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Among vegetable oils, chia oil has been gaining interest in recent years due to its high linolenic acid content (ALA, 18:3 ω3).

To assess composite endpoints combining glycemic control (HbA1c7.0%, ≤6.5%, or5.7%) with weight loss (≥5%, ≥10%, or ≥15%) and without hypoglycemia with tirzepatide in type 2 diabetes (T2D).Data from the phase 3 SURPASS program were evaluated post hoc by trial. Participants with T2D were randomized to tirzepatide (5, 10, and 15 mg), placebo (SURPASS-1,5), semaglutide 1 mg (SURPASS-2), or titrated basal insulin (SURPASS-3,4). The proportions of participants achieving the composite endpoints were compared between tirzepatide and the respective comparator groups at week 40/52.The proportions of participants achieving an HbA1c value of7.0% with ≥5% weight loss and without hypoglycemia ranged from 43% to 82% with tirzepatide across the SURPASS-1 to -5 trials versus 4%-5% with placebo, 51% with semaglutide 1 mg, and 5% with basal insulin (p0.001 versus all comparators). The proportions of participants achieving an HbA1c value of7.0% with ≥10% or ≥15% weight loss and without hypoglycemia were significantly higher with all tirzepatide doses versus comparators across trials (p0.001 or p0.05). Similar results were observed for all other combinations of endpoints with an HbA1c value of ≤6.5% or5.7%, with more tirzepatide-treated participants achieving these endpoints versus those in the comparator groups, including semaglutide.Across the SURPASS-1 to -5 clinical trials, more tirzepatide-treated participants with T2D achieved clinically meaningful composite endpoints, which included reaching glycemic targets with various degrees of weight loss and without hypoglycemia, than those in the comparator groups. This article is protected by copyright. All rights reserved.

This article reviews the efficacy and safety data of tirzepatide, a once-weekly, novel glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 (GLP-1) receptor agonist approved in the United States, the European Union, and other regions for the treatment of type 2 diabetes. All doses of tirzepatide demonstrated superiority in reducing A1C and body weight from baseline versus placebo or active comparators. The safety profile of tirzepatide was consistent with that of the GLP-1 receptor agonist class, with mild to moderate and transient gastrointestinal side effects being the most common adverse events. With clinically and statistically significant reductions in A1C and body weight without increased risk of hypoglycemia in various populations, tirzepatide has demonstrated potential as a first-in-class treatment option for many people with type 2 diabetes.

The gold standard for nutrition studies is clinical trials but they are expensive and variable, and do not always provide the mechanistic information required, hence the increased use of in vitro and increasingly in silico simulations of digestion. In this review, we give examples of the main simulations being used to model upper gastrointestinal tract digestion. This review ranges from the selection of enzymes to the interpretation of results from static models to fully dynamic models. We describe the modifications made to accommodate different demographic groups (infants, the elderly, etc.). We list examples of the application of the different models as well as giving the advantages and disadvantages. A model is only useful if it predicts or aids the understanding of physiological behaviour. Thus, the final section of the review makes a comparison of results obtained from experiments undertaken using in vitro simulations with those obtained in vivo. This comparison will help the reader understand the appropriateness of each model for the type of measurement to be undertaken. In particular, human studies tend to measure bioactive concentrations in blood and not in the gastrointestinal tract whereas in vitro studies often only produce data on release of nutrients into the gut lumen. This is the difficulty of comparing bioaccessibility as generated in vitro with bioavailability as generated in vivo. It is apparent that the models being used are increasingly being validated with in vivo data and this bodes well for the future.

peer-reviewed Caseins and whey proteins are known as ‘slow’ and ‘fast’ proteins, respectively, based on their amino acid absorption rate. However, there is limited understanding of the mechanisms controlling their behaviour during gastro-intestinal transit. A protein model system (8% total protein) with varying casein:whey protein ratios (0:100, 20:80, 50:50 and 80:20) were subjected to in vitro gastro-intestinal digestion using a semi-dynamic gastric model, a static intestinal model and an ex vivo absorption model (Ussing chambers). The casein-rich (≥50%) samples showed the formation of solid coagula that were persistent throughout gastric digestion, which caused a delay in nutrient emptying, slower digestion and leucine absorption kinetics. In contrast, whey proteins formed more soluble aggregates during the gastric phase, which led to faster gastric emptying, rapid intestinal hydrolysis, and higher and faster leucine absorption. This work shows the key role of the gastric restructuring for the overall digestive mechanism and kinetics of food, in particular proteins.

