scholarly journals Study Protocol: A 2-Month Cross-Over Controlled Feeding Trial Investigating the Effect of Animal and Plant Protein Intake on the Metabolome and Cardiometabolic Health

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 1281-1281
Author(s):  
Gaïa Lépine ◽  
François Mariotti ◽  
Jean-François Huneau ◽  
Nathalie Poupin ◽  
Marie Tremblay-Franco ◽  
...  
Keyword(s):  
Endothelial Function ◽  
Plant Protein ◽  
Metabolic Phenotype ◽  
Cardiometabolic Health ◽  
High Fat ◽  
Feeding Trial ◽  
Dietary Shift ◽  
Inflammatory Status ◽  
Fasted State ◽  
Fat Meal

Abstract Objectives A dietary shift in favor of plant protein (PP) sources over animal protein (AP) sources has been advocated for both sustainability and health reasons, this dietary transition being noticeably associated to decreased cardiovascular and diabetes risks. The differences in amino acid composition between PP and AP may have several effects on the metabolic pathways, and in turn health impacts, which are still poorly characterized. This project aims at characterizing, with a combination of “omics” approaches, the metabolic reorientations induced by a dietary shift from AP to PP sources and understanding their health effects in a population at cardiometabolic risk. Methods We will conduct a cross-over randomized feeding trial (NCT04236518) in 20 healthy overweight males (BMI 25–35), aged 25–55, with an enlarged waist circumference (> 94cm) and high plasma triglycerides (>1.5g/L). Participants will be assigned for 1 month each to 2 diets containing predominantly either AP (65% AP:35% PP) or PP (35% AP:65% PP) in a randomized order, separated by a 2-week wash-out period. Lunch and diner will be directly provided while dietary guidelines will be given for breakfast and snacks. Blood, urine and stool samples will be collected at the fasted state every 2 weeks. At the end of each dietary intervention, blood and urine will be collected following a high fat meal, which challenges metabolism and vascular homeostasis. Plasma and urine non-targeted metabolomics analyses (LC-MS) will be combined with Peripheral Blood Mononuclear Cell (PBMC) transcriptomics and fluxomics analyses (D2O tracer) to get a comprehensive overview of the metabolic phenotype associated with AP or PP intake. Flow-Mediated Dilatation (FMD) and Flow Laser Doppler (FLD) will be used to measure respectively macrovascular endothelial function and microvascular skin blood flow at the fasted state and after the high-fat meal. We will also measure anthropometric parameters and analyze biochemistry and inflammatory markers. Results Not applicable (protocols abstract). Conclusions We expect the multi-omics fingerprinting to reveal subtle metabolic differences associated to AP or PP intake, with a positive effect of PP intake. Improved inflammatory status and endothelial function are also expected to be associated to PP intake. Funding Sources INRAE and Roquette Frères.

scholarly journals A Scoping Review: Metabolomics Signatures Associated With Animal or Plant Protein Intake and Their Potential Relation to Cardiometabolic Risk

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 509-509
Author(s):  
Gaïa Lépine ◽  
Hélène Fouillet ◽  
Didier Rémond ◽  
Jean-François Huneau ◽  
François Mariotti ◽  
...  
Keyword(s):  
Amino Acids ◽  
Scoping Review ◽  
Cardiometabolic Risk ◽  
Plant Protein ◽  
Metabolic Effects ◽  
Metabolic Phenotype ◽  
Cardiometabolic Health ◽  
Potential Implication ◽  
Dietary Shift ◽  
Increased Risk

