One of the more well-characterized muscle-building supplements is the branched-chain amino acid leucine, which has clearly been shown to inhibit muscle protein breakdown while simultaneously increasing the rate of muscle protein synthesis, ultimately promoting substantial muscle growth.1 Leucine consumption promotes muscle protein accumulation and muscle growth by activating the extremely important nutrient-sensing molecule mTOR, which directly turns off muscle protein degradation while activating muscle protein synthesis. Several studies have shown mTOR activation by leucine intake specifically during and after resistance exercise.2,3
Although it has been well established that leucine consumption during and after resistance exercise promotes muscle growth, the verdict is still out regarding the performance-enhancing effect from leucine consumption before training. Some of the uncertainty about leucine’s pre-workout consumption stems from the fact that leucine consumption decreases energy production within the muscle cell, potentially diminishing muscle performance during exercise. Another concern about pre-workout leucine consumption involves the likely desensitization of the potent muscle-building hormone insulin, resulting from additional leucine consumed before working out. The final concern involves the negative influence that leucine consumption may have on the central nervous system (CNS) where pre-workout leucine consumption might increase the rate of CNS fatigue, promoting overall sluggishness that decreases exercise performance.

Pre-workout Leucine Decreases Muscle Cell Energy

In order to build muscle, you’d think that you need to be in an anabolic state at all times— which might also make you believe that the ubiquitous consumption of muscle-building compounds, like leucine, should enhance muscle growth. Yet the reality is being constantly in an anabolic state is not optimal for muscle size and strength. This is mainly because maximal muscle growth requires the perfect blend of muscle-building anabolism combined with energy-producing catabolism. In other words, if you want to build muscle, something has to supply them with energy to function. Well, that’s where catabolic processes like glycogenolysis, the breakdown of glycogen into glucose for energy, play a huge role mainly because intense weightlifting requires glucose for energy. So, although leucine potently stimulates muscle growth, it also prevents the breakdown of glycogen into glucose4, reducing available energy that is necessary for muscle contraction. Of course, reduced muscular contraction decreases strength output— which likely compromises the ability to get huge.

Too Much Leucine Diminishes Muscle Growth

Insulin is the most potent muscle-building hormone produced in the human body, possessing the ability to drastically increase muscle protein synthesis and enhance muscle growth.5 Insulin achieves this muscle-building effect by binding to the insulin receptor and setting off a cascade of signaling events that eventually activates the enzyme mTOR, triggering muscle growth.6,7 However, insulin signaling is very sensitive to overstimulation— where too much insulin signaling can rapidly trigger negative feedback mechanisms that turn down insulin-driven muscle growth. In addition to the well-known influence that glucose has on insulin secretion and activity, one of the more potent insulin activators is leucine. Interestingly, several studies have shown that insulin resistance can occur with increased amino acid consumption, especially the branched-chain amino acid leucine.8,9 The exact mechanism by which leucine modulates insulin sensitivity is currently unclear. Although the decreased insulin sensitivity may be associated with greater insulin secretion induced by leucine10,11, potentially inducing insulin resistance. Of course, insulin resistance from too much leucine consumption would reduce all of insulin’s anabolic properties, meaning a decrease in muscle protein accumulation and therefore muscle growth.

Leucine Consumption Before Your Workout Promotes Sluggishness and Fatigue

The CNS, composed of the brain and spinal cord, serves as the main “processing center” for the entire nervous system that controls all the workings of your body. Neurons, or nerve cells, are the core components of the CNS that function to receive and confer all of this body-regulating information by electrical and chemical signaling. Neuronal electrical signaling is ultimately converted at the nerve ending or synapse into chemical signaling utilizing neurotransmitters that diffuse across the synapse to adjacent neurons, triggering further electrical signaling down those neurons, which eventually control numerous processes in the body.
Serotonin is a neurotransmitter secreted within the neuronal synapse that induces sleep and drowsiness. Intense exercise has been shown to increase the release of serotonin in the brain, putatively contributing to exercise-induced fatigue. Initially, it was thought that the increase in serotonin alone triggered fatigue. However, it turns out that greater fatigue from exercise is influenced more specifically by an increase in the ratio of serotonin to another neurotransmitter known as dopamine.12
The neurotransmitter dopamine has well-defined roles including increased mental arousal, improved motor control and greater levels of motivation, which all tend to improve exercise performance. Therefore, a lower serotonin to dopamine ratio, by either decreasing performance-inhibiting serotonin or increasing performance-enhancing dopamine, should improve exercise capacity. Interestingly, leucine consumption has been shown to inhibit serotonin production by preventing transport of the serotonin-precursor tryptophan into the brain.13 Because tryptophan is a building block for serotonin, lower tryptophan in the brain reduces serotonin production— suggesting that leucine consumption before exercise could actually mitigate exercise-induced fatigue.
On the other hand, a recent study by Choi et al.14 showed that leucine also competitively inhibits dopamine production by preventing the uptake of the dopamine-precursor tyrosine into the brain. Since greater brain dopamine function improves physical performance, the finding that leucine reduces dopamine levels in the brain highlights why leucine consumption, especially before exercise when motivation and energy levels are paramount, may have a detrimental influence on physical performance despite leucine’s ability to also reduce serotonin levels.
In conclusion, leucine’s capacity to trigger anabolic processes, such as muscle growth and glycogen production, makes the timing of leucine consumption very important. While leucine consumption during and after lifting weights effectively prevents muscle breakdown while enhancing muscle growth, consuming leucine before your workout appears to have several drawbacks that negatively influence exercise performance— suggesting that pre-workout leucine consumption is not best for optimal muscular performance.

For most of Michael Rudolph’s career he has been engrossed in the exercise world as either an athlete (he played college football at Hofstra University), personal trainer or as a Research Scientist (he earned a B.Sc. in Exercise Science at Hofstra University and a Ph.D. in Biochemistry and Molecular Biology from Stony Brook University). After earning his Ph.D., Michael investigated the molecular biology of exercise as a fellow at Harvard Medical School and Columbia University for over eight years. That research contributed seminally to understanding the function of the incredibly important cellular energy sensor AMPK— leading to numerous publications in peer-reviewed journals including the journal Nature. Michael is currently a scientist working at the New York Structural Biology Center doing contract work for the Department of Defense on a project involving national security.

Disclaimer: Michael Rudolph does not benefit financially from the sale of Advanced Molecular Labs (AML) products.

Anabolism is defined as the synthesis of complex molecules from more simple ones. While there are many different anabolic pathways in the human body, the one that has the greatest impact on muscle growth involves the synthesis of complex muscle proteins from simpler building blocks, known as amino acids, where the accumulation of muscle protein stemming from this anabolic process ultimately drives muscle growth.
In terms of diet, it is well established that muscle protein levels can be increased considerably after consuming the amino acid leucine, especially during and after weight training. This occurs primarily because leucine consumption activates the nutrient-sensing molecule mTOR— which directly turns on muscle protein synthesis while inhibiting muscle protein breakdown, causing muscle protein accumulation that drives muscle growth.
The direct link between leucine and muscle anabolism has engendered the idea that more leucine consumption should be better for muscle growth. Unfortunately, that just is not the case— as leucine consumption also triggers additional anabolic processes that effectively lower the amount of available energy to the muscle cell, making the consumption of leucine before exercise detrimental to performance. In addition, leucine intake before training alters brain neurochemistry, resulting in sluggishness that hinders performance.
As a result, leucine supplementation protocols must take into account the temporal influence of ingestion in order to optimize muscle growth, while also allowing for ample production of energy and the right neurotransmitters for maximum performance in the gym.

Leucine Consumption During and After Working Out Stimulates Muscle Growth

Several studies have shown mTOR activation by leucine intake directly after resistance exercise. One study by Walker et al.1 showed that leucine consumption shortly after working out increased mTOR activity for several hours post-workout, leading to greater muscle protein synthesis as compared to an exercised group that was not fed leucine. A second investigation by Pasiakos et al.2 demonstrated that consumption of leucine immediately after exercise increased muscle protein synthesis by as much as 33 percent.
At the same time as leucine consumption enhances muscle protein synthesis after resistance training, it also decreases muscle protein breakdown during and following exercise by activating mTOR 3, which turns off the enzyme AMPK.4 AMPK [AMP-activated protein kinase] is the muscle cell’s energy gauge that promotes the breakdown of protein into amino acids when muscle cell energy is low, so the amino acids can be used for energy to restore the cell’s energy status. Therefore, leucine consumption during and after workouts prevents the AMPK-driven breakdown of lean body mass, which enhances the hypertrophic response of muscle tissue.

Pre-Workout Leucine Decreases Muscle Cell Energy

As previously mentioned, the anabolic effect of leucine is not always best for performance in the weight room. This is especially true when consuming leucine before hitting the gym, as leucine activates the conversion of glucose into glycogen while simultaneously preventing the breakdown of glycogen into glucose.5 Both of these outcomes considerably reduce the available energy necessary for muscular contraction. Of course, reduced muscular contraction will decrease strength output, which at the end of the day compromises the ability to gain muscle mass and strength.

Too Much Leucine Likely Inhibits Insulin-Driven Muscle Growth

Insulin is the most potent muscle-building hormone produced in the human body, possessing the ability to drastically increase muscle protein synthesis and enhance muscle growth.6 Insulin achieves this muscle-building effect by binding to the insulin receptor and setting off a cascade of signaling events that eventually activates the enzyme mTOR, triggering muscle growth.7,8 However, insulin signaling is very sensitive to overstimulation, where too much insulin signaling can rapidly trigger negative feedback mechanisms that turn down insulin-driven muscle growth.
In addition to the well-known influence that glucose has on insulin secretion and activity, one of the more potent insulin activators is leucine. Interestingly, several studies have shown that insulin resistance can occur with increased amino acid consumption, especially the branched-chain amino acid leucine.9,10 The exact mechanism by which leucine modulates insulin sensitivity is currently unclear. The decreased insulin sensitivity may be associated with greater insulin secretion induced by leucine11,12, potentially inducing insulin resistance. Of course, insulin resistance from too much leucine consumption would reduce all of insulin’s anabolic properties, meaning a decrease in muscle protein accumulation and therefore muscle growth.

