Impact of food processing on the blood cholesterol-lowering effect of cereal beta-glucan

Lead Research Organisation: King's College London
Department Name: Diabetes & Nutritional Sciences

Abstract

About 60% of the population have fasting blood cholesterol concentrations high enough to be a risk factor for coronary heart disease, which is responsible for the deaths of >60,000 people annually in the UK, many of which are potentially preventable with appropriate changes to diet and lifestyle. Water soluble types of dietary fibre (SDF), confer many health benefits; in particular, oat and barley beta-glucan (BG) is effective at reducing blood cholesterol and lipid concentrations and this has been recognised by European Food Safety Authority (EFSA). However, further processing of BG in foods can reduce its efficacy, and so a recommended intake of BG of at least 3 g/day requires large quantities (>100g) of unprocessed cereals such as oats and barley to be consumed daily. Most consumers would find this difficult or unpalatable, so approaches are required to incorporate BG into palatable, commonly consumed foods with demonstrable blood cholesterol and lipid lowering properties.

Despite the clear health benefits of BG, its mechanisms of action are still not well understood. It has been suggested that the ability of BG to lower cholesterol is triggered by the interference of this polymer and other types of SDF with various stages of lipid digestion, thus reducing or delaying lipid uptake. This then disturbs the recycling of bile salts (bio-surfactants produced by the liver which aid lipid digestion) from the gut back into the liver. Bile salts are cholesterol derivatives, so increased production of bile salts in the liver could reduce plasma cholesterol concentrations. It is not clear which aspects of lipid digestion are affected by BG, and therefore which molecular properties are crucial for its functionality.

The aim of this proposal is to determine the mechanisms of action of SDF and in particular BG on lipid digestion. Various mechanisms have been proposed, and they mostly involve the lipid digestion and transport processes. Therefore in vitro lipid digestion studies will allow us to study in detail all the different stages of lipid digestion including lipase activity and adsorption, bile salt adsorption and transport, and micelle formation and transport. The molecular and biochemical properties of BG and other other types of SDF will be determined using a range of state of the art techniques, including analytical centrifugation, and will allow us to determine which properties are important for functionality. Based on these findings, the effect of processing on BG will be studied to determine exactly why processing attenuates its ability to reduce blood cholesterol and lipids. This knowledge will then allow us to propose strategies by which SDF can be incorporated into palatable, manufactured foods and still retain their ability to reduce blood cholesterol and lipid concentrations.

Technical Summary

The effect of beta-glucan (BG), a water-soluble form of fibre, in lowering LDL cholesterol concentrations has been demonstrated by many research groups. This beneficial impact has been accepted as a valid health claim for BG, in non-processed or minimally processed forms of oats and barley, by EFSA. The mechanism(s) of action of BG are strongly linked to its capacity to generate high viscosity in the gastrointestinal tract and a subsequent decrease in bile reabsorption through decreases in rates of digestion, inhibition of lipolysis and/or transport of mixed micelles. The BG may also directly interact with lipase, bile salts and the mucus layer, leading to decreased bile recycling. However, the precise mechanisms are still not fully understood. Moreover, the cholesterol-lowering activity of BG varies significantly depending on food type, processing and storage conditions, mainly due to depolymerisation and poor solubility of BG.

The main aims of this project therefore are to understand (a) the mechanism(s) by which BG lowers blood cholesterol and (b) how the processing of BG-containing foods attenuates this capacity of the polymer. A multidisciplinary approach involving a range of in vitro methods, biochemical (e.g. in vitro digestion, enzyme kinetics) and biophysical (e.g. rheology, fluorescence microscopy), will be used. Samples of purified BG and BG-containing cereals and real foods (porridge & biscuits) will be characterised (e.g. molecular weight, polymer dissolution), before and after food processing, and their behaviour during in vitro digestion and their interactions with BS and lipase(s), will be studied. These samples will be subjected to a range of sophisticated in vitro digestion models allowing viscosity and interactions to be determined during breakdown and transport. This work will provide new information on how BG can be processed and added to food matrices in a way that maintains optimal health effects.

