Comparative evaluation of muscle proteolysis by a compartmental model of 3-methylhistidine

Measurement of urinary 3-methylhistidine (3MH) excretion is the primary in vivo method to measure muscle protein breakdown. This method requires quantitative collection of urine and is based on the assumption that no metabolism of 3MH occurs once released from actin and myosin. This is true in most in most species but in sheep and pigs a proportion is retained in muscle as a dipeptide balenine. In none of these species does urine 3MH yield any data on the metabolism of 3MH. The included studies propose that 3MH metabolism in sheep, cattle, pigs, dogs and humans can be defined from a single bolus dose of 3- (methyl-[superscript]2H[subscript]3) -methylhistidine tracer. A minimum of three exponentials was required to describe the plasma decay curve adequately. The kinetic linear-time variant models of 3MH in the whole animal were constructed by using the SAAM/CONSAM computer modeling program. Three different configurations of a three compartment model are described: (1) a simple 3-compartment model, in which plasma kinetics are described by compartment 1, out of which all species had a undefinable exit; (2) a plasma-urinary 3-compartment model with two exits, a urinary exit out of compartment 1 and a second exit out of compartment 3 was used in sheep; and (3) a plasma 3-compartment model with an exit out of the tissue compartment 3 was used in pigs. The models define steady state masses and fluxes of 3MH between three compartments in the body and, importantly entry into the system or de novo production of 3MH. The de novo production of 3MH for humans, cattle, dogs, sheep and pigs were 3.1, 3.4, 12.1, 11.6 and 7.0 [mu] mol· kg[superscript]-1· d[superscript]-1, respectively. The de novo 3MH production corresponded to fractional breakdown rates of muscle protein of 1.72%/d for cattle, 3.99%/d for dogs, 5.40%/d for sheep and 2.80%/d for pigs. From the complete model of 3MH metabolism a similar practical isotopic model (minimal) was constructed. This was accomplished by lumping the three compartments together into one metabolic pool of 3MH. This minimal 1-compartment model utilized plasma samples obtained from 720 to 4320 min after isotope injection. The de novo production of 3MH as calculated by the model was not different from that calculated via the traditional collection of urinary 3MH (humans, 3.09 vs. 2.57 [mu] mol· kg[superscript]-1· -d[superscript]-1, respectively, P \u3e 0.30: cattle, 3.41 vs. 3.20 [mu] mol· kg[superscript]-1· d[superscript]-1, respectively, P \u3e 0.25). However, 3MH production estimated by the model compared to urinary production was different in dogs (92.7 vs 71.6 [mu] mol/d, respectively, P \u3c 0.10). Additionally, although numbers are limited, the data suggest that the model compartments may be an indicator of body muscle mass (r = 0.95, P \u3c 0.01) in humans and (r = 0.59, P = 0.0061 in pigs. These data indicate the compartmental model, allows the assessment of muscle proteolysis and 3MH kinetics without collection of urine

Method for measuring muscle mass

A method for determining muscle mass in a human subject useful for monitoring athletic conditioning, weight loss programs, nutritional deficiencies, and disease states which cause muscle wasting is provided comprising administration of a bolus dose of a metabolic marker for 3-methylhistidine, the use of a three-compartment model to describe data from blood samples collected periodically thereafter, and calculation of muscle mass as a function of specific values generated by the model

beta-Hydroxy-beta-methylbutyrate free acid reduces markers of exercise-induced muscle damage and improves recovery in resistance-trained men