Leucine Consumption Before Your Workout Promotes Sluggishness and Fatigue

The central nervous system (CNS), composed of the brain and spinal cord, serves as the main “processing center” for the entire nervous system that controls all the workings of your body. Neurons, or nerve cells, are the core components of the CNS that function to receive and confer all of this body-regulating information by neuronal signaling. Each neuronal signal is converted at the nerve ending or synapse into chemical signaling via neurotransmitters that diffuse across the synapse to adjacent neurons— triggering further signaling down the neuron, eventually controlling many different bodily functions.
Serotonin is a neurotransmitter secreted within the neuronal synapse that induces sleep and drowsiness. Intense exercise has been shown to increase the release of serotonin in the brain, putatively contributing to exercise-induced fatigue. Initially, it was thought that the increase in serotonin alone triggered fatigue. However, it turns out that greater fatigue from exercise is influenced more specifically by an increase in the ratio of serotonin to another neurotransmitter known as dopamine.13 The neurotransmitter dopamine has well-defined roles including increased mental arousal, improved motor control and greater levels of motivation, which all tend to improve exercise performance.
Interestingly, a recent study by Choi et al.14 showed that leucine competitively inhibits dopamine production by preventing the uptake of the dopamine-precursor tyrosine into the brain. Since greater brain dopamine function improves physical performance, the finding that leucine reduces dopamine levels in the brain highlights why leucine consumption, especially before exercise when motivation and energy levels are paramount, may have a detrimental influence on physical performance.
In conclusion, leucine’s capacity to trigger anabolic processes, such as muscle growth and glycogen production, makes the timing of leucine consumption very important. While leucine consumption during and after lifting weights effectively prevents muscle breakdown while enhancing post-workout muscle protein synthesis, consuming leucine before your workout appears to have several drawbacks that negatively influence exercise performance, indicating that leucine consumption before training likely prevents optimal function and achievement.

For most of Michael Rudolph’s career he has been engrossed in the exercise world as either an athlete (he played college football at Hofstra University), personal trainer or as a Research Scientist (he earned a B.Sc. in Exercise Science at Hofstra University and a Ph.D. in Biochemistry and Molecular Biology from Stony Brook University). After earning his Ph.D., Michael investigated the molecular biology of exercise as a fellow at Harvard Medical School and Columbia University for over eight years. That research contributed seminally to understanding the function of the incredibly important cellular energy sensor AMPK— leading to numerous publications in peer-reviewed journals including the journal Nature. Michael is currently a scientist working at the New York Structural Biology Center doing contract work for the Department of Defense on a project involving national security.

Strength training promotes muscle growth and strength, but not without first driving the body into a catabolic state that breaks down specific muscle tissue components, such as glycogen and protein, to supply the energy required for muscular function during exercise. Naturally, the diminished protein and glycogen levels within the muscle cell must be replenished to prevent the potential loss of lean body mass and diminished exercise performance. The post-workout consumption of lean protein and complex carbohydrates is an important part of the replenishing process augmenting muscle growth and performance. In addition, post-workout consumption of leucine, creatine and betaine have also been shown to potently replenish the muscle cell, enhancing muscle growth and function.

Leucine Stimulates Post-workout Anabolism

The consumption of leucine is one of the more effective ways to reverse exercise-induced protein degradation in muscle. Leucine intake has been shown to directly stimulate muscle protein synthesis and inhibit muscle protein breakdown, ultimately promoting muscle growth by activating the nutrient-sensing molecule mTOR. In fact, the muscle-building effect of leucine consumption has been shown in several studies to be most potent after resistance training.
A study by Walker et al.1 showed that leucine consumption immediately after working out increased mTOR activity for many hours post-workout, leading to greater muscle protein synthesis, compared to a second group that did not take leucine after the workout. A second investigation by Pasiakos et al.2 demonstrated that consumption of leucine immediately after exercise increased muscle protein synthesis by as much as 33 percent.
Leucine consumption has also been shown to decrease the breakdown of muscle protein following exercise, once again by activating mTOR. The activation of mTOR from leucine intake results in the inactivation of the energy-sensing molecule AMPK.3,4 Since AMPK normally stimulates the conversion of protein into amino acids for energy during periods of low energy, such as exercise, to restore the energy status of the muscle cell, leucine’s ability to inactivate AMPK prevents AMPK-driven degradation of muscle protein. AMPK also promotes the breakdown of muscle glycogen into glucose, meaning leucine consumption can also restore muscle glycogen levels, especially after exercise.5

Creatine Monohydrate Boosts Muscle Energy, Size and Strength

Creatine monohydrate is one of the most well characterized muscle-building supplements on the market. Numerous studies over the years have shown the positive influence of creatine monohydrate supplementation on high-intensity exercise performance. This body of evidence clearly indicates that creatine supplementation can increase power output during intense exercise, while also stimulating muscle hypertrophy.6 The unique capacity of creatine to boost size and power stems, in part, from creatine’s ability to function as a primary energy storage molecule that rapidly reverses the depletion of muscle cell energy (ATP) during muscular contraction. The maintenance of energy levels in the muscle cell prolongs the capacity for muscular contraction, promoting superior exercise performance and greater muscle growth.7 Creatine also drives muscle growth by triggering many different cellular mechanisms, including the stimulation of muscle cell formation8 and increased muscle protein synthesis.9

Combining Leucine With Creatine Monohydrate Limits Myostatin Function

The muscle-depleting molecule myostatin vigorously thwarts muscle growth by blocking several key anabolic processes, such as the formation of new muscle fibers10 and mTOR-driven muscle protein synthesis.11 Because of the extraordinary capacity of myostatin to keep muscle growth in check, the slightest reduction in myostatin activity will generate notable gains in muscle growth.
While many reports in the scientific literature clearly show the independent muscle-building effects of leucine and creatine monohydrate, the combined use of both compounds has only recently been shown to reduce the negative influence of myostatin on muscle growth. A study by Mobley et al.12 showed that a mixture containing leucine and creatine monohydrate reversed myostatin-induced atrophy in isolated muscle cells by preventing the inhibition of newly formed muscle fibers, and therefore muscle growth.

Pump Up With Betaine

Betaine, also known as trimethylglycine, is a natural osmolyte found in the cell that protects the cell against dehydration by increasing cellular water retention through osmosis. The ability of betaine to maintain hydration reduces the negative impact that dehydration can have on exercise performance, such as increased heart rate, increased rate of glycogen degradation and increased lactate levels.
Furthermore, the ability of betaine to function as an osmolyte conceivably enhances muscle hypertrophy by causing the muscle fiber to swell. In fact, research has shown that muscle cell swelling stimulates protein synthesis and decreases protein breakdown, resulting in muscle growth.13,14 Although the underlying mechanisms are unclear, it has been suggested that cell swelling is perceived as a threat to cellular integrity. This perceived threat triggers certain cellular-signaling cascades to reinforce structural components of the muscle cell, by promoting the synthesis of certain structural proteins within the cell, resulting in increased muscle size.15

Betaine Synergistically Enhances Creatine Function for Greater Strength

Some of betaine’s muscle-building effects likely come from its capacity to donate a methyl group, which simply consists of one carbon atom and three hydrogen atoms, in certain biosynthetic reactions resulting in the increased production of creatine.
Furthermore, betaine’s ability to function as a methyl donor also increases the uptake of creatine into the muscle cell by stimulating the conversion of homocysteine into methionine, which effectively lowers homocysteine levels. Since higher homocysteine levels have been shown to impair insulin signaling16, lower homocysteine levels caused by betaine should improve insulin sensitivity, and therefore the insulin-driven uptake of creatine into the muscle cell. Altogether, the ability of betaine to increase creatine production and muscle cell uptake is likely the primary reason why betaine has been shown to significantly increase anaerobic power in key lifts like the bench press and squat.17
In summary, the essential replenishment of muscle protein and glycogen levels from the post-workout consumption of leucine, combined with the synergistic muscle-building compounds creatine and betaine, will provide a robust biochemical milieu within the muscle cell— driving exceptional growth and strength. Leucine, creatine and BetaPower™ Betaine are found in Advanced Molecular Labs’ (AML) Postworkout. For more information, go to advancedmolecularlabs.com.

The branched-chain amino acid (BCAA) is an amino acid with a side-chain consisting of covalently linked carbon atoms that form a branch-like structure thus eliciting their name. There are the three BCAAs found in the body: leucine, isoleucine and valine. Supplementation with BCAAs has been very popular primarily because of the apparent ability of BCAAs to increase muscle growth. The problem is that all three BCAAs do not equally promote muscle growth. In fact, it’s not even close as leucine is, by far, the most potent stimulator of muscle growth while isoleucine and valine come in a very distant second and third place, respectively [1] [2]. That said, isoleucine and valine do provide some performance enhancing effects. However, the simultaneous consumption of all 3 BCAAs should be avoided as many of the performance enhancing effects caused from the independent ingestion of a particular BCAA can be diminished by the simultaneous ingestion of all 3 BCAAs. Furthermore, the counterproductive influence caused by taking all 3 BCAAs at the same time likely increases the amount of BCAA required to produce the desired performance enhancing effect and greater BCAA intake further depletes the positive influence from BCAA consumption as too much BCAA intake promotes insulin resistance [3] stunting muscle growth and thus performance.

Leucine is the most potent muscle-building BCAA

Out of all 3 BCAAs, leucine elicits the strongest anabolic response by potently activating the nutrient sensing enzyme mTOR which directly enhances muscle protein synthesis while preventing muscle protein breakdown resulting in muscle growth. Several scientific studies highlight potent mTOR activation by the amino acid leucine. One study by Walker et al. [4] showed that leucine consumption shortly after working out increased mTOR activity leading to greater post-workout muscle protein synthesis as compared to an exercised group that was not fed leucine. While another scientific inquiry by Pasiakos et al. [5] demonstrated that consumption of leucine immediately after exercise specifically enhanced muscle protein synthesis by as much as 33%.

Leucine consumption has also been shown to decrease muscle protein breakdown once again by activating mTOR [6] which has the capacity to turn off the energy-sensing enzyme AMPK. Inactivation of AMPK prevents its normal function of initiating the breakdown of protein into amino acids for energy in order to restore energy levels within the cell when cellular energy is low. Altogether, the ability of leucine to robustly increase muscle protein production while decreasing protein degradation increases muscle protein levels resulting in considerable muscle hypertrophy.

The antagonistic function of isoleucine and leucine on muscle cell energy indicates independent consumption

Despite the limited capacity of isoleucine to trigger muscle protein synthesis and therefore muscle growth relative to leucine [1] [2], isoleucine outperforms leucine when it comes to supplying the muscle cell with energy from glucose. This occurs because isoleucine intake increases the influx of glucose into the muscle cell and increases the rate at which glucose is converted into energy within muscle [7]. In contrast, leucine consumption only increases glucose influx into the muscle cell. After that, glucose is then converted into glycogen for energy storage instead of being immediately burned for energy [8].