Planned Impact

The proposed project will benefit relevant stakeholders outside the academic communities, including the commercial sector, public sector bodies and the general public. It addresses one of the UK's major diet-related health challenges, cardiovascular disease (CVD). The project objective is also relevant to the BBSRC strategy priorities as it will "improve our understanding of the links between diet and health" by "optimisation of product formulation through new uses of existing ingredients, novel ingredients and novel formulations of ingredients." It therefore has huge potential long-term impact on a wide range of stakeholders from consumers to policy makers.

The number of individuals diagnosed with CVD in the UK has remained roughly static over the last 15-20 years at 5% of the adult population with 35% of cases being over the age of 55. Raised blood cholesterol is an important risk factor for CVD. Each year more than 150,000 deaths are caused by CVD in the UK. Associated with this alarming death rate, the annual financial cost exceeds £30bn, with cholesterol-lowering drugs alone costing the NHS approximately £500 million. Dietary interventions appear to be more appealing solutions, especially since this approach may simultaneously have positive effects on other diet-related conditions such as obesity and type II diabetes.

Our work will be particularly useful to the food industry and may lead to innovative applications in the future, such as the development of 'functional ingredients and foods' that have the capacity to consistently reduce blood cholesterol concentrations. The design of foods made from oats or barley beta-glucan would benefit public health. The main beneficiaries will be the DRINC members, especially those that are involved in the processing of oats and barley.

Individual consumers will have new knowledge regarding the health benefits of certain fibre-containing foods, together with a wider choice of manufactured foods with specific, proven health benefits. However, care has to be taken with the health communication aspects, since the consumption of these foods may only be effective as part of a healthy balanced diet. The foods ought to have comparable consumer acceptability, making it more convenient for consumers to adopt healthier dietary options. The long-term health benefits of reducing obesity and the risks associated with diabetes will benefit the lifelong health and well-being of individuals and improve their quality of life into old age.
The research should also help policy-makers in formulating new dietary advice and guidelines from new data on plant foods (oats and barley). The applicants regularly give talks at schools and media interviews about their research.

The applicants at the three academic centres will have regular meetings to discuss research findings. The consortium of food companies in DRINC will be offered first-market access to intellectual property if the results of the research lead to industrial applications. All the academic centres at KCL, IFR and Nottingham have mechanisms in place for exploring industrial applications from the research work. The applicants, research staff and PhD student will all play some role in undertaking impact activities. Many of the applicants have relevant experience for achieving successful knowledge exchange and impact with the beneficiaries. The applicants have also a long history of Knowledge Exchange and Commercialisation activities, particularly with the food industry, including industrial grants, patents, exploitation activities and dissemination events.

Publications

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Wilde PJ (2019) Oat and lipolysis: Food matrix effect. in Food chemistry

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Mackie A (2017) Oatmeal particle size alters glycemic index but not as a function of gastric emptying rate in American Journal of Physiology-Gastrointestinal and Liver Physiology

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Mackie AR (2017) Oatmeal particle size alters glycemic index but not as a function of gastric emptying rate. in American journal of physiology. Gastrointestinal and liver physiology

 
Description The research has started to produce insights into the mechanisms underpinning the health effects of beta-glucans. The viscosity of beta-glucan alone does not appear to be responsible for changes in lipid digestion, but some form of interaction with more complex structured forms of the oat/beta-glucan material seems to be involved. We are currently looking at how this impacts on the organisation of the lipids in the food matrix.

A novel assay for determining the rate and extent of hydration of oat beta-glucan (dietary fibre) has been developed and provides a useful means of characterising the physiological activity of this polysaccharide. This new method has also allowed us to evaluate the effects of food processing, notably mechanical (milling) and hydrothermal treatments, of oats on beta-glucan dissolution and solution viscosity, an important predictor of its nutritional properties (e.g. blood cholesterol-lowering).

