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Nutrient timing revisited: is there a post-exercise anabolic window?
J Int Soc Sports Nutr. 2013; 10: 5.
Published online Jan 29, 2013. doi: 10.1186/1550-2783-10-
Alan Albert Aragon and Brad Jon Schoenfeld
Abstract
Nutrient timing is a popular nutritional strategy that involves the consumption of combinations of nutrients--primarily protein and carbohydrate--in and around an exercise session. Some have claimed that this approach can produce dramatic improvements in body composition. It has even been postulated that the timing of nutritional consumption may be more important than the absolute daily intake of nutrients. The post-exercise period is widely considered the most critical part of nutrient timing. Theoretically, consuming the proper ratio of nutrients during this time not only initiates the rebuilding of damaged muscle tissue and restoration of energy reserves, but it does so in a supercompensated fashion that enhances both body composition and exercise performance. Several researchers have made reference to an anabolic “window of opportunity” whereby a limited time exists after training to optimize training-related muscular adaptations. However, the importance - and even the existence - of a post-exercise ‘window’ can vary according to a number of factors. Not only is nutrient timing research open to question in terms of applicability, but recent evidence has directly challenged the classical view of the relevance of post-exercise nutritional intake with respect to anabolism. Therefore, the purpose of this paper will be twofold: 1) to review the existing literature on the effects of nutrient timing with respect to post-exercise muscular adaptations, and; 2) to draw relevant conclusions that allow practical, evidence-based nutritional recommendations to be made for maximizing the anabolic response to exercise.
Introduction
Over the past two decades, nutrient timing has been the subject of numerous research studies and reviews. The basis of nutrient timing involves the consumption of combinations of nutrients--primarily protein and carbohydrate--in and around an exercise session. The strategy is designed to maximize exercise-induced muscular adaptations and facilitate repair of damaged tissue [1]. Some have claimed that such timing strategies can produce dramatic improvements in body composition, particularly with respect to increases in fat-free mass [2]. It has even been postulated that the timing of nutritional consumption may be more important than the absolute daily intake of nutrients [3].
The post-exercise period is often considered the most critical part of nutrient timing. An intense resistance training workout results in the depletion of a significant proportion of stored fuels (including glycogen and amino acids) as well as causing damage to muscle fibers. Theoretically, consuming the proper ratio of nutrients during this time not only initiates the rebuilding of damaged tissue and restoration of energy reserves, but it does so in a supercompensated fashion that enhances both body composition and exercise performance. Several researchers have made reference to an “anabolic window of opportunity” whereby a limited time exists after training to optimize training-related muscular adaptations [3-5].
However, the importance – and even the existence – of a post-exercise ‘window’ can vary according to a number of factors. Not only is nutrient timing research open to question in terms of applicability, but recent evidence has directly challenged the classical view of the relevance of post-exercise nutritional intake on anabolism. Therefore, the purpose of this paper will be twofold: 1) to review the existing literature on the effects of nutrient timing with respect to post-exercise muscular adaptations, and; 2) to draw relevant conclusions that allow evidence-based nutritional recommendations to be made for maximizing the anabolic response to exercise.
Glycogen Repletion
A primary goal of traditional post-workout nutrient timing recommendations is to replenish glycogen stores. Glycogen is considered essential to optimal resistance training performance, with as much as 80% of ATP production during such training derived from glycolysis [6]. MacDougall et al. [7] demonstrated that a single set of elbow flexion at 80% of 1 repetition maximum (RM) performed to muscular failure caused a 12% reduction in mixed-muscle glycogen concentration, while three sets at this intensity resulted in a 24% decrease. Similarly, Robergs et al. [8] reported that 3 sets of 12 RM performed to muscular failure resulted in a 26.1% reduction of glycogen stores in the vastus lateralis while six sets at this intensity led to a 38% decrease, primarily resulting from glycogen depletion in type II fibers compared to type I fibers. It therefore stands to reason that typical high volume bodybuilding-style workouts involving multiple exercises and sets for the same muscle group would deplete the majority of local glycogen stores.
