Biliary lipid composition in patients with cholesterol and pigment gallstones and gallstone-free subjects: deoxycholic acid does not contribute to formation of cholesterol gallstones

BACKGROUND: Four main disturbances have been attributed to cholesterol gallstone disease: hypersecretion of cholesterol from the liver with cholesterol supersaturation in bile; disturbed motility with defective absorption and secretion by the gallbladder; increased crystallisation of cholesterol in the gallbladder bile; and slow intestinal transit with increased amount of deoxycholic acid in the bile acid pool. We aimed to evaluate the biliary lipid composition in a large series of gallstone patients, with emphasis on the amount of deoxycholic acid and with respect to number of stones, compared to gallstone free subjects. MATERIALS AND METHODS: Bile was sampled during operations through puncture of the gallbladder from 145 cholesterol gallstone patients, 23 patients with pigment stones and 87 gallstone free patients undergoing cholecystectomy. Biliary lipid composition, cholesterol saturation, bile acid composition, nucleation time and cholesterol crystals were analysed. RESULTS: The patients with cholesterol gallstones showed higher molar percentage of cholesterol, lower total biliary lipid concentration, higher cholesterol saturation, shorter nucleation time and higher proportion of crystals in bile than the other groups. The nucleation time was significantly shorter in multiple cholesterol gallstone patients, but this was not due to higher cholesterol saturation. Male cholesterol gallstone patients showed higher cholesterol levels, lower total biliary lipid concentration, and higher cholesterol saturation in bile than female patients. There was no difference in biliary content of deoxycholic acid, but significantly lower content of cholic acid in gallstone patients compared to gallstone free patients. CONCLUSIONS: We conclude that deoxycholic acid does not contribute to gallstone formation in cholesterol gallstone patients. The short nucleation time in patients with multiple cholesterol stones is not due to higher cholesterol saturation.     

Simulation of the metabolism and enterohepatic circulation of endogenous chenodeoxycholic acid in man using a physiological pharmacokinetic model

The metabolism and enterohepatic circulation of chenodeoxycholic acid (CDC), a major primary bile acid in man, has been stimulated using a multicompartmental physiological pharmacokinetic model which was previously reported and used to simulate the metabolism of cholic acid. The model features compartments and linear transfer coefficients. Compartments, which are defined as the pools of single chemical species in well defined anatomical volumes, are aggregated into nine 'spaces' based on anatomical and physiological considerations (liver, gall-bladder, bile ducts, duodeno-jejunum, ileum, colon, portal blood, sinusoidal blood, and general circulation). Each space contains several compartments which correspond to the compounds present in that space, for example, the compound in question and its biotransformation products. For CDC (as for cholic acid in the previous simulation) each space contains three compartments corresponding to the unconjugated bile acid, its glycine amidate, and its taurine amidate. Transfer coefficients, which denote the fractional amount of the compartment's contents exiting per unit time, are categorized according to function: flow, for example gall-bladder contraction (which involves transfer of all substances contained in the space at the same fractional rate); biotransformation (which transfers the substrate from one compartment to another within the same space); or transport (which denotes movements between contiguous compartments, belonging to different spaces across a diffusion membrane or a cellular barrier). The model is made time-dependent by incorporating meals which trigger gall-bladder emptying and modify intestinal flow. The transfer coefficients in the cholic acid model were modified for the CDC model since there is indirect evidence that CDC amidates (probably chenodeoxycholylglycine) are absorbed from the duodeno-jejunum and the first pass hepatic clearance of CDC species differs from that of cholyl species. The model was then used with all existing experimental data to simulate CDC metabolism in healthy humans over a 24-h period during which three meals were ingested. Satisfactory agreement was obtained between simulated and experimental data indicating that this model continues to be useful for describing the metabolism of bile acids and may also be of value for describing the metabolism of drugs whose metabolism is similar to that of bile acids.     

