Background: Postprandial lipemia is a risk factor for cardiovascular disease. The potential impacts of the type/nature of dietary protein on postprandial lipemia and associated dysregulations have been insufficiently investigated.
Objective: We investigated the postprandial effect of including in a high-fat meal some milk protein fractions that markedly differ in their physicochemical properties and composition [either casein (CAS), whey protein (WHE), or α-lactalbumin-enriched whey protein (LAC)].
Methods: The protein fractions were incorporated as 15% energy in a high-fat meal in a 3-period, crossover postprandial study of 10 healthy overweight men with an elevated waist circumference (>94 cm). We measured postprandial changes in plasma lipids, amino acids, glucose, and oxidative stress markers, vascular function (using pulse contour analysis), and low-grade inflammation (using plasma markers). We also characterized in vitro the meal structures, including the size of the fat globule, and possible changes during digestion.
Results: The type of protein did not affect postprandial plasma glucose, amino acids, insulin, or nonesterified fatty acids, but, compared with WHE and LAC, which did not differ, CAS markedly reduced postprandial triglycerides (TGs), achieving a 22 ± 10% reduction in the 6-h area under the curve (P < 0.05). Similar trends were shown for plasma chylomicrons [apolipoprotein (apo)B-48; P < 0.05]. However, there were no significant differences between the meals regarding postprandial oxidative stress (plasma hydroperoxides and malondialdehyde), endothelial dysfunction (salbutamol-induced changes in pulse contour analysis), or low-grade inflammation. In vitro studies showed that when the pH of the meal decreased to stomach pH values, the reduction in the solubility of casein resulted in a phase separation between fat and protein, whereas the proteins in the other meals remained suspended with fat globules.
Conclusion: In healthy overweight men, casein has specific physical interactions with fat that affect postprandial TGs, leading to the formation of fewer chylomicrons or an increase in chylomicron clearance. This trial was registered at clinicaltrials.gov as NCT00931151.
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http://dx.doi.org/10.3945/jn.115.216812 | DOI Listing |
J Pharmacokinet Pharmacodyn
January 2025
PTC Therapeutics, Warren, NJ, USA.
Sepiapterin is an exogenously synthesized new chemical entity that is structurally equivalent to endogenous sepiapterin, a biological precursor of tetrahydrobiopterin (BH), which is a cofactor for phenylalanine hydroxylase. Sepiapterin is being developed for the treatment of hyperphenylalaninemia in pediatric and adult patients with phenylketonuria (PKU). This study employed concentration-QT interval analysis to assess QT prolongation risk following sepiapterin treatment.
View Article and Find Full Text PDFMol Pharm
January 2025
Department of Pharmacy, National and Kapodistrian University of Athens, Zografou 15771, Greece.
The simulation of antral conditions for estimating drug apparent equilibrium solubility after a high-calorie, high-fat meal is challenging. In this study, (1) we measured the apparent equilibrium solubility of two model lipophilic drugs, ketoconazole and danazol, in antral aspirates collected at various time points after a minced high-calorie, high-fat meal and a glass of water 30 min after initiation of meal administration, and we designated one point estimate for ketoconazole and one point estimate for danazol; (2) we evaluated the usefulness of FeSSGF-V2 and FEDGAS pH = 3 in reproducing the two point estimates; (3) we evaluated potential compositions of FeSSGF-V3 that simulate the pH, the buffer capacity toward both less acidic and more acidic values, and the antral lipid and protein contents with easily accessible, commercially available products, and (4) we identified the most useful composition of FeSSGF-V3 for reproducing the two point estimates. For both model drugs, apparent solubility in FeSSGF-V2 and in FEDGAS pH 3 deviated substantially from the corresponding point estimate.
View Article and Find Full Text PDFAAPS J
January 2025
Clinical Pharmacology Modeling and Simulation, Amgen, One Amgen Center Drive, Thousand Oaks, CA, 91320-0777, USA.
Sotorasib is a novel KRAS inhibitor that has shown robust efficacy, safety, and tolerability in patients with KRAS mutation. The objectives of the population pharmacokinetic (PK) analysis were to characterize sotorasib population PK in healthy subjects and patients with advanced solid tumors with KRAS mutation from 6 clinical studies, evaluate the effects of intrinsic and extrinsic factors on PK parameters, and perform simulations to further assess the impact of identified covariates on sotorasib exposures. A two-compartment disposition model with three transit compartments for absorption and time-dependent clearance and bioavailability well described sotorasib PK.
View Article and Find Full Text PDFJ Nutr Health Aging
January 2025
Department of Nutritional Sciences, Oklahoma State University, Stillwater, 74075 OK, United States. Electronic address:
Objectives: Postprandial inflammation post-high-fat meals may be linked to cardiovascular disease (CVD). CVD incidence increases with age; however, whether older adults experience greater postprandial inflammation remains unclear. We examined whether analyzing age categorically versus continuously influenced relationships between age and postprandial inflammatory measures.
View Article and Find Full Text PDFJ Am Nutr Assoc
January 2025
Department of Food Science and Nutrition, Faculty of Food Engineering, Universidade Estadual de Campinas - UNICAMP, Campinas, SP, Brazil.
A high-fat meal can cause postprandial hyperlipemia, initiating an acute inflammatory response. New structured lipids (SLs) free from trans and palm fatty acids are emerging as food structurants. We evaluated the postprandial response and inflammatory profiles in Swiss mice after oral administration of SLs in high-fat meals.
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