Amino Acid Absorption Kinetics Research Articles

Administration of Free Amino Acids Improves Exogenous Amino Acid Availability when Compared with Intact Protein in Critically Ill Patients: A Randomized Controlled Study

BackgroundProtein digestion and amino acid absorption appear compromised in critical illness. The provision of enteral feeds with free amino acids rather than intact protein may improve postprandial amino acid availability. ObjectiveOur objective was to quantify the uptake of diet-derived phenylalanine after the enteral administration of intact protein compared with an equivalent amount of free amino acids in critically ill patients. MethodsSixteen patients who were mechanically ventilated in intensive care unit (ICU) at risk of malabsorption received a primed continuous infusion of L-[ring-2H5]-phenylalanine and L-[ring-3,5-2H2]-tyrosine after an overnight fast. Patients were randomly allocated to receive 20 g intrinsically L-[1-13C]-phenylalanine-labeled milk protein or an equivalent amount of amino acids labeled with free L-[1-13C]-phenylalanine via a nasogastric tube over a 2-h period. Protein digestion and amino acid absorption kinetics and whole-body protein net balance were assessed throughout a 6-h period. ResultsAfter enteral nutrient infusion, both plasma phenylalanine and leucine concentrations increased (P-time < 0.001), with a more rapid and greater rise after free amino acid compared with intact protein administration (P-time × treatment = 0.003). Diet-derived phenylalanine released into the circulation was 25% greater after free amino acids compared with intact protein administration [68.7% (confidence interval {CI}: 62.3, 75.1%) compared with 43.8% (CI: 32.4, 55.2%), respectively; P < 0.001]. Whole-body protein net balance became positive after nutrient administration (P-time < 0.001) and tended to be more positive after free amino acid in provision (P-time × treatment = 0.07). ConclusionsThe administration of free amino acids as opposed to intact protein further increases postprandial plasma amino acid availability in critically ill patients, allowing more diet-derived phenylalanine to become available to peripheral tissues.This trial was registered at clinicaltrials.gov as NCT04791774.

SNAPIG: a model to study nutrient digestion and absorption kinetics in growing pigs based on diet and ingredient properties

Current feed formulation and evaluation practices rely on static values for the nutritional value of feed ingredients and assume additivity. Hereby, the complex interplay among nutrients in the diet and the highly dynamic digestive processes are ignored. Nutrient digestion kinetics and diet × animal interactions should be acknowledged to improve future predictions of the nutritional value of complex diets. Therefore, an in silico nutrient-based mechanistic digestion model for growing pigs was developed: “SNAPIG” (Simulating Nutrient digestion and Absorption kinetics in PIGs). Aiming to predict the rate and extent of nutrient absorption from diets varying in ingredient composition and physicochemical properties, the model represents digestion kinetics of ingested protein, starch, fat, and non-starch polysaccharides, through passage, hydrolysis, absorption, and endogenous secretions of nutrients along the stomach, proximal small intestine, distal small intestine, and caecum + colon. Input variables are nutrient intake and the physicochemical properties (i.e. solubility, and rate and extent of degradability). Data on the rate and extent of starch and protein hydrolysis of different ingredients per digestive segment were derived from in vitro assays. Passage of digesta from the stomach was modelled as a function of feed intake level, dietary nutrient solubility and diet viscosity. Model evaluation included testing against independent data from in vivo studies on nutrient appearance in (portal) blood of growing pigs. When simulating diets varying in physicochemical properties and nutrient source, SNAPIG can explain variation in glucose absorption kinetics (postprandial time of peak, TOP: 20–100 min observed vs 25–98 min predicted), and predict variation in the extent of ileal protein and fat digestion (root mean square prediction errors (RMSPE) = 12 and 16%, disturbance error = 12 and 86%, and concordance correlation coefficient = 0.34 and 0.27). For amino acid absorption, the observed variation in postprandial TOP (61 ± 11 min) was poorly predicted despite accurate mean predictions (58 ± 34 min). Recalibrating protein digestion and amino acid absorption kinetics require data on net-portal nutrient appearance, combined with observations on digestion kinetics, in pigs fed diets varying in ingredient composition. Currently, SNAPIG can be used to forecast the time and extent of nutrient digestion and absorption when simulating diets varying in ingredient and nutrient composition. It enhances our quantitative understanding of nutrient digestion kinetics and identifies knowledge gaps in this field of research. Already useful as research tool, SNAPIG can be coupled with a postabsorptive metabolism model to predict the effects of dietary and feeding-strategies on the pig’s growth response.

