Effect of in vitro food oral coating and lubricity on satiety: a randomized controlled trial using milk protein beverages.

We investigated the effects of complex textural attributes of food i.e. lubricity and oral coating, on appetite ratings, food intake, salivary and gut peptides for the first time. Milk protein-rich beverages (whey and casein) were instrumentally analyzed (tribology, viscosity and adsorption, latter representing oral coating) using in vitro measurements. Then these protein beverage preloads differing in their coating properties (low coating, medium coating and high coating) were assessed in two cross-over satiety trials (Study 1, n=37; Study 2, n=15; Total n= 52). Fullness ratings increased in the high coating beverage condition (p<0.05) only after 20 min with limited effects on other time points, suggesting a sporadic effect of oral coating on appetite ratings (n=37). There was a correlation between concentration of protein in saliva and appetite ratings; the higher the concentration of protein in saliva the lower the desire to eat (r = - 0.963; p <0.05) and prospective food consumption ratings (r =- 0.980; p <0.05). Human saliva was more lubricating after ingesting preload with high coating properties, thus explaining the results on appetite ratings. There was no effect of oral coating on energy intake and gut peptides (n=15), suggesting that complex textural attributes having influence on oral processing might not have any effect on the later parts of the satiety cascade. Oral coating/ lubricity appears to have a subtle and sporadic effect on appetite suppression, which needs further investigation with changing macronutrients/energy load and degree of coating/ lubricity.

Ergothioneine supplementation in people with metabolic syndrome (ErgMS): protocol for a randomised, double-blind, placebo-controlled pilot study.

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.

Linking physiologically-based pharmacokinetic and genome-scale metabolic networks to understand estradiol biology.

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.

Efficacy of dietary and physical activity intervention in non-alcoholic fatty liver disease: a systematic review.

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.