The laboratory parameters-derived CoLab score as an indicator of the host response in ICU COVID-19 patients decreases over time: a prospective cohort study.

The CoLab score was developed and externally validated to rule out COVID-19 among suspected patients presenting at the emergency department. We hypothesized a within-patient decrease in the CoLab score over time in an intensive care unit (ICU) cohort. Such a decrease would create the opportunity to potentially rule out the need for isolation when the infection is overcome. Using linear mixed-effects models, data from the Maastricht Intensive Care COVID (MaastrICCht) cohort were used to investigate the association between time and the CoLab score. Models were adjusted for sex, APACHE II score, ICU mortality, and daily SOFA score. The CoLab score decreased by 0.30 points per day (95% CI - 0.33 to - 0.27), independent of sex, APACHE II, and Mortality. With increasing SOFA score over time, the CoLab score decreased more strongly (- 0.01 (95% CI - 0.01 to - 0.01) additional decrease per one-point increase in SOFA score.) The CoLab score decreased in ICU patients on mechanical ventilation for COVID-19, with a one-point reduction per three days, independent of sex, APACHE II, and ICU mortality, and somewhat stronger with increasing multi-organ failure over time. This suggests that the CoLab score would decrease below a threshold where COVID-19 can be excluded.

The CoLab score is associated with SARS-CoV-2 viral load during admission in individuals admitted to the intensive care unit: the CoLaIC cohort study.

OBJECTIVES: The present study examines the temporal association between the changes in SARS-CoV-2 viral load during infection and whether the CoLab-score can facilitate de-isolation. METHODS: Nasal swabs and blood samples were collected from ICU-admitted SARS-CoV-2 positive patients at Maastricht UMC+ from March 25, 2020 to October 1, 2021. The CoLab-score was calculated based on 10 blood parameters and age and can range from -43 to 6. Three mixed effects analyses compared patient categories based on initial PCR Ct values (low; Ct≤20, mid; 20>Ct≤30, high; Ct>30), serial PCR Ct values to CoLab-scores over time, and the association between within-patient delta Ct values and CoLab-scores. RESULTS: In 324 patients, the median Ct was 33, and the median CoLab-score was -1.78. Mid (n=110) and low (n=41) Ct-categories had higher CoLab-scores over time (+0.60 points, 95 % CI; 0.04-1.17, and +0.28 points, 95 % CI -0.49 to 1.04) compared to the high Ct (n=87) category. Over time, higher serial Ct values were associated with lower serial CoLab-scores, decreasing by -0.07 points (95 % CI; -0.11 to -0.02) per day. Increasing delta Ct values were associated with a decreasing delta CoLab-score of -0.12 (95 % CI; -0.23; -0.01). CONCLUSIONS: The study found an association between lower viral load on admission and reduced CoLab-score. Additionally, a decrease in viral load over time was associated with a decrease in CoLab-score. Therefore, the CoLab-score may make patient de-isolation an option based on the CoLab-score.

Validating a clinical laboratory parameter-based deisolation algorithm for patients with COVID-19 in the intensive care unit using viability PCR: the CoLaIC multicentre cohort study protocol.

INTRODUCTION: To investigate whether biochemical and haematological changes due to the patient's host response (CoLab algorithm) in combination with a SARS-CoV-2 viability PCR (v-PCR) can be used to determine when a patient with COVID-19 is no longer infectious.We hypothesise that the CoLab algorithm in combination with v-PCR can be used to determine whether or not a patient with COVID-19 is infectious to facilitate the safe release of patients with COVID-19 from isolation. METHODS AND ANALYSIS: This study consists of three parts using three different cohorts of patients. All three cohorts contain clinical, vital and laboratory parameters, as well as logistic data related to isolated patients with COVID-19, with a focus on intensive care unit (ICU) stay. The first cohort will be used to develop an algorithm for the course of the biochemical and haematological changes of the host response of the COVID-19 patient. Simultaneously, a second prospective cohort will be used to investigate the algorithm derived in the first cohort, with daily measured laboratory parameters, next to conventional SARS-CoV-2 reverse transcriptase PCRs, as well as v-PCR, to confirm the presence of intact SARS-CoV-2 particles in the patient. Finally, a third multicentre cohort, consisting of retrospectively collected data from patients with COVID-19 admitted to the ICU, will be used to validate the algorithm. ETHICS AND DISSEMINATION: This study was approved by the Medical Ethics Committee from Maastricht University Medical Centre+ (cohort I: 2020-1565/300523) and Zuyderland MC (cohorts II and III: METCZ20200057). All patients will be required to provide informed consent. Results from this study will be disseminated via peer-reviewed journals and congress/consortium presentations.

