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ModernBCAA is designed to exploit the fundamental role that BCAAs, in particular, l-leucine, play in the enhancement of anabolic signalling, initiation translation, and muscle protein synthesis. There are several aspects of the "science behind the formulation", and a lot of these center around the unique role that leucine, the chief BCAA and EAA, plays in the initiation and mediation of anabolic signalling and muscle protein synthesis. In what follows, I will comment on some of these aspects.
One reason for the usual recommendation of protein ingestion (with some carbohydrates) post-exercise, for instance, is that exercise not only depletes glycogen stores, but also leads to a negative protein balance and ultimate reduction in mTOR signalling (via increased AMPK expression) and muscle protein synthesis. Herein comes the advantage of consuming a leucine-enriched BCAA compex such as ModernBCAA. To put it simply, BCAAs, particularly leucine, stimulate anabolic signalling through a variety of molecular mechanisms that are both mTOR-dependent and mTOR-independent. Although mechanical strain and growth factors can also activate mTOR (mammalian target of rapamycin), leucine remains one of the most potent activators of mTOR. The mTOR signalling pathway has a wide variety of functions that include the regulation of cell proliferation, cell growth, hypertrophy, and muscle protein synthesis. By activating mTOR, leucine triggers translation initiation and translational control. Translation initiation involves a chain of events that are required to ensure ribosomal complex assembly and the binding of target mRNA. So, besides being an important constituent of protein, leucine acts as a critical regulator of translation initiation of muscle protein synthesis; it is also an important regulator of the insulin phosphoinositol 3-kinase (PI3K) signalling cascade and glycemic regulation (including glucose homeostasis); it also acts as an important nitrogen donor for the production of alanine and glutamine (one reason that justifies a leucine-enriched BCAA complex such as ModernBCAA, as leucine is involved in the synthesis of other substrates important in anabolic processes); and it also acts as an important inhibitor of muscle protein degradation.
Still on PI3K, leucine, the most anabolic amino acid around, is a powerful regulator of the insulin phosphoinositol 3-kinase (PI3-K) signal cascade. Growth factors such as insulin and IGF-1 can also induce PI3K activation independently of leucine. PI3K activation usually ignites several downstream signalling events involved in cell differentiation and growth, with the serine/threonine kinase Akt/PKB (protein kinase B), being a downstream effector of PI3K. Akt/PKB phosphorylates glycogen synthase kinase 3 (GSK3), ultimately inducing an increase in muscle protein synthesis via enhanced action of eukaryotic initiation factor 2B (eIF2B). This implies that BCAAs can penetrate cells and initiate translation, independent of insulin, thus further underlining the key significance of BCAAs, especially leucine, in anabolic-anticatabolic processes. This also justifies the leucine-bias of the ModernBCAA formula.
So, in the context of the foregoing, it is not only important, but also very beneficial, to consume some leucine-enriched BCAA complex such as ModernBCAA intra-workout as well as post-workout, to take full advantage of the exercise-induced anabolic stimulus, by trigerring anabolic signalling, cell growth and hypertrophy, multiple-mechanism protein synthesis, as well as eNOS (endothelial nitric oxide synthase, also known as NOS3) signalling pathways. eNOS, as you know, is one isoform of the NOS enzyme that is responsible for producing nitric oxide and modulating vascular signals (including vasodilation and the "pump").
We have already established that intra- and post-exercise dosing of a leucine-enriched BCAA complex, such as ModernBCAA, are useful, both to counteract the exercise-induced transient inhibition in protein synthesis during exercise (itself due to the activation of AMPK caused by lowered cellular status reflected by decreased ATP/AMP ratio and glycogen depletion. AMPK activation leads to phosphorylation of the so-called tuberous sclerosis complex 2 (TSC2), an upstream negative mediator of the Ras homolog enriched in brain (Rheb) and mTOR), as well as to take advantage of ModernBCAA's positive effect on muscle protein synthesis and anabolic recovery, both via mTOR-dependent (for instance, positive upstream mTOR effectors such as Rheb, positive downstream mediators such as ribosomal proteins and kinases (p70S6k and rpS6), as well as appropriate eukaryotic initiation and elongation factors), and mTOR-independent pathways (for instance, eEF2 and eIF4G). These are molecular mechanisms that are fundamentally linked to leucine, and as such justify its significance in ModernBCAA's formulation.
