The effect of combined ß-lactoglobulin supplementation and resistance exercise training prior to limb immobilisation on muscle protein synthesis rates in healthy young adults: study protocol for a randomised controlled trial.

BACKGROUND: The decline in skeletal muscle mass experienced following a short-term period (days to weeks) of muscle disuse is mediated by impaired rates of muscle protein synthesis (MPS). Previous RCTs of exercise or nutrition prehabilitation interventions designed to mitigate disuse-induced muscle atrophy have reported limited efficacy. Hence, the aim of this study is to investigate the impact of a complex prehabilitation intervention that combines ß-lactoglobulin (a novel milk protein with a high leucine content) supplementation with resistance exercise training on disuse-induced changes in free-living integrated rates of MPS in healthy, young adults. METHODS/DESIGN: To address this aim, we will recruit 24 healthy young (18-45 years) males and females to conduct a parallel, double-blind, 2-arm, randomised placebo-controlled trial. The intervention group will combine a 7-day structured resistance exercise training programme with thrice daily dietary supplementation with 23 g of ß-lactoglobulin. The placebo group will combine the same training programme with an energy-matched carbohydrate (dextrose) control. The study protocol will last 16 days for each participant. Day 1 will be a familiarisation session and days 2-4 will be the baseline period. Days 5-11 represent the 'prehabilitation period' whereby participants will combine resistance training with their assigned dietary supplementation regimen. Days 12-16 represent the muscle disuse-induced 'immobilisation period' whereby participants will have a single leg immobilised in a brace and continue their assigned dietary supplementation regimen only (i.e. no resistance training). The primary endpoint of this study is the measurement of free-living integrated rates of MPS using deuterium oxide tracer methodology. Measurements of MPS will be calculated at baseline, over the 7-day prehabilitation period and over the 5-day immobilisation period separately. Secondary endpoints include measurements of muscle mass and strength that will be collected on days 4 (baseline), 11 (end of prehabilitation) and 16 (end of immobilisation). DISCUSSION: This novel study will establish the impact of a bimodal prehabilitation strategy that combines ß-lactoglobulin supplementation and resistance exercise training in modulating MPS following a short-term period of muscle disuse. If successful, this complex intervention may be translated to clinical practice with application to patients scheduled to undergo, for example, hip or knee replacement surgery. TRIAL REGISTRATION: NCT05496452. Registered on August 10, 2022. PROTOCOL VERSION: 16-12-2022/1.

Discovery of bactericides as an acute mitochondrial membrane damage inducer.

Mitochondria evolved from endosymbiotic bacteria to become essential organelles of eukaryotic cells. The unique lipid composition and structure of mitochondrial membranes are critical for the proper functioning of mitochondria. However, stress responses that help maintain the mitochondrial membrane integrity are not well understood. One reason for this lack of insight is the absence of efficient tools to specifically damage mitochondrial membranes. Here, through a compound screen, we found that two bis-biguanide compounds, chlorhexidine and alexidine, modified the activity of the inner mitochondrial membrane (IMM)-resident protease OMA1 by altering the integrity of the IMM. These compounds are well-known bactericides whose mechanism of action has centered on their damage-inducing activity on bacterial membranes. We found alexidine binds to the IMM likely through the electrostatic interaction driven by the membrane potential as well as an affinity for anionic phospholipids. Electron microscopic analysis revealed that alexidine severely perturbated the cristae structure. Notably, alexidine evoked a specific transcriptional/proteostasis signature that was not induced by other typical mitochondrial stressors, highlighting the unique property of alexidine as a novel mitochondrial membrane stressor. Our findings provide a chemical-biological tool that should enable the delineation of mitochondrial stress-signaling pathways required to maintain the mitochondrial membrane homeostasis.

Presleep Protein Supplementation Does Not Improve Recovery During Consecutive Days of Intense Endurance Training: A Randomized Controlled Trial.

Recent studies demonstrate that protein ingestion immediately before sleep improves muscle recovery during the night following resistance exercise. Whether this feeding strategy benefits recovery from endurance training has yet to be established. The aim of this study was to investigate the effects of whey protein isolate ingested every night before sleep on subsequent performance and circulatory markers of muscular recovery during a week of intensified endurance training mimicking a training camp. In a parallel design, 32 trained runners underwent a 1-week intervention with a rigorously controlled diet (carbohydrate = 7.2 g·kg-1·day-1, protein = 1.8 g·kg-1·day-1, and fat = 1.0 g·kg-1·day-1) and exercise program (11 sessions) while receiving either a protein (0.5 g·kg-1·day-1) or carbohydrate (0.5 g·kg-1·day-1) beverage every night before sleep. Blood samples were obtained on the morning of Days 1, 4, 7, and 8 and analyzed for markers of muscle damage (creatine kinase, lactate dehydrogenase, and myoglobin). The postintervention 5-km time-trial performance was significantly impaired in both groups (11 ± 24 s, p < .01). Plasma creatine kinase (227% ± 221%, p < .01), lactate dehydrogenase (18% ± 22%, p < .01), and myoglobin (72% ± 62%, p < .01) increased gradually throughout the week with no difference between the groups (p > .05). In conclusion, the presleep protein ingestion did not reduce the decline in performance or ameliorate the rise of circulatory markers of muscle damage during a week of intensified training when compared with the isocaloric carbohydrate ingestion.