Serum Low Density Lipoprotein Cholesterol Concentration Is Not Dependent on Cholesterol Synthesis and Absorption in Healthy Humans

Introduction. Pharmacological reduction of cholesterol (C) synthesis and C absorption lowers serum low-density lipoprotein C (LDL-C) concentrations. We questioned whether high baseline C synthesis or C absorption translates into high serum LDL-C concentrations or if there was no connection. Therefore, we studied the association between serum LDL-C and C synthesis or C absorption in healthy subjects. Methods. Three published data sets of young subjects on different diets (study 1), mildly hypercholesterolemic subjects without cardiovascular disease (study 2) and healthy controls of the Framingham study (study 3) were used. The three study populations varied in sex, age, and weight. C synthesis and C fractional absorption rate (FAR) were measured with fecal sterol balance and stable isotope techniques (studies 1 and 2). Additionally, serum lathosterol and campesterol concentrations corrected for the serum total C concentration (R_lathosterol and R_campesterol) were used as markers for hepatic C synthesis and C FAR, respectively (studies 1–3). Linear regression analysis was applied to evaluate associations between LDL-C, C synthesis, and C absorption. Results. Seventy-three, 37, and 175 subjects were included in studies 1, 2, and 3, respectively. No statistically significant associations were found between LDL-C and the measured C synthesis and C FAR, nor for R_lathosterol and R_campesterol in any of the study groups. This lack of associations was confirmed by comparing the male subjects of studies 1 and 2. Study 1 subjects had a 50% lower serum LDL-C than the study 2 subjects (p < 0.01), but not a lower C synthesis, C FAR, R-lathosterol, or R_campesterol. Conclusions. Under physiological conditions, C synthesis and C FAR are not major determinants of circulating serum LDL-C concentrations in healthy subjects. The results need to be confirmed in large-scale studies in healthy subjects and patients at risk for cardiovascular disease.     

Responses of surrogate markers of cholesterol absorption and synthesis to changes in cholesterol metabolism during various amounts of fat and cholesterol feeding among healthy men

Serum ratios to cholesterol of lathosterol, and of cholestanol, campesterol and sitosterol measure respective relative cholesterol synthesis and absorption, but their clinical applicability is not known in evaluation of cholesterol metabolism under different dietary conditions. We compared relative synthesis and absorption of cholesterol to the respective absolute ones in healthy male volunteers (n 29) on four subsequent diets: baseline home (HD), low-cholesterol low-fat (LCLF), high-cholesterol low-fat (HCLF) and low-cholesterol high-fat (LCHF). Serum lipids, lipoproteins, sterols, fractional cholesterol absorption and sterol synthesis were examined. HCLF and LCHF decreased fractional cholesterol absorption by approximately 23-27 % from baseline HD (P < 0.05) and increased the levels of total and LDL-cholesterol in serum from LCLF by approximately 9-14 % (P < 0.05). On HCLF, bile acid synthesis was high (P < 0.05 for each), and absolute cholesterol synthesis tended to be higher than on HD and LCHF (NS). Relative synthesis was positively associated with absolute cholesterol synthesis, but inversely with relative absorption during each diet (P < 0.05). The relative absorption markers were interrelated in each diet, and were also associated with fractional absorption of cholesterol in each diet but HD. In conclusion, relative markers of cholesterol absorption and synthesis reflect changes in cholesterol metabolism despite the amount of dietary fat and cholesterol consumed, but their validity with this respect is strengthened by controlled diets in metabolic studies. Additions of cholesterol and fat to a diet low in fat and cholesterol cause practically equal changes in the serum lipid profiles, whereas synthesis of cholesterol (NS) and bile acids (P < 0.05) were higher with the high-cholesterol feeding.     

