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1.
Pilot Feasibility Stud ; 7(1): 193, 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34715934

RESUMO

BACKGROUND: Ergothioneine is a naturally occurring metabolite of histidine found in many foods and in high amounts in mushrooms. In vivo, ergothioneine acts as an antioxidant and is widely distributed in most mammalian tissues. While ergothioneine is sold as a dietary supplement for its antioxidant and anti-inflammatory properties, to date there are no published intervention trials examining its health benefits in humans. The aim of this work was to develop a study protocol for a pilot interventional trial that will establish the primary and secondary outcomes, and the power required, for a definitive randomised controlled trial to test the hypothesis that ergothioneine supplementation is beneficial for people with metabolic syndrome. METHODS: We have designed the ErgMS study as a single-centre, randomised, double-blind, placebo-controlled, 3-arm parallel, pilot intervention trial, which aims to supplement participants with either placebo, 5 or 30 mg/day ergothioneine for 12 weeks. Measurements of metabolic syndrome risk factors, serum markers of oxidative stress (lipid peroxidation), inflammation, blood platelet function and liver function will take place at baseline, and after 6 weeks and 12 weeks of supplementation. In addition, we will examine if there are any changes in the serum metabolome in response to ergothioneine supplementation. Linear regression and two-way ANOVA will be utilised to analyse the association between ergothioneine and measured variables. DISCUSSION: The ErgMS study will be the first study to address the question does ergothioneine supplementation have health benefits for people with metabolic syndrome. Study results will provide preliminary data as to which dose may improve inflammatory markers in adults with metabolic syndrome and will inform dose and primary outcome selection for a definitive randomised controlled trial. TRIAL REGISTRATION: ISRCTN, ISRCTN25890011 Registered February 10th, 2021.

2.
Appetite ; 165: 105427, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34051275

RESUMO

With a dramatic increase in overweight and population with obesity over the last decades, there is an imminent need to tackle this issue using novel strategies. Addressing obesity issues by generating satiety in food to reduce energy intake has been one of those prominent strategies and often textural interventions have been used to generate satiety, specifically in short-term trials. This study aimed to investigate the role of preloads varying in their oral lubricating properties on appetite sensations, food intake, salivary friction and concentration of salivary biomarkers (proteins, α-amylase and mucins) in collected human saliva (n = 17 healthy participants). The preloads were model foods (flavoured hydrogels) either high or low in their lubricating properties, assessed both by instrumental and sensorial measurements. The results showed that hunger and desire to eat decreased immediately after preload and remained decreased for 10 and 20 min, respectively, after preload in the high lubricating condition compared to control (all p < 0.05). Fullness increased immediately after preload and remained increased for 10 and 20 min, respectively, after preload in high lubricating condition compared to control (p < 0.05). However, after controlling the values for baseline, such significant effect of the intervention did not exist anymore. Only the effect of time is observed. Consuming high lubricating hydrogels showed no effect on food intake and salivary biomarkers in this pilot study. Salivary lubrication correlated with feeling of fullness. Considering the issue of large time-interval (30 min) between preload and next meal in this study, it is worthwhile investigating the immediate effects of oral lubrication on appetite control, food intake and salivary biomarkers.


Assuntos
Apetite , Saciação , Biomarcadores , Ingestão de Alimentos , Ingestão de Energia , Humanos , Lubrificação , Projetos Piloto
3.
BMC Syst Biol ; 11(1): 141, 2017 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-29246152