Abstract Objectives The dietary shift from animal protein (AP) sources to plant protein (PP) sources is promoted for both environmental and health reasons. Indeed, PP are associated to lower cardiovascular and diabetes risks compared to AP, but the underlying mechanisms remain mostly unknown. Metabolomics, which has a unique ability to provide an integrative snapshot of the metabolic status of an individual, is a valuable tool to investigate the different metabolic pathways activated by AP or PP intake and to provide biomarkers of their metabolic effects. This scoping review aimed at gathering and analyzing the available data on the metabolomics signatures associated to PP or AP intake, for discussing the metabolic effects underlying these signatures and their potential implication for cardiometabolic health. Methods We selected a total of 23 human studies comparing the urine, plasma or serum metabolomes associated to diets with contrasted AP and PP intakes, such as vegetarian and omnivore diets, and collected all discriminant metabolites across diets. Results Out of the 447 discriminant metabolites, 44 were repeatedly reported across studies, amino acids (AA) and AA-related products accounting for a high proportion. Branch-chained amino acids (BCAA), aromatic amino acids (AAA), glutamate, short-chained acylcarnitines and Trimethylamine-N-Oxide (TMAO) were associated to AP while glycine was associated to PP intake. TCA cycle intermediates and products from AAA gut microbiota degradation were also often reported, but the direction of their associations with AP or PP remained unclear. As regard to their implication for cardiometabolic health, BCAA, AAA, glutamate, short-chained acylcarnitines and TMAO are known to be associated to increased risk while glycine is rather associated with a decreased risk. Conclusions AP or PP intakes result in different metabolomics signatures, several metabolites being plausible candidates to at least partially explain their differential associations with cardiometabolic risk. Additional studies with a specific focus on protein type, deep dietary data and tight intake control are needed to better characterize the associated metabolic phenotype and understand how it could mediate AP or PP effects on cardiometabolic risk. Funding Sources INRAE

Clinical pharmacokinetics of bdtx-189, an inhibitor of allosteric ErbB mutations, in patients with advanced solid malignancies in MasterKey-01 study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3097-3097
Author(s):  
Nigel Waters ◽  
Manish R. Patel ◽  
Alison M. Schram ◽  
Jordi Rodon Ahnert ◽  
Shekeab Jauhari ◽  
...  
Keyword(s):  
Dose Escalation ◽  
Drug Exposure ◽  
Target Range ◽  
Dosing Regimen ◽  
High Fat ◽  
Clinical Pharmacokinetics ◽  
Median Tmax ◽  
Fasted State ◽  
Rapid Absorption ◽  
Fat Meal

3097 Background: Allosteric oncogenic mutations occur outside the canonical ATP-binding site of EGFR and HER2, and there are no approved therapies that target such mutations. BDTX-189 is a potent, selective, irreversible inhibitor of 48 allosteric EGFR and HER2 mutant variants under clinical evaluation in the ongoing MasterKey-01 trial (NCT04209465). BDTX-189 was designed to rapidly and irreversibly occupy the active site of targeted ErbB mutants, leading to sustained pharmacodynamic (PD) effects, and with selectivity over EGFR-WT in order to minimize EGFR-WT mediated toxicities. The pharmacokinetic (PK) profile was designed for rapid absorption and fast elimination to maintain target occupancy while minimizing prolonged drug exposure that could contribute to off-target associated toxicities. Methods: In MasterKey-01, BDTX-189 was administered orally once daily in continuous 21-day cycles, taken fasted. Dose escalation included cohorts of 1-2 patients receiving doses between 25 and 200 mg QD followed by 5-7 patients receiving 400 mg, 800 mg, or 1,200 mg QD fasted. The possible effects of a high fat meal on the PK of BDTX-189 were assessed in a subset of patients receiving single doses of 400 mg BDTX-189 fasted and immediately after a high-fat breakfast in a randomized crossover fashion with 3 days between doses. In addition, a dose escalation cohort investigating administration of BDTX-189 non-fasted was enrolled at 800 mg QD. Serial blood samples for analysis of plasma BDTX-189 concentrations were collected after each dose on C1D1 and C1D15. BDTX-189 levels were determined using LC-MS, and data analyzed using non-compartmental methods. Results: After single and multiple doses, BDTX-189 was rapidly absorbed (median tmax 1-2 h), with an elimination t1/2 of 2-6 h. Dose-dependent increases in exposure from 200 to 800 mg QD fasted were observed, with no apparent accumulation or decline in exposures observed at steady-state. Administration of BDTX-189 with a high-fat meal increased AUC approximately 1.7-fold with minimal effect on Cmax, relative to administration in the fasted state. At 800 mg QD, mean AUC was similar in the non-fasting state relative to fasting and was within the target efficacious range defined by mouse models harboring allo-ErbB mutated tumors. Median tmax and t1/2 values were similar after administration in the non-fasted and fasted states. Conclusions: BDTX-189 demonstrated rapid absorption and a short PK half-life consistent with the desired PK/PD profile, with exposures in the efficacious target range based on preclinical data. The pilot high fat food-effect data and non-fasting QD dosing regimen show similar or improved systemic exposure relative to dosing in the fasted state. The MasterKey-01 trial is ongoing, including refinement of the dosing regimen and identification of the recommended phase 2 dose. Clinical trial information: NCT04209465.

scholarly journals Acute Effect of High-Fat Meal on Endothelial Function in Moderately Dyslipidemic Subjects

2005 ◽  
Vol 25 (2) ◽  
pp. 406-410 ◽  
Author(s):  
C. Giannattasio ◽  
A. Zoppo ◽  
G. Gentile ◽  
M. Failla ◽  
A. Capra ◽  
...  
Keyword(s):  
Endothelial Function ◽  
Acute Effect ◽  
High Fat ◽  
Fat Meal

scholarly journals Is the effect of prior exercise on postprandial lipaemia the same for a moderate-fat meal as it is for a high-fat meal?