The antagonistic effects of isoleucine and leucine on glucose metabolism within the muscle cell indicates that co-consumption of these two BCAAs is likely unproductive and should be avoided. On the other hand, the use of isoleucine and leucine at different times should generate superior performance enhancement particularly if isoleucine use occurs before training to maximize energy production and leucine use takes place post-workout to increase the anabolic response to training.

Furthermore, the ability of isoleucine to convert glucose into energy within the muscle cell plausibly contributes to the inhibitory effect that isoleucine has on insulin function as higher energy levels from isoleucine consumption tend to inactivate certain isoforms of the energy-sensing enzyme AMPK [9]. Inactivation of AMPK lowers the capacity that AMPK has to augment the insulin signaling pathway resulting in a weaker overall insulin response that reduces the capacity to pack on muscle mass.

Taking valine and leucine together negates any positive impact on certain neurotransmitters within the brain promoting sluggishness and fatigue while you train

Although the BCAA valine doesn’t effectively drive muscle growth [1] [2], it can improve exercise performance by lowering production of the neurotransmitter serotonin during exercise by directly inhibiting transport of the serotonin-precursor tryptophan resulting in a diminished conversion of tryptophan into serotonin [10]. Since serotonin tends to bring about sluggishness and fatigue in the gym, the reduction in serotonin levels from valine intake enhances performance. So, it seems pretty simple, take a handful of BCAAs containing valine before your workout to lower serotonin levels and reduce fatigue and you’ll be good to go.

Well, unfortunately it’s not that simple. As it turns out, greater fatigue from exercise is actually influenced more heavily by the ratio of serotonin to another neurotransmitter dopamine [11] where higher serotonin to dopamine ratios increase fatigue. Thus, simply taking BCAAs isn’t going to effectively reduce tiredness because BCAAs do more than simply lower serotonin. In fact, the BCAA leucine also prevents the uptake of the dopamine-precursor tyrosine into the brain ultimately reducing dopamine production [12]. Of course, this would counteract any positive effect that valine might have by reducing serotonin levels as the simultaneous reduction in dopamine levels would reestablish a serotonin to dopamine ratio that promotes fatigue. So, once again the antagonistic functions of BCAAs, in this case valine and leucine, reveals that co-ingesting them is unproductive and they should be consumed separately with valine intake before exercise to optimally hinder preworkout fatigue and leucine after training to induce relaxation that promotes full recuperation.

Too much BCAA intake provokes insulin resistance potentially reducing muscle growth

Insulin is one of the most potent muscle-building hormones in the human body possessing the ability to drastically increase muscle protein synthesis and enhance muscle growth [13]. Insulin achieves this muscle building effect by binding to the insulin receptor and setting off a cascade of signaling events that eventually activates the enzyme mTOR triggering muscle growth [14]. Because of its potency, the insulin signaling cascade is very sensitive to over stimulation where extraneous activation of the insulin signaling pathway rapidly triggers negative feedback mechanisms ultimately resulting in diminished muscle growth.

Interestingly, several studies have shown that BCAAs can over stimulate the insulin signaling machinery resulting in reduced insulin signaling [15] [16] and ultimately insulin resistance [3]. On the contrary, leucine consumption alone has been shown to actually rescue insulin signaling deficiency [17] despite the strong influence that leucine has on insulin secretion and signaling activity which, in theory, should have a propensity to decrease insulin function via the previously mentioned negative feedback mechanism that occurs with too much insulin signaling. Although the exact mechanism by which leucine improves insulin function is not completely understood, it appears that leucine’s strong influence on muscle growth generates a large demand for energy as muscle tissue is very active metabolically thus requiring considerable energy. As a result, leucine intake also triggers the production of energy primarily by burning fat [18] [19]. The loss of body fat augments the response to insulin signaling thus overcoming, to some degree, the negative influence that leucine can have on insulin signaling via over stimulation.
In summary, the optimal use of BCAAs for performance enhancement involves more than just simply consuming BCAAs before and after working out to boost muscle growth. The correct use requires the proper timing of leucine, isoleucine, and valine intake to prevent their antagonistic effects on each other thus maximizing the performance enhancing effects of BCAA consumption. Moreover, the removal of any counteracting effects from proper timing of BCAA intake further enhances the muscle-building effect by lowering the effective dosage required for each BCAA which reduces the negative impact that extraneous BCAA consumption can have on insulin-driven muscle growth.

CLICK HERE TO ORDER AML’S POST-WORKOUT TODAY!

Many people can lose weight for a few months, but many struggle to maintain that weight loss over longer periods of time. One explanation for the inability of long-term weight loss is that dieting initiates homeostatic mechanisms that reduce energy expenditure within the body, ultimately promoting a positive energy balance that results in a return to previous weight levels. Of course, reduced energy expenditure from low caloric intake also makes it difficult for anyone trying to exclusively gain lean muscle mass, as depleted energy expenditure also inhibits fat loss. Consequently, the capacity to blunt this diet-induced reduction in energy use should enhance the ability to decrease body fat and keep it off, too.

Thermogenically Increase Energy Expenditure

Attempts to advance weight loss, and weight-loss maintenance, by increasing energy expenditure have recently embraced the use of several naturally occurring compounds, including capsaicin, which is the agent in chili peppers that provides the hot and spicy flavor. Capsaicin has been shown to potently increase energy expenditure by stimulating a process known as thermogenesis.1 Although the mechanism of action is not completely understood, some of the details include capsaicin activation of the TRPV1 receptor found within the oral cavity, and gastrointestinal tract, which triggers the release of noradrenaline. The release of noradrenaline then increases energy expenditure and fatty acid oxidation within brown adipose tissue (BAT) by stimulating thermogenesis, which uncouples the normally linked process of fatty acid oxidation with cellular energy production in the form of ATP. As a result, instead of the energy from fat being used to synthesize ATP, which requires active processes like muscular contraction to increase energy expenditure, energy is instead directly converted into heat, increasing energy expenditure.
The ability of capsaicin to curtail the decreased energy expenditure caused by dieting should improve the ability to shed, and maintain the loss of, unwanted body fat for considerable periods of time. Furthermore, thermogenically induced energy expenditure is not inhibited by caloric restriction like many other energy-consuming processes that are turned down by the previously mentioned homeostatic mechanisms. This, of course, means that no matter how hard you diet, capsaicin will still boost energy expenditure. In fact, the more severe the diet, the more likely you are to benefit from capsaicin— as greater levels of caloric restriction more potently diminish metabolic rate, giving capsaicin a greater opportunity to supplement this deficiency in energy expenditure.

Reignite a Sluggish Metabolism

In order to see if capsaicin could, in fact, diminish the reduced energy expenditure brought on by dieting, a recent study by Jannsens et al.2 looked at the influence that capsaicin had on energy expenditure levels in test subjects who consumed 75 percent of their normal caloric intake, with or without capsaicin. The results of the study showed that the group taking capsaicin had an effective negative energy balance of 20.5 percent, meaning they had a reduction in energy expenditure of 4.5 percent, while the group that did not consume capsaicin showed an effective negative energy balance of 19.2 percent, or a reduced energy expenditure of 5.8 percent. So, the group consuming capsaicin had a 1.3 percent higher energy expenditure relative to the control group, clearly demonstrating that capsaicin increased energy expenditure while dieting. In addition, the group taking capsaicin also showed a significant increase in fat oxidation, while there was no significant increase in fat oxidation in the control group. The increased fat burning induced by capsaicin will likely enhance body composition by promoting a reduction in fat mass.
This study by Jannsens et al. also demonstrated that the effects of capsaicin on energy expenditure and fatty acid oxidation require several days of capsaicin intake, at a dosage of 2.6 milligrams per day. This study clearly showed that energy expenditure and fatty acid oxidation did not increase in the first day, but did increase after a few days of capsaicin intake— and that consuming an amount of capsaicin lower than 2.6 milligrams per day had no influence on energy expenditure or fat burning.

Elevate Testosterone While Dieting

In addition to caloric restriction promoting a sluggish metabolic rate, caloric restriction also has the capacity to reduce testosterone production3, which likely contributes to the unwanted loss of muscle mass typically seen while dieting. The reason for this effect has to do, in part, with the low energy levels that come with caloric restriction, which slows down many biochemical processes that are not absolutely essential for survival. Regrettably, one of the non-essential processes turned down while dieting is the production of testosterone, meaning testosterone levels typically decline after extensive caloric restriction.
Fortunately, there may be a solution to this dieting dilemma, as it has recently been shown that capsaicin can reverse the negative impact that hypocaloric diets have on testosterone production. According to a study by Llhan et al.4, capsaicin accomplishes this by reducing production of the peptide hormone ghrelin, which is normally secreted by an empty stomach to tell the brain to increase hunger and promote food intake. It turns out that ghrelin also inhibits the production of testosterone, meaning that low-caloric diets— that naturally increase production of ghrelin, because the stomach is more likely to be empty— also decrease testosterone production. In fact, this study clearly shows that a dose of capsaicin lowered ghrelin levels in the testosterone-producing cells within the testes of rats, resulting in a large increase in testosterone.
This study also showed, somewhat surprisingly, that capsaicin actually increased serum levels of ghrelin throughout the rest of the body, which would suggest that capsaicin intake would decrease testosterone production— which, as previously mentioned, did not happen in this study. So, in rats, it appears that ghrelin influences testosterone production through an unknown mechanism that may involve the direct regulation of the testosterone-producing cells within the testes. On the other hand, in humans, it seems as if capsaicin has a more systemic effect, as capsaicin intake has been shown to decrease serum ghrelin levels5 and increase testosterone levels.6
In closing, the unique ability of capsaicin to increase energy expenditure and boost testosterone levels while consuming a low-calorie diet makes capsaicin a perfect choice for bodybuilders, especially during pre-contest training, when one is trying to shed as much body fat as possible without losing any muscle mass. Capsaicin also represents a very effective way for the non-bodybuilder to lose weight and keep it off, as many dieters today typically yo-yo back to their original weight, in large part because their metabolic rate becomes so sluggish, which promotes a positive energy balance that brings back those unwanted pounds that were so hard to lose in the first place.

For most of Michael Rudolph’s career he has been engrossed in the exercise world as either an athlete (he played college football at Hofstra University), personal trainer or as a research scientist (he earned a B.Sc. in Exercise Science at Hofstra University and a Ph.D. in Biochemistry and Molecular Biology from Stony Brook University). After earning his Ph.D., Michael investigated the molecular biology of exercise as a fellow at Harvard Medical School and Columbia University for over eight years. That research contributed seminally to understanding the function of the incredibly important cellular energy sensor AMPK— leading to numerous publications in peer-reviewed journals including the journal Nature. Michael is currently a scientist working at the New York Structural Biology Center doing contract work for the Department of Defense on a project involving national security.