Serum Phytosterols Are Not Associated with Inflammatory Markers in Two Cross-Sectional,Swiss Population-Based Studies (The CoLaus|PsyCoLaus Study)

Background: The association between inflammation and dietary sterols remains poorly assessed at the population level. Aims: To assess the possible association between serum levels of various phytosterols (PS) and inflammatory markers. Methods: Serum levels of six PS (campesterol, campestanol, stigmasterol, sitosterol, sitostanol, brassicasterol), four cholesterol synthesis markers (lathosterol, lanosterol, desmosterol, dihydroxylanosterol) and one cholesterol absorption marker (cholestanol) were measured together with levels of CRP, IL-6 and TNF-α in two cross-sectional surveys of a population-based, prospective study. Results: CRP levels were negatively associated with levels of cholestanol and of sterols of plant origin, although some associations were not statistically significant. CRP levels were positively associated with cholesterol synthesis markers in the first but not in the second follow-up. IL-6 levels were negatively associated with cholestanol in both follow-ups. No associations between IL-6 levels and PS were found in the first follow-up, while significant negative associations with campesterol, sitosterol, brassicasterol, sitostanol and campesterol:TC ratio were found in the second follow-up. TNF-α levels were negatively associated with cholestanol in both follow-ups. These associations did not withstand adjusting for sex, age, BMI and statin administration. Conclusions: In a population-based study, PS serum levels were not significantly associated with inflammatory markers.     

Plasma markers of cholesterol homeostasis and apolipoprotein B-100 kinetics in the metabolic syndrome

OBJECTIVE: The metabolic syndrome is characterized by defective hepatic apolipoprotein B-100 (apoB) metabolism. Hepato-intestinal cholesterol metabolism may contribute to this abnormality. RESEARCH METHODS AND PROCEDURES: We examined the association of cholesterol absorption and synthesis with the kinetics of apoB in 35 obese subjects with the metabolic syndrome. Plasma ratios of campesterol and lathosterol to cholesterol were used to estimate cholesterol absorption and synthesis, respectively. Very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein apoB kinetics were studied using stable isotopy and mass spectrometry. Kinetic parameters were derived using multicompartmental modeling. RESULTS: Compared with controls, the obese subjects had significantly lower plasma ratios of campesterol, but higher plasma ratios of lathosterol (p < 0.05 in both). This was associated with elevated VLDL-apoB secretion rate (p < 0.05) and delayed fractional catabolism of IDL and low-density lipoprotein-apoB (p < 0.01). In the obese group, plasma ratios of campesterol correlated inversely with VLDL-apoB secretion (r = -0.359, p < 0.05), VLDL-apoB (r = -0.513, p < 0.01) and IDL-apoB (r = -0.511, p < 0.01) pool size, and plasma lathosterol ratio (r = -0.366, p < 0.05). Subjects with low cholesterol absorption had significantly higher VLDL-apoB secretion, VLDL-apoB and IDL-apoB pool size, and plasma lathosterol ratio (p < 0.05 in both) than those with high cholesterol absorption. DISCUSSION: Subjects with the metabolic syndrome have oversecretion of VLDL-apoB and decreased catabolism of apoB-containing particles and low absorption and high synthesis rates of cholesterol. These changes in cholesterol homeostasis may contribute to the kinetic defects in apoB metabolism in the metabolic syndrome.     

Dietary plant sterols alter the serum plant sterol concentration but not the cholesterol precursor sterol concentrations in young children (the STRIP Study). Special Turku Coronary Risk Factor Intervention Project.

Plant sterol supplementation reduces serum cholesterol concentration but may increase serum plant sterol concentrations, especially in children. We determined whether natural dietary plant sterols derived mainly from vegetable oil or margarine in early childhood affect serum concentrations of plant sterols (campesterol and sitosterol) and cholesterol precursor sterols (Delta-8 cholestenol, desmosterol, and lathosterol), reflecting endogenous cholesterol synthesis. We measured the serum sterol concentrations using gas liquid chromatography in 20 healthy 13-mo-old intervention children in a randomized, prospective study designed to decrease exposure of the children to known environmental atherosclerosis risk factors and in 20 control children. The diet of the intervention children was rich in plant sterols due to replacement of milk fat with vegetable fat, whereas the diet of the control children contained only small amounts of plant sterols. The intervention children consumed twice as much plant sterols as the control children (P < 0.001). Their serum concentrations of campesterol and sitosterol were 75% and 44% higher, respectively, than those in the control children (P < 0.001 for both), but serum cholesterol precursor sterol concentrations did not differ between the two groups. We conclude that doubling dietary plant sterol intake almost doubles serum plant sterol concentrations in 13-mo-old children, but has no effect on endogenous cholesterol synthesis. Relative intestinal absorption of natural plant sterols from the diet in early childhood is similar to that in adults.     