2010 ◽  
Vol 105 (4) ◽  
pp. 506-516 ◽  
Author(s):  
Nicholas M. Hurren ◽  
Frank F. Eves ◽  
Andrew K. Blannin
Keyword(s):  
Test Meal ◽  
Venous Blood ◽  
Exercise Bout ◽  
Moderate Intensity ◽  
High Fat ◽  
Moderate Intensity Exercise ◽  
Postprandial Lipaemia ◽  
Fasted State ◽  
Prior Exercise ◽  
Fat Meal

Moderate-intensity exercise can lower the TAG response to a high-fat meal; however, the British diet is moderate in fat, and no study to date has compared the effect of such exercise on responses to high-fat and moderate-fat meals. The present work investigated the effect of brisk walking performed 13 h before intake of both high-fat and moderate-fat meals on postprandial plasma TAG concentrations. Eight inactive, overweight men completed four separate 2 d trials, i.e. rest (Con) or a 90-min treadmill walk (Ex) on the evening of day 1, followed by the ingestion of a moderate-fat (Mod) or high-fat (High) meal on the morning of day 2. High-fat meals contained 66 % of total energy as fat, while the percentage was 35 % for moderate-fat meals; both the meals were, however, isoenergetic. On day 2, venous blood was sampled in the fasted state, 30 and 60 min after ingesting the test meal and then hourly until 6 h post-meal. Exercise reduced plasma TAG concentrations significantly (P < 0·001), with no exercise × meal interaction (P = 0·459). Walking reduced the total TAG response to a high-fat meal by 29 % (relative to High Con); the same bout of exercise performed before ingesting a moderate-fat meal lowered total TAG by 26 % (compared with Mod Con). The ability of a single moderate-intensity aerobic exercise bout to lower postprandial TAG concentrations is just as great, in percentage terms, when the test meal ingested is of a moderate rather than a high fat content.

The Effect of a High-Fat Meal on Endothelial Function in Physically Active Versus Sedentary Adults

2007 ◽  
Vol 39 (Supplement) ◽  
pp. S84 ◽  
Author(s):  
Jaume Padilla ◽  
Ryan A. Harris ◽  
Kevin P. Hanlon ◽  
Shelby S. Sutton ◽  
Alyce D. Fly ◽  
...  
Keyword(s):  
Endothelial Function ◽  
High Fat ◽  
Physically Active ◽  
Fat Meal

BH4 improves postprandial endothelial function after a high-fat meal in men and postmenopausal women

2017 ◽  
Vol 24 (5) ◽  
pp. 555-562 ◽  
Author(s):  
Yashesh Shah ◽  
Leon Bass ◽  
Gareth W. Davison ◽  
Nichole Seigler ◽  
Jennifer S. Pollock ◽  
...  
Keyword(s):  
Endothelial Function ◽  
Postmenopausal Women ◽  
High Fat ◽  
Fat Meal

Impairment of endothelial function after a high-fat meal in patients with coronary artery disease

2001 ◽  
Vol 12 (7) ◽  
pp. 561-565 ◽  
Author(s):  
Shui-Ping Zhao ◽  
Ling Liu ◽  
Mei Gao ◽  
Qi-Chang Zhou ◽  
Yu-Ling Li ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Endothelial Function ◽  
High Fat ◽  
Artery Disease ◽  
Fat Meal

A comparison between active- and reactive-hyperaemia-induced brachial artery vasodilation

2006 ◽  
Vol 110 (3) ◽  
pp. 387-392 ◽  
Author(s):  
Jaume Padilla ◽  
Ryan A. Harris ◽  
Alyce D. Fly ◽  
Lawrence D. Rink ◽  
Janet P. Wallace
Keyword(s):  
Endothelial Function ◽  
Brachial Artery ◽  
Repeated Measures ◽  
Reactive Hyperaemia ◽  
High Fat ◽  
Low Fat ◽  
Balanced Design ◽  
Treatment Conditions ◽  
Main Effects ◽  
Fat Meal