Time Courses of Gastric Volume and Content after Different Types of Casein Ingestion in Healthy Men: A Randomized Crossover Study

Few studies have evaluated differences in the curd-forming ability of casein on gastric volume and content directly after ingestion in humans. This study evaluated the time course of gastric volume and curd conditions in the stomach after protein ingestion. This was an open-labeled, randomized crossover trial. Ten healthy men [age: 33.4 ± 7.3 y; BMI (kg/m2): 21.9 ± 0.9] received 350 g of 3 isonitrogenous and isocaloric protein drinks containing 30 g micellar casein (MCN), sodium caseinate (SCN), or whey protein concentrate (WPC). The gastric antrum cross-sectional area (CSA) and curd in the stomach were measured using ultrasonography within 5 h after ingestion. The differences between test foods were tested using the MIXED model and post hoc tests using Fisher's protected least significant difference. The incremental AUC of the gastric antrum CSA after MCN ingestion was 1.3-fold and 1.5-fold higher than that after the ingestion of SCN and WPC, respectively (both P < 0.05), but not different between SCN and WPC. The number of participants with curds ≥20 mm with a high echogenicity clot observed in the stomach within 5 h after MCN ingestion was significantly greater than that after the ingestion of other proteins (n = 9 for MCN, n = 2 for SCN, and n = 0 for WPC; bothP < 0.01). The regression line slopes on total plasma amino acid concentration and gastric antrum CSA were significantly different between the participants with and without curds. In contrast to SCN and WPC, MCN ingestion resulted in slow kinetics of gastric antrum CSA. Differences in curd formation of casein in the stomach affect gastric emptying and plasma amino acid absorption kinetics after ingestion in healthy men. This trial was registered at University Hospital Medical Information Network Clinical Trials Registry as UMIN000038388 (https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000043746).

Protein Matrix Impacts Essential Amino Acid Response To Feeding

It is well established that muscle protein turnover is highly response to increases in plasma essential amino acids (EAA). Digestion and amino acid absorption kinetics appear to strongly modulate post-prandial muscle protein synthesis. Despite this relationship, little is known about the effects of the protein matrix on plasma EAA appearance. PURPOSE: To assess if protein matrix alters plasma EAA pharmacokinetics (PK). METHODS: 24 healthy young individuals (24.7 ± 4.7y; BMI = 24.6 ± 3.2 kg/m2) completed this study. Participants consumed one of the following protein matrices: whey protein isolate (W; 6.8 g of EAA), beef sirloin (B; 7.0 g of EAA), or free form EAA enriched W (FW; 5.6 g of EAA). Blood samples were collected before and four hours following the ingestion of W, B, and FW. Plasma EAA were analyzed via LC-MS/MS. Standard pK values were calculated: area under the curve above baseline (AUCi), max EAA concentration (Cmax), EAA concentration change from baseline to EAACmax (ΔEAA), rate to Cmax, and time to Cmax. To examine group differences in EAA pK a one-way analysis of variance with Tukey post hoc test was performed with significance accepted at P ≤ 0.05. RESULTS: Significant group differences were noted for all measured pK (p ≤ 0.005). Post hoc comparisons indicated AUCi was significantly lower in W (50705.6 ± 13483.3 μmol/L/min) as compared to FW (84793.8 ± 15989.7 μmol/L/min; p = 0.004) and B (77084.6 ± 25076.0 μmol/L/min; p = 0.028). Cmax, ΔEAA, and rate to Cmax was significantly higher in FW (Cmax = 1,920 ± 242.6 μmol/L; ΔEAA = 1012.4 ± 200.8 μmol/L; rate to Cmax = 30.1 ± 13.0 μmol/L/min) as compared to W (Cmax = 1343.1 ± 144.4 μmol/L, p ≤ 0.001; ΔEAA = 556.9 ± 160.1 μmol/L, p ≤ 0.001; rate to Cmax = 13.6 ± 7.6 μmol/L/min, p = 0.003) and B (Cmax = 1339.9 ± 213.5 μmol/L, p ≤ 0.001; ΔEAA = 543.8 ± 164.2 μmol/L, p ≤ 0.001; rate to Cmax = 4.9 ± 2.7 μmol/L/min, p ≤ 0.001). Lastly, the time to Cmax was slowest in B (135.0 ± 62.1 mins) as compared to W (47.5 ± 14.9 mins; p ≤ 0.001) and FW (36.3 ± 7.4 mins; p ≤ 0.001). CONCLUSION: Despite similar EAA content, pharmacokinetics were significantly different between treatments. Despite the lowest EAA content, FW resulted in the greatest plasma EAA availability and quickest time to peak. These results indicate that protein/amino acid digestion is a primary determinant of plasma EAA availability.

