Benefits Of A Ketone Ester Drink

Utility of a ketone ester drink, along with adequate glucose, in enhancing muscle glycogen synthesis is shown here, abstract:

INTRODUCTION:

Physical endurance can be limited by muscle glycogen stores, in that glycogen depletion markedly reduces external work. During carbohydrate restriction, the liver synthesises the ketone bodies, D-β-hydroxybutyrate and acetoacetate, from fatty acids. In animals and in the presence of glucose, D-β-hydroxybutyrate promotes insulin secretion and increases glycogen synthesis. Here we determined whether a dietary ketone ester, combined with plentiful glucose, can increase post-exercise glycogen synthesis in human skeletal muscle.

METHODS:

Following an interval-based glycogen-depletion exercise protocol, 12 well-trained male athletes completed a randomized, 3-arm, blinded crossover recovery study that consisted of consumption of either a taste-matched, zero-calorie control or a ketone monoester drink, followed by a 10 mM glucose clamp or saline infusion for two hours. The three post-exercise conditions were; control drink then saline infusion, control drink then hyperglycemic clamp or ketone ester drink then hyperglycemic clamp. Skeletal muscle glycogen content was determined in muscle biopsies of vastus lateralis taken before and after the two-hour clamps.

RESULTS:

The ketone ester drink increased blood D-β-hydroxybutyrate concentrations to a maximum of 5.3 vs. 0.7 mM for the control drink (p < 0.0001). During the two-hour glucose clamps, insulin levels were two-fold higher (31 vs. 16 mU/l, p < 0.01) and glucose uptake 32% faster (1.66 vs. 1.26 g/kg, p<0.001). The ketone drink increased by 61 g the total glucose infused over 2 h, from 197 g to 258 g, and muscle glycogen was 50% higher (246 vs.164 mmoles glycosyl units/kg dry weight, p < 0.05) than after the control drink.

CONCLUSION:

In the presence of constant high glucose concentrations, a ketone ester drink increased endogenous insulin levels, glucose uptake and muscle glycogen synthesis.

Myoststin Knockout Improves Cachexia And Inhibits Tumor Growth

Cachexia- induced muscle wasting is a problem in cancer. This paper tests the hypothesis that knocking out myostatin expression could help with this problem, since myostatin inhibits muscle growth and differentiation.  In mice, this hypothesis proved correct and also some inhibition of tumor growth was also observed - these are all encouraging findings.  The abstract of the paper:

Cachexia is a muscle-wasting syndrome that contributes significantly to morbidity and mortality of many patients with advanced cancers. However, little is understood about how the severe loss of skeletal muscle characterizing this condition occurs. In the current study, we tested the hypothesis that the muscle protein myostatin is involved in mediating the pathogenesis of cachexia-induced muscle wasting in tumor-bearing mice. Myostatin gene inactivation prevented the severe loss of skeletal muscle mass induced in mice engrafted with Lewis lung carcinoma (LLC) cells or in Apc(Min) (/+) mice, an established model of colorectal cancer and cachexia. Mechanistically, myostatin loss attenuated the activation of muscle fiber proteolytic pathways by inhibiting the expression of atrophy-related genes, MuRF1 and MAFbx/Atrogin-1, along with autophagy-related genes. Notably, myostatin loss also impeded the growth of LLC tumors, the number and the size of intestinal polyps in Apc(Min) (/+) mice, thus strongly increasing survival in both models. Gene expression analysis in the LLC model showed this phenotype to be associated with reduced expression of genes involved in tumor metabolism, activin signaling, and apoptosis. Taken together, our results reveal an essential role for myostatin in the pathogenesis of cancer cachexia and link this condition to tumor growth, with implications for furthering understanding of cancer as a systemic disease.

More research is needed.

Protein Intake Timing

Here is a paper from several years ago that asserts that protein intake distribution – consuming most of the protein at one meal or spreading it out more evenly throughout the day – does not affect muscle building.  Hence the authors conclude:

We conclude that over an 8-week intervention period, the protein intake distribution pattern in mixed meals does not play an important role in determining anabolic response, muscle strength, or functional outcomes. 

One caveat is that it is uncertain whether the subjects were doing any resistance exercising. For example, you may expect to observe better results consuming a lot of protein just after the workout (and/or before and after) than distributed throughout the day, but this needs to be confirmed.  If the subjects were just regularly active, then perhaps intake time does not matter.  More study is required.