A healthy diet is a must if you want to give your body essential vitamins and minerals to stay healthy and perform well during workouts. Unfortunately, the modern diet is typically nutrient-deficient, meaning that most people don’t get the required daily amount of essential vitamins and minerals, thus increasing the risk of disease and ill health.

Multivitamins are designed to provide the correct dose of essential vitamins and minerals that may be missing from the diet, promoting overall good health. However, recent scientific studies have shown that many multivitamin products could be hindering rather than helping, thanks to their excessive amounts of minerals such as iron, copper, manganese and calcium.

Too high a dose of these minerals can lead to oxidative damage, a condition that develops when cells are unable to neutralize and counteract the effects of harmful free radicals in the body. Oxidative stress triggers an immune response in the body, leading to a state of chronic inflammation. This chronic inflammation is closely related to diseases such as insulin resistance, type 2 diabetes, cardiovascular disease and even cancer.

Too Much Iron Causes Inflammation

Iron is an essential trace element that the body needs to thrive. However, excess iron can cause inflammation and contribute to disease.

Iron within the cells is bound to a protein called ferritin, which prevents unwanted iron release. Increased dietary iron means the body will need to raise ferritin levels to bind it, and these higher ferritin levels trigger inflammation in the body.

It has also been suggested that too much iron intake can exceed the storage capacity of ferritin, resulting in the release of free iron and more oxidative damage as a result.

Increased iron also causes the body to activate the immune system, which leads to chronic inflammation.

The increased inflammation from excess iron brings about the risk of obesity, diabetes and even Alzheimer’s disease. It’s clear that excess iron is toxic to the body, and with many people already eating foods fortified with iron such as bread, cereals and pasta, it’s easy to overdose if supplements are added into the mix.

Copper Leads To Oxidative Damage

The trace element copper causes oxidative damage that is comparable in severity to the damage caused by iron. Studies have shown that copper supplements, when ingested alongside a high-fat diet, could contribute to the onset of Alzheimer’s disease. Too much copper accumulation has been associated with impaired cognitive function and the growth of certain cancers.

Too much copper causes oxidative damage to the neurons and can lead to serious disease.

The Risks Of Excessive Manganese Consumption

Excessive consumption of the element manganese has been identified as a health risk. An accumulation of manganese causes neurotoxicity and can even lead to the brain disorder manganism. Elevated manganese levels have also been linked to Parkinson’s disease.

Manganese accumulates in brain cells known as astrocytes, which are essential for providing the correct nutrients to neurons. Once there, manganese causes the cells to malfunction, preventing them from providing those essential nutrients, and ultimately leading to decreased neural functioning and increased neurodegeneration.

Manganese also contributes to harmful levels of free radicals in the body.

Too Much Calcium Increases Cardiovascular Risk

Calcium is well known for its ability to improve bone health. Calcium is an essential mineral for healthy nerve function, muscular contraction and the regulation of certain hormones. It’s understandable that many multivitamins are formulated with a considerable amount of calcium.

However, recent studies have shown that calcium supplementation might not benefit bone health as much as once thought, and in addition could actually be detrimental to cardiovascular health.

Once recent study suggested that calcium supplements, as opposed to dietary calcium, could increase the risk of death from cardiovascular disease.

Get The Vitamins You Need Without Damage Or Inflammation

It’s clear that using multivitamins that contain iron, copper, manganese and calcium could be rather counterproductive, leading to inflammation and disease. That’s why AML has formulated our Thermo Heat Multi formula to give you all the vitamins and minerals you need for muscle health, without these four potentially damaging compounds.

Buy Thermo Heat Multi Here

The ultimate stack is the perfect union of ingredients that seamlessly complement each other in many ways, ultimately generating superior muscular performance. Advanced Molecular Labs (AML) has created the ultimate pre-workout stack with the release of its new product, AML Power Rep™. When stacked with its recently released AML Preworkout, AML Power Rep™ provides the ultimate in pre-workout supplementation. This powerful combination will load your muscles with energy and vastly improve muscular strength and endurance, so you can push your body to new limits for longer periods of time— and revitalize a sluggish central nervous system (CNS) for greater motivation to get into the gym and start pounding the weights with extreme intensity and resilience!

The optimal timing for this stack would be to drink AML Preworkout one hour before entering the gym, giving enough time for the supplement to boost energy and motivation. Then, right before you start training, take the recommended dosage of AML Power Rep™ for an additional boost that will provide endless energy, mental focus and strength for the entire workout.

ENERGETIC BUZZ FROM STACKING CAFFEINE, THEACRINE AND P-SYNEPHRINE

Caffeine is a solid foundation for any pre-workout supplementation protocol. That is because caffeine triggers a number of mechanisms that enhance exercise performance, including greater muscular contraction force, increased cellular energy production within muscle tissue and stimulation of the CNS. While increased contractile forces and energy production within muscle from caffeine can improve muscular strength and endurance, caffeine’s ability to stimulate the CNS improves exercise performance in multiple ways. Caffeine activates the CNS by directly inhibiting the adenosine receptor in the brain, triggering the release of two neurotransmitters, dopamine and adrenaline.1 This surge of dopamine and adrenaline amps-up the neurochemical environment within the brain, reducing fatigue and sluggishness for greater concentration and intensity while training in the gym.2 The surge of neurotransmitters also improves overall energy and mood3, making it an ideal pre-workout supplement and a key ingredient in AML Preworkout.

Although caffeine is a remarkable performance-enhancing supplement that should be part of any serious pre-workout supplement, stacking it with theacrine and p-synephrine, two compounds found in AML Power Rep™, will heighten some of the impressive ergogenic effects of caffeine, based on their independent ability to improve energy production and reduce fatigue. Theacrine is a protoalkaloid, with a similar chemical structure to caffeine, and it triggers dopamine release in a similar fashion to caffeine, improving arousal and motivation. This effect was shown in an initial study where theacrine increased energy, diminished fatigue and improved concentration, just like caffeine.4 However, unlike caffeine, which can produce a tolerance after as little as four days of consumption5, theacrine use for up to seven days showed no signs of desensitization.

The research indicates that the combined intake of caffeine with theacrine should enhance mood and energy, with no decrease in potency, for longer periods of time— effectively increasing overall arousal and focus before hitting the gym.5 Furthermore, the combined use of caffeine and theacrine plausibly stimulates the release of greater levels of dopamine, as a second study by Kuhman et al.6 showed that combining theacrine with caffeine had a greater impact on feelings of energy and mood relative to the consumption of caffeine alone, demonstrating an additive effect from consuming both caffeine and theacrine.

AML Preworkout is also loaded with tyrosine and the tropical plant Mucuna pruriens, which contains the dopamine precursor L-dopa.7 Together, both of these ingredients effectively increase dopamine production as well8,9, meaning their combined intake with caffeine and theacrine in this potent pre-workout stack will foster even greater focus and concentration while training.

Stacking caffeine with the second protoalkaloid in AML Power Rep™, p-synephrine, will give rise to even greater energy levels within the muscle cell, delivering superior muscular endurance, as p-synephrine also converts glucose and fat into energy10 for the muscle cell, just like caffeine. The apparent improvement in muscular energy levels was demonstrated in a study by Ratamess et al.11, which found that taking 100 milligrams of p-synephrine (the same amount in AML Power Rep™ ) right before you start training improved performance, increasing the total amount of repetitions completed during the study— demonstrating improved muscle endurance.

LESS PAIN FOR GREATER STRENGTH GAINS WITH THE ULTIMATE PRE-WORKOUT STACK!

Another performance-enhancing effect from stacking AML Preworkout with AML Power Rep™ will be an extraordinary capacity to reduce the pain associated with weight training. The capacity to blunt pain tends to reduce perceived exertion during exercise, increasing the capacity to train with higher levels of intensity for longer periods of time, ultimately increasing the training effect. This analgesic effect will come from three of the ingredients in this stack: ATP, caffeine and theacrine.

The pain-reducing effect from all three compounds is triggered when each binds to a specific set of purine receptors embedded within the cell membrane of certain spinal cord and peripheral neurons. The interaction with the purine receptor initiates certain cellular-signaling cascades within these neurons, mitigating pain sensitivity. This ability to minimize pain likely contributes to the lower rating of perceived exertion (RPE) reported by test subjects after consuming caffeine. In a recent review of 21 independent studies investigating the influence of caffeine on RPE, it was found that caffeine reduced RPE during exercise by 5.6 percent.12 In addition, this review also showed that caffeine improved exercise performance by 11.2 percent, suggesting that the lowered RPE during exercise from caffeine use likely represents one of the performance-enhancing mechanisms triggered by caffeine. Theacrine also exerts an analgesic effect. One study showed that oral consumption of theacrine in mice reduced pain perception from a hot plate, and pain associated with the injection of the compound acetic acid.13

The ability of caffeine to reduce pain perception during exercise, and enhance muscular performance, implies that ATP and theacrine can do the same. Thus far, there are no studies linking either ATP or theacrine intake to reduced RPE, despite their obvious pain-reducing effects. However, it is reasonable to propose that ATP and theacrine can minimize RPE during training, and enhance exercise performance. In fact, the muscle-enhancing effects demonstrated in the study by Wilson et al.14, where 12 weeks of ATP supplementation (400 milligrams of ATP from Peak ATPÆ before your workout, the same amount found in AML Power Rep™!) increased total-body strength, are likely produced to some degree by the analgesic effect of ATP— as greater muscular contraction force can be stimulated by the removal of pain sensation. Taken together, these studies indicate that stacking caffeine, ATP and theacrine will provide a heightened analgesic effect, allowing for exceptional training intensity and immediate strength gains.

INFINITE ENDURANCE FROM THE ULTIMATE STACK

Another indispensable capacity of pre-workout supplementation is the ability to improve muscular endurance. Stacking AML Preworkout with AML Power Rep™ will reduce muscular fatigue and improve muscular endurance tremendously! Not only will this reduce the rate of perceived exertion, allowing for more intense training, as previously mentioned— but this much ATP will boost nitric oxide and prostacyclin and  improve muscular endurance by potently stimulating vasodilation. ATP is stored in red blood cells. When oxygen is low in the working muscle, the red blood cell releases ATP, resulting in vasodilation and greater blood flow (up to 59%) to the working muscle groups that enhances nutrient and oxygen delivery15,16, resulting in greater muscular endurance.