The Muscle Protein Synthetic Response to the Ingestion of a Plant-Derived Protein Blend Does Not Differ from an Equivalent Amount of Milk Protein in Healthy Young Males.

BACKGROUND: Plant-derived proteins are considered to have lesser anabolic properties when compared with animal-derived proteins. The attenuated rise in muscle protein synthesis rates following ingestion of plant-derived compared with animal-derived protein has been, at least partly, attributed to deficiencies in specific amino acids such as leucine, lysine, and/or methionine. Combining different plant-derived proteins could provide plant-derived protein blends with a more balanced amino acid profile. OBJECTIVES: This study aimed to compare postprandial muscle protein synthesis rates following the ingestion of 30 g milk protein with a 30 g blend combining wheat, corn, and pea protein in healthy young men. METHODS: In a randomized, double-blind, parallel-group design, 24 young males (aged 24 ± 4 y) received a primed continuous l-[ring-13C6]-phenylalanine infusion after which they ingested 30 g milk protein (MILK) or a 30 g plant-derived protein blend combining 15 g wheat, 7.5 g corn, and 7.5 g pea protein (PLANT-BLEND). Blood and muscle biopsies were collected frequently for 5 h to assess postprandial plasma amino acid profiles (secondary outcome) and subsequent muscle protein synthesis rates (primary outcome). Data were analyzed by 2-factor repeated measures ANOVA and 2-samples t tests. RESULTS: MILK increased plasma essential amino acid concentrations more than PLANT-BLEND over the 5 h postprandial period (incremental AUC = 151 ± 31 compared with 79 ± 12 mmol·300 min·L-1, respectively; P < 0.001). Ingestion of both MILK and PLANT-BLEND increased myofibrillar protein synthesis rates (P < 0.001), with no significant differences between treatments (0.053 ± 0.013%/h and 0.064 ± 0.016%/h, respectively; P = 0.08). CONCLUSIONS: Ingestion of 30 g plant-derived protein blend combining wheat-, corn-, and pea-derived protein increases muscle protein synthesis rates in healthy young males. The muscle protein synthetic response to the ingestion of 30 g of this plant-derived protein blend does not differ from the ingestion of an equivalent amount of a high-quality animal-derived protein.Clinical trial registry number for Nederlands Trial Register: NTR6548 (https://trialsearch.who.int/Trial2.aspx?TrialID=NTR6548).

Declines in muscle protein synthesis account for short-term muscle disuse atrophy in humans in the absence of increased muscle protein breakdown.

BACKGROUND: We determined the short-term (i.e. 4 days) impacts of disuse atrophy in relation to muscle protein turnover [acute fasted-fed muscle protein synthesis (MPS)/muscle protein breakdown (MPB) and integrated MPS/estimated MPB]. METHODS: Healthy men (N = 9, 22 ± 2 years, body mass index 24 ± 3 kg m-2 ) underwent 4 day unilateral leg immobilization. Vastus lateralis (VL) muscle thickness (MT) and extensor strength and thigh lean mass (TLM) were measured. Bilateral VL muscle biopsies were collected on Day 4 at t = -120, 0, 90, and 180 min to determine integrated MPS, estimated MPB, acute fasted-fed MPS (l-[ring-13 C6 ]-phe), and acute fasted tracer decay rate representative of MPB (l-[15 N]-phe and l-[2 H8 ]-phe). Protein turnover cell signalling was measured by immunoblotting. RESULTS: Immobilization decreased TLM [pre: 7477 ± 1196 g, post: 7352 ± 1209 g (P < 0.01)], MT [pre: 2.67 ± 0.50 cm, post: 2.55 ± 0.51 cm (P < 0.05)], and strength [pre: 260 ± 43 N m, post: 229 ± 37 N m (P < 0.05)] with no change in control legs. Integrated MPS decreased in immob vs. control legs [control: 1.55 ± 0.21% day-1 , immob: 1.29 ± 0.17% day-1 (P < 0.01)], while tracer decay rate (i.e. MPB) (control: 0.02 ± 0.006, immob: 0.015 ± 0.015) and fractional breakdown rate (FBR) remained unchanged [control: 1.44 ± 0.51% day-1 , immob: 1.73 ± 0.35% day-1 (P = 0.21)]. Changes in MT correlated with those in MPS but not FBR. MPS increased in the control leg following feeding [fasted: 0.043 ± 0.012% h-1 , fed: 0.065 ± 0.017% h-1 (P < 0.05)] but not in immob [fasted: 0.034 ± 0.014% h-1 , fed: 0.049 ± 0.023% h-1 (P = 0.09)]. There were no changes in markers of MPB with immob (P > 0.05). CONCLUSIONS: Human skeletal muscle disuse atrophy is driven by declines in MPS, not increases in MPB. Pro-anabolic therapies to mitigate disuse atrophy would likely be more effective than therapies aimed at attenuating protein degradation.