In addition, there is evidence that glycogen serves to mediate intracellular signaling. This appears to be due, at least in part, to its negative regulatory effects on AMP-activated protein kinase (AMPK). Muscle anabolism and catabolism are regulated by a complex cascade of signaling pathways. Several pathways that have been identified as particularly important to muscle anabolism include mammalian target of rapamycin (mTOR), mitogen-activated protein kinase (MAPK), and various calcium- (Ca2+) dependent pathways. AMPK, on the other hand, is a cellular energy sensor that serves to enhance energy availability. As such, it blunts energy-consuming processes including the activation of mTORC1 mediated by insulin and mechanical tension, as well as heightening catabolic processes such as glycolysis, beta-oxidation, and protein degradation [9]. mTOR is considered a master network in the regulation of skeletal muscle growth [10,11], and its inhibition has a decidedly negative effect on anabolic processes [12]. Glycogen has been shown to inhibit purified AMPK in cell-free assays [13], and low glycogen levels are associated with an enhanced AMPK activity in humans in vivo[14].
Creer et al. [15] demonstrated that changes in the phosphorylation of protein kinase B (Akt) are dependent on pre-exercise muscle glycogen content. After performing 3 sets of 10 repetitions of knee extensions with a load equating to 70% of 1 repetition maximum, early phase post-exercise Akt phosphorylation was increased only in the glycogen-loaded muscle, with no effect seen in the glycogen-depleted contralateral muscle. Glycogen inhibition also has been shown to blunt S6K activation, impair translation, and reduce the amount of mRNA of genes responsible for regulating muscle hypertrophy [16,17]. In contrast to these findings, a recent study by Camera et al. [18] found that high-intensity resistance training with low muscle glycogen levels did not impair anabolic signaling or muscle protein synthesis (MPS) during the early (4 h) postexercise recovery period. The discrepancy between studies is not clear at this time.
Glycogen availability also has been shown to mediate muscle protein breakdown. Lemon and Mullin [19] found that nitrogen losses more than doubled following a bout of exercise in a glycogen-depleted versus glycogen-loaded state. Other researchers have displayed a similar inverse relationship between glycogen levels and proteolysis [20]. Considering the totality of evidence, maintaining a high intramuscular glycogen content at the onset of training appears beneficial to desired resistance training outcomes.
Studies show a supercompensation of glycogen stores when carbohydrate is consumed immediately post-exercise, and delaying consumption by just 2 hours attenuates the rate of muscle glycogen re-synthesis by as much as 50% [21]. Exercise enhances insulin-stimulated glucose uptake following a workout with a strong correlation noted between the amount of uptake and the magnitude of glycogen utilization [22]. This is in part due to an increase in the translocation of GLUT4 during glycogen depletion [23,24] thereby facilitating entry of glucose into the cell. In addition, there is an exercise-induced increase in the activity of glycogen synthase—the principle enzyme involved in promoting glycogen storage [25]. The combination of these factors facilitates the rapid uptake of glucose following an exercise bout, allowing glycogen to be replenished at an accelerated rate.
There is evidence that adding protein to a post-workout carbohydrate meal can enhance glycogen re-synthesis. Berardi et al. [26] demonstrated that consuming a protein-carbohydrate supplement in the 2-hour period following a 60-minute cycling bout resulted in significantly greater glycogen resynthesis compared to ingesting a calorie-equated carbohydrate solution alone. Similarly, Ivy et al. [27] found that consumption of a combination of protein and carbohydrate after a 2+ hour bout of cycling and sprinting increased muscle glycogen content significantly more than either a carbohydrate-only supplement of equal carbohydrate or caloric equivalency. The synergistic effects of protein-carbohydrate have been attributed to a more pronounced insulin response [28], although it should be noted that not all studies support these findings [29]. Jentjens et al. [30] found that given ample carbohydrate dosing (1.2 g/kg/hr), the addition of a protein and amino acid mixture (0.4 g/kg/hr) did not increase glycogen synthesis during a 3-hour post-depletion recovery period.