In addition to the greater blood flow triggered by the dose of ATP within this stack, AML Preworkout also contains the potent nitric oxide-boosting compound citrulline malate, along with watermelon and grape skin extracts, which contain polyphenol antioxidant compounds that powerfully stimulate nitric oxide production17 and potently induce vasodilation, meaning increased levels of vasodilation that further improve muscular endurance.

MORE PERFORMANCE  ENHANCEMENT

FROM THE  ULTIMATE PRE-WORKOUT STACK

AML Preworkout is also loaded with several other compounds that will improve exercise performance. Within muscle cells, beta-alanine functions as a key building block for carnosine, the primary buffer within muscle tissue that counters the negative impact of lactic acid on exercise capacity. Several independent studies have clearly illustrated the positive influence of beta-alanine on carnosine production in muscle. In these studies, a significant increase in muscle carnosine of approximately 40 to 50 percent was measured after beta-alanine ingestion over a four- to eight-week time frame.18, 19 In addition to beta-alanine supporting carnosine synthesis, beta-alanine intake has also been shown to reduce muscle acidosis. In one study, subjects consuming beta-alanine for four weeks showed a much slower rise in acidity during high-intensity exercise.20 Moreover, the muscle-buffering function associated with beta-alanine intake has also been shown to improve endurance, as illustrated in a study where subjects ingesting beta-alanine demonstrated major improvements while performing a medium-intensity, high-repetition squat workout, compared to a placebo group.21

EXTREME MUSCLE GROWTH

FROM THE ULTIMATE STACK

The final element of the ultimate pre-workout stack is the capacity to increase muscular size and strength. AML Preworkout is loaded with creatine monohydrate and natural betaine (from BetaPower™), which stimulates greater production of creatine for a remarkably effective muscle-building effect. Creatine monohydrate is one of the most heavily used supplements22, packing on substantial muscle size and strength. Many studies over the years have demonstrably shown that short-term creatine monohydrate supplementation increases strength output during intense exercise. Furthermore, creatine supplementation with heavy weight training has the potential to stimulate muscle hypertrophy.23 In addition, AML Preworkout contains betaine, which supplies a methyl group required for the biosynthesis of the muscle-building creatine molecule.24 Supporting this function, it has been shown that betaine ingestion significantly increases anaerobic power in the bench press and squat. Interestingly, additional studies have also shown that betaine increased muscle protein synthesis and lean body mass while also reducing abdominal fat25, 26, likely because of its impact on creatine biosynthesis.

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For most of Michael Rudolph’s career he has been engrossed in the exercise world as either an athlete (he played college football at Hofstra University), personal trainer or as a research scientist (he earned a B.Sc. in Exercise Science at Hofstra University and a Ph.D. in Biochemistry and Molecular Biology from Stony Brook University). After earning his Ph.D., Michael investigated the molecular biology of exercise as a fellow at Harvard Medical School and Columbia University for over eight years. That research contributed seminally to understanding the function of the incredibly important cellular energy sensor AMPK— leading to numerous publications in peer-reviewed journals including the journal Nature. Michael is currently a scientist working at the New York Structural Biology Center doing contract work for the Department of Defense on a project involving national security.

High-fat diets are typically associated with gains in body fat, essentially because of the higher caloric density of fat. However, studies have shown that diets rich in omega-3 fatty acids found in fish oil, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), can actually reduce body fat.^1-3 Both of these fatty acids are polyunsaturated fatty acids that contain a carboxylic acid group attached to a rather long chain of covalently linked carbon atoms. As polyunsaturated fats, they also have several double bonds within their carbon chain, which significantly alters their chemical structure relative to other dietary fats such as saturated and monounsaturated fatty acids. The difference in chemical structure gives omega-3 fatty acids, like EPA and DHA, the unique capacity to reduce body fat while also decreasing inflammation— which together contribute to the many health benefits linked with their consumption, such as a lower risk for heart disease as well as certain cancers.^4,5

Although the precise mechanisms responsible for these effects are not completely understood, there are several possible explanations. To begin with, EPA and DHA burn fat by increasing the level and activity of mitochondria within the cell, resulting in greater fatty acid oxidation. Omega-3 fatty acids also minimize body fat by stimulating thermogenesis, which not only oxidizes body fat but also increases energy expenditure, further contributing to the reduction in body fat.

The anti-inflammatory effects associated with omega-3 fatty acids come from their ability to reduce the production of pro-inflammatory molecules known as prostaglandins⁶, by directly inhibiting the key enzyme involved in prostaglandin biosynthesis.⁷ In addition, the ability of omega-3 fatty acids to reduce body fat by increasing fatty acid oxidation and thermogenesis also contributes to their capacity to reduce the inflammatory response, as a loss of body fat actually reduces both the size and biochemical activity of fat cells. The diminished biochemical function of these fat cells actually depresses their release of pro-inflammatory cytokines, such as TNF-alpha, ultimately diminishing inflammation. The anti-inflammatory effects of omega-3 fatty acids have also been shown to increase insulin sensitivity, imparting a more anabolic environment that positively influences muscle growth.

Burn Fat and Sugar

Omega-3 fatty acids are one of the most common dietary supplements. This is mainly because of their proficiency at cutting body fat that is accomplished, in part, by increasing the expression of certain genes that increase the biosynthesis of the fat-torching subcellular organelle, the mitochondria.⁸ The PGC-1 alpha gene is one of the genes turned on by omega-3 intake that cranks up mitochondrial biosynthesis.⁹ Because the mitochondria are the power-producing organelles within the cell that burn fat for energy, the increase in mitochondria from omega-3 fatty acid consumption increases the capacity to oxidize fat and promote fat loss.

The use of omega-3 fatty acids has also been shown to boost the rate at which glucose is burned within muscle cells by stimulating glycolysis.⁸ Interestingly, the increase in glycolysis promoted greater levels of glucose uptake within the muscle cell by increasing the amount of the glucose transporter GLUT4 in the muscle cell membrane. The greater amount of GLUT4 transporters in the muscle cell membranes likely contributes to the ability of omega-3 fatty acids to enhance insulin signaling, as greater levels of GLUT4 in the muscle cell membrane will facilitate glucose transport into the muscle cell, reducing the amount of insulin required to shuttle glucose into the cell. The lower requirement for insulin will enhance insulin signaling by minimizing the negative feedback mechanisms that typically inhibit insulin signaling in response to excessive insulin levels.

Enhance the Anabolic Effect of Insulin

The ability of omega-3 fatty acids to improve insulin-mediated glucose metabolism means that omega-3s should also be able to boost insulin-triggered muscle protein synthesis, and therefore muscle growth. In order to verify this effect, a study by Gingras et al.¹⁰ looked at the impact of omega-3 fats on muscle protein synthesis in response to insulin. In this study, they showed that long-chain omega-3 fatty acids function as specific activators of mTOR and muscle protein synthesis by way of the insulin-signaling pathway. They also demonstrated that long-chain omega-3 fatty acids enhance the insulin-mTOR-protein synthesis-signaling pathway by diminishing whole-body inflammation, which has been shown to cause insulin insensitivity. Furthermore, they show that consumption of long-chain omega-3 fatty acids produced an increase in amino acid incorporation into muscle protein synthesis by 108 percent.

Anti-catabolic Effect Prevents Muscle Loss

In addition to their anabolic influence, omega-3 fats can also have a strong anti-catabolic effect by blocking the muscle-depleting influence of cortisol. The hormone cortisol is a steroid hormone that is normally released by the adrenal glands in response to stressful events such as caloric restriction. A few of its primary functions include increasing blood sugar and assisting in the metabolism of fats, carbohydrates and proteins.^11,12

Most caloric-restrictive diets lower carbohydrate consumption. When carbohydrate consumption is decreased from dieting, cortisol acts to reestablish glucose levels by converting non-carbohydrate fuel sources such as fatty acids and amino acids into glucose, a process known as gluconeogenesis. This cortisol-driven function consumes the immediately available stockpile of amino acids, causing the body to break down muscle tissue into amino acids for energy. Although cortisol release cannot be prevented, it can be controlled. Regulating the release of cortisol can be achieved by a diet rich in the EPA and DHA, as a study by Noreen et al.¹³ showed that six weeks of supplementation with 1,600 milligrams of EPA and 800 milligrams of DHA per day significantly preserved lean mass and decreased fat mass. These changes correlated with a reduction in salivary cortisol levels, demonstrating that these fatty acids lowered cortisol while preventing the loss of muscle mass.

Thermogenic-Driven Fat Loss and Increased Metabolic Rate

Thermogenesis occurs when the production of cellular energy, in the form of ATP, is uncoupled with fatty acid oxidation. As a result, instead of the energy from fat being used to synthesize ATP, it is instead converted into heat— which effectively increases energy expenditure, contributing to a higher metabolic rate that facilitates the ability to lose weight. Brown adipose tissue (BAT) is the most thermogenic tissue in the body because it is loaded with the uncoupling protein-1 (UCP-1) that can directly uncouple fat oxidation with ATP production driving thermogenesis. Omega-3 fatty acids trigger thermogenesis, in large part, by increasing the amount of BAT. This effect was shown in a study by Oudart et al.¹⁴ where researchers fed rats a high-fat diet with and without the omega-3 fatty acids EPA and DHA for four weeks. The group ingesting EPA and DHA showed an increase in thermogenic-activity that corresponded to an increase in the mass of their BAT, indicating that omega-3 intake increases the production of BAT-boosting thermogenesis.

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For most of Michael Rudolph’s career he has been engrossed in the exercise world as either an athlete (he played college football at Hofstra University), personal trainer or as a research scientist (he earned a B.Sc. in Exercise Science at Hofstra University and a Ph.D. in Biochemistry and Molecular Biology from Stony Brook University). After earning his Ph.D., Michael investigated the molecular biology of exercise as a fellow at Harvard Medical School and Columbia University for over eight years. That research contributed seminally to understanding the function of the incredibly important cellular energy sensor AMPK— leading to numerous publications in peer-reviewed journals including the journal Nature. Michael is currently a scientist working at the New York Structural Biology Center doing contract work for the Department of Defense on a project involving national security.

A true revolution absolutely requires a paradigm shift that fundamentally contradicts previously held notions. The widely held belief that all body fat is bad is currently being heavily scrutinized, due to the recent discovery of a different type of fat in humans known as brown fat. This type of body fat can actually burn off energy in the form of heat by a process known as thermogenesis, which can ultimately reduce overall body fat. This discovery has provided the requisite paradigm shift spawning a new revolution in weight loss that is the primary focus of the recently released book, Thermo Heat™ Weight Loss Revolution by Advanced Research Media.