Ingestion of Free Amino Acids Compared with an Equivalent Amount of Intact Protein Results in More Rapid Amino Acid Absorption and Greater Postprandial Plasma Amino Acid Availability Without Affecting Muscle Protein Synthesis Rates in Young Adults in a Double-Blind Randomized Trial

BackgroundThe rate of protein digestion and amino acid absorption determines the postprandial rise in circulating amino acids and modulates postprandial muscle protein synthesis rates. ObjectiveWe sought to compare protein digestion, amino acid absorption kinetics, and the postprandial muscle protein synthetic response following ingestion of intact milk protein or an equivalent amount of free amino acids. MethodsTwenty-four healthy, young participants (mean ± SD age: 22 ± 3 y and BMI 23 ± 2 kg/m2; sex: 12 male and 12 female participants) received a primed continuous infusion of l-[ring-2H5]-phenylalanine and l-[ring-3,5–2H2]-tyrosine, after which they ingested either 30 g intrinsically l-[1–13C]-phenylalanine–labeled milk protein or an equivalent amount of free amino acids labeled with l-[1–13C]-phenylalanine. Blood samples and muscle biopsies were obtained to assess protein digestion and amino acid absorption kinetics (secondary outcome), whole-body protein net balance (secondary outcome), and mixed muscle protein synthesis rates (primary outcome) throughout the 6-h postprandial period. ResultsPostprandial plasma amino acid concentrations increased after ingestion of intact milk protein and free amino acids (both P < 0.001), with a greater increase following ingestion of the free amino acids than following ingestion of intact milk protein (P-time × treatment < 0.001). Exogenous phenylalanine release into plasma, assessed over the 6-h postprandial period, was greater with free amino acid ingestion (76 ± 9%) than with milk protein treatment (59 ± 10%; P < 0.001). Ingestion of free amino acids and intact milk protein increased mixed muscle protein synthesis rates (P-time < 0.001), with no differences between treatments (from 0.037 ± 0.015%/h to 0.053 ± 0.014%/h and 0.039 ± 0.016%/h to 0.051 ± 0.010%/h, respectively; P-time × treatment = 0.629). ConclusionsIngestion of a bolus of free amino acids leads to more rapid amino acid absorption and greater postprandial plasma amino acid availability than ingestion of an equivalent amount of intact milk protein. Ingestion of free amino acids may be preferred over ingestion of intact protein in conditions where protein digestion and amino acid absorption are compromised.

Insects are a viable protein source for human consumption: from insect protein digestion to postprandial muscle protein synthesis in vivo in humans: a double-blind randomized trial

ABSTRACTBackgroundInsects have recently been identified as a more sustainable protein-dense food source and may represent a viable alternative to conventional animal-derived proteins.ObjectivesWe aimed to compare the impacts of ingesting lesser mealworm– and milk-derived protein on protein digestion and amino acid absorption kinetics, postprandial skeletal muscle protein synthesis rates, and the incorporation of dietary protein–derived amino acids into de novo muscle protein at rest and during recovery from exercise in vivo in humans.MethodsIn this double-blind randomized controlled trial, 24 healthy, young men ingested 30 g specifically produced, intrinsically l-[1-13C]-phenylalanine and l-[1-13C]-leucine labeled lesser mealworm– or milk-derived protein after a unilateral bout of resistance-type exercise. Primed continuous l-[ring-2H5]-phenylalanine, l-[ring-3,5-2H2]-tyrosine, and l-[1-13C]-leucine infusions were applied, with frequent collection of blood and muscle tissue samples.ResultsA total of 73% ± 7% and 77% ± 7% of the lesser mealworm and milk protein–derived phenylalanine was released into the circulation during the 5 h postprandial period, respectively, with no significant differences between groups (P < 0.05). Muscle protein synthesis rates increased after both lesser mealworm and milk protein concentrate ingestion from 0.025 ± 0.008%/h to 0.045 ± 0.017%/h and 0.028 ± 0.010%/h to 0.056 ± 0.012%/h at rest and from 0.025 ± 0.012%/h to 0.059 ± 0.015%/h and 0.026 ± 0.009%/h to 0.073 ± 0.020%/h after exercise, respectively (all P < 0.05), with no differences between groups (both P > 0.05). Incorporation of mealworm and milk protein-derived l-[1-13C]-phenylalanine into de novo muscle protein was greater after exercise than at rest (P < 0.05), with no differences between groups (P > 0.05).ConclusionsIngestion of a meal-like amount of lesser mealworm–derived protein is followed by rapid protein digestion and amino acid absorption and increases muscle protein synthesis rates both at rest and during recovery from exercise. The postprandial protein handling of lesser mealworm does not differ from ingesting an equivalent amount of milk protein concentrate in vivo in humans.This trial was registered at www.trialregister.nl as NL6897.

Postprandial amino acid availability after intake of intact or hydrolyzed meat protein in a mixed meal in healthy elderly subjects: a randomized, single blind crossover trial.

