Imperial College London

ProfessorGaryFrost

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Chair in Nutrition & Dietetics
 
 
 
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Contact

 

+44 (0)20 7594 0959g.frost Website

 
 
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Location

 

Commonwealth BiuldingHammersmith HospitalHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

521 results found

O'Gorman A, Gibbons H, Ryan MF, Gibney ER, Gibney MJ, Frost GS, Roche HM, Brennan Let al., 2017, Exploring the Links between Diet and Health in an Irish Cohort: A Lipidomic Approach, JOURNAL OF PROTEOME RESEARCH, Vol: 16, Pages: 1280-1287, ISSN: 1535-3893

Journal article

Garcia Perez I, Posma JM, Gibson R, Chambers ES, Hansen TH, Vestergaard H, Hansen T, Beckmann M, Pedersen O, Elliott P, Stamler J, Nicholson JK, Draper J, Mathers JC, Holmes E, Frost Get al., 2017, Objective assessment of dietary patterns using metabolic phenotyping: a randomized, controlled, crossover trial, The Lancet Diabetes & Endocrinology, Vol: 5, Pages: 184-195, ISSN: 2213-8587

Background: The burden of non-communicable diseases, such as obesity, diabetes, coronary heart disease and cancer, can be reduced by the consumption of healthy diets. Accurate monitoring of changes in dietary patterns in response to food policy implementation is challenging. Metabolic profiling allows simultaneous measurement of hundreds of metabolites in urine, many of them influenced by food intake. We aim to classify people according to dietary behaviour and enhance dietary reporting using metabolic profiling of urine.Methods: To develop metabolite models from 19 healthy volunteers who attended a clinical research unit for four day periods on four occasions. We used the World Health Organisation’s healthy eating guidelines (increase fruits, vegetables, wholegrains, dietary fibre and decrease fats, sugars, and salt) to develop four dietary interventions lasting for four days each that ranged from a diet associated with a low to high risk of developing non-communicable disease. Urine samples were measured by 1H-NMR spectroscopy. This study is registered as an International Standard Randomized Controlled Trial, number ISRCTN 43087333. INTERMAP U.K. (n=225) and a healthy-eating Danish cohort (n=66) were used as free-living validation datasets.Findings: There was clear separation between the urinary metabolite profiles of the four diets. We also demonstrated significant stepwise differences in metabolite levels between the lowest and highest metabolic risk diets and developed metabolite models for each diet. Application of the derived metabolite models to independent cohorts confirmed the association between urinary metabolic and dietary profiles in INTERMAP (P<0•001) and the Danish cohort (P<0•001).Interpretation: Urinary metabolite models, developed in a highly controlled environment, can classify groups of free-living people into consumers of dietary profiles associated with lower or higher non-communicable disease risk based on multivariate m

Journal article

Posma JM, Garcia Perez I, Heaton JC, Burdisso P, Mathers JC, Draper J, Lewis M, Lindon JC, Frost G, Holmes E, Nicholson JKet al., 2017, An integrated analytical and statistical two-dimensional spectroscopy strategy for metabolite identification: application to dietary biomarkers, Analytical Chemistry, Vol: 89, Pages: 3300-3309, ISSN: 1086-4377

A major purpose of exploratory metabolic profiling is for the identification of molecular species that are statistically associated with specific biological or medical outcomes; unfortunately the structure elucidation process of unknowns is often a major bottleneck in this process. We present here new holistic strategies that combine different statistical spectroscopic and analytical techniques to improve and simplify the process of metabolite identification. We exemplify these strategies using study data collected as part of a dietary intervention to improve health and which elicits a relatively subtle suite of changes from complex molecular profiles. We identify three new dietary biomarkers related to the consumption of peas (N-methyl nicotinic acid), apples (rhamnitol) and onions (N-acetyl-S-(1Z)-propenyl-cysteine-sulfoxide) that can be used to enhance dietary assessment and assess adherence to diet. As part of the strategy, we introduce a new probabilistic statistical spectroscopy tool, RED-STORM (Resolution EnhanceD SubseT Optimization by Reference Matching), that uses 2D J-resolved ¹H-NMR spectra for enhanced information recovery using the Bayesian paradigm to extract a subset of spectra with similar spectral signatures to a reference. RED-STORM provided new information for subsequent experiments (e.g. 2D-NMR spectroscopy, Solid-Phase Extraction, Liquid Chromatography prefaced Mass Spectrometry) used to ultimately identify an unknown compound. In summary, we illustrate the benefit of acquiring J-resolved experiments alongside conventional 1D ¹H-NMR as part of routine metabolic profiling in large datasets and show that application of complementary statistical and analytical techniques for the identification of unknown metabolites can be used to save valuable time and resource.