RESUMO

BACKGROUND: Estrogen is a vital hormone that regulates many biological functions within the body. These include roles in the development of the secondary sexual organs in both sexes, plus uterine angiogenesis and proliferation during the menstrual cycle and pregnancy in women. The varied biological roles of estrogens in human health also make them a therapeutic target for contraception, mitigation of the adverse effects of the menopause, and treatment of estrogen-responsive tumours. In addition, endogenous (e.g. genetic variation) and external (e.g. exposure to estrogen-like chemicals) factors are known to impact estrogen biology. To understand how these multiple factors interact to determine an individual's response to therapy is complex, and may be best approached through a systems approach. METHODS: We present a physiologically-based pharmacokinetic model (PBPK) of estradiol, and validate it against plasma kinetics in humans following intravenous and oral exposure. We extend this model by replacing the intrinsic clearance term with: a detailed kinetic model of estrogen metabolism in the liver; or, a genome-scale model of liver metabolism. Both models were validated by their ability to reproduce clinical data on estradiol exposure. We hypothesise that the enhanced mechanistic information contained within these models will lead to more robust predictions of the biological phenotype that emerges from the complex interactions between estrogens and the body. RESULTS: To demonstrate the utility of these models we examine the known drug-drug interactions between phenytoin and oral estradiol. We are able to reproduce the approximate 50% reduction in area under the concentration-time curve for estradiol associated with this interaction. Importantly, the inclusion of a genome-scale metabolic model allows the prediction of this interaction without directly specifying it within the model. In addition, we predict that PXR activation by drugs results in an enhanced ability of the liver to excrete glucose. This has important implications for the relationship between drug treatment and metabolic syndrome. CONCLUSIONS: We demonstrate how the novel coupling of PBPK models with genome-scale metabolic networks has the potential to aid prediction of drug action, including both drug-drug interactions and changes to the metabolic landscape that may predispose an individual to disease development.


Assuntos
Estradiol/farmacocinética , Genoma Humano , Fígado/metabolismo , Redes e Vias Metabólicas , Modelos Biológicos , Administração Intravenosa , Administração Oral , Adolescente , Adulto , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/sangue , Anticonvulsivantes/farmacocinética , Área Sob a Curva , Interações Medicamentosas , Estradiol/administração & dosagem , Estradiol/sangue , Estrogênios/administração & dosagem , Estrogênios/sangue , Estrogênios/farmacocinética , Feminino , Glucose/metabolismo , Humanos , Pessoa de Meia-Idade , Receptor 1 de Sinal de Orientação para Peroxissomos/metabolismo , Fenitoína/administração & dosagem , Fenitoína/sangue , Fenitoína/farmacocinética , Distribuição Tecidual , Adulto Jovem
4.
BMJ Open Gastroenterol ; 4(1): e000139, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28761689

RESUMO

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide, with prevalence above 30% in many adult populations. Strongly associated with obesity, weight loss through diet and physical activity is the mainstay of its management. Weight loss can be difficult to achieve and maintain however, and uncertainty exists as to which lifestyle changes are most effective. OBJECTIVE: The aim of this work was to systematically evaluate randomised controlled trials assessing diet, exercise or combination interventions aimed at reducing steatosis or markers of NAFLD activity. DESIGN: Medline, Scopus and Cochrane databases were searched from 1 January 1980 through to 31 July 2016, for intervention trials assessing the effects of diet, weight loss, exercise or any combination thereof, on NAFLD disease markers in human adults. Risk of publication bias and study quality was assessed using the American Dietetic Association Quality Criteria Checklist. RESULTS: From a total of 1710 identified records, 24 articles met the inclusion and exclusion criteria; 6 assessed weight loss using dietary restriction, 10 assessed exercise and 8 were combination interventions. While all of the trials demonstrated significant reduction in steatosis and/or markers of NAFLD activity, combination interventions appear to be the most effective at improving NAFLD. Results suggest that 5-10% weight loss using a modestly hypocaloric diet of 500 kcal less per day than calculated energy requirement, in combination with 30-60 min exercise on 3-5 days per week should be recommended. CONCLUSIONS: We conclude this amount of weight loss is achievable in the trial setting but is challenging in the clinical environment. High-intensity, multidisciplinary intervention in specialist clinics is likely to be required in order to manage NAFLD by lifestyle modification alone. This systematic review protocol was registered prospectively at PROSPERO as CRD42016032764.

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