Age dependent differences in human bile acid metabolism and 7 alpha-dehydroxylation

Abstract. It has been suggested that transformation of secondary bile acids into (co)carcinogenic compounds may have a role in the development of cancer of the large bowel. Because of age dependent differences of this disease we undertook a study of cholic and deoxycholic acid metabolism of eleven young adults (group A, 20–30 years old) and eleven elderly persons (group B, 55–75 years old) with a double isotope dilution method. Daily food intake was standardized individually and gut transit time measured with radio-opaque pellets and labelled chromium chloride.
The 7α-dehydroxylation fractions (the ratio of deoxycholic acid input rate from the large bowel to cholic acid synthesis rate) were higher in group B ( P < 0.01) due to higher deoxycholic acid input rates ( P < 0.005), especially when individuals from both groups with rapid gut transit were compared. As contributory factor was recognized the higher fractional turnover rate of cholic acid in group B. Pool sizes and synthesis rates of cholic acid and gut transit times were similar. In group A, but not in B, gut transit times correlated with deoxycholic acid input rates ( P <0.01).
The differences in bile acid metabolism may be related to a more effective colonic absorption of deoxycholic acid in the elderly persons with a concomitant decrease of active ileal absorption of cholic acid in the elderly persons. Differences in diet or gut transit time between both groups do not seem to be the underlying mechanism.     

Serum lipids, biliary lipid composition, and bile acid metabolism in vegetarians as compared to normal controls

Since dietary factors have been implicated in various diseases, such as coronary heart disease, gallstone formation and colonic cancer, possibly by affecting cholesterol and bile acid metabolism, we studied serum lipid levels, biliary lipid composition, cholic acid and deoxycholic acid kinetics in a group of young healthy male vegetarians and in age, sex and weight matched control subjects. Daily intake of nutrients was higher with respect to polyunsaturated fatty acids, carbohydrates and dietary fibre in the vegetarian group. Although mean serum lipid levels in the vegetarian were 8-28% lower than in the control subjects, differences were not statistically significant. Biliary lipid and biliary bile acid composition were similar in both groups. Bile acid kinetics, measured after simultaneous injection of [3H]cholic acid and [14C]deoxycholic acid, showed a slightly lower output of cholic acid and a slightly higher input of deoxycholic acid in the vegetarians, this causing a significantly (P less than 0.025) higher 7 alpha-dehydroxylation fraction (input deoxycholic acid divided by synthesis of cholic acid) in the vegetarians. Our results in young males suggest that bile acid conservation is associated with a vegetarian diet, but do not support the supposition that a vegetarian diet reduces deoxycholate formation.     

Effects of a standardized wheat bran preparation on biliary lipid composition and bile acid metabolism in young healthy males

The effects of adding bran to the normal diet on biliary lipid composition and bile acid metabolism in a group of young healthy males was studied. A chemically standardized coarse wheat bran product, with serum lipid lowering properties, in a dose of 0.5 kg-1 body weight per day was used. Bran feeding for 4 or 8 weeks did not change biliary lipid and biliary bile acid composition. Faecal bile acid and neutral sterol composition was similar before and after 8 weeks of bran. Bile acid kinetics, measured by double isotope dilution after simultaneous injection of [3H]cholic acid and [14C]deoxycholic acid, showed only minor differences before and during bran ingestion. The most surprising finding was an increase in 7 alpha-dehydroxylation fraction (input of deoxycholic acid divided by synthesis of cholic acid) in six out of seven subjects after 4 weeks of brain and in all four subjects after 8 weeks of bran. In conclusion, the bran product we used is not effective in lowering the biliary cholesterol saturation in healthy young males. Nor does it reduce deoxycholate input in our subjects even after 8 weeks of bran.     

Sex differences in salicylic acid metabolism in streptozotocin induced diabetes in rats

The metabolism of salicylic acid was studied in male and female streptozotocin-induced diabetic Wistar rats. Results obtained showed that in both sexes there was a significant increase in urinary excretion of salicyluric acid in diabetic rats when compared to controls (P less than or equal to 0.001). Within the diabetic groups, there was a significant increase in the urinary excretion of salicyluric acid in the female in comparison to the male rats (P less than or equal to 0.01). A statistically significant increase was observed in urinary excretion of salicyl-glucuronic acid in diabetic female compared to control female rats (P less than or equal to 0.01) while comparison of diabetic male to control male showed a significant decrease in urinary excretion of salicyl-glucuronic acid (P less than or equal to 0.01). Comparison of the diabetic female and male groups showed a high statistically significant difference in urinary excretion of salicyl-glucuronic acid. The diabetic ration, ie diabetic/control was significantly higher in female than in male rats with respect to salicyl-glucuronic acid (P less than or equal to 0.001) and total urinary excretion (P less than or equal to 0.01). The diabetic ratio may likely reflect the true significance of the roles played by the two metabolic pathways. The results suggest sex differences in the metabolism of salicylic acid; this may also be the case in other disease states.     