Change in the cholesterol metabolism associated with the combined inhibition of synthesis and absorption

Lowering lipid levels in the cardiovascular prevention we confine ourselves to measure the cholesterol level and care less for the background effects. Namely blood cholesterol level beyond the amount consumed with the diet highly depends on balance of intestinal absorption/secretion and synthesis. Studying the rate of absorption and synthesis has come only recently into the foreground of interest. Many observations proved that using even the strongest cholesterol lowering drug - beyond reducing the synthesis in the liver - may be associated with an up to 50 percent increase of the intestinal cholesterol absorption. When studying the effectiveness of statins in everyday practice we measure only the decrease of serum cholesterol level as the final result, and do not examine the changes in the synthesis and absorption. The amount of cholesterol synthesized or absorbed can be determined in an indirect way by measuring that of the non-cholesterol sterols (phytosterols). The absorption markers are campesterol, sitosterol, avenasterol as well as cholestanol. The biosynthesis of cholesterol correlates with the level of lathosterol, cholestanol, desmostenol. In practice the concentration of lathosterol or lathosterol/cholesterol can be considered the marker of synthesis and the campesterol or campesterol/cholesterol ratio the marker of absorption. So recent study results show that while inhibiting the cholesterol synthesis with statin the cholesterol absorption increases and the absorption inhibitor ezetimibe is associated with boost of synthesis. The increase in absorption caused by statins can be reduced or prevented by combining with ezetimibe. These data confirm that combination of statin and ezetimibe, inhibiting simultaneously both the synthesis and absorption provides the most effective cholesterol-level lowering with the least side-effects.     

Antibodies against low density oxidized lipoproteins in type 2 diabetics

Oxidative modification of low density lipoproteins (LDL) is an important factor in the development of macrovascular atherosclerotic complications in patiens with type 2 diabetes mellitus. Recently autoantibodies against oxidized LDL (anti-oxLDL) have been suggested as a potential marker of LDL oxidation in vivo. The purpose of this study was to investigate the presence and levels of anti-oxLDL in patients with type 2 diabetes compared to healthy persons. We determined the serum concentrations of anti-oxLDL in 20 type 2 diabetic patiens with different degree and type of atherosclerotic vascular damage. Two healthy population groups: 20 young blood donors and 20 age and gender matched persons were used as controls. Anti-oxLDL positivity rates were distinctively higher in both control groups. Concentrations of anti-oxLDL were significantly lower in diabetic patients compared to both control groups. The incidence rates and levels of anti-oxLDL in both control groups were similar. Anti-oxLDL levels in the diabetes group did not correlate with the degree of macrovascular damage, serum total cholesterol, LDL cholesterol and triglyceride concentrations. We did not find any significant relationship between anti-oxLDL and other oxidative stress factors (superoxide dismutase, malondialdehyde, C and E vitamins). We suppose that anti-oxLDL may have an antiatherogenic protective role in healthy people but are not applicable to be an in vivo marker of LDL oxidation and macrovascular atherosclerotic vascular damage.     

Serum plant sterols and cholesterol precursors reflect cholesterol absorption and synthesis in volunteers of a randomly selected male population

To investigate the regulation of serum levels of cholesterol precursor sterols and plant sterols, these noncholesterol sterols, fatty acids, and various parameters of cholesterol metabolism were analyzed in 63 volunteers from a randomly selected Finnish male population sample of 100 subjects, aged 50 years, who had normal dietary habits. Serum levels of cholesterol precursors, desmosterol and lathosterol (in terms of micrograms/mg cholesterol), were negatively related to both the fractional and absolute absorption of dietary cholesterol and serum high density lipoprotein (HDL) cholesterol, and positively related to overall cholesterol synthesis and serum very low density lipoprotein (VLDL) cholesterol. Serum levels of the plant sterols, campesterol and sitosterol, exhibited positive correlations with the polyunsaturated/saturated fatty acid ratio of dietary fat, the linoleic acid contents of plasma and dietary lipids, the amount of dietary plant sterols (as indicated by fecal output), fractional and absolute absorption of dietary cholesterol, and HDL cholesterol, but were inversely related to the overall cholesterol synthesis and VLDL cholesterol. Stepwise multiple regression analysis revealed that the serum level of campesterol was associated with fractional cholesterol absorption, dietary plant sterols, and biliary cholesterol secretion, and that of sitosterol with dietary plant sterols, cholesterol synthesis, fractional cholesterol absorption, and biliary cholesterol secretion. Thus, the serum non-cholesterol sterols are significant indicators of cholesterol absorption and synthesis even under basal conditions and, since gas liquid chromatographic determination of these sterols is quite simple, their measurement may be valuable for monitoring cholesterol metabolism in large-scale epidemiologic studies.     