Journal article

Cheung W, Keski-Rahkonen P, Assi N, Ferrari P, Freisling H, Rinaldi S, Slimani N, Zamora-Ros R, Rundle M, Frost G, Gibbons H, Carr E, Brennan L, Cross AJ, Pala V, Panico S, Sacerdote C, Palli D, Tumino R, Kuehn T, Kaaks R, Boeing H, Floegel A, Mancini F, Boutron-Ruault M-C, Baglietto L, Trichopoulou A, Naska A, Orfanos P, Scalbert Aet al., 2017, A metabolomic study of biomarkers of meat and fish intake, American Journal of Clinical Nutrition, Vol: 105, Pages: 600-608, ISSN: 0002-9165

Background: Meat and fish intakes have been associated with various chronic diseases. The use of specific biomarkers may help to assess meat and fish intake and improve subject classification according to the amount and type of meat or fish consumed.Objective: A metabolomic approach was applied to search for biomarkers of meat and fish intake in a dietary intervention study and in free-living subjects from the European Prospective Investigation into Cancer and Nutrition (EPIC) study.Design: In the dietary intervention study, 4 groups of 10 subjects consumed increasing quantities of chicken, red meat, processed meat, and fish over 3 successive weeks. Twenty-four-hour urine samples were collected during each period and analyzed by high-resolution liquid chromatography–mass spectrometry. Signals characteristic of meat or fish intake were replicated in 50 EPIC subjects for whom a 24-h urine sample and 24-h dietary recall were available and who were selected for their exclusive intake or no intake of any of the 4 same foods.Results: A total of 249 mass spectrometric features showed a positive dose-dependent response to meat or fish intake in the intervention study. Eighteen of these features best predicted intake of the 4 food groups in the EPIC urine samples on the basis of partial receiver operator curve analyses with permutation testing (areas under the curve ranging between 0.61 and 1.0). Of these signals, 8 metabolites were identified. Anserine was found to be specific for chicken intake, whereas trimethylamine-N-oxide showed good specificity for fish. Carnosine and 3 acylcarnitines (acetylcarnitine, propionylcarnitine, and 2-methylbutyrylcarnitine) appeared to be more generic indicators of meat and meat and fish intake, respectively.Conclusion: The meat and fish biomarkers identified in this work may be used to study associations between meat and fish intake and disease risk in epidemiologic studies. This trial was registered at clinicaltrials.gov as NCT01684

Journal article

Petropoulou K, Salt L, Warren F, Domoney C, Wilde P, Frost Get al., 2017, A seed trait studied by gregor mendel in pisum Sativum L. (PEA): Potential prevention of type 2 diabetes, Legumes for Global Food Security, Pages: 129-156, ISBN: 9781536122657

Pulses have been attracting much interest in recent years from academia, industry and the general public. The attraction has been driven largely by the health benefits that pulses offer compared with refined, processed cereal based foods, coupled with the clear low environmental impact of these crops [1, 2]. Although the consumption of pulses is only a small fraction of that of staple crops such as wheat, maize and rice, the popularity of pulse foods is increasing, particularly in developed countries [3]. In the UK, consumer trends are moving towards a more varied diet, bringing in alternative sources of protein, carbohydrate and micronutrients and a move away from conventional cereals. Although some of these trends are based upon little or no rigorous scientific evidence, there are some clear health benefits associated with consumption of certain pulses. In this article, we will describe one such benefit that is the focus of a collaborative research programme which aims to improve our knowledge from basic plant science and genetics, through processing and consumption of foods and the physiological basis of associated health benefits. The programme aims to study how the type of starch contained in naturally occurring variants of pea seeds can help prevent the onset of type 2 diabetes. The specific aim is to understand how, through manipulating starch biosynthesis, the amount of fermentable carbohydrates reaching the bacterial community in the human colon might be increased. Fermentation of this carbohydrate is thought to produce metabolites which improve our ability to control blood sugar levels.

Book chapter

Gibbons H, Carr E, Frost GS, McNulty BA, Nugent AP, Walton J, Flynn A, Gibney MJ, Brennan Let al., 2016, Metabolomic based identification of clusters that reflect dietary patterns, Proceedings of the Nutrition Society, Vol: 75, Pages: E175-E175, ISSN: 0029-6651

Journal article

Lloyd AJ, Zubair H, Willis ND, Wilson T, Xie L, Tailliart K, Chambers ES, Garcia-Perez I, Holmes E, Frost G, Mathers JC, Beckmann M, Draper Jet al., 2016, Quantification of dietary biomarkers in spot urine samples reflects the intake of foods of UK high public health importance, Publisher: Cambridge University Press (CUP), Pages: E248-E248, ISSN: 0029-6651

