Caloric Meal Research Articles

A randomized, open-label two-period crossover pilot study to evaluate the relative bioavailability in the fed state of atovaquone-proguanil (Atoguanil™) versus atovaquone-proguanil hydrochloride (Malarone®) in healthy adult participants

Atoguanil™ is a novel complex of atovaquone (ATV) and proguanil (PG) with enhanced ATV bioavailability compared to Malarone®. This pilot study assessed whether the relative bioavailability (Frel) of ATV, PG, and the primary PG metabolite cycloguanil (CG) following a single oral dose in the fed state of Atoguanil was similar to Malarone despite a 50% lower ATV dose. This open-label, single-dose, randomized 2-period, 2-treatment, balanced crossover study was conducted between 17th November 2021 and 18th March 2022. Eligible participants (aged 18–55 years) were randomized (1:1) in period 1 to Atoguanil (ATV/PG 500/348 mg) or Malarone (ATV/PG hydrochloride 1000/400 mg) administered following a high-fat, high caloric meal. After a 24-day washout period, participants crossed treatment arms. For the doses tested, Frel was assumed similar if 90%CIs were between 80 and 125% for the geometric mean ratio of the least square mean differences for each exposure parameter. In 15 evaluable participants, Frel was similar for ATV Cmax (93.6% [90%CI 83.6, 104.9]) but not AUC0-inf (77.8% [67.4, 89.8]), for PG AUC0-inf (95.6% [92.1, 99.2]) but not Cmax (82.4% [75.8, 89.5]), and for both CG Cmax (100.8% [95.0, 107.0]) and AUC0-inf (102.9% [98.4, 107.7]). Nine adverse events occurred; all were of mild severity and not considered treatment related. At the doses tested, ATV Frel was lower following Atoguanil versus Malarone based on AUC0-inf, though when adjusted for dose Frel increased by 156%. Both drugs were well tolerated with no safety concerns. ClinicalTrials.gov: NCT04866602 (April 26th, 2021)

Importance of early weight loss and other predictors of lower weight loss in a commercial program: A secondary data analysis.

There is substantial inter-individual variability in response to weight loss interventions and emerging evidence suggests that weight loss during the early weeks of an intervention may be predictive of longer-term weight loss. This secondary analysis of data from a commercial program therefore examined 1) the associations between early weight loss (i.e., week 4) with final visit weight loss and duration on the program, and 2) other predictors of lower weight loss at final visit. Client charts of adults with overweight or obesity (N=748) were analyzed. Clients were stratified into categories of weight loss at the week 4 (< and ≥2%, 3% and 4%) and final visits (< and ≥5% and 10%). Multivariate logistic regression was used to assess predictors of <5% and <10% final visit weight loss. The odds ratios for losing <5% or <10% of weight at the final visit were higher (49.0 (95% CI: 13.84, 173.63) and 20.1 (95% CI: 6.96, 58.06)) for clients who lost <2% or <3% compared to those who lost ≥2% or ≥3% at week 4. Other predictors of not losing a clinically relevant amount of weight included female sex, use of higher calorie meal plans and shorter time in the program, among others. Those who lost ≥2% at week 4 also had a significantly greater percent program completion (109.2±75.2% vs. 82.3±82.4, p<0.01) compared with those who did not meet the 2% threshold. Lower 4-week weight loss was identified as a strong predictor of not losing a clinically relevant amount of weight. These results may be useful for the early identification of individuals who can be targeted for additional counseling and support to aid in attaining weight loss goals.

The energy content of meals with a similar macronutrient distribution may have a greater impact on appetite sensations than food preferences in adolescents with obesity: A secondary analysis

PurposeThe energy and macronutrient composition of a meal has been shown to influence postprandial appetitive responses, but it is not clear how energy content independent of macronutrient distribution affects postprandial appetite in adolescents with obesity. Extracting data from a primary study testing the effect of energy turnover on appetite, this secondary analysis assessed how fixed meals varying in energy content with similar macronutrient distributions influences postprandial appetite sensations and food reward. MethodsUsing a randomised, counterbalanced crossover design, N = 14 adolescents with obesity (Mage = 12.71, SDage = 0.99; 10 female) consumed fixed lunch meals with similar macronutrient content starting at 750 kcal in energy and progressively increasing by 250 kcal on three different test days. Liking and wanting for food images varying in fat and taste were assessed at baseline and immediately after meal consumption. Appetite sensations were assessed in half-hour intervals from baseline to 1-h post-meal. ResultsThe area under the curve for subjective hunger (p < .001, ω = 0.36), desire to eat (p < .001, ω = 0.54), and prospective food consumption (p = .004, ω = 0.32) were significantly lower after consumption of the higher calorie meals relative to the lowest. Explicit wanting for sweet foods increased after intake of the intermediate calorie meal yet decreased after the highest calorie meal (p = .014, ω = 0.09). Conversely, implicit wanting sweet bias increased after consumption of the test meal independent of energy content (p < .001, ω = 0.15). ConclusionThe consumption of additional calories without a meaningful change in macronutrient distribution may affect appetite sensations more reliably than hedonic responses to energy-dense foods in adolescents with obesity.

