Effect of mulberry fruit extract on glucose fluxes after a wheat porridge meal:a dual isotope study in healthy human subjects

Background: Previous research has shown the efficacy of mulberry extracts for lowering post-prandial glucose (PPG) responses. The postulated mechanism is slowing of glucose absorption, but effects on glucose disposal or endogenous production are also possible. This research assessed the effect of a specified mulberry fruit extract (MFE) on these three glucose flux parameters. Methods: The study used a double-blind, randomized, controlled, full cross-over design. In 3 counter-balanced treatments, 12 healthy adult male subjects, mean (SD) age 24.9 (2.50) years and body mass index 22.5 (1.57) kg/m2, consumed porridge prepared from 13C-labelled wheat, with or without addition of 0.75 g MFE, or a solution of 13C-glucose in water. A co-administered 2H-glucose venous infusion allowed for assessment of glucose disposal. Glucose flux parameters, cumulative absorption (time to 50% absorption, T50%abs), and PPG positive incremental area under the curve from 0 to 120 min (+iAUC0–120) were determined from total and isotopically labelled glucose in plasma. As this exploratory study was not powered for formal inferential statistical tests, results are reported as the mean percent difference (or minutes for T50%abs) between treatments with 95% CI. Results: MFE increased mean T50%abs by 10.2 min, (95% CI 3.9–16.5 min), and reduced mean 2 h post-meal rate of glucose appearance by 8.4% (95% CI −14.9 to −1.4%) and PPG + iAUC0-120 by 11% (95% CI −26.3 to −7.3%), with no significant changes in glucose disposal or endogenous production. Conclusions: The PPG-lowering effect of MFE is primarily mediated by a reduced rate of glucose uptake.</p

Quantifying the shifts in physicochemical property space introduced by the metabolism of small organic molecules

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Intestinal phase-II metabolism of quercetin in HT29 cells, 3D human intestinal tissues and in healthy volunteers: a qualitative comparison using LC-IMS-MS and LC-HRMS

Flavonoids are a large class of dietary molecules, among which quercetin is the most ubiquitous, which undergo an extensive intestinal phase-II metabolism. We compared the in vivo metabolism of quercetin in healthy volunteers with two in vitro models, HT29 cells and 3 D human intestinal tissues. Supernatants of the in vitro experiments and the human intestinal fluids (HIF) were analyzed by LC-IMS-MS and LC-HRMS in a qualitative way. Quercetin glucuronides, sulfates and their methyl conjugates were detected in all three systems. The metabolic profiles were found to be different, both in terms of the metabolites produced and their relative proportions. In particular, quercetin sulfates were almost absent in supernatants from HT29 cells incubations while they were a major metabolite in HIF and also found in 3 D intestinal tissues incubations. IMS provided structural information as well as a third dimension of characterization, while HRMS brought increased sensitivity and MS/MS confirmation. HT29 cells are a useful tool to generate phase-II metabolites but do not represent the in vivo situation. 3 D intestinal tissues appear as a more relevant tool to study the intestinal phase-II metabolism of flavonoids.status: publishe

Intestinal disposition of quercetin and its phase-II metabolites after oral administration in healthy volunteers

OBJECTIVES: Quercetin is one of the main dietary flavonoids and undergoes a substantial intestinal phase-II metabolism. Quercetin conjugates have been detected in plasma and in urine, but their presence in the small intestine has not been assessed. This study aimed to investigate the intestinal metabolism and metabolite excretion of quercetin by the human small intestinal wall after oral dosing. METHODS: Six healthy volunteers were given a capsule of 500 mg of quercetin with 240 ml of water. Duodenal fluids were collected using the intraluminal sampling technique for 4 h and analysed by LC-MS/MS. KEY FINDINGS: Phase-II metabolites of quercetin were detected and quantified in aspirated intestinal fluids. Metabolites appeared almost immediately after administration, indicating an intestinal metabolism and apical excretion into the lumen. Quercetin-3'-O-glucuronide was found to be the main intestinal metabolite. Our results could not conclude on the enterohepatic recycling of quercetin or its metabolites, although several individual profiles showed distinctive peaks. CONCLUSIONS: This study highlights the intestinal metabolism and excretion of quercetin and its conjugates in humans and gives insights into the relevant concentrations which should be used to investigate potential food-drug interactions in vitro.status: publishe