Whey Protein Supplementation Is Superior to Leucine-Matched Collagen Peptides to Increase Muscle Thickness During a 10-Week Resistance Training Program in Untrained Young Adults.

The purpose of this study was to investigate the effects of supplementation of whey protein (WP) versus leucine-matched collagen peptides (CP) on muscle thickness MT and performance after a resistance training (RT) program in young adults. Twenty-two healthy untrained participants were randomly assigned to either a WP (n = 11) or leucine-matched CP (n = 11) group and then submitted to a supervised 10-week RT program (3 days/week). The groups were supplemented with an equivalent amount of WP (35 g, containing 3.0 g of leucine) and CP (35 g, containing 1.0 g of leucine and 2.0 g of free leucine) during the intervention period (after each workout and in the evening on nontraining days). MT of the vastus lateralis and biceps brachii, isokinetic peak torque and mean power output of the elbow flexors, and peak power output of the lower body were assessed before and after the RT program. The WP group experienced a greater (interaction, p < .05) increase in the vastus lateralis (effect size, WP = 0.68 vs. CP = 0.38; % Δ, WP = 8.4 ± 2.5 vs. CP = 5.6 ± 2.6%) and biceps brachii muscle thickness (effect size, WP = 0.61 vs. CP = 0.35; % , WP = 10.1 ± 3.8 vs. CP = 6.0 ± 3.2%), with a similar increase in muscle performance (peak torque, mean power output, and peak power output) between groups (time p < .05). Supplementation with WP was superior to leucine content-matched CP supplementation in increasing muscle size, but not strength and power, after a 10-week RT program in young adults.

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.

BACKGROUND: The rate of protein digestion and amino acid absorption determines the postprandial rise in circulating amino acids and modulates postprandial muscle protein synthesis rates. OBJECTIVE: We 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. METHODS: Twenty-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. RESULTS: Postprandial 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). CONCLUSIONS: Ingestion 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.

Transcriptomic links to muscle mass loss and declines in cumulative muscle protein synthesis during short-term disuse in healthy younger humans.

Muscle disuse leads to a rapid decline in muscle mass, with reduced muscle protein synthesis (MPS) considered the primary physiological mechanism. Here, we employed a systems biology approach to uncover molecular networks and key molecular candidates that quantitatively link to the degree of muscle atrophy and/or extent of decline in MPS during short-term disuse in humans. After consuming a bolus dose of deuterium oxide (D2 O; 3 mL.kg-1 ), eight healthy males (22 ± 2 years) underwent 4 days of unilateral lower-limb immobilization. Bilateral muscle biopsies were obtained post-intervention for RNA sequencing and D2 O-derived measurement of MPS, with thigh lean mass quantified using dual-energy X-ray absorptiometry. Application of weighted gene co-expression network analysis identified 15 distinct gene clusters ("modules") with an expression profile regulated by disuse and/or quantitatively connected to disuse-induced muscle mass or MPS changes. Module scans for candidate targets established an experimentally tractable set of candidate regulatory molecules (242 hub genes, 31 transcriptional regulators) associated with disuse-induced maladaptation, many themselves potently tied to disuse-induced reductions in muscle mass and/or MPS and, therefore, strong physiologically relevant candidates. Notably, we implicate a putative role for muscle protein breakdown-related molecular networks in impairing MPS during short-term disuse, and further establish DEPTOR (a potent mTOR inhibitor) as a critical mechanistic candidate of disuse driven MPS suppression in humans. Overall, these findings offer a strong benchmark for accelerating mechanistic understanding of short-term muscle disuse atrophy that may help expedite development of therapeutic interventions.