Further evidence for sensitivity to energy density and a two-component model of meal size: Analysis of meal calorie intakes in Argentina and Malaysia

Previously, we demonstrated a non-linear association between meal caloric intake and meal energy density (ED, kcal/g) in data from a controlled trial in the US and from free-living participants in the UK [1]. In both datasets, meal caloric intake increased with ED in lower energy-dense meals (below ∼1.75 kcal/g) and decreased in higher energy-dense meals (above ∼1.75 kcal/g). In the current study, we sought to explore whether this pattern extends to data from free-living participants in Argentina (N = 2738 meals) and Malaysia (N = 4658 meals). Again, a significant breakpoint was found in both the Argentinean (2.04 kcal/g (SE = 0.06)) and Malaysian (2.17 kcal/g (SE = 0.06)) datasets with mean centered meal caloric intake increasing with ED below the breakpoint and decreasing above the breakpoint. These results lend further support for our two-component theoretical model of meal size (g) in which a volume signal is dominant in lower energy-dense meals and a calorie-content signal is dominant in higher energy-dense meals. Together, our research adds to evidence supporting human sensitivity to calories and exposes a complexity in the correspondence between meal energy content and meal size in everyday (non-manipulated) meals. Further research is needed to provide causal evidence for this sensitivity and whether individual variation impacts meal size and energy balance.

Selected personal resources and nutritional behaviours of Polish handball players.

Diet, as one of the factors influencing exercise capacity depends, among others, on individual conditions. The aim of the study was to analyse the nutritional behaviours of Polish handball players depending on their level of generalised self-efficacy as well as disposable optimism and satisfaction with life. The study was carried out among a group of 142 men, aged 20-34, professionally training handball, using the author's original nutritional behaviour questionnaire and the Generalised Self-Efficacy Scale (GSES), the Life Orientation Scale (LOT-R) and Satisfaction with Life Scale (SWLS). Statistical analysis of the results was conducted by estimating Spearman's signed rank correlation coefficients, assuming the significance level of p <0.05. To the highest degree, the handball players fulfilled recommendations regarding the regular consumption of at least 3 meals a day, adequate fluid supplementation in conditions of physical exercise and eating the most caloric meal before or after main training sessions. Along with the increase in sense of efficacy (GSES), the scale of reducing sweet and salty snacks increased (p<0.05). Increasing optimism was conducive to proper hydration (p<0.05) and avoidance of sweet and salty snacks (p<0.05). With the increase in sense of satisfaction with life, the implementation of recommendations regarding the consumption of dairy products and vegetable fats, as well as adequate fluid supplementation in conditions of physical exercise, increased (p<0.05). In the studied group of handball players, a limited scale of implementing qualitative nutritional recommendations for athletes was demonstrated. Moreover, positive correlations were noted between the analysed personal resources and some rational nutritional behaviours of the athletes, especially in terms of avoiding non-recommended products and correct fluid replenishment.

StomachSim: An in-silico simulator of gastric biomechanics with application to pyloroplasty

Aim: We have developed StomachSim, an in-silico simulator that is designed to simulate the biomechanics and fluid mechanics of a wide range of gastric conditions as well as gastric surgical procedures. Here we demonstrate its use in quantifying the effects of motility disorders and pyloroplasty on the hydrolysis and emptying of a liquid meal inside the stomach. Methods: A physiologically realistic model of the stomach, including the antral motility, is synthesized based on in-vivo imaging, and the mixing and gastric emptying are simulated using computational fluid dynamics (CFD). The enzymatic biochemistry for protein hydrolysis is also implemented by incorporating the secretion of a proteolytic enzyme from the proximal stomach walls and the subsequent enzymatic reaction with the protein dissolved in the liquid meal. Using this model, we measured the effect of stomach motility and the diameter of the pyloric orifice on the retropulsive and pyloric jets, the rate of hydrolysis in different regions, and the emptying of gastric contents. Results: This study presents a proof-of-concept for the application of StomachSim in gastric disorders and surgeries. The emptying rate of our model for the healthy case agreed with the in-vivo measurements of similar caloric density liquid meals. A stomach with a 50% lower motility amplitude had a 35% lower net emptying rate and a 41% lower emptying rate of the hydrolyzed protein. Furthermore, the emptying rate showed a non-linear variation with respect to the motility of the stomach. For a simulated pyloroplasty procedure where the pyloric orifice diameter is doubled and the orifice stays open permanently, the emptying rate of the lower motility case doubled over its original value. Conclusion: StomachSim offers a novel and potentially effective modality for examining the effect of gastric conditions and gastric surgical procedures on gastric function. Our simulations show that gastroparesis and pyloroplasty not only affect the emptying rate but also alter the mixing of contents thereby changing the rate of hydrolysis. The model helped quantify the changes in the flow of contents in the antro-duodenal region for varying degrees of gastroparesis and pyloroplasty. The authors acknowledge support from NSF award CBET 2019405 and NIH award 1R21GM139073-01. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