Resistance Training Restores Muscle Sensitivity To Feeding

An interesting paper on exercise, feeding, and muscle; abstract:

Normally, skeletal muscle mass is unchanged, beyond periods of growth, but it begins to decline in the fourth or fifth decade of life. The mass of skeletal muscle is maintained by ingestion of protein-containing meals. With feeding, muscle protein synthesis (MPS) is stimulated and a small suppression of muscle protein breakdown (MPB) occurs, such that protein balance becomes positive (MPS>MPB). As the postprandial period subsides and a transition toward fasting occurs, the balance of muscle protein turnover becomes negative again (MPB>MPS). Thus, during maintenance of skeletal muscle mass, the long-term net result is that MPS is balanced by MPB. Acutely, however, it is of interest to determine what regulates feeding-induced increases in MPS, since it appears that, in a number of scenarios (for example aging, disuse, and wasting diseases), a suppression of MPS in response to feeding is a common finding. In fact, recent findings point to the fact that loss of skeletal muscle mass with disuse and aging is due not chronic changes in MPS or MPB, but to a blunted feeding-induced rise in MPS. Resistance exercise is a potent stimulator of MPS and appears to synergistically enhance the gains stimulated by feeding. As such, resistance exercise is an important countermeasure to disuse atrophy and to age-related declines in skeletal muscle mass. What is less well understood is how the intensity and volume of the resistance exercise stimulus is sufficient to result in rises in MPS. Recent advances in this area are discussed here, with a focus on human in vivo data.

To summarize: feeding, particularly of protein, favors muscle buildup as opposed t breakdown and fasting does the opposite.  Muscle loss with age seems linked to suppressed muscle buildup from feeding and this suppression can be reduced by resistance training.  Therefore, resistance training helps to reduce/prevent age-related muscle loss, possibly through enhancing feeding-related stimulation of muscle protein synthesis.  Hence the importance of resistance training and (protein) feeding (albeit of course not in excess).

Resistance Training And Muscle Metabolism

Here is a paper from several years ago formally demonstrating what bodybuilders have long put into practice: resistance training affects protein turnover in skeletal muscle so as to result in muscle growth.  Abstract:

PURPOSE:

Acute bouts of resistance exercise and subsequent training alters protein turnover in skeletal muscle. The mechanisms responsible for the changes in basal post-absorptive protein turnover and its impact on muscle hypertrophy following resistance exercise training are unknown. Our goal was to determine whether post-absorptive muscle protein turnover following 12 weeks of resistance exercise training (RET) plays a role in muscle hypertrophy. In addition, we were interested in determining potential molecular mechanisms responsible for altering post-training muscle protein turnover.

METHODS:

Healthy young men (n = 31) participated in supervised whole body progressive RET at 60-80% 1 repetition maximum (1-RM), 3 days/week for 3 months. Pre- and post-training vastus lateralis muscle biopsies and blood samples taken during an infusion of 13C6 and 15N phenylalanine and were used to assess skeletal muscle protein turnover in the post-absorptive state. Lean body mass (LBM), muscle strength (determined by dynamometry), vastus lateralis muscle thickness (MT), myofiber type-specific cross-sectional area (CSA), and mRNA were assessed pre- and post-RET.

RESULTS:

RET increased strength (12-40%), LBM (~5%), MT (~15%) and myofiber CSA (~20%) (p < 0.05). Muscle protein synthesis (MPS) increased 24% while muscle protein breakdown (MPB) decreased 21%, respectively. These changes in protein turnover resulted in an improved net muscle protein balance in the basal state following RET. Further, the change in basal MPS is positively associated (r = 0.555, p = 0.003) with the change in muscle thickness.

CONCLUSION:

Post-absorptive muscle protein turnover is associated with muscle hypertrophy during resistance exercise training.

It is always comforting when science supports popular conception.

Gene Editing For Muscular Dystrophy

Here is a paper from several years ago discussing promising results with gene therapy in a mouse model of muscular dystrophy.  Abstract:

Gene replacement therapies utilizing adeno-associated viral (AAV) vectors hold great promise for treating Duchenne muscular dystrophy (DMD). A related approach uses AAV vectors to edit specific regions of the DMD gene using CRISPR/Cas9. Here we develop multiple approaches for editing the mutation in dystrophic mdx4cv mice using single and dual AAV vector delivery of a muscle-specific Cas9 cassette together with single-guide RNA cassettes and, in one approach, a dystrophin homology region to fully correct the mutation. Muscle-restricted Cas9 expression enables direct editing of the mutation, multi-exon deletion or complete gene correction via homologous recombination in myogenic cells. Treated muscles express dystrophin in up to 70% of the myogenic area and increased force generation following intramuscular delivery. Furthermore, systemic administration of the vectors results in widespread expression of dystrophin in both skeletal and cardiac muscles. Our results demonstrate that AAV-mediated muscle-specific gene editing has significant potential for therapy of neuromuscular disorders.