Consumption of High-Leucine-Containing Protein Bar Following Breakfast Impacts Aminoacidemia and Subjective Appetite in Older Persons.

BACKGROUND: Limited data are available examining dietary interventions for optimizing protein and leucine intake to stimulate muscle protein synthesis (MPS) in older humans. OBJECTIVES: We aimed to investigate the aminoacidemia and appetite responses of older adults after consuming breakfast, a meal frequently consumed with high-carbohydrate and below-par amounts of protein and leucine for stimulating MPS. METHODS: Five men and 3 women (means ± SD; age: 74 ± 7 y, BMI: 25.7 ± 4.9 kg/m2, fat- and bone-free mass: 63 ± 7 kg) took part in this experiment in which they consumed breakfasts with low-protein (LP = 13 ± 2 g), high-protein (HP = 32 ± 5 g), and LP followed by a protein- and leucine-enriched bar formulation 2 h later (LP + Bar = 29 ± 2 g). The LP, HP, and LP + Bar breakfast conditions contained 519 ± 86 kcal, 535 ± 83 kcal, and 739 ± 86 kcal, respectively. Blood samples were drawn for 6 h and analyzed for amino acid, insulin, and glucose concentrations. Visual analog scales were assessed for hunger, fullness, and desire to eat. RESULTS: The net AUC for essential amino acid (EAA) exposure was similar between the LP + Bar and HP conditions but greater in the HP condition compared with the LP condition. Peak leucinemia was higher in the LP + Bar condition compared with the HP, and both were greater than the LP condition. Net leucine exposure was similar between HP and LP + Bar, and both were greater than LP. Hunger was similarly reduced in LP + Bar and HP, and LP + Bar resulted in a greater hunger reduction than LP. Both LP + Bar and HP resulted in greater net fullness scores than LP. CONCLUSIONS: Consuming our bar formulation increased blood leucine availability and net exposure to EAAs to a similar degree as consuming a high-protein meal. High-protein at breakfast results in a greater net exposure to EAAs and leucine, which could support MPS in older persons. This study was registered at clinicaltrials.gov as NCT03712761.

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

BACKGROUND: Dietary 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. OBJECTIVE: We assessed the impact of protein type, protein dose, and age on dietary protein digestion and amino acid absorption kinetics in vivo in humans. METHODS: We 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. RESULTS: A 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). CONCLUSIONS: Protein 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.

The effect of oral essential amino acids on incretin hormone production in youth and ageing.

BACKGROUND: The effect of substantive doses of essential amino acids (EAA) on incretin and insulin production, and the impact of age upon this effect, is ill-defined. METHODS: A 15-g oral EAA drink was administered to young (N = 8; 26 ± 4.4 years) and older (N = 8; 69 ± 3.8 years) healthy volunteers. Another group of younger volunteers (N = 9; 21 ± 1.9 years) was given IV infusions to achieve equivalent plasma amino acids (AA) profiles. Plasma AA, insulin, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) were quantified over 2 hours. RESULTS: In younger recruits, EAA-induced rapid insulinaemia and aminoacidaemia with total amino acids(AA), EAA and branched chain amino acids (BCAA) matched between oral and IV groups. Insulin peaked at 39 ± 29 pmol L-1 at 30 minutes following oral feeding compared to 22 ± 9 pmol L-1 at 60 minutes following IV feeding (P: NS). EAA peaked at 3395 µmol L-1 at 45 minutes during IV infusion compared to 2892 µmol L-1 following oral intake (Feeding effect: P < 0.0001. Oral vs IV feeding: P: NS). There was an 11% greater increase in insulin levels in the 120 minutes duration of the study in response to oral EAA as opposed to IV EAA. GIP increased following oral EAA (452 pmol L-1 vs 232 pmol L-1, P < 0.05). Age did not impact insulin or incretins production. CONCLUSION: Postprandial rises in EAA levels lead to rapid insulinaemia which is higher with oral compared with IV EAA, that is attributed more to GIP and unaffected by age. This finding supports EAA, on their own or as part of high-protein meal, as nutritive therapeutics in impaired glycaemia and ageing.

Omega-3 fatty acid supplementation attenuates skeletal muscle disuse atrophy during two weeks of unilateral leg immobilization in healthy young women.

