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Leucine supplementation of a low-protein mixed macronutrient beverage enhances myofibrillar protein synthesis in young men: A double-blind, randomized trial
Abstract
Leucine is a key amino acid involved in the regulation of skeletal muscle protein synthesis.
We assessed the effect of the supplementation of a lower-protein mixed macronutrient beverage with varying doses of leucine or a mixture of branched chain amino acids (BCAAs) on myofibrillar protein synthesis (MPS) at rest and after exercise.
In a parallel group design, 40 men (21 ± 1 y) completed unilateral knee-extensor resistance exercise before the ingestion of 25 g whey protein (W25) (3.0 g leucine), 6.25 g whey protein (W6) (0.75g leucine), 6.25 g whey protein supplemented with leucine to 3.0 g total leucine (W6+Low-Leu), 6.25 g whey protein supplemented with leucine to 5.0 g total leucine (W6+High-Leu), or 6.25 g whey protein supplemented with leucine, isoleucine, and valine to 5.0 g total leucine. A primed continuous infusion of l-[ring-(13)C6] phenylalanine with serial muscle biopsies was used to measure MPS under baseline fasted and postprandial conditions in both a rested (response to feeding) and exercised (response to combined feeding and resistance exercise) leg.
The area under the blood leucine curve was greatest for the W6+High-Leu group compared with the W6 and W6+Low-Leu groups (P < 0.001). In the postprandial period, rates of MPS were increased above baseline over 0-1.5 h in all treatments. Over 1.5-4.5 h, MPS remained increased above baseline after all treatments but was greatest after W25 (∼267%) and W6+High-Leu (∼220%) treatments (P = 0.002).
A low-protein (6.25 g) mixed macronutrient beverage can be as effective as a high-protein dose (25 g) at stimulating increased MPS rates when supplemented with a high (5.0 g total leucine) amount of leucine. These results have important implications for formulations of protein beverages designed to enhance muscle anabolism. This trial was registered at clinicaltrials.gov as NCT 1530646.
... As noted previously, early work in rodents (7,10) demonstrated that the independent provision of leucine enhanced MPS to a similar extent as supplying a complete mixture of all three BCAA. Similarly, some (31,32) , but not all (33,34) Accepted manuscript supplementation of a protein-containing meal (35,36,37,38) or leucine-enriched EAA intake (39) can further stimulate MPS rates in humans. Stimulation of postprandial MPS rates in response to EAA ingestion in humans appears contingent upon mTOR complex 1 (mTORC1) activation since administration of the mTORC1 inhibitor rapamycin blunts the postprandial stimulation of MPS rates in response to EAA ingestion (40) . ...
... As the current review is primarily focused on studies evaluating the effects of the provision of a complete mixture of isolated BCAA, the studies discussed in this review have provided BCAA as free amino acids. It is important to highlight that the included studies vary in that some have provided BCAA via intravenous infusion (133,134,135,136) , oral consumption (2,35,76,137,138,139,140,141,142,143,144,145) Accepted manuscript muscle (2,35,76,133,134,135,136,137,139,145) , studied participants under post-exercise conditions (35,76,138,139,140,141,142,143,144,145) , studied younger adults (2,35,76,133,134,135,136,138,139,140,141,142,143,144,145) , and studied older adults (137) . The included studies also vary in the BCAA dose and amount of energy provided, the corresponding ratio of isoleucine, leucine, and valine within a given dose, nature of the control/comparator treatment(s), and timing of sample collection. ...
... As the current review is primarily focused on studies evaluating the effects of the provision of a complete mixture of isolated BCAA, the studies discussed in this review have provided BCAA as free amino acids. It is important to highlight that the included studies vary in that some have provided BCAA via intravenous infusion (133,134,135,136) , oral consumption (2,35,76,137,138,139,140,141,142,143,144,145) Accepted manuscript muscle (2,35,76,133,134,135,136,137,139,145) , studied participants under post-exercise conditions (35,76,138,139,140,141,142,143,144,145) , studied younger adults (2,35,76,133,134,135,136,138,139,140,141,142,143,144,145) , and studied older adults (137) . The included studies also vary in the BCAA dose and amount of energy provided, the corresponding ratio of isoleucine, leucine, and valine within a given dose, nature of the control/comparator treatment(s), and timing of sample collection. ...
Branched-chain amino acids (BCAA: leucine, isoleucine, and valine) are three of the nine indispensable amino acids, and are frequently consumed as a dietary supplement by athletes and recreationally active individuals alike. The popularity of BCAA supplements is largely predicated on the notion that they can stimulate rates of muscle protein synthesis (MPS) and suppress rates of muscle protein breakdown (MPB), the combination of which promotes a net anabolic response in skeletal muscle. To date, several studies have shown that BCAA (particularly leucine) increase the phosphorylation status of key proteins within the mechanistic target of rapamycin (mTOR) signalling pathway involved in the regulation of translation initiation in human muscle. Early research in humans demonstrated that BCAA provision reduced indices of whole-body and MPB; however, there was no stimulatory effect of BCAA on MPS. In contrast, recent work has demonstrated that BCAA intake can stimulate postprandial MPS rates at rest and can further increase MPS rates during recovery after a bout of resistance exercise. The purpose of this evidence-based narrative review is to critically appraise the available research pertaining to studies examining the effects of BCAA on MPS, MPB, and associated molecular signalling responses in humans. Overall, BCAA can activate molecular pathways that regulate translation initiation, reduce indices of whole-body and MPB, and transiently stimulate MPS rates. However, the stimulatory effect of BCAA on MPS rates is less than the response observed following ingestion of a complete protein source providing the full complement of indispensable amino acids.
... The skeletal muscle plays a crucial role in maintaining body homeostasis, accounting for over 75% of all insulinmediated glucose disposal [9]. Disruptions in skeletal muscle function can negatively impact metabolic processes [9]; in contrast, muscle strength has a positive correlation with increased insulin sensitivity and a negative association with cardiovascular (CVD) risk and mortality [10][11][12][13]. Additionally, the loss of muscle mass (MM) is linked to intramuscular lipid infiltration, a characteristic commonly found in skeletal muscle in obese patients [8]. ...
... The primary metabolic process for preserving muscle mass in the body is protein turnover, which involves a balance between muscle protein synthesis and degradation [11]. The essential amino acids (EAAs), particularly leucine, are crucial in protein synthesis stimulation [12]. Dietary amino acids with exercise training induce a synergic effect on protein turnover, enhancing skeletal muscle mass [17]. ...
... The supplementation with branched-chain amino acids (BCAA) formulas was recently proposed as a promising approach to managing elderly obese or sarcopenic patients [12,16,[21][22][23]. These BCAA-based supplements have been shown to optimize muscle protein synthesis during an energy deficit, counteracting protein disarrangement and preserving energy homeostasis in acute and chronic hypercatabolic conditions without impacting on renal function [24,25]. ...
Background:
Weight loss is associated with a reduction in all body compartments, including muscle mass (MM), and this effect produces a decrease in function and muscle strength. Our objective was to assess the impact of protein or amino acid supplements on MM loss in middle-aged men (age < 65 years) with severe obesity (BMI > 35 kg/m2) during weight loss.
Materials and methods:
We conducted a single-site randomized controlled trial (Clinicaltrials.gov NCT05143398) with 40 in-patient male subjects with severe obesity. Participants underwent an intervention program consisting of a low-calorie balanced diet and structured physical activity. They were randomly assigned to 4-week treatment groups: (1) control (CTR, N = 10), (2) protein (P, N = 10), (3) branched-chain amino acid (BCAA, N = 10), and (4) essential amino acid mixture with tricarboxylic acid cycle intermediates (PD-E07, N = 10) supplementation.
Results:
Following 4 weeks of intervention, all groups showed similar reductions in body weight compared to baseline. When examining the delta values, a notable increase in muscle mass (MM) was observed in the PD-E07 intervention group [MM (kg): 2.84 ± 3.57; MM (%): 3.63 ± 3.14], in contrast to the CTR group [MM (kg): -2.46 ± 3.04; MM (%): -0.47 ± 2.28], with a statistical significance of p = 0.045 and p = 0.023, respectively. However, the MM values for the P group [MM (kg): -2.75 ± 5.98, p = 0.734; MM (%): -0.44 ± 4.02, p = 0.990] and the BCAA group [MM (kg): -1 ± 3.3, p = 0.734; MM (%): 0.34 ± 2.85, p = 0.956] did not exhibit a statistically significant difference when compared to the CTR group.
Conclusions:
Amino acid-based supplements may effectively mitigate the loss of MM typically observed during weight reduction. Further validation through large-scale studies is necessary.
... The BCAAs are Leucine, Isoleucine, and Valine, and benefits related to energy metabolism in the muscle are attributed to them [17]. Specifically, leucine has been shown to promote muscle protein synthesis, decrease central fatigue and improve performance [18][19][20][21][22]. ...
... Another study published by The American Journal of Clinical Nutrition [18] assesses the combination in the consumption of protein in different doses together with different amounts of leucine, as well as the improvement in the synthesis of muscle protein associated with this consumption. The results show that the addition of a higher dose of leucine to a smaller amount of protein (6.25 g) improved the myofibrillar protein synthesis rate (MPS) to the same level as that observed with four times more protein of serum (25 g). ...
... The results show that the addition of a higher dose of leucine to a smaller amount of protein (6.25 g) improved the myofibrillar protein synthesis rate (MPS) to the same level as that observed with four times more protein of serum (25 g). That is, suboptimal protein doses may be more effective in stimulating MPS by adding a high proportion of free leucine [18]. Although more work is needed on this idea, in addition to protein intake, evidence supports an acute intake of 700-3000 mg of leucine, in addition to a balanced range of EAA [20,50,51]. ...
Recent years have seen a rise in the popularity of the consumption of sports-related supplements. However, the hypothesis is raised that it is necessary to analyze the quality aspects of these supplements in relation to the information provided on the label, to avoid associated risks and obtain the greatest possible benefit from their consumption. Therefore, the aim of this study has been to carry out an analysis or screening of the protein supplements that are currently marketed in Spain. We analyzed the labels of 52 protein sports supplements available both in physical stores and online. The analysis consisted of addressing three relevant aspects considering the labeling: (a) the legislative framework in which the supplements are marketed, (b) the quality of the protein, and (c) the presence of other ingredients according to the specifications of the label. In the legislative context, there do not seem to be any specific regulations to guarantee consumer protection, which can lead to unfair practices and misleading advertising. Most of the supplements analyzed to comply with the requirements of their current regulations. However, claims about their benefits that are not allowed under European legislation have been found in some of them. Regarding composition and according to label information, the supplements have been found to provide a sufficient dose of protein in terms of recommended protein intake per serving. Regarding the presence of other ingredients and according to the information on the label, most of them, except for egg supplements, contain other ingredients. Colostrum was also found in one of the supplements evaluated. The conclusions of the study reveal that, due to a lack of knowledge or misleading advertising practices, supplements are often not used properly. The information provided is essential for both professionals and consumers to avoid the risks associated with consumption, such as unintentional doping, interactions between ingredients that reduce the quality of the supplement, and consumption of supplements inappropriately, among others.
... Ingestion of an adequate dose of protein results in subsequent hyperaminoacidemia and stimulation of myofibrillar protein synthesis (MyoPS) in humans (Rennie et al. 2004). In addition, supplementation of fast and slow digestible proteins (e.g., whey and casein) enriched with crystalline leucine results in a rapid and sustained increase in circulating essential amino acids and effectively stimulates MyoPS in young and old adults Churchward-Venne et al. 2014;Kramer et al. 2015;Kramer et al. 2017). Milk-based proteins have the highest protein quality scores, whether measured as protein digestibility-corrected amino acid score or digestible indispensable amino acid score (FAO 2013). ...
... The participants visited the laboratory on eleven separate occasions, and specific details of the study design appear in Fig. 2. At least one week before the oral deuterium oxide intake sessions for determining MyoPS and the underpinning mechanisms, study participants underwent familiarization with the study protocol and a whole-body dualenergy X-ray absorptiometry scan (GE-Lunar iDXA; Aymes Medical, Newmarket, ON) to measure body composition. Additionally, participants performed unilateral/contralateral strength testing, which involved a five repetition maximum (RM) test of standard seated leg press and seated leg extension exercise in the same manner as previously described Churchward-Venne et al. 2014;Oikawa et al. 2020). Following baseline testing, participants began an 11-day controlled diet designed to meet Appl. ...
... The protein and leucine-enriched bar supplement contained ∼16 g of a blend of micellar casein (AMCO, Burlington, NJ, USA), whey protein (Hilmar, Hilmar, CA, USA), whey protein hydrolysate (Hilmar, Hilmar, CA, USA), 1.5 g of freeleucine (Ajinomoto, Raleigh, NC, USA), 22 g low-glycemic carbohydrates (Ciranda, Hudson, WI, USA), and 11 g monounsaturated fat (Golden Barrel, Honey Brook, PA, USA). The total leucine content of the bar was ∼3 g, which results in a robust elevation in aminoacidemia (particularly leucinemia) and previous studies indicate that leucinemia induces stimulation of MyoPS at the vastus lateralis (Churchward-Venne et al. 2014;Devries et al. 2018a;Traylor et al. 2021). Covance (Eurofins) produced the bars; their nutrient content is given in Table 2. ...
Leucine is a critical amino acid stimulating myofibrillar protein synthesis (MyoPS). The consumption of higher leucine-containing drinks stimulates MyoPS, but we know less about higher leucine solid foods. Here, we examined the effect of short-term resistance exercise training (STRT) combined with supplementation of a protein and leucine-enriched bar, compared with STRT alone, on integrated (%/day) rates of MyoPS and anabolic protein signaling. In a nonblinded, randomized crossover trial, eight young adults performed four sessions of STRT without or while consuming the study bar (STRT+Leu, 16 g of protein containing ∼3 g of leucine) for two 4-day phases, separated by 2 days nonexercise (Rest) washout. In combination with serial muscle biopsies, deuterated water permitted the measurement of MyoPS and protein signaling phosphorylation. MyoPS during STRT (1.43 ± 0.06%/day) and STRT+Leu (1.53 ± 0.06%/day) were greater than Rest (1.31 ± 0.05%/day), and MyoPS during STRT+Leu (1.53 ± 0.06%/day) was greater than STRT alone (1.43 ± 0.06%/day). STRT+Leu increased the ratio of phosphorylated to total mechanistic target of rapamycin and 4EBP1 compared to Rest. Engaging in STRT increased integrated MyoPS and protein signaling in young adults and was enhanced with increased protein intake derived from a leucine-enriched protein bar. This study was registered at clinicaltrials.gov as NCT03796897.