胆腑舒胶囊对实验性胆囊结石胆汁卵磷脂、总胆汁酸、粘蛋白及血清脂代谢的影响

目的 :观察胆腑舒胶囊对家兔实验性胆固醇结石的溶石作用及机制。方法 :血清脂代谢指标在全自动生化仪上完成。胆汁中总胆固醇 (TC)、总胆汁酸分别用硫磷铁法、磷钼酸比色法测定。胆汁中卵磷脂、粘蛋白分别运用硝化磷钼酸氨萘磺酸法、磷钨酸沉淀酚试剂法测定。结果 :胆腑舒胶囊可有效地降低血清 TC、甘油三酯 (TG)、低密度脂蛋白胆固醇 (L DL C)及胆汁中胆固醇、粘蛋白浓度 ,提高胆汁中总胆汁酸、卵磷脂含量。结论 :胆腑舒胶囊能较好地溶、排胆囊胆固醇结石 ,其机制与调节脂质代谢、改善致石性胆汁及纠正胆囊动力学等作用有关     

A stable model of respiratory distress by small injections of oleic acid in pigs

Objective Development of a stable model of respiratory distress in pigs with oleic acid, fulfilling clinical criteria of the adult respiratory distress syndrome (ARDS).Design Eight pigs (9.1±0.7 kg) were anesthetized with pentobarbital, paralyzed with tubocurarine and mechanically ventilated with an of 0.6, an IE ratio of 23 and a PEEP of 0.2 kPa. Oleic acid (dissolved 11 in 96% alcohol) was administered in a series of multiple injections of 0.1 ml until was lower than 8 kPa.Measurements and results Careful titration of the oleic acid injections on guidance of the established a reproducible respiratory distress ( =7.3±0.8 kPa), in which gas exchange and hemodynamic variables were stable for at least 4 h. The number of oleic acid injections (22±11, mean and SD) varied between the animals.Conclusions With the use of multiple injections of oleic acid, a stable model of early respiratory distress in pigs can be achieved, in spite of individual differences in sensitivity. Such a stable model allows for a diversity of studies on early respiratory distress.Prof. Dr. C.A. Wagenvoort died on November 23rd, 1995     

脂肪酸代谢在恶性肿瘤发生机制及分子影像中的应用

恶性肿瘤的增殖需要多种能量物质包括糖、脂肪和蛋白质。代谢重编程为恶性肿瘤提供能量,促进肿瘤的发生发展。沃伯格效应被认为是肿瘤代谢的主要方式,在这个过程中葡萄糖利用增加,为肿瘤代谢提供能量;利用此特性18F-FDG显像因能准确反应肿瘤生物学特征、位置、进展和对治疗的反应,PET等分子影像已广泛应用于肿瘤诊断和治疗并发挥不可替代作用。此外,肿瘤还需要脂肪酸代谢产物调控蛋白质翻译后修饰,提供脂质信号分子及膜磷脂以抵抗化疗药物的作用等。利用肿瘤细胞脂肪酸合成增加这一特性,放射性核素标记短链脂肪酸可用于肿瘤显像。本文对肿瘤脂肪酸代谢及其分子影像学相关研究做一综述。      

Bile acid content of gallbladder bile and stones in type lib and IV hyperlipoproteinemia

We examined the bile acid composition of gallbladder bile using reversed-phase high performance liquid chromatography (HPLC), in normolipemic and hyperlipidemic (types IIb and IV) patients with cholelithiasis and compared them with normal subjects. Similarly, bile acid composition was determined in the gallstones of these patients.No free bile acids were found in any of the samples examined. We observed that gallbladder bile and gallstones of patients with type IV hyperlipidemia showed a significant increase in the percentage of glyco-conjugated bile acids and reduction in taurine conjugates.Based on this finding we postulate that in addition to biliary lipid composition bile acid composition may also play a role in the pathogenesis of cholesterol gallstone formation.     