Omega-3 (n-3) fatty acid supplementation enhances muscle protein synthesis and muscle size. Whether n-3 fatty acid supplementation attenuates human muscle disuse atrophy is unknown. We determined the influence of n-3 fatty acid supplementation on muscle size, mass, and integrated rates of myofibrillar protein synthesis (MyoPS) following 2 wk of muscle disuse and recovery in women. Twenty women (BMI = 23.0 ± 2.3 kg/m2, age = 22 ± 3 yr) underwent 2 wk of unilateral limb immobilization followed by 2 wk of return to normal activity. Starting 4 wk prior to immobilization, participants consumed either 5 g/d of n-3 fatty acid or an isoenergetic quantity of sunflower oil (control). Muscle size and mass were measured pre- and postimmobilization, and after recovery. Serial muscle biopsies were obtained to measure integrated (daily) MyoPS. Following immobilization, the decline in muscle volume was greater in the control group compared to the n-3 fatty acid group (14 vs. 8%, P < 0.05) and was not different from preimmobilization at recovery in the n-3 fatty acid group; however, it was still lower in the control group ( P < 0.05). Muscle mass was reduced in the control group only ( P < 0.05). MyoPS was higher in the n-3 group compared with the control group at all times ( P < 0.05). We conclude that n-3 fatty acid supplementation attenuates skeletal muscle disuse atrophy in young women, which may be mediated by higher rates of MyoPS.-McGlory, C., Gorissen, S. H. M., Kamal, M., Bahniwal, R., Hector, A. J., Baker, S. K., Chabowski, A., Phillips, S. M. Omega-3 fatty acid supplementation attenuates skeletal muscle disuse atrophy during two weeks of unilateral leg immobilization in healthy young women.

Aminoacidemia following ingestion of native whey protein, micellar casein, and a whey-casein blend in young men.

We examined the aminoacidemic, glycemic, and insulinemic responses following ingestion of 25 g of native whey protein, micellar casein, and a 1:1 blend of whey and casein in randomized order in young adult men. Blood samples were drawn at baseline and at regular intervals for 6 h following ingestion. Area under curve and peak plasma essential amino acid concentrations after the ingestion of the protein blend were similar to whey and greater compared with casein.

The Muscle Protein Synthetic Response to Whey Protein Ingestion Is Greater in Middle-Aged Women Compared With Men.

Rationale: Muscle mass maintenance is largely regulated by the postprandial rise in muscle protein synthesis rates. It remains unclear whether postprandial protein handling differs between women and men. Methods: Healthy men (43 ± 3 years; body mass index, 23.4 ± 0.4 kg/m2; n = 12) and women (46 ± 2 years; body mass index, 21.3 ± 0.5 kg/m2; n = 12) received primed continuous infusions of l-[ring-2H5]-phenylalanine and l-[ring-3,5-2H2]-tyrosine and ingested 25 g intrinsically l-[1-13C]-phenylalanine-labeled whey protein. Blood samples and muscle biopsies were collected to assess dietary protein digestion and amino acid absorption kinetics as well as basal and postprandial myofibrillar protein synthesis rates. Results: Plasma phenylalanine and leucine concentrations rapidly increased after protein ingestion (both P < 0.001), with no differences between middle-aged women and men (Time × Sex, P = 0.307 and 0.529, respectively). The fraction of dietary protein-derived phenylalanine that appeared in the circulation over the 5-hour postprandial period averaged 56 ± 1% and 53 ± 1% in women and men, respectively (P = 0.145). Myofibrillar protein synthesis rates increased (Time, P = 0.010) from 0.035 ± 0.004%/h and 0.030 ± 0.002%/h in the postabsorptive state (t test, P = 0.319) to 0.045 ± 0.002%/h and 0.034 ± 0.002%/h in the 5-hour postprandial phase in middle-aged women and men, respectively, with higher postprandial myofibrillar protein synthesis rates in women compared with men (t test, P = 0.005). Middle-aged women showed a greater increase in myofibrillar protein synthesis rates during the early (0 to 2 hours) postprandial period compared with men (Time × Sex, P = 0.001). Conclusions: There are no differences in postabsorptive myofibrillar protein synthesis rates between middle-aged women and men. The myofibrillar protein synthetic response to the ingestion of 25 g whey protein is greater in women than in men.

Protein content and amino acid composition of commercially available plant-based protein isolates.