Despite a sound theoretical basis, the practical significance of expeditiously repleting glycogen stores remains dubious. Without question, expediting glycogen resynthesis is important for a narrow subset of endurance sports where the duration between glycogen-depleting events is limited to less than approximately 8 hours [31]. Similar benefits could potentially be obtained by those who perform two-a-day split resistance training bouts (i.e. morning and evening) provided the same muscles will be worked during the respective sessions. However, for goals that are not specifically focused on the performance of multiple exercise bouts in the same day, the urgency of glycogen resynthesis is greatly diminished. High-intensity resistance training with moderate volume (6-9 sets per muscle group) has only been shown to reduce glycogen stores by 36-39% [8,32]. Certain athletes are prone to performing significantly more volume than this (i.e., competitive bodybuilders), but increased volume typically accompanies decreased frequency. For example, training a muscle group with 16-20 sets in a single session is done roughly once per week, whereas routines with 8-10 sets are done twice per week. In scenarios of higher volume and frequency of resistance training, incomplete resynthesis of pre-training glycogen levels would not be a concern aside from the far-fetched scenario where exhaustive training bouts of the same muscles occur after recovery intervals shorter than 24 hours. However, even in the event of complete glycogen depletion, replenishment to pre-training levels occurs well-within this timeframe, regardless of a significantly delayed post-exercise carbohydrate intake. For example, Parkin et al [33] compared the immediate post-exercise ingestion of 5 high-glycemic carbohydrate meals with a 2-hour wait before beginning the recovery feedings. No significant between-group differences were seen in glycogen levels at 8 hours and 24 hours post-exercise. In further support of this point, Fox et al. [34] saw no significant reduction in glycogen content 24 hours after depletion despite adding 165 g fat collectively to the post-exercise recovery meals and thus removing any potential advantage of high-glycemic conditions.
Protein Breakdown
Another purported benefit of post-workout nutrient timing is an attenuation of muscle protein breakdown. This is primarily achieved by spiking insulin levels, as opposed to increasing amino acid availability [35,36]. Studies show that muscle protein breakdown is only slightly elevated immediately post-exercise and then rapidly rises thereafter [36]. In the fasted state, muscle protein breakdown is significantly heightened at 195 minutes following resistance exercise, resulting in a net negative protein balance [37]. These values are increased as much as 50% at the 3 hour mark, and elevated proteolysis can persist for up to 24 hours of the post-workout period [36].
Although insulin has known anabolic properties [38,39], its primary impact post-exercise is believed to be anti-catabolic [40-43]. The mechanisms by which insulin reduces proteolysis are not well understood at this time. It has been theorized that insulin-mediated phosphorylation of PI3K/Akt inhibits transcriptional activity of the proteolytic Forkhead family of transcription factors, resulting in their sequestration in the sarcoplasm away from their target genes [44]. Down-regulation of other aspects of the ubiquitin-proteasome pathway are also believed to play a role in the process [45]. Given that muscle hypertrophy represents the difference between myofibrillar protein synthesis and proteolysis, a decrease in protein breakdown would conceivably enhance accretion of contractile proteins and thus facilitate greater hypertrophy. Accordingly, it seems logical to conclude that consuming a protein-carbohydrate supplement following exercise would promote the greatest reduction in proteolysis since the combination of the two nutrients has been shown to elevate insulin levels to a greater extent than carbohydrate alone [28].
However, while the theoretical basis behind spiking insulin post-workout is inherently sound, it remains questionable as to whether benefits extend into practice. First and foremost, research has consistently shown that, in the presence of elevated plasma amino acids, the effect of insulin elevation on net muscle protein balance plateaus within a range of 15–30 mU/L [45,46]; roughly 3–4 times normal fasting levels. This insulinogenic effect is easily accomplished with typical mixed meals, considering that it takes approximately 1–2 hours for circulating substrate levels to peak, and 3–6 hours (or more) for a complete return to basal levels depending on the size of a meal. For example, Capaldo et al. [47] examined various metabolic effects during a 5-hour period after ingesting a solid meal comprised of 75 g carbohydrate 37 g protein, and 17 g fat. This meal was able to raise insulin 3 times above fasting levels within 30 minutes of consumption. At the 1-hour mark, insulin was 5 times greater than fasting. At the 5-hour mark, insulin was still double the fasting levels. In another example, Power et al. [48] showed that a 45g dose of whey protein isolate takes approximately 50 minutes to cause blood amino acid levels to peak. Insulin concentrations peaked 40 minutes after ingestion, and remained at elevations seen to maximize net muscle protein balance (15-30 mU/L, or 104-208 pmol/L) for approximately 2 hours. The inclusion of carbohydrate to this protein dose would cause insulin levels to peak higher and stay elevated even longer. Therefore, the recommendation for lifters to spike insulin post-exercise is somewhat trivial. The classical post-exercise objective to quickly reverse catabolic processes to promote recovery and growth may only be applicable in the absence of a properly constructed pre-exercise meal.