The absorption of dietary proteins affects the anabolic response, among others protein synthesis. For elderly, optimal amino acid absorption is warranted to preserve the amino acid pool of the body, especially skeletal muscle proteins. Therefore, the aim of this study was to characterize if hydrolyzing meat protein (HMP) would improve the amino acid absorption after ingestion of meat compared to equal amounts of the same meat proteins but present in a different structure; steak or minced meat. With a crossover study design on 12 healthy older adults (> 65 years of age, BMI 18.5-30), the amino acid absorption kinetics were explored by ingesting 0.55 g protein/kg LBM as a mixed meal together with intrinsically [2H5]phenylalanine labeled meat proteins prepared as a STEAK, MINCED meat, or HMP. Plasma [2H5]phenylalanine enrichment as well as AA concentrations were measured by mass spectrometry from blood samples drawn during a 5-h postprandial period. After HMP ingestion, [2H5]phenylalanine was faster absorbed in the initial 2 h compared to STEAK and MINCED. The peak time in AA concentrations was faster in HMP compared to STEAK and MINCED. However, the peak AA concentrations were not different between STEAK, MINCED, and HMP. Although HMP showed to have the fastest initial amino acid appearance in older adults, the peak EAA concentrations were similar after ingesting meal with either STEAK, MINCED, or HMP in the 5-h postprandial period.

Gut amino acid absorption in humans: Concepts and relevance for postprandial metabolism

<h2>Summary</h2> Dietary amino acid absorption kinetics are an important determinant of protein quality. The term "amino acid digestibility" is commonly used to refer to the amount of ingested amino acids that become available following absorption. However, one should differentiate between the subsequent processes of converting protein into smaller constituents (protein digestion) and luminal amino acid uptake (amino acid absorption). Amino acid "absorbability" or "bioavailability" is assessed by quantifying the disappearance of amino acids across (part of) the gastrointestinal tract. The assessment of fecal, apparent ileal (AID), standardized ileal (SID), and true ileal disappearance (TID), reflect amino acid absorbability with increasing accuracy, due to correction for microbial metabolism in the large intestine, basal gut endogenous amino acid losses, and total gut endogenous amino acids losses, respectively. A substantial amount of absorbed amino acids undergo first-pass splanchnic extraction, but the majority is immediately released in the circulation and becomes available for peripheral tissues. The assessment of amino acid "bioavailability" or "absorbability" is used in protein quality ranking systems such as the Digestible Indispensable Amino Acid Score (DIAAS). However, such scores neglect that the rate of absorption is also an important determinant of postprandial metabolism. In addition, amino acid absorption and/or its rate are highly dependent on factors such as the duration of the postprandial assessment period. Therefore, amino acid absorption kinetics should be assessed under the relevant experimental conditions. To this end, an oral-intravenous dual tracer approach can be applied to assess dietary protein derived amino acid release into the circulation and allows the assessment of the subsequent impact on postprandial whole-body protein metabolism.

Comprehensive assessment of post-prandial protein handling by the application of intrinsically labelled protein in vivo in human subjects.

All human tissues are in a constant state of remodelling, regulated by the balance between tissue protein synthesis and breakdown rates. It has been well-established that protein ingestion stimulates skeletal muscle and whole-body protein synthesis. Stable isotope-labelled amino acid methodologies are commonly applied to assess the various aspects of protein metabolism in vivo in human subjects. However, to achieve a more comprehensive assessment of post-prandial protein handling in vivo in human subjects, intravenous stable isotope-labelled amino acid infusions can be combined with the ingestion of intrinsically labelled protein and the collection of blood and muscle tissue samples. The combined application of ingesting intrinsically labelled protein with continuous intravenous stable isotope-labelled amino acid infusion allows the simultaneous assessment of protein digestion and amino acid absorption kinetics (e.g. release of dietary protein-derived amino acids into the circulation), whole-body protein metabolism (whole-body protein synthesis, breakdown and oxidation rates and net protein balance) and skeletal muscle metabolism (muscle protein fractional synthesis rates and dietary protein-derived amino acid incorporation into muscle protein). The purpose of this review is to provide an overview of the various aspects of post-prandial protein handling and metabolism with a focus on insights obtained from studies that have applied intrinsically labelled protein under a variety of conditions in different populations.

Ingestion of a bolus of free amino acids is followed by more rapid amino acid absorption and greater postprandial plasma amino acid availability when compared to the ingestion of an equivalent amount of intact protein

Rationale: The rate of protein digestion and amino acid absorption determines the postprandial rise in circulating amino acids and modulates postprandial muscle protein synthesis rates. This study compares protein digestion and amino acid absorption kinetics and the subsequent muscle protein synthetic response following ingestion of intact protein versus the equivalent amount of free crystalline amino acids.