The postprandial rise in essential amino acid (EAA) concentrations modulates the increase in muscle protein synthesis rates after protein ingestion. The EAA content and AA composition of the dietary protein source contribute to the differential muscle protein synthetic response to the ingestion of different proteins. Lower EAA contents and specific lack of sufficient leucine, lysine, and/or methionine may be responsible for the lower anabolic capacity of plant-based compared with animal-based proteins. We compared EAA contents and AA composition of a large selection of plant-based protein sources with animal-based proteins and human skeletal muscle protein. AA composition of oat, lupin, wheat, hemp, microalgae, soy, brown rice, pea, corn, potato, milk, whey, caseinate, casein, egg, and human skeletal muscle protein were assessed using UPLC-MS/MS. EAA contents of plant-based protein isolates such as oat (21%), lupin (21%), and wheat (22%) were lower than animal-based proteins (whey 43%, milk 39%, casein 34%, and egg 32%) and muscle protein (38%). AA profiles largely differed among plant-based proteins with leucine contents ranging from 5.1% for hemp to 13.5% for corn protein, compared to 9.0% for milk, 7.0% for egg, and 7.6% for muscle protein. Methionine and lysine were typically lower in plant-based proteins (1.0 ± 0.3 and 3.6 ± 0.6%) compared with animal-based proteins (2.5 ± 0.1 and 7.0 ± 0.6%) and muscle protein (2.0 and 7.8%, respectively). In conclusion, there are large differences in EAA contents and AA composition between various plant-based protein isolates. Combinations of various plant-based protein isolates or blends of animal and plant-based proteins can provide protein characteristics that closely reflect the typical characteristics of animal-based proteins.

The prebiotic inulin improves substrate metabolism and promotes short-chain fatty acid production in overweight to obese men.

BACKGROUND AND AIMS: Human gut microbiota play an important role in maintaining human health. Dietary fibers, i.e. prebiotics, are fermented by human gut microbiota into the short-chain fatty acids (SCFAs) acetate, propionate, and butyrate. SCFAs promote fat oxidation and improve metabolic health. Therefore, the prebiotic inulin might be an effective dietary strategy to improve human metabolism. We aimed to investigate the acute metabolic effects of ingesting inulin compared with digestible carbohydrates and to trace inulin-derived SCFAs using stable isotope tracer methodology. METHODS: In a double-blind, randomized, placebo-controlled crossover design, 14 healthy, overweight to obese men consumed a high-fat milkshake containing A) 24 g inulin of which 0.5 g was U-13C-inulin (INU) or B) 24 g maltodextrin placebo (PLA), with a wash-out period of at least five days. Fat oxidation was measured via an open-circuit ventilated hood and blood samples were collected up to 7 h after ingestion. Plasma, breath, and fecal samples were collected, and appetite and satiety scores were assessed. RESULTS: Fat oxidation increased in the early postprandial phase (0-3 h), and both plasma glucose and insulin were lower after INU ingestion compared with PLA (all P < 0.05). Plasma free fatty acids were higher in the early, and lower in the late postprandial period after INU ingestion. Inulin was fermented into SCFAs as indicated by higher plasma acetate concentrations after INU compared with PLA (P < 0.05). In addition, we found continuous increases in plasma 13C-SCFA enrichments (P < 0.05 from t = 120 onwards) and breath 13CO2 enrichments after INU intake. There were no effects on plasma triglycerides, free glycerol, satiety hormones GLP-1 and PYY, and appetite and satiety scores. CONCLUSIONS: Ingestion of the prebiotic inulin improves fat oxidation and promotes SCFA production in overweight to obese men. Overall, replacing digestible carbohydrates with the fermentable inulin may favor human substrate metabolism. CLINICAL TRIAL REGISTRY: The trial was registered at clinicaltrials.gov under number NCT02009670.

Perspective: Protein Requirements and Optimal Intakes in Aging: Are We Ready to Recommend More Than the Recommended Daily Allowance?

The Dietary Reference Intakes set the protein RDA for persons >19 y of age at 0.8 g protein ⋅ kg body weight-1 ⋅ d-1. A growing body of evidence suggests, however, that the protein RDA may be inadequate for older individuals. The evidence for recommending a protein intake greater than the RDA comes from a variety of metabolic approaches. Methodologies centered on skeletal muscle are of paramount importance given the age-related decline in skeletal muscle mass and function (sarcopenia) and the degree to which dietary protein could mitigate these declines. In addition to evidence from short-term experimental trials, observational data show that higher protein intakes are associated with greater muscle mass and, more importantly, better muscle function with aging. We are in dire need of more evidence from longer-term intervention trials showing the efficacy of protein intakes that are higher than the RDA in older persons to support skeletal muscle health. We propose that it should be recommended that older individuals consume ≥1.2 g protein · kg-1 · d-1 and that there should be an emphasis on the intake of the amino acid leucine, which plays a central role in stimulating skeletal muscle anabolism. Critically, the often-cited potential negative effects of consuming higher protein intakes on renal and bone health are without a scientific foundation in humans.