That's very promising.  What's going on more recently? Future posts here will explore the progress in this and other similar projects using gene therapy tested in mouse models. This is why basic science research is so important, as the methods utilized are ultimately derived from such research.

Exercise Non-Responders?

Are any people real “non-responders” to exercise?  This paper says “no” – those people just need a “higher dose” of exercise in order to see a response. In this case, the exercise was aimed at “cardiorespiratory fitness,“ but presumably the same applies to muscle-building as well. This does not mean, of course, that with a sufficiently high dose everyone will ultimately obtain the same results. Some people are indeed “hard gainers.” But they should be able to achieve some reasonable gains, albeit not at the level of all those “easy gainers.” 

Dietary Interventions For Sarcopenia

Sarcopenia is the loss of muscle with normal aging.  What dietary interventions can help improve muscle mass in these patients?  Abstract:

BACKGROUND: Inadequate nutritional intake and altered response of aging muscles to anabolic stimuli from nutrients contribute to the development of sarcopenia. Nutritional interventions show inconsistent results in sarcopenic older adults, which might be influenced by their basal nutritional status.

OBJECTIVE: To test if baseline serum 25-hydroxyvitamin D (25(OH)D) concentrations and dietary protein intake influenced changes in muscle mass and function in older adults who received nutritional intervention.

METHODS AND DESIGN: Post-hoc analysis was performed in the PROVIDE study that was a randomized controlled, double blind trial among 380 sarcopenic older adults. This study showed that those who received a vitamin D and leucine-enriched whey protein medical nutrition drink for 13 weeks gained more appendicular muscle mass (aMM), and improved lower-extremity function as assessed by the chair stand test compared with controls. To define low and high groups, a baseline serum concentration of 50 nmol/L 25(OH)D and baseline dietary protein intake of 1.0 g/kg/d were used as cut offs.

RESULTS: At baseline, participants with lower 25(OH)D concentrations showed lower muscle mass, strength and function compared with participants with a high 25(OH)D, while the group with lower protein intake (g/kg/day) had more muscle mass at baseline compared with the participants with higher protein intake. Participants with higher baseline 25(OH)D concentrations and dietary protein intake had, independent of other determinants, greater gain in appendicular muscle mass, skeletal muscle index (aMM/h2), and relative appendicular muscle mass (aMM/body weight × 100%) in response to the nutritional intervention. There was no effect modification of baseline 25(OH)D status or protein intake on change in chair-stand test.

CONCLUSIONS: Sufficient baseline levels of 25(OH)D and protein intake may be required to increase muscle mass as a result of intervention with a vitamin D and protein supplement in sarcopenic older adults. This suggests that current cut-offs in the recommendations for vitamin D and protein intake could be considered the "minimum" for adults with sarcopenia to respond adequately to nutrition strategies aimed at attenuating muscle loss.

It may not be surprising that patients with higher baseline vitamin D and protein intake showed greater muscle gains when given the enriched drink intervention.  It is curious that at baseline, while the higher vitamin D intake group had greater muscle mass, it was the lower protein intake group that had greater muscle mass.  The higher protein intake group had more women that the lower group, less weight and less fat, so there are a number of factors to consider.  The bottom line though is that gain of muscle above baseline required sufficient vitamin D and protein.