The body has two forms of fat: white fat, or the unwanted fat that can lie directly underneath the skin, detracting from the physique, and brown fat, which often is found in the shoulder blade region or the neck. Unlike white fat, brown fat is good, as it can actually burn calories. The more brown fat you have, the more calories you burn. Brown fat is packed with mitochondria loaded with UCP-1, the protein that uncouples fat burning with ATP (energy) production instead converting the energy into heat via thermogenesis, making the mitochondria effectively the “furnace” of the cell. The emergence of brown fat as a readily available fat-burning furnace is revolutionary, but, like any fire, it requires the proper kindling materials. The ability to get lean by producing extra brown fat or enhancing the activity of existing brown fat represents a promising way to burn fat and lose weight. Several landmark discoveries and approaches to enhancing brown fat function are being explored at major research centers and universities worldwide, with great excitement. Brown fat research is a hot topic today. Thermo Heat™ Weight Loss Revolution is a groundbreaking, scientific plan based on research involving brown adipose tissue (BAT) or brown fat.

Thermo Heat™ Weight Loss Revolution offers its readers a nutrition, diet and exercise program that targets brown fat, along with an informational guide on the best thermogenic nutritional supplements. Additionally, a section of the book is devoted to appropriate brown fat-activating food choices and easy-to-follow thermogenic, fat-burning meal plans. Followers of this scientifically developed program will find that they are able to harness the power of brown fat, maximize their energy expenditure, reach and maintain their ideal weight and achieve reduced body fat while preserving a lean, muscular physique— improving overall health and well-being. The subsequent paragraphs briefly review the contents of the book, which goes into the critical details required to really understand the remarkable capacity of brown fat to stimulate the thermogenic loss of those unwanted pounds, and how to maintain that weight loss for a lifetime.

IGNITING YOUR BODY’S FAT-BURNING FURNACE

Many “fat-burning” products claim that they will be able to reduce body fat and make you lean by increasing the rate at which fat is burned (oxidized) in your body. While statements like this appear, at first glance, to be plausible, they are essentially inaccurate. That is because an increase in fatty acid oxidation within white fat simply converts the energy produced during fatty acid oxidation into the high-energy compound adenosine triphosphate (ATP). The increased energy production in the form of ATP resulting from burning fat is not accompanied by an increased level of energy expenditure, which generates an overall energy surplus that prevents the reduction of body fat— as the body will simply convert much of this ATP surplus back into body fat within a rather short period of time. So, the fundamental problem with merely converting body fat into ATP is that this process does not increase the amount of energy expenditure, which is the only valid way to reduce body fat.

This newfound information regarding energy expenditure evoked interest in thermogenesis— which systematically drives fatty acid oxidation while simultaneously increasing energy expenditure by uncoupling the process of fat burning from the production of cellular energy (ATP). It is important to note that there are marked differences between how white adipose tissue burns fat and the way brown adipose tissue burns fat. When white adipose tissue burns up its fatty deposits, the energy generated is stored in the form of ATP; the outcome of this is that there is only a minimal expenditure of energy. Conversely, when brown fat is called upon to utilize its stores of fat, the biochemical process known as thermogenesis (the generation of heat) is stimulated and, with it, the generation of energy in the form of heat instead of ATP. And the human body has the ability to release this heat energy, effectively increasing energy expenditure, which promotes efficient fat loss and the production of lean muscle mass. Brown fat, but not white adipose tissue, has the ability to increase energy expenditure thermogenically because it contains the protein UCP-1 (also known as thermogenin). This protein is unique in that it inhibits fatty acid oxidation from generating ATP. Instead, the energy derived from brown fat gets converted into heat, which radiates off into the atmosphere.

Of all the cells of the human body, it is the brown fat cell that is the most proficient in undergoing thermogenesis due to its high concentration of mitochondria that are chock-full of UCP-1. However, there is only a small quantity of this fat-burning cell in the adult human body, and the stimuli that cause brown fat to undergo thermogenesis are not always desirable ones. The chief mechanism that permits brown fat thermogenesis is exposure to prolonged cold temperatures, which brings about the activation of transient receptor potential vanilloid (TRPV) receptor sites within the brain. TRPV triggers the sympathetic nervous system to release its noradrenaline stores, which once released, interact with the beta-adrenergic receptors that are embedded inside the cell membranes of brown adipose tissue. This process initiates uncoupled fatty acid oxidation, generating heat instead of ATP, which then radiates through the skin to provide us with a protective “thermo blanket.” Although exposure to cold temperatures for two hours or more can trigger brown fat activity and fat loss¹, such an approach is fraught with danger. Not only is this modality time consuming and uncomfortable, but the slightest error can lead to the consequences of hypothermia, which include panniculitis, shock, gangrene, frostbite and even death.

It has been demonstrated that factors other than cold can activate those members of the TRPV family that are located outside the brain. At this time, the most studied group is capsaicin, the spice found in chili peppers that contributes to its hot and spicy flavor. Capsaicin has an affinity for binding directly to TRPV receptor sites found throughout the entire length of the gastrointestinal tract, including the oral cavity. These TRPV receptors act very similarly to the TRPV-1 receptor sites found within the brain. They, too, have the ability to activate the sympathetic nervous system and turn on thermogenesis within brown adipose tissue. Several studies indicate that just a single ingestion of capsaicin has the ability to activate brown fat thermogenesis.^2,3 Even more interesting is the clinical finding that long-term consumption of capsaicin can significantly increase thermogenesis in brown adipose tissue and produce a reduction in body fat. Other compounds have been identified that also induce brown fat thermogenesis, either by directly stimulating noradrenaline release or by activating the adrenergic receptor sites found within brown fat. Several other thermogenic compounds can directly influence brown adipose tissue capacity to increase intercellular UCP-1 production. Enhanced thermogenesis is the beneficial result.

THERMO HEAT™ IGNITES YOUR BODY’S FAT-BURNING FURNACE

Overall, there has been an abundance of scientific evidence that demonstrates thermogenesis increases energy expenditure while it decreases body fat levels in adults.^4,5,6 Additionally, researchers have made great strides in uncovering several naturally occurring compounds that help turn on thermogenic-induced fat loss. After years of delving through the literature and scrutinizing countless articles on fat reduction and thermogenesis, Advanced Molecular Labs (AML) has selectively incorporated several of these ingredients into the cutting-edge product Thermo Heat™ that is going to transform the capacity for fat loss by vigorously increasing fatty acid oxidation and energy expenditure!

SUPPRESS APPETITE WITH THERMO HEAT™

While increased fat loss and energy expenditure are two key elements in the battle against body fat, their enhancement will likely initiate homeostatic mechanisms that conserve bodyweight by triggering hunger, resulting in increased food consumption. This will not only be counterproductive in achieving further fat loss, but may also contribute significantly to regaining some or most of the lost weight. Consequently, the barrier to success that food craving and increased appetite represent must also be addressed if the loss of body fat is to be maintained. Thermo Heat™, used in conjunction with the nourishing diet program found in the Thermo Heat™ Weight Loss Revolution, will help address the difficulties associated with increased hunger typically caused by weight loss with its exclusive blend of body fat-attacking compounds that also help potently suppress appetite.

BURN FAT WHILE YOU SLEEP WITH THERMO HEAT™ NIGHTTIME

Although the scientists at AML appreciate the role that stimulants have in promoting fat loss and exercise performance, they are cognizant of the disruption they can have on our circadian rhythm, including the sleep-wake cycle. It is while we sleep that the growth and repair of our overused muscles take place. Sleep is also when most weight loss occurs. As physiologic sleep is an integral component of any successful weight-loss and exercise program, Steve Blechman and AML formulated a nighttime preparation that complements AML’s daytime product. This product, Thermo Heat™ Nighttime, when consumed with an evening meal or at bedtime, can elevate nocturnal levels of thermogenic fat burning, aid in managing stress and promote restful sleep. It achieves this goal by replacing Thermo Heat’s™ stimulatory components (tyrosine, caffeine, p-synephrine and thyroid hormone activators) with several others that are capable of inducing relaxation, curbing appetite and burning fat.

ADVANCE METABOLIC FUNCTION WITH THERMO HEAT™ MULTI

It is well known that human health is enhanced when diets are rich in essential vitamins and minerals. These micronutrients promote and sustain a wide array of the metabolic processes required for the maintenance of proper physiologic function. The term “essential” indicates that the body itself is unable to manufacture these key components (intrinsic) and that outside (extrinsic) sources have to be relied on to meet the body’s needs. As today’s diets tend to be calorically dense and nutritionally deficient, most of us fail to consume even the “minimal” daily requirement of many of these essential vitamins and minerals. Meeting the minimal daily requirements of many nutrients allows us to stay healthy.⁷ Multivitamin and mineral supplements have been available to the public at large for nearly a century, and were initially designed to fill the significant nutritional voids in most diets, even back then. Most of today’s multivitamins and mineral products fall short in their objectives as being an adjunct to enhance performance. Ongoing research at AML, covered in-depth for the reader in the Thermo Heat™ Weight Loss Revolution, has enabled production of a revolutionary new product, Thermo Heat™ Multi, which has the capacity to help fight free radicals and enhance metabolism as no other multivitamin or mineral product has ever done before, maximizing overall metabolic health.  Thermo Heat™ Multi contains a blend of vitamins that have long been shown to enhance health and wellness, along with other compounds that boost thyroid function and reduce oxidative stress. Thermo Heat™ Multi also has a novel blend of spices and polyphenols to help suppress appetite and thermogenically incinerate fat.

THE THERMO HEAT™ HIIT WORKOUT

In general, the more calories burned during exercise results in more body fat burned. So, you might assume, based on this knowledge, that burning as many calories as possible with more cardiovascular exercise would improve your physique more rapidly— making you more ripped and muscular in no time at all. However, the assumption that cardiovascular exercise optimally promotes the development of your physique and will make you lean and muscular more quickly has not been observed clinically. In fact, extensive cardiovascular training diminishes anabolism and increases catabolism, and so it will inhibit your ability to increase muscle and preserve lean body mass.