As plant proteins are increasingly used as a source of amino acids in the diet, studies on in vitro digestion of plant proteins are key to understand the different factors affecting proteolysis, with the ultimate goal of optimising the nutritional composition/intake of plant protein-rich products. More realistic scenarios including the most likely food matrix and physiologically relevant gastrointestinal (GI) conditions should be considered when assessing the in vitro digestion of proteins. The research described here compares the extent of hydrolysis of proteins from peanuts and wheat bread, in particular the vicilin-like 7S globulin (Ara h 1) and gliadin, respectively, with three GI scenarios simulating either infant, early phase adult (fed state) or late phase adult (fasted state) conditions. The digestibility of these proteins, in isolation or when naturally present in the respective food matrix, has been evaluated with SDS-PAGE, LC-MS/MS and a spectrophotometric assay. Results from the food matrices showed lower extent of total protein GI digestion under simulated infant conditions, intermediate behaviour under fed state adult conditions and larger extent under fasted state adult conditions. This was also the case for isolated gliadin. However, isolated Ara h 1 only showed lower extent of proteolysis in the gastric phase under infant conditions, reaching a similar extent to both adult conditions over the course of the intestinal phase. The food matrix seems to have delayed the proteolysis. Choosing an appropriate GI scenario as well as the matrix of the end food product is paramount when assessing in vitro protein digestion.

An innovative procedure for plant chloroplasts isolation has been proposed, which consists of juice extraction by physical fractionation from plant material and recovery of its chloroplast-rich fraction (CRF) by centrifugation. This simple method has been applied to pea vine haulm subjected to different post-harvest treatments: blanching, storage at different relative humidity values and fermentation. Additionally, freeze storage of the extracted juice was carried out. The macronutrient (total lipids, proteins, ash and carbohydrates) and micronutrient (fatty acids, chlorophylls, β-carotene, α-tocopherol and ascorbic acid) content and composition of the CRF have been determined. The CRF isolated from fresh pea vine haulm is a potential source of essential micronutrients (α-linolenic acid, β-carotene, α-tocopherol) and carbohydrates, whereas the post-harvest treatments trialled have a detrimental effect on the nutritional content. Industrial applications for the recovered nutritionally rich fraction, such as food supplement ingredient or animal feeding, are likely envisaged, while optimising the use of green haulm.

Calcium plays an important dual role in lipid digestion: promoting removal of long-chain fatty acids from the oil–water interface by forming insoluble calcium soaps while also limiting their bioaccessibility. This becomes more significant in food containing high calcium concentration, such as dairy products. Nevertheless, scarce attention has been paid to the effect of calcium on the interfacial properties during lipid digestion, despite this being largely an interfacial reaction. This study focused on the dynamics of the formation of calcium soaps at the oil–water interface during lipolysis by pancreatic lipase in the absence and presence of the two primary human bile salts (sodium glycocholate or sodium glycochenodeoxycholate). The competitive adsorption of lipase, bile salts, and lipolysis products, as well as the formation of calcium soaps in the presence of increasing concentrations of calcium were mainly characterized by recording the interfacial tension and dilatational modulus in situ. In the absence of bile salts, calcium complexes with fatty acids at the oil–water interface forming a relatively strong viscoelastic network of calcium soaps over time. The dilatational modulus of the calcium soap network is directly related to the interfacial concentration of lipolysis products and the calcium bulk concentration. Calcium soaps are also visualized forming a continuous rough layer on the surface of oil droplets immersed in simulated intestinal aqueous phase. Despite bile salts having different surface activity, they play a similar role on the interfacial competition with lipase and lipolysis products although altering their kinetics. The presence of bile salts disrupts the network of calcium soaps, as suggested by the decrease in the dilatational modulus and the formation of calcium soap islands on the surface of the oil droplets. The accelerant effect of calcium on lipolysis is probably because of fatty acid complexation and subsequent removal from the interface rather than reduced electrostatic repulsion between lipase and bile salt molecules and promoted lipase adsorption. The work shown here has implications for the delivery of oil-soluble bioactives in the presence of calcium.