Characterising the muscle anabolic potential of dairy, meat and plant-based protein sources in older adults.

The age-related loss of skeletal muscle mass and function is caused, at least in part, by a reduced muscle protein synthetic response to protein ingestion. The magnitude and duration of the postprandial muscle protein synthetic response to ingested protein is dependent on the quantity and quality of the protein consumed. This review characterises the anabolic properties of animal-derived and plant-based dietary protein sources in older adults. While approximately 60 % of dietary protein consumed worldwide is derived from plant sources, plant-based proteins generally exhibit lower digestibility, lower leucine content and deficiencies in certain essential amino acids such as lysine and methionine, which compromise the availability of a complete amino acid profile required for muscle protein synthesis. Based on currently available scientific evidence, animal-derived proteins may be considered more anabolic than plant-based protein sources. However, the production and consumption of animal-derived protein sources is associated with higher greenhouse gas emissions, while plant-based protein sources may be considered more environmentally sustainable. Theoretically, the lower anabolic capacity of plant-based proteins can be compensated for by ingesting a greater dose of protein or by combining various plant-based proteins to provide a more favourable amino acid profile. In addition, leucine co-ingestion can further augment the postprandial muscle protein synthetic response. Finally, prior exercise or n-3 fatty acid supplementation have been shown to sensitise skeletal muscle to the anabolic properties of dietary protein. Applying one or more of these strategies may support the maintenance of muscle mass with ageing when diets rich in plant-based protein are consumed.

Co-ingesting milk fat with micellar casein does not affect postprandial protein handling in healthy older men.

BACKGROUND & AIM: Dietary protein digestion and absorption plays an important role in modulating postprandial muscle protein synthesis. The impact of co-ingesting other macronutrients with dietary protein on protein digestion and absorption and the subsequent muscle protein synthetic response remains largely unexplored. This study investigated the impact of co-ingesting milk fat with micellar casein on dietary protein-derived amino acid appearance in the circulation and the subsequent postprandial muscle protein synthetic response in healthy older men. METHODS: Twenty-four healthy, older males (age: 65 ± 1 y, BMI: 25.7 ± 0.5 kg/m2) received a primed continuous infusion of L-[ring-2H5]-phenylalanine and L-[1-13C]-leucine and ingested 20 g intrinsically L-[1-13C]-phenylalanine and L-[1-13C]-leucine-labeled casein with (PRO + FAT; n = 12) or without (PRO; n = 12) 26.7 g milk fat. Plasma samples and muscle biopsies were collected in both the postabsorptive and postprandial state. RESULTS: Release of dietary protein-derived phenylalanine into the circulation increased following protein ingestion (P < 0.001) and tended to be higher in PRO compared with PRO + FAT (Time × Treatment P = 0.076). No differences were observed in dietary protein-derived plasma phenylalanine availability (52 ± 2 vs 52 ± 3% in PRO vs PRO + FAT, respectively; P = 0.868). Myofibrillar protein synthesis rates did not differ between treatments, calculated using either the L-[ring-2H5]-phenylalanine (0.036 ± 0.003 vs 0.036 ± 0.004 %/h after PRO vs PRO + FAT, respectively; P = 0.933) or L-[1-13C]-leucine (0.051 ± 0.004 vs 0.046 ± 0.004 %/h, respectively; P = 0.480) tracer. In accordance, no differences were observed in myofibrillar protein-bound L-[1-13C]-phenylalanine enrichments between treatments (0.018 ± 0.002 vs 0.014 ± 0.001 MPE, respectively; P = 0.173). CONCLUSION: Co-ingesting milk fat with micellar casein does not impair protein-derived phenylalanine appearance in the circulation and does not modulate postprandial myofibrillar protein synthesis rates. CLINICAL TRIAL REGISTRATION NUMBER: NCT01680146 (http://www.clinicaltrials.gov/).