Get_Swole
MuscleChemistry Registered Member
I know some of these are pretty damn long, but im sure someone else would enjoy reading them besides just me.
Anabolic Effects of Branched Chain Amino Acids
By: Robbie Durand, M.A.
There is little doubt that efficient recovery of protein metabolism is critical to the anabolic process and preservation of skeletal muscle hypertrophy. Amino acid supplementation has been demonstrated to heighten recovery during bodybuilding programs by increasing protein synthesis, reducing muscle protein breakdown, and reducing muscle damage. The free amino acids in humans are classified as essential and non-essential. Essential amino acids need to be obtained from the diet whereas nonessential are endogenously (produced from within the body). In terms of muscle protein synthesis, only the essential amino acids are needed. For example, after an intense resistance exercise program when subjects are administered either a mixture of non-essential or essential amino acids alone. Only essential amino increased protein synthesis rates, non-essential amino acids had no effect (20). Amino acids are well known to stimulate insulin, growth hormone, and IGF-I and may even enhance testosterone production. In the journal of Metabolism the anabolic effects of essential amino acids were documented as they prevented strength loss during an intense overreaching program. Overreaching is an accumulation of training stress resulting in a short-term decrement in performance capacity followed by a super compensation effect. In that study, seventeen resistance-trained men were randomly assigned to either an essential amino acid group or placebo group before embarking on a five-week training program designed to overtrain them. Each participant ingested the amino acid supplement separate from meals (i.e. 1 hour before a meal and 2 hours after a meal). In relation to the exercise bout, supplement doses were taken 1 to 2 hours pre- and post exercise. Thus, the sequence was a morning dose, afternoon dose before workout, afternoon dose after workout, and evening dose. After one week of overreaching, 1RM on the bench press had decreased in the placebo group, but not the essential amino acid group. Both groups then showed similar increases in strength in week's three to five, but total testosterone levels were higher in the amino acid group during most of the study (6). The study indicates amino acid supplementation is effective in preventing the initial strength loss seen when first starting a high-volume program, probably by creating an anabolic environment and reducing muscle damage. It has also been demonstrated that ingestion or infusion of essential amino provides a potent anabolic stimulus in both healthy young and elderly subjects (1,2,3,4). Two studies have reported that when whey protein or essential amino acids are matched for their effects on net muscle protein synthesis both supplements stimulated protein synthesis rates, but the increase was greatest in the essential amino acid group (5, 41). Other studies have shown that consuming essential amino acids (15 g of essential amino acids and 30 g of sucrose) between whole meals produces a greater anabolic effect than ingestion of liquid meal replacement (protein 23g, carbohydrate 126g, and fat 30g) (1).
Amino Acids, Resistance Exercise, and Protein Synthesis
High protein intakes increase the retention of nitrogen and place and bodybuilders in a more anabolic environment. For example, Tarnopolsky and colleagues found that when bodybuilders were administered 0.8, 1.4, and 2.4 grams of protein per kg of bodyweight that nitrogen balance was negative in the low protein condition, and increased from moderate to high protein conditions (7). Protein as you know is broken down in to amino acids. All bodybuilders know you need protein and sufficient calories to increase muscle mass but new research suggest that the timing of amino acid intake is essential for increasing muscle mass. For years, bodybuilders were told that there was a heightened 45 minute "window of opportunity" after exercise in which anabolic reactions take place. So why is it so important to get essential amino acids into your system after exercise? One reason is that heavy intense exercise stimulates cortisol production, which results in increases in muscle protein breakdown. Researchers wanted to know what happened when you infuse subjects with cortisol and the effects essential amino acids had on cortisol. Administration of essential amino acids not only increased protein synthesis after cortisol infusions but acutely reversed the effects of cortisol (4). After resistance exercise protein synthesis have been documented to be increased for up to 48 hours following an intense resistance exercise program (19), however there is some truth to the “window of opportunity” theory. Studies have reported that a delay in protein consumption after exercise may delay protein synthesis rates. For example, after intense leg exercise subjects were fed an oral nutrient supplement (10 g protein, 8 g carbohydrate, and 3 g fat) which was administered either immediately after exercise or 3 hours after exercise. Researchers found that the net uptake of amino acids and glucose immediately after exercise led to more substrate and energy availability within the leg for protein synthesis. Although leg protein breakdown was not significantly different between the two treatments, leg protein synthesis was increased more than threefold when they consumed a protein supplement immediately after exercise vs. 3 hours later. Hence, there was a net increase in leg protein when nutrients were ingested immediately after exercise, which was in contrast to the net loss of leg protein when nutrients were given 3 h after exercise (13). For an even greater effect on increasing protein synthesis rates, researchers have discovered that using an amino acid/carbohydrate beverage before exercise led to a greater protein synthesis than taken immediately after exercise (14). It seems that in order to receive the optimal effects of protein supplements the “window of opportunity” theory should be changed to consuming protein supplements or amino acid supplements before and after exercise for optimal anabolic gains. The anabolic response of muscle protein synthesis to exercise results from the metabolic changes induced by the muscular concentration and the availability of amino acids. Although many bodybuilders are still using protein supplements, remember only the essential amino acids are needed for increasing protein synthesis rates. Of the eight essential amino acids, researchers have further narrowed the anabolic activity of essential amino acids down to the branched chain amino acids.