一种测定总胆红素的新方法

[目的]建立一种快速、简便、稳定、高灵敏度，适应于血清、血浆测定的总胆红素的新方法。[方法]用聚氧乙烯月桂醚（Brij-35）作为加速剂使结合胆红素与未结合胆红素同重氮对氨基苯磺酸反应，形成偶氮胆红素。[结果]本试剂测定中的总胆红素，在样品加入试剂后5min显色达到终点，显色后最少可稳定3h不退色，试剂空白与水接近。反应成色后最大吸收峰在510nm，线形范围可达324nmol／L，回收率97．2％-102；4％。批内变异系数（CV）为0．58％，与复星长征总胆红素试剂相关性良好。Y=0．976X＋0．862r=0．999P〉0．05。[结论]本方法测定总胆红素具有操作快速、简便，结果稳定等优点，适用于血清及血浆总胆红素的手工测定及自动化分析。     

Fatty acid metabolism assessed by 125I-iodophenyl 9-methylpentadecanoic acid (9MPA) and expression of fatty acid utilization enzymes in volume-overloaded hearts

BACKGROUND: The peroxisome proliferator-activated receptor (PPAR) alpha is a member of the nuclear receptor superfamily and regulates gene expression of fatty acid utilization enzymes. In cardiac hypertrophy and heart failure by pressure-overload, myocardial energy utilization reverts to the fetal pattern, and metabolic substrate switches from fatty acid to glucose. However, myocardial metabolism in volume-overloaded hearts has not been rigorously studied. The aim of the present study was to examine fatty acid metabolism and protein expressions of PPARalpha and fatty acid oxidation enzymes in volume-overloaded rabbit hearts. METHODS: Volume-overload was induced by carotid-jugular shunt formation. Sham-operated rabbits were used as control. Chronic volume-overload increased left ventricular weight and ventricular cavity size, and relative wall thickness was decreased, indicating eccentric cardiac hypertrophy. (125)I-iodophenyl 9-methylpentadecanoic acid (9MPA) was intravenously administered, and animals were sacrificed at 5 min after injection. The 9MPA was rapidly metabolized to iodophenyl-3-methylnonanoic acid (3MNA) by beta-oxidation. Lipid extraction from the myocardium was performed by the Folch method, and radioactivity distribution of metabolites was assayed by thin-layer chromatography. The protein was extracted from the left ventricular myocardium, and levels of PPARalpha and fatty acid oxidation enzymes were examined by Western blotting. RESULTS: Myocardial distribution of 9MPA tended to be more heterogeneous in shunt than in sham rabbits (P = 0.06). In volume-overloaded hearts by shunt, the conversion from 9MPA to 3MNA by beta-oxidation was faster than the sham-control hearts (P < 0.05). However, protein levels of PPARalpha and fatty acid utilization enzymes were unchanged in shunt rabbits compared with sham rabbits. CONCLUSIONS: These data suggest that myocardial fatty acid metabolism is enhanced in eccentric cardiac hypertrophy by volume-overload without changes in protein expressions of PPARalpha and fatty acid utilization enzymes. Our data may provide a novel insight into the subcellular mechanisms for the pathological process of cardiac remodelling in response to mechanical stimuli.     

汉族、维吾尔族和哈萨克族人群内脏脂肪素水平与尿酸、脂代谢指标的相关性

摘要：目的：分析新疆地区汉族、维吾尔族（维族）和哈萨克族（哈族）内脏脂肪素（visfatin）水平与尿酸（UA）、脂代谢指标的相关性。 方法：2011年于新疆少数民族聚居区采集汉族、维族和哈族人群血液标本,检测血清UA和三酰甘油（TG）、总胆固醇（TC）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）等脂代谢指标,用ELISA法检测血清内脏脂肪素含量,分析内脏脂肪素与UA、脂代谢指标的相关性。 结果：汉族、维族和哈族血清内脏脂肪素水平分别为（38.42±33.60）、（32.68±26.87）和（86.36±17.68）ng/mL,哈族高于汉族和维族（P均＜0.05）。汉族UA升高组、TG升高组、HDL-C降低组及肥胖组内脏脂肪素水平均升高（P均＜0.05）。维族UA升高组、TG升高组内脏脂肪素水平均升高（P均＜0.05）,哈族UA升高组、肥胖组内脏脂肪素水平均升高（P均＜0.05）。3个民族内脏脂肪素与UA均呈正相关（r汉=0.305,P＜0.01;r维=0.130,P＜0.05;r哈=0.137,P＜0.05）。汉族和维族血清内脏脂肪素与TG均呈正相关（r汉=0.260,P＜0.01;r维=0.178,P＜0.01）,汉族内脏脂肪素与HDL-C呈负相关（r汉=－0.105,P＜0.05）。 结论：血内脏脂肪素水平存在民族差异,且在UA代谢和脂代谢紊乱过程中有改变。     

Effects of hemicolectomy on bile acid metabolism in relation to colon carcinogenesis in man