Effect of mulberry fruit extract on glucose fluxes after a wheat porridge meal:a dual isotope study in healthy human subjects

Background: Previous research has shown the efficacy of mulberry extracts for lowering post-prandial glucose (PPG) responses. The postulated mechanism is slowing of glucose absorption, but effects on glucose disposal or endogenous production are also possible. This research assessed the effect of a specified mulberry fruit extract (MFE) on these three glucose flux parameters. Methods: The study used a double-blind, randomized, controlled, full cross-over design. In 3 counter-balanced treatments, 12 healthy adult male subjects, mean (SD) age 24.9 (2.50) years and body mass index 22.5 (1.57) kg/m2, consumed porridge prepared from 13C-labelled wheat, with or without addition of 0.75 g MFE, or a solution of 13C-glucose in water. A co-administered 2H-glucose venous infusion allowed for assessment of glucose disposal. Glucose flux parameters, cumulative absorption (time to 50% absorption, T50%abs), and PPG positive incremental area under the curve from 0 to 120 min (+iAUC0–120) were determined from total and isotopically labelled glucose in plasma. As this exploratory study was not powered for formal inferential statistical tests, results are reported as the mean percent difference (or minutes for T50%abs) between treatments with 95% CI. Results: MFE increased mean T50%abs by 10.2 min, (95% CI 3.9–16.5 min), and reduced mean 2 h post-meal rate of glucose appearance by 8.4% (95% CI −14.9 to −1.4%) and PPG + iAUC0-120 by 11% (95% CI −26.3 to −7.3%), with no significant changes in glucose disposal or endogenous production. Conclusions: The PPG-lowering effect of MFE is primarily mediated by a reduced rate of glucose uptake.</p

Impact of Proteins on the Uptake, Distribution, and Excretion of Phenolics in the Human Body

Polyphenols, a complex group of secondary plant metabolites, including flavonoids and phenolic acids, have been studied in depth for their health-related benefits. The activity of polyphenols may, however, be hampered when consumed together with protein-rich food products, due to the interaction between polyphenols and proteins. To that end we have tested the bioavailability of representatives of a range of polyphenol classes when consumed for five days in different beverage matrices. In a placebo-controlled, randomized, cross-over study, 35 healthy males received either six placebo gelatine capsules consumed with 200 mL of water, six capsules with 800 mg polyphenols derived from red wine and grape extracts, or the same dose of polyphenols incorporated into 200 mL of either pasteurized dairy drink, soy drink (both containing 3.4% proteins) or fruit-flavoured protein-free drink . At the end of the intervention urine and blood was collected and analysed for a broad range of phenolic compounds using Gas Chromatography–Mass Spectrometry (GC-MS), Liquid Chromatography–Multiple Reaction Monitoring–Mass Spectrometry (LC-MRM-MS), and Nuclear Magnetic Resonance (NMR) spectroscopy techniques. The plasma and urine concentrations of the polyphenols identified increased with all formats, including the protein-rich beverages. Compared to capsule ingestion, consumption of polyphenol-rich beverages containing either dairy, soy or no proteins had minor to no effect on the bioavailability and excretion of phenolic compounds in plasma (118% ± 9%) and urine (98% ± 2%). We conclude that intake of polyphenols incorporated in protein-rich drinks does not have a major impact on the bioavailability of a range of different polyphenols and phenolic metabolites

Intragastric layering of lipids delays lipid absorption and increases plasma CCK but has minor effects on gastric emptying and appetite

Foltz M, Maljaars J, Schuring EA, van der Wal RJ, Boer T, Duchateau GS, Peters HP, Stellaard F, Masclee AA. Intragastric layering of lipids delays lipid absorption and increases plasma CCK but has minor effects on gastric emptying and appetite. Am J Physiol Gastrointest Liver Physiol 296: G982-G991, 2009. First published March 26, 2009; doi:10.1152/ajpgi.90579.2008.-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-[C-13] 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 C-13-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 +/- 7 min; OT: 75 +/- 10 min; P +/- 0.01) and time at maximum concentration (EM: 162 +/- 18 min; OT: 280 +/- 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