Effects of dietary cholesterol and fat on serum non-cholesterol sterols according to different apolipoprotein E subgroups among healthy men

The impact of apo E phenotypes on applicability of relative cholesterol synthesis (lathosterol:cholesterol) and absorption (ratios of cholestanol, campesterol and sitosterol to cholesterol) during diets of various cholesterol and fat content is unclear. We examined and compared with each other both relative and absolute synthesis and absorption among twenty-nine men, of whom eight, nine and twelve had apo E phenotypes 2 (2/2, 2/3, 2/4), 3 (3/3) and 4 (3/4, 4/4), respectively. Serum lipids, lipoproteins, sterols and cholesterol metabolism were examined on four subsequent diets: high-cholesterol high-fat (home diet; HD), low-cholesterol low-fat (LCLF), high-cholesterol low-fat (HCLF) and low-cholesterol high-fat (LCHF). LDL-cholesterol (LDL-C) level was about 40 % lower (P < 0.05) in apo E2 than apo E3 and E4 groups irrespective of dietary fat and cholesterol. Serum proportions of phytosterols were determined apo E-dependently on LCLF and HCLF, and those of lathosterol, cholestanol and campesterol were increased in apo E2 and E3 groups (P < 0.05 for each v. HD). Serum proportion of sitosterol reflected almost consistently apo E phenotype (r range+0.308 to+0.383; P range 0.214-0.011). Relative cholesterol synthesis and absorption reflected respective absolute values during each diet in the apo E4 group (r range+0.713 to+0.893; P < 0.05 for each), but only during HD (r+0.594; P = 0.015) in the apo E2+E3 group. The consumption of a high amount of fat did not interfere with cholesterol metabolism or serum levels of LDL-C differently in apo E phenotypes. Surrogate sterol markers of cholesterol metabolism reflected absolute ones (especially in the apo E4 group) and apo E phenotypes despite variable amounts of dietary cholesterol and fat.     

RELATIONSHIP BETWEEN ABSORPTION OF CHOLESTEROL AND SERUM PLANT STEROLS

Serum levels of β-sitosterol and campesterol are related to the fractional absorption of cholesterol and may serve as markers for cholesterol absorption.     

High serum phytosterol levels in short bowel patients on parenteral nutrition support

BACKGROUND & AIMS: Patients with short bowel syndrome (SBS) are often depending on parenteral nutrition support (PNS), sometimes complicated by liver dysfunction. Phytosterols in parenteral lipid emulsions have been suspected to be responsible for cholestasis in paediatric nutrition support. The aim of the present study was to evaluate phytosterol intake and serum phytosterol levels in adult SBS patients. METHODS: We quantified serum levels of phytosterols, cholesterol, and markers for bile acid and cholesterol synthesis, by gas or liquid chromatography in 21 healthy controls, and in 24 adult SBS-patients, 8 with and 16 without PNS. Phytosterols and cholesterol in parenteral lipid emulsions were also quantified. RESULTS: Serum levels in SBS-patients without PNS; with PNS; and in controls, were on average for phytosterols 11; 63; and 23 micromol/l (P<0.05 for differences), cholesterol 4,2; 3,8; and 5,1 mmol/l, lathosterol 808; 824; and 228 micromol/100 mmol cholesterol, and 7alpha-hydroxy-4-cholesten-3-one 207;191; and 18 nmol/l, respectively (P<0.05 between controls and SBS). Phytosterols in lipid emulsions ranged from 591 to 958 micromol/l. CONCLUSIONS: SBS-patients on PNS have higher serum levels of phytosterols than other SBS-patients and controls, possibly because of phytosterols in lipid emulsions. Patients with SBS, regardless of nutrition support, have lower serum levels of cholesterol but higher cholesterol and bile acid synthesis compared to controls.     