An understanding of causal relations between diet and health is hindered by the lack of robust biological markers of food exposure (1).The rapid development of metabolomics technology offers opportunity for the identification of urine biomarkers for the intake of arange of foods of high public health importance (2), (3). Using high mass resolution mass spectrometry and machine learning data analysis,we have discovered potential urinary biomarkers in controlled clinical studies with a range of analytical techniques (2). To haveutility for population monitoring, we aim to validate biomarker performance in free-living individuals using urine samples collected inthe home with a minimal impact on normal daily activities.Two complementary multiple reaction monitoring (MRM) routines using triple quadrupole mass spectrometry (QQQ-MS) havebeen developed to quantify concurrently dietary exposure biomarkers of more than 20 foods of high public health importance inthe UK. MRM quantification of metabolite levels in spot urines collected either before bed time or a first morning void identifieda sub-set of potential biomarkers that demonstrated robust linkage with reported dietary intake (examples in Table 1). Figure 1demonstrates the ability of selected biomarkers to report exposure in relation to muscle meat intake from lunch time to bedtime(Beefburger; 106gm, Chicken breast; 130gm; Processed Ham; 40·5 gm) in 6 free-living individuals. Anserine was strongly, and specifically,associated with poultry intake, whilst the urinary outputs of 3-methyl histidine and carnosine reflect striated muscle intake,with levels substantially reduced when meals contain lower quality, and processed, meats with reduced levels of striated musclecontent.

Conference paper

Oude Griep LM, Chekmeneva E, Stamler J, Van Horn L, Chan Q, Ebbels TMD, Holmes E, Frost GS, Elliott Pet al., 2016, Urinary hippurate and proline betaine relative to fruit intake, blood pressure, and body mass index, Summer meeting 2016: New technology in nutrition research and practice, Publisher: Cambridge University Press (CUP), Pages: E178-E178, ISSN: 0029-6651

Conference paper

Petropoulou K, Chambers ES, Morrison DJ, Preston T, Godsland IF, Wilde P, Narbad A, Parker R, Salt L, Morris VJ, Domoney C, Persaud SJ, Holmes E, Penson S, Watson J, Stocks M, Buurman M, Luterbacher M, Frost Get al., 2016, Identifying crop variants with high resistant starch content to maintain healthy glucose homeostasis, Nutrition Bulletin, Vol: 41, Pages: 372-377, ISSN: 1467-3010

Identifying dietary tools that prevent disordered insulin secretion from pancreatic β-cells is an attractive strategy to combat the increasing prevalence of type 2 diabetes. Dietary resistant starch has been linked to improvements in the function of β-cells, possibly via increased colonic fermentation and production of short-chain fatty acids (SCFAs). Increasing the resistant starch content of commonly consumed foods could therefore maintain glucose homeostasis at the population level. As part of Biotechnology and Biological Sciences Research Council (BBSRC) Diet and Health Research Industry Club (DRINC) initiative, variants of Pisum sativum L. (pea) are being investigated to identify the features of pea starch that make it resistant to digestion and available for colonic fermentation and SCFA production. Parallel in vitro and in vivo studies are being conducted using both whole pea seeds and pea flour to facilitate a better understanding of how cells in the pea cotyledons are affected by processing and, in turn, how this influences starch digestibility. Trials in human volunteers are being used to monitor a full spectrum of short- and long-term physiological responses relevant to pancreatic β-cell function and glucose homeostasis. This project is providing new insights into variants of crops that are associated with the specific types of resistant starch that provide the best protection against defects in insulin secretion and function.

Journal article

Lee S, Norheim F, Langleite TM, Noreng HJ, Storås TH, Afman LA, Frost G, Bell JD, Thomas EL, Kolnes KJ, Tangen DS, Stadheim HK, Gilfillan GD, Gulseth HL, Birkeland KI, Jensen J, Drevon CA, Holen T, NutriTech Consortiumet al., 2016, Effect of energy restriction and physical exercise intervention on phenotypic flexibility as examined by transcriptomics analyses of mRNA from adipose tissue and whole body magnetic resonance imaging., Physiological Reports, Vol: 4, ISSN: 2051-817X

Overweight and obesity lead to changes in adipose tissue such as inflammation and reduced insulin sensitivity. The aim of this study was to assess how altered energy balance by reduced food intake or enhanced physical activity affect these processes. We studied sedentary subjects with overweight/obesity in two intervention studies, each lasting 12 weeks affecting energy balance either by energy restriction (~20% reduced intake of energy from food) in one group, or by enhanced energy expenditure due to physical exercise (combined endurance- and strength-training) in the other group. We monitored mRNA expression by microarray and mRNA sequencing from adipose tissue biopsies. We also measured several plasma parameters as well as fat distribution with magnetic resonance imaging and spectroscopy. Comparison of microarray and mRNA sequencing showed strong correlations, which were also confirmed using RT-PCR In the energy restricted subjects (body weight reduced by 5% during a 12 weeks intervention), there were clear signs of enhanced lipolysis as monitored by mRNA in adipose tissue as well as plasma concentration of free-fatty acids. This increase was strongly related to increased expression of markers for M1-like macrophages in adipose tissue. In the exercising subjects (glucose infusion rate increased by 29% during a 12-week intervention), there was a marked reduction in the expression of markers of M2-like macrophages and T cells, suggesting that physical exercise was especially important for reducing inflammation in adipose tissue with insignificant reduction in total body weight. Our data indicate that energy restriction and physical exercise affect energy-related pathways as well as inflammatory processes in different ways, probably related to macrophages in adipose tissue.