On the other hand, high-intensity interval training (HIIT) burns plenty of calories and body fat without promoting muscle breakdown. In addition, recent research has confirmed the role of HIIT in increasing the levels and activity of the transcriptional co-activator peroxisome proliferator-activated receptor-gamma activator-1 alpha (PGC-1 alpha).⁸ PGC-1 alpha is able induce the expression of the protein, irisin, which has the ability to bind to the receptor sites situated on the surface of white adipose tissue (WAT).⁹ It was observed that the induction of BAT-associated proteins, such as UCP-1 (the thermogenic driver), increased during this interaction and irisin has the unique ability to alter the structure of WAT so that it bears a striking similarity to BAT. This conversion of WAT into a BAT-like cell resulted in significant increases in total-body energy expenditure and promoted more efficient fat burning. Altogether, the Thermo Heat™ HIIT Workout is a scientifically proven fat-incinerating exercise plan that preserves lean muscle mass. The correctly combined use of this workout with the potent, thermogenic-enhancing Thermo-Heat™ products described in detail in the Thermo Heat™ Weight Loss Revolution should further catapult, and maintain, thermogenic-driven weight loss.

Thermo Heat™ Weight Loss Revolution also provides the reader with a comprehensive Thermo Heat™ thermogenic nutrition and meal plan that clearly explains the optimal use of macronutrients to further boost the thermogenic loss of unwanted body fat. This fantastic nutritional strategy also describes other thermogenic spicy foods and healthy fats that have the ability to stimulate thermogenesis and help the body burn fat. In addition, this section of the book contains several appetizing Thermo Heat™ thermogenic fat-burning recipes that will support a healthier diet that enhances the capacity to torch body fat.

Thermo Heat™ Weight Loss Revolution can be purchased on amazon.com or advancedmolecularlabs.com.

For most of Michael Rudolph’s career he has been engrossed in the exercise world as either an athlete (he played college football at Hofstra University), personal trainer or as a research scientist (he earned a B.Sc. in Exercise Science at Hofstra University and a Ph.D. in Biochemistry and Molecular Biology from Stony Brook University). After earning his Ph.D., Michael investigated the molecular biology of exercise as a fellow at Harvard Medical School and Columbia University for over eight years. That research contributed seminally to understanding the function of the incredibly important cellular energy sensor AMPK— leading to numerous publications in peer-reviewed journals including the journal Nature. Michael is currently a scientist working at the New York Structural Biology Center doing contract work for the Department of Defense on a project involving national security.

Use Promo Code: THERMOBOOK to receive a free digital book with any ThermoHeat Product Purchase – Only Valid at advancedmolecularlabs.com

The branched-chain amino acid (BCAA) is an amino acid with a side chain consisting of covalently linked carbon atoms that form a branch-like structure, thus eliciting their name. There are three BCAAs found in the body: leucine, isoleucine and valine. Supplementation with BCAAs is widespread, mainly because of the apparent ability of BCAAs to increase muscle growth. The trouble is that all three BCAAs do not promote muscle growth equally. In fact, leucine is by far the most potent stimulator of muscle growth, while isoleucine and valine come in a very distant second and third place, respectively.^1,2

Leucine Boosts Muscle Growth Without Diminishing Insulin’s Anabolic Action

The major anabolic effect caused by BCAA intake involves insulin. Insulin is one of the most potent muscle-building hormones in the human body, possessing the ability to drastically increase muscle protein synthesis, which enhances muscle growth.³ Insulin achieves this muscle-building effect by binding to the insulin receptor embedded within the muscle cell membrane, setting off a cascade of molecular-signaling events that eventually activates the enzyme mTOR. As a result of mTOR activation, protein synthesis surges within the muscle cell, triggering muscle growth.⁴ The insulin-signaling cascade is very sensitive to overstimulation, where extraneous activation of the insulin-signaling cascade rapidly triggers negative feedback mechanisms that can result in diminished muscle growth. Several studies have shown that the simultaneous consumption of all three BCAAs can overstimulate the insulin signaling machinery, reducing insulin function and insulin resistance.^5,6

Because leucine is the most potent of the BCAAs at boosting insulin activity and muscle growth, leucine is probably the best candidate to overstimulate insulin signaling, making this BCAA the most likely culprit to reduce insulin function. However, leucine consumption alone has actually been shown to rescue insulin-signaling deficiency⁷, despite the strong influence that leucine has on insulin secretion and signaling activity. Leucine’s strong influence should, in theory, increase the propensity to inhibit insulin function via the previously mentioned negative feedback mechanism that occurs with too much insulin signaling. Although the exact mechanism by which leucine improves insulin function is not completely understood, it appears that leucine’s strong influence on muscle growth generates a greater demand for energy, as muscle tissue is very active metabolically and requires a lot of energy. Because of the increased energy demand, leucine intake also triggers mitochondrial growth within the cell, improving the production of energy by burning more fat.⁸ The loss of body fat augments the response to insulin signaling, thus overcoming, to a large degree, the negative influence that leucine potentially has on insulin signaling by too much stimulation.

Isoleucine Improves Insulin Function

On the other hand, the remaining two BCAAs, isoleucine and valine, are much less anabolic than leucine— essentially because isoleucine doesn’t stimulate insulin-driven muscle growth at all⁹ and valine triggers a very weak insulin response.¹⁰ So, neither isoleucine or valine should cause insulin resistance either, as neither BCAA likely overstimulates— and thus turns off— insulin function. As for isoleucine, this premise holds true as isoleucine has been shown to actually improve insulin sensitivity by specifically increasing the influx of glucose into the muscle cell and the rate at which glucose is converted into energy within muscle.⁹ The enhanced capacity to shuttle glucose into the muscle cell reduces the required secretion of insulin from the pancreas. The diminished need for insulin secretion reduces the overall amount of insulin signaling, diminishing feedback inhibition caused by overstimulation, which ultimately augments insulin sensitivity. Incidentally, the enhanced energy production within the muscle cell caused by the isoleucine most certainly enhances muscular performance, likely contributing to muscle growth.

Valine Metabolite Causes Insulin Resistance

Oddly enough, the weak insulinogenic effect caused by valine does not mitigate the negative impact of this BCAA on insulin resistance, as valine has been shown to induce insulin resistance. In fact, higher levels of valine are observed in the blood of diabetic mice, rats and humans¹¹, while mice that were fed a diet without valine improved insulin sensitivity after only one day, while a valine-free diet for an entire week decreased blood glucose levels— indicating improved insulin function.¹² So, how could this be? Especially when valine most certainly does not overstimulate, and desensitize, insulin signaling. One potential explanation is that unlike leucine— which avoids insulin resistance by increasing mitochondrial-driven fat loss— valine does not encourage mitochondrial biogenesis, or function, precluding any protective impact associated with fat loss on insulin resistance.

Valine also appears to inhibit insulin signaling in a unique way, likely making this BCAA the most detrimental for muscle growth. This recently discovered effect of valine was reported in the journal Nature Medicine, where research demonstrated that the valine catabolite 3-hydroxyisobutyrate (3-HIB) promoted the accumulation of fat within muscle tissue by directly stimulating fatty acid uptake into the muscle.¹³ The accumulation of intramuscular fat activates certain signaling cascades within the muscle cell that diminish insulin signaling, leading to insulin resistance. This study further corroborated the impact of the valine metabolite 3-HIB on insulin function by showing that inhibiting the production of 3-HIB in muscle cells prevented the uptake of fat. Interestingly, other studies supporting the negative influence of 3-HIB on insulin signaling have shown that 3-HIB levels are elevated in the muscle of human subjects with diabetes.^14,15 Taken together, these results reveal a novel mechanism for valine-induced insulin resistance in muscle tissue that most likely diminishes the capacity to pack on muscle mass.

In closing, the use of BCAAs for muscle growth involves more than merely ingesting a handful of BCAAs after training to get huge. The optimal use of BCAAs requires an informed consumption schedule that prioritizes the use of leucine as this BCAA is, by far, the most potent stimulator of muscle growth— and, perhaps just as importantly, leucine actually enhances the potent anabolic action of insulin. While, on the contrary, isoleucine and valine are much less capable of boosting muscle growth. In addition, it is just as important to consider the potential muscle-depleting impact associated with valine use, as recently discovered evidence demonstrates that valine intake can inhibit insulin signaling, likely reducing your ability to pack on muscle mass.

For most of Michael Rudolph’s career he has been engrossed in the exercise world as either an athlete (he played college football at Hofstra University), personal trainer or as a research scientist (he earned a B.Sc. in Exercise Science at Hofstra University and a Ph.D. in Biochemistry and Molecular Biology from Stony Brook University). After earning his Ph.D., Michael investigated the molecular biology of exercise as a fellow at Harvard Medical School and Columbia University for over eight years. That research contributed seminally to understanding the function of the incredibly important cellular energy sensor AMPK— leading to numerous publications in peer-reviewed journals including the journal Nature. Michael is currently a scientist working at the New York Structural Biology Center doing contract work for the Department of Defense on a project involving national security.

Ever since the discovery of the chemical structure of DNA in 1953, man has been on a relentless quest to find ways to enhance the body’s production of anabolic hormones, specifically in relation to its effects on the building muscle after weight training – otherwise known as hypertrophy. Numerous “groundbreaking” ingredients have come and gone over the years, often will much less bang than they promised. However, more recent research has unveiled that consuming certain all-natural compounds immediately post workout can enhance muscular growth to remarkably high levels. AML’s team of formulators has sorted through the science to craft two products that when taken together for The Ultimate Post-Workout Stack!

AML Post Workout and AML Muscle Growth will enhance muscle growth, lean body mass, strength, power and recovery like no other post-workout stack ever has before. These two cutting-edge products are chock-full of a anabolic compounds, all in clinically efficacious doses. Just to highlight a few, stacking AML Post Workout and Muscle Growth gives you:

• 5g Leucine
• 5g Creatine Monohydrate
• 2.5g Betaine
• 3g HMB
• 750mg Phosphatidic Acid
• 4,000 IUs Vitamin D3

This exceptional mixture of research-backed ergogenics was designed to precisely trigger an anabolic environment that will generate massive muscle growth.

Boost Muscle Growth & Prevent Muscle Breakdown With Leucine and HMB

Leucine is the most well known, and well researched, of the Branched-Chain Amino Acids (BCAAs). It’s been shown to stimulate muscle protein synthesis and inhibit muscle protein breakdown by directly activating the mTOR pathway. In fact, one study by Walker et al.¹ showed that leucine consumption, immediately post workout, increased mTOR activity for several hours after training— leading to greater muscle protein synthesis when compared to a second group that did not take leucine.

Additionally, one of Leucine’s primary metabolites, HMB, also triggers considerable muscle growth. The difference between the two is that HMB supports muscle growth by reducing muscle protein breakdown instead of stimulating muscle protein synthesis like leucine does. In fact, one study found that 3g of HMB (the precise dose included in AML Muscle Growth!) attenuated muscle protein breakdown by a whopping 57 percent.⁴

Other research gives evidence of HMB’s ability to reduce muscle protein catabolism — ie muscle breakdown — and shows that HMB actually increases muscle growth and strength when combined with resistance training.⁵ As a result, consuming both Leucine and HMB not only drive the synthesis of new muscle protein but will also prevent the breakdown of existing muscle protein, resulting in extraordinary levels of hypertrophy – sheer muscular growth.