Alterations in lipidic metabolism in hemodialysis patients

Background: Chronic kidney failure is associated with dyslipidemia and accelerated atherosclerosis. Aim: To study lipidic metabolism alterations in patients with chronic kidney failure on hemodialysis. Methods: The study interested 45 hemodialysis patients with a mean age of 49.04 ±15.92 years old and 45 healthy controls. A blood sample was collected from each patient and control to measure total cholesterol, triglycerides, HDL- cholesterol, LDL-cholesterol, apolipoproteins AI and B100, lipoprotein (a) and C Reactive Protein. Results: A significant increase of serum triglycerides (p= 0.002), lipoprotein (a) (p = 0.001) and C Reactive Protein (p = 0.008) was observed in patients when compared with healthy controls. A significant decrease of serum total cholesterol (p=0.01), HDLcholesterol (p<0.001), LDL-cholesterol (p=0.005) and apolipoprotein AI (p<0.001) was also observed in patients. Conclusion: Disorders of lipidic metabolism are frequent in hemodialysis patients. These alterations can lead to cardiovascular disease in uremic patients.     

Divergent changes in serum sterols during a strict uncooked vegan diet in patients with rheumatoid arthritis

The effects of a strict uncooked vegan diet on serum lipid and sterol concentrations were studied in patients with rheumatoid arthritis. The subjects were randomized into a vegan diet group (n 16), who consumed a vegan diet for 2-3 months, or into a control group (n 13), who continued their usual omnivorous diets. Serum total and LDL-cholesterol and -phospholipid concentrations were significantly decreased by the vegan diet. The levels of serum cholestanol and lathosterol also decreased, but serum cholestanol:total cholesterol and lathosterol:total cholesterol did not change. The effect of a vegan diet on serum plant sterols was divergent as the concentration of campesterol decreased while that of sitosterol increased. This effect resulted in a significantly greater sitosterol:campesterol value in the vegan diet group than in the control group (1.48 (SD 0.39) v. 0.72 (SD 0.14); P < 0.001). A higher concentration of campesterol compared with sitosterol is normal in omnivorous subjects and can be explained by lower absorption and esterification rates of sitosterol. Our results suggest that a strict uncooked vegan diet changes the relative absorption rates of these sterols and/or their biliary clearance.     

Serum plant sterols and their relation to cholesterol absorption

beta-Sitosterol and campesterol were measured in serum lipoproteins of 17 subjects from two families. The serum levels of the two phytosterols were closely correlated with each other (r = 0.974), less consistently with serum cholesterol (r = 0.489), and not at all with serum triglycerides. As compared to cholesterol, serum free and esterified phytosterols tended to be accumulated in HDL where the phytosterol/cholesterol ratios were almost 40% higher than in VLDL and LDL. The serum phytosterol concentrations, the phytosterol/cholesterol ratios, especially in VLDL and LDL, and the fractional absorption of cholesterol were higher in women than in men. The levels of the phytosterols in whole serum and in each lipoprotein were significantly correlated with the percentage absorption of dietary cholesterol but were independent of the amount of dietary cholesterol and plant sterols. Our findings suggest that, in general, serum levels of noncholesterol sterols are effectively determined by the absorption which in turn is proportionate to the fractional absorption of cholesterol.     

Non-nutritive bioactive constituents of plants: phytosterols

Normal human diet contains small amounts of phytosterols, mainly sitosterol and campesterol. Intestinal absorption of these plant sterols is low, about one tenth of that of cholesterol, such that their serum concentrations are also low, about 0.1 to 1% of the cholesterol levels. Like cholesterol they are transported by lipoproteins, mainly by LDL, and secreted unchanged in bile. Addition of plant sterols, or especially of their delta-5 saturated derivatives plant stanols into diet as fat-soluble esters inhibit cholesterol absorption and lower serum cholesterol similarly in short-term studies. Long-term consumption of plant stanol esters lowers serum cholesterol to the extent expected to reduce clinical manifestation of coronary heart disease by over 20% without detectable side effects, cholesterol lowering being especially effective in combination with cholesterol synthesis inhibitors statins.     