Protein Type, Protein Dose, and Age Modulate Dietary Protein Digestion and Phenylalanine Absorption Kinetics and Plasma Phenylalanine Availability in Humans

ABSTRACTBackgroundDietary protein ingestion stimulates muscle protein synthesis by providing amino acids to the muscle. The magnitude and duration of the postprandial increase in muscle protein synthesis rates are largely determined by dietary protein digestion and amino acid absorption kinetics.ObjectiveWe assessed the impact of protein type, protein dose, and age on dietary protein digestion and amino acid absorption kinetics in vivo in humans.MethodsWe included data from 18 randomized controlled trials with a total of 602 participants [age: 53 ± 23 y; BMI (kg/m2): 24.8 ± 3.3] who consumed various quantities of intrinsically l-[1-13C]-phenylalanine–labeled whey (n = 137), casein (n = 393), or milk (n = 72) protein and received intravenous infusions of l-[ring-2H5]-phenylalanine, which allowed us to assess protein digestion and phenylalanine absorption kinetics and the postprandial release of dietary protein–derived phenylalanine into the circulation. The effect of aging on these processes was assessed in a subset of 82 young (aged 22 ± 3 y) and 83 older (aged 71 ± 5 y) individuals.ResultsA total of 50% ± 14% of dietary protein–derived phenylalanine appeared in the circulation over a 5-h postprandial period. Casein ingestion resulted in a smaller (45% ± 11%), whey protein ingestion in an intermediate (57% ± 10%), and milk protein ingestion in a greater (65% ± 13%) fraction of dietary protein–derived phenylalanine appearing in the circulation (P < 0.001). The postprandial availability of dietary protein–derived phenylalanine in the circulation increased with the ingestion of greater protein doses (P < 0.05). Protein digestion and phenylalanine absorption kinetics were attenuated in older when compared with young individuals, with 45% ± 10% vs. 51% ± 14% of dietary protein–derived phenylalanine appearing in the circulation, respectively (P = 0.001).ConclusionsProtein type, protein dose, and age modulate dietary protein digestion and amino acid absorption kinetics and subsequent postprandial plasma amino acid availability in vivo in humans. These trials were registered at clinicaltrials.gov as NCT00557388, NCT00936039, NCT00991523, NCT01317511, NCT01473576, NCT01576848, NCT01578590, NCT01615276, NCT01680146, NCT01820975, NCT01986842, and NCT02596542, and at http://www.trialregister.nl as NTR3638, NTR3885, NTR4060, NTR4429, and NTR4492.

Casein Protein Processing Strongly Modulates Post-Prandial Plasma Amino Acid Responses In Vivo in Humans.

Micellar casein is characterized as a slowly digestible protein source, and its structure can be modulated by various food processing techniques to modify its functional properties. However, little is known about the impact of such modifications on casein protein digestion and amino acid absorption kinetics and the subsequent post-prandial plasma amino acid responses. In the present study, we determined post-prandial aminoacidemia following ingestion of isonitrogenous amounts of casein protein (40 g) provided as micellar casein (Mi-CAS), calcium caseinate (Ca-CAS), or cross-linked sodium caseinate (XL-CAS). Fifteen healthy, young men (age: 26 ± 4 years, BMI: 23 ± 1 kg·m−2) participated in this randomized cross-over study and ingested 40 g Mi-Cas, Ca-CAS, and XL-CAS protein, with a ~1 week washout between treatments. On each trial day, arterialized blood samples were collected at regular intervals during a 6 h post-prandial period to assess plasma amino acid concentrations using ultra-performance liquid chromatography. Plasma amino acid concentrations were higher following the ingestion of XL-CAS when compared to Mi-CAS and Ca-CAS from t = 15 to 90 min (all p < 0.05). Plasma amino acid concentrations were higher following ingestion of Mi-CAS compared to Ca-CAS from t = 30 to 45 min (both p < 0.05). Plasma total amino acids iAUC were higher following the ingestion of XL-CAS when compared to Ca-CAS (294 ± 63 vs. 260 ± 75 mmol·L−1, p = 0.006), with intermediate values following Mi-CAS ingestion (270 ± 63 mmol·L−1, p > 0.05). In conclusion, cross-linked sodium caseinate is more rapidly digested when compared to micellar casein and calcium caseinate. Protein processing can strongly modulate the post-prandial rise in plasma amino acid bioavailability in vivo in humans.

Ingestion of Free Amino Acids as Opposed to Intact Protein Increases Amino Acid Absorption but Does Not Further Augment Postprandial Muscle Protein Synthesis Rates