Moreover, there is evidence that the effect of protein breakdown on muscle protein accretion may be overstated. Glynn et al. [49] found that the post-exercise anabolic response associated with combined protein and carbohydrate consumption was largely due to an elevation in muscle protein synthesis with only a minor influence from reduced muscle protein breakdown. These results were seen regardless of the extent of circulating insulin levels. Thus, it remains questionable as to what, if any, positive effects are realized with respect to muscle growth from spiking insulin after resistance training.
Protein Synthesis
Perhaps the most touted benefit of post-workout nutrient timing is that it potentiates increases in MPS. Resistance training alone has been shown to promote a twofold increase in protein synthesis following exercise, which is counterbalanced by the accelerated rate of proteolysis [36]. It appears that the stimulatory effects of hyperaminoacidemia on muscle protein synthesis, especially from essential amino acids, are potentiated by previous exercise [35,50]. There is some evidence that carbohydrate has an additive effect on enhancing post-exercise muscle protein synthesis when combined with amino acid ingestion [51], but others have failed to find such a benefit [52,53].
Several studies have investigated whether an “anabolic window” exists in the immediate post-exercise period with respect to protein synthesis. For maximizing MPS, the evidence supports the superiority of post-exercise free amino acids and/or protein (in various permutations with or without carbohydrate) compared to solely carbohydrate or non-caloric placebo [50,51,54-59]. However, despite the common recommendation to consume protein as soon as possible post-exercise [60,61], evidence-based support for this practice is currently lacking. Levenhagen et al. [62] demonstrated a clear benefit to consuming nutrients as soon as possible after exercise as opposed to delaying consumption. Employing a within-subject design,10 volunteers (5 men, 5 women) consumed an oral supplement containing 10 g protein, 8 g carbohydrate and 3 g fat either immediately following or three hours post-exercise. Protein synthesis of the legs and whole body was increased threefold when the supplement was ingested immediately after exercise, as compared to just 12% when consumption was delayed. A limitation of the study was that training involved moderate intensity, long duration aerobic exercise. Thus, the increased fractional synthetic rate was likely due to greater mitochondrial and/or sarcoplasmic protein fractions, as opposed to synthesis of contractile elements [36]. In contrast to the timing effects shown by Levenhagen et al. [62], previous work by Rasmussen et al. [56] showed no significant difference in leg net amino acid balance between 6 g essential amino acids (EAA) co-ingested with 35 g carbohydrate taken 1 hour versus 3 hours post-exercise. Compounding the unreliability of the post-exercise ‘window’ is the finding by Tipton et al. [63] that immediate pre-exercise ingestion of the same EAA-carbohydrate solution resulted in a significantly greater and more sustained MPS response compared to the immediate post-exercise ingestion, although the validity of these findings have been disputed based on flawed methodology [36]. Notably, Fujita et al [64] saw opposite results using a similar design, except the EAA-carbohydrate was ingested 1 hour prior to exercise compared to ingestion immediately pre-exercise in Tipton et al. [63]. Adding yet more incongruity to the evidence, Tipton et al. [65] found no significant difference in net MPS between the ingestion of 20 g whey immediately pre- versus the same solution consumed 1 hour post-exercise. Collectively, the available data lack any consistent indication of an ideal post-exercise timing scheme for maximizing MPS.
It also should be noted that measures of MPS assessed following an acute bout of resistance exercise do not always occur in parallel with chronic upregulation of causative myogenic signals [66] and are not necessarily predictive of long-term hypertrophic responses to regimented resistance training [67]. Moreover, the post-exercise rise in MPS in untrained subjects is not recapitulated in the trained state [68], further confounding practical relevance. Thus, the utility of acute studies is limited to providing clues and generating hypotheses regarding hypertrophic adaptations; any attempt to extrapolate findings from such data to changes in lean body mass is speculative, at best.