This work has also shown two other key findings, in that the beta-glucan released from the matrix appears to induce depletion flocculation, which is consistent with the structure of the different oat materials studied. In addition the complex matrix of the oat materials appears to bind or sequester bile salts, which would also slow down lipid digestion. Pure beta-glucans do not appear to bind bile salts, further suggesting that beta-glucans alone are not as effective as more complex, less processed forms of oat products. These findings are starting to reveal insights into how the complexity of food matrices can have multi-factorial impacts on digestion and absorption, and not one single factor is responsible for health benefits.
Exploitation Route The research outcomes will be of potential interest to the Agriculture, Food & Drink, Manufacturing, including Industrial Biotechnology, and Healthcare sectors.

For example, our research findings could help food companies formulate new ingredients with enhanced nutritional properties, which could be used to produce new functional ingredients and food products (e.g. foods containing oat beta-glucan that are more effective at reducing blood cholesterol concentrations).
Sectors Agriculture, Food and Drink,Healthcare,Manufacturing, including Industrial Biotechology

 
Description The research findings are providing insights into the mechanisms underpinning the health benefits of cereal beta-glucans. This has led to commercial interest from food companies interested in the effects of fibre in foods, notably the effects of beta-glucan on blood cholesterol concentrations. For example, there have been discussions with the food industry about how different varieties of oats could be processed to maintain or even enhance their nutritional properties, such as preventing degradation of oat beta-glucan (i.e. retain its high average molecular weight) and also improves its capacity to hydrate and increase solution viscosity. Recently (2020) a food company interested in producing high fibre products in non-wheat breads has shown interest in collaborating with King's College London. Also, a new project funded by the food industry to study the effects of fibre on gut function, especially macronutrient digestion and absorption and its potential impact on metabolism, will begin in 2019-2020. Due to the Covid pandemic, there have been delays during the period 2020-22 in consolidating these potential collaborations with the food industry. However, further discussions are planned for 2022 with an international baking company to discuss the nutritional enhancement of wheat bread with a range of dietary fibre supplements. Also, this project has led to a new interlaboratory study for comparing different methods to determine the weight-average molecular weight and molecular weight distribution of six cereal beta-glucan isolates of nutritional importance (Ballance et al., 2022, Food Hydrocolloids, 127, [107510]. https://doi.org/10.1016/j.foodhyd.2022.107510). The results of this study are important for defining reliable and accurate methods for determining the molecular weight of water-soluble types of dietary fibre and are useful to academic researchers and technologists working in the food industry for characterising nutritional properties of fibre, not just cereal types but other edible plant sources .
First Year Of Impact 2020
Sector Agriculture, Food and Drink,Healthcare,Manufacturing, including Industrial Biotechology
Impact Types Economic

 
Title In vitro digestion of lipids in cereal tissue 
Description The development of in vitro digestibility assays to (a) model the rate and extent of lipid digestion of complex oat tissue, and (b) to determine the hydration kinetics of mixed-linkage beta-glucan from oat materials. (DOIs: 10.1016/j.carbpol.2017.02.077; 10.1016/j.jff.2017.09.011) 
Type Of Material Model of mechanisms or symptoms - in vitro 
Year Produced 2017 
Provided To Others? Yes  
Impact New in vitro methods to characterise the structure and properties of oat tissues, could potenially replace animal experiments or reduce the number of experimental animals used in research. 
 