Exercise Type And Neuromuscular Adaptions

Can the type of exercise influence what kind of neuromuscular adaptions result?  Does high intensity training cause different types of adaptions than does lower-intensity endurance training, as the “gym gurus: tell us?  The answer seems to be yes.  Abstract:

PURPOSE:
Using a novel technique of high-density surface electromyography (HDEMG) decomposition and motor unit (MU) tracking, we compared changes in the properties of vastus medialis (VM) and vastus lateralis (VL) MUs following endurance (END) and high-intensity interval training (HIIT).
METHODS:
Sixteen men were assigned to an END or HIIT group (n=8 each) and performed six training sessions over 14 days. Each session consisted of 8-12×60s intervals at 100% peak power output (PPO) separated by 75s of recovery (HIIT) or 90-120min continuous cycling at ~65% VO2peak (END). Pre and post intervention, participants performed: 1) incremental cycling to determine VO2peak and PPO and 2) maximal (MVC), submaximal (10, 30, 50 and 70% MVC) and sustained (until task failure at 30% MVC) isometric knee extensions while HDEMG signals were recorded from the VM and VL. EMG signals were decomposed (submaximal contractions) into individual MUs by convolutive blind source separation. Finally, MUs were tracked across sessions by semi-blind source separation.
RESULTS:
After training, END and HIIT improved VO2peak similarly (by 5.0 and 6.7%, respectively). The HIIT group showed enhanced maximal knee extension torque by ~7% (p=0.02) and was accompanied by an increase in discharge rate for high-threshold MUs (≥50% knee extension MVC) (p<0.05). In contrast, the END group increased their time to task failure by ~17%, but showed no change in MU discharge rates (p>0.05).
CONCLUSIONS:
HIIT and END induce different adjustments in MU discharge rate despite similar improvements in cardiopulmonary fitness. Moreover, the changes induced by HIIT are specific for high-threshold motor units. For the first time we show that HIIT and END induce specific neuromuscular adaptations, possibly related to differences in exercise load intensity and training volume.

Therefore, the findings of this study show that high-intensity HIIT and endurance-oriented END result in exercise type-specific neuromuscular adaptions, which is completely consistent with the “gym info” popular conception that different types of exercise can induce specific types of nervous system and muscular adaptions and therefore one can tailor exercise type for the desired effect.

Protein And Fat Free mass in Female Resistance Training

In a group of female athletes undergoing resistance training, a high protein diet improved fat free mass gain but was not required for gains in strength.  This is an interesting finding that may or may not be generally applicable to all resistance trainers.  It can make sense if one presumes maximal hypertrophy requires significant extra protein, but that the neural and muscular adaptions required for strength do not.  However, more study is required to determine how applicable this is for, e.g., the advance trainee, including men.  Abstract:

Aspiring female physique athletes are often encouraged to ingest relatively high levels of dietary protein in conjunction with their resistance-training programs. However, there is little to no research investigating higher vs. lower protein intakes in this population. This study examined the influence of a high vs. low protein diet in conjunction with an 8-week resistance training program in this population. Seventeen females (21.2±2.1 years; 165.1±5.1 cm; 61±6.1 kg) were randomly assigned to a high protein diet (HP: 2.5g/kg/day; n=8) or a low protein diet (LP: 0.9g/kg/day, n=9) and were assessed for body composition and maximal strength prior to and after the 8-week protein intake and exercise intervention. Fat-free mass (FFM) increased significantly more in the HP group as compared to the LP group (p=0.009), going from 47.1 ± 4.5kg to 49.2 ± 5.4kg (+2.1kg) and from 48.1 ± 2.7kg to 48.7 ± 2 (+0.6kg) in the HP and LP groups, respectively. Fat mass significantly decreased over time in the HP group (14.1 ± 3.6kg to 13.0 ± 3.3kg; p<0.01) but no change was observed in the LP group (13.2 ± 3.7kg to 12.5 ± 3.0kg). While maximal strength significantly increased in both groups, there were no differences in strength improvements between the two groups. In aspiring female physique athletes, a higher protein diet is superior to a lower protein diet in terms of increasing FFM in conjunction with a resistance training program.

Muscle Damage Not Required For Muscle Growth In Resistance Training?

Muscle growth die to resistance may not be dependent on muscle damage (and subsequent repair of that damage) induced by training. If true, this is contrary to the paradigm of bodybuilding.  Abstract:

Resistance training (RT)-induced skeletal muscle hypertrophy is a highly intricate process. Despite substantial advances, we are far from understanding exactly how muscle hypertrophy develops during RT. The aim of the present review is to discuss new insights related to the role of skeletal muscle damage and muscle protein synthesis (MPS) in mediating RT-induced hypertrophy. Specifically, the thesis that in the early phase of RT (≤ 4 previous RT sessions) increases in muscle cross-sectional area are mostly attributable to muscle damage-induced muscle swelling; then (after ~ 10 sessions), a modest magnitude of muscle hypertrophy ensues; but only during a latter phase of RT (after ~ 18 sessions) is true muscle hypertrophy observed. We argue that the initial increases in MPS post-RT are likely directed to muscle repair and remodelling due to damage, and do not correlate with eventual muscle hypertrophy induced by several RT weeks. Increases in MPS post-RT session only contribute to muscle hypertrophy after a progressive attenuation of muscle damage, and even more significantly when damage is minimal. Furthermore, RT protocols that do not promote significant muscle damage still induce similar muscle hypertrophy and strength gains compared to conditions that do promote initial muscle damage. Thus, we conclude that muscle damage is not the process that mediates or potentiates RT-induced muscle hypertrophy.