... The aliphatic side chain of BCAAs, featuring a branch of a carbon atom attached to three or more carbon atoms, confers high hydrophobicity, making BCAAs particularly effective in maintaining the stability of folded proteins and performing functions for globular proteins [20,21]. Leucine, for example, is considered the most effective BCAA for stimulating muscle protein synthesis and muscle hypertrophy, acting as a "trigger" and turning on the synthesis of new muscle protein [22]. While the effectiveness of protein supplementation in muscle hypertrophy and performance is well documented, the role of BCAAs alone is less clear. ...
... Numerous studies have shown that BCAA supplementation may improve muscle hypertrophy and strength performance [23]. However, conflicting evidence exists regarding their efficacy compared to complete protein supplements that provide all essential amino acids [22,24]. ...
Background:
Branched-chain amino acids (BCAAs) are widely studied for their effects on muscle recovery and performance.
Aims:
This study examined the effects of BCAA supplementation on anthropometric data, physical performance, delayed onset muscle soreness (DOMS), and fatigue in recreational weightlifters.
Methods:
The trial involved 100 participants (50 men and 50 women), randomized into BCAA and placebo groups. Subjects in the BCAA group took five daily capsules of 500 mg L-leucine, 250 mg L-isoleucine, and 250 mg L-valine for six months. A two-way ANOVA was used to analyze the main and interaction effects of sex and treatment.
Results:
Notable findings include significant improvements in muscle recovery, as indicated by reduced DOMS, particularly in women who showed a decrement of 18.1 ± 9.4 mm compared to 0.8 ± 1.2 mm in the placebo group of a horizontal 100 mm line. Fatigue perception was also significantly lower in the BCAA group, with women reporting a greater decrease (2.6 ± 1.5 scores) compared to the placebo group (0.6 ± 0.7 scores). Strength gains were prominent, especially in men, with a 10% increase in bench press maximum observed in the BCAA group. The interaction between sex and treatment was significant, suggesting sex-specific responses to BCAA supplementation.
Conclusions:
These results underscore the effectiveness of BCAA supplementation in enhancing muscle recovery, reducing fatigue, and improving strength. This study also highlights sex-specific responses, with women benefiting more in terms of DOMS and fatigue reduction, while men experienced greater strength gains, suggesting a need for tailored supplementation strategies.
... MPS only remained elevated 3e5 h postexercise following 25 g WP consumption, likely due to EAA availability being rate limiting with the other supplements [74]. However, the same authors later demonstrated MPS to remain elevated 1.5e4.5 h post-exercise to a greater extent following both 25 g WP (~267%) and high-dose LEU-enriched WP (6.25 g WP, 5 g LEU) (~220%) [121]. However, MPS in this study [121] was calculated over a different time-period (0e1.5 h and 1.5e4.5 h post-feed) compared to the previous study (1e3 h and 3e5 h post-feed) [74]. ...
... However, the same authors later demonstrated MPS to remain elevated 1.5e4.5 h post-exercise to a greater extent following both 25 g WP (~267%) and high-dose LEU-enriched WP (6.25 g WP, 5 g LEU) (~220%) [121]. However, MPS in this study [121] was calculated over a different time-period (0e1.5 h and 1.5e4.5 h post-feed) compared to the previous study (1e3 h and 3e5 h post-feed) [74]. Importantly, it should be highlighted that the timings of SKM biopsies following exercise and nutritional interventions are crucial in determining rates of acute MPS. ...
Muscle protein synthesis (MPS) and muscle protein breakdown (MPB) are influenced through dietary protein intake and physical (in)activity, which it follows, regulate skeletal muscle (SKM) mass across the lifespan. Following consumption of dietary protein, the bio-availability of essential amino acids (EAA), and primarily leucine (LEU), drive a transient increase in MPS with an ensuing refractory period before the next MPS stimulation is possible (due to the "muscle full" state). At the same time, MPB is periodically constrained via reflex insulin actions. Layering exercise on top of protein intake increases the sensitivity of SKM to EAA, therefore extending the muscle full set-point (∼48 h), to permit long-term remodelling (e.g., hypertrophy). In contrast, ageing and physical inactivity are associated with a premature muscle full set-point in response to dietary protein/EAA and contractile activity. Of all the EAA, LEU is the most potent stimulator of the mechanistic target of rapamycin complex 1 (mTORC1)-signalling pathway, with the phosphorylation of mTORC1 substrates increasing ∼3-fold more than with all other EAA. Furthermore, maximal MPS stimulation is also achieved following low doses of LEU-enriched protein/EAA, negating the need for larger protein doses. As a result, LEU supplementation has been of long term interest to maximise muscle anabolism and subsequent net protein accretion, especially when in tandem with resistance exercise. This review highlights current knowledge vis-à-vis the anabolic effects of LEU supplementation in isolation, and in enriched protein/EAA sources (i.e., EAA and/or protein sources with added LEU), in the context of ageing, exercise and unloading states.
... are.22203514, Agergaard et al., 2017;Areta et al., 2014;Atherton et al., 2017;Beals et al., 2018;Borack et al., 2016;Brook et al., 2021;Bukhari et al., 2015;Burd et al., 2010Burd et al., , 2015Burd, Andrews, et al., 2012;Chan et al., 2019;Churchward-Venne, Breen, et al., 2014;Churchward-Venne, Cotie, et al., 2014;Devries et al., 2018aDevries et al., , 2018bDickinson et al., 2014;Dideriksen et al., 2016;Dreyer et al., 2008;Fujita et al., 2009;Gwin et al., 2021;Hermans et al., 2021Hermans et al., , 2022Luiking et al., 2014;McGlory et al., 2016;McKendry et al., 2016;Mikkelsen et al., 2015;Monteyne, Coelho, Porter, Abdelrahman, Jameson, Jackman, et al., 2020;Oikawa et al., 2020;Pinckaers et al., 2022;Reidy et al., 2013;Reitelseder et al., 2019;Symons et al., 2011;Van Vliet et al., 2017;West et al., 2009;Wilkinson et al., 2018). Studies which met all the inclusion criteria except not taking a basal muscle biopsy (i.e., Dideriksen et al., 2011) were excluded in order to calculate delta change from basal MPS. ...
... The lack of any observed associations, within this systematic review, may be explained by "noise" in the data being too great to pin down one single plasma variable, whereas the leucine dose represented a composite of the total protein dose and all postprandial leucinemic factors thereby revealing the relationship. However, once other variables are introduced, such as comparing different protein sources (Chan et al., 2019;Churchward-Venne, Breen, et al., 2014;Dideriksen et al., 2011;Reidy et al., 2013), isolated vs whole foods (Burd et al., 2015;Mitchell, McGregor, et al., 2015;Van Vliet et al., 2017), meal ingestion (Kim et al., 2016;Symons et al., 2011) or co-ingestion with other macronutrients (Gorissen et al., 2014;Hamer et al., 2013;Koopman et al., 2007;Staples et al., 2011), the relationship is far less clear. We Monteyne, Coelho, Porter, Abdelrahman, Jameson, Jackman, et al., 2020;West et al., 2022) and others (Burd et al., 2015;Chan et al., 2019;Van Vliet et al., 2017) have observed a dissociation between circulating leucine concentrations and MPS in a series of recent studies, specifically involving whole food approaches. ...
Background
Dietary protein ingestion augments post (resistance) exercise muscle protein synthesis (MPS) rates. It is thought that the dose of leucine ingested within the protein (leucine threshold hypothesis) and the subsequent plasma leucine variables (leucine trigger hypothesis; peak magnitude, rate of rise, and total availability) determine the magnitude of the postprandial postexercise MPS response.
Methods
A quantitative systematic review was performed extracting data from studies that recruited healthy adults, applied a bout of resistance exercise, ingested a bolus of protein within an hour of exercise, and measured plasma leucine concentrations and MPS rates (delta change from basal).
Results
Ingested leucine dose was associated with the magnitude of the MPS response in older, but not younger, adults over acute (0–2 h, r ² = 0.64, p = 0.02) and the entire postprandial (>2 h, r ² = 0.18, p = 0.01) period. However, no single plasma leucine variable possessed substantial predictive capacity over the magnitude of MPS rates in younger or older adults.
Conclusion
Our data provide support that leucine dose provides predictive capacity over postprandial postexercise MPS responses in older adults. However, no threshold in older adults and no plasma leucine variable was correlated with the magnitude of the postexercise anabolic response.
... Acute leucine supplementation in young and elderly human populations has been found to increase muscle protein synthesis [93][94][95][96][97][98]. Limited works explore leucine supplementation during CC. ...
... Currently, all data specifically exploring the relationship between leucine supplementation and CC symptomology attenuation seem to remain solely in pre-clinical animal models and will be described in this review. Acute leucine supplementation in young and elderly human populations has been found to increase muscle protein synthesis [93][94][95][96][97][98]. Limited works explore leucine supplementation during CC. ...
Cancer cachexia (CC) is a complex syndrome of bodily wasting and progressive functional decline. Unlike starvation, cachexia cannot be reversed by increased energy intake alone. Nonetheless, targeted nutritional support is a necessary component in multimodal syndrome management. Due to the highly catabolic nature of cancer cachexia, amino acid supplementation has been proposed. Interestingly, leucine has been found to increase protein synthesis and decrease protein degradation via mTORC1 pathway activation. Multiple pre-clinical studies have explored the impact of leucine supplementation in cachectic tumor-bearing hosts. Here, we provide an overview of leucine’s proposed modes of action to preserve lean mass in cachexia and review the current pre-clinical literature related to leucine supplementation during CC. Current research indicates that a leucine-rich diet may attenuate CC symptomology; however, these works are difficult to compare due to methodological differences. There is need for further pre-clinical work exploring leucine’s potential ability to modulate protein turnover and immune response during CC, as well as the impact of additive leucine on tumor growth.
... The intake of protein is expected to increase the serum levels of amino acids, and most, if not all, amino acid concentrations peak 30-60 min after a protein-rich meal [27][28][29][30]. We therefore measured the concentration of 28 different amino acids and amino acid derivatives in serum 30 and 60 min postprandially using HPLC-MS/MS ( Figure 2). ...
... We found that 22 out of 28 amino acids/amino acid derivatives increased significantly after the intake of protein ( Figure 2 and Figure S1). Most of these amino acids reached the highest concentration after 60 min, while some seemed to peak at 30 min, in line with what has been reported earlier [27][28][29][30]. While no differences in the total amino acid or total essential amino acid concentration were observed between the intake of fishmeal and whey, the difference in the postprandial response was significant for cystathionine and 2-aminobutyric acid (AMBA) and for the four amino acids arginine, glycine, methionine and serine, which all appeared to give a larger or faster increase with fishmeal as compared to whey (Figure 2). ...
Fish is considered an important part of a healthy diet, in part due to the content of long chain omega-3 fatty acids. However, both lean and fatty fish have beneficial health effects, suggesting that micronutrients and proteins may play a role. In a randomised, controlled, cross-over trial, five healthy male participants consumed 5.2 g of protein from either salmon fishmeal or whey. Blood samples were taken before and 30 and 60 min after intake. The concentration of glucose, lipids, hormones and metabolites, including 28 different amino acids and derivatives, were measured in serum or plasma. Cultured HepG2 cells were incubated with or without serum from the participants, and transcriptomic profiling was performed using RNA sequencing. The ingestion of both salmon fishmeal and whey reduced the glucose and triglyceride levels in serum. Protein intake, independent of the source, increased the concentration of 22 amino acids and derivatives in serum. Fishmeal increased the concentration of arginine, methionine, serine, glycine, cystathionine and 2-aminobutyric acid more than whey did. Incubation with postprandial serum resulted in large transcriptomic alterations in serum-fasted HepG2 cells, with the differential expression of >4500 protein coding genes. However, when comparing cells cultivated in fasting serum to postprandial serum after the ingestion of fishmeal and whey, we did not detect any differentially regulated genes, neither with respect to the protein source nor with respect to the time after the meal. The comparable nutrigenomic effects of fishmeal and whey do not change the relevance of fish by-products as an alternative food source.
... Muscle protein synthesis and whole-body net protein balance demonstrate a dose-response to ingested protein (Holwerda et al., 2019;Moore et al., 2009;Park et al., 2020;Witard et al., 2014), which may be influenced in part by the leucine content of the protein and/or subsequent circulating leucinamia (Churchward-Venne et al., 2014). Consistent with the anabolic potential of leucine, a leucine dose-response was observed for dietary leucine oxidation that, due to a similar relative percentage ingested oxidation between conditions, translated into a reciprocal dose-response in leucine retention that was greatest in WPI and lowest in NEAA. ...
Marine-derived proteins, such as blue whiting-derived protein hydrolysates (BWPH), represent high-quality sources of dietary protein, but their ability to support postexercise anabolism is not established. The impact of BWPH on whole-body anabolism was compared with an isonitrogenous whey protein isolate (WPI) and nonessential amino acid (NEAA) control in 10 trained young males (31 ± 4 years) who, on three separate visits, performed a session of whole-body resistance exercise and then consumed, in randomized crossover fashion, BWPH, WPI, or NEAA (0.33 g/kg; 19, 33, and 0 mg/kg leucine, respectively) with L-[1-13 C]leucine. Breath, blood, and urine samples were collected for 6-hr postprandial to assess dietary leucine oxidation, amino acid (AA) concentrations, and 3-methylhistidine: creatinine ratio. Peak and area under the curve concentrations for leucine, branched-chain amino acids, and essential amino acids were greater in WPI compared with BWPH (all p < .05) but with no differences in time to peak concentration. Total oxidation reflected leucine intake (WPI > BWPH > NEAA; p < .01), whereas relative oxidation was greater (p < .01) in WPI (28.6 ± 3.6%) compared with NEAA (21.3 ± 4.2%), but not BWPH (28.6 ± 8.8%). Leucine retention, a proxy for whole-body protein synthesis, was greater in WPI (185.6 ± 9.5 μmol/kg) compared with BWPH (109.3 ± 14.1 μmol/kg) and NEAA (5.74 ± 0.30 μmol/kg; both p < .01), with BWPH being greater than NEAA (p < .01). Urinary 3-methylhistidine: creatinine ratio did not differ between conditions. Both WPI and BWPH produced essential aminoacidemia and supported whole-body anabolism after resistance exercise, but a higher intake of BWPH to better approximate the leucine and EAA content of WPI may be needed to produce an equivalent anabolic response.
... Also, testing the effect of an acute gavage of leucine/KIC is a limitation, as people typically consume BCAA daily, in a chronic manner. However, it is important to elucidate how leucine/KIC gavage acutely affects specific mechanisms related to health because of the increasing prevalence of the use of single amino acids for anabolic effects [78,79] and overall health [80,81]. Future long-term studies are warranted to see if long term treatment of KIC differs in its effect from an acute gavage. ...
