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This study aimed to assess the antioxidant capacity of lemon flavonoid extract Eriomin® (LE) and its impact on cholesterol metabolism in the context of healthy aging. We orally treated 24-month-old male Wistar rats with an LE (40 mg/kg) suspended in 0.3 mL of sunflower oil. At the same time, control groups received an equal volume of sunflower oil (CON) or remained untreated (ICON) daily for 4 weeks. We examined LEs effects on superoxide dismutase and catalase- and glutathione-related enzyme activities, the concentration of lipid peroxides and protein carbonyls, total oxidant status (TOS) and antioxidant status (TAS), and oxidative stress index (OSI) in the liver, jejunum, and ileum. We also measured total cholesterol, its biosynthetic precursors (lanosterol, lathosterol, desmosterol), its degradation products (bile acid precursors) in the serum, liver, jejunum, and ileum, and serum phytosterols (intestinal absorption markers). LE reduced TOS, TAS, and OSI (p < 0.05) compared with control values, indicating its consistent antioxidant action in all examined organs. LE lowered hepatic desmosterol (p < 0.05) while also reducing 7α- and 24-hydroxycholesterol levels in the liver and ileum (p < 0.01). Serum cholesterol, hepatic gene expression, and the immunostaining intensity of CYP7A1 were unchanged. In conclusion, LE exerted non-enzymatic antioxidant effects and reduced cholesterol degradation, reducing its biosynthesis products, thereby maintaining serum cholesterol levels.

Apnea diving is characterized by extreme hypoxia and hypercapnia. Possible pathophysiological processes concerning the cardiovascular system are not yet fully understood. Hypoxia has effects on triglyceride metabolism and circulating blood lipids. To date, in voluntary apnea divers, no short-time hypoxia expositions focusing on plasma triglycerides, lipoprotein and cholesterol derived oxysterols levels have been performed. We hypothesize that short time hypoxemia leads to altered triglyceride, cholesterol, and oxysterol plasma levels in voluntary apnea divers.

Abstract Bile acids (BA) have recently been shown to increase energy expenditure in mice, but this concept has not been tested in humans. Therefore, we investigated the relationship between plasma BA levels and energy expenditure in humans. Type 2 diabetic (T2DM) patients (n = 12) and gender, age and BMI-matched healthy controls (n = 12) were studied before and after 8 weeks of treatment with a BA sequestrant. In addition, patients with liver cirrhosis (n = 46) were investigated, since these display elevated plasma BA together with increased energy expenditure. This group was compared to gender-, age- and BMI-matched healthy controls (n = 20). Fasting plasma levels of total BA and individual BA species as well as resting energy expenditure were determined. In response to treatment with the BA sequestrant, plasma deoxycholic acid (DCA) levels decreased in controls (-60%, p < 0.05) and T2DM (-32%, p < 0.05), while chenodeoxycholic acid (CDCA) decreased in controls only (-33%, p < 0.05). Energy expenditure did not differ between T2DM and controls at baseline and, in contrast to plasma BA levels, was unaffected by treatment with the BA sequestrant. Total BA as well as individual BA species did not correlate with energy expenditure at any time throughout the study. Patients with cirrhosis displayed on average an increase in energy expenditure of 18% compared to values predicted by the Harris-Benedict equation, and plasma levels of total BA (up to 12-fold) and individual BA (up to 20-fold) were increased over a wide range. However, neither total nor individual plasma BA levels correlated with energy expenditure. In addition, energy expenditure was identical in patients with a cholestatic versus a non-cholestatic origin of liver disease while plasma total BA levels differed four-fold between the groups. In conclusion, in the various (patho)physiological conditions studied, plasma BA levels were not associated with changes in energy expenditure. Therefore, our data do not support an important role of circulating BA in the control of human energy metabolism.

The article discusses the Nutrients' Special Issue "From dietary cholesterol to blood cholesterol," focusing on human cholesterol (C) metabolism. Topics include the complex aspects of C metabolism, the lack of a straightforward association between dietary cholesterol and blood cholesterol, and the role of phytosterols in C absorption and their potential impact on cardiovascular disease risk.