Training Data: Morning Or Afternoon?

In general resistance training goes better in the afternoon than in the morning, although this morning deficit can be overcome by regular morning training.  Comparisons between control, morning, and afternoon resistance training groups show more or less similar responses in both morning and afternoon groups, but certain aspects of skeletal muscle cell signaling may differ. In my own experience, but performance seems better in the afternoon, but I still often to morning training when time allows for the sake of convenience, and it works well also; as the paper says, you can become adapted to either over time.  Abstract:

It has been clearly established that maximal force and power is lower in the morning compared to noon or afternoon hours. This morning neuromuscular deficit can be diminished by regularly training in the morning hours. However, there is limited and contradictory information upon hypertrophic adaptations to time-of-day-specific resistance training. Moreover, no cellular or molecular mechanisms related to muscle hypertrophy adaptation have been studied with this respect. Therefore, the present study examined effects of the time-of-day-specific resistance training on muscle hypertrophy, phosphorylation of selected proteins, hormonal concentrations and neuromuscular performance. Twenty five previously untrained males were randomly divided into a morning group (n = 11, age 23 ± 2 yrs), afternoon group (n = 7, 24 ± 4 yrs) and control group (n = 7, 24 ± 3 yrs). Both the morning and afternoon group underwent hypertrophy-type of resistance training with 22 training sessions over an 11-week period performed between 07:30-08:30 h and 16:00-17:00 h, respectively. Isometric MVC was tested before and immediately after an acute loading exclusively during their training times before and after the training period. Before acute loadings, resting blood samples were drawn and analysed for plasma testosterone and cortisol. At each testing occasion, muscle biopsies from m. vastus lateralis were obtained before and 60 min after the acute loading. Muscle specimens were analysed for muscle fibre cross-sectional areas (CSA) and for phosphorylated p70S6K, rpS6, p38MAPK, Erk1/2, and eEF2. In addition, the right quadriceps femoris was scanned with MRI before and after the training period. The control group underwent the same testing, except for MRI, between 11:00 h and 13:00 h but did not train. Voluntary muscle strength increased significantly in both the morning and afternoon training group by 16.9% and 15.2 %, respectively. Also muscle hypertrophy occurred by 8.8% and 11.9% (MRI, p < 0.001) and at muscle fibre CSA level by 21% and 18% (p < 0.01) in the morning and afternoon group, respectively. No significant changes were found in controls within these parameters. Both pre- and post-training acute loadings induced a significant (p < 0.001) reduction in muscle strength in all groups, not affected by time of day or training. The post-loading phosphorylation of p70S6Thr421/Ser424 increased independent of the time of day in the pre-training condition, whereas it was significantly increased in the morning group only after the training period (p < 0.05). Phosphorylation of rpS6 and p38MAPK increased acutely both before and after training in a time-of-day independent manner (p < 0.05 at all occasions). Phosphorylation of p70S6Thr389, eEF2 and Erk1/2 did not change at any time point. No statistically significant correlations were found between changes in muscle fibre CSA, MRI and cell signalling data. Resting testosterone was not statistically different among groups at any time point. Resting cortisol declined significantly from pre- to post-training in all three groups (p < 0.05). In conclusion, similar levels of muscle strength and hypertrophy could be achieved regardless of time of the day in previously untrained men. However, at the level of skeletal muscle signalling, the extent of adaptation in some parameters may be time of day dependent.