J Int Soc Sports Nutr. 2013; 10: 5.
Published online Jan 29, 2013. doi: 10.1186/1550-2783-10-
Alan Albert Aragon and Brad Jon Schoenfeld
Abstract
Nutrient timing is a popular nutritional strategy that involves the consumption of combinations of nutrients--primarily protein and carbohydrate--in and around an exercise session. Some have claimed that this approach can produce dramatic improvements in body composition. It has even been postulated that the timing of nutritional consumption may be more important than the absolute daily intake of nutrients. The post-exercise period is widely considered the most critical part of nutrient timing. Theoretically, consuming the proper ratio of nutrients during this time not only initiates the rebuilding of damaged muscle tissue and restoration of energy reserves, but it does so in a supercompensated fashion that enhances both body composition and exercise performance. Several researchers have made reference to an anabolic “window of opportunity” whereby a limited time exists after training to optimize training-related muscular adaptations. However, the importance - and even the existence - of a post-exercise ‘window’ can vary according to a number of factors. Not only is nutrient timing research open to question in terms of applicability, but recent evidence has directly challenged the classical view of the relevance of post-exercise nutritional intake with respect to anabolism. Therefore, the purpose of this paper will be twofold: 1) to review the existing literature on the effects of nutrient timing with respect to post-exercise muscular adaptations, and; 2) to draw relevant conclusions that allow practical, evidence-based nutritional recommendations to be made for maximizing the anabolic response to exercise.
Introduction
Over the past two decades, nutrient timing has been the subject of numerous research studies and reviews. The basis of nutrient timing involves the consumption of combinations of nutrients--primarily protein and carbohydrate--in and around an exercise session. The strategy is designed to maximize exercise-induced muscular adaptations and facilitate repair of damaged tissue [1]. Some have claimed that such timing strategies can produce dramatic improvements in body composition, particularly with respect to increases in fat-free mass [2]. It has even been postulated that the timing of nutritional consumption may be more important than the absolute daily intake of nutrients [3].
The post-exercise period is often considered the most critical part of nutrient timing. An intense resistance training workout results in the depletion of a significant proportion of stored fuels (including glycogen and amino acids) as well as causing damage to muscle fibers. Theoretically, consuming the proper ratio of nutrients during this time not only initiates the rebuilding of damaged tissue and restoration of energy reserves, but it does so in a supercompensated fashion that enhances both body composition and exercise performance. Several researchers have made reference to an “anabolic window of opportunity” whereby a limited time exists after training to optimize training-related muscular adaptations [3-5].
However, the importance – and even the existence – of a post-exercise ‘window’ can vary according to a number of factors. Not only is nutrient timing research open to question in terms of applicability, but recent evidence has directly challenged the classical view of the relevance of post-exercise nutritional intake on anabolism. Therefore, the purpose of this paper will be twofold: 1) to review the existing literature on the effects of nutrient timing with respect to post-exercise muscular adaptations, and; 2) to draw relevant conclusions that allow evidence-based nutritional recommendations to be made for maximizing the anabolic response to exercise.
Glycogen Repletion
A primary goal of traditional post-workout nutrient timing recommendations is to replenish glycogen stores. Glycogen is considered essential to optimal resistance training performance, with as much as 80% of ATP production during such training derived from glycolysis [6]. MacDougall et al. [7] demonstrated that a single set of elbow flexion at 80% of 1 repetition maximum (RM) performed to muscular failure caused a 12% reduction in mixed-muscle glycogen concentration, while three sets at this intensity resulted in a 24% decrease. Similarly, Robergs et al. [8] reported that 3 sets of 12 RM performed to muscular failure resulted in a 26.1% reduction of glycogen stores in the vastus lateralis while six sets at this intensity led to a 38% decrease, primarily resulting from glycogen depletion in type II fibers compared to type I fibers. It therefore stands to reason that typical high volume bodybuilding-style workouts involving multiple exercises and sets for the same muscle group would deplete the majority of local glycogen stores.