Journal article

Brooks L, Viardot A, Tsakmaki A, Stolarczyk E, Howard JK, Cani PD, Everard A, Sleeth ML, Psichas A, Anastasovskaj J, Bell JD, Bell-Anderson K, Mackay CR, Ghatei MA, Bloom SR, Frost G, Bewick GAet al., 2016, Fermentable carbohydrate stimulates FFAR2-dependent colonic PYY cell expansion to increase satiety, Molecular Metabolism, Vol: 6, Pages: 48-60, ISSN: 2212-8778

ObjectiveDietary supplementation with fermentable carbohydrate protects against body weight gain. Fermentation by the resident gut microbiota produces short-chain fatty acids, which act at free fatty acid receptor 2 (FFAR2). Our aim was to test the hypothesis that FFAR2 is important in regulating the beneficial effects of fermentable carbohydrate on body weight and to understand the role of gut hormones PYY and GLP-1. MethodsWild-type or Ffar2-/-mice were fed an inulin supplemented or control diet. Mice were metabolically characterised and gut hormone concentrations, enteroendocrine cell density measurements were carried out. Intestinal organoids and colonic cultures were utilised to substantiate the in vivo findings.ResultsWe provide new mechanistic insight into how fermentable carbohydrate regulates metabolism. Using mice that lack FFAR2, we demonstrate that the fermentable carbohydrate, inulin, acts via this receptor to drive an 87% increase in the density of cells that produce the appetite-supressing hormone peptide YY (PYY), reduce food intake and prevent diet-induced obesity. Conclusion Our results demonstrate that FFAR2 is predominantly involved in regulating the effects of fermentable carbohydrate on metabolism and does so, in part, by enhancing PYY cell density and release. This highlights the potential for targeting enteroendocrine cell differentiation to treat obesity.

Journal article

Pingitore A, Chambers ES, Hill T, Maldonado IR, Liu B, Bewick G, Morrison DJ, Preston T, Wallis GA, Tedford C, Gonzalez RC, Huang GC, Choudhary P, Frost G, Persaud SJet al., 2016, The diet-derived short chain fatty acid propionate improves beta-cell function in humans and stimulates insulin secretion from human islets in vitro, DIABETES OBESITY & METABOLISM, Vol: 19, Pages: 257-265, ISSN: 1462-8902

Journal article

Maitland K, 2016, Validation of triple pass 24-hour dietary recall in Ugandan children by simultaneous weighed food assessment, BMC Nutrition, Vol: 2, Pages: 1-9, ISSN: 2055-0928

BackgroundUndernutrition remains highly prevalent in African children, highlighting the need for accurately assessing dietary intake. In order to do so, the assessment method must be validated in the target population. A triple pass 24 h dietary recall with volumetric portion size estimation has been described but not previously validated in African children. This study aimed to establish the relative validity of 24-h dietary recalls of daily food consumption in healthy African children living in Mbale and Soroti, eastern Uganda compared to simultaneous weighed food records.MethodsQuantitative assessment of daily food consumption by weighed food records followed by two independent assessments using triple pass 24-h dietary recall on the following day. In conjunction with household measures and standard food sizes, volumes of liquid, dry rice, or play dough were used to aid portion size estimation. Inter-assessor agreement, and agreement with weighed food records was conducted primarily by Bland-Altman analysis and secondly by intraclass correlation coefficients and quartile cross-classification.ResultsNineteen healthy children aged 6 months to 12 years were included in the study. Bland-Altman analysis showed 24-h recall only marginally under-estimated energy (mean difference of 149 kJ or 2.8 %; limits of agreement −1618 to 1321 kJ), protein (2.9 g or 9.4 %; −12.6 to 6.7 g), and iron (0.43 mg or 8.3 %; −3.1 to 2.3 mg). Quartile cross-classification was correct in 79 % of cases for energy intake, and 89 % for both protein and iron. The intraclass correlation coefficient between the separate dietary recalls for energy was 0.801 (95 % CI, 0.429–0.933), indicating acceptable inter-observer agreement.ConclusionsDietary assessment using 24-h dietary recall with volumetric portion size estimation resulted in similar and acceptable estimates of dietary intake compared with weighed food records and thus is considered a valid method for daily dietary in

Journal article

Boyd S, Charani E, Lyons T, Frost G, Holmes AHet al., 2016, Information provision for antibacterial dosing in the obese patient: a sizeable absence?, Journal of Antimicrobial Chemotherapy, ISSN: 1460-2091

Journal article

Carter MC, Hancock N, Albar SA, Brown H, Greenwood DC, Hardie LJ, Frost GS, Wark PA, Cade JEet al., 2016, Development of a New Branded UK Food Composition Database for an Online Dietary Assessment Tool, Nutrients, Vol: 8, ISSN: 2072-6643

