One Week of Single Leg Immobilization Lowers Muscle Connective Protein Synthesis Rates in Healthy, Young Adults

PURPOSE: Short periods of limb immobilization lower myofibrillar protein synthesis rates. Within skeletal muscle, the extracellular matrix of connective proteins is recognized as an important factor determining the capacity to transmit contractile force. Little is known regarding the impact of immobilization and subsequent recovery on muscle connective protein synthesis rates. This study examined the impact of one week of leg immobilization and two weeks of subsequent ambulant recovery on daily muscle connective protein synthesis rates. METHODS: Thirty healthy, young (24 ± 5 y) men were subjected to 7 days of one-legged knee immobilization followed by 14 days of ambulant recovery. Deuterium oxide ingestion was applied over the entire period and muscle biopsy samples were collected before immobilization, after immobilization, and after recovery to measure muscle connective protein synthesis rates and mRNA expression of key extracellular matrix proteins (collagen I, collagen III), glycoproteins (fibronectin, tenascin-C), and proteoglycans (fibromodulin, and decorin). A two-way repeated measures (time x leg) ANOVA was used to compare changes in muscle connective protein synthesis rates during immobilization and recovery. RESULTS: During immobilization, muscle connective protein synthesis rates were lower in the immobilized (1.07 ± 0.30 %/d) compared with the non-immobilized (1.48 ± 0.44 %/d; P < 0.01) leg. When compared to the immobilization period, connective protein synthesis rates in the immobilized leg increased during subsequent recovery (1.48 ± 0.64 %/d; P < 0.01). Following recovery, skeletal muscle collagen I, collagen III, fibronectin, fibromodulin, and decorin mRNA expression increased when compared to the post-immobilization timepoint (all P < 0.001). CONCLUSIONS: One week of leg immobilization lowers muscle connective protein synthesis rates. Muscle connective protein synthesis rates increase during subsequent ambulant recovery, which is accompanied by increased mRNA expression of key extracellular matrix proteins

Collagen Protein Ingestion during Recovery from Exercise Does Not Increase Muscle Connective Protein Synthesis Rates

INTRODUCTION: Protein ingestion during recovery from exercise has been reported to augment myofibrillar protein synthesis rates, without increasing muscle connective protein synthesis rates. It has been suggested that collagen protein may be effective in stimulating muscle connective protein synthesis. The present study assessed the capacity of both whey and collagen protein ingestion to stimulate post-exercise myofibrillar and muscle connective protein synthesis rates. METHODS: In a randomized, double-blind, parallel design, 45 young male (n = 30) and female (n = 15) recreational athletes (age: 25 ± 4 y; BMI: 24.1 ± 2.0 kg/m2) were selected to receive primed continuous intravenous infusions with L-[ring-13C6]-phenylalanine and L-[3,5-2H2]-tyrosine. Following a single session of resistance type exercise, subjects were randomly allocated to one of three groups ingesting either 30 g whey protein (WHEY, n = 15), 30 g collagen protein (COLL, n = 15) or a non-caloric placebo (PLA, n = 15). Blood and muscle biopsy samples were collected over a subsequent 5-hour recovery period to assess both myofibrillar and muscle connective protein synthesis rates. RESULTS: Protein ingestion increased circulating plasma amino acid concentrations (P < 0.05). The post-prandial rise in plasma leucine and essential amino acid concentrations was greater in WHEY compared with COLL, whereas plasma glycine and proline concentrations increased more in COLL compared with WHEY (P < 0.05). Myofibrillar protein synthesis rates averaged 0.041 ± 0.010, 0.036 ± 0.010 and 0.032 ± 0.007 %/h in WHEY, COLL and PLA, respectively, with only WHEY resulting in higher rates when compared with PLA (P < 0.05). Muscle connective protein synthesis rates averaged 0.072 ± 0.019, 0.068 ± 0.017, and 0.058 ± 0.018 %/h in WHEY, COLL and PLA, respectively, with no significant differences between groups (P = 0.09). CONCLUSIONS: Ingestion of whey protein during recovery from exercise increases myofibrillar protein synthesis rates. Neither collagen nor whey protein ingestion further increased muscle connective protein synthesis rates during the early stages of post-exercise recovery in both male and female recreational athletes

