Attenuation of Resting but Not Load-Mediated Protein Synthesis in Prostate Cancer Patients on Androgen Deprivation.

CONTEXT: Androgen deprivation therapy (ADT) is a common prostate cancer (PCa) treatment but results in muscular atrophy. Periodic increases in muscle protein synthesis (MPS) that occur after resistance exercise or protein intake may ameliorate this muscle loss, but the impact of these anabolic stimuli during ADT is unclear. OBJECTIVE: To determine the acute MPS response to whey protein supplementation with and without resistance exercise during ADT. DESIGN: Acute response in PCa patients vs age-matched controls (CON). SETTING: Academic laboratory setting. PARTICIPANTS: PCa patients on ADT (N = 8) and CON (N = 10). INTERVENTION: A standardized diet was consumed for 2 days prior to performing unilateral knee extension resistance exercise followed by ingestion of 40 g of whey protein. MAIN OUTCOME MEASURES: Bilateral biopsies and stable isotope infusions were used to determine MPS rates at rest after protein ingestion with and without resistance exercise. RESULTS: Baseline MPS during ADT was suppressed relative to CON (P = 0.01). Protein consumption stimulated MPS in both groups (approximate twofold increase, both P < 0.001), but to a greater extent in CON (P = 0.003). Protein plus resistance exercise increased MPS (∼3.4-fold increase, both P < 0.001) to a greater extent than did protein alone (P < 0.001), but with no difference between groups (P = 0.380). CONCLUSIONS: ADT reduces basal and protein feeding-induced rises in MPS; however, combined protein ingestion with resistance exercise stimulated MPS to a similar degree as CON. Testosterone appears to play a role in maintaining muscle mass but is not necessary to initiate a robust response in MPS following resistance exercise when combined with protein ingestion.

Effect of post-exercise protein-leucine feeding on neutrophil function, immunomodulatory plasma metabolites and cortisol during a 6-day block of intense cycling.

Whey protein and leucine ingestion following exercise increases muscle protein synthesis and could influence neutrophil function during recovery from prolonged intense exercise. We examined the effects of whey protein and leucine ingestion post-exercise on neutrophil function and immunomodulators during a period of intense cycling. In a randomized double-blind crossover, 12 male cyclists ingested protein/leucine/carbohydrate/fat (LEUPRO 20/7.5/89/22 g h(-1), respectively) or isocaloric carbohydrate/fat control (CON 119/22 g h(-1)) beverages for 1-3 h post-exercise during 6 days of high-intensity training. Blood was taken pre- and post-exercise on days 1, 2, 4 and 6 for phorbol myristate acetate (PMA)-stimulated neutrophil superoxide (O2 (-)) production, immune cell counts, amino acid and lipid metabolism via metabolomics, hormones (cortisol, testosterone) and cytokines (interleukin-6, interleukin-10). During recovery on day 1, LEUPRO ingestion increased mean concentrations of plasma amino acids (glycine, arginine, glutamine, leucine) and myristic acid metabolites (acylcarnitines C14, myristoylcarnitine; and C14:1-OH, hydroxymyristoleylcarnitine) with neutrophil priming capacity, and reduced neutrophil O2 production (15-17 mmol O2 (-) cell(-1) ± 90 % confidence limits 20 mmol O2 (-) cell(-1)). On day 2, LEUPRO increased pre-exercise plasma volume (6.6 ± 3.8 %) but haematological effects were trivial. LEUPRO supplementation did not substantially alter neutrophil elastase, testosterone, or cytokine concentrations. By day 6, however, LEUPRO reduced pre-exercise cortisol 21 % (±15 %) and acylcarnitine C16 (palmitoylcarnitine) during exercise, and increased post-exercise neutrophil O2 (-) (33 ± 20 mmol O2 (-) cell(-1)), relative to control. Altered plasma amino acid and acylcarnitine concentrations with protein-leucine feeding might partly explain the acute post-exercise reduction in neutrophil function and increased exercise-stimulated neutrophil oxidative burst on day 6, which could impact neutrophil-dependent processes during recovery from intense training.

A protein-leucine supplement increases branched-chain amino acid and nitrogen turnover but not performance.

PURPOSE: This study aimed to determine the effect of postexercise protein-leucine coingestion with CHO-lipid on subsequent high-intensity endurance performance and to investigate candidate mechanisms using stable isotope methods and metabolomics. METHODS: In this double-blind, randomized, crossover study, 12 male cyclists ingested a leucine/protein/CHO/fat supplement (LEUPRO 7.5/20/89/22 g · h(-1), respectively) or isocaloric CHO/fat control (119/22 g · h(-1)) 1-3 h after exercise during a 6-d training block (intense intervals, recovery, repeated-sprint performance rides). Daily protein intake was clamped at 1.9 g · kg(-1) · d(-1) (LEUPRO) and 1.5 g · kg(-1) · d(-1) (control). Stable isotope infusions (1-(13)C-leucine and 6,6-(2)H2-glucose), mass spectrometry-based metabolomics, and nitrogen balance methods were used to determine the effects of LEUPRO on whole-body branched-chain amino acid (BCAA) and glucose metabolism and protein turnover. RESULTS: After exercise, LEUPRO increased BCAA levels in plasma (2.6-fold; 90% confidence limits = ×/÷ 1.1) and urine (2.8-fold; ×/÷ 1.2) and increased products of BCAA metabolism plasma acylcarnitine C5 (3.0-fold; ×/÷ 0.9) and urinary leucine (3.6-fold; ×/÷ 1.3) and ß-aminoisobutyrate (3.4-fold; ×/÷ 1.4), indicating that ingesting ~10 g leucine per hour during recovery exceeds the capacity to metabolize BCAA. Furthermore, LEUPRO increased leucine oxidation (5.6-fold; ×/÷ 1.1) and nonoxidative disposal (4.8-fold; ×/÷ 1.1) and left leucine balance positive relative to control. With the exception of day 1 (LEUPRO = 17 ± 20 mg N · kg(-1), control = -90 ± 44 mg N · kg(-1)), subsequent (days 2-5) nitrogen balance was positive for both conditions (LEUPRO = 130 ± 110 mg N · kg(-1), control = 111 ± 86 mg N · kg(-1)). Compared with control feeding, LEUPRO lowered the serum creatine kinase concentration by 21%-25% (90% confidence limits = ± 14%), but the effect on sprint power was trivial (day 4 = 0.4% ± 1.0%, day 6 = -0.3% ± 1.0%). CONCLUSIONS: Postexercise protein-leucine supplementation saturates BCAA metabolism and attenuates tissue damage, but effects on subsequent intense endurance performance may be inconsequential under conditions of positive daily nitrogen balance.