The current UK food composition tables are limited, containing ~3300 mostly generic food and drink items. To reflect the wide range of food products available to British consumers and to potentially improve accuracy of dietary assessment, a large UK specific electronic food composition database (FCDB) has been developed. A mapping exercise has been conducted that matched micronutrient data from generic food codes to "Back of Pack" data from branded food products using a semi-automated process. After cleaning and processing, version 1.0 of the new FCDB contains 40,274 generic and branded items with associated 120 macronutrient and micronutrient data and 5669 items with portion images. Over 50% of food and drink items were individually mapped to within 10% agreement with the generic food item for energy. Several quality checking procedures were applied after mapping including; identifying foods above and below the expected range for a particular nutrient within that food group and cross-checking the mapping of items such as concentrated and raw/dried products. The new electronic FCDB has substantially increased the size of the current, publically available, UK food tables. The FCDB has been incorporated into myfood24, a new fully automated online dietary assessment tool and, a smartphone application for weight loss.

Journal article

Polyviou T, MacDougall K, Chambers ES, Viardot A, Psichas A, Jawaid S, Harris HC, Edwards CA, Simpson L, Murphy KG, Zac-Varghese SE, Blundell JE, Dhillo WS, Bloom SR, Frost GS, Preston T, Tedford MC, Morrison DJet al., 2016, Randomised clinical study: inulin short-chain fatty acid esters for targeted delivery of short-chain fatty acids to the human colon., Alimentary Pharmacology and Therapeutics, Vol: 44, Pages: 662-672, ISSN: 0269-2813

BACKGROUND: Short-chain fatty acids (SCFA) produced through fermentation of nondigestible carbohydrates by the gut microbiota are associated with positive metabolic effects. However, well-controlled trials are limited in humans. AIMS: To develop a methodology to deliver SCFA directly to the colon, and to optimise colonic propionate delivery in humans, to determine its role in appetite regulation and food intake. METHODS: Inulin SCFA esters were developed and tested as site-specific delivery vehicles for SCFA to the proximal colon. Inulin propionate esters containing 0-61 wt% (IPE-0-IPE-61) propionate were assessed in vitro using batch faecal fermentations. In a randomised, controlled, crossover study, with inulin as control, ad libitum food intake (kcal) was compared after 7 days on IPE-27 or IPE-54 (10 g/day all treatments). Propionate release was determined using (13) C-labelled IPE variants. RESULTS: In vitro, IPE-27-IPE-54 wt% propionate resulted in a sevenfold increase in propionate production compared with inulin (P < 0.05). In vivo, IPE-27 led to greater (13) C recovery in breath CO2 than IPE-54 (64.9 vs. 24.9%, P = 0.001). IPE-27 also led to a reduction in energy intake during the ad libitum test meal compared with both inulin (439.5 vs. 703.9 kcal, P = 0.025) and IPE-54 (439.5 vs. 659.3 kcal, P = 0.025), whereas IPE-54 was not significantly different from inulin control. CONCLUSIONS: IPE-27 significantly reduced food intake suggesting colonic propionate plays a role in appetite regulation. Inulin short-chain fatty acid esters provide a novel tool for probing the diet-gut microbiome-host metabolism axis in humans.

Journal article

Hettiarachchi P, Wickremasinghe AR, Frost GS, Deen KI, Pathirana AA, Murphy KG, Jayaratne SDet al., 2016, Resection of the large bowel suppresses hunger and food intake and modulates gastrointestinal fermentation., Obesity, Vol: 24, Pages: 1723-1730, ISSN: 1930-7381

OBJECTIVE: To assess appetite and gut hormone levels in patients following partial (PR) or total resection (TR) of the large bowel. METHODS: A comparative cross sectional study was carried out with healthy controls (n = 99) and patients who had undergone PR (n = 64) or TR (n = 12) of the large bowel. Participants consumed a standard (720 kcal) breakfast meal at 0830 (t = 0) h followed by lactulose (15 g) and a buffet lunch (t = 210 min). Participants rated the subjective feelings of hunger at t = -30, 0, 30, 60, 120, and 180 min. Breath hydrogen (BH) concentrations were also evaluated. In a matched subset (11 controls, 11 PR and 9 TR patients) PYY and GLP-1 concentrations were measured following breakfast. The primary outcome measure was appetite, as measured using visual analogue scales and the buffet lunch. The secondary outcome was BH concentrations following a test meal. RESULTS: PR and TR participants had lower hunger and energy intake at the buffet lunch meal compared to controls. PR subjects had higher BH concentrations compared to controls and TR subjects. BH levels correlated with circulating GLP-1 levels at specific time points. CONCLUSIONS: PR or TR of the large bowel reduced feelings of hunger and energy intake, and PR increased gastrointestinal fermentation.