PRAX-562-101: A Phase 1 Trial Evaluating the Safety, Tolerability, Pharmacokinetics and Food Effect of PRAX-562 in Healthy Volunteers (P8-9.011)

<h3>Objective:</h3> We report findings from a first-in-human trial evaluating safety, tolerability, and pharmacokinetics (PK) of single and multiple ascending doses of PRAX-562, as well as the effect of food on PK of a single dose in healthy adults. <h3>Background:</h3> PRAX-562 is a next-generation sodium channel blocker in development for treatment of DEEs with a unique profile that may translate to improved tolerability over standard-of-care. <h3>Design/Methods:</h3> PRAX-562-101 was a Phase 1 trial in healthy participants aged 18–55 years. Parts A (n=64) and B (n=32) were randomized, placebo-controlled and evaluated single (2.5–150mg) and multiple (30–120mg, 14 days QD) ascending oral doses of PRAX-562, respectively. Part C (n=16) was an open-label, randomized, crossover design evaluating the PK of a single oral dose (90mg) in fasted and fed states. Part C participants were randomized to receive PRAX-562 in the fed (following a high-fat/high calorie meal) or fasted (≥10h after the last, and 4h before the next, meal) state. <h3>Results:</h3> 112 participants were enrolled (n=88 PRAX-562, n=24 placebo). PRAX-562 was well-tolerated with no clinically significant safety findings in vital signs, laboratory results, physical exams, ECGs, or C-SSRS data; TEAEs were mostly mild (&gt;92%). Exposure increased dose proportionally over the evaluated dose range. PRAX-562 rapidly appeared in plasma with time to C_max between 2–3h, and detectable levels over a dose interval. 90mg in the fed state resulted in a slight increase in C_max (9%), delay in t_max (4 vs. 2.5h), and modest increase in AUC (14%) vs. the fasted state. <h3>Conclusions:</h3> PRAX-562 was well tolerated in healthy participants at single doses up to 150mg (fasted) in Part A, at multiple doses up to 120mg QD for 14 days (fasted) in Part B, and at a single dose of 90mg in fed and fasted states in Part C. Our findings suggest that PRAX-562 can be administered without regard for food. <b>Disclosure:</b> Dr. Pfister has received personal compensation for serving as an employee of PTC Therapeutics. Dr. Pfister has received stock or an ownership interest from PTC Therapeutics. Dr. Mahalingam has nothing to disclose. Dr. Oldham has received personal compensation for serving as an employee of Praxis Precision Medicines. Dr. Patel has received personal compensation for serving as an employee of Praxis Precision Medicines, Inc.. Dr. Patel has received personal compensation for serving as an employee of Noven Pharmaceuticals. Dr. Patel has stock in Praxis Precision Medicines, Inc.. Dr. Jacotin has received personal compensation for serving as an employee of Praxis Precision Medicines. Dr. Jacotin has received personal compensation for serving as an employee of Takeda. Dr. Jacotin has stock in Takeda. Dr. Jacotin has stock in Certara. Dr. Jacotin has stock in Clover Health. Dr. Jacotin has stock in Coinbase. Marjie Hard has nothing to disclose. Dr. Puryear has received personal compensation for serving as an employee of Praxis Precision Medicine. Dr. Puryear has stock in Praxis Precision Medicines. Dr. Ravina has received personal compensation for serving as an employee of Praxis Precision Medicines. Dr. Ravina has stock in Praxis. Dr. Souza has received personal compensation for serving as an employee of Praxis Precision Medicines. Dr. Souza has stock in Praxis Precision Medicines. Steven Petrou has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Praxis Precision Medicines. Steven Petrou has stock in Praxis Precision Medicines. The institution of Steven Petrou has received research support from Praxis Precision Medicines. The institution of Steven Petrou has received research support from Medical Research Future Fund. Steven Petrou has received intellectual property interests from a discovery or technology relating to health care. Steven Petrou has received intellectual property interests from a discovery or technology relating to health care.