Evaluating the gastrointestinal (GI) fate of proteins is part of the assessment to determine whether proteins are safe to consume. In vitro digestion tests are often used for screening purposes in the evaluation of potential allergenicity. However, the current pepsin resistant test used by the European Food Safety Authority, only corresponds to fasted gastric conditions representative of a late phase adult stomach. In addition, these tests are performed on isolated proteins and the effect of the food matrix and processing are not systematically considered. The aim of this research is to compare three different static in vitro GI scenarios that are physiologically relevant. Namely, an infant, early phase (fed state) adult and late phase (fasted state) adult model. These protocols are applied to well-characterised isolated dairy (β-lactoglobulin and β-casein) and egg (lysozyme and ovalbumin) proteins and the impact of food matrix/processing on their proteolysis is also investigated. A combination of SDS-PAGE, LC-MS/MS and spectrophotometric assay was used for the evaluation of the proteolysis. Results highlight differences across the three GI scenarios whether on isolated proteins or within food matrices. The infant model led to incomplete digestion, leaving intact egg proteins, either isolated or in the food matrix, and intact β-lactoglobulin in the milk. In addition, peptides greater than 9 amino acids were found throughout the intestinal phase for all proteins studied, regardless of the scenario. This reinforces the difficulty of linking protein digestibility to potential allergenicity because many other factors are involved that need further investigation.

The primary objective of the assessment of novel proteins is to evaluate whether they are safe to consume, including potential allergenicity. As part of a suite of assessments, the in vitro digestion of protein has been seen as a useful exercise. Thus, in line with the guidance offered by the EFSA GMO Panel we are using an early phase and a late phase gastric simulation as well as a simulation of the infant gastric compartment, all followed by intestinal phases. These digestion scenarios were used with a panel of 10 proteins from plant and animal origin that were proteins with distinct allergenic potential. The results from the SDS‐PAGE and densitometry show significant and mainly expected differences between the different digestion scenarios. The milk proteins were fully digested in the intestinal phase but the BLG was largely resistant to pepsin. In contrast, the egg proteins showed significant persistence except under late phase conditions. For the plant proteins, KTI and ConA were largely resistant to all conditions whereas LIP and AP were only resistant to infant conditions. Similarly, Ara h 1 showed some resistance to infant gastric conditions. The LC‐MS analysis of peptides was able to highlight a number of clusters where differences were seen between the digestion scenarios and these could in some cases be mapped onto the primary sequence and where relevant compared with known allergenic epitopes. Under the different digestion scenarios, we were able to show significant differences in the persistence of peptides larger than 9 amino acids and significant overlap of abundant peptides from early phase intestinal digestion and known epitopes for a number of proteins. Although, linking these differences to immunological responses (epitope mapping) still seems to be quite challenging, there are clear differences between scenarios and strong potential for improved risk assessment.