Intestinal intubation studies have demonstrated that lipids induce satiety, but the contribution of lipid processing by the stomach on satiety remains poorly understood. In this explorative, randomized, placebo-controlled, crossover study we tested whether delayed lipid absorption, increased cholecystokinin (CCK), decelerated gastric emptying (GE), and increased satiety can be achieved by controlling lipid distribution in the stomach. Six healthy men were intubated nasogastrically. Two treatments were performed and repeated in duplicate. In the oil-on-top treatment (OT), subjects received a fat-free liquid meal (LM, 325 ml, 145 kcal) followed by intragastric infusion of 4 g of high-oleic-acid rapeseed oil (4.6 ml, 36 kcal) labeled with 77 mg glyceryl-[[sup.13]C]trioleate. In the emulsion treatment (EM, control), 4 g of labeled rapeseed oil was incorporated into the LM (325 ml, 181 kcal); 4.6 ml of saline was infused as a control. In OT and EM a second LM was consumed at time t = 270 min. Plasma [sup.13]C-C18:1, CCK and satiety were measured over 480 min. GE was determined by the paracetamol absorption test. OT delayed oleic acid absorption shown by an increased lag time of absorption (EM: 37 [+ or -] 7 min; OT: 75 [+ or -] 10 min; P < 0.01) and time at maximum concentration (EM: 162 [+ or -] 18 min; OT: 280 [+ or -] 33 min; P = 0.01). OT released more CCK than EM (P = 0.03), including increased CCK after the second meal. OT accelerated initial GE until 30 min postprandial. OT showed a tendency (P = 0.06) to suppress hunger and increase satiety and fullness 120-270 min postprandially. The results demonstrate that low amounts of lipids, when separated from the aqueous phase of a meal, delay lipid absorption and increase CCK. An escalating-dose study should determine whether this could have implications for the development of weight-control foods. hunger; satiety; oleic acid; paracetamol absorption test; liquid meal

Human milk contains prebiotic oligosaccharides, which stimulate the growth of intestinal bifidobacteria and lactobacilli. It is unclear whether the prebiotic capacity of human milk contributes to the larger bile salt pool size and the more efficient fat absorption in infants fed human milk compared with formula. We determined the effect of prebiotic oligosaccharides on bile salt metabolism in rats. Rats were fed a control diet or an isocaloric diet containing a mixture of galactooligosaccharides (GOS), long-chain fructooligosaccharides (IcFOS), and acidified oligosaccharides (AOS) for 3 wk. We determined synthesis rate, pool size, and fractional turnover rate (FTR) of the primary bile salt cholate by using stable isotope dilution methodology. We quantified bile flow and biliary bile salt secretion rates through bile cannulation. Prebiotic intervention resulted in significant changes in fecal and colonic flora: the proportion of lactobacilli increased 344% (P < 0.01) in colon content and 139% (P < 0.01) in feces compared with the control group. The number of bifidobacteria also increased 366% (P < 0.01) in colon content and 282% in feces after the prebiotic treatment. Furthermore, pH in both colon and feces decreased significantly with 1.0 and 0.5 pH point, respectively. However, despite this alteration of intestinal bacterial flora, no significant effect on relevant parameters of bile salt metabolism and cholate kinetics was found. The present data in rats do not support the hypothesis that prebiotics naturally present in human milk contribute to a larger bile salt pool size or altered bile salt pool kinetics. bile salt kinetics; infant nutrition; cholate

Cholestasis is associated with systemic accumulation of bile salts and with deficiency of bile in the intestinal lumen. During the past years bile salts have been identified as signaling molecules that regulate lipid, glucose, and energy metabolism. Bile salts have also been shown to activate signaling routes leading to proliferation, apoptosis, or differentiation. It is unclear, however, whether cholestasis affects the constitution and absorptive capacity of the intestinal epithelium in vivo. We studied small intestinal morphology, proliferation, apoptosis, expression of intestinespecific genes, and carbohydrate absorption in cholestatic (1 wk bile duct ligation), bile-deficient (1 wk bile diversion), and control (sham) rats. Absorptive capacity was assessed by determination of plasma [[sup.2]H]- and [[sup.13]C]glucose concentrations after intraduodenal administration of [[sup.2]H]glucose and naturally enriched [[sup.13]C]sucrose, respectively. Small intestinal morphology, proliferation, apoptosis, and gene expression of intestinal transcription factors (mRNA levels of Cdx-2, Gata-4, and Hnf-1[alpha], and Cdx-2 protein levels) were similar in cholestatic, bile-deficient, and control rats. The (unlabeled) blood glucose response after intraduodenal administration was delayed in cholestatic animals, but the absorption over 180 min was quantitatively similar between the groups. Plasma concentrations of [[sup.2]H]glucose and [[sup.13]C]glucose peaked to similar extents in all groups within 7.5 and 30 min, respectively. Absorption of [[sup.2]H]glucose and [[sup.13]C]glucose in plasma was similar in all groups. The present data indicate that neither accumulation of bile salts in the body, nor their intestinal deficiency, two characteristic features of cholestasis, affect rat small intestinal proliferation, differentiation, apoptosis, or its capacity to digest and absorb carbohydrates. small intestine; cholestasis; bile deficiency; carbohydrate absorption