Abstract 2795: A food effect and esomeprazole drug-drug interaction study of RLY-4008, a highly selective FGFR2 inhibitor, in healthy subjects

Abstract Background/Introduction: Effective therapies for FGFR2-driven cholangiocarcinoma (CCA) and other advanced solid tumors remain unmet medical needs. RLY-4008 is a potent, highly selective and irreversible FGFR2 inhibitor designed to target both primary FGFR2 oncogenic alterations and clinically relevant resistance mutations. RLY-4008 is currently being studied in a Phase 1/2 clinical trial to treat patients with FGFR2-driven CCA. To guide RLY-4008 dosing in cancer patients, we report here results from a clinical study to assess the effect of food and proton pump inhibitor (PPI) esomeprazole (ESO) on the pharmacokinetics (PK) of RLY-4008 in healthy subjects (HS). Methods: This was a randomized, open-label, three-period, fed and fasted two-treatment crossover and fixed sequence, drug-drug interaction study to assess the effect of food and ESO on RLY-4008 PK. Twenty-four HS were enrolled to receive single oral doses of 50 mg RLY-4008 (fasted or fed with a high fat, high calorie meal) or RLY-4008 with ESO (fasted), with ≥7 days washout between each treatment. RLY-4008 PK was assessed up to 120 hours post dose. The effect of food and ESO was assessed using log-transformed RLY-4008 Cmax and AUC by linear mixed-effect modeling and calculating point estimates and associated 90% confidence intervals (CI) of geometric least squares mean ratios (LSGMR). Safety and tolerability were assessed through discharge/end of study. Results: Twenty-four HS were enrolled and completed the study. The median Tmax of RLY-4008 was similar when administered fasted, with food or with ESO. LSGMRs of Cmax, AUC(0-tlast) and AUC (0-inf) between RLY-4008 administered with food and fasted were 87%, 105%, and 106%, respectively, and the associated 90% CIs were 77-97%, 100-110%, and 100-110%, respectively. The LSGMRs and associated 90% CIs of AUCs were fully contained within 80% to 125%, while the lower bound of 90% confidence of Cmax LSGMR was below 80%. The 13% reduction in RLY-4008 Cmax with food was not considered clinically relevant. LSGMRs of Cmax, AUC(0-tlast) and AUC (0-inf) between RLY-4008 administered with ESO and alone were 110%, 113%, and 113%, respectively, and the associated 90% CIs were 102-119%, 109-117%, and 109-117%, respectively, and were fully contained within 80% to 125%. RLY-4008 was safe and well tolerated in HS when administered fasted, fed or with ESO. Conclusion: Food and ESO does not have a clinically relevant effect on RLY-4008 PK in HS, indicating that RLY-4008 can be dosed with or without food and can be dosed with PPIs, H2-blockers and anti-acids in cancer patients. Citation Format: Jinshan Shen, Rishikesh Sawant, Rick Blakesley, Kai Yu Jen, Fabien Ricard, Xiaoyan Li, Cassandra Key, Djuro Karanovic. A food effect and esomeprazole drug-drug interaction study of RLY-4008, a highly selective FGFR2 inhibitor, in healthy subjects [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2795.

Peripheral administration of neuropeptide W inhibits gastric emptying in rats: The role of small diameter afferent fibers and cholecystokinin receptors

Neuropeptide W (NPW), a novel hypothalamic peptide, contributes to the central regulation of food intake and energy balance, and suppresses feeding behavior when administered centrally. The aim of our study was to investigate the role of peripherally administered NPW in the modulation of gastric emptying, and to evaluate the participation of afferent fibers, cholecystokinin (CCK) receptors and gastric smooth muscle contractility in the regulatory effects of NPW on gastric motility. In Sprague-Dawley male rats equipped with gastric fistula, gastric emptying rate of the saline and peptone solutions was measured following subcutaneous administration of NPW (0.1 or 5 μg/kg) preceded by subcutaneous injections of saline, CCK-1 or CCK-2 receptor antagonists. Another group of rats with cannulas were injected subcutaneously with capsaicin for afferent denervation before commencing emptying trials. The effect of NPW on carbachol-induced gastric contractility and the role of CCK receptors in gastric smooth muscle contractility were also assessed in gastric strips. Peripheral injection of NPW delayed gastric emptying rate of both caloric and non-caloric liquid test meals, while administration of CCK-1 or CCK-2 receptor antagonists or denervation of small diameter afferents reversed NPW–induced delay in gastric emptying. Moreover, NPW inhibited antrum contractility in the organ bath. Our results revealed that peripherally administered NPW delayed liquid emptying from the stomach via the involvement of small diameter afferent neurons and CCK receptors, and thereby this regulatory role may contribute to its central regulatory role in controlling food intake and energy balance.

Food-Related Carbonyl Stress in Cardiometabolic and Cancer Risk Linked to Unhealthy Modern Diet.