Journal article

Hickson M, Frost G, Dhillo WS, Moss C, Bottin Jet al., 2016, Increased Peptide YY blood concentrations, not decreased acyl-ghrelin, are associated with reduced hunger and food intake in healthy older women: preliminary evidence, Appetite, Vol: 105, Pages: 320-327, ISSN: 1095-8304

With ageing there is frequently a loss of appetite, termed anorexia of ageing, which can result in under-nutrition. We do not know how appetite control alters with ageing. The objective of this study was to investigate whether differences in the release of, and response to, gastrointestinal appetite hormones is altered in young compared to old healthy volunteers. We hypothesised that an increase in PYY and GLP-1 or a decrease ghrelin may result in a decreased appetite. A comparative experimental design, using a cross-sectional sample of ages from a healthy population, matched for sex and BMI was used. The study compared total ghrelin, acyl-ghrelin, PYY, GLP-1 and subjective appetite responses to ingestion of a standardised 2781kj (660kcal) test meal. 31 female volunteers aged between 21-92yrs took part. Multiple linear regression showed that both age and sex had an independent effect on energy intake. Subjective appetite scores showed that hunger, pleasantness to eat, and prospective food intake were significantly lower in the older age groups. PYY incremental area under the curve (IAUC) was greater in the oldest old compared to younger ages f(3,27)=2.9, p=0.05. No differences in GLP-1, ghrelin or acyl-ghrelin were observed in the older compared to younger age groups. Our data suggest that there may be increases in postprandial PYY(3-36) levels in female octogenarians, potentially resulting in reduced appetite. There does not appear to be any change in ghrelin or acyl-ghrelin concentrations with ageing.

Journal article

Bottin JH, Swann JR, Cropp E, Chambers ES, Ford HE, Ghatei MA, Frost GSet al., 2016, Mycoprotein reduces energy intake and postprandial insulin release without altering glucagon-like peptide-1 and peptide tyrosine-tyrosine concentrations in healthy overweight and obese adults: a randomised-controlled trial, British Journal of Nutrition, Vol: 116, Pages: 360-374, ISSN: 1475-2662

Dietary mycoprotein decreases energy intake in lean individuals. The effects in overweight individuals are unclear, and the mechanisms remain to be elucidated. This study aimed to investigate the effect of mycoprotein on energy intake, appetite regulation, and the metabolic phenotype in overweight and obese volunteers. In two randomised-controlled trials, fifty-five volunteers (age: 31 (95 % CI 27, 35) years), BMI: 28·0 (95 % CI 27·3, 28·7) kg/m2) consumed a test meal containing low (44 g), medium (88 g) or high (132 g) mycoprotein or isoenergetic chicken meals. Visual analogue scales and blood samples were collected to measure appetite, glucose, insulin, peptide tyrosine-tyrosine (PYY) and glucagon-like peptide-1 (GLP-1). Ad libitum energy intake was assessed after 3 h in part A (n 36). Gastric emptying by the paracetamol method, resting energy expenditure and substrate oxidation were recorded in part B (n 14). Metabonomics was used to compare plasma and urine samples in response to the test meals. Mycoprotein reduced energy intake by 10 % (280 kJ (67 kcal)) compared with chicken at the high content (P=0·009). All mycoprotein meals reduced insulin concentrations compared with chicken (incremental AUClow (IAUClow): -8 %, IAUCmedium: -12 %, IAUChigh: -21 %, P=0·004). There was no significant difference in glucose, PYY, GLP-1, gastric emptying rate and energy expenditure. Following chicken intake, paracetamol-glucuronide was positively associated with fullness. After mycoprotein, creatinine and the deamination product of isoleucine, α-keto-β-methyl-N-valerate, were inversely related to fullness, whereas the ketone body, β-hydroxybutyrate, was positively associated. In conclusion, mycoprotein reduces energy intake and insulin release in overweight volunteers. The mechanism does not involve changes in PYY and GLP-1. The metabonomics analysis may bring new understanding to the appetite regulatory properties of food.

Journal article

Byrne CS, Chambers ES, Alhabeeb H, Chhina N, Morrison DJ, Preston T, Tedford C, Fizpatrick J, Irani C, Busza A, Garcia-Perez I, Fountana S, Holmes E, Goldstone AP, Frost GSet al., 2016, Increased colonic propionate reduces anticipatory reward responses in the human striatum to high-energy foods, American Journal of Clinical Nutrition, Vol: 104, ISSN: 1938-3207