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) both play a role in the control of glucose homeostasis, and GIP is implicated in the regulation of energy storage. The capacity of carbohydrates to induce secretion of these incretin hormones could be one of the factors determining the metabolic quality of different types of carbohydrates. We analyzed the correlation between the rate of intestinal absorption of (starch-derived) glucose and plasma concentrations of GLP-1 and GIP after ingestion of glucose and starchy foods with a different content of rapidly and slowly available glucose. In a crossover study, glucose, insulin, GLP-1, and GIP concentrations were monitored for 6 h after consumption of glucose, uncooked cornstarch (UCCS) or corn pasta in 7 healthy men. All test meals were naturally labeled with [sup.13]C. Using a primed, continuous D-[6,6- [sup.2][H.sub.2]]glucose infusion, the rate of appearance of exogenous glucose (RaEx) was estimated, reflecting the rate of intestinal glucose absorption. GLP-1 concentrations increased significantly from 180 to 300 min after ingestion of UCCS, the starch product with a high content of slowly available glucose. A high GIP response in the early postprandial phase (15-90 min) occurred after consumption of glucose. There was a strong positive within-subject correlation between RaEx and GIP concentrations (r = 0.73, P < 0.01) across the test meals. Rapidly and slowly digestible carbohydrates differ considerably in their ability to stimulate secretion of incretin hormones; the metabolic consequences of such differences warrant exploration. KEY WORDS: * starch * glucose absorption * glucagon like peptide-1 * glucose-dependent insulinotropic peptide * stable isotopes

Fibrates are drugs of choice in patients with hypertriglyceridemia (HTG), but may increase the risk for gallstones by decreasing bile acid synthesis. Fish oil might be a therapeutic alternative, but its effect on bile acid metabolism in humans is unknown. We compared the effects of triglyceride-lowering therapy by fish oil or bezafibrate on cholesterol synthesis and bile acid metabolism in HTG. Cholesterol synthesis, bile acid pool sizes, and synthesis rates were compared between 9 male HTG patients and 10 normolipidemic controls matched for age, sex, and BMI. Effects of bezafibrate or fish oil were studied only in HTG patients in a randomized crossover trial. Patients had 14- fold higher serum triglyceride concentrations and greater cholesterol synthesis, as indicated by a 107% higher ratio of serum lathosterol to cholesterol (P < 0.01) than controls. The groups did not differ in bile acid metabolism. Both bezafibrate and fish oil reduced serum TG concentration (-68 and -51% vs. baseline, respectively). Compared with baseline, bezafibrate therapy was associated with reduced cholesterol synthesis (-25%, P = 0.009) without changes in bile acid synthesis rate and pool size. In contrast, fish oil increased bile acid synthesis (+31% vs. baseline, P = 0.07 and +53% vs. bezafibrate, P = 0.02) and altered bile acid distribution, as reflected by an increased ratio of the cholic acid (CA) synthesis rate to the chenodeoxycholic acid (CDCA) synthesis rate (+35% vs baseline, P = 0.05 and + 32% vs bezafibrate, P = 0.07) without effects on bile acid pool size or cholesterol synthesis. In conclusion, cholesterol synthesis is greater in HTG patients than in controls, whereas bile acid synthesis does not differ. Bezafibrate and fish oil have similar triglyceride-lowering capacities, but distinct effects on cholesterol synthesis. Bile acid synthesis is increased by fish oil, but not by bezafibrate therapy. KEY WORDS: * triglycerides * bezafibrate * fish oil * bile acid synthesis