In addition, there is evidence that glycogen serves to mediate intracellular signaling. This appears to be due, at least in part, to its negative regulatory effects on AMP-activated protein kinase (AMPK). Muscle anabolism and catabolism are regulated by a complex cascade of signaling pathways. Several pathways that have been identified as particularly important to muscle anabolism include mammalian target of rapamycin (mTOR), mitogen-activated protein kinase (MAPK), and various calcium- (Ca2+) dependent pathways. AMPK, on the other hand, is a cellular energy sensor that serves to enhance energy availability. As such, it blunts energy-consuming processes including the activation of mTORC1 mediated by insulin and mechanical tension, as well as heightening catabolic processes such as glycolysis, beta-oxidation, and protein degradation [9]. mTOR is considered a master network in the regulation of skeletal muscle growth [10,11], and its inhibition has a decidedly negative effect on anabolic processes [12]. Glycogen has been shown to inhibit purified AMPK in cell-free assays [13], and low glycogen levels are associated with an enhanced AMPK activity in humans in vivo[14].
Creer et al. [15] demonstrated that changes in the phosphorylation of protein kinase B (Akt) are dependent on pre-exercise muscle glycogen content. After performing 3 sets of 10 repetitions of knee extensions with a load equating to 70% of 1 repetition maximum, early phase post-exercise Akt phosphorylation was increased only in the glycogen-loaded muscle, with no effect seen in the glycogen-depleted contralateral muscle. Glycogen inhibition also has been shown to blunt S6K activation, impair translation, and reduce the amount of mRNA of genes responsible for regulating muscle hypertrophy [16,17]. In contrast to these findings, a recent study by Camera et al. [18] found that high-intensity resistance training with low muscle glycogen levels did not impair anabolic signaling or muscle protein synthesis (MPS) during the early (4 h) postexercise recovery period. The discrepancy between studies is not clear at this time.
Glycogen availability also has been shown to mediate muscle protein breakdown. Lemon and Mullin [19] found that nitrogen losses more than doubled following a bout of exercise in a glycogen-depleted versus glycogen-loaded state. Other researchers have displayed a similar inverse relationship between glycogen levels and proteolysis [20]. Considering the totality of evidence, maintaining a high intramuscular glycogen content at the onset of training appears beneficial to desired resistance training outcomes.
Studies show a supercompensation of glycogen stores when carbohydrate is consumed immediately post-exercise, and delaying consumption by just 2 hours attenuates the rate of muscle glycogen re-synthesis by as much as 50% [21]. Exercise enhances insulin-stimulated glucose uptake following a workout with a strong correlation noted between the amount of uptake and the magnitude of glycogen utilization [22]. This is in part due to an increase in the translocation of GLUT4 during glycogen depletion [23,24] thereby facilitating entry of glucose into the cell. In addition, there is an exercise-induced increase in the activity of glycogen synthase—the principle enzyme involved in promoting glycogen storage [25]. The combination of these factors facilitates the rapid uptake of glucose following an exercise bout, allowing glycogen to be replenished at an accelerated rate.
There is evidence that adding protein to a post-workout carbohydrate meal can enhance glycogen re-synthesis. Berardi et al. [26] demonstrated that consuming a protein-carbohydrate supplement in the 2-hour period following a 60-minute cycling bout resulted in significantly greater glycogen resynthesis compared to ingesting a calorie-equated carbohydrate solution alone. Similarly, Ivy et al. [27] found that consumption of a combination of protein and carbohydrate after a 2+ hour bout of cycling and sprinting increased muscle glycogen content significantly more than either a carbohydrate-only supplement of equal carbohydrate or caloric equivalency. The synergistic effects of protein-carbohydrate have been attributed to a more pronounced insulin response [28], although it should be noted that not all studies support these findings [29]. Jentjens et al. [30] found that given ample carbohydrate dosing (1.2 g/kg/hr), the addition of a protein and amino acid mixture (0.4 g/kg/hr) did not increase glycogen synthesis during a 3-hour post-depletion recovery period.