BCAAs can also be useful during an endurance exercise such as cardio. In particular, exercise itself leads to a considerable increase in BCAA oxidation, implying a need to replenish BCAA concentrations. Furthermore, BCAAs can help ameliorate the fall in muscle protein synthesis (MPS) during endurance exercise. This drop in MPS is initiated by a fall in the ATP/ADP ratio, leading to activation of AMPK, and the suppression of mTOR signalling and mRNA translation. So, BCAAs not only support MPS, but also inhibit skeletal muscle protein degradation (catabolism). Furthermore, endurance exercise triggers an inhibition of protein chain elongation in an intensity-dependent manner. This occurs via a calcium-induced activation of a specific calmodulin-dependent protein kinase, an event that can be countered by BCAA ingestion. Beyond these, BCAAs reduce the incidence of central fatigue syndrome during exercise. A key cause of this central fatigue is the over expression of tryptophan in the brain, leading to a high concentration of the neurotransmitter S-hydroxytryptamine in some neurons. As both tryptophan and BCAAs are shuttled into the brain by the so-called large amino-acid transporter, the consumption of BCAAs pre- or during cardio acts to limit the uptake of tryptophan into the brain, leading to less brain fatigue. And so on. Hence, BCAAs can be useful during cardio, with leucine playing a central role.
Furthermore, as is well known, resistance exercise provokes a reduction in adenosine triphosphate (ATP), while increasing the cellular concentration of adenosine monophosphate (AMP), and depleting glycogen stores. The increase in AMP and decrease in glycogen concentrations correspond to a reduction in cellular energy status. This lower energy status induces the activation of AMPK, leading to the phosphorylation of upstream mediators of mTOR, ultimately leading to reduced mTOR signalling and its direct impact (negative) on muscle protein synthesis. The consumption of BCAAs, however, may act, via mechanisms upstream and downstream of mTOR, to boost muscle protein synthesis. Put differently, the consumption of BCAAs during resistance exercise may work to counter the exercise-induced transient negative impact on protein synthesis caused by resistance exercise.
These are, to my mind, pertinent explanations, not only of the central importance of BCAAs in molecular mechanisms relating to anabolic signalling, but also of the dominant role that leucine plays in this complex orchestration of upstream and downstream mechanisms relating to protein synthesis and anabolism, clearly justifying leucine's bias in our ModernBCAA formula.
One reason for the usual recommendation of protein ingestion (with some carbohydrates) post-exercise, for instance, is that exercise not only depletes glycogen stores, but also leads to a negative protein balance and ultimate reduction in mTOR signalling (via increased AMPK expression) and muscle protein synthesis. Herein comes the advantage of consuming a leucine-enriched BCAA compex such as ModernBCAA. To put it simply, BCAAs, particularly leucine, stimulate anabolic signalling through a variety of molecular mechanisms that are both mTOR-dependent and mTOR-independent. Although mechanical strain and growth factors can also activate mTOR (mammalian target of rapamycin), leucine remains one of the most potent activators of mTOR. The mTOR signalling pathway has a wide variety of functions that include the regulation of cell proliferation, cell growth, hypertrophy, and muscle protein synthesis. By activating mTOR, leucine triggers translation initiation and translational control. Translation initiation involves a chain of events that are required to ensure ribosomal complex assembly and the binding of target mRNA. So, besides being an important constituent of protein, leucine acts as a critical regulator of translation initiation of muscle protein synthesis; it is also an important regulator of the insulin phosphoinositol 3-kinase (PI3K) signalling cascade and glycemic regulation (including glucose homeostasis); it also acts as an important nitrogen donor for the production of alanine and glutamine (one reason that justifies a leucine-enriched BCAA complex such as ModernBCAA, as leucine is involved in the synthesis of other substrates important in anabolic processes); and it also acts as an important inhibitor of muscle protein degradation.
Still on PI3K, leucine, the most anabolic amino acid around, is a powerful regulator of the insulin phosphoinositol 3-kinase (PI3-K) signal cascade. Growth factors such as insulin and IGF-1 can also induce PI3K activation independently of leucine. PI3K activation usually ignites several downstream signalling events involved in cell differentiation and growth, with the serine/threonine kinase Akt/PKB (protein kinase B), being a downstream effector of PI3K. Akt/PKB phosphorylates glycogen synthase kinase 3 (GSK3), ultimately inducing an increase in muscle protein synthesis via enhanced action of eukaryotic initiation factor 2B (eIF2B). This implies that BCAAs can penetrate cells and initiate translation, independent of insulin, thus further underlining the key significance of BCAAs, especially leucine, in anabolic-anticatabolic processes. This also justifies the leucine-bias of the ModernBCAA formula.