But that’s only the start – there are more can’t-miss ingredients, some of them familiar and some of them new:

Build Muscle With Creatine

No other single ingredient has been more thoroughly studied and safely proven successful than Creatine Monohydrate. The vast array of studies on this clinically-backed muscle-builder demonstrate that creatine supplementation increases power output during intense exercise while also stimulating muscle growth.⁶

The unique capacity of creatine to boost size and power stems in part from creatine’s ability to rapidly reverses the depletion of muscle cell energy (ATP) during muscular contraction. This ultimately recharges energy levels within the muscle cell faster, prolonging muscular contraction for superior muscle growth and performance.⁷ Lastly, creatine has also been shown to stimulate new muscle cell formation⁸ and increase muscle protein synthesis.⁹  All of these combined effects make Creatine the hallmark ingredient of safe, natural muscle growth and no athlete should miss out on its incredible effects.

Prevent Muscle Atrophy With Leucine, Creatine and HMB

We all know that resistance training breaks down muscle tissue, but do you know why? It all traces back to a powerful, little gains-destroying protein called myostatin. This tissue-depleting molecule prevents muscle growth by inhibiting the formation of new muscle fibers¹⁰, while also decreasing mTOR-driven muscle protein synthesis.¹¹ High levels of myostatin equate with low levels of gains. So how do we keep it at bay?

This question has led researchers to hunt for a solutions to limit the deleterious effects of myostatin and keep the growth coming year after year. A recent study by Mobley et al.¹² showed that a mixture containing leucine, calcium-HMB, and creatine monohydrate reversed myostatin-induced atrophy in muscle cells. Because of the great potential of this combination of ergogenics, stacking AML Post Workout and AML Muscle Growth Post-Workout Stack — which provides all three compounds— will limit myostatin’s effectiveness opening the door to unprecedented levels of muscle growth!

Pump Up With Betaine

Betaine— also known as trimethylglycine— is a natural compound found in the cell that protects the cell against dehydration by increasing cellular water retention via osmosis. Betaine’s ability to function as an cell volumizer supports muscle hypertrophy by causing the muscle fiber to swell. In fact, research has shown that muscle cell swelling stimulates protein synthesis and decreases protein breakdown, resulting in muscle growth.^13,14

Additionally, betaine also plays a key role in the biosynthesis (formation) of creatine— implying that betaine should mimic the muscle-building effects of creatine to some degree. Indeed, studies have proven that betaine ingestion — preferably the clinically-verified 2.5 grams per day — does significantly increase anaerobic power in the bench press and squat. This is conceivably because of betaine’s ability to increase creatine levels within muscle tissue.¹⁵

Unchained Muscle Growth With Vitamin D3 & Leucine

Vitamin D has traditionally only been thought to be important for bone health; however, more recent research on this critical vitamin have shown that it actually functions as a powerful prohormone that drives muscle growth by regulating the expression of many important muscle-building genes, namely testosterone.^16,1718

Many athletes have a love-hate relationship with carbohydrates. Ideally, we want to take them and get them shuttled into the muscle cells, not fat! Thankfully, a separate function controlled by vitamin D enhances insulin sensitivity by increasing the expression of the insulin receptor gene. This results in more insulin receptors on the surface of the muscle cell, which causes a more sensitive signaling response to insulin. Ultimately, the enhanced insulin response drives more muscle growth and carbohydrate intake into the actual muscle — something every athlete wants!

Other recent studies have also shown the capacity of vitamin D3 to increase insulin receptor levels within the muscle cell, providing a more robust anabolic response to leucine intake. A study by Salles et al.¹⁹ looked at the influence that vitamin D3 had on leucine-activated insulin signaling in muscle cells. Since we know that leucine consumption drives muscle protein synthesis, the researchers wanted the see if vitamin D3 could enhance leucine activation of the insulin pathway.

As it turns out, vitamin D3 does in fact enhance the ability of leucine to activate the insulin signaling process, and it also increases the rate of muscle protein synthesis. This is one of those times where the results backed up the theory: there was an increase in insulin signaling and muscle protein production and it was mainly due to the increased activity in these insulin receptor genes. The end result meant that vitamin D3 yielded more insulin receptors embedded within the muscle cell, fostering a greater anabolic response within the muscle cell.

Point being? Don’t miss out on your Vitamin D3 if you want to make the best use of your food and testosterone supply. Too many workout stacks don’t include it, but AML is not so short-sighted. Along with Leucine makes a fantastic 1-2 punch for gaining lean muscle.

Advanced mTOR-driven Muscle Growth With Phosphatidic Acid

Now it’s time to introduce you to a new supplement ingredient that you may not have heard of, but it’s one many fitness fanatics are calling the “next big thing”.

Phosphatidic Acid (PA) is a phospholipid found in the cell membrane involved in many different cell signals, including the primary one that stimulates muscle growth. Several recent scientific studies have shown that an increase in PA is responsible for the activation of mTOR signaling during and after resistance exercise. The big surprise is that it works alone, and without increased IGF-1, as was previously thought. A study by O’Neill et al.²⁰ showed that incubating muscle cells with PA does induce an increase in mTOR signaling, and increased mTOR signaling means more muscle cell activation and growth.

The Phosphatidic Acid Muscle Growth Study: A massive success

With the knowledge that PA increases mTOR-driven muscle protein synthesis, another group of researchers tested whether PA could actually increase muscular size and strength in trained athletes – the holy grail of natural supplements. In this study by Hoffman et al.²¹, the team investigated the influence that PA had on strength in 16 resistance-trained subjects. The subjects were split into two groups, with one receiving 750mg of PA per day and the other group taking a placebo.

During the experiment, each subject lifted weights four days a week at 70% of their one-repetition maximum (1RM) for all lifts during the entire eight-week trial period. At the end of the experimental period, each subject was tested for strength and body composition. The results showed that subjects ingesting 750mg phosphatidic acid demonstrated a 12.7% increase in squat strength and a 2.6% increase in muscle mass! The group consuming a placebo, on the other hand, showed much less improvement in squat strength and virtually no increase in muscle mass.

These results show that the real-life results back up the theory behind them, making Phosphatidic Acid your next can’t-miss supplement.

Taking everything into consideration, a proper Post Workout Stack will activate the mTOR pathway via two separate ways: one by an insulin-independent way using PA, and the other in an insulin-dependent fashion by compounds such as leucine. For this reason, AML has included both PA and Leucine as components in The Ultimate Post Workout Stack, and athletes with any goal and any diet type can get in on the gains.

Remember, muscle is broken down during training, and it’s only when the weights are set down that recovery and most importantly, repair and growth can occur. Advanced Molecular Labs has done the latest research for you and has taken the guesswork out of what to consume following intense exercise. The AML Post Workout and AML Muscle Growth Stack provide everything you would need to recover faster and see superior growth!

Pre Order Now the Muscle Growth Post Workout Stack

Phosphatidic acid (PA) is a compound consisting of a glycerol backbone with two fatty acid chains linked to the first and second carbon atoms, and a phosphate group bonded to the third carbon atom on the glycerol backbone. PA is a phospholipid typically embedded within the cell membrane, where it functions as a second messenger involved in many different cellular-signaling cascades.¹ By way of its cellular signaling capacity, PA can elicit an anabolic response in muscle cells.

In fact, muscular contraction is thought to activate certain enzymes that biosynthesize PA in muscle cells, effectively increasing PA levels and activating mTOR-stimulated muscle protein synthesis, which promotes muscle growth. There have been several studies demonstrating this effect. One of these studies by Cleland et al.² showed that electrically stimulated muscle contraction in rats led to a twofold increase in PA concentrations. While another investigation by O’Neill et al.³ demonstrated that elevations in PA occur in response to eccentric contractions, and this elevation in PA activated mTOR signaling for more than 12 hours.

Oral consumption of PA has also been shown to increase plasma concentrations of PA as rapidly as 30 minutes after consumption, with PA concentrations remaining elevated for as long as seven hours.⁴ Taken together, the elevation of PA in the body from oral supplementation, combined with its endogenous production from weight training, should result in greater muscle hypertrophy relative to resistance training alone.

PA Boosts Muscle Growth and Strength

Because of the potential of PA supplementation for muscle growth, several groups have investigated its muscle-building capacity. One seminal study by Hoffman et al.⁵ looked at the influence that soy-derived PA had on muscle growth and strength in 16 test subjects with significant weightlifting experience. The subjects were split into two groups, with one group receiving 750 milligrams of PA per day and the other group taking a placebo. During the experiment, each subject lifted weights four days a week at 70 percent of their one-repetition maximum (1RM) for all lifts during the entire eight-week trial period. Each subject was tested for strength and body composition at the end of the experimental period. The results showed that subjects ingesting PA demonstrated a 12.7 percent increase in squat strength and a 2.6 percent increase in muscle mass, while subjects consuming placebo showed only a 9.3 percent improvement in squat strength and a 0.1 percent change in muscle mass. Results from this study strongly indicate that PA ingestion combined with resistance training enhanced size and strength.

Soy-derived PA More Potently Drives Muscle Growth

While PA clearly plays a critical role in the stimulation of mTOR-driven muscle growth, different sources of PA, such as soy or egg, have a slightly different chemical makeup— with varying levels of unsaturated or saturated fatty acid chains at the first and second carbon positions within its glycerol backbone. This variation in chemical composition of PA could influence the impact on muscle growth— as it has been proposed that PA with one saturated and one unsaturated fatty acid, such as soy-derived PA, is more likely to promote cellular signaling events such as mTOR-activated muscle growth, relative to PA containing two saturated fatty acids as found in egg-derived PA, which is apparently more biochemically inert as a signaling compound.⁶

In order to screen for more efficient muscle-building forms of PA, a study by Joy et al.⁷ looked at the different impact of several kinds of phospholipids, including both egg and soy-derived PA, on muscle growth and strength. The study involved two independent experiments, where the first experiment looked at the ability of egg and soy-derived PA to activate mTOR in isolated muscle cells within a test tube (in vitro), and the second experiment measured muscle growth rates in humans consuming 750 milligrams of soy-derived PA while performing an eight-week, periodized weight-training program.

In the first experiment conducted by Joy et al., researchers found that out of all the phospholipids