Anabolic Effects of Branched Chain Amino Acids
The branched-chain amino acids (BCAAs) are leucine, isoleucine, and valine. BCAA's seem to have fallen out of favor with most bodybuilders in favor of creatine and other products for muscle growth. Creatine is a great product but it has no effect of on human protein synthesis rates after resistance exercise (42) whereas the anabolic effect of BCAA on muscle growth, protein synthesis, and recovery is undisputable. See Table 1 for a list of documented anabolic effect of BCAA's. One study reported that when BCAA were administered before a 1-hour run, BCAA's administration before exercise resulted in post-recovery elevations in GH and testosterone. The T response was not modified during running exercise but increased during the recovery period after BCAA administration (43). The BCAA's are needed for the maintenance of muscle tissue and appear to preserve muscle stores of glycogen (a storage form of carbohydrate that can be converted into energy). BCAAs also help prevent muscle protein breakdown during exercise. Protein synthesis in skeletal muscle is produced by intake of a mixed meal is largely due to BCAA's. For example, infusions of a mixture of amino acids that contain all the amino acids except BCAA's have no effect on protein synthesis (29). BCAA have an advantage to the bodybuilder that is dieting as they have minimal calories, they are metabolized strictly in muscle, and are highly anabolic. Of the BCAA, leucine appears to be the most important of in stimulating protein. More recent studies have extended the earlier investigation to show that leucine in the most potent of the BCAA in enhancing mRNA translation of protein synthesis. In contrast to administration of either isoleucine or valine alone which have no effect on protein synthesis, leucine is unique as it is the most important regulator of protein synthesis in skeletal muscle (17). For example, a recent study reported that administration of leucine alone to fasted rats invoked the same stimulation of protein synthesis in skeletal muscle as observed after consumption of a complete meal (16). Additionally, studies using isolated muscle preparations have reported that leucine alone is sufficient to enhance protein synthesis rates (27). What's interesting about leucine is that it appears to be specific for muscle protein synthesis as opposed to other organs. For example, oral administration of leucine has no effect on global rates of protein synthesis in the liver which many amino acids have. This means muscle seems to have first takes on leucine absorption in contrast to other amino acids that are metabolized in the gut. Thus, it seems that the regulatory role of leucine may be specific to muscle (18). Leucine has a much greater impact on being incorporated into muscle than any other amino acids. A Swedish research study reported that when patients had leucine infusions followed by muscle biopsies, increases in muscle protein synthesis rates were observed and the intracellular concentrations of muscle leucine increased 3-fold in muscle, but the concentrations of most other intracellular amino acids had no change (40). The research suggests that leucine is capable of stimulating muscle protein synthesis by itself.
BCAA/Leucine and Insulin: A Powerful Anabolic Combination.