Acute effect of dietary stanyl ester dose on post-absorptive alpha-tocopherol, beta-carotene, retinol and retinyl palmitate concentrations

Stanyl esters dissolved in margarine inhibit cholesterol absorption, lower sterol absorption in general, and lower serum total cholesterol, LDL-cholesterol and plant sterol levels. To find out whether stanyl esters inhibit absorption of fat-soluble vitamins and beta-carotene in acute experiments, we performed two fat-tolerance tests fortified with vitamins (retinol 0.9-3.7 mg, alpha-tocopherol 70-581 mg), beta-carotene (25-150 mg) and squalene (0.5 g) with and without 1 g of stanyl ester added to the test meal in ten healthy men. The concentrations or areas under the curves (AUC) of cholesterol, triacylglycerols, squalene and alpha-tocopherol, beta-carotene and retinyl palmitate showed typical postprandial changes in serum, chylomicrons, VLDL and VLDL infranatant (intermediate-density lipoproteins, LDL and HDL) over 24 h after the test meal without stanyl esters, and they were not affected by the addition of stanyl esters. The post-absorptive serum campesterol concentration and campesterol : cholesterol were significantly lowered at 6-9 h by stanyl ester supplementation, reflecting reduced sterol absorption efficiency. Changes in vitamin and beta-carotene AUC did not correlate with the given doses. In conclusion, the present study shows that stanyl esters dissolved in margarine do not detectably interfere in a short-term study with the absorption of alpha-tocopherol, beta-carotene or retinol measured by a 24 h oral fat-load test.     

Fecal steroids and colorectal cancer

The fecal steroid profiles of healthy subjects were compared with those of colorectal cancer (CRC) patients. The multicomponent profiles did not differ qualitatively in that CRC patients, like control subjects, had similar fecal steroids. The major bile acids detected in fecal extracts were lithocholic acid (LCA) and deoxycholic acid (DCA). The major sterol of animal origin was cholesterol and its bacterial metabolite coprostanol, whereas the major plant sterols were ß‐sitosterol, stigmasterol, campesterol, and their corresponding bacterial metabolites. CRC patients excreted higher amounts of total major bile acids (LCA and DCA) than did the control group, but this difference was not significant. However, the LCA‐to‐DCA ratio was much higher in the CRC group [(1.43, p < 0.01) compared with the control group (0.72)]. The control group excreted significantly higher amounts of total neutral sterols (p < 0.001), sterols of animal origin (p < 0.001), and plant sterols (p < 0.001) compared with the CRC group; the plant sterols represented a much lower proportion of excreted total neutral sterols in the CRC group (p > 0.001) compared with the control group.

We propose the following hypotheses. 1) The LCA‐to‐DCA ratio may be an important discriminant market for CRC susceptibility. 2) The fecal LCA‐to‐DCA ratio may depend on the differential hepatic synthesis of their respective precursors chenodeoxycholic acid (CDCA) and cholic acid. 3) Hepatic synthesis of CDC A may be increased by more efficient conservation of dietary cholesterol because it has been shown that cholesterol of exogenous origin is the main precursor of this bile acid. 4) Cholesterol absorption may be augmented in CRC patients because of the low intake of plant sterols, which are known to suppress cholesterol absorption.     

Safety and immunogenicity of a 2009 influenza A (H1N1) vaccine in hemodialysis patients

A worldwide vaccination campaign against the 2009 pandemic influenza A (H1N1) virus was launched among high-risk subjects, including hemodialysis patients. The long-term immunogenicity of an influenza vaccine has not been investigated in hemodialysis patients. This study aimed to (1) assess the long-term immunogenicity of a monovalent non-adjuvanted influenza A (H1N1) vaccine in hemodialysis patients and (2) determine the safety of this vaccine. We conducted a prospective cohort study of 44 hemodialysis patients and 149 healthy controls in 2010. All of the participants received a single dose of the monovalent non-adjuvanted 2009 influenza A (H1N1) vaccine. The level of antibodies was measured at baseline and at 4 and 24 weeks post-vaccination using a hemagglutination inhibition assay. The outcomes were the percentages of participants who achieved seroconversion and seroprotection (titer ≥1:40) 4 and 24 weeks after vaccination. At 4 weeks post-vaccination, seroconversion was observed in 17 (38.6%) of the hemodialysis patients and 94 (63.1%) of the controls (P = 0.056), and protective titers were obtained in 22 (50%) of the hemodialysis patients and 100 (67.1%) of the controls (P = 0.426). At 24 weeks post-vaccination, immunogenicity decreased in both the hemodialysis patients and the controls, but there were no significant differences between the hemodialysis patients and the controls in the seroconversion rate (27.3% versus 36.9%, P = 0.526) or the seroprotection rate (38.6% versus 48.3%, P = 0.996). No differences in adverse events were observed between the hemodialysis patients and the controls. In summary, the 2009 influenza A (H1N1) vaccine elicits a similar immune response in both hemodialysis patients and healthy controls, but immunity declines 24 weeks after vaccination in both groups. Hemodialysis patients should at least be vaccinated annually against the influenza virus.     