Because of their unusual chemical structure, bile salts (BS) play a fundamental role in intestinal lipid digestion and transport. BS have a planar arrangement of hydrophobic and hydrophilic moieties, which enables the BS molecules to form peculiar self-assembled structures in aqueous solutions. This molecular arrangement also has an influence on specific interactions of BS with lipid molecules and other compounds of ingested food and digestive media. Those comprise the complex scenario in which lipolysis occurs. In this review, we discuss the BS synthesis, composition, bulk interactions and mode of action during lipid digestion and transport. We look specifically into surfactant-related functions of BS that affect lipolysis, such as interactions with dietary fibre and emulsifiers, the interfacial activity in facilitating lipase and colipase anchoring to the lipid substrate interface, and finally the role of BS in the intestinal transport of lipids. Unravelling the roles of BS in the processing of lipids in the gastrointestinal tract requires a detailed analysis of their interactions with different compounds. We provide an update on the most recent findings concerning two areas of BS involvement: lipolysis and intestinal transport. We first explore the interactions of BS with various dietary fibres and food emulsifiers in bulk and at interfaces, as these appear to be key aspects for understanding interactions with digestive media. Next, we explore the interactions of BS with components of the intestinal digestion environment, and the role of BS in displacing material from the oil-water interface and facilitating adsorption of lipase. We look into the process of desorption, solubilisation of lipolysis, products and formation of mixed micelles. Finally, the BS-driven interactions of colloidal particles with the small intestinal mucus layer are considered, providing new findings for the overall assessment of the role of BS in lipid digestion and intestinal transport. This review offers a unique compilation of well-established and most recent studies dealing with the interactions of BS with food emulsifiers, nanoparticles and dietary fibre, as well as with the luminal compounds of the gut, such as lipase-colipase, triglycerides and intestinal mucus. The combined analysis of these complex interactions may provide crucial information on the pattern and extent of lipid digestion. Such knowledge is important for controlling the uptake of dietary lipids or lipophilic pharmaceuticals in the gastrointestinal tract through the engineering of novel food structures or colloidal drug-delivery systems.

Uptake relates to the term bioaccessibility, which is the fraction of a dose that is potentially available for absorption or uptake after digestion. Transcellular uptake can take place via two modes of transport: active and passive. The process of evaluation of digestion and uptake of bio-nanosystems in food containing bioactive compounds starts with the modeling of in vivo characteristics by using in vitro methods. Interactions within the food matrix before and after intake need further understanding to unravel the fate during digestion and absorption. The availability of the interior network for the incorporation of bioactive compounds can potentially increase uptake, absorption, and bioavailability. The rate and extent of lipid digestion also depends on other initial parameters, such as the emulsifier type, oil type and oil content used, and stability under gastrointestinal conditions. The emulsifier type can also have an impact on the interfacial stability upon digestion and permeability across the intestinal barrier.

The primary objective of the assessment of novel proteins is to evaluate whether they are safe to consume, including potential allergenicity. As part of a suite of assessments, the in vitro digestion of protein has been seen as a useful exercise. Thus, in line with the guidance offered by the EFSA GMO Panel we are using an early phase and a late phase gastric simulation as well as a simulation of the infant gastric compartment, all followed by intestinal phases. These digestion scenarios were used with a panel of 10 proteins from plant and animal origin that were proteins with distinct allergenic potential. The results from the SDS‐PAGE and densitometry show significant and mainly expected differences between the different digestion scenarios. The milk proteins were fully digested in the intestinal phase but the BLG was largely resistant to pepsin. In contrast, the egg proteins showed significant persistence except under late phase conditions. For the plant proteins, KTI and ConA were largely resistant to all conditions whereas LIP and AP were only resistant to infant conditions. Similarly, Ara h 1 showed some resistance to infant gastric conditions. The LC‐MS analysis of peptides was able to highlight a number of clusters where differences were seen between the digestion scenarios and these could in some cases be mapped onto the primary sequence and where relevant compared with known allergenic epitopes. Under the different digestion scenarios, we were able to show significant differences in the persistence of peptides larger than 9 amino acids and significant overlap of abundant peptides from early phase intestinal digestion and known epitopes for a number of proteins. Although, linking these differences to immunological responses (epitope mapping) still seems to be quite challenging, there are clear differences between scenarios and strong potential for improved risk assessment.