Leucine appears to regulate the energy status of the cell and intracellular concentrations of several growth factors (21). Dietary levels of BCAA or Leucine reach the blood virtually unaltered from the levels in the diet; thus leucine, reaches the peripheral muscle in direct proportion to the diet (22). Supplemental leucine allows for a muscle to achieve maximum protein synthesis and anabolic recovery (23, 24). Insulin and amino acids are needed for a synergist effect to create an anabolic environment in muscle. Researchers tested how anabolic insulin was by itself and in conjunction with amino acids. Insulin by itself was anti-catabolic in muscle by inhibiting protein breakdown whereas amino acids plus insulin largely increased protein anabolism in by stimulating protein synthesis and reducing muscle tissue breakdown. Thus their is a synergistic effect between insulin and amino acids. This is why it so important to get a combination carbohydrate/ amino acids beverage after exercise. Subsequent studies have reported that insulin infused in the brachial artery in a fasted state caused 20-fold increase in insulin but failed to stimulate muscle protein synthesis but inhibited muscle protein breakdown (32). The results support the concept that both insulin and amino acids are needed to increase muscle protein synthesis rates, insulin by itself does not increase muscle protein synthesis rates. To further support this research, if rats are administered diazoxide which prevents a rise in insulin, the stimulatory effects of protein synthesis by amino acid infusion are suppressed (15). An interesting property of the amino acid leucine is that leucine can stimulate protein synthesis thru an insulin independent mechanism. For example, protein synthesis in diabetic rats are suppressed by 35%, however leucine administration to diabetic rats increases protein synthesis by ~50%, but the rate remains below the that of non-diabetic rats (38). Overall the results demonstrate that leucine can cause increases in protein synthesis rates that are independent of insulin (18). One of the problems researchers discovered when trying to discover the mechanism that leucine increases protein synthesis is that leucine can stimulate insulin release and it was speculated that leucine administration may be causing a rise in insulin which enhanced protein synthesis rates, however subsequent studies have shown that when arterial levels of leucine are measured after ingestion of BCAA's no significant increase in arterial insulin was detected suggesting that leucine has a direct effect on muscle protein synthesis rates without insulin (31). Overall, the research suggests that Leucine can stimulate protein synthesis in skeletal muscle through both insulin-dependent and independent mechanisms.
Fasting and calorie restriction results in an increase in leucine appearance rate in the blood, an index of whole body protein breakdown. The increase in leucine appearance is consistent with a decline in insulin, because insulin normally suppresses protein breakdown. Additionally, fasting increases the hormone glucagon which has a catabolic effect on leucine ( 8 ). In skeletal muscle, exposure to glucocorticoids such as cortisol is characterized by a reduction in protein synthetic rate coincident with hampered protein synthesis rates, however oral administration of leucine reversed the catabolic effects of dexamethasone with a 1 hour of administration (28).
Get Your Swell On For Increased Protein Synthesis Rates!!
So what is it about exercise that increases protein synthesis rates? Blood flow is greatly enhances after exercise to working muscle and blood is shunted away from other organs. This result is a greater delivery of amino acids to muscle tissue, and a low percentage of amino acids being absorbed by the gut. Therefore pre-workout leucine or BCAA timing is essential for creating an anabolic response. In animal studies, BCAA's including Leucine was highly influenced by blood flow to muscles as occurs during exercise suggesting that leucine or BCAA taken before exercise will be greatly enhance muscle protein synthesis rates due to enhanced blood flow to muscle. A recent study this month reported that when insulin was infused into subjects the change in muscle protein synthesis was predicted by changes in muscle blood flow and amino acid availability, whereas insulin concentrations and delivery did not significantly predict the response of protein synthesis (33). Taken together, these studies suggest that leucine along with enhanced blood flow significantly increases protein synthesis rates.