Aging, Androgens, Wnt, And Muscle

Fewer androgen receptors in muscle with age leads to less Wnt5a expression and that leads to less muscle - one explanation for muscle loss with age?  This study was in rats. Abstract:

We sought to determine whether age-related gastrocnemius muscle mass loss was associated with parallel decrements in androgen receptor (AR) or select Wnt signaling markers. To test this hypothesis, serum free and total testosterone (TEST) as well as gastrocnemius AR and Wnt signaling markers were analyzed in male Fischer 344 rats that were 3/6/12/18 and 24 months (mo) old (n=9 per group). Free and total TEST were greatest in 6 mo rats, and AR protein and Wnt5 protein levels linearly declined with aging. There were associations between Wnt5 protein levels and relative gastrocnemius mass (r=0.395, p=0.007) as well as AR and Wnt5 protein levels (r=0.670, p<0.001). We next tested the hypothesis that Wnt5 affects muscle fiber size by treating C2C12-derived myotubes lower (75 ng/mL) and higher (150 ng/mL) concentrations of recombinant Wnt5a protein. Both treatments increased myotube size (p<0.05) suggesting this ligand may affect muscle fiber size in vivo. We next tested if Wnt5a protein levels were androgen-modulated by examining 10 mo old male Fischer 344 rats (n=10-11 per group) that were orchiectomized and treated with testosterone-enanthate (TEST-E), trenbolone enanthate (TREN), a non-aromatizable synthetic testosterone analogue, or a vehicle (ORX only) for 4 weeks. Interestingly, TEST-E and TREN treatments increased Wnt5a protein in the androgen-sensitive levator ani/bulbocavernosus (LABC) muscle compared ORX only (p<0.05). To summarize, aromatizable and non-aromatizable androgens increase Wnt5a protein expression in skeletal muscle, age-related decrements in muscle AR may contribute Wnt5a protein decrements, and our in vitro data imply this mechanism may contribute to age-related muscle loss.

How Much Protein Can The Body Use In A Single Meal For Muscle-Building?

There is controversy about how much protein can be properly utilized by the body per meal for purposes of muscle building.  There is a school of thought that says that, essentially, anything over 20-25 grams per meal will be wasted; on the other hand, bodybuilding tradition advocated considerably higher per meal intakes (leading to much higher per day intakes compared to the typical recommendations).  A study examines the question and comes down on the side supporting the higher levels of protein intake; they write: “The preponderance of data indicate that while consumption of higher protein doses (> 20 g) results in greater AA oxidation, this is not the fate for all the additional ingested AAs as some are utilized for tissue-building purposes. Based on the current evidence, we conclude that to maximize anabolism one should consume protein at a target intake of 0.4 g/kg/meal across a minimum of four meals in order to reach a minimum of 1.6 g/kg/day. Using the upper daily intake of 2.2 g/kg/day reported in the literature spread out over the same four meals would necessitate a maximum of 0.55 g/kg/meal.”  Abstract:

Controversy exists about the maximum amount of protein that can be utilized for lean tissue-building purposes in a single meal for those involved in regimented resistance training. It has been proposed that muscle protein synthesis is maximized in young adults with an intake of ~ 20-25 g of a high-quality protein; anything above this amount is believed to be oxidized for energy or transaminated to form urea and other organic acids. However, these findings are specific to the provision of fast-digesting proteins without the addition of other macronutrients. Consumption of slower-acting protein sources, particularly when consumed in combination with other macronutrients, would delay absorption and thus conceivably enhance the utilization of the constituent amino acids. The purpose of this paper was twofold: 1) to objectively review the literature in an effort to determine an upper anabolic threshold for per-meal protein intake; 2) draw relevant conclusions based on the current data so as to elucidate guidelines for per-meal daily protein distribution to optimize lean tissue accretion. Both acute and long-term studies on the topic were evaluated and their findings placed into context with respect to per-meal utilization of protein and the associated implications to distribution of protein feedings across the course of a day. The preponderance of data indicate that while consumption of higher protein doses (> 20 g) results in greater AA oxidation, this is not the fate for all the additional ingested AAs as some are utilized for tissue-building purposes. Based on the current evidence, we conclude that to maximize anabolism one should consume protein at a target intake of 0.4 g/kg/meal across a minimum of four meals in order to reach a minimum of 1.6 g/kg/day. Using the upper daily intake of 2.2 g/kg/day reported in the literature spread out over the same four meals would necessitate a maximum of 0.55 g/kg/meal.

This conclusion is supported by this other study, which also advocates higher per meal protein intakes.

Please note that this advice – from these studies and not from this blog – deals with effects on muscle building and not overall health.  Whether or not additional protein intake is good for you is something that you need to determine in conjunction with your physician, nutritionist, etc.  For example, people with kidney problems or some digestive disorders probably should not be consuming this much protein, and then there is the issue of how much saturated fat is being consumed, if animal proteins are utilized.