Plasma levels of branched-chain amino acids and their metabolites, the branched-chain ketoacids are increased in insulin resistance. Our previous studies showed that leucine and its metabolite KIC suppress insulin-stimulated glucose uptake in L6 myotubes along with the activation of the S6K1-IRS-1 pathway. Because other tissue and fiber types can be differentially regulated by KIC, we analyzed the effect of KIC gavage on whole-body insulin sensitivity and insulin signaling in vivo. We hypothesized that KIC gavage would reduce whole-body insulin sensitivity and increase S6K1-IRS-1 phosphorylation in various tissues and muscle fibers. Five-week-old male Sprague-Dawley rats were starved for 24 hours and then gavaged with 0.75ml/100g of water, leucine (22.3g/L) or KIC (30g/L) twice, ten minutes apart. They were then euthanized at different time points post-gavage (0.5-3h), and muscle, liver, and heart tissues were dissected. Other sets of gavaged animals underwent an insulin tolerance test. Phosphorylation (ph) of S6K1 (Thr389), S6 (Ser235/6) and IRS-1 (Ser612) was increased at 30 minutes post leucine gavage in skeletal muscles irrespective of fiber type. Ph-S6 (Ser235/6) was also increased in liver and heart 30 minutes after leucine gavage. KIC gavage increased ph-S6 (Ser235/6) in the liver. Neither Leucine nor KIC influenced whole-body insulin tolerance, nor ph-Akt (Ser473) in skeletal muscle and heart. BCKD-E1 α abundance was highest in the heart and liver, while ph-BCKD-E1 α (Ser293) was higher in the gastrocnemius and EDL compared to the soleus. Our data suggests that only leucine activates the S6K1-IRS-1 signaling axis in skeletal muscle, liver and heart, while KIC only does so in the liver. The effect of leucine and KIC on the S6K1-IRS-1 signaling pathway is uncoupled from whole-body insulin sensitivity. These results suggest that KIC and leucine may not induce insulin resistance, and the contributions of other tissues may regulate whole-body insulin sensitivity in response to leucine/KIC gavage.
... 19 In a double-blind trial of low-protein mixed macronutrient beverages with the BCAA Leucine supplemented, Churchward-Venne et al. concluded that muscle protein synthesis rates are increased with a high concentration of leucine by measuring myofibrillar protein. 3 Leucine is essential for inhibiting Sestrin-2 for the amino-acid-dependent MTORC1 activation in muscle cells protein synthesis at the lysosome. In the study, the investigators gave a high concentration (5.0 g total leucine) plus 6 grams of whey protein supplementation to supply an increase in myofibrillar protein synthesis in young men and elevated leucine levels in the blood amino acids, including Arginine for inhibition of TSC1 and TSC1 at the ribosome and to allow and to allow Rheb GTP to bind mTORC1 and activate it for protein synthesis. ...
Introduction: Prior studies of the acute benefits of protein supplementation have determined a benefit in improving post-exercise muscle anabolism and aiding the recovery of muscle function and performance. Previous acute protein supplement studies in post-exercise protein synthesis and anabolic intracellular signaling reported no attenuation in muscle damage or elevated muscle function. The aim of this study is to implement a specific content of essential amino acids with resistance and aerobic exercises to quantify the difference in strength, endurance, and flexibility during the delayed onset muscle soreness common with a new exercise protocol. Methods: We enrolled 42 participants (22 EAA and 20 Controls) completed an hour-long aerobic and resistance exercise protocol including flexibility, resistance, and aerobic exercises for three consecutive days. The study participants were randomly assigned to the EAA (6.6g) per day (EAA + Gatorade) group or the control (Gatorade) group. The data was analyzed in a double-blinded format. Results: Both groups improved the initial flexibility respectively throughout the three exercise days but were not significantly different (p=0.32) in the sit and reach. For the resistance/power activities, the EAA group improved in the repetitions for push-ups (p=0.014 vs 0.21) and dips (0.0002 vs 0.59) compared to the controls. The EAA group was faster although not statistically significant in the 20-meter sprint and improved in the 1.5-mile run during the third day (P=0.002 vs 0.48) compared to the control group. Conclusions: The data in the results supports that acute ingestion of the essential amino acid supplements provides increased physical performance and decreases the DOMS symptoms in sedentary participants over the three-day trial period of exercise.
... Studies suggest that hydroxy methyl butyrate (HMB) may play a beneficial role in maintaining and building muscle mass, with randomized control trials indicating its positive impact in cancer patients and older adults. Further well-designed and high-quality trials are required to comprehensively explore broader clinical benefits of leucine and HMB supplementation [36,[53][54][55][56][57][58]. ...
Sarcopenia is a widely prevalent skeletal muscle condition that progresses over time and is associated with adverse outcomes. It is characterized by an accelerated loss of muscle mass and functional ability. Proposed causes of sarcopenia include aging, physical inactivity, malnutrition, hormonal disturbances, inflammation, and neurodegenerative changes. According to the IAPEN INDIA (India Association for Parenteral and Enteral Nutrition), nutritional management should be integrated into the diagnostic process for all chronic diseases, including cancer. Studies recommend aggressive nutritional management, providing an energy intake of >30 kcal/kg/day and protein intake of >1.2g/kg/day for patients with sarcopenia. Published literature suggests that adequate intake of antioxidants, such as vitamin D, E, and C, along with Omega-3 fatty acids, creatine, and L-carnitine, might be beneficial for preserving and improving sarcopenia, and functional outcomes. In summary, nutritional management complemented with resistance exercise, under strict supervision, is key to preventing and treating sarcopenia in cancer patients.
... In our study, we fed older males 25 g of protein twice daily, with each serving of whey and pea protein-containing twice the amount of EAAs and 140% (1.68 g) and 131% (1.62 g) more leucine, respectively, compared with collagen (0.70 g). Combining the protein supplement (whey and pea) with the breakfast and lunch meals likely surpassed the muscle-specific leucine threshold necessary to switch on the protein synthetic machinery, containing the EAAs needed to maintain a heightened MPS response to feeding [43][44][45][46]. However, the limited EAA, particularly leucine, content in the collagen supplement was likely insufficient to initiate an acute increase in MPS, which, when repeated, led to lower rates of integrated MPS. ...
... However, RETgenerated mechanical signaling can result in dramatically different strength outcomes between individuals despite their training being of similar intensity (10,11), so those engaged in weight lifting often manipulate training variables, modify their diet, and/or use dietary supplements in an attempt to facilitate anabolic responses to their training efforts. High-protein diets, protein supplements (12)(13)(14), and supplements such as beta-hydroxy beta-methyl butyrate (HMB) and creatine (15)(16)(17) can help optimize post-exercise muscle protein synthesis. Additionally, safe, conveniently dosed, plant-based products are increasingly being explored for their ability to support RET responses. ...
Resistance exercise training (RET) is used to improve muscular strength and function. This study tested the hypothesis that RET alongside daily supplementation of a Sphaeranthus indicus and Mangifera indica extract blend (SMI) would augment bench press (BP) and leg extension (LE) strength and repetitions to failure (RTF) compared to RET alone. Ninety-nine men (age 22 ± 3) completed the trial after randomization into one of four groups: (A1) 425 mg SMI plus one RET set; (A2) 850 mg SMI plus one RET set; (P1) placebo plus one RET set; and (P2) placebo plus two RET sets. RET sets were 6–8 BP and LE repetitions at 80% of a progressive one repetition maximum (1-RM), performed 3x/week for 8 weeks. Strength and RTF were evaluated at baseline and days 14, 28, and 56 while serum values of total testosterone (TT), free testosterone (FT), and cortisol (C) values were evaluated at baseline and day 56. RET significantly (p < 0.05) increased 1-RM, RTF, and T measures above baselines regardless of group assignment, but the increases were greater in the supplemented groups. At week 8, A1 bench pressed more than P1 (71.5.5 ± 17.5 kg vs. 62.0 ± 15.3 kg, p = 0.003), while A2 pressed 13.8 ± 3.0 kg more (95% CI 5.7–21.8, p < 0.001) than P1 and 9.9 ± 13.0 kg more (95% CI 1.7–18.2, p = 0.01) than P2. Also at week 8, the mean LE 1-RM of A1 (159.4 ± 22.6 kg) and A2 (162.2 ± 22.9 kg) was greater (p < 0.05) than that of P1 (142.2 ± 25.6 kg) and P2 (146.5 ± 19.7 kg). Supplementation improved RTF, TT, and FT values over those measured in exercise alone (p < 0.05), while C levels in A2 (9.3 ± 3.8 μg/dL) were lower than P2 (11.7 ± 3.8 μg/dL, p < 0.05). Daily supplementation with SMI was well tolerated and may help optimize muscle adaptive responses to RET in men.
... These include limits to the number (and therefore timing) of muscle biopsy collections, which restrict the temporal resolution of the data (at least compared with that of in vitro or rodent studies). To illustrate, in vivo, evidence in humans has demonstrated that even small (0.75-3 g) quantities of leucine-enriched IAAs and branched-chain amino acids alone are capable of robustly stimulating MPS rates [32,[50][51][52][53]. In these cases, however, MPS typically rises only transiently compared with larger boluses, delivering what is essentially an optimal magnitude response but for a suboptimal duration [32,52]. ...
The regulation of postprandial muscle protein synthesis (MPS) with or without physical activity has been an intensely studied area within nutrition and physiology. The leucine content of dietary protein and the subsequent plasma leucinemia it elicits postingestion is often considered the primary drivers of the postprandial MPS response. This concept, generally known as the leucine “trigger” hypothesis, has also been adopted within more applied aspects of nutrition. Our view is that recent evidence is driving a more nuanced picture of the regulation of postprandial MPS by revealing a compelling dissociation between ingested leucine or plasma leucinemia and the magnitude of the postprandial MPS response. Much of this lack of coherence has arisen as experimental progress has demanded relevant studies move beyond reliance on isolated amino acids and proteins to use increasingly complex protein-rich meals, whole foods, and mixed meals. Our overreliance on the centrality of leucine in this field has been reflected in 2 recent systematic reviews. In this perspective, we propose a re-evaluation of the pre-eminent role of these leucine variables in the stimulation of postprandial MPS. We view the development of a more complex intellectual framework now a priority if we are to see continued progress concerning the mechanistic regulation of postprandial muscle protein turnover, but also consequential from an applied perspective when evaluating the value of novel dietary protein sources.
... These data are in line with previous work from our group (Aussieker et al., 2023;Gorissen et al., 2016) as well as others Yang et al., 2012) and show the impact of ingesting a high-quality protein source, such as whey, on postprandial plasma amino acid concentrations during recovery from exercise. It has been well established that the postprandial increase in plasma EAA concentrations, and plasma leucine in particular, following ingestion of 20-30 g whey protein strongly increases myofibrillar protein synthesis rates during recovery from exercise (Churchward-Venne et al., 2013;Witard et al., 2014;Yang et al., 2012). However, whey protein ingestion during recovery from exercise does not seem to augment muscle connective protein synthesis rates (Aussieker et al., 2023;Mikkelsen et al., 2015). ...
Whey protein ingestion during recovery from exercise increases myofibrillar but not muscle connective protein synthesis rates. It has been speculated that whey protein does not provide sufficient glycine to maximize postexercise muscle connective protein synthesis rates. In the present study, we assessed the impact of coingesting different amounts of collagen with whey protein as a nutritional strategy to increase plasma glycine availability during recovery from exercise. In a randomized, double-blind, crossover design, 14 recreationally active men (age: 26 ± 5 years; body mass index: 23.8 ± 2.1 kg·m ⁻² ) ingested in total 30 g protein, provided as whey protein with 0 g (WHEY), 5 g (WC05); 10 g (WC10), and 15 g (WC15) of collagen protein immediately after a single bout of resistance exercise. Blood samples were collected frequently over 6 hr of postexercise recovery to assess postprandial plasma amino acid kinetics and availability. Protein ingestion strongly increased plasma amino acid concentrations ( p < .001) with no differences in plasma total amino acid availability between treatments ( p > .05). The postprandial rise in plasma leucine and essential amino acid availability was greater in WHEY compared with the WC10 and WC15 treatments ( p < .05). Plasma glycine and nonessential amino acid concentrations declined following whey protein ingestion but increased following collagen coingestion ( p < .05). Postprandial plasma glycine availability averaged −8.9 ± 5.8, 9.2 ± 3.7, 23.1 ± 6.5, and 39.8 ± 11.0 mmol·360 min/L in WHEY, WC05, WC10, and WC15, respectively (incremental area under curve values, p < .05). Coingestion of a small amount of collagen (5 g) with whey protein (25 g) is sufficient to prevent the decline in plasma glycine availability during recovery from lower body resistance-type exercise in recreationally active men.
... The postprandial increase in circulating EAA and leucine in particular, after protein 360 ingestion, is a key regulator of MPS rates (29)(30)(31)(32). While previous studies have examined the 361 effects of protein co-ingestion with carbohydrate (33)(34)(35) replace glucose as the primary fuel for the brain, supplying >50% of the brain's energy (44). ...
Background
Ketone bodies may have anabolic effects in skeletal muscle via their capacity to stimulate protein synthesis. Whether orally ingested exogenous ketones can stimulate postprandial myofibrillar protein synthesis (MyoPS) rates with and without dietary protein co-ingestion is unknown.
Objectives
This study aimed to evaluate the effects of ketone monoester intake and elevated blood β-hydroxybutyrate (β-OHB) concentration, with and without dietary protein co-ingestion, on postprandial MyoPS rates and mechanistic target of rapamycin complex 1 (mTORC1) pathway signaling.
Methods
In a randomized, double-blind, parallel group design, 36 recreationally active healthy young males (age: 24.2 ± 4.1 y; body fat: 20.9% ± 5.8%; body mass index: 23.4 ± 2 kg/m²) received a primed continuous infusion of L-[ring-²H5]-phenylalanine and ingested one of the following: 1) the ketone monoester (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (KET), 2) 10 g whey protein (PRO), or 3) the combination of both (KET+PRO). Blood and muscle biopsy samples were collected during basal and postprandial (300 min) conditions to assess β-OHB, glucose, insulin, and amino acid concentrations, MyoPS rates, and mTORC1 pathway signaling.