Leucine Increases mTOR
The BCAA leucine plays multiple roles in metabolism beyond the minimum requirement as an essential substrate for synthesis of new proteins. The potential for leucine to impact protein synthesis, insulin signaling, and production of alanine and glutamine is dependent on dietary intake and increasing leucine concentration in skeletal muscle (35, 36). In terms of anabolic activity, L-Leucine could be called the “Highlander Amino Acid: There Can Be Only One!” Leucine stimulates protein synthesis rates greater than any other amino acid. Additionally, a recent study reported that addition of leucine to a protein based supplement led to a greater protein synthesis than intake of protein supplement alone after a resistance exercise program (30). It has now been established that leucine, stimulates protein synthesis through signaling pathways that involve mTOR (10, 11). What the hell is mTOR? mTOR stands for the Mammalian Target Of Rapamycin. mTOR is a master regulator of muscle growth (cell size and division) by sensing amino acid availability and cellular energy level (25). mTOR itself is though to serve as an ATP-sensor. mTOR appears to have important effects on stimulating a variety of growth signals, resulting in protein synthesis rates. Resistance exercise, amino acids, or a combination of both are all known regulators of mTOR. When BCAA's are administered to subjects during and after one session of leg extensions, an increase in mTOR was found in recovery period (29). The exact mechanism in which mTOR regulates muscle hypertrophy is unknown. Interestingly, IGF-I dependent muscle hypertrophy is dependent on mTOR pathway. Studies have reported that if mTOR is inhibited by drugs, neither insulin, amino acids, or resistance exercise will cause increases in proteins synthesis rates (26). Overall, the available evidence strongly suggests that mTOR plays a crucial role in controlling muscle cell growth.
Leucine before Competitions: Reducing Appetite and Maintaining an Anabolic Environment
Another benefit of leucine has been found this month in terms of bodybuilding. mTOR is not only found in muscle but also in brain areas that regulate food intake. The research is still premature but rats that are administered L-leucine have a reduction in appetite. In several experiments, L-leucine decreases food intake, interesting L-valine another BCAA had no effect on food intake and did not stimulate mTOR activity in the brain areas regulating food intake (34). Leucine is now known to interact with the insulin-signaling pathway with apparent modulation of the downstream signal for control of protein synthesis, resulting in maintenance of muscle protein during periods of restricted energy intake. Oral intake of 2.5 g of leucine stimulates muscle protein synthesis after exercise or an overnight fast (23, 37). These studies support the role of leucine as a key amino acid for reversing catabolic conditions. Two weight loss trials using diets designed to provide 10 g/d of leucine (125 g/d of dietary protein) with a minimum of 2.5 g of leucine at each of three meals. In comparisons with subjects following the USDA Food Guide Pyramid, subjects consuming the protein-rich diets lost more weight and were more effective in correcting body composition during weight loss (39). Consumption of the protein-rich diet resulted in greater loss of body fat and attenuated loss of lean tissue consistent with a protein sparing mechanism for leucine. It seems reasonable that if a bodybuilder is getting ready for a competition, adding a few grams of L-Leucine to his diet may reduce appetite yet still maintain an anabolic environment.
Leucine and Aging.
Aging is associated with a decrease in muscle mass along with concomitant decrease in anabolic hormones, interesting there is also a decrease in protein synthesis which has been termed "anabolic resistance." This is shown by a decrease sensitivity and responsiveness of protein synthesis in muscle in both rats and humans. It has been reported that muscle protein anabolism to combined hyperaminoaciedmia and glucose mediated hyperinsulinemia was impaired in the elderly (29). Interestingly, a recent study reported that when younger (8 months old) and older rats (22-months-old) protein breakdown rates were higher in older rats compared to younger rats, but when older rats are fed a diet which is supplemented with 5% Leucine, there is a rejuvenation of muscle and an inhibition of protein breakdown similar to young rats (12). Thus, aging seems to be associated with a decrease in leucine-induced stimulation of muscle protein synthesis. When older animals are fed a high Leucine supplemented meal, it will not only restore a significant stimulation of muscle protein synthesis but this effect can be maintained for ten days (30). The long-term utilization of leucine-rich diets may therefore limit muscle protein wasting during aging.
BCAA supplements were the most popular bodybuilding supplement in the early 90's before creatine, however the reported anabolic effects of BCAA’s particularly leucine has caught the eye of many researchers in terms of increasing muscle mass, reducing muscle breakdown, and new research on reducing food intake. It has been known for many years that muscle hypertrophy comes about via an increase in the rate of protein synthesis. Leucine and BCAA have potent anabolic effects by increasing mTOR activity resulting in enhanced activation of muscle proteins. Carbohydrates, nonessential amino acids, and other amino acids do not have the stimulatory effects on protein synthesis when compared with leucine. However, in most cases, the combination of BCAA with carbohydrates produces an additive effect on the stimulation of the mTOR pathway, producing maximal rates of protein synthesis during recovery.