The measurement of brachial artery vasodilation in response to a hyperaemic stimulus has been used extensively to assess changes in endothelial function. However, whether or not similar changes occur in response to an active hyperaemic stimulus is unknown. The purpose of the present study was to compare brachial artery vasodilation in response to an active compared with a reactive hyperaemic stimulus following a known perturbation of endothelial function. Eight apparently healthy adults were assigned to four treatment conditions in a counter-balanced design: (i) low-fat meal with active hyperaemic stimulus (LFM-A), (ii) high-fat meal with active hyperaemic stimulus (HFM-A), (iii) low-fat meal with reactive hyperaemic stimulus (LFM-R), and (iv) high-fat meal with reactive hyperaemic stimulus (HFM-R). Meals were ingested at 08:00 hours on each treatment day. Brachial artery vasodilation was assessed via ultrasound 4 h after ingestion of each meal. The active hyperaemic stimulus was induced by 5 min of rhythmic handgrip exercise, whereas reactive hyperaemia was induced by 5 min of forearm occlusion. Brachial artery vasodilation was expressed as the percentage change in diameter from baseline to post-active/reactive hyperaemia. Using a 2×2 repeated measures ANOVA, a significant stimulus×meal interaction (P=0.025) was found. Simple main effects revealed no difference (P=0.541) in brachial artery vasodilation between LFM-A (5.75±1.64%) and HFM-A (6.39±1.45%); however, a significant decrease (P=0.014) in brachial artery vasodilation was found in the HFM-R (4.29±1.64%) compared with the LFM-R (7.18±1.13%) treatment. In conclusion, the measurement of brachial artery vasodilation in response to active hyperaemia did not detect a change in endothelial function following a single perturbation meal, whereas reactive hyperaemia did.

Dasatinib Can Be Administered Orally with or without a Meal.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4569-4569 ◽  
Author(s):  
Sanjeev Kaul ◽  
Chiyuan Wu ◽  
Shelley Mayfield ◽  
James Manning ◽  
Anne Blackwood-Chirchir
Keyword(s):  
Adverse Events ◽  
Healthy Adult ◽  
Geometric Mean ◽  
Plasma Concentrations ◽  
Mass Spectrometric Method ◽  
High Fat ◽  
Low Fat ◽  
Fasted State ◽  
Tandem Mass Spectrometric ◽  
Fat Meal

Abstract Background: Food can change the bioavailability of a drug, which can have clinically significant consequences. This study was conducted to investigate the effect of food on the oral bioavailability of dasatinib (SPRYCEL®) in healthy adult subjects. Methods: Fifty-four healthy adult subjects received a single dose of dasatinib 100 mg dose, as 2 x 50 mg film-coated tablets after an overnight fast and within 10 minutes after the ingestion of a low-fat meal (315 kcal [20% fat, 68% carbohydrates, and 12% protein]) and a high-fat meal (985 kcal [52% fat, 34% carbohydrates, and 14% protein]) in a randomly assigned sequence. Individual treatments were separated by at least a 7-day washout period. Serial blood samples were collected for 24 hours after each treatment to determine dasatinib plasma concentrations using a validated liquid chromatography/tandem mass spectrometric method. Dasatinib pharmacokinetic (PK) parameters were determined using a non-compartmental method. Safety was monitored throughout the study. Results: Of the 54 healthy adult subjects (85% male, 61% Caucasian, mean age 32 y, and weight 80 kg), 48 completed the study. There were no serious adverse events. Adverse events and laboratory abnormalities were, in general, typical of those seen with dasatinib administration. PK results are summarized in the table below. Conclusions: Compared to the fasted state, a low-fat meal decreased Cmax and AUC of dasatinib by 21%; a high-fat meal decreased Cmax by 24% and increased AUC by 14%. These results are not expected to be of clinical relevance and, therefore, dasatinib may be taken without regard to meals. The drug was generally safe and well-tolerated when administered in the fed or fasted state. Statistical Analysis of PK Parameters for Dasatinib Treatment PK Parameter Geometric Mean Ratios (95% Confidence Intervals) Fed versus Fasted Low-Fat Meal Cmax 1.216 (1.047, 1.413) AUC 1.212 (1.100, 1.336) High-Fat Meal Cmax 0.758 (0.651, 0.882) AUC 1.140 (1.034, 1.257)

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