Results
Capillary blood β-OHB concentration increased similarly during postprandial conditions in KET and KET+PRO, with both being greater than PRO from 30 to 180 min (treatment × time interaction: P < 0.001). Postprandial plasma leucine and essential amino acid (EAA) incremental area under the curve (iAUC) over 300 min was greater (treatment: both P < 0.001) in KET+PRO compared with PRO and KET. KET, PRO, and KET+PRO stimulated postprandial MyoPS rates (0–300 min) higher than basal conditions [absolute change: 0.020%/h; (95% CI: 0.013, 0.027%/h), 0.014%/h (95% CI: 0.009, 0.019%/h), 0.019%/h (95% CI: 0.014, 0.024%/h), respectively (time: P < 0.001)], with no difference between treatments (treatment: P = 0.383) or treatment × time interaction (interaction: P = 0.245). mTORC1 pathway signaling responses did not differ between treatments (all P > 0.05).
Conclusions
Acute oral intake of a ketone monoester, 10 g whey protein, or their co-ingestion in the overnight postabsorptive state elicit a similar stimulation of postprandial MyoPS rates in healthy young males.
This trial was registered at clinicaltrials.gov as NCT04565444 (https://clinicaltrials.gov/study/NCT04565444).
... Among EAAs, leucine (Leu) has been shown to be particularly important for MPS, as it is the only stimulator of mTORC1 signaling identified in muscle cells over the physiological range of amino acid levels in blood [6]. The amount of Leu in ingested proteins or EAA mixtures determines the extent of the MPS response at rest and after exercise [7][8][9][10][11]. The amino acid composition of whey protein is considered to be suitable for stimulating MPS, owing to its high Leu content and absorbability [12,13]. ...
Leucine (Leu), an essential amino acid, is known to stimulate protein synthesis in the skeletal muscle via mTOR complex 1 (mTORC1) activation. However, the intrinsic contribution of other amino acids to Leu-mediated activation of mTORC1 signaling remains unexplored. This study aimed to identify amino acids that can promote mTORC1 activity in combination with Leu and to assess the effectiveness of these combinations in vitro and in vivo. We found that tyrosine (Tyr) enhanced Leu-induced phosphorylation of S6 kinase (S6K), an indicator of mTORC1 activity, although it exerted no such effect individually. This booster effect was observed in C2C12 cells, isolated murine muscle, and the skeletal muscles of mice orally administered the amino acids. To explore the molecular mechanisms underlying this Tyr-mediated booster effect, the expression of the intracellular Leu sensors, Sestrin1 and 2, was suppressed, and the cells were treated with Leu and Tyr. This suppression enabled Tyr alone to induce S6K phosphorylation and enhanced the booster effect, suggesting that Tyr possibly contributes to mTORC1 activation when Sestrin-GAP activity toward Rags 2 (GATOR2) is dissociated through Sestrin knockdown or the binding of Sestrins to Leu. Collectively, these results indicate that Tyr is a key regulator of Leu-mediated protein synthesis.
... In one study, modest dosages of Leucine supplementation increased fat loss and efficiently boosted muscle protein synthesis in food-restricted rats (Rieu et al., 2004). Myofibrillar muscle protein synthesis in males can be stimulated by a low-protein (6.25 g) mixed macronutrient beverage including a high-protein (5 g total Leu) dosage (Churchward-Venne et al., 2014). In 1989 researchers looked at how men and women's paths diverged. ...
Leucine, a branched-chain amino acid, is essential in regulating animal growth and development. Recent research has uncovered the mechanisms underlying Leucine’s anabolic effects on muscle and other tissues, including its ability to stimulate protein synthesis by activating the mTORC1 signaling pathway. The co-ingestion of carbohydrates and essential amino acids enhances Leucine’s anabolic effects. Moreover, Leucine has been shown to benefit lipid metabolism, and insulin sensitivity, making it a promising strategy for preventing and treating metabolic diseases, including type 2 diabetes and obesity. While emerging evidence indicates that epigenetic mechanisms may mediate Leucine’s effects on growth and development, more research is needed to elucidate its mechanisms of action fully. Specific studies have demonstrated that Leucine promotes muscle growth and metabolic health in animals and humans, making it a promising therapeutic agent. However, it is essential to note that Leucine supplementation may cause digestive issues or interact with certain medications, and More study is required to determine definitively optimal dosages. Therefore, it is important to understand how Leucine interacts with other nutrients, dietary factors, and lifestyle habits to maximize its benefits. Overall, Leucine’s importance in human nutrition is far-reaching, and its potential to prevent muscle loss and enhance athletic performance warrants further investigation.
... While plantbased proteins have been considered inferior to animal or dairy-based proteins in the past due to sub-optimal amino acid profiles (Pinckaers et al. 2021;Shaw et al. 2022), recent evidence suggests plant-based protein to be no different than consuming whey protein for improving measures of body composition or strength when the plant-based protein contains a variety of sources to match the amino acid profile of whey (Nichele et al. 2022;Teixeira et al. 2022 be an interesting plant-based protein to choose as a singlesource protein or as the base for a plant-based protein due to a high concentration of branched-chain amino acids (leucine, isoleucine, and valine; BCAAs) (Wang et al. 2008). Leucine is important for stimulating the mammalian target of rapamycin complex, a pathway involved in muscle protein synthesis (Churchward-Venne et al. 2014;Condon and Sabatini 2019). Hemp also contains a high concentration of isoleucine and valine and has a high BCAA: tryptophan ratio. ...
Purpose
Hemp contains protein with high concentrations of the branched-chain amino acids leucine, isoleucine, and valine and oils that have anti-inflammatory properties. Our purpose was to investigate the effects of hemp supplementation during resistance training in trained young adults.
Methods
Males (n = 22, 29 ± 8y) and females (n = 12, 30 ± 9y) were randomized (double-blind) to receive 60 g/d of hemp (containing 40 g protein and 9 g oil) or 60 g/d of soy (matched for protein and calories) during eight weeks of resistance training (~ 4x/week). Before and after the intervention, participants were assessed for whole-body lean tissue and fat mass (dual-energy X-ray absorptiometry), regional muscle hypertrophy (ultrasound), strength (1-repetition maximum leg press, bench press, biceps curl), voluntary activation (interpolated twitch technique), resting twitch properties (single pulse; 0.5 ms) (before and after a fatigue test), markers of inflammation (Interleukin 6 and C-reactive protein), and bone resorption (urinary N-telopeptides).
Results
Hemp supplementation increased elbow flexor muscle thickness in females (2.6 ± 0.4–3.1 ± 0.5 cm, p = 0.012) while soy supplementation increased elbow flexor muscle thickness in males (3.7 ± 0.4–4.0 ± 0.5 cm, p < 0.01). Twitch torque and rate of torque development were preserved after a fatigue test in males consuming hemp compared to males on soy (p < 0.001).
Conclusion
Overall, hemp provides some sex-specific beneficial effects on measures of muscle accretion and torque under fatiguing conditions in resistance trained young adults. ClinicalTrials.gov Identifier: NCT02529917, registered August 11, 2015.
... The leucine effect seems to be dose-dependent. Leucine added as supplement (3-5 g) to either whey protein or EAA solutions in either younger or older men, showed comparable increments in skeletal muscle myofibrillar protein synthesis (MyoPS), at variance with no sustained stimulation observed in control subjects receiving only 1.8 g leucine [251,252]. However, the leucine effect in skeletal muscle of aged people might be impaired, as mTORC1 activation is defective, and sensitivity and responsiveness of muscle protein synthesis to amino acids decreased [253]. ...
The development of sarcopenia in the elderly is associated to many potential factors and/or processes, that impair the renovation and the maintenance of skeletal muscle mass and strength as ageing progresses. Among them, a defect by skeletal muscle to respond to anabolic stimuli is to be considered. Common anabolic stimuli/signals in skeletal muscle are hormones (insulin, growth hormones, IGF-1, androgens, β-agonists such epinephrine), substrates (amino acids as protein precursors on top, but also glucose and fat, as source of energy), metabolites (such as β-agonists and HMB), some cytokines, various biochemical/ intracellular mediators), physical exercise, neurogenic and immune-modulating factors, etc. Each of them may exhibit a reduced effect upon skeletal muscle as ageing progresses. In this review article, we will concisely overview the effects of anabolic signals on muscle metabolism, as well as currently available evidence of a resistance, at skeletal muscle level, to any of the above-mentioned anabolic factors, from both in vitro and in vivo studies.
... The postprandial availability of essential amino acids, particularly branched-chain amino acids (BCAA), such as Leucine (Leu), isoleucine (Ile), and valine (Val) significantly influences human myofibrillar protein synthesis (MPS), hence muscle formation and functioning (Atherton, Smith, Etheridge, Rankin, & Rennie, 2010). Specifically, Leu supplementation has been shown to enhance integrative myofibrillar protein synthesis in both old and young men (Churchward-Venne et al., 2014;Murphy et al., 2016). A multi-million-dollar industry of BCAA or Leu sports supplements has grown around this concept, albeit with unwarranted results (Wolfe, 2017). ...
Essential proteinogenic branched-chain amino acids (BCAA), particularly leucine (Leu) have been investigated for their role in enhancing human myofibrillar protein synthesis and biomedical research on tumor models. However, only a few protein sources in our current food system have high enough BCAA or Leu coefficients (% of total amino acids) to be considered as supplements for food, sport, or biomedical research. Mostly dairy-sourced proteins such as casein and whey or rarely plant source such as maize gluten are typically regarded as the gold standards. This study hypothesized that protein isolates derived from the whole-body homogenate (including the chitinous exoskeleton) of procambarid crayfish might exhibit unusually high BCAA and Leu content. The study provides open-access data on the amino acid compositions of two procambarid crayfish (Procambarus virginalis and P. clarkii), as well as a comparison with casein. The mentioned crayfish species could offer 6.36–7.39 g Leu 100 g−1 dry matter (at 43–48% protein only). Crayfish whole-body protein isolates exhibit a Leu coefficient (18.41±2.51% of total amino acids) and a BCAA coefficient (28.76±2.39% of total amino acids), which is comparable to or higher than of casein (Leu coefficient 8.65±0.08%; BCAA coefficient 20.03±0.73%). However, it is important to interpret these results with caution, due to the challenges associated with leucine and isoleucine separation, as well as potential interactions within the sample matrices. Hence, international validation of these findings is recommended.
... Previously, we demonstrated greater training-induced increases in strength, muscle thickness, lean mass, and bone formation after daily GY consumption compared with an isoenergetic, semi-solid carbohydrate pudding during a 12-week resistance training intervention in healthy young males (Bridge et al. 2019(Bridge et al. , 2020. However, the postprandial aminoacidemic response, and particularly the branched-chain amino acid (BCAA) response of GY, owing to its importance in stimulating MPS (Churchward-Venne et al. 2014), has yet to be examined on its own and in relation to other protein foods. More specifically, the postprandial plasma response of leucine, the most notable and preferential stimulator of MPS among the BCAAs (Devries et al. 2018a(Devries et al. , 2018b, is important to investigate on its own, to better assess the utility of our experimental supplements as potential muscle-supporting, protein-rich, wholefoods. ...
We examined postprandial branched-chain amino acid (BCAA), insulin, and glucose responses in blood for 4 h following the consumption of two isonitrogenous doses (2 × 20 g protein) of Greek-style yogurt (GY) and skimmed milk (MILK) in young males. Peak leucine and BCAA concentrations and areas under the curve were greater after GY versus MILK, and time to maximal leucine/BCAA concentrations was similar between conditions. We demonstrated that different protein-matched wholefood dairy products elicit different postprandial aminoacidemic responses.
... Inname van drie gram leucine in combinatie met een beperkte eiwitinname (25 gram) stimuleert de spiereiwitsynthese echter in vergelijkbare mate als consumptie van 25 gram hoogwaardig eiwit (Churchward-Venne et al. 2014). Dit gegeven is vooral van belang wanneer niet met elke maaltijd voldoende eiwit geconsumeerd kan worden of wanneer de eiwitkwaliteit laag is. ...
... In skeletal muscle, the main anabolic component of protein is leucine. Leucine triggers muscle protein synthesis independently from hyperaminoacidaemia [13] and the addition of leucine to a low protein beverage is as effective as a high-protein whey beverage at stimulating myofibrillar protein synthesis in healthy men [14]. How muscle fibers 'sense' leucine is complex, but emerging evidence indicates that fluctuations in intracellular leucine signal towards different components of the mammalian target of rapamycin complex 1 (mTORC1) [15,16]. ...
Objective:
Exercise enhances the sensitivity of mammalian target of rapamycin complex 1 (mTORC1) to amino acids, in particular leucine. How long this enhanced sensitivity lasts, and which mechanisms control enhanced leucine-mediated mTORC1 activation following exercise is currently unknown.
Methods:
C57BL/6J mice were exercised for one night in a resistance-braked running wheel after a 12-day acclimatization period. Mice were gavaged with a submaximal dose of L-leucine or saline acutely or 48 hours after exercise cessation, following 3 h food withdrawal. Muscles were excised 30 min after leucine administration. To study the contribution of mTORC1, we repeated those experiments but blocked mTORC1 activation using rapamycin immediately before the overnight running bout and one hour before the first dose of leucine. mTORC1 signaling, muscle protein synthesis and amino acid sensing machinery were assessed using immunoblot and qPCR. Leucine uptake was measured using L-[14C(U)]-leucine tracer labeling.
Results:
When compared to sedentary conditions, leucine supplementation more potently activated mTORC1 and protein synthesis in acutely exercised muscle. This effect was observed in m. soleus but not in m. tibialis anterior nor m. plantaris. The synergistic effect in m. soleus was long-lasting as key downstream markers of mTORC1 as well as protein synthesis remained higher when leucine was administered 48 h after exercise. We found that exercise enhanced the expression of amino acid transporters and promoted uptake of leucine into the muscle, leading to higher free intramuscular leucine levels. This coincided with increased expression of activating transcription factor 4 (ATF4), a main transcriptional regulator of amino acid uptake and metabolism, and downstream activation of amino acid genes as well as leucyl-tRNA synthetase (LARS), a putative leucine sensor. Finally, blocking mTORC1 using rapamycin did not reduce expression and activation of ATF4, suggesting that the latter does not act downstream of mTORC1. Rather, we found a robust increase in eukaryotic initiation factor 2α (eIF2α) phosphorylation, suggesting that the integrated stress response pathway, rather than exercise-induced mTORC1 activation, drives long-term ATF4 expression in skeletal muscle after exercise.
Conclusions:
The enhanced sensitivity of mTORC1 to leucine is maintained at least 48 h after exercise. This shows that the anabolic window of opportunity for protein ingestion is not restricted to the first hours immediately following exercise. Increased mTORC1 sensitivity to leucine coincided with enhanced leucine influx into muscle and higher expression of genes involved in leucine sensing and amino acid metabolism. Also, exercise induced an increase in ATF4 protein expression. Altogether, these data suggest that muscular contractions switch on a coordinated program to enhance amino acid uptake as well as intramuscular sensing of key amino acids involved in mTORC1 activation and the stimulation of muscle protein synthesis.