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Anabolic Effects of Branched Chain Amino Acids
By: Robbie Durand, M.A.
There is little doubt that efficient recovery of protein metabolism is critical to the anabolic process and preservation of skeletal muscle hypertrophy. Amino acid supplementation has been demonstrated to heighten recovery during bodybuilding programs by increasing protein synthesis, reducing muscle protein breakdown, and reducing muscle damage. The free amino acids in humans are classified as essential and non-essential. Essential amino acids need to be obtained from the diet whereas nonessential are endogenously (produced from within the body). In terms of muscle protein synthesis, only the essential amino acids are needed. For example, after an intense resistance exercise program when subjects are administered either a mixture of non-essential or essential amino acids alone. Only essential amino increased protein synthesis rates, non-essential amino acids had no effect (20). Amino acids are well known to stimulate insulin, growth hormone, and IGF-I and may even enhance testosterone production. In the journal of Metabolism the anabolic effects of essential amino acids were documented as they prevented strength loss during an intense overreaching program. Overreaching is an accumulation of training stress resulting in a short-term decrement in performance capacity followed by a super compensation effect. In that study, seventeen resistance-trained men were randomly assigned to either an essential amino acid group or placebo group before embarking on a five-week training program designed to overtrain them. Each participant ingested the amino acid supplement separate from meals (i.e. 1 hour before a meal and 2 hours after a meal). In relation to the exercise bout, supplement doses were taken 1 to 2 hours pre- and post exercise. Thus, the sequence was a morning dose, afternoon dose before workout, afternoon dose after workout, and evening dose. After one week of overreaching, 1RM on the bench press had decreased in the placebo group, but not the essential amino acid group. Both groups then showed similar increases in strength in week's three to five, but total testosterone levels were higher in the amino acid group during most of the study (6). The study indicates amino acid supplementation is effective in preventing the initial strength loss seen when first starting a high-volume program, probably by creating an anabolic environment and reducing muscle damage. It has also been demonstrated that ingestion or infusion of essential amino provides a potent anabolic stimulus in both healthy young and elderly subjects (1,2,3,4). Two studies have reported that when whey protein or essential amino acids are matched for their effects on net muscle protein synthesis both supplements stimulated protein synthesis rates, but the increase was greatest in the essential amino acid group (5, 41). Other studies have shown that consuming essential amino acids (15 g of essential amino acids and 30 g of sucrose) between whole meals produces a greater anabolic effect than ingestion of liquid meal replacement (protein 23g, carbohydrate 126g, and fat 30g) (1).
Amino Acids, Resistance Exercise, and Protein Synthesis
High protein intakes increase the retention of nitrogen and place and bodybuilders in a more anabolic environment. For example, Tarnopolsky and colleagues found that when bodybuilders were administered 0.8, 1.4, and 2.4 grams of protein per kg of bodyweight that nitrogen balance was negative in the low protein condition, and increased from moderate to high protein conditions (7). Protein as you know is broken down in to amino acids. All bodybuilders know you need protein and sufficient calories to increase muscle mass but new research suggest that the timing of amino acid intake is essential for increasing muscle mass. For years, bodybuilders were told that there was a heightened 45 minute "window of opportunity" after exercise in which anabolic reactions take place. So why is it so important to get essential amino acids into your system after exercise? One reason is that heavy intense exercise stimulates cortisol production, which results in increases in muscle protein breakdown. Researchers wanted to know what happened when you infuse subjects with cortisol and the effects essential amino acids had on cortisol. Administration of essential amino acids not only increased protein synthesis after cortisol infusions but acutely reversed the effects of cortisol (4). After resistance exercise protein synthesis have been documented to be increased for up to 48 hours following an intense resistance exercise program (19), however there is some truth to the “window of opportunity” theory. Studies have reported that a delay in protein consumption after exercise may delay protein synthesis rates. For example, after intense leg exercise subjects were fed an oral nutrient supplement (10 g protein, 8 g carbohydrate, and 3 g fat) which was administered either immediately after exercise or 3 hours after exercise. Researchers found that the net uptake of amino acids and glucose immediately after exercise led to more substrate and energy availability within the leg for protein synthesis. Although leg protein breakdown was not significantly different between the two treatments, leg protein synthesis was increased more than threefold when they consumed a protein supplement immediately after exercise vs. 3 hours later. Hence, there was a net increase in leg protein when nutrients were ingested immediately after exercise, which was in contrast to the net loss of leg protein when nutrients were given 3 h after exercise (13). For an even greater effect on increasing protein synthesis rates, researchers have discovered that using an amino acid/carbohydrate beverage before exercise led to a greater protein synthesis than taken immediately after exercise (14). It seems that in order to receive the optimal effects of protein supplements the “window of opportunity” theory should be changed to consuming protein supplements or amino acid supplements before and after exercise for optimal anabolic gains. The anabolic response of muscle protein synthesis to exercise results from the metabolic changes induced by the muscular concentration and the availability of amino acids. Although many bodybuilders are still using protein supplements, remember only the essential amino acids are needed for increasing protein synthesis rates. Of the eight essential amino acids, researchers have further narrowed the anabolic activity of essential amino acids down to the branched chain amino acids.