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 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 may provide plant-derived protein blends with a more balanced amino acid profile. OBJECTIVE: This study aimed to compare post-prandial 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 males. DESIGN: In a randomized, double blind, parallel-group design, 24 young males (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 post-prandial plasma amino acid profiles (secondary outcome) and subsequent muscle protein synthesis rates (primary outcome). Data were analyzed by two way-repeated measures ANOVA and two-samples t-tests. RESULTS: MILK increased plasma essential amino acid concentrations more than PLANT-BLEND over the 5 h postprandial period (incremental area under curve 151±31 vs 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 and 0.064 ± 0.016%∙h-1, respectively; P = 0.08). CONCLUSION: Ingestion of 30 g of a 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: Nederlands Trial Register: NTR6548 https://www.trialregister.nl/

Resistance Exercise Training Increases Muscle Mass and Strength in Prostate Cancer Patients on Androgen Deprivation Therapy

PURPOSE: To assess the effects of 20 weeks resistance exercise training with or without protein supplementation on body composition, muscle mass, muscle strength, physical performance and aerobic capacity in prostate cancer patients receiving androgen deprivation therapy (ADT). METHODS: Sixty prostate cancer patients receiving ADT were randomly assigned to perform 20 weeks of resistance exercise training with supplementation of 31 g whey protein (EX+PRO, n = 30) or placebo (EX+PLA, n = 30), consumed immediately after exercise and every night before sleep. A separate control group (CON, n = 36) only received usual care. At baseline and after 20 weeks, body composition (dual-energy X-ray absorptiometry), muscle mass (computed tomography scan), muscle strength (1-repetition maximum strength tests), physical performance (Timed Up and Go Test, 30-second Chair Stand Test, Stair Climb Test), aerobic capacity (cardiopulmonary exercise test) and habitual dietary intake (food diary), were assessed. Data were analyzed using a two-factor repeated-measures ANOVA. RESULTS: Over time, muscle mass and strength increased in EX+PRO and EX+PLA and decreased in CON. Total fat mass and fat percentage increased in EX+PRO and CON, but not in EX+PLA. Physical performance did not significantly change over time in either group. Aerobic capacity was maintained in EX+PLA, while it decreased in EX+PRO and CON. Habitual protein intake (without supplements) averaged >1.0 g·kg body weight-1·day-1, with no differences over time or between groups. CONCLUSIONS: In prostate cancer patients, resistance exercise training counteracts the adverse effects of ADT on body composition, muscle mass, muscle strength and aerobic capacity, with no additional benefits of protein supplementation

Higher muscle protein synthesis rates following ingestion of an omnivorous meal compared with an isocaloric and isonitrogenous vegan meal in healthy, older adults

BACKGROUND: Plant-derived proteins are considered to have lesser anabolic properties when compared with animal-derived proteins. The anabolic properties of isolated proteins do not necessarily reflect the anabolic response to the ingestion of whole-foods. The presence or absence of the various components that constitute the whole-food matrix can strongly impact protein digestion and amino acid absorption and, as such, modulate post-prandial muscle protein synthesis rates. So far, no study has compared the anabolic response following ingestion of an omnivorous versus a vegan meal. OBJECTIVE: To compare post-prandial muscle protein synthesis rates following ingestion of a whole-food meal providing 100 g lean ground beef versus an isonitrogenous, isocaloric whole-food plant-based meal in healthy, older adults. METHODS: In a randomized, counter-balanced, cross-over design, 16 older (65-85 y) adults (8 males, 8 females) underwent 2 test days. On one day, participants consumed a whole-food omnivorous meal containing beef as the primary source of protein (0.45 g protein·kg BM; MEAT). On the other day, participants consumed an isonitrogenous and isocaloric whole-food vegan meal containing unprocessed plant-based whole-foods (PLANT). Primed continuous L-[ring- C ]-phenylalanine infusions were applied with blood and muscle biopsies being collected frequently for 6 h to assess post-prandial plasma amino acid profiles and muscle protein synthesis rates. Data are presented as means±SDs and were analyzed by two way-repeated measures ANOVA and paired-samples t-tests. RESULTS: MEAT increased plasma essential amino acid concentrations more than PLANT over the 6 h post-prandial period (incremental area under curve 87±37 vs 38±54 mmol·6 h·L respectively; P-interaction&lt;0.01). Ingestion of MEAT resulted in ~47% higher post-prandial muscle protein synthesis rates when compared to the ingestion of PLANT (0.052±0.023 and 0.035±0.021 %·h , respectively; paired-samples t-test: P=0.037). CONCLUSION: Ingestion of a whole-food meal containing beef, results in greater post-prandial muscle protein synthesis rates when compared to the ingestion of an isonitrogenous whole-food plant-based meal in older adults. https://clinicaltrials.gov/study/NCT05151887. CLINICAL TRIAL REGISTRATION: Https://clinicaltrials.gov/study/NCT05151887