... [35,36] Lysine and Threonine are deficient in grains, while methionine, tryptophan, and cystine are deficient in pulses/legumes/beans, and lysine is deficient in nuts and seeds. [37] Tryptophan is also deficient in maize. As a result, people who take a VD must eat a wide array of protein sources to meet their diverse requirements for amino acids. ...
Statement of Retraction
We, the Editors and Publisher of International Journal of Food Properties, have retracted the following article:
Aftab Ahmed, Muhammad Afzaal, Shinawar Waseem Ali, Hafiz Shehzad Muzammil, Ammar Masood, Muhammad Awais Saleem, Farhan Saeed, Muzzamal Hussain, Amara Rasheed & Entessar Al Jbawi (2022) Effect of vegan diet (VD) on sports performance: a mechanistic review of metabolic cascades, International Journal of Food Properties, 25:1, 2022-2043, DOI: 10.1080/10942912.2022.2120495
The authors requested the withdrawal of the article on 4th June 2023, citing a ‘conflict of interest’. Whilst reviewing this request for withdrawal, we were also made aware of concerns on 5th June 2023 that Figures 1& 2 and table 1 in this article have substantial overlap with the following article:
Shaw, K.A., Zello, G.A., Rodgers, C.D. et al. Benefits of a plant-based diet and considerations for the athlete. Eur J Appl Physiol 122, 1163–1178 (2022). https://doi.org/10.1007/s00421-022-04902-w
While Figure 2 is fully referenced, neither Figure 1 nor Table 1 have been properly referenced or acknowledged.
Upon query, the authors have not been able to provide a satisfactory explanation for this overlap. As this is a breach of our Editorial Policies, we are retracting the article from the journal.
We have been informed in our decision-making by our editorial policies and integrity and the COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.
... The branched-chain amino acids (BCAAs) content in essential amino acids (EAAs) is important for protein quality, and leucine has been reported to promote MPS, in particular, by stimulating the mammalian rapamycin complex 1 (mTORC1) signaling pathway [13,14]. Furthermore, regulation of blood amino acid (AA) levels must consider quantity, quality, and the timing of protein intake because a positive correlation has been reported between BCAA levels (in particular, leucine) and MPS rate [3,[13][14][15]. ...
Background: The rate of protein digestion and amino acid (AA) absorption determines the postprandial rise in circulating AA and modulates postprandial muscle protein synthesis (MPS) rates. Furthermore, it is necessary to consider the timing of protein ingestion, along with its quantity and quality, to regulate the blood AA concentration. Chicken breasts are a popular food among athletes as they are a good source of animal protein, containing sufficient essential amino acids (EAAs) and branched-chain amino acids (BCAAs). Low-molecular-weight chicken peptides (Cpep), a novel protein supplement, were isolated from chicken breasts. Blood AA dynamics, which have a significant influence on MPS rates, were observed and compared with commercially available whey- and soy-derived protein supplements.Objectives: We evaluated blood AA dynamics after Cpep intake compared with whey protein (WP), and soy protein (SP).Methods: Three groups of six healthy adult men volunteers (age 39 ± 10 years) ingested 0.3 g/kg (protein/body weight) of Cpep, WP, and SP. The concentrations of AA in the plasma were measured before and after the ingestion period and their kinetics were compared.Results: Cpep comprises free amino acids or peptides, and their average molecular weights are lower than those of WP and SP. The absorption dynamics of AA in the plasma were evaluated. After Cpep intake, EAA and BCAA concentrations peaked at 30 min and levels of EAA and BCAA were higher than those after WP and SP ingestion at 15 and 30 min, respectively. Conversely, the levels of total AA, EAA, and BCAA decreased 45 min after Cpep intake compared with WP and SP intakes. In contrast, WP and SP showed similar blood AA dynamics with a peak at 60 min.Conclusions: Cpep is absorbed significantly faster than WP and SP, making it a useful option for efficient protein intake to maintain and increase muscle mass.Keywords: chicken-derived peptides, blood amino acid dynamics, branched-chain amino acid, muscle protein synthesis
... That said, the value of dietary leucine or supplementary leucine appears to be more relevant in cases where protein (single meal and/or total diet) is suboptimal. For example, lower amounts of TP with high leucine content can stimulate MPS to a similar extent as a larger amount of protein that provides a similar amount of leucine (25,63). Leucine may also be used as a proxy for protein quality of a meal or diet. ...
Background
Research on the role of protein in the diet has evolved beyond a focus on quantity to include the impact of its quality and distribution across meal times in an effort to optimize dietary protein recommendations.
Objective
To determine the association of dietary protein amount, type, and intake pattern with grip strength in adults.
Design
Data from the National Health and Nutrition Examination Survey (NHANES) 2011–2014 for adults 19 + years (N = 9,214) were used with exclusions for pregnant and lactating women. Intakes of dietary total protein (TP), animal protein (AP, including dairy), plant protein (PP), and leucine (Leu) were determined using day 1 24 h dietary recall data after adjusting for the complex sample design of NHANES. Regression analyses were used to assess the association of dietary protein and leucine intake quartiles, and whether consuming > 20 g of dietary protein at one or more meals was related to grip strength with adjustment for age, gender, and ethnicity.
Results
Mean intake of TP among adults aged 19 + years was 83.6 ± 0.5 g/day, and 2/3rd of this was from animal sources (including dairy). Grip strength increased (p < 0.05) with increasing quartiles of TP, AP, PP, and leucine among all adults 19 + years (β = 1.340.19, 1.27 ± 0.19, 0.76 ± 0.20, and 1.33 ± 0.23, respectively), 19–50 years (β = 1.14 ± 0.27, 1.06 ± 0.25, 0.77 ± 0.30, and 1.18 ± 0.27, respectively), and 51 + years (β = 0.95 ± 0.26, 1.08 ± 0.27, and 1.05 ± 0.27, respectively, for TP, AP, and Leu); however, the increase was more pronounced for AP than PP. Grip strength also increased (p < 0.05) with increasing the number of meal occasions containing > 20 g of dietary protein (β = 1.50 ± 0.20, 1.41 ± 0.25, and 0.91 ± 0.37 for 19+, 19–50, and 51 + years, respectively), and significant increases were detected for two meals compared to zero meals.
Conclusion
Dietary protein quantity, quality, and distribution should be considered collectively when looking to optimize protein intake to support muscle strength and function.
... Leucine has been reported to play a crucial role in activating mTORC1 and, consequently, stimulating muscle protein synthesis (Devries et al., 2018). The addition of free leucine to low dietary protein activates mTORC1, thereby amplifying the anabolic response and enhancing muscle anabolism, as reported in previous studies (Churchward-Venne et al., 2014). In contrast, there is no evidence of a beneficial effect in healthy young subjects when free leucine is added to intact protein (Van Loon, 2012). ...
Whey protein isolate (WPI) and whey protein hydrolysate (WPH) contains more protein than whey protein concentrate. However, to achieve a better taste, most commercial products mix WPI and WPH with whey protein concentrate (WPC). This study aimed to compare postprandial blood amino acids following ingestion of three beverages: WPImixed with WPC (WPI-mixed), WPH-mixed with WPI (WPH-mixed), and placebo. A total of ten healthy men aged between 18 and 30, who regularly engaged in exercise training, were recruited as participants. They each received 350 mL of each beverage on separate days and 6-day apart. Concentrations of plasma essential amino acids (EAA), branched-chain amino acids (BCAA), and leucine (Leu) were measured in blood samples taken from participants every 15 mins for 2 hrs. Plasma concentrations of EAA, BCAA, and Leu increased after ingestion of the WPI-mixed and WPH-mixed beverages versus the placebo beverage (P<0.05). Plasma EAA did not differ between WPI- mixed and WPmixed trials. In contrast, plasma concentrations of BCAA after WPI-mixed were higher than after WPH-mixed at 30 mins. The same was observed for Leu at 30 and 75 mins after ingestion. The higher plasma BCAA and Leu in the WPI-mixed trial versus the WPHmixed trial may have been due to the presence of short-chain peptides, as bioactive peptides, in WPH-mixed, which were absorbed. In conclusion, there was no difference in plasma EAA, but plasma concentrations of leucine and BCAA were higher in the WPImixed trial than WPH-mixed trial. Therefore, future research should investigate bioactive peptides along with plasma amino acids.
Function declines throughout life although phenotypical manifestations in terms of frailty or disability are only seen in the later periods of our life. The causes underlying lifelong function decline are the aging process "per se", chronic diseases, and lifestyle factors. These three etiological causes result in the deterioration of several organs and systems which act synergistically to finally produce frailty and disability. Regardless of the causes, the skeletal muscle is the main organ affected by developing sarcopenia. In the first section of the manuscript, as an introduction, we review the quantitative and qualitative age-associated skeletal muscle changes leading to frailty and sarcopenia and their impact in the quality of life and independence in the elderly. The reversibility of frailty and sarcopenia are discussed in the second and third sections of the manuscript. The most effective intervention to delay and even reverse frailty is exercise training. We review the role of different training programs (resistance exercise, cardiorespiratory exercise, multicomponent exercise, and real-life interventions) not only as a preventive but also as a therapeutical strategy to promote healthy aging. We also devote a section in the text to the sexual dimorphic effects of exercise training interventions in aging. How to optimize the skeletal muscle anabolic response to exercise training with nutrition is also discussed in our manuscript. The concept of anabolic resistance and the evidence of the role of high-quality protein, essential amino acids, creatine, vitamin D, β-hydroxy-β-methylbutyrate, and Omega-3 fatty acids, is reviewed. In the last section of the manuscript, the main genetic interventions to promote robustness in preclinical models are discussed. We aim to highlight the molecular pathways that are involved in frailty and sarcopenia. The possibility to effectively target these signaling pathways in clinical practice to delay muscle aging is also discussed.
Introduction
Skeletal muscle satellite cells (SC) contribute to the adaptive process of resistance exercise training (RET) and may be influenced by nutritional supplementation. However, little research exists on the impact of multi-ingredient supplementation on the SC response to RET.
Purpose
We tested the effect of a multi-ingredient supplement (MIS) including whey protein, creatine, leucine, calcium citrate, and vitamin D on SC content and activity as well as myonuclear accretion, SC and myonuclear domain compared with a collagen control (COL) throughout a 10-wk RET program.
Methods
Twenty-six participants underwent a 10-wk linear RET program while consuming either the MIS or COL supplement twice daily. Muscle biopsies were taken from the vastus lateralis at baseline and 48 h after a bout of damaging exercise, before and after RET. Muscle tissue was analyzed for SC and myonuclear content, domain, acute SC activation, and fiber cross-sectional area (fCSA).
Results
MIS resulted in a greater increase in type II fCSA following 10 wk of RET (effect size (ES) = 0.89) but not myonuclear accretion or SC content. Change in myonuclei per fiber was positively correlated with type I and II and total fiber hypertrophy in the COL group only, indicating a robust independent effect of MIS on fCSA. Myonuclear domain increased similarly in both groups, whereas SC domain remained unchanged following RET. SC activation was similar between groups for all fiber types in the untrained state but showed a trend toward greater increases with MIS after RET (ES = 0.70).
Conclusions
SC responses to acute damaging exercise and long-term RET are predominantly similar in MIS and COL groups. However, MIS can induce greater increases in type II fCSA with RET and potentially SC activation following damage in the trained state.
The intensive care unit (ICU) environment is one of the most challenging for skeletal muscle health. The atrophy associated with clinical care is distinct from that seen with inactivity or immobilization in the absence of disease and is exacerbated by aging. The substantial muscle loss in the ICU is likely due to the presence of inflammation, elevated proteolysis, bedrest, and undernutrition. Skeletal muscle parameters (e.g., mass, composition/quality) at admission are predictive of mortality and other clinically important outcomes. Treatment goals to mitigate muscle loss should be early mobilization and adequate nutrient supply, especially protein, using an individualized approach to support the maintenance and recovery of skeletal muscle.
Introduction
Protein supplementation increases post-exercise muscle protein synthesis rates and, as such, supports exercise-induced muscle conditioning. Collagen protein has been suggested as the preferred protein source to stimulate muscle connective protein synthesis rates during recovery from exercise. Here we assessed the effects of hydrolyzed collagen peptide supplementation on both myofibrillar as well as muscle connective protein synthesis rates during one week of strenuous resistance exercise training.
Methods
In a randomized, double-blind, parallel design, 25 young men (24 ± 3 y, 76.9 ± 6.4 kg) were selected to perform one week of intense resistance-type exercise training. Subjects were randomly assigned into two groups receiving either 15 g hydrolyzed collagen peptides (COL) or a non-caloric placebo (PLA) twice daily during the intervention. Subjects were administered deuterated water ( ² H 2 O) daily, with blood and skeletal muscle tissue samples being collected prior to and after the intervention to determine daily myofibrillar and muscle connective protein synthesis rates.
Results
Post-absorptive plasma glycine, proline, and hydroxyproline concentrations increased following collagen peptide supplementation (p < 0.05) and showed higher levels when compared to the placebo group (p < 0.05). Daily muscle connective protein synthesis rates during the intervention period exceeded myofibrillar protein synthesis rates (1.99 ± 0.38 versus 1.34 ± 0.23 %/d, respectively; p < 0.001). Collagen peptide supplementation did not result in higher myofibrillar or muscle connective protein synthesis rates (1.34 ± 0.19 and 1.97 ± 0.47 %/d, respectively) when compared to the placebo group (1.34 ± 0.27 and 2.00 ± 0.27 %/d, respectively; p > 0.05).
Conclusions
Collagen peptide supplementation (2 x 15 g daily) does not increase myofibrillar or muscle connective protein synthesis rates during one week of intense resistance exercise training in young, recreational athletes.
As a result of advances in medical treatments and associated policy over the last century, life expectancy has risen substantially and continues to increase globally. However, the disconnect between lifespan and ‘health span’ (the length of time spent in a healthy, disease-free state) has also increased, with skeletal muscle being a substantial contributor to this. Biological ageing is accompanied by declines in both skeletal muscle mass and function, termed sarcopenia. The mechanisms underpinning sarcopenia are multifactorial and are known to include marked alterations in muscle protein turnover and adaptations to the neural input to muscle. However, to date, the relative contribution of each factor remains largely unexplored. Specifically, muscle protein synthetic responses to key anabolic stimuli are blunted with advancing age, whilst alterations to neural components, spanning from the motor cortex and motoneuron excitability to the neuromuscular junction, may explain the greater magnitude of function losses when compared with mass. The consequences of these losses can be devastating for individuals, their support networks, and healthcare services; with clear detrimental impacts on both clinical (e.g., mortality, frailty, and post-treatment complications) and societal (e.g., independence maintenance) outcomes. Whether declines in muscle quantity and quality are an inevitable component of ageing remains to be completely understood. Nevertheless, strategies to mitigate these declines are of vital importance to improve the health span of older adults. This review aims to provide an overview of the declines in skeletal muscle mass and function with advancing age, describes the wide-ranging implications of these declines, and finally suggests strategies to mitigate them, including the merits of emerging pharmaceutical agents.