BACKGROUND: Short-chain fatty acids (SCFAs), metabolites produced through the microbial fermentation of nondigestible dietary components, have key roles in energy homeostasis. Animal research suggests that colon-derived SCFAs modulate feeding behavior via central mechanisms. In humans, increased colonic production of the SCFA propionate acutely reduces energy intake. However, evidence of an effect of colonic propionate on the human brain or reward-based eating behavior is currently unavailable. OBJECTIVES: We investigated the effect of increased colonic propionate production on brain anticipatory reward responses during food picture evaluation. We hypothesized that elevated colonic propionate would reduce both reward responses and ad libitum energy intake via stimulation of anorexigenic gut hormone secretion. DESIGN: In a randomized crossover design, 20 healthy nonobese men completed a functional magnetic resonance imaging (fMRI) food picture evaluation task after consumption of control inulin or inulin-propionate ester, a unique dietary compound that selectively augments colonic propionate production. The blood oxygen level-dependent (BOLD) signal was measured in a priori brain regions involved in reward processing, including the caudate, nucleus accumbens, amygdala, anterior insula, and orbitofrontal cortex (n = 18 had analyzable fMRI data). RESULTS: Increasing colonic propionate production reduced BOLD signal during food picture evaluation in the caudate and nucleus accumbens. In the caudate, the reduction in BOLD signal was driven specifically by a lowering of the response to high-energy food. These central effects were partnered with a decrease in subjective appeal of high-energy food pictures and reduced energy intake during an ad libitum meal. These observations were not related to changes in blood peptide YY (PYY), glucagon-like peptide 1 (GLP-1), glucose, or insulin concentrations. CONCLUSION: Our results suggest that colonic propionate production may play

Journal article

Sahuri-Arisoylu M, Brody LP, Parkinson JR, Parkes H, Navaratnam N, Miller AD, Thomas EL, Frost G, Bell JDet al., 2016, Reprogramming of hepatic fat accumulation and 'browning' of adipose tissue by the short-chain fatty acid acetate, International Journal of Obesity, Vol: 40, Pages: 955-963, ISSN: 1476-5497

Background/Objectives: Short-chain fatty acids, produced by microbiome fermentation of carbohydrates, have been linked to a reduction in appetite, body weight and adiposity. However, determining the contribution of central and peripheral mechanisms to these effects has not been possible.Subjects/Methods: C57BL/6 mice fed with either normal or high-fat diet were treated with nanoparticle-delivered acetate, and the effects on metabolism were investigated.Results: In the liver, acetate decreased lipid accumulation and improved hepatic function, as well as increasing mitochondrial efficiency. In white adipose tissue, it inhibited lipolysis and induced 'browning', increasing thermogenic capacity that led to a reduction in body adiposity.Conclusions: This study provides novel insights into the peripheral mechanism of action of acetate, independent of central action, including ‘browning’ and enhancement of hepatic mitochondrial function.

Journal article

Albar SA, Alwan NA, Evans CEL, Greenwood DC, Cade JE, Brown HC, Carter MC, Hancock N, Hardie LJ, Morris MA, White KL, Ford HE, Frost GS, Mulla UZ, Petropoulou KA, Wark PAet al., 2016, Agreement between an online dietary assessment tool (myfood24) and an interviewer-administered 24-h dietary recall in British adolescents aged 11-18 years, British Journal of Nutrition, Vol: 115, Pages: 1678-1686, ISSN: 0007-1145

myfood24 Is an online 24-h dietary assessment tool developed for use among British adolescents and adults. Limited information is available regarding the validity of using new technology in assessing nutritional intake among adolescents. Thus, a relative validation of myfood24 against a face-to-face interviewer-administered 24-h multiple-pass recall (MPR) was conducted among seventy-five British adolescents aged 11–18 years. Participants were asked to complete myfood24 and an interviewer-administered MPR on the same day for 2 non-consecutive days at school. Total energy intake (EI) and nutrients recorded by the two methods were compared using intraclass correlation coefficients (ICC), Bland–Altman plots (using between and within-individual information) and weighted κ to assess the agreement. Energy, macronutrients and other reported nutrients from myfood24 demonstrated strong agreement with the interview MPR data, and ICC ranged from 0·46 for Na to 0·88 for EI. There was no significant bias between the two methods for EI, macronutrients and most reported nutrients. The mean difference between myfood24 and the interviewer-administered MPR for EI was −230 kJ (−55 kcal) (95 % CI −490, 30 kJ (−117, 7 kcal); P=0·4) with limits of agreement ranging between 39 % (3336 kJ (−797 kcal)) lower and 34 % (2874 kJ (687 kcal)) higher than the interviewer-administered MPR. There was good agreement in terms of classifying adolescents into tertiles of EI (κ w =0·64). The agreement between day 1 and day 2 was as good for myfood24 as for the interviewer-administered MPR, reflecting the reliability of myfood24. myfood24 Has the potential to collect dietary data of comparable quality with that of an interviewer-administered MPR.

Journal article

Pingitore A, Gonzales-Abuin N, Huang GC, Bewick G, Frost G, Persaud SJet al., 2016, Short chain fatty acids potentiate insulin secretion via FFA2, DIABETIC MEDICINE, Vol: 33, Pages: 40-40, ISSN: 0742-3071

Journal article

Thangarajah D, Chapell KE, Mandalia S, Frost G, Fell JMet al., 2016, Abdominal obesity in Paediatric Crohn's disease is associated with adipokine dysregulation, JOURNAL OF CROHNS & COLITIS, Vol: 10, Pages: S355-S355, ISSN: 1873-9946