Anabolic Effects of Branched Chain Amino Acids
The branched-chain amino acids (BCAAs) are leucine, isoleucine, and valine. BCAA's seem to have fallen out of favor with most bodybuilders in favor of creatine and other products for muscle growth. Creatine is a great product but it has no effect of on human protein synthesis rates after resistance exercise (42) whereas the anabolic effect of BCAA on muscle growth, protein synthesis, and recovery is undisputable. See Table 1 for a list of documented anabolic effect of BCAA's. One study reported that when BCAA were administered before a 1-hour run, BCAA's administration before exercise resulted in post-recovery elevations in GH and testosterone. The T response was not modified during running exercise but increased during the recovery period after BCAA administration (43). The BCAA's are needed for the maintenance of muscle tissue and appear to preserve muscle stores of glycogen (a storage form of carbohydrate that can be converted into energy). BCAAs also help prevent muscle protein breakdown during exercise. Protein synthesis in skeletal muscle is produced by intake of a mixed meal is largely due to BCAA's. For example, infusions of a mixture of amino acids that contain all the amino acids except BCAA's have no effect on protein synthesis (29). BCAA have an advantage to the bodybuilder that is dieting as they have minimal calories, they are metabolized strictly in muscle, and are highly anabolic. Of the BCAA, leucine appears to be the most important of in stimulating protein. More recent studies have extended the earlier investigation to show that leucine in the most potent of the BCAA in enhancing mRNA translation of protein synthesis. In contrast to administration of either isoleucine or valine alone which have no effect on protein synthesis, leucine is unique as it is the most important regulator of protein synthesis in skeletal muscle (17). For example, a recent study reported that administration of leucine alone to fasted rats invoked the same stimulation of protein synthesis in skeletal muscle as observed after consumption of a complete meal (16). Additionally, studies using isolated muscle preparations have reported that leucine alone is sufficient to enhance protein synthesis rates (27). What's interesting about leucine is that it appears to be specific for muscle protein synthesis as opposed to other organs. For example, oral administration of leucine has no effect on global rates of protein synthesis in the liver which many amino acids have. This means muscle seems to have first takes on leucine absorption in contrast to other amino acids that are metabolized in the gut. Thus, it seems that the regulatory role of leucine may be specific to muscle (18). Leucine has a much greater impact on being incorporated into muscle than any other amino acids. A Swedish research study reported that when patients had leucine infusions followed by muscle biopsies, increases in muscle protein synthesis rates were observed and the intracellular concentrations of muscle leucine increased 3-fold in muscle, but the concentrations of most other intracellular amino acids had no change (40). The research suggests that leucine is capable of stimulating muscle protein synthesis by itself.
BCAA/Leucine and Insulin: A Powerful Anabolic Combination.