Tesis Univ. Granada. Departamento de Física Aplicada, Este trabajo ha sido financiado por: Ministerio de Ciencia e Innovación, bajo los proyectos MAT2007-66662-C02-01, MAT2010-20370 y JCI-2009-03823; Junta de Adnalucía, proyectos P07-FQM-03099 y P09-FQM-4698; Universidad de Granada, proyecto CEIBiotic 20F12/16; así como al proyecto EU-FP7-PERG07-GA-2010-268315-ColloDi

The development of emulsion-based products through optimisation of ingredients, reduction in energy-input during manufacture, while fulfilling healthy attributes, are major objectives within the food industry. Instant emulsions can meet these features, but comprehensive studies are necessary to investigate the effect of the initial formulation on the final microstructure and, in turn, on the in vitro lipolysis, comprising the double aim of this work. The instant emulsion is formed within 1.5–3 min after pouring the aqueous phase into the oil phase which contains a mixture of emulsifier (Tween 20), swelling particles (Sephadex) and thickeners (hydroxypropylmethylcellulose, HPMC, and guar gum, GG) under mild shearing (180 rpm). The creation of oil-in-water emulsions is monitored in situ by viscosity analysis, the final microstructure visualised by microscopy and the release of free fatty acids under simulated intestinal conditions quantified by titration. Increasing the concentration and molecular weight (Mw) of GG leads to smaller emulsion droplets due to increased bulk viscosity upon shearing. This droplet size reduction is magnified when increasing the Mw of HPMC or swelling capacity of viscosifying particles. In addition, in the absence of the emulsifier Tween 20, the sole use of high-Mw HPMC is effective in emulsification due to combined increased bulk viscosity and interfacial activity. Hence, optimisation of the ingredient choice and usage level is possible when designing microstructures. Finally, emulsions with larger droplet size (>20 μm) display a slower rate and lower extent of lipolysis, while finer emulsions (droplet size ≤20 μm) exhibit maximum rate and extent profiles. This correlates with the extent of emulsion destabilisation observed under intestinal conditions.

The development of emulsion-based products through optimisation of ingredients, reduction in energy-input during manufacture, while fulfilling healthy attributes, are major objectives within the food industry. Instant emulsions can meet these features, but comprehensive studies are necessary to investigate the effect of the initial formulation on the final microstructure and, in turn, on the in vitro lipolysis, comprising the double aim of this work. The instant emulsion is formed within 1.5–3 min after pouring the aqueous phase into the oil phase which contains a mixture of emulsifier (Tween 20), swelling particles (Sephadex) and thickeners (hydroxypropylmethylcellulose, HPMC, and guar gum, GG) under mild shearing (180 rpm). The creation of oil-in-water emulsions is monitored in situ by viscosity analysis, the final microstructure visualised by microscopy and the release of free fatty acids under simulated intestinal conditions quantified by titration. Increasing the concentration and molecular weight (Mw) of GG leads to smaller emulsion droplets due to increased bulk viscosity upon shearing. This droplet size reduction is magnified when increasing the Mw of HPMC or swelling capacity of viscosifying particles. In addition, in the absence of the emulsifier Tween 20, the sole use of high-Mw HPMC is effective in emulsification due to combined increased bulk viscosity and interfacial activity. Hence, optimisation of the ingredient choice and usage level is possible when designing microstructures. Finally, emulsions with larger droplet size (>20 μm) display a slower rate and lower extent of lipolysis, while finer emulsions (droplet size ≤20 μm) exhibit maximum rate and extent profiles. This correlates with the extent of emulsion destabilisation observed under intestinal conditions.