Carbonyl stress is a condition characterized by an increase in the steady-state levels of reactive carbonyl species (RCS) that leads to accumulation of their irreversible covalent adducts with biological molecules. RCS are generated by the oxidative cleavage and cellular metabolism of lipids and sugars. In addition to causing damage directly, the RCS adducts, advanced glycation end-products (AGEs) and advanced lipoxidation end-products (ALEs), cause additional harm by eliciting chronic inflammation through receptor-mediated mechanisms. Hyperglycemia- and dyslipidemia-induced carbonyl stress plays a role in diabetic cardiovascular complications and diabetes-related cancer risk. Moreover, the increased dietary exposure to AGEs/ALEs could mediate the impact of the modern, highly processed diet on cardiometabolic and cancer risk. Finally, the transient carbonyl stress resulting from supraphysiological postprandial spikes in blood glucose and lipid levels may play a role in acute proinflammatory and proatherogenic changes occurring after a calorie dense meal. These findings underline the potential importance of carbonyl stress as a mediator of the cardiometabolic and cancer risk linked to today’s unhealthy diet. In this review, current knowledge in this field is discussed along with future research courses to offer new insights and open new avenues for therapeutic interventions to prevent diet-associated cardiometabolic disorders and cancer.

Significance of Postprandial Insulin and Triglycerides to Evaluate the Metabolic Response of Composite Meals Differing in Nutrient Composition – A Randomized Cross-Over Trial

Background and aimsGlucoTRIG, based on postprandial plasma insulin and triglyceride concentrations, has been recently developed as a novel index to determine the postprandial metabolic response to the meals. This study aimed to test GlucoTRIG as a measure for ranking composite meals for their metabolic effects.MethodsIn a randomized cross-over trial, healthy adult volunteers (both males and females; n = 10 for each meal) consumed three is caloric (2000 kj) test meals (meal 1, meal 2, meal 3) of varying macronutrient composition. Postmeal consumption, venous blood samples were collected to determine plasma insulin and plasma triglycerides for estimating the GlucoTRIG value using (Triglycerides180min × Insulin180min) - (Triglycerides0min × Insulin0min).ResultsThe GlucoTRIG values differed significantly (p = 0.0085) across meals. The statistical significance remains even after adjusting for confounding variables such as baseline diet, insulin, and triglycerides. The meal (M3) with a high fiber, low total fat content and containing less refined foods (fruits, beans, vegetables, plain yogurt) exhibited a significantly (p = 0.007) lower GlucoTRIG value (10 ± 7.7) compared to the other two meals, M1 (77 ± 19.8) and M2 (38 ± 12.1) which contained low processed foods, and were relatively high in fat and low in fiber meals. No statistically significant differences were observed between M1 and M2 meal.ConclusionsGlucoTRIG is a physiologically based index that may be useful to rank composite meals for reducing the risk of metabolic diseases. Further research focusing on the application of GlucoTRIG to foods, meals, and diets is warranted.ACTRN12619000973112 (Australian New Zealand Clinical Trials Registry, ANZCTR).

Small bowel water content assessed by MRI in health and disease: a collation of single-centre studies.

New developments in MRI have allowed the non-invasive, accurate measurement of the small bowel water content (SBWC). To collate studies measuring SBWC following ingestion of a range of foods in both health and disease to provide data for adequately powering future studies in this area. This collation brings together 29 studies including 954 participants (530 healthy, 54 diverticulosis, 255 IBS, 53 functional constipation, 12 cystic fibrosis, 15 Crohn's disease, 20 coeliac disease, 15 scleroderma) which have been carried out in a single centre using comparable study designs. Fasting SBWC (mean 82 [SD 65]mL) shows high variability with a small decline with advancing age (healthy volunteers only; individual patient data). Fasting values are increased in untreated coeliac disease (202 [290]mL, P=0.004). Post-prandial SBWC shows less intra-individual variability than fasting values in healthy volunteers. SBWC is increased by eating, most markedly by high fat meals but also by fibre, both viscous and particulate. Indigestible residue accumulates in late post-prandial period but empties soon after ingestion of a high calorie meal which produces a significant drop (by 50 [52]mL) in healthy volunteers. The associated fall in SBWC is abnormal in people with cystic fibrosis (SBWC reduced by 10 [121]mL, P=0.002) and in people with irritable bowel syndrome with diarrhoea (SBWC reduced by 17 [43] mL, P=0.007). SBWC as assessed by MRI is a valuable biomarker indicating the balance of secretion and absorption in health and disease and the impact of treatments.

Changes in the calorie and nutrient content of purchased fast food meals after calorie menu labeling: A natural experiment.