Despite a sound theoretical basis, the practical significance of expeditiously repleting glycogen stores remains dubious. Without question, expediting glycogen resynthesis is important for a narrow subset of endurance sports where the duration between glycogen-depleting events is limited to less than approximately 8 hours [31]. Similar benefits could potentially be obtained by those who perform two-a-day split resistance training bouts (i.e. morning and evening) provided the same muscles will be worked during the respective sessions. However, for goals that are not specifically focused on the performance of multiple exercise bouts in the same day, the urgency of glycogen resynthesis is greatly diminished. High-intensity resistance training with moderate volume (6-9 sets per muscle group) has only been shown to reduce glycogen stores by 36-39% [8,32]. Certain athletes are prone to performing significantly more volume than this (i.e., competitive bodybuilders), but increased volume typically accompanies decreased frequency. For example, training a muscle group with 16-20 sets in a single session is done roughly once per week, whereas routines with 8-10 sets are done twice per week. In scenarios of higher volume and frequency of resistance training, incomplete resynthesis of pre-training glycogen levels would not be a concern aside from the far-fetched scenario where exhaustive training bouts of the same muscles occur after recovery intervals shorter than 24 hours. However, even in the event of complete glycogen depletion, replenishment to pre-training levels occurs well-within this timeframe, regardless of a significantly delayed post-exercise carbohydrate intake. For example, Parkin et al [33] compared the immediate post-exercise ingestion of 5 high-glycemic carbohydrate meals with a 2-hour wait before beginning the recovery feedings. No significant between-group differences were seen in glycogen levels at 8 hours and 24 hours post-exercise. In further support of this point, Fox et al. [34] saw no significant reduction in glycogen content 24 hours after depletion despite adding 165 g fat collectively to the post-exercise recovery meals and thus removing any potential advantage of high-glycemic conditions.
Protein Breakdown
Another purported benefit of post-workout nutrient timing is an attenuation of muscle protein breakdown. This is primarily achieved by spiking insulin levels, as opposed to increasing amino acid availability [35,36]. Studies show that muscle protein breakdown is only slightly elevated immediately post-exercise and then rapidly rises thereafter [36]. In the fasted state, muscle protein breakdown is significantly heightened at 195 minutes following resistance exercise, resulting in a net negative protein balance [37]. These values are increased as much as 50% at the 3 hour mark, and elevated proteolysis can persist for up to 24 hours of the post-workout period [36].
Although insulin has known anabolic properties [38,39], its primary impact post-exercise is believed to be anti-catabolic [40-43]. The mechanisms by which insulin reduces proteolysis are not well understood at this time. It has been theorized that insulin-mediated phosphorylation of PI3K/Akt inhibits transcriptional activity of the proteolytic Forkhead family of transcription factors, resulting in their sequestration in the sarcoplasm away from their target genes [44]. Down-regulation of other aspects of the ubiquitin-proteasome pathway are also believed to play a role in the process [45]. Given that muscle hypertrophy represents the difference between myofibrillar protein synthesis and proteolysis, a decrease in protein breakdown would conceivably enhance accretion of contractile proteins and thus facilitate greater hypertrophy. Accordingly, it seems logical to conclude that consuming a protein-carbohydrate supplement following exercise would promote the greatest reduction in proteolysis since the combination of the two nutrients has been shown to elevate insulin levels to a greater extent than carbohydrate alone [28].
However, while the theoretical basis behind spiking insulin post-workout is inherently sound, it remains questionable as to whether benefits extend into practice. First and foremost, research has consistently shown that, in the presence of elevated plasma amino acids, the effect of insulin elevation on net muscle protein balance plateaus within a range of 15–30 mU/L [45,46]; roughly 3–4 times normal fasting levels. This insulinogenic effect is easily accomplished with typical mixed meals, considering that it takes approximately 1–2 hours for circulating substrate levels to peak, and 3–6 hours (or more) for a complete return to basal levels depending on the size of a meal. For example, Capaldo et al. [47] examined various metabolic effects during a 5-hour period after ingesting a solid meal comprised of 75 g carbohydrate 37 g protein, and 17 g fat. This meal was able to raise insulin 3 times above fasting levels within 30 minutes of consumption. At the 1-hour mark, insulin was 5 times greater than fasting. At the 5-hour mark, insulin was still double the fasting levels. In another example, Power et al. [48] showed that a 45g dose of whey protein isolate takes approximately 50 minutes to cause blood amino acid levels to peak. Insulin concentrations peaked 40 minutes after ingestion, and remained at elevations seen to maximize net muscle protein balance (15-30 mU/L, or 104-208 pmol/L) for approximately 2 hours. The inclusion of carbohydrate to this protein dose would cause insulin levels to peak higher and stay elevated even longer. Therefore, the recommendation for lifters to spike insulin post-exercise is somewhat trivial. The classical post-exercise objective to quickly reverse catabolic processes to promote recovery and growth may only be applicable in the absence of a properly constructed pre-exercise meal.