So, in the context of the foregoing, it is not only important, but also very beneficial, to consume some leucine-enriched BCAA complex such as ModernBCAA intra-workout as well as post-workout, to take full advantage of the exercise-induced anabolic stimulus, by trigerring anabolic signalling, cell growth and hypertrophy, multiple-mechanism protein synthesis, as well as eNOS (endothelial nitric oxide synthase, also known as NOS3) signalling pathways. eNOS, as you know, is one isoform of the NOS enzyme that is responsible for producing nitric oxide and modulating vascular signals (including vasodilation and the "pump").
We have already established that intra- and post-exercise dosing of a leucine-enriched BCAA complex, such as ModernBCAA, are useful, both to counteract the exercise-induced transient inhibition in protein synthesis during exercise (itself due to the activation of AMPK caused by lowered cellular status reflected by decreased ATP/AMP ratio and glycogen depletion. AMPK activation leads to phosphorylation of the so-called tuberous sclerosis complex 2 (TSC2), an upstream negative mediator of the Ras homolog enriched in brain (Rheb) and mTOR), as well as to take advantage of ModernBCAA's positive effect on muscle protein synthesis and anabolic recovery, both via mTOR-dependent (for instance, positive upstream mTOR effectors such as Rheb, positive downstream mediators such as ribosomal proteins and kinases (p70S6k and rpS6), as well as appropriate eukaryotic initiation and elongation factors), and mTOR-independent pathways (for instance, eEF2 and eIF4G). These are molecular mechanisms that are fundamentally linked to leucine, and as such justify its significance in ModernBCAA's formulation.
BCAAs can also be useful during an endurance exercise such as cardio. In particular, exercise itself leads to a considerable increase in BCAA oxidation, implying a need to replenish BCAA concentrations. Furthermore, BCAAs can help ameliorate the fall in muscle protein synthesis (MPS) during endurance exercise. This drop in MPS is initiated by a fall in the ATP/ADP ratio, leading to activation of AMPK, and the suppression of mTOR signalling and mRNA translation. So, BCAAs not only support MPS, but also inhibit skeletal muscle protein degradation (catabolism). Furthermore, endurance exercise triggers an inhibition of protein chain elongation in an intensity-dependent manner. This occurs via a calcium-induced activation of a specific calmodulin-dependent protein kinase, an event that can be countered by BCAA ingestion. Beyond these, BCAAs reduce the incidence of central fatigue syndrome during exercise. A key cause of this central fatigue is the over expression of tryptophan in the brain, leading to a high concentration of the neurotransmitter S-hydroxytryptamine in some neurons. As both tryptophan and BCAAs are shuttled into the brain by the so-called large amino-acid transporter, the consumption of BCAAs pre- or during cardio acts to limit the uptake of tryptophan into the brain, leading to less brain fatigue. And so on. Hence, BCAAs can be useful during cardio, with leucine playing a central role.
Furthermore, as is well known, resistance exercise provokes a reduction in adenosine triphosphate (ATP), while increasing the cellular concentration of adenosine monophosphate (AMP), and depleting glycogen stores. The increase in AMP and decrease in glycogen concentrations correspond to a reduction in cellular energy status. This lower energy status induces the activation of AMPK, leading to the phosphorylation of upstream mediators of mTOR, ultimately leading to reduced mTOR signalling and its direct impact (negative) on muscle protein synthesis. The consumption of BCAAs, however, may act, via mechanisms upstream and downstream of mTOR, to boost muscle protein synthesis. Put differently, the consumption of BCAAs during resistance exercise may work to counter the exercise-induced transient negative impact on protein synthesis caused by resistance exercise.
These are, to my mind, pertinent explanations, not only of the central importance of BCAAs in molecular mechanisms relating to anabolic signalling, but also of the dominant role that leucine plays in this complex orchestration of upstream and downstream mechanisms relating to protein synthesis and anabolism, clearly justifying leucine's bias in our ModernBCAA formula.