Abstract Objectives The rate of protein digestion and amino acid absorption determines the postprandial rise in circulating amino acids and, as such, modulates postprandial muscle protein synthesis rates. This study compares protein digestion and amino acid absorption kinetics and the subsequent muscle protein synthetic response following ingestion of intact protein versus an equivalent amount of free, crystalline amino acids. Methods Twenty-four healthy, young subjects (age: 22 ± 3 y, BMI: 23 ± 2 kg·m−2, sex: 12 M/12F) ingested 30 g intrinsically L-[1–13C]-phenylalanine and L-[1–13C]-leucine labeled milk protein (PROT; n = 12) or an equivalent amount of free amino acids (AA; n = 12). In addition, subjects received primed continuous L-[ring-2H5]-phenylalanine, L-[ring-3,5–2H2]-tyrosine, and L-[1–13C]-leucine infusions. Blood samples and muscle biopsies were obtained frequently to assess protein digestion and amino acid absorption kinetics and subsequent muscle protein synthesis rates over a 6 h postprandial period. An unpaired t-test was used to compare overall exogenous phenylalanine release in plasma. For other parameters repeated measures ANOVA were applied to determine differences between groups over time (time as within, and group as between-subjects factor). Data are expressed as mean ± SD. Results Postprandial plasma amino acid concentrations and exogenous phenylalanine appearance rates increased after ingestion of PROT and AA (both, P &amp;lt; 0.001), with a greater increase following ingestion of AA when compared to PROT (time*group interaction P &amp;lt; 0.001). Exogenous phenylalanine release in plasma assessed over the 6 h postprandial period, was greater in AA (76 ± 9%) compared with PROT (59 ± 10%; P &amp;lt; 0.001). Ingestion of AA and PROT strongly increased muscle protein synthesis rates based upon L-[ring-2H5]-phenylalanine (time effect P &amp;lt; 0.001), with no differences between groups (from 0.037 ± 0.015 to 0.053 ± 0.014%·h−1 and from 0.039 ± 0.016 to 0.051 ± 0.010%·h−1, respectively; time*group interaction P = 0.629). Conclusions Ingestion of free amino acids as opposed to intact milk protein is followed by more rapid amino acid absorption and greater postprandial plasma amino acid availability, but this does not further augment postprandial muscle protein synthesis rates. Funding Sources This research did not receive external funding.

Basal and Postprandial Myofibrillar Protein Synthesis Rates Do Not Differ between Lean and Obese Middle-Aged Men

ABSTRACTBackgroundExcess lipid availability has been associated with the development of anabolic resistance. As such, obesity may be accompanied by impairments in muscle protein metabolism.ObjectiveWe hypothesized that basal and postprandial muscle protein synthesis rates are lower in obese than in lean men.MethodsTwelve obese men [mean ± SEM age: 48 ± 2 y; BMI (in kg/m2): 37.0 ± 1.5; body fat: 32 ± 2%] and 12 age-matched lean controls (age: 43 ± 3 y; BMI: 23.4 ± 0.4; body fat: 21 ± 1%) received primed continuous L-[ring-2H5]-phenylalanine and L-[ring-3,5-2H2]-tyrosine infusions and ingested 25 g intrinsically L-[1-13C]-phenylalanine labeled whey protein. Repeated blood and muscle samples were obtained to assess protein digestion and amino acid absorption kinetics, and basal and postprandial myofibrillar protein synthesis rates.ResultsExogenous phenylalanine appearance rates increased after protein ingestion in both groups (P < 0.001), with a total of 53 ± 1% and 53 ± 2% of dietary protein–derived phenylalanine appearing in the circulation over the 5-h postprandial period in lean and obese men, respectively (P = 0.82). After protein ingestion, whole-body protein synthesis and oxidation rates increased to a greater extent in lean men than in the obese (P-interaction < 0.05), resulting in a higher whole-body protein net balance in the lean than in the obese (7.1 ± 0.2 and 4.6 ± 0.4 µmol phenylalanine · h−1 · kg−1, respectively; P-interaction < 0.001). Myofibrillar protein synthesis rates increased from 0.030 ± 0.002 and 0.028 ± 0.003%/h in the postabsorptive period to 0.034 ± 0.002 and 0.035 ± 0.003%.h−1 in the 5-h postprandial period (P = 0.03) in lean and obese men, respectively, with no differences between groups (P-interaction = 0.58).ConclusionsBasal, postabsorptive myofibrillar protein synthesis rates do not differ between lean and obese middle-aged men. Postprandial protein handling, including protein digestion and amino acid absorption, and the postprandial muscle protein synthetic response after the ingestion of 25 g whey protein are not impaired in obese men. This trial was registered at www.trialregister.nl as NTR4060.

Leucine coingestion augments the muscle protein synthetic response to the ingestion of 15 g of protein following resistance exercise in older men.

Older adults have shown an attenuated postexercise increase in muscle protein synthesis rates following ingestion of smaller amounts of protein compared with younger adults. Consequently, it has been suggested that older adults require the ingestion of more protein to increase postexercise muscle protein synthesis rates compared with younger adults. We investigated whether coingestion of 1.5 g of free leucine with a single 15-g bolus of protein further augments the postprandial muscle protein synthetic response during recovery from resistance-type exercise in older men. Twenty-four healthy older men (67 ± 1 yr) were randomly assigned to ingest 15 g of milk protein concentrate (MPC80) with (15G+LEU; n = 12) or without (15G; n = 12) 1.5 g of free leucine after performing a single bout of resistance-type exercise. Postprandial protein digestion and amino acid absorption kinetics, whole body protein metabolism, and postprandial myofibrillar protein synthesis rates were assessed using primed, continuous infusions with l-[ring-2H5]phenylalanine, l-[ring-2H2]tyrosine, and l-[1-13C]leucine combined with ingestion of intrinsically l-[1-13C]phenylalanine-labeled milk protein. A total of 70 ± 1% (10.5 ±0.2 g) and 75 ± 2% (11.2 ± 0.3 g) of the protein-derived amino acids were released in the circulation during the 6-h postexercise recovery phase in 15G+LEU and 15G, respectively (P < 0.05). Postexercise myofibrillar protein synthesis rates were 16% (0.058 ± 0.003 vs. 0.049 ± 0.002%/h, P < 0.05; based on l-[ring-2H5]phenylalanine) and 19% (0.071 ± 0.003 vs. 0.060 ± 0.003%/h, P < 0.05; based on l-[1-13C]leucine) greater in 15G+LEU compared with 15G. Leucine coingestion further augments the postexercise muscle protein synthetic response to the ingestion of a single 15-g bolus of protein in older men.