This study assessed postprandial plasma aminoacidemia, glycemia, insulinemia and appetite responses to ingestion of a novel salmon-derived protein peptide (Salmon PP) compared with milk protein isolate (Milk PI). In a randomised, participant-blind crossover design, 11 healthy adults (M=5, F=6; Mean±SD age: 22±3 years; BMI: 24±3 kg·m-2) ingested 0.3g·kg·body mass-1 of Salmon PP or Milk PI. Arterialised blood samples were collected whilst fasted and over a 240-min postprandial period. Appetite sensations were measured via Visual Analogue Scales. An ad libitum buffet-style test meal was administered after each trial. The incremental area under the curve (iAUC) plasma essential amino acid response was similar between Salmon PP and Milk PI. The iAUC plasma leucine response was significantly greater following Milk PI ingestion (P<0.001), whereas temporal and iAUC plasma total amino acid (P=0.001), non-essential amino acid (P=0.002), glycine (P=0.0025) and hydroxyproline (P<0.001) responses were greater following Salmon PP ingestion. Plasma insulin increased similarly above postabsorptive values following Salmon PP and Milk PI ingestion, whilst plasma glucose was largely unaltered. Indices of appetite were similarly altered following Salmon PP and Milk PI ingestion, and total energy and macronutrient intake during the ad libitum meal was similar between Salmon PP and Milk PI. The postprandial plasma essential amino acid, glycine, proline and hydroxyproline response to Salmon PP ingestion suggest this novel protein source could support muscle and possibly connective tissue adaptive remodelling, which warrants further investigation, particularly as the plasma leucine response to Salmon PP ingestion was inferior to Milk PI.
The development of sarcopenia in the elderly is associated with many potential factors and/or processes that impair the renovation and maintenance of skeletal muscle mass and strength as ageing progresses. Among them, a defect by skeletal muscle to respond to anabolic stimuli is to be considered. Common anabolic stimuli/signals in skeletal muscle are hormones (insulin, growth hormones, IGF-1, androgens, and β-agonists such epinephrine), substrates (amino acids such as protein precursors on top, but also glucose and fat, as source of energy), metabolites (such as β-agonists and HMB), various biochemical/intracellular mediators), physical exercise, neurogenic and immune-modulating factors, etc. Each of them may exhibit a reduced effect upon skeletal muscle in ageing. In this article, we overview the role of anabolic signals on muscle metabolism, as well as currently available evidence of resistance, at the skeletal muscle level, to anabolic factors, from both in vitro and in vivo studies. Some indications on how to augment the effects of anabolic signals on skeletal muscle are provided.
Due to the high prevalence of sarcopenia among elderly and old patients, early prevention and treatment of sarcopenia and its complications are relevant. Protein supplements can be used to maintain muscle strength and mass during aging. The possibility of using branched-chain amino acids (BCAAs) in the treatment and prevention of sarcopenia in geriatric patients is of scientific interest. BCAAs promote the synthesis and inhibit the degradation of muscle tissue proteins, are involved in the regulation of tissue sensitivity to insulin, ammonia utilization, the tricarboxylic acid cycle, etc. Search strategy. The search for scientific articles for literature review was carried out in the PubMed and PubMed Central databases. The selection criterion was scientific articles published up to December 2022. We used the following search keywords: “branched-chain amino acids”, “BCAA”, “body composition”, “sarcopenia”, “aging”. The 2019 European Working Group on Sarcopenia in Older People 2 (EWGSOP2) Consensus was included in the list of articles. Conclusions. The possibility of using BCAAs in elderly and old patients for the prevention and treatment of sarcopenia is a relevant topic that continues to be actively studied. The effectiveness of BCAA supplementation in the diet is debatable as long as sufficient protein is consumed daily. On the other hand, BCAA supplementation may be justified in cases where it is not possible to consume enough high-quality protein in the diet. More research is needed on this topic.
Molecular recognition towards peptides and proteins with high affinity by synthetic supramolecular hosts is important but challenging. In this work, we investigate the molecular recognition of the synthetic cucurbit[7]uril (CB[7]) to 17 designed N-terminal Leu-containing tripeptides in aqueous medium by molecular dynamics (MD) simulation and screen out tripeptides with high binding affinity. It is found that, compared to LGG, only the third residue is Arg (R), the binding affinity of CB[7] to LGR reaches nanomolar level with binding equilibrium constant (Ka) of 1.1 × 109 M-1. The CB[7] recognition to the N-terminal Leu-containing tripeptides is highly sequence dependent; whether changing the sequence order (from LGR to LRG) or increasing the sequence length (from LGR to LGGR), Ka decreases by about three orders of magnitude. Interestingly, substituting N-terminal Leu for its isomer Ile, the binding of CB[7] to tripeptides weakens significantly with Ka decreasing by 3-8 orders of magnitude. Thus CB[7] can effectively distinguish N-terminal Leu-containing tripeptides from N-terminal Ile-containing tripeptides. Importantly, we predict that when R is as C-terminus, regardless of N-terminal residue being of aromatic type or Leu, the binding strength is always close to the nanomolar level. Therefore, R can be introduced to rationally design novel peptides with high binding affinity to CB[7] in practical applications.
Food and agricultural by-products are leftovers or wastes from parts of foods, fruits, vegetables and animal sources which are obtained after processing. Agricultural by-products includes peels and rinds from citrus fruits, pineapple, mango, and banana. Other notable ones are pomace from apple, olive, red beet, and those from wine making. Also, whey from milk, straws, hulls, and brans from grains are among top agricultural by-products. These by-products often impact the environment and the social-economic sectors when they are disposed. But with the recent advances in biotechnology and scientific research, scientists have found usefulness in some of these byproducts as sources of valuable nutraceuticals, a term used to refer to chemical entities present in foods that has the propensity to impact health for disease prevention and treatment. This book entitled ‘Food and agricultural by-products as important source of valuable nutraceuticals’ presents detailed information about major agricultural byproducts that are rich in nutraceuticals. The nature and the type of nutraceuticals that they contains and their health promoting benefits were presented. The editors and chapter contributors are renowned experts from key institutions around the globe. This book will be useful to students, teachers, food chemists, nutritionists, nutritional biochemists, food biotechnologists among others.
Maintaining muscle quality throughout life is crucial to human health and well-being. Muscle is the most extensive form of protein storage in the human body; skeletal muscle mass is determined by the balance between muscle protein synthesis (MPS) and muscle protein breakdown (MPB). MPB provides amino acids needed by various organs; however, excessive MPB, especially with aging, may cause loss of muscle mass and a decline in motor function, even threatening life. The turnover of muscle protein is vital to the health of humans. Thus, while the study of MPS and MPB has theoretical and practical significance, the network that controls MPS is very complicated and we cannot discuss both MPS and MPB in a single review. Therefore, this review mainly discusses the regulation of MPS, especially by amino acids. Amino acids regulate protein synthesis in cell and animal models, but compelling evidence for amino acids promoting protein synthesis in human muscles is ambiguous. In particular, studies on the stimulation of human MPS by branched-chain amino acids (BCAAs) have been inconsistent. Amino acids other than BCAAs such as threonine and tryptophan may also have MPS-stimulating effects, and alternatives to BCAAs, such as Beta-Hydroxy-Beta-Methyl butyrate (HMB) and branched-chain ketoacids (BCKAs) are also worthy of further investigation explore. Amino acids coordinate protein synthesis and degradation through the mechanistic target of rapamycin complex 1 (mTORC1); however, the amino acid-mTORC1-protein synthesis pathway is complex, and new insights into amino acid control continue to emerge. Understanding how amino acids control MPS is of forward-looking significance for treating muscle mass loss during human aging.
Banana is a staple fruit because it is available all through the year and it also serves as a source of income and food to a great number of people. Banana peel is the major byproduct of banana processing which account for 30% of the banana fruit and also constitute to environmental hazard. Banana peels are promising byproduct for different applications in nutraceuticals and medicinal usage due to the high dietary fiber and phenolic content present in them. Numerous studies have identified banana peels as a rich source of phytochemical compounds, mainly antioxidants such as phenolics, flavonoids, gallocatechin, anthocyanins delphinidin and cyaniding, and catecholamines, carotenoids, vitamins and minerals. This chapter consulted literature and presented scientific evidence of banana peels as a source of nutraceuticals.
Mango fruit and its by-product contain an abundant source of beneficial compounds such as polyphenols, carotenoids, dietary fiber and vitamin E. About 15–20% of the total weight of fresh mango represents by its peel. Likewise, peel wastes from the fruit may contain beneficial properties similar to that generally found in fruit.
As one of the signifcant by-products of mango fruit, the peels rich in health-enhancing constituents, particularly phenolic compounds, can be incorporated into nutraceutical, pharmaceutical, and functional food products. mango peel contains mangiferin, pectin, anthocyanins, β-carotene, gallic acid, galloyl glucose, and lutein. Comparative studies on mango peel indicate that higher total polyphenol content is found in the ripened than the unripe peel.
Along with food processing, the production of agro-industrial waste in the world increases, despite the fact that it is a rich source of nutrients and bioactive compounds. In developing countries, waste materials from the agricultural industry can significantly help in obtaining valuable components for the production of various types of bio-based products. The aim of the work is to manage potato peel waste from the agri-food processing industry and to propose new nutritional and industrial applications for them. Food processing by-products are an inexpensive, affordable, and valuable starting material for the extraction of value-added products such as dietary fiber, natural antioxidants, biopolymers, and natural food additives. Potato peel waste, which is produced by various processes, such as extraction, fermentation, and other processes, can be transformed into products such as biofuels, dietary fiber, bio-fertilizers, biogas, biosorbent, antioxidants and various food additives. This work explores the use of potato skins as a source of nutraceuticals for food and non-food purposes, e.g., extraction, use of bioactive ingredients, biotechnological use, livestock feed and other applications. The practical approach will be able to be used in developing awareness of the proper management of agricultural waste, as well as in their application for the synthesis of many compounds such as lactic acid, biosorbent, biohydrogen, enzymes, etc., which serve as a basis for developing links between industry and sharing with new ideas and technologies.
In line with global paradigm shift towards the promotion of environmentally friendly and sustainable solutions to prevailing challenges in all facets of human endeavor, it has become increasingly paramount to explore and exploit naturally-occurring sources of nutraceuticals available in plants such as fruits and vegetables for their physiological and pharmacological benefits in promoting human health and wellbeing as well as prevention and management of infectious and non-infectious diseases. Research evidence has shown that citrus fruits, particularly orange peel, which contains significantly high quantity dietary fibers, phenolic compounds, and phytochemical agents, promote wellbeing due to its extensive anti-inflammatory, anti-oxidant, anti-obesity, anti-cancerous, anti-diabetic and anti-hypercholesterolemic properties. These properties, as well as considerably little to no side effects in comparison to pharmaceuticals (medicinal drugs) continues to endear the global population to the health benefits of nutraceuticals.KeywordsNutraceuticalsCitrusOrange peelHealth benefits
Nutraceuticals are foods with nutritional and health-promoting benefits. Sorghum and its products are veritable and invaluable sources of nutraceuticals. Sorghum species (sorghum valgare and sorghum bicolour) are members of the poaceae grass family and major source of cereals and foods in West Africa, India, China and North America. Their nutritive benefits are connected to their starch and protein contents, while their therapeutic potentials are traceable to the high concentration of phenolic acids, flavonoids, anthocyanins and polyphenols present in them. This chapter focuses on the phytochemical composition, nutritional, health promoting benefits and various applications of sorghum and its bye products.
Whey protein is a mixture of proteins obtained from whey, the liquid milk component that separates during the production of cheese and other dairy products. While the major whey protein components include α-lactalbumin, β-lactoglobulin, BSA, and the fraction of proteose-peptone, the minor whey protein components include immunoglobulins, lactoferrins, ceruloplasmins, as well as certain enzymes such as lipase, xanthine oxidase, and lysozyme. Three types of whey proteins include whey protein isolate, whey protein concentrate, and whey protein hydrolysate, with various compositions. Whey protein has high protein efficiency ratio (PER), high biological value (BV), and contains sulfur containing amino acids, including methionine and cysteine, that boost immune functions by intracellular conversion to glutathione. Whey proteins are suitable for nutraceuticals and functional food formulations due to their anticarcinogenic, anti-diabetic, antihypertensive, antioxidant, cardioprotective, hypotensive, immune improvement, and immunomodulatory properties, among others. However, more control studies are required to explore their applications for other targeted therapies.
Background: Resistance exercise leads to net muscle protein accretion through a synergistic interaction of exercise and feeding. Proteins from different sources may differ in their ability to support muscle protein accretion because of different patterns of postprandial hyperaminoacidemia.
Objective: We examined the effect of consuming isonitrogenous, isoenergetic, and macronutrient-matched soy or milk beverages (18 g protein, 750 kJ) on protein kinetics and net muscle protein balance after resistance exercise in healthy young men. Our hypothesis was that soy ingestion would result in larger but transient hyperaminoacidemia compared with milk and that milk would promote a greater net balance because of lower but prolonged hyperaminoacidemia.
Design: Arterial-venous amino acid balance and muscle fractional synthesis rates were measured in young men who consumed fluid milk or a soy-protein beverage in a crossover design after a bout of resistance exercise.
Results: Ingestion of both soy and milk resulted in a positive net protein balance. Analysis of area under the net balance curves indicated an overall greater net balance after milk ingestion (P < 0.05). The fractional synthesis rate in muscle was also greater after milk consumption (0.10 ± 0.01%/h) than after soy consumption (0.07 ± 0.01%/h; P = 0.05).
Conclusions: Milk-based proteins promote muscle protein accretion to a greater extent than do soy-based proteins when consumed after resistance exercise. The consumption of either milk or soy protein with resistance training promotes muscle mass maintenance and gains, but chronic consumption of milk proteins after resistance exercise likely supports a more rapid lean mass accrual.