It is important to understand how interfacial composition influences the digestion of coated interfaces in order to rationally design emulsion based food products with specific digestion profiles. This study has been designed to investigate the effects of gastrointestinal digestion on protein covered interfaces. In this work, we have used a new apparatus fully designed and assembled at the University of Granada: the OCTOPUS. This new device enables the design of a customised static sequential in vitro digestion process in a single droplet. Physiological conditions of each compartment/step of the digestion process are met through subphase exchange of artificial digestive media, hence mimicking the transit through the gastrointestinal tract. We can measure in situ the evolution of the interfacial tension throughout the whole simulated gastrointestinal transit and the mechanical properties of the interfacial layer (interfacial dilatational modulus) after each digestion stage (mouth, stomach, small intestines). The in vitro digestion model used here focuses on pepsinolysis and lipolysis of two dairy proteins: β-lactoglobulin (BLG) and β-casein (BCS) adsorbed at the olive oil–water interface. The results show different susceptibilities of interfacial layers of BLG and BCS to pepsinolysis; while pepsinolysis of adsorbed BLG weakens the interfacial network, pepsinolysis of adsorbed BCS strengthens it as measured by the dilatational moduli. These numbers provide an interfacial scenario for previous findings on emulsification of these proteins, which was found to improve BLG pepsinolysis but somehow protected BCS from pepsinolysis in the stomach. The desorption profiles provide quantification of the extent of lipid digestion in subsequent simulated intestinal fluid containing lipase. The extent of lipid hydrolysis was found to be similar in BLG and BCS covered interfaces and comparable to that in the absence of coverage (pure oil–water interface) indicating that proteins do not comprise a barrier to lipolysis. This similar susceptibility is attributed to the similar interfacial properties of the interfaces reaching the duodenum despite the structural differences between native BCS and BLG, thus demonstrating the impact of the transit through the gut on lipolysis. This research allows identification of the interfacial mechanisms affecting enzymatic hydrolysis of proteins and lipolysis. The results can be exploited in tailoring novel food matrices with improved functional properties such as decreased digestibility, controlled energy intake and low allergenicity.

Cellulose ethers are usually used as secondary emulsifiers. Different types of commercial hydroxypropylmethylcellulose (HPMC) have been used here as the main emulsifier of oil-in-water emulsions to probe their impact on the lipid digestibility under simulated intestinal conditions. The droplet size distribution and ζ-potential of the emulsions subjected to in-vitro lipolysis have been compared with that of control samples (non-digested). The lipolysis has been quantified over time by means of the pH-stat method. The displacement of HPMC from the oil-water interface by bile salts has been assessed by interfacial tension technique. Results show that HPMC delays the lipid digestion of emulsions regardless of the Mw and methoxyl content. The destabilisation of emulsions under intestinal conditions as well as the resistance of HPMC to be displaced from the emulsion interface by bile salts may contribute to this feature. This provides new insights into the mechanisms whereby dietary fibre reduces fat absorption.

Introduction The development of the coaxial double capillary 15years ago opened up the possibility to undertake accurate desorption and penetration studies of interfacial layers in the pendant drop technique. Drop and bubble methods offer several advantages with respect to other interfacial techniques. They allow a more stringent control of the environmental conditions, use smaller amounts of material and provide a much higher interface/volume ratio than in conventional Langmuir Troughs. Experimental The coaxial capillary was developed 15years ago at the University of Granada as an accessory for the pendant drop surface film balance. It allows exchanging the subphase of the drop without disturbing the surface film and preserving the drop volume throughout the subphase exchange. Hence, this methodology enables one to carry out a great variety of interfacial studies well beyond the usual adsorption profiles. Penetration studies, sequential adsorption measurements, desorption kinetics, reversibility of adsorption and testing of enzymatic treatments on interfacial layers are amongst the principal applications. The coaxial capillary has been recently upgraded to a multi-exchange device which has boosted its applicability. It can be now used to address multilayer formation, create soft interfacial nano-composites such as membranes, polyelectrolyte assemblies and simulate in vitro digestion in a single droplet. Applications This review aims to compile the experimental work done, using the pendant drop subphase exchange in the last decade, and how its use has provided new insights into the surface/interfacial properties of many different materials. Special emphasis is placed on recent work regarding simulation of in vitro digestion in order to address issues relating to metabolism degradation profiles. The use of this methodology when dealing with interfacial studies allows setting the foundations of interfacial engineering technology. Based on subphase exchange experiments, we aim to develop models for competitive adsorption of different compounds at the interface and build up layer-by-layer interfacial structures. Future challenges comprise the design of finely adjusted nanoengineering systems, based on multilayer assemblies with tailored functionalities, to match the application demand.