Dose-Dependent Increases in Whole-Body Net Protein Balance and Dietary Protein-Derived Amino Acid Incorporation into Myofibrillar Protein During Recovery from Resistance Exercise in Older Men

ABSTRACTBackgroundAge-related decline in skeletal muscle mass is at least partly attributed to anabolic resistance to food intake. Resistance exercise sensitizes skeletal muscle tissue to the anabolic properties of amino acids.ObjectiveThe present study assessed protein digestion and amino acid absorption kinetics, whole-body protein balance, and the myofibrillar protein synthetic response to ingestion of different amounts of protein during recovery from resistance exercise in older men.MethodsForty-eight healthy older men [mean ± SEM age: 66 ± 1 y; body mass index (kg/m2): 25.4 ± 0.3] were randomly assigned to ingest 0, 15, 30, or 45 g milk protein concentrate after a single bout of resistance exercise consisting of 4 sets of 10 repetitions of leg press and leg extension and 2 sets of 10 repetitions of lateral pulldown and chest press performed at 75–80% 1-repetition maximum. Postprandial protein digestion and amino acid absorption kinetics, whole-body protein metabolism, and myofibrillar protein synthesis rates were assessed using primed, continuous infusions of l-[ring-2H5]-phenylalanine, l-[ring-2H2]-tyrosine, and l-[1-13C]-leucine combined with ingestion of intrinsically l-[1-13C]-phenylalanine and l-[1-13C]-leucine labeled protein.ResultsWhole-body net protein balance showed a dose-dependent increase after ingestion of 0, 15, 30, or 45 g of protein (0.015 ± 0.002, 0.108 ± 0.004, 0.162 ± 0.008, and 0.215 ± 0.009 μmol Phe · kg−1 · min−1, respectively; P < 0.001). Myofibrillar protein synthesis rates were higher after ingesting 30 (0.0951% ± 0.0062%/h, P = 0.07) or 45 g of protein (0.0970% ± 0.0062%/h, P < 0.05) than after 0 g (0.0746% ± 0.0051%/h). Incorporation of dietary protein–derived amino acids (l-[1-13C]-phenylalanine) into de novo myofibrillar protein showed a dose-dependent increase after ingestion of 15, 30, or 45 g protein (0.0171 ± 0.0017, 0.0296 ± 0.0030, and 0.0397 ± 0.0026 mole percentage excess, respectively; P < 0.05).ConclusionsDietary protein ingested during recovery from resistance exercise is rapidly digested and absorbed. Whole-body net protein balance and dietary protein-derived amino acid incorporation into myofibrillar protein show dose-dependent increases. Ingestion of ≥30 g protein increases postexercise myofibrillar protein synthesis rates in older men. This trial was registered at Nederlands Trial Register as NTR4492.

The Effect of Casein Ingestion within a Milk Matrix on Muscle Protein Synthesis

Isolated micellar casein has been classified as a slow protein because of its slow digestion and amino acid absorption kinetics. These result further in a more moderate and sustained amino acid availability in the plasma and subsequently lower muscle protein synthesis (MPS) rate when, for example, compared with whey. However, the milk matrix with lactose, fat and various minerals may modulate the effect of casein on MPS. Therefore, this study aimed to compare the effects of the ingestion of casein dissolved in bovine milk serum to the ingestion of isolated casein on myofibrillar protein synthesis. In this parallel group randomized trial, 32 healthy older men (age: 71 ± 1 y) received a primed continuous infusion of L-[ring-2 H5 ]phenylalanine, L-[1-13C]leucine, and L-[ring-3,5-2 H2 ]tyrosine and blood and muscle samples were taken to assess myofibrillar fractional synthetic rate (FSR) under basal postabsorptive conditions and after a single bolus of 25 g intrinsically L-[1-13C]phenylalanine and L-[1-13C]leucine-labeled casein either in an isolated form (ISOCAS; n = 16) or dissolved in bovine milk serum (MILK-CAS; n = 16). The ingestion of 25 g of casein significantly (P &lt; 0.05) increased MPS rates in both groups when assessed over the late postprandial period (t = 120 – 300 min). Ingestion of MILK-CAS and ISO-CAS did not significantly stimulate MPS rates when assessed over the early (t = 0 – 120 min) and overall (t = 0 – 300 min) postprandial FSR compared to postabsorptive (t = -120 – 0 min) FSR. No significant differences were observed between the two groups over the early, late or entire postprandial period (P &gt; 0.05). The ingestion of additional normal milk matrix to micellar casein does not modulate overall myofibrillar protein synthesis rates in older men when compared to the ingestion of micellar casein dissolved in water. Therefore, there is neither a benefit, nor a detrimental effect of ingesting micellar casein within a normal milk matrix instead of the isolated form to increase MPS.