The results of our previous study suggested that in addition to the small intestinal lactase activity and transit time, colonic processing of lactose may play a role in lactose intolerance. We investigated whether colonic fermentation of lactose is correlated with lactose intolerance. After 28 Chinese subjects had undergone 1 glucose (placebo) and 2 lactose challenges, consistent lactose tolerant (n = 7) and intolerant (n = 5) subjects with no complaints after glucose administration were classified on the basis of the 6-h symptom scores. Before the challenges, fecal samples were collected for in vitro incubation with lactose. The incubation was carried out in a static system under anaerobic conditions for 5 h during which samples were taken for measurement of short-chain fatty acids, lactate, lactose, glucose, and galactose. Fecal bacterial composition was determined by fluorescent in situ hybridization. The tolerant and intolerant groups did not differ in the rate or degree of hydrolysis of lactose or production of glucose and galactose. The intolerant group produced D- and L-lactate, acetate, propionate, and butyrate significantly faster than the tolerant group. In the intolerant group, the amounts of acetate, propionate, butyrate, and L-lactate produced were higher than those in the tolerant group. Fecal bacterial composition did not differ between the 2 groups. The results indicate that the degree and rate of lactose hydrolysis in the colon do not play a role in lactose intolerance. However, after lactose is hydrolyzed, a faster and higher production of microbial intermediate and end metabolites may be related to the occurrence of symptoms. KEY WORDS: * lactose intolerance * fecal microbiota * fermentation

In this study, we investigated in rats if hydroxycitric acid (HCA) reduces the postprandial glucose response by affecting gastric emptying or intestinal glucose absorption. We compared the effect of regulator HCA (310 mg/kg) and vehicle (control) on the glucose response after an intragastric or intraduodenal glucose load to investigate the role of altered gastric emptying. Steele's one-compartment model was used to investigate the effect of HCA on systemic glucose appearance after an intraduodenal glucose load, using [[U-.sup.13]C]-labeled glucose and D-[6,[6-.sup.2][H.sub.2]]-labeled glucose. Because an effect on postabsorptive glucose clearance could not be excluded, the effect of HCA on the appearance of enterally administered glucose in small intestinal tissue, liver, and portal and systemic circulation was determined by [[U-.sup.14]C]glucose infusion. Data show that HCA treatment delays the intestinal absorption of enterally administered glucose at the level of the small intestinal mucosa in rats. HCA strongly attenuated postprandial blood glucose levels after both intragastric (P < 0.01) and intraduodenal (P < 0.001) glucose administration, excluding a major effect of HCA on gastric emptying. HCA delayed the systemic appearance of exogenous glucose but did not affect the total fraction of glucose absorbed over the study period of 150 min. HCA treatment decreased concentrations of [[U-.sup.14]C]glucose in small intestinal tissue at 15 min after [[U-.sup.14]C]glucose administration (P < 0.05), in accordance with the concept that HCA delays the enteral absorption of glucose. These data support a possible role for HCA as food supplement in lowering postprandial glucose profiles. gastric emptying; Steele's one-compartment model; postprandial glucose response

Protein energy malnutrition is present in 18 to 56% of hemodialysis patients. Because hemodialysis has been regarded as a catabolic event, we studied whether consumption of a protein- and energy-enriched meal improves the whole body protein balance during dialysis in chronic hemodialysis (CHD) patients. Patients were studied on a single day between dialysis (HD- protocol) in the morning while fasting and in the afternoon while consuming six small test meals. Patients were also studied during two separate dialysis sessions (HD+ protocol). Patients were fasted during one and consumed the meals during the other. Whole body protein metabolism was studied by primed constant infusion of L-[1-[sup.13]C]valine. During HD-, feeding changed the negative whole body protein balance observed during fasting to a positive protein balance. Dialysis deepened the negative balance during fasting, whereas feeding during dialysis induced a positive balance comparable to the HD- protocol while feeding. Plasma valine concentrations during the studies were correlated with whole body protein synthesis and inversely correlated with whole body protein breakdown. We conclude that the consumption of a protein- and energy-enriched meal by CHD patients while dialyzing can strongly improve whole body protein balance, probably because of the increased amino acid concentrations in blood. protein turnover; stable isotope; valine