Bile acids are probably important in colon carcinogenesis. Regional differences in bile acid metabolism within the colon were studied to illuminate the preferential distal occurrence of colon cancer in Western countries. Faeces (24 h) were collected for bile acid measurement from 25 patients with hemicolectomy (nine left and 16 right) and 17 adenoma patients with an intact colon (control subjects). Duodenal bile and cytolytic and alkaline phosphatase activity of faecal water were also studied. The median percentage of deoxycholic acid (DCA) was lower in the hemicolectomy groups [left 48% (range 38–57%), right 45% (2–62%) vs. control subjects 59% (38–70%), P  < 0.05]. In duodenal bile, the proportion of DCA in left [4% (1–25%)] was lower than in the patients with right hemicolectomy [19% (0–69%)] and control subjects [24% (7–50%)], P  < 0.05. Faecal concentration of protonated DCA was higher in those with right hemicolectomy (0.101 μmol g⁻¹) than in those with left hemicolectomy (0.048 μmol g⁻¹), which coincided with a higher cytolytic [right 49% (3–93%), left 2% (1–37%)] and alkaline phosphatase activity [right 6.7 U mL⁻¹ (1.2–40.1 U mL⁻¹), left (2.0 U mL⁻¹ (1–25.7 U mL⁻¹), both P  < 0.02]. These findings suggest differences in bile acid metabolism between the proximal and distal colon that may contribute to the disparity in cancer risk.     

120例银屑病患者尿酸水平、血脂代谢及其临床诊断意义

目的探讨120例银屑病患者尿酸、血脂代谢及其临床诊断意义。方法选取120例银屑病患者。检测所有患者的尿酸、血脂,比较银屑病组与对照组TC、TG、HDL-C、LDL-C、ApoA1、ApoB、尿酸值,比较不同类型银屑病患者血脂代谢情况。结果银屑病组TC、HDL-C、ApoA1水平显著低于对照组(P0.05),TG水平显著高于对照组(P0.05)。脓疱型患者TC、HDL-C、LDL-C、ApoA1、ApoB水平显著低于其他2组(P0.05);银屑病组男、女血清尿酸值均显著高于对照组(P0.05)。结论分析银屑病患者尿酸、各项血脂代谢具有非常重要的诊断意义。     

慢性乙型肝炎患者血糖、血脂及尿酸代谢异常率的调查分析

目的调查慢性乙型肝炎(CHB)患者糖代谢、脂代谢及尿酸(UA)代谢异常发生率,并探讨其发生机制。方法选择2018年4月至2020年1月本院收治的176例CHB患者作为观察组,选择同期176例健康体检者作为对照组。回顾性分析两组的临床资料。比较两组糖代谢指标[空腹血糖(FPG)、糖化血红蛋白(HbA1c)、空腹胰岛素(INS)]、脂代谢指标[总胆固醇(TC)、甘油三酯(TG)、内脂素]及UA水平,分析CHB患者的糖代谢、脂代谢及UA代谢异常发生率。结果观察组的FPG、HbA1c、INS水平高于对照组(P<0.05)。观察组的TC、TG、内脂素水平高于对照组(P<0.05)。重度组的FPG、HbA1c、INS、TC及内脂素异常率高于轻度组、中度组,中度组的HbA1c、INS及内脂素异常率高于轻度组(P<0.05)。结论CHB患者存在糖代谢、脂代谢异常,随着病情进展容易合并代谢紊乱,临床工作者应重视此类患者的血糖、血脂监测,发现异常时予以合理治疗以控制病情进展。     

Bile acid metabolism in hypothyroid subjects: response to substitution therapy

Bile acid kinetics and biliary lipid composition were determined in ten hypothyroid patients before and after treatment with L-thyroxine. Hypothyroid patients had normal synthesis rates of cholic acid and chenodeoxycholic acid. Hormone treatment, which lowered plasma cholesterol by about 35%, stimulated the formation of chenodeoxycholic acid by about 40% but did not significantly change the synthesis of cholic acid or total primary bile acids. The mean relative biliary concentration of deoxycholic acid was decreased from 30% to 19% and that of chenodeoxycholic acid was concomitantly increased. Cholesterol saturation of bile was decreased by treatment in six of the patients, but the mean value before treatment (135 +/- 13%) was not significantly different from that obtained after treatment (108 +/- 9%). It is suggested that the hypocholesterolaemic effect of thyroid hormones is not primarily due to an increased degradation of cholesterol to bile acids. Similar to what is observed in heterozygous familial hypercholesterolaemia, the defective receptor mediated degradation of plasma low density lipoproteins in hypothyroidism is thus apparently associated with a quantitatively normal catabolic rate of cholesterol to bile acids.     