Body Position Modulates Gastric Emptying and Affects the Post-Prandial Rise in Plasma Amino Acid Concentrations Following Protein Ingestion in Humans.

Dietary protein digestion and amino acid absorption kinetics determine the post-prandial muscle protein synthetic response. Body position may affect gastrointestinal function and modulate the post-prandial rise in plasma amino acid availability. We aimed to assess the impact of body position on gastric emptying rate and the post-prandial rise in plasma amino acid concentrations following ingestion of a single, meal-like amount of protein. In a randomized, cross-over design, eight healthy males (25 ± 2 years, 23.9 ± 0.8 kg·m−2) ingested 22 g protein and 1.5 g paracetamol (acetaminophen) in an upright seated position (control) and in a −20° head-down tilted position (inversion). Blood samples were collected during a 240-min post-prandial period and analyzed for paracetamol and plasma amino acid concentrations to assess gastric emptying rate and post-prandial amino acid availability, respectively. Peak plasma leucine concentrations were lower in the inversion compared with the control treatment (177 ± 15 vs. 236 ± 15 mmol·L−1, p < 0.05), which was accompanied by a lower plasma essential amino acid (EAA) response over 240 min (31,956 ± 6441 vs. 50,351 ± 4015 AU; p < 0.05). Peak plasma paracetamol concentrations were lower in the inversion vs. control treatment (5.8 ± 1.1 vs. 10.0 ± 0.6 mg·L−1, p < 0.05). Gastric emptying rate and post-prandial plasma amino acid availability are significantly decreased after protein ingestion in a head-down tilted position. Therefore, upright body positioning should be considered when aiming to augment post-prandial muscle protein accretion in both health and disease.

Ingestion of Casein in a Milk Matrix Modulates Dietary Protein Digestion and Absorption Kinetics but Does Not Modulate Postprandial Muscle Protein Synthesis in Older Men1–3

Background: The slow digestion and amino acid absorption kinetics of isolated micellar casein have been held responsible for its relatively lower postprandial muscle protein synthetic response compared with rapidly digested proteins such as isolated whey. However, casein is normally consumed within a milk matrix. We hypothesized that protein digestion and absorption kinetics and the subsequent muscle protein synthetic response after micellar casein ingestion are modulated by the milk matrix.Objective: The aim of this study was to determine the impact of a milk matrix on casein protein digestion and absorption kinetics and postprandial muscle protein synthesis in older men.Methods: In a parallel-group design, 32 healthy older men (aged 71 ± 1 y) received a primed continuous infusion of L-[ring-2H5]-phenylalanine, L-[ring-3,5-2H2]-tyrosine, and L-[1-13C]-leucine, and ingested 25 g intrinsically L-[1-13C]-phenylalanine and L-[1-13C]-leucine labeled casein dissolved in bovine milk serum (Cas+Serum) or water (Cas). Plasma samples and muscle biopsies were collected in the postabsorptive state and for 300 min in the postprandial period to examine whole-body and skeletal muscle protein metabolism.Results: Casein ingestion increased plasma leucine and phenylalanine concentrations and L-[1-13C]-phenylalanine enrichments, with a more rapid rise after Cas vs. Cas+Serum. Nonetheless, dietary protein–derived phenylalanine availability did not differ between Cas+Serum (47 ± 2%, mean ± SEM) and Cas (46 ± 3%) when assessed over the 300-min postprandial period (P = 0.80). The milk matrix did not modulate postprandial myofibrillar protein synthesis rates from 0 to 120 min (0.038 ± 0.005 vs. 0.031 ± 0.007%/h) or from 120 to 300 min (0.052 ± 0.004 vs. 0.067 ± 0.005%/h) after Cas+Serum vs. Cas. Similarly, no treatment differences in muscle protein–bound L-[1-13C]-phenylalanine enrichments were observed at 120 min (0.003 ± 0.001 vs. 0.002 ± 0.001) or 300 min (0.015 ± 0.002 vs. 0.016 ± 0.002 mole percent excess) after Cas+Serum vs. Cas.Conclusions: Casein ingestion in a milk matrix delays protein digestion and absorption but does not modulate postprandial muscle protein synthesis when compared to the ingestion of micellar casein only in healthy older men. This trial was registered at Nederlands Trial Register as NTR4429.

Pattern of protein ingestion to maximise muscle protein synthesis after resistance exercise

Pattern of protein ingestion to maximise muscle protein synthesis after resistance exercise