So what is best for muscle building and what is best for overall health are not the same thing.

Perchance To Dream…But Not When Lifting

Muscle strength in lifting, particularly heavy compound movements, is impaired by lack of sufficient sleep; thus: 

Inadequate sleep impairs maximal muscle strength in compound movements when performed without specific interventions designed to increase motivation. Strategies to assist groups facing inadequate sleep to effectively perform resistance training may include supplementing their motivation by training in groups or ingesting caffeine; or training prior to prolonged periods of wakefulness.

If the situation is unavoidable, then do what you can, but the optimal thing is to just get enough sleep (easier said than done in many cases, I know….).

Creatine And Resistance Exercise For Older Individuals

Creatine supplementation has been shown to be helpful in building muscle mass and strength in older individuals undergoing resistance training; however, the mechanisms of action have not been definitively established.  Abstract:

The loss of muscle mass and strength with aging results in significant functional impairment. Creatine supplementation has been used in combination with resistance training as a strategy for increasing lean tissue mass and muscle strength in older adults, but results across studies are equivocal. We conducted a systematic review and meta-analysis of randomized controlled trials of creatine supplementation during resistance training in older adults with lean tissue mass, chest press strength, and leg press strength as outcomes by searching PubMed and SPORTDiscus databases. Twenty-two studies were included in our meta-analysis with 721 participants (both men and women; with a mean age of 57-70 years across studies) randomized to creatine supplementation or placebo during resistance training 2-3 days/week for 7-52 weeks. Creatine supplementation resulted in greater increases in lean tissue mass (mean difference =1.37 kg [95% CI =0.97-1.76]; p<0.00001), chest press strength (standardized mean difference [SMD] =0.35 [0.16-0.53]; p=0.0002), and leg press strength (SMD =0.24 [0.05-0.43]; p=0.01). A number of mechanisms exist by which creatine may increase lean tissue mass and muscular strength. These are included in a narrative review in the discussion section of this article. In summary, creatine supplementation increases lean tissue mass and upper and lower body muscular strength during resistance training of older adults, but potential mechanisms by which creatine exerts these positive effects have yet to be evaluated extensively.

Load And Resistance Training Results

Take home point: to build muscle only, one can use both heavy or lighter resistance.  To build strength, heavy is required.  Thus, if you want both, tend to train on the heavy side – but caveat emptor about injury risk and of course it is your responsibility to get medical consultation before starting any sort of physical activity program.  

Abstract:

The purpose of this paper was to conduct a systematic review of the current body of literature and a meta-analysis to compare changes in strength and hypertrophy between low- versus high-load resistance training protocols. Searches of PubMed/MEDLINE, Cochrane Library and Scopus were conducted for studies that met the following criteria: 1) an experimental trial involving both low- (≤60% 1 RM) and high- (>60% 1 RM) load training; 2) with all sets in the training protocols being performed to momentary muscular failure; 3) at least one method of estimating changes in muscle mass and/or dynamic, isometric or isokinetic strength was used; 4) the training protocol lasted for a minimum of 6 weeks; 5) the study involved participants with no known medical conditions or injuries impairing training capacity. A total of 21 studies were ultimately included for analysis. Gains in 1RM strength were significantly greater in favor of high- versus low-load training, while no significant differences were found for isometric strength between conditions. Changes in measures of muscle hypertrophy were similar between conditions. The findings indicate that maximal strength benefits are obtained from the use of heavy loads while muscle hypertrophy can be equally achieved across a spectrum of loading ranges.

Protein Types And Muscle Building

By Adrem68 at Dutch Wikipedia - Transferred from nl.wikipedia to Commons., Public Domain, https://commons.wikimedia.org/w/index.php?curid=3224328

Aging individuals lose muscle mass for a variety of reasons, one of which is reduced muscle protein being synthesized after ingestion of dietary protein.  A study has shown that animal proteins are more anabolic (muscle building) than plant proteins.  However, as the authors seem to have social and political motivations here (e.g., environmental concerns), they state mechanism whereby plant-based proteins can be more effective for muscle building: ingestion of a greater amount of protein, combining plant proteins to get a better intake of amino acids (“the mixing plant foods for a complete protein profile,” I assume), leucine co-ingestion, and “prior exercise or n-3 fatty acid supplementation” can better sensitize muscle to the protein. Abstract:

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.