BackgroundCalorie menu labeling is a policy that requires food establishments to post the calories on menu offerings to encourage healthy food choice. Calorie labeling has been implemented in the United States since May 2018 per the Affordable Care Act, but to the best of our knowledge, no studies have evaluated the relationship between calorie labeling and meal purchases since nationwide implementation of this policy. Our objective was to investigate the relationship between calorie labeling and the calorie and nutrient content of purchased meals after a fast food franchise began labeling in April 2017, prior to the required nationwide implementation, and after nationwide implementation of labeling in May 2018, when all large US chain restaurants were required to label their menus.Methods and findingsWe obtained weekly aggregated sales data from 104 restaurants that are part of a fast food franchise for 3 national chains in 3 US states: Louisiana, Mississippi, and Texas. The franchise provided all sales data from April 2015 until April 2019. The franchise labeled menus in April 2017, 1 year prior to the required nationwide implementation date of May 2018 set by the US Food and Drug Administration. We obtained nutrition information for items sold (calories, fat, carbohydrates, protein, saturated fat, sugar, dietary fiber, and sodium) from Menustat, a publicly available database with nutrition information for items offered at the top revenue-generating US restaurant chains. We used an interrupted time series to find level and trend changes in mean weekly calorie and nutrient content per transaction after franchise and nationwide labeling. The analytic sample represented 331,776,445 items purchased across 67,112,342 transactions. Franchise labeling was associated with a level change of −54 calories/transaction (95% confidence interval [CI]: −67, −42, p < 0.0001) and a subsequent 3.3 calories/transaction increase per 4-week period (95% CI: 2.5, 4.1, p < 0.0001). Nationwide implementation was associated with a level decrease of −82 calories/transaction (95% CI: −88, −76, p < 0.0001) and a subsequent −2.1 calories/transaction decrease per 4-week period (95% CI: −2.9, −1.3, p < 0.0001). At the end of the study, the model-based predicted mean calories/transaction was 4.7% lower (change = −73 calories/transaction, 95% CI: −81, −65), and nutrients/transaction ranged from 1.8% lower (saturated fat) to 7.0% lower (sugar) than what we would expect had labeling not been implemented. The main limitations were potential residual time-varying confounding and lack of individual-level transaction data.ConclusionsIn this study, we observed that calorie labeling was associated with small decreases in mean calorie and nutrient content of fast food meals 2 years after franchise labeling and nearly 1 year after implementation of labeling nationwide. These changes imply that calorie labeling was associated with small improvements in purchased meal quality in US chain restaurants.

Food Purchases in an Online Virtual Restaurant

Abstract Objectives Food is commonly purchased at fast-food restaurants and improving food choices at these establishments may be a key contributor to improving the nation's diet. A better understanding of the barriers to dietary change when purchasing foods at fast-food restaurants may aid the development of new interventions to improve dietary choices. The objective of this study is to determine the costs and benefits of choosing a lower calorie meal in a 3D virtual representation of a fast-food restaurant. Methods In this ongoing study, a 3D model of a fast-food restaurant was created and accessed by participants through the internet. The foods on the menu, their nutritional content and price were based on foods served at popular fast-food restaurants. After completing a demographic questionnaire, participants were placed at the entrance of a 3D virtual restaurant where the rated their subjective appetite and rated the expected palatability and satiety of the foods on the menu. Participants were then randomized to one of two conditions: free-choice or goal-orientated (asked to choose a meal that was 700kcal). The participant could then view all menu items on a representation of an electronic ordering kiosk in the store and was asked to ‘purchase’ a meal. After the meal was selected, participants were asked to rate the palatability and expected satiety of that meal. The cost and nutritional content of the meal was determined. Results Preliminary data are presented but as the study is in progress statistical analysis has not currently been performed. Twenty-three participants have currently completed the study. The energy purchased in the free condition is 941kcal while in the constrained condition it is 722 kcal. The cost of the constrained meal is $6.93 and the free meal is $7.16. People in the free condition have taken 65.2 seconds to order whereas people in the constrained condition have taken 72.3 seconds. Conclusions This ongoing study illustrated the potential for collecting data about food choices using virtual worlds. This approach may provide new insights into how people make food decisions. Funding Sources This project received no funding.

Effects of late-night eating of easily-or slowly-digestible meals on sleep, hypothalamo-pituitary-adrenal axis, and autonomic nervous system in healthy young males.

Aim of the current study was to assess the effects of the digestibility of late-night high calorie meal on sleep and the activities of the hypothalamo-pituitary-adrenal (HPA) and autonomous nervous system (ANS) in healthy young males. For that purpose, effects of an easily digestible meal (starch+sugar-rich meal, SSR, i.e., dessert) or a slowly digestible meal (protein+fat-rich, PFR, i.e. kebab) were investigated in a crossover design in 16 participants (20-26 year old). They did not eat anything after 07:00 PM on Day 0; had an SSR meal on Day 1 and a PFR meal on Day 2 at 10:00 PM. HPA and ANS activities were measured by cortisol awakening response (CAR) and heart rate variability (HRV), respectively. The participants provided salivary samples for CAR; had a 5-min continuous electrocardiogram recording for HRV; and filled in sleep questionnaires. Late-night eating of SSR and PFR diets increased the area under the curve of CAR (p<0.05) but did not affect HRV parameters (p>0.05). PFR meal significantly disturbed sleep (p<0.05). The data suggests that increased activity of HPA, but not ANS, might be involved in pathophysiology of late-night eating and that this might be due to disturbed sleep if slowly-digestible meal is consumed.