A 12-gene pharmacogenetic panel to prevent adverse drug reactions: an open-label, multicentre, controlled, cluster-randomised crossover implementation study

© 2023Background: The benefit of pharmacogenetic testing before starting drug therapy has been well documented for several single gene–drug combinations. However, the clinical utility of a pre-emptive genotyping strategy using a pharmacogenetic panel has not been rigorously assessed. Methods: We conducted an open-label, multicentre, controlled, cluster-randomised, crossover implementation study of a 12-gene pharmacogenetic panel in 18 hospitals, nine community health centres, and 28 community pharmacies in seven European countries (Austria, Greece, Italy, the Netherlands, Slovenia, Spain, and the UK). Patients aged 18 years or older receiving a first prescription for a drug clinically recommended in the guidelines of the Dutch Pharmacogenetics Working Group (ie, the index drug) as part of routine care were eligible for inclusion. Exclusion criteria included previous genetic testing for a gene relevant to the index drug, a planned duration of treatment of less than 7 consecutive days, and severe renal or liver insufficiency. All patients gave written informed consent before taking part in the study. Participants were genotyped for 50 germline variants in 12 genes, and those with an actionable variant (ie, a drug–gene interaction test result for which the Dutch Pharmacogenetics Working Group [DPWG] recommended a change to standard-of-care drug treatment) were treated according to DPWG recommendations. Patients in the control group received standard treatment. To prepare clinicians for pre-emptive pharmacogenetic testing, local teams were educated during a site-initiation visit and online educational material was made available. The primary outcome was the occurrence of clinically relevant adverse drug reactions within the 12-week follow-up period. Analyses were irrespective of patient adherence to the DPWG guidelines. The primary analysis was done using a gatekeeping analysis, in which outcomes in people with an actionable drug–gene interaction in the study group versus the control group were compared, and only if the difference was statistically significant was an analysis done that included all of the patients in the study. Outcomes were compared between the study and control groups, both for patients with an actionable drug–gene interaction test result (ie, a result for which the DPWG recommended a change to standard-of-care drug treatment) and for all patients who received at least one dose of index drug. The safety analysis included all participants who received at least one dose of a study drug. This study is registered with ClinicalTrials.gov, NCT03093818 and is closed to new participants. Findings: Between March 7, 2017, and June 30, 2020, 41 696 patients were assessed for eligibility and 6944 (51·4 % female, 48·6% male; 97·7% self-reported European, Mediterranean, or Middle Eastern ethnicity) were enrolled and assigned to receive genotype-guided drug treatment (n=3342) or standard care (n=3602). 99 patients (52 [1·6%] of the study group and 47 [1·3%] of the control group) withdrew consent after group assignment. 652 participants (367 [11·0%] in the study group and 285 [7·9%] in the control group) were lost to follow-up. In patients with an actionable test result for the index drug (n=1558), a clinically relevant adverse drug reaction occurred in 152 (21·0%) of 725 patients in the study group and 231 (27·7%) of 833 patients in the control group (odds ratio [OR] 0·70 [95% CI 0·54–0·91]; p=0·0075), whereas for all patients, the incidence was 628 (21·5%) of 2923 patients in the study group and 934 (28·6%) of 3270 patients in the control group (OR 0·70 [95% CI 0·61–0·79]; p <0·0001). Interpretation: Genotype-guided treatment using a 12-gene pharmacogenetic panel significantly reduced the incidence of clinically relevant adverse drug reactions and was feasible across diverse European health-care system organisations and settings. Large-scale implementation could help to make drug therapy increasingly safe. Funding: European Union Horizon 2020