Leucine appears to regulate the energy status of the cell and intracellular concentrations of several growth factors (21). Dietary levels of BCAA or Leucine reach the blood virtually unaltered from the levels in the diet; thus leucine, reaches the peripheral muscle in direct proportion to the diet (22). Supplemental leucine allows for a muscle to achieve maximum protein synthesis and anabolic recovery (23, 24). Insulin and amino acids are needed for a synergist effect to create an anabolic environment in muscle. Researchers tested how anabolic insulin was by itself and in conjunction with amino acids. Insulin by itself was anti-catabolic in muscle by inhibiting protein breakdown whereas amino acids plus insulin largely increased protein anabolism in by stimulating protein synthesis and reducing muscle tissue breakdown. Thus their is a synergistic effect between insulin and amino acids. This is why it so important to get a combination carbohydrate/ amino acids beverage after exercise. Subsequent studies have reported that insulin infused in the brachial artery in a fasted state caused 20-fold increase in insulin but failed to stimulate muscle protein synthesis but inhibited muscle protein breakdown (32). The results support the concept that both insulin and amino acids are needed to increase muscle protein synthesis rates, insulin by itself does not increase muscle protein synthesis rates. To further support this research, if rats are administered diazoxide which prevents a rise in insulin, the stimulatory effects of protein synthesis by amino acid infusion are suppressed (15). An interesting property of the amino acid leucine is that leucine can stimulate protein synthesis thru an insulin independent mechanism. For example, protein synthesis in diabetic rats are suppressed by 35%, however leucine administration to diabetic rats increases protein synthesis by ~50%, but the rate remains below the that of non-diabetic rats (38). Overall the results demonstrate that leucine can cause increases in protein synthesis rates that are independent of insulin (18). One of the problems researchers discovered when trying to discover the mechanism that leucine increases protein synthesis is that leucine can stimulate insulin release and it was speculated that leucine administration may be causing a rise in insulin which enhanced protein synthesis rates, however subsequent studies have shown that when arterial levels of leucine are measured after ingestion of BCAA's no significant increase in arterial insulin was detected suggesting that leucine has a direct effect on muscle protein synthesis rates without insulin (31). Overall, the research suggests that Leucine can stimulate protein synthesis in skeletal muscle through both insulin-dependent and independent mechanisms.
Fasting and calorie restriction results in an increase in leucine appearance rate in the blood, an index of whole body protein breakdown. The increase in leucine appearance is consistent with a decline in insulin, because insulin normally suppresses protein breakdown. Additionally, fasting increases the hormone glucagon which has a catabolic effect on leucine ( 8 ). In skeletal muscle, exposure to glucocorticoids such as cortisol is characterized by a reduction in protein synthetic rate coincident with hampered protein synthesis rates, however oral administration of leucine reversed the catabolic effects of dexamethasone with a 1 hour of administration (28).
Get Your Swell On For Increased Protein Synthesis Rates!!
So what is it about exercise that increases protein synthesis rates? Blood flow is greatly enhances after exercise to working muscle and blood is shunted away from other organs. This result is a greater delivery of amino acids to muscle tissue, and a low percentage of amino acids being absorbed by the gut. Therefore pre-workout leucine or BCAA timing is essential for creating an anabolic response. In animal studies, BCAA's including Leucine was highly influenced by blood flow to muscles as occurs during exercise suggesting that leucine or BCAA taken before exercise will be greatly enhance muscle protein synthesis rates due to enhanced blood flow to muscle. A recent study this month reported that when insulin was infused into subjects the change in muscle protein synthesis was predicted by changes in muscle blood flow and amino acid availability, whereas insulin concentrations and delivery did not significantly predict the response of protein synthesis (33). Taken together, these studies suggest that leucine along with enhanced blood flow significantly increases protein synthesis rates.