Exploration of a predictive model based on genes associated with fatty acid metabolism and clinical treatment for head and neck squamous cell carcinoma

BackgroundHead and neck squamous cell carcinoma (HNSCC) is one of the most prevalent malignant tumors of the head and neck and presents high risks of recurrence and poor prognosis postoperatively. The aim of this study was to establish a predictive model based on fatty acid metabolism (FAM) genes to forecast the prognosis of HNSCC patients and the subsequent treatment strategies.MethodsWe accessed the TCGA and GEO databases for HNSCC genes and clinical data. The FAM risk score model was created and validated using a combination of univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) regression analysis. Combining risk scores and clinical characteristics, a nomogram was established and assessed. Subsequently, the function, gene mutation, immune difference, and chemotherapeutic drug sensitivity of the groups with high‐ and low‐risk scores were analyzed. Consequently, the mode''s validity was evaluated comprehensively by combining single gene analysis.ResultsThe FAM risk score model for predicting HNSCC prognosis had certain validity. Patients in the high‐ and low‐risk groups had genetic mutations, and the prognosis was the poorest for the high‐risk groups with high genetic mutations. The patients with low‐risk scores were suitable for immunotherapy since they had increased infiltration of immune cells. In contrast, the patients in the other groups were more suitable for chemotherapy.ConclusionThe results of this study demonstrated that the FAM risk score model may predict the prognosis of HSNCC and has a certain therapeutic guidance value.     

唑来膦酸与伊班膦酸钠对老年男性骨质疏松患者骨代谢指标影响差异的研究

目的:探讨新一代二磷酸盐唑来膦酸与常用药伊班膦酸钠对老年男性骨质疏松患者骨代谢指标影响的差异。方法:60例老年男性骨质疏松患者在每日给予钙尔奇D 0.6 g和骨化三醇胶丸0.25μg的治疗基础上,均静脉滴注2 mg伊班膦酸钠1次。3个月后将患者随机分为两组,一组仍静脉滴注伊班膦酸钠2 mg,另一组静脉滴注5 mg唑来膦酸。于治疗3个月后比较两组患者治疗前后及治疗后两组间甲状旁腺激素、β-胶原分解片段、降钙素、骨钙素、血清磷、血清钙差异。结果:①两组治疗后甲状旁腺激素、β-胶原分解片段均较治疗前下降(P<0.05),降钙素、骨钙素、血清磷、血清钙则无明显差异。②治疗后唑来膦酸组甲状旁腺激素、β-胶原分解片段较伊班膦酸钠组低(P<0.05);血钙也较伊班膦酸钠组低,但比较差异无统计学意义。结论:与伊班膦酸钠比较,静脉应用唑来膦酸对老年男性骨质疏松患者的甲状旁腺激素、β-胶原分解片段可能具更强的短期抑制作用。     

The effect of folic acid on the homocysteine metabolism in human umbilical vein endothelial cells (HUVECs)

Mild hyperhomocysteinaemia is associated with increased risk for vascular disease. We studied homocysteine export from human umbilical vein endothelial cells (HUVECs) by measuring total homocysteine (tHcy) concentrations in the culture medium. Under standard culture conditions tHcy concentrations in the HUVEC culture medium increased by constant amounts after 24, 48 and 72 h [mean = 2.5 (SD ± 0.7) μmol L⁻¹ homocysteine every 24 h]. As the cells are the only source of homocysteine increase in the culture medium, we designate this as homocysteine export from HUVEC. Folic acid supplementation to the culture medium lowered the homocysteine export in a dose-dependent manner. Methyl-tetrahydrofolate (MeTHF) and folinic acid (a stable precursor of MeTHF) were in this respect about 10 times more effective than folic acid. A 50% reduction in the homocysteine export was seen with 10–30 nmol L⁻¹ MeTHF supplementation; reduction to almost zero was seen with 100–300 nmol L⁻¹ MeTHF. Additions to the culture medium of the other vitamins involved in the homocysteine metabolism, such as vitamin B₁₂, vitamin B₆ and flavin adenine dinucleotide, did not show any effect on homocysteine export. Because homocysteine export reflects an imbalance in the homocysteine metabolism, our observations showed a susceptible dependency of this metabolism on folic acid in endothelial cells.