Assessment of the sublingual microcirculation with the GlycoCheck system: Reproducibility and examination conditions.

The glycocalyx is an extracellular layer lining the lumen of the vascular endothelium, protecting the endothelium from shear stress and atherosclerosis and contributes to coagulation, immune response and microvascular perfusion. The GlycoCheck system estimates glycocalyx' thickness in vessels under the tongue from perfused boundary region (PBR) and microvascular perfusion (red blood cell (RBC) filling) via a camera and dedicated software. Evaluating reproducibility and influence of examination conditions on measurements with the GlycoCheck system. Open, randomised, controlled study including 42 healthy smokers investigating day-to-day, side-of-tongue, inter-investigator variance, intraclass-correlation (ICC) and influence of examination conditions at intervals from 0-180 minutes on PBR and RBC filling. Mean (SD) age was 24.9 (6.1) years, 52% were male. There was no significant intra- or inter-investigator variation for PBR or RBC filling nor for PBR for side-of-tongue. A small day-to-day variance was found for PBR (0.012μm, p = 0.007) and RBC filling (0.003%, p = 0.005) and side-of-tongue, RBC filling (0.025%, p = 0.009). ICC was modest but highly improved by increasing measurements. Small significant influence of cigarette smoking (from 40-180 minutes), high calorie meal intake and coffee consumption was found. The latter two peaking immediately and tapering off but remained significant up to 180 minutes, highest PBR changes for the three being 0.042μm (p<0.05), 0.183μm (p<0.001) and 0.160μm (p<0.05) respectively. Measurements with the GlycoCheck system have a moderate reproducibility, but highly increases with multiple measurements and a small day-to-day variability. Smoking, meal and coffee intake had effects up to 180 minutes, abstinence is recommended at least 180 minutes before GlycoCheck measurements. Future studies should standardise conditions during measurements.

Caloric and Macronutrient Intake and Meal Timing Responses to Repeated Sleep Restriction Exposures Separated by Varying Intervening Recovery Nights in Healthy Adults.

Sleep restriction (SR) reliably increases caloric intake. It remains unknown whether such intake cumulatively increases with repeated SR exposures and is impacted by the number of intervening recovery sleep opportunities. Healthy adults (33.9 ± 8.9y; 17 women, Body Mass Index: 24.8 ± 3.6) participated in a laboratory protocol. N = 35 participants experienced two baseline nights (10 h time-in-bed (TIB)/night; 22:00–08:00) followed by 10 SR nights (4 h TIB/night; 04:00–08:00), which were divided into two exposures of five nights each and separated by one (n = 13), three (n = 12), or five (n = 10) recovery nights (12 h TIB/night; 22:00–10:00). Control participants (n = 10) were permitted 10 h TIB (22:00–08:00) on all nights. Food and drink consumption were ad libitum and recorded daily. Compared to baseline, sleep-restricted participants increased daily caloric (+527 kcal) and saturated fat (+7 g) intake and decreased protein (−1.2% kcal) intake during both SR exposures; however, intake did not differ between exposures or recovery conditions. Similarly, although sleep-restricted participants exhibited substantial late-night caloric intake (671 kcal), such intake did not differ between exposures or recovery conditions. By contrast, control participants showed no changes in caloric intake across days. We found consistent caloric and macronutrient intake increases during two SR exposures despite varying intervening recovery nights. Thus, energy intake outcomes do not cumulatively increase with repeated restriction and are unaffected by recovery opportunities.

Weight Change During a Clinical Weight Management Program: An Observational Cohort Study

ABSTRACT Background: The objective of this analysis was to describe weight loss results at 12 months of a clinical weight management program in which patients selected their treatment preference. Methods: 3,007 patients (mean ± SD; age = 50 ± 12 years, body mass index = 42 ± 8 kg·m−2, 80% female, 51% black) enrolled in the program at Henry Ford Hospital self-selected a 1,200 to 2,000 kcals hypocaloric, 1,000 to 1,500 kcals low calorie, or 500 to 900 kcals very low calorie meal plan. Meal plans were instructed by a dietitian and the low calorie and very low calorie meal plans incorporated the use of commercial meal replacements. Regular biweekly appointments were conducted by a clinical exercise physiologist. Program termination was at the patient's discretion. Change in body weight was analyzed at 12 months by linear mixed modeling and using the baseline observation carried forward method with repeated measure analysis of variance. Results: Average program participation was 5 months. Based on an intent-to-treat linear mixed modeling, the very low calorie group had the greatest 12-month weight loss (−13.9 ± 1.0 kg), followed by the low calorie and hypocaloric groups (−9.5 ± 0.6 and −6.0 ± 0.4 kg, respectively; P &amp;lt; 0.05 for both low calorie and hypocaloric vs very low calorie plan). The baseline observation carried forward analysis also demonstrated significant weight loss in all groups at 12 months. Conclusion: In this real-world weight management program setting of patients who self-selected a meal plan and length of participation, both very low calorie and low calorie plans resulted in more weight loss at 12 months than the hypocaloric plan.