More On CRISPR Gene Therapy

By Nielsrca - Own work based on figures in Nature Protocols, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=45011253

CRISPR: why the excitement?

Here’s a reason why – gene therapy for muscular dystrophy (in mice – [possibly showing potential for humans).  Abstract:

Rationale: Duchenne muscular dystrophy (DMD) is a severe inherited form of muscular dystrophy caused by mutations in the reading frame of the dystrophin gene disrupting its protein expression. Dystrophic cardiomyopathy is a leading cause of death in DMD patients and currently no effective treatment exists to halt its progression. Recent advancement in genome editing technologies offers a promising therapeutic approach in restoring dystrophin protein expression. However, the impact of this approach on DMD cardiac function has yet to be evaluated. Therefore, we assessed the therapeutic efficacy of CRISPR (clustered regularly interspaced short palindromic repeats)-mediated genome editing on dystrophin expression and cardiac function in mdx/Utr+/- mice after a single systemic delivery of recombinant adeno-associated virus (AAV). Objective: To examine the efficiency and physiological impact of CRISPR-mediated genome editing on cardiac dystrophin expression and function in dystrophic mice. Methods and Results: Here we packaged SaCas9/gRNA constructs into an AAV vector and systemically delivered them to mdx/Utr+/- neonates. We showed that CRIPSR-mediated genome editing efficiently excised the mutant exon 23 in dystrophic mice and immunofluorescence data supported the restoration of dystrophin protein expression in dystrophic cardiac muscles to a level approaching 40%. Moreover, there was a noted restoration in the architecture of cardiac muscle fibers and a reduction in the extent of fibrosis in dystrophin deficient hearts. The contractility of cardiac papillary muscles was also restored in CRISPR-edited cardiac muscles compared to untreated controls. Furthermore, our targeted deep sequencing results confirmed that our AAV-CRISPR-Cas9 strategy was very efficient in deleting the ~23 kb of intervening genomic sequences. Conclusions: This study provides evidence for using CRISPR-based genome editing as a potential therapeutic approach for restoring dystrophic cardiomyopathy structurally and functionally.

And then there is this:

Here we describe the correction of the heterozygous MYBPC3 mutation in human preimplantation embryos with precise CRISPR-Cas9-based targeting accuracy…

Train To Failure?

By Source, Fair use, https://en.wikipedia.org/w/index.php?curid=33634102

If Mike Mentzer (pictured at left), the champion of "heavy duty" training to failure, was still around, he’d probably not be pleased about this study. Abstract:

This study investigated the effects of a 10-week resistance training to failure on neuromuscular adaptations in young women. Eighty-nine active young women were randomly assigned to one of three groups: 1) repetitions to failure (RF; three sets of repetitions to failure); 2) repetitions not to failure with equalized volume (RNFV; four sets of 7 repetitions); and 3) repetitions not to failure (RNF; three sets of 7 repetitions). All groups performed the elbow flexor exercise (bilateral biceps curl) and trained 2 days per week using 70% of 1RM. There were significant increases (p<0.05) in muscle strength after 5 (15.9% for RF, 18.4% for RNF, and 19.9% for RNFV) and 10 (28.3% for RF, 26.8% for RNF, and 28.3% for RNFV) weeks of training, with no significant differences between groups. Additionally, muscular endurance increased after 5 and 10 weeks, with no differences between groups. However, peak torque (PT) increased significantly at 180°.s-1 in the RNFV (13.7%) and RNF (4.1%) groups (p<0.05), whereas no changes were observed in the RF group (-0.5%). Muscle thickness increased significantly (p<0.05) in the RF and RNFV groups after 5 (RF: 8.4% and RNFV: 2.3%) and 10 weeks of training (RF: 17.5%, and RNFV: 8.5%), whereas no significant changes were observed in the RNF group (3.9 and 2.1% after 5 and 10 weeks, respectively). These data suggest that short-term training of repetitions to failure do not yield additional overall neuromuscular improvements in young women.

Of course, there are caveats.  Does this apply only to young women?  The women were labeled as “active” – but one can argue that more advanced bodybuilders, as opposed to beginners, would require “training to failure” for optimum muscle growth.  Of course, many people, including top bodybuilders, grow muscle without training to failure, but some are these are genetically gifted people and some may be utilizing anabolic drugs. And who knows if they would have made more progress training differently.  Or, maybe not. Essentially, the “jury is still out” on this question.  I give no recommendations here.  Do what works best for you, and we will await further studies.