Effects of plant sterol esters in skimmed milk and vegetable-fat-enriched milk on serum lipids and non-cholesterol sterols in hypercholesterolaemic subjects: a randomised, placebo-controlled, crossover study

Plant sterol (PS)-supplemented foods are recommended to help in lowering serum LDL-cholesterol (LDL-C). Few studies have examined the efficacy of PS-enriched skimmed milk (SM) or semi-SM enriched with vegetable fat (PS-VFM). There is also insufficient information on factors predictive of LDL-C responses to PS. We examined the effects of PS-SM (0·1 % dairy fat) and PS-VFM (0·1 % dairy fat plus 1·5 % vegetable fat) on serum lipids and non-cholesterol sterols in hypercholesterolaemic individuals. In a placebo-controlled, crossover study, forty-three subjects with LDL-C>1300 mg/l were randomly assigned to three 4-week treatment periods: control SM, PS-SM and PS-VFM, with 500 ml milk with or without 3·4 g PS esters (2 g free PS). Serum concentrations of lipids and non-cholesterol sterols were measured. Compared to control, LDL-C decreased by 8·0 and 7·4 % (P < 0·015, both) in the PS-SM and PS-VFM periods, respectively. Serum lathosterol:cholesterol (C) ratios increased by 11-25 %, while sitosterol:C and campesterol:C ratios increased by 70-120 % with both the PS-fortified milk. Adjusted LDL-C reductions were variably enhanced in participants with basal low serum lathosterol/C or conversely high sitosterol/C and campesterol/C. Subjects with post-treatment serum PS:C ratios above the median showed mean LDL-C changes of - 5·9 to - 10·4 %, compared with 1·7 to - 2·9 % below the median. In conclusion, consumption of 2 g/d of PS as PS-SM and PS-VFM lowered LDL-C in hypercholesterolaemic subjects to a similar extent. Basal and post-treatment changes in markers of cholesterol metabolism indicating low cholesterol synthesis and high cholesterol absorption predicted improved LDL-C responses to PS.     

炎症因子与胰岛素抵抗和2型糖尿病大血管病变的相关性研究

目的探讨炎症因子C-反应蛋白（CRP）与胰岛素抵抗（IR）和2型糖尿病（T2DM）大血管病变的关系。方法用颗粒增强免疫沉淀法测定T2DM合并大血管病变（70例）、T2DM无大血管病变（60例）及正常对照组（90名）的血清超敏CRP（usCRP）水平变化；用HOMA—IR模型作为估计IR的指标；将CRP与HOMA—IR、空腹胰岛素（FINS）、同型半胱氨酸（Hcy）、空腹血糖（FBG）、体重指数（BMI）、腰臀比（WHR）、甘油三酯（TG）等作相关分析。结果T2DM合并大血管病变组血清usCRP水平明显高于T2DM无大血管病变组及正常对照组（P〈0．01），T2DM无大血管病变组高于正常对照组（P〈0．01）。当调整SBP、FBG、TG、WHR等因素的影响后，协方差结果显示usCRP在T2DM合并大血管病变组仍高于T2DM无大血管病变组及正常对照组（P〈0．05），T2DM无大血管病变组高于正常对照组（P〈0．05）。在T2DM合并大血管病变组，Person相关分析显示，usCRP与FINS、HOMA-IR、TG呈正相关（P值分别〈0．05、〈0．01和〈0．05），与Hcy等无关。逐步线性回归结果显示，TG、HOMA—IR是影响CRP的主要因素。结论CRP可能是T2DM和T2DM大血管病变的危险因子，CRP可能通过胰岛素抵抗参与了T2DM大血管病变的发生和发展。