Journal article

Thangarajah D, Chapell KE, Mandalia S, Frost G, Fell JMet al., 2016, Aberrant adipose tissue partitioning with abdominal obesity, defined by MRI, is a hallmark of paediatric Crohn's disease, JOURNAL OF CROHNS & COLITIS, Vol: 10, Pages: S362-S363, ISSN: 1873-9946

Journal article

Brown AC, Taheri S, Dornhorst A, Kapoor N, McGowan B, Leeds AR, Frost Get al., 2016, Using a low energy formula diet in obese patients with long-standing insulin-treated Type 2 diabetes produces significantly greater weight loss, improvement in glucose control and insulin reductions compared to gold standard clinical care over a 12 week period, DIABETIC MEDICINE, Vol: 33, Pages: 69-69, ISSN: 0742-3071

Journal article

Garcia-Perez I, Posma JM, Chambers ES, Nicholson JK, C Mathers J, Beckmann M, Draper J, Holmes E, Frost Get al., 2016, An analytical pipeline for quantitative characterization of dietary intake: application to assess grape intake., Journal of Agricultural and Food Chemistry, Vol: 64, Pages: 2423-2431, ISSN: 1520-5118

Lack of accurate dietary assessment in free-living populations requires discovery of new biomarkers reflecting food intake qualitatively and quantitatively to objectively evaluate effects of diet on health. We provide a proof-of-principle for an analytical pipeline to identify quantitative dietary biomarkers. Tartaric acid was identified as dose-responsive urinary biomarker of grape intake and subsequently quantified in volunteers who followed a series of 4-day dietary interventions incorporating 0g/day, 50g/day, 100g/day and 150g/day of grapes in standardized diets from a randomized controlled clinical trial. The most accurate quantitative prediction of grape intake was obtained in 24h urine samples which have the strongest linear relationship between grape intake and tartaric acid excretion (r2=0.90). This new methodological pipeline for estimating nutritional intake based on coupling dietary intake information and quantified nutritional biomarkers was developed and validated in a controlled dietary intervention study, showing that this approach can improve the accuracy of estimating nutritional intakes.

Journal article

Stradling C, Thomas GN, Hemming K, Frost G, Garcia-Perez I, Redwood S, Taheri Set al., 2016, Randomised controlled pilot study to assess the feasibility of a Mediterranean Portfolio dietary intervention for cardiovascular risk reduction in HIV dyslipidaemia: a study protocol., BMJ Open, Vol: 6, ISSN: 2044-6055

INTRODUCTION: HIV drug treatment has greatly improved life expectancy, but increased risk of cardiovascular disease remains, potentially due to the additional burdens of infection, inflammation and antiretroviral treatment. The Mediterranean Diet has been shown to reduce cardiovascular risk and mortality in the general population, but no evidence exists for this effect in the HIV population. This study will explore the feasibility of a randomised controlled trial (RCT) to examine whether a Mediterranean-style diet that incorporates a portfolio of cholesterol-lowering foods, reduces cardiovascular risk in people with HIV dyslipidaemia. METHODS AND ANALYSIS: 60 adults with stable HIV infection on antiretroviral treatment and low-density lipoprotein cholesterol >3 mmol/L will be recruited from 3 West Midlands HIV services. Participants will be randomised 1:1 to 1 of 2 dietary interventions, with stratification by gender and smoking status. Participants allocated to Diet1 will receive advice to reduce saturated fat intake, and those to Diet2 on how to adopt the Mediterranean Portfolio Diet with additional cholesterol-lowering foods (nuts, stanols, soya, oats, pulses). Measurements of fasting blood lipids, body composition and arterial stiffness will be conducted at baseline, and month 6 and 12 of the intervention. Food intake will be assessed using the Mediterranean Diet Score, 3-day food diaries and metabolomic biomarkers. Questionnaires will be used to assess quality of life and process evaluation. Qualitative interviews will explore barriers and facilitators to making dietary changes, and participant views on the intervention. Qualitative data will be analysed using the Framework Method. Feasibility will be assessed in terms of trial recruitment, retention, compliance to study visits and the intervention. SD of outcomes will inform the power calculation of the definitive RCT. ETHICS: The West Midlands Ethics Committee has approved this study and informed consent f

Journal article

Beckmann M, Joosen AM, Clarke MM, Mugridge O, Frost G, Engel B, Taillart K, Lloyd AJ, Draper J, Lodge JKet al., 2016, Changes in the human plasma and urinary metabolome associated with acute dietary exposure to sucrose and the identification of potential biomarkers of sucrose intake, MOLECULAR NUTRITION & FOOD RESEARCH, Vol: 60, Pages: 444-457, ISSN: 1613-4125

Journal article

Gibson R, Eriksen R, Chan Q, Vergnaud AC, Singh D, Heard A, Spear J, Aresu M, McRobie D, Elliott P, Frost Get al., 2016, Sex differences in the relationship between work patterns and diet in British police force employees: a nested cross-sectional study, Proceedings of the Nutrition Society, Vol: 75, Pages: E20-E20, ISSN: 0029-6651

Journal article

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