The nature of the deficit underlying age-related muscle wasting remains controversial. To test whether it could be due to a poor anabolic response to dietary amino acids, we measured the rates of myofibrillar and sarcoplasmic muscle protein synthesis (MPS) in 44 healthy young and old men, of similar body build, after ingesting different amounts of essential amino acids (EAA). Basal rates of MPS were indistinguishable, but the elderly showed less anabolic sensitivity and responsiveness of MPS to EAA, possibly due to decreased intramuscular expression, and activation (phosphorylation) after EAA, of amino acid sensing/signaling proteins (mammalian target of rapamycin, mTOR; p70 S6 kinase, or p70(S6k); eukaryotic initiation factor [eIF]4BP-1; and eIF2B). The effects were independent of insulin signaling since plasma insulin was clamped at basal values. Associated with the anabolic deficits were marked increases in NFkappaB, the inflammation-associated transcription factor. These results demonstrate first, EAA stimulate MPS independently of increased insulin availability; second, in the elderly, a deficit in MPS in the basal state is unlikely; and third, the decreased sensitivity and responsiveness of MPS to EAA, associated with decrements in the expression and activation of components of anabolic signaling pathways, are probably major contributors to the failure of muscle maintenance in the elderly. Countermeasures to maximize muscle maintenance should target these deficits.
The loss of muscle mass with aging has been, at least partly, attributed to a blunted muscle protein synthetic response to food intake. Leucine coingestion has been reported to stimulate postprandial insulin release and augment postprandial muscle protein accretion. We assessed the clinical benefits of 6 mo of leucine supplementation in elderly, type 2 diabetes patients. Sixty elderly males with type 2 diabetes (age, 71 ± 1 y; BMI, 27.3 ± 0.4 kg/m(2)) were administered 2.5 g L-leucine (n = 30) or a placebo (n = 30) with each main meal during 6 mo of nutritional intervention (7.5 g/d leucine or placebo). Body composition, muscle fiber characteristics, muscle strength, glucose homeostasis, and basal plasma amino acid and lipid concentrations were assessed prior to, during, and after intervention. Lean tissue mass did not change or differ between groups and at 0, 3, and 6 mo were 61.9 ± 1.1, 62.2 ± 1.1, and 62.0 ± 1.0 kg, respectively, in the leucine group and 62.2 ± 1.3, 62.2 ± 1.3, and 62.2 ± 1.3 kg in the placebo group. There also were no changes in body fat percentage, muscle strength, and muscle fiber type characteristics. Blood glycosylated hemoglobin did not change or differ between groups and was 7.1 ± 0.1% in the leucine group and 7.2 ± 0.2% in the placebo group. Consistent with this, oral glucose insulin sensitivity and plasma lipid concentrations did not change or differ between groups. We conclude that prolonged leucine supplementation (7.5 g/d) does not modulate body composition, muscle mass, strength, glycemic control, and/or lipidemia in elderly, type 2 diabetes patients who habitually consume adequate dietary protein.
The relationship between mammalian target of rapamycin complex 1 (mTORC1) signaling and muscle protein synthesis during instances of amino acid surplus in humans is based solely on correlational data. Therefore, the goal of this study was to use a mechanistic approach specifically designed to determine whether increased mTORC1 activation is requisite for the stimulation of muscle protein synthesis following L-essential amino acid (EAA) ingestion in humans. Examination of muscle protein synthesis and signaling were performed on vastus lateralis muscle biopsies obtained from 8 young (25 ± 2 y) individuals who were studied prior to and following ingestion of 10 g of EAA during 2 separate trials in a randomized, counterbalanced design. The trials were identical except during 1 trial, participants were administered a single oral dose of a potent mTORC1 inhibitor (rapamycin) prior to EAA ingestion. In response to EAA ingestion, an ~60% increase in muscle protein synthesis was observed during the control trial, concomitant with increased phosphorylation of mTOR (Ser(2448)), ribosomal S6 kinase 1 (Thr(389)), and eukaryotic initiation factor 4E binding protein 1 (Thr(37/46)). In contrast, prior administration of rapamycin completely blocked the increase in muscle protein synthesis and blocked or attenuated activation of mTORC1-signaling proteins. The inhibition of muscle protein synthesis and signaling was not due to differences in either extracellular or intracellular amino acid availability, because these variables were similar between trials. These data support a fundamental role for mTORC1 activation as a key regulator of human muscle protein synthesis in response to increased EAA availability. This information will be useful in the development of evidence-based nutritional therapies targeting mTORC1 to counteract muscle wasting associated with numerous clinical conditions.
Essential amino acids (EAA) stimulate skeletal muscle protein synthesis (MPS) in humans. Leucine may have a greater stimulatory effect on MPS than other EAA and/or decrease muscle protein breakdown (MPB). To determine the effect of 2 different leucine concentrations on muscle protein turnover and associated signaling, young men (n = 6) and women (n = 8) ingested 10 g EAA in 1 of 2 groups: composition typical of high quality proteins (CTRL; 1.8 g leucine) or increased leucine concentration (LEU; 3.5 g leucine). Participants were studied for 180 min postingestion. Fractional synthetic rate and leg phenylalanine and leucine kinetics were assessed on muscle biopsies using stable isotopic techniques. Signaling was determined by immunoblotting. Arterial leucine concentration and delivery to the leg increased in both groups and was significantly higher in LEU than in CTRL; however, transport into the muscle and intracellular availability did not differ between groups. MPS increased similarly in both groups 60 min postingestion. MPB decreased at 60 min only in LEU, but net muscle protein balance improved similarly. Components of mammalian target of rapamycin (mTOR) signaling were improved in LEU, but no changes were observed in ubiquitin-proteasome system signaling. Changes in light chain 3 and mTOR association with Unc-51-like kinase 1 indicate autophagy decreased more in LEU. We conclude that in 10 g of EAA, the leucine content typical of high quality proteins (~1.8 g) is sufficient to induce a maximal skeletal muscle protein anabolic response in young adults, but leucine may play a role in autophagy regulation.
We aimed to determine the effect of resistance exercise intensity (%1 repetition maximum-1RM) and volume on muscle protein synthesis, anabolic signaling, and myogenic gene expression.
Fifteen men (21+/-1 years; BMI=24.1+/-0.8 kg/m2) performed 4 sets of unilateral leg extension exercise at different exercise loads and/or volumes: 90% of repetition maximum (1RM) until volitional failure (90FAIL), 30% 1RM work-matched to 90%FAIL (30WM), or 30% 1RM performed until volitional failure (30FAIL). Infusion of [ring-13C6] phenylalanine with biopsies was used to measure rates of mixed (MIX), myofibrillar (MYO), and sarcoplasmic (SARC) protein synthesis at rest, and 4 h and 24 h after exercise. Exercise at 30WM induced a significant increase above rest in MIX (121%) and MYO (87%) protein synthesis at 4 h post-exercise and but at 24 h in the MIX only. The increase in the rate of protein synthesis in MIX and MYO at 4 h post-exercise with 90FAIL and 30FAIL was greater than 30WM, with no difference between these conditions; however, MYO remained elevated (199%) above rest at 24 h only in 30FAIL. There was a significant increase in AktSer473 at 24h in all conditions (P=0.023) and mTORSer2448 phosphorylation at 4 h post-exercise (P=0.025). Phosporylation of Erk1/2Tyr202/204, p70S6KThr389, and 4E-BP1Thr37/46 increased significantly (P<0.05) only in the 30FAIL condition at 4 h post-exercise, whereas, 4E-BP1Thr37/46 phosphorylation was greater 24 h after exercise than at rest in both 90FAIL (237%) and 30FAIL (312%) conditions. Pax7 mRNA expression increased at 24 h post-exercise (P=0.02) regardless of condition. The mRNA expression of MyoD and myogenin were consistently elevated in the 30FAIL condition.
These results suggest that low-load high volume resistance exercise is more effective in inducing acute muscle anabolism than high-load low volume or work matched resistance exercise modes.
Muscle protein breakdown (MPB) is increased following resistance exercise, but ingestion of carbohydrate during postexercise recovery can decrease MPB with no effect on muscle protein synthesis (MPS). We sought to determine whether a combination of essential amino acids (EAA) with low carbohydrate or high carbohydrate could effectively reduce MPB following resistance exercise and improve muscle protein net balance (NB). We hypothesized that higher levels of carbohydrate and resulting increases in circulating insulin would inhibit MPB and associated signaling, resulting in augmented NB. Thirteen male subjects were assigned to one of two groups receiving equivalent amounts of EAA (approximately 20 g) but differing carbohydrate levels (low = 30, high = 90 g). Groups ingested nutrients 1 h after an acute bout of leg resistance exercise. Leg phenylalanine kinetics (e.g., MPB, MPS, NB), signaling proteins, and mRNA expression were assessed on successive muscle biopsies using stable isotopic techniques, immunoblotting, and real-time quantitative PCR, respectively. MPB tended to decrease (P < 0.1) and MPS increased (P < 0.05) similarly in both groups following nutrient ingestion. No group differences were observed, but muscle ring finger 1 (MuRF1) protein content and MuRF1 mRNA expression increased following resistance exercise and remained elevated following nutrient ingestion, while autophagy marker (light-chain 3B-II) decreased after nutrient ingestion (P < 0.05). Forkhead box-O3a phosphorylation, total muscle atrophy F-box (MAFbx) protein, and MAFbx and caspase-3 mRNA expression were unchanged. We conclude that the enhanced muscle protein anabolic response detected when EAA+carbohydrate are ingested postresistance exercise is primarily due to an increase in MPS with minor changes in MPB, regardless of carbohydrate dose or circulating insulin level.
This study examined the impact of leucine (Leu) derived from complete meals on stimulation of skeletal muscle protein synthesis (MPS). Expt. 1 examined time course changes in translation initiation and MPS after a meal. Male rats ( approximately 300 g) were trained for 5 d to eat 3 meals/d providing 20, 50, and 30% of energy from whey protein, carbohydrates, and fats, respectively. Plasma and skeletal muscle were collected at time 0 (baseline) after 12 h of food deprivation and then at 45, 90, 135, 180, and 300 min after a 4-g meal. Plasma Leu increased at 45 min and remained elevated through 180 min. MPS peaked at 45-90 min and returned to baseline by 180 min. Plasma Leu correlated with phosphorylation of ribosomal protein p70 S6 kinase (r = 0.723; P < 0.05), eukaryotic initiation factor 4E binding protein-1 (r = 0.773; P < 0.05), and MPS (r = 0.608; P < 0.05) over time. Expt. 2 examined 3 levels of protein intake (10, 20, and 30% of energy) from 2 sources (wheat and whey) with different Leu contents ( approximately 6.8 and approximately 10.9%, respectively) on stimulation of initiation and MPS. Rats were trained to eat 3 meals/d providing 14, 56, and 30% of energy from protein, carbohydrates, and fats. On d 6, MPS was evaluated at 90 min after rats consumed 1 of the 6 test meals. Whey protein stimulated initiation and MPS more than wheat and the differential response related to greater plasma Leu responses in the whey groups. These studies demonstrate that peak activation but not duration of MPS is proportional to the Leu content of a meal.
Leucine is known to stimulate muscle protein synthesis and anabolism. However, evidence for the efficacy of additional leucine to enhance the response of muscle anabolism to resistance exercise and protein ingestion is unclear. Thus, we investigated the response of net muscle protein balance to ingestion of additional leucine with protein in association with resistance exercise. Two groups of untrained subjects performed an intense bout of leg resistance exercise following ingestion of 1 of 2 drinks: flavored water (PL) or 16.6g of whey protein+ 3.4g of leucine (W+L). Arteriovenous amino acid balance across the leg was measured to assess the anabolic response of muscle in each group. Arterial amino acid concentrations increased in response to ingestion of W+L. Amino acid concentrations peaked between 60 and 120min after ingestion, and then declined to baseline values. Valine concentration decreased to levels significantly lower than baseline. Net balance of leucine, threonine, and phenylalanine did not change following PL ingestion, but increased and remained elevated above baseline for 90120min following W+L ingestion. Leucine (138 37 and23 23mg), phenylalanine (58 28 and38 14mg), and threonine (138 37 and23 23mg) uptake was greater for W+L than for PL over the 5.5h following drink ingestion. Our results indicate that the whey protein plus leucine in healthy young volunteers results in an anabolic response in muscle that is not greater than the previously reported response to whey protein alone.
It has been reported that the blunted muscle protein synthetic response to food intake in the elderly can be normalized by increasing the leucine content of a meal.
The objective was to assess the effect of 3 mo of leucine supplementation on muscle mass and strength in healthy elderly men.
Thirty healthy elderly men with a mean (+/-SEM) age of 71 +/- 4 y and body mass index (BMI; in kg/m(2)) of 26.1 +/- 0.5 were randomly assigned to either a placebo-supplemented (n = 15) or leucine-supplemented (n = 15) group. Leucine or placebo (2.5 g) was administered with each main meal during a 3-mo intervention period. Whole-body insulin sensitivity, muscle strength (one-repetition maximum), muscle mass (measured by computed tomography and dual-energy X-ray absorptiometry), myosin heavy chain isoform distribution, and plasma amino acid and lipid profiles were assessed before, during, and/or after the intervention period.
No changes in skeletal muscle mass or strength were observed over time in either the leucine- or placebo-supplemented group. No improvements in indexes of whole-body insulin sensitivity (oral glucose insulin sensitivity index and the homeostasis model assessment of insulin resistance), blood glycated hemoglobin content, or the plasma lipid profile were observed. Conclusion: Long-term leucine supplementation (7.5 g/d) does not augment skeletal muscle mass or strength and does not improve glycemic control or the blood lipid profile in healthy elderly men. This trial was registered at clinicaltrials.gov as NCT00807508.
We investigated the effects of the nature of the flooding amino acid on the rate of incorporation of tracer leucine into human skeletal muscle sampled by biopsy. Twenty-three healthy young men (24.5 +/- 5. 0 yr, 76.2 +/- 8.3 kg) were studied in groups of four or five. First, the effects of flooding with phenylalanine, threonine, or arginine (all at 0.05 g/kg body wt) on the incorporation of tracer [13C]leucine were studied. Then the effects of flooding with labeled [13C]glycine [0.1 g/kg body wt, 20 atoms percent excess (APE)] and [13C]serine (0.05 g/kg body wt, 15 APE) on the incorporation of simultaneously infused [13C]leucine were investigated. When a large dose of phenylalanine or threonine was administered, incorporation of the tracer leucine was significantly increased (from 0.036 to 0. 067 %/h and 0.037 to 0.070 %/h, respectively; each P < 0.01). However, when arginine, glycine, or serine was administered as a flooding dose, no stimulation of tracer leucine incorporation could be observed. These results, together with those previously obtained, suggest that large doses of individual essential, but not nonessential, amino acids are able to stimulate incorporation of constantly infused tracer amino acids into human muscle protein.