The purpose of the present study was to determine the effects of short-term supplementation with the free acid form of beta-hydroxy-beta-methylbutyrate (HMB-FA) on indices of muscle damage, protein breakdown, recovery and hormone status following a high-volume resistance training session in trained athletes. A total of twenty resistance-trained males were recruited to participate in a high-volume resistance training session centred on full squats, bench presses and dead lifts. Subjects were randomly assigned to receive either 3 g/d of HMB-FA or a placebo. Immediately before the exercise session and 48 h post-exercise, serum creatine kinase (CK), urinary 3-methylhistadine (3-MH), testosterone, cortisol and perceived recovery status (PRS) scale measurements were taken. The results showed that CK increased to a greater extent in the placebo (329%) than in the HMB-FA group (104%) (P=0.004, d=1.6). There was also a significant change for PRS, which decreased to a greater extent in the placebo (9.1 (SEM 0.4) to 4.6 (SEM 0.5)) than in the HMB-FA group (9.1 (SEM 0.3) to 6.3 (SEM 0.3)) (P=0.005, d = -0.48). Muscle protein breakdown, measured by 3-MH analysis, numerically decreased with HMB-FA supplementation and approached significance (P=0.08, d = 0.12). There were no acute changes in plasma total or free testosterone, cortisol or C-reactive protein. In conclusion, these results suggest that an HMB-FA supplement given to trained athletes before exercise can blunt increases in muscle damage and prevent declines in perceived readiness to train following a high-volume, muscle-damaging resistance-training session

A double-blind placebo controlled trial into the impacts of HMB supplementation and exercise on free-living muscle protein synthesis, muscle mass and function, in older adults

Age-related sarcopenia and dynapenia are associated with frailty and metabolic diseases. Resistance exercise training (RET) adjuvant to evidence-based nutritional intervention(s) have been shown as mitigating strategies. Given that HMB supplementation during RET improves lean body mass in younger humans (Wilson et al., 2014), and that we have shown that HMB acutely stimulates muscle protein synthesis (MPS) and inhibits breakdown; we hypothesized that chronic supplementation of HMB adjuvant to RET would enhance MPS and muscle mass/function in older people.We recruited 16 healthy older men (PLA: 68.5±1.0y, HMB: 67.8±1.1y) for a randomised double-blind-placebo (PLA) controlled trial (HMB 3 x 1g/day vs. PLA) involving a 6-week unilateral progressive RET regime (6 x 8 repetitions, 75% 1-RM, 3.wk-1). D2O dosing was performed over the first two weeks (0-2w) and last two weeks (4-6w) with bilateral vastus lateralis (VL) biopsies at 0-2 and 4-6 weeks (each time 75±2 min after a single bout of RE) for quantification of early and later MPS responses and post-RE myogenic gene expression. Thigh lean mass was measured by DXA, VL thickness and architecture (fibre length and pennation angle) by ultrasound at 0/3/6 weeks, and strength by knee extensor 1-RM testing and MVC by isokinetic dynamometry (approx. every 10 days).RET induced strength increases (1-RM) in the exercised leg in both groups (398±22N to 499±30N HMB vs. 396±29N to 510±43N PLA (both

Nutritional Supplementation of the Leucine Metabolite β-hydroxy-β- Methylbutyrate (HMB) During Resistance Training

The effects of supplementation of the leucine metabolite β-hydroxy-β- methylbutyrate (HMB) were examined in a resistance training study. Thirty- nine men and 36 women between the ages of 20-40 y were randomized to either a placebo (P) supplemented or HMB supplemented (3.0 g HMB/d) group in two gender cohorts. All subjects trained three times per week for 4 wk. In the HMB group, plasma creatine phosphokinase levels tended to be suppressed compared to the placebo group following the 4 wk of resistance training (HMB:174.4 ± 26.8 to 173.5 ± 17.0 U/L; P:155.0 ± 20.8 to 195.2 ± 23.5 U/L). There were no significant differences in strength gains based on prior training status or gender with HMB supplementation. The HMB group had a greater increase in upper body strength than the placebo group (HMB:7.5 ± 0.6 kg; P:5.2 ± 0.6 kg; P = 0.008). The HMB groups increased fat-free weight by 1.4 ± 0.2 kg and decreased percent fat by 1.1% ± 0.2% while the placebo groups increased fat-free weight by 0.9 ± 0.2 kg and decreased percent fat by 0.5% ± 0.2% (fat-free weight P = 0.08, percent fat P = 0.08, HMB compared to placebo). In summary, this is the first short-term study to investigate the roles of gender and training status on the effects of HMB supplementation on strength and body composition. This study showed, regardless of gender or training status, HMB may increase upper body strength and minimize muscle damage when combined with an exercise program