Gallbladder Disease in Patients with Various Types of Hyperlipoproteinemia

Bile acid kinetics were determined in 15 normolipidemic and 61 hyperlipidemic subjects with the aid of [(14)C]cholic acid and [(3)H]chenodeoxycholic acid. The diet was standardized and of natural type. The total bile acid formation was within normal limits in patients with hyperlipoproteinemia types IIa and IIb. On the average the production of cholic acid (C) represented less than 50% of the total bile acid synthesis in both groups. The corresponding value recorded for the controls was 64+/-2% (mean+/-SEM). The synthesis of C in hyperlipoproteinemia type IIa was significantly below normal. Of the 27 patients with the type IV pattern, 18 had a synthesis of C and C + chenodeoxycholic acid (CD) that exceeded the upper range recorded for the controls. In these subjects the C formation represented 73+/-3% of the total bile acid synthesis. Similar findings were also encountered in the five patients with the type V lipoprotein pattern studied. The bile acid pool size of the 11 patients with hyperlipoproteinemia type IV, who had been cholecystectomized or suffered from cholelithiasis, was 900 mg smaller on the average than that of the other subjects with the same type of hyperlipoproteinemia. However, the pool size in the former subjects still tended to be higher than that of the control subjects without evidence of gallbladder "disease". In all groups of subjects the formation of bile acids tended to be higher in the male than in the female subjects. Bile acid synthesis showed no linear correlation to actual body weight, relative body weight, or body surface area. A moderate weight reduction in five patients (one with type IIb and four with type IV pattern) was followed by a 50% reduction of the C and CD synthesis.