Leucine Increases mTOR
The BCAA leucine plays multiple roles in metabolism beyond the minimum requirement as an essential substrate for synthesis of new proteins. The potential for leucine to impact protein synthesis, insulin signaling, and production of alanine and glutamine is dependent on dietary intake and increasing leucine concentration in skeletal muscle (35, 36). In terms of anabolic activity, L-Leucine could be called the “Highlander Amino Acid: There Can Be Only One!” Leucine stimulates protein synthesis rates greater than any other amino acid. Additionally, a recent study reported that addition of leucine to a protein based supplement led to a greater protein synthesis than intake of protein supplement alone after a resistance exercise program (30). It has now been established that leucine, stimulates protein synthesis through signaling pathways that involve mTOR (10, 11). What the hell is mTOR? mTOR stands for the Mammalian Target Of Rapamycin. mTOR is a master regulator of muscle growth (cell size and division) by sensing amino acid availability and cellular energy level (25). mTOR itself is though to serve as an ATP-sensor. mTOR appears to have important effects on stimulating a variety of growth signals, resulting in protein synthesis rates. Resistance exercise, amino acids, or a combination of both are all known regulators of mTOR. When BCAA's are administered to subjects during and after one session of leg extensions, an increase in mTOR was found in recovery period (29). The exact mechanism in which mTOR regulates muscle hypertrophy is unknown. Interestingly, IGF-I dependent muscle hypertrophy is dependent on mTOR pathway. Studies have reported that if mTOR is inhibited by drugs, neither insulin, amino acids, or resistance exercise will cause increases in proteins synthesis rates (26). Overall, the available evidence strongly suggests that mTOR plays a crucial role in controlling muscle cell growth.
Leucine before Competitions: Reducing Appetite and Maintaining an Anabolic Environment
Another benefit of leucine has been found this month in terms of bodybuilding. mTOR is not only found in muscle but also in brain areas that regulate food intake. The research is still premature but rats that are administered L-leucine have a reduction in appetite. In several experiments, L-leucine decreases food intake, interesting L-valine another BCAA had no effect on food intake and did not stimulate mTOR activity in the brain areas regulating food intake (34). Leucine is now known to interact with the insulin-signaling pathway with apparent modulation of the downstream signal for control of protein synthesis, resulting in maintenance of muscle protein during periods of restricted energy intake. Oral intake of 2.5 g of leucine stimulates muscle protein synthesis after exercise or an overnight fast (23, 37). These studies support the role of leucine as a key amino acid for reversing catabolic conditions. Two weight loss trials using diets designed to provide 10 g/d of leucine (125 g/d of dietary protein) with a minimum of 2.5 g of leucine at each of three meals. In comparisons with subjects following the USDA Food Guide Pyramid, subjects consuming the protein-rich diets lost more weight and were more effective in correcting body composition during weight loss (39). Consumption of the protein-rich diet resulted in greater loss of body fat and attenuated loss of lean tissue consistent with a protein sparing mechanism for leucine. It seems reasonable that if a bodybuilder is getting ready for a competition, adding a few grams of L-Leucine to his diet may reduce appetite yet still maintain an anabolic environment.
Leucine and Aging.
Aging is associated with a decrease in muscle mass along with concomitant decrease in anabolic hormones, interesting there is also a decrease in protein synthesis which has been termed "anabolic resistance." This is shown by a decrease sensitivity and responsiveness of protein synthesis in muscle in both rats and humans. It has been reported that muscle protein anabolism to combined hyperaminoaciedmia and glucose mediated hyperinsulinemia was impaired in the elderly (29). Interestingly, a recent study reported that when younger (8 months old) and older rats (22-months-old) protein breakdown rates were higher in older rats compared to younger rats, but when older rats are fed a diet which is supplemented with 5% Leucine, there is a rejuvenation of muscle and an inhibition of protein breakdown similar to young rats (12). Thus, aging seems to be associated with a decrease in leucine-induced stimulation of muscle protein synthesis. When older animals are fed a high Leucine supplemented meal, it will not only restore a significant stimulation of muscle protein synthesis but this effect can be maintained for ten days (30). The long-term utilization of leucine-rich diets may therefore limit muscle protein wasting during aging.
BCAA supplements were the most popular bodybuilding supplement in the early 90's before creatine, however the reported anabolic effects of BCAA’s particularly leucine has caught the eye of many researchers in terms of increasing muscle mass, reducing muscle breakdown, and new research on reducing food intake. It has been known for many years that muscle hypertrophy comes about via an increase in the rate of protein synthesis. Leucine and BCAA have potent anabolic effects by increasing mTOR activity resulting in enhanced activation of muscle proteins. Carbohydrates, nonessential amino acids, and other amino acids do not have the stimulatory effects on protein synthesis when compared with leucine. However, in most cases, the combination of BCAA with carbohydrates produces an additive effect on the stimulation of the mTOR pathway, producing maximal rates of protein synthesis during recovery.
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