The objectives of the present study were twofold: 1) to determine whether leucine is unique among the branched-chain amino acids (BCAA) in its ability to stimulate protein synthesis in skeletal muscle of food-deprived rats; and 2) to investigate whether changes in muscle protein synthesis after leucine administration involve a signaling pathway that includes the protein kinase mammalian target of rapamycin (mTOR). In the first set of experiments, food-deprived (18 h) male rats (200 g) were orally administered saline or 270 mg valine, isoleucine or leucine. In the second set of experiments, food-deprived rats were injected intravenously with rapamycin (0.75 mg/kg), a specific inhibitor of mTOR, before leucine administration. Only leucine stimulated protein synthesis in skeletal muscle above saline-treated controls (P: < 0.05). Furthermore, leucine was most effective among the BCAA at enhancing phosphorylation of eukaryotic initiation factor (eIF), 4E binding protein 1 (4E-BP1) and the 70-kDa ribosomal protein S6 kinase (S6K1). Leucine-dependent hyperphosphorylation of 4E-BP1 increased the availability of eIF4E to form the active eIF4G.eIF4E complex. To a lesser extent, isoleucine also enhanced phosphorylation of 4E-BP1 and S6K1. Rapamycin inhibited protein synthesis in both leucine-treated and food-deprived rats. Additionally, rapamycin prevented the stimulatory effects of leucine on eIF4E availability for binding eIF4G and inhibited leucine-dependent phosphorylation of S6K1. The data demonstrate that leucine is unique among the BCAA in its ability to stimulate protein synthesis in muscle of food-deprived rats. We show for the first time that leucine-dependent stimulation of translation initiation in vivo occurs via a rapamycin-sensitive pathway.
Enhanced protein synthesis in skeletal muscle after ingestion of a balanced meal in postabsorptive rats is mimicked by oral leucine administration. To assess the contribution of insulin to the protein synthetic response to leucine, food-deprived (18 h) male rats (approximately 200 g) were intravenously administered a primed-constant infusion of somatostatin (60 microg + 3 microg.kg(-1).h(-1)) or vehicle beginning 1 h before administration of leucine (1.35 g L-leucine/kg) or saline (control). Rats were killed 15, 30, 45, 60, or 120 min after leucine administration. Compared with controls, serum insulin concentrations were elevated between 15 and 45 min after leucine administration but returned to basal values by 60 min. Somatostatin maintained insulin concentrations at basal levels throughout the time course. Protein synthesis was increased between 30 and 60 min, and this effect was blocked by somatostatin. Enhanced assembly of the mRNA cap-binding complex (composed of eukaryotic initiation factors eIF4E and eIF4G) and hyperphosphorylation of the eIF4E-binding protein 1 (4E-BP1), the 70-kDa ribosomal protein S6 kinase (S6K1), and the ribosomal protein S6 (rp S6) were observed as early as 15 min and persisted for at least 60 min. Somatostatin attenuated the leucine-induced changes in 4E-BP1 and S6K1 phosphorylation and completely blocked the change in rp S6 phosphorylation but had no effect on eIF4G small middle dot eIF4E assembly. Overall, the results suggest that the leucine-induced enhancement of protein synthesis and the phosphorylation states of 4E-BP1 and S6K1 are facilitated by the transient increase in serum insulin. In contrast, assembly of the mRNA cap-binding complex occurs independently of increases in insulin and, by itself, is insufficient to stimulate rates of protein synthesis in skeletal muscle after leucine administration.
Amino acid availability regulates cellular physiology by modulating gene expression and signal transduction pathways. However, although the signalling intermediates between nutrient availability and altered gene expression have become increasingly well documented, how eukaryotic cells sense the presence of either a nutritionally rich or deprived medium is still uncertain. From recent studies it appears that the intracellular amino acid pool size is particularly important in regulating translational effectors, thus, regulated transport of amino acids across the plasma membrane represents a means by which the cellular response to amino acids could be controlled. Furthermore, evidence from studies with transportable amino acid analogues has demonstrated that flux through amino acid transporters may act as an initiator of nutritional signalling. This evidence, coupled with the substrate selectivity and sensitivity to nutrient availability classically associated with amino acid transporters, plus the recent discovery of transporter-associated signalling proteins, demonstrates a potential role for nutrient transporters as initiators of cellular nutrient signalling. Here, we review the evidence supporting the idea that distinct amino acid "receptors" function to detect and transmit certain nutrient stimuli in higher eukaryotes. In particular, we focus on the role that amino acid transporters may play in the sensing of amino acid levels, both directly as initiators of nutrient signalling and indirectly as regulators of external amino acid access to intracellular receptor/signalling mechanisms.
Nutritional supplementation may be used to treat muscle loss with aging (sarcopenia). However, if physical activity does not increase, the elderly tend to compensate for the increased energy delivered by the supplements with reduced food intake, which results in a calorie substitution rather than supplementation. Thus, an effective supplement should stimulate muscle anabolism more efficiently than food or common protein supplements. We have shown that balanced amino acids stimulate muscle protein anabolism in the elderly, but it is unknown whether all amino acids are necessary to achieve this effect.
We assessed whether nonessential amino acids are required in a nutritional supplement to stimulate muscle protein anabolism in the elderly.
We compared the response of muscle protein metabolism to either 18 g essential amino acids (EAA group: n = 6, age 69 +/- 2 y; +/- SD) or 40 g balanced amino acids (18 g essential amino acids + 22 g nonessential amino acids, BAA group; n = 8, age 71 +/- 2 y) given orally in small boluses every 10 min for 3 h to healthy elderly volunteers. Muscle protein metabolism was measured in the basal state and during amino acid administration via L-[ring-(2)H(5)]phenylalanine infusion, femoral arterial and venous catheterization, and muscle biopsies.
Phenylalanine net balance (in nmol x min(-1). 100 mL leg volume(-1)) increased from the basal state (P < 0.01), with no differences between groups (BAA: from -16 +/- 5 to 16 +/- 4; EAA: from -18 +/- 5 to 14 +/- 13) because of an increase (P < 0.01) in muscle protein synthesis and no change in breakdown.
Essential amino acids are primarily responsible for the amino acid-induced stimulation of muscle protein anabolism in the elderly.
The present study was designed to determine postexercise muscle protein synthesis and whole body protein balance following the combined ingestion of carbohydrate with or without protein and/or free leucine. Eight male subjects were randomly assigned to three trials in which they consumed drinks containing either carbohydrate (CHO), carbohydrate and protein (CHO+PRO), or carbohydrate, protein, and free leucine (CHO+PRO+Leu) following 45 min of resistance exercise. A primed, continuous infusion of L-[ring-13C6]phenylalanine was applied, with blood samples and muscle biopsies collected to assess fractional synthetic rate (FSR) in the vastus lateralis muscle as well as whole body protein turnover during 6 h of postexercise recovery. Plasma insulin response was higher in the CHO+PRO+Leu compared with the CHO and CHO+PRO trials (+240 +/- 19% and +77 +/- 11%, respectively, P < 0.05). Whole body protein breakdown rates were lower, and whole body protein synthesis rates were higher, in the CHO+PRO and CHO+PRO+Leu trials compared with the CHO trial (P < 0.05). Addition of leucine in the CHO+PRO+Leu trial resulted in a lower protein oxidation rate compared with the CHO+PRO trial. Protein balance was negative during recovery in the CHO trial but positive in the CHO+PRO and CHO+PRO+Leu trials. In the CHO+PRO+Leu trial, whole body net protein balance was significantly greater compared with values observed in the CHO+PRO and CHO trials (P < 0.05). Mixed muscle FSR, measured over a 6-h period of postexercise recovery, was significantly greater in the CHO+PRO+Leu trial compared with the CHO trial (0.095 +/- 0.006 vs. 0.061 +/- 0.008%/h, respectively, P < 0.05), with intermediate values observed in the CHO+PRO trial (0.0820 +/- 0.0104%/h). We conclude that coingestion of protein and leucine stimulates muscle protein synthesis and optimizes whole body protein balance compared with the intake of carbohydrate only.
The nature of the deficit underlying age-related muscle wasting remains controversial. To test whether it could be due to a poor anabolic response to dietary amino acids, we measured the rates of myofibrillar and sarcoplasmic muscle protein synthesis (MPS) in 44 healthy young and old men, of similar body build, after ingesting different amounts of essential amino acids (EAA). Basal rates of MPS were indistinguishable, but the elderly showed less anabolic sensitivity and responsiveness of MPS to EAA, possibly due to decreased intramuscular expression, and activation (phosphorylation) after EAA, of amino acid sensing/signaling proteins (mammalian target of rapamycin, mTOR; p70 S6 kinase, or p70(S6k); eukaryotic initiation factor [eIF]4BP-1; and eIF2B). The effects were independent of insulin signaling since plasma insulin was clamped at basal values. Associated with the anabolic deficits were marked increases in NFkappaB, the inflammation-associated transcription factor. These results demonstrate first, EAA stimulate MPS independently of increased insulin availability; second, in the elderly, a deficit in MPS in the basal state is unlikely; and third, the decreased sensitivity and responsiveness of MPS to EAA, associated with decrements in the expression and activation of components of anabolic signaling pathways, are probably major contributors to the failure of muscle maintenance in the elderly. Countermeasures to maximize muscle maintenance should target these deficits.
The progressive loss of skeletal muscle mass with aging is attributed to a disruption in the regulation of skeletal muscle protein turnover.
We investigated the effects on whole-body protein balance and mixed-muscle protein synthesis rates of the ingestion of carbohydrate with or without protein and free leucine after simulated activities of daily living.
Eight elderly (75 +/- 1 y) and 8 young (20 +/- 1 y) lean men were randomly assigned to 2 crossover experiments in which they consumed either carbohydrate (CHO) or carbohydrate plus protein and free leucine (CHO+Pro+Leu) after performing 30 min of standardized activities of daily living. Primed, continuous infusions with L-[ring-13C6]phenylalanine and L-[ring-2H2]tyrosine were applied, and blood and muscle samples were collected to assess whole-body protein turnover and the protein fractional synthetic rate in the vastus lateralis muscle over a 6-h period.
Whole-body phenylalanine and tyrosine flux were significantly higher in the young than in the elderly men (P < 0.01). Protein balance was negative in the CHO experiment but positive in the CHO+Pro+Leu experiment in both groups. Mixed-muscle protein synthesis rates were significantly greater in the CHO+Pro+Leu than in the CHO experiment in both the young (0.082 +/- 0.005%/h and 0.060 +/- 0.005%/h, respectively; P < 0.01) and the elderly (0.072 +/- 0.006%/h and 0.043 +/- 0.003%/h, respectively; P < 0.01) subjects, with no significant differences between groups.
Co-ingestion of protein and leucine with carbohydrate after activities of daily living improves whole-body protein balance, and the increase in muscle protein synthesis rates is not significantly different between lean young and elderly men.
Background:
The progressive loss of skeletal muscle mass with aging is attributed to a disruption in the regulation of skeletal muscle protein turnover.
Objective:
We investigated the effects on whole-body protein balance and mixed-muscle protein synthesis rates of the ingestion of carbohydrate with or without protein and free leucine after simulated activities of daily living.
Design:
Eight elderly (75 +/- 1 y) and 8 young (20 +/- 1 y) lean men were randomly assigned to 2 crossover experiments in which they consumed either carbohydrate (CHO) or carbohydrate plus protein and free leucine (CHO+Pro+Leu) after performing 30 min of standardized activities of daily living. Primed, continuous infusions with L-[ring-13C6]phenylalanine and L-[ring-2H2]tyrosine were applied, and blood and muscle samples were collected to assess whole-body protein turnover and the protein fractional synthetic rate in the vastus lateralis muscle over a 6-h period.
Results:
Whole-body phenylalanine and tyrosine flux were significantly higher in the young than in the elderly men (P < 0.01). Protein balance was negative in the CHO experiment but positive in the CHO+Pro+Leu experiment in both groups. Mixed-muscle protein synthesis rates were significantly greater in the CHO+Pro+Leu than in the CHO experiment in both the young (0.082 +/- 0.005%/h and 0.060 +/- 0.005%/h, respectively; P < 0.01) and the elderly (0.072 +/- 0.006%/h and 0.043 +/- 0.003%/h, respectively; P < 0.01) subjects, with no significant differences between groups.
Conclusions:
Co-ingestion of protein and leucine with carbohydrate after activities of daily living improves whole-body protein balance, and the increase in muscle protein synthesis rates is not significantly different between lean young and elderly men.
The present study was designed to assess the effects of dietary leucine supplementation on muscle protein synthesis and whole body protein kinetics in elderly individuals. Twenty healthy male subjects (70 +/- 1 years) were studied before and after continuous ingestion of a complete balanced diet supplemented or not with leucine. A primed (3.6 mu mol kg(-1)) constant infusion (0.06 mu mol kg(-1) min(-1)) of L-[1-C-13]phenylalanine was used to determine whole body phenylalanine kinetics as well as fractional synthesis rate (FSR) in the myofibrillar fraction of muscle proteins from vastus lateralis biopsies. Whole body protein kinetics were not affected by leucine supplementation. In contrast, muscle FSR, measured over the 5-h period of feeding, was significantly greater in the volunteers given the leucine-supplemented meals compared with the control group (0.083 +/- 0.008 versus 0.053 +/- 0.009% h(-1), respectively, P < 0.05). This effect was due only to increased leucine availability because only plasma free leucine concentration significantly differed between the control and leucine-supplemented groups. We conclude that leucine supplementation during feeding improves muscle protein synthesis in the elderly independently of an overall increase of other amino acids. Whether increasing leucine intake in old people may limit muscle protein loss during ageing remains to be determined.
The authors undertook 2 crossover-designed studies to characterize plasma amino acid (AA) responses to the intake of 20 g of protein. In Study 1, 15 untrained and overnight-fasted subjects consumed 20 g protein from skim milk, soy milk, beefsteak, boiled egg, and a liquid meal supplement. In Study 2, 10 fasted endurance-trained subjects consumed 20 g protein from a protein-rich sports bar at rest and after a 60-min submaximal ride. Plasma AA concentrations were measured immediately before and for 180 min after food ingestion using a gas-chromatography flame-ionization detection technique. A pharmacokinetic analysis was undertaken for profiles of total AAs (TAA), essential AAs, branched-chain AAs (BCAA), and leucine. Although area-under-the-curve values for plasma TAA were similar across protein sources, the pattern of aminoacidemia showed robust differences between foods, with liquid forms of protein achieving peak concentrations twice as quickly after ingestion as solid protein-rich foods (e.g., ~50 min vs ~100 min) and skim milk achieving a significantly faster peak leucine concentration than all other foods (~25 min). Completing exercise before ingesting protein sources did not cause statistically significant changes in the pattern of delivery of key AAs, BCAAs, and leucine apart from a 20-40% increase in the rate of elimination. These results may be useful to plan the type and timing of intake of protein-rich foods to maximize the protein synthetic response to various stimuli such as exercise.