Description Dr Susan Tosh - Ottawa University 
Organisation University of Ottawa
Country Canada 
Sector Academic/University 
PI Contribution We wrote a review: Grundy, M. M. L., Fardet, A., Tosh, S. M., Rich, G. T., & Wilde, P. J. (2018). Processing of oat: the impact on oat's cholesterol lowering effect. Food and Function.
Collaborator Contribution Dr Tosh provided us some of the beta-glucan used in the project. This was a beta-glucan preparation that was not commercially available but had a high purity and molecular weight.
Impact This material was used in the work presented in our manuscripts: Grundy, M. M.-L., Quint, J., Rieder, A., Ballance, S., Dreiss, C. A., Butterworth, P. J., & Ellis, P. R. (2017a). Impact of hydrothermal and mechanical processing on dissolution kinetics and rheology of oat ß-glucan. Carbohydrate Polymers, 166, 387-397. Grundy, M. M.-L., Quint, J., Rieder, A., Ballance, S., Dreiss, C. A., Cross, K. L., Gray, R., Bajka, B. H., Butterworth, P. J., Ellis, P. R., & Wilde, P. J. (2017b). The impact of oat structure and ß-glucan on in vitro lipid digestion. Journal of Functional Foods, 38(Part A), 378-388. Another manuscript that includes this material is currently under review in Food Hydrocolloids: Myriam Grundy, David Julian McClements, Simon Ballance, Pete Wilde, Influence of oat components on lipid digestion using an in vitro model: impact of viscosity and depletion flocculation mechanism.
Start Year 2015
 
Description MG: Impact of food processing on the blood cholesterol-lowering effect of cereal beta-glucan 
Organisation NOFIMA Ås
Country Norway 
Sector Private 
PI Contribution We were repsonsible for some of the characterisation work on oat materials, including the chemical composition and beta-glucan content of these materials, and also the dissolution kinetic studies of beta-glucan release.
Collaborator Contribution The Nofima group contributed some of the chemical and physical characterisation of the oat materials, including the polysaccharide analysis, solution rheology and molecular weight measurements of beta-glucan.
Impact The research collaboration has already resulted in a publication in Carbohydrate Polymers on a collaborative study of the impact of hydrothermal and mechanical processing on dissolution kinetics and rheology of oat beta-glucan.
Start Year 2015
 
Description Nofima - Dr Simon Ballance 
Organisation NOFIMA Ås
Country Norway 
Sector Private 
PI Contribution We gave an opportunity to Simon Ballance and his team in Nofima to work on beta-glucan in the context of lipid digestion.
Collaborator Contribution Simon Ballance provided the oat flakes, flour and BG32 (bran), and some of the purified bata-glucan (BG90). He also help us with the molecular weight measurements of the polysaccharides.
Impact From this collaboration, two publications were produced. Simon also permitted to collaborate with Frederic Prothon from Swedish Oat (now Naturex).
Start Year 2015
 
Description CBC Wellness Lecture 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Lunchtime Webinar for Cambridge Bioscience Campus and affiliates as part of their Wellness Webinars
Food Structure, appetite and energy intake: can you have your cake and eat it
Year(s) Of Engagement Activity 2022
 
Description Food Industry 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact Discussion about research findings to audience of food industry members, which has led to continued discussions about possible applications of new functional food ingredients in the area of food structure and health. especially the role of oat beta-glucan.
Year(s) Of Engagement Activity 2018,2019,2020
 
Description IFST Lecture Sept 2022 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited to give a public lecture to IFST (Institute of Food Science & Technology) on food structure, appetite and energy intake
Year(s) Of Engagement Activity 2022
 
Description School of Life Course Sciences Intiative 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact Research Associates symposium organised by the new School of Life Course Sciences at King's College London, to stimulate increased interests in research and encourage cross-disciplinary research activities.
Year(s) Of Engagement Activity 2018
 
Description Special Interest Group 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Undergraduate students
Results and Impact Discussion with nutritionists and dieticians (attendance, ~50) about the importance of food structure, including oats and behaviour of soluble dietary fibre, in influencing gut health, metabolism and health benefits.
Year(s) Of Engagement Activity 2017,2018,2019,2020
 
Description Wellbeing Lecture on food structure and appetite 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Other audiences
Results and Impact Webinar for the Healthy Eating - Wellbeing activity for all staff on the Norwich Research Park
Food Structure, appetite and energy intake: can you have your cake and eat it ?
Year(s) Of Engagement Activity 2021