SAT-515 Anorexia and Severe Hypothyroidism Driving Persistent Ascites and Liver Injury

Background Unintentional weight loss, ascites, and altered mental status typically raise concerns for hepatologic-cardiac-oncologic disease. Herein we present a case that after exhaustive workup the etiology of the aforementioned findings was attributed to a combination of anorexia and severe hypothyroidism, states where slowed metabolism and altered nutritional status can interact synergistically. Clinical Case A 71 y/o lady with a history of hypothyroidism after RAI for Graves’ disease, anxiety, depression, presented with 20-30 lbs unintentional weight loss over 5 months. She had poor appetite, nausea, constipation, increased abdominal girth, anasarca, fatigue, weakness, and altered mental status. On exam she had bradycardia, hypotension and hypothermia (BP 97/51, HR 54, RR 18, Temp 94, BMI 15.8). Labs revealed a TSH of 36, FT4 0.98, Tbili 0.3, alk phos 491, AST 435, ALT 651, gGT 151, albumin 2.3, prealbumin 14.7, INR 1.03, and pancytopenia. Treatment with IV levothyroxine resulted in mental status improvement. Over the next few months extensive testing revealed mild element deficiencies (zinc 44- nl range 60 - 130 mcg/dL, vit A 32- nl range 38 - 98 mcg/dL), no evident infectious/hematologic or inflammatory disease. Despite 3 paracenteses, 2 liver biopsies, multiple imaging studies (abdominal U/S, ECHO, XRs, CT chest/abdomen/pelvis, MRI abdomen/pelvis, enterography, MRI brain, PET scan), EGD/colonoscopy, bone marrow bx, and explorative laparoscopic abdominal surgery, no clear explanation was found. During the workup her liver enzymes remained elevated, TSH and fT4 normalized, but T3 remained low at 50 (76 - 181 ng/dL). Psychiatric evaluation revealed mild cognitive impairment, presumed to be secondary to depression and underlying disease. By exclusion, she was diagnosed with anorexia with a possible component of persistent hypothyroidism. She was fed through NG tube and followed closely by nutrition with a personalized high protein and calorie meal plan. Eight months later she had gained 5 lbs, her liver enzymes/electrolytes and CBC normalized, and most of her symptoms resolved. Conclusion Hypothyroidism can cause LFT abnormalities, and though rare, there are >50 cases of hypothyroidism induced ascites reported. Usually LFTs and ascites normalize promptly with hormone supplementation. However, our patient’s case was complicated by severe anorexia, with nutritional status essentially equivalent to kwashiorkor sufferers. Though extremely rare in the developed world and in adults, kwashiorkor like physiology has been described in patients with anorexia, with impressive liver abnormalities, presumed to be due to autophagy. Though certainly this is a rare diagnosis, it does point to the fact that in our test driven culture, it is worth pausing, re-evaluating history and physical and thinking outside the box prior to subjecting our patients to countless tests and procedures.

Chocolate for breakfast prevents circadian desynchrony in experimental models of jet-lag and shift-work

Night-workers, transcontinental travelers and individuals that regularly shift their sleep timing, suffer from circadian desynchrony and are at risk to develop metabolic disease, cancer, and mood disorders, among others. Experimental and clinical studies provide evidence that food intake restricted to the normal activity phase is a potent synchronizer for the circadian system and can prevent the detrimental metabolic effects associated with circadian disruption. As an alternative, we hypothesized that a timed piece of chocolate scheduled to the onset of the activity phase may be sufficient stimulus to synchronize circadian rhythms under conditions of shift-work or jet-lag. In Wistar rats, a daily piece of chocolate coupled to the onset of the active phase (breakfast) accelerated re-entrainment in a jet-lag model by setting the activity of the suprachiasmatic nucleus (SCN) to the new cycle. Furthermore, in a rat model of shift-work, a piece of chocolate for breakfast prevented circadian desynchrony, by increasing the amplitude of the day-night c-Fos activation in the SCN. Contrasting, chocolate for dinner prevented re-entrainment in the jet-lag condition and favored circadian desynchrony in the shift-work models. Moreover, chocolate for breakfast resulted in low body weight gain while chocolate for dinner boosted up body weight. Present data evidence the relevance of the timing of a highly caloric and palatable meal for circadian synchrony and metabolic function.