Moreover, there is evidence that the effect of protein breakdown on muscle protein accretion may be overstated. Glynn et al. [49] found that the post-exercise anabolic response associated with combined protein and carbohydrate consumption was largely due to an elevation in muscle protein synthesis with only a minor influence from reduced muscle protein breakdown. These results were seen regardless of the extent of circulating insulin levels. Thus, it remains questionable as to what, if any, positive effects are realized with respect to muscle growth from spiking insulin after resistance training.
Protein Synthesis
Perhaps the most touted benefit of post-workout nutrient timing is that it potentiates increases in MPS. Resistance training alone has been shown to promote a twofold increase in protein synthesis following exercise, which is counterbalanced by the accelerated rate of proteolysis [36]. It appears that the stimulatory effects of hyperaminoacidemia on muscle protein synthesis, especially from essential amino acids, are potentiated by previous exercise [35,50]. There is some evidence that carbohydrate has an additive effect on enhancing post-exercise muscle protein synthesis when combined with amino acid ingestion [51], but others have failed to find such a benefit [52,53].
Several studies have investigated whether an “anabolic window” exists in the immediate post-exercise period with respect to protein synthesis. For maximizing MPS, the evidence supports the superiority of post-exercise free amino acids and/or protein (in various permutations with or without carbohydrate) compared to solely carbohydrate or non-caloric placebo [50,51,54-59]. However, despite the common recommendation to consume protein as soon as possible post-exercise [60,61], evidence-based support for this practice is currently lacking. Levenhagen et al. [62] demonstrated a clear benefit to consuming nutrients as soon as possible after exercise as opposed to delaying consumption. Employing a within-subject design,10 volunteers (5 men, 5 women) consumed an oral supplement containing 10 g protein, 8 g carbohydrate and 3 g fat either immediately following or three hours post-exercise. Protein synthesis of the legs and whole body was increased threefold when the supplement was ingested immediately after exercise, as compared to just 12% when consumption was delayed. A limitation of the study was that training involved moderate intensity, long duration aerobic exercise. Thus, the increased fractional synthetic rate was likely due to greater mitochondrial and/or sarcoplasmic protein fractions, as opposed to synthesis of contractile elements [36]. In contrast to the timing effects shown by Levenhagen et al. [62], previous work by Rasmussen et al. [56] showed no significant difference in leg net amino acid balance between 6 g essential amino acids (EAA) co-ingested with 35 g carbohydrate taken 1 hour versus 3 hours post-exercise. Compounding the unreliability of the post-exercise ‘window’ is the finding by Tipton et al. [63] that immediate pre-exercise ingestion of the same EAA-carbohydrate solution resulted in a significantly greater and more sustained MPS response compared to the immediate post-exercise ingestion, although the validity of these findings have been disputed based on flawed methodology [36]. Notably, Fujita et al [64] saw opposite results using a similar design, except the EAA-carbohydrate was ingested 1 hour prior to exercise compared to ingestion immediately pre-exercise in Tipton et al. [63]. Adding yet more incongruity to the evidence, Tipton et al. [65] found no significant difference in net MPS between the ingestion of 20 g whey immediately pre- versus the same solution consumed 1 hour post-exercise. Collectively, the available data lack any consistent indication of an ideal post-exercise timing scheme for maximizing MPS.
It also should be noted that measures of MPS assessed following an acute bout of resistance exercise do not always occur in parallel with chronic upregulation of causative myogenic signals [66] and are not necessarily predictive of long-term hypertrophic responses to regimented resistance training [67]. Moreover, the post-exercise rise in MPS in untrained subjects is not recapitulated in the trained state [68], further confounding practical relevance. Thus, the utility of acute studies is limited to providing clues and generating hypotheses regarding hypertrophic adaptations; any attempt to extrapolate findings from such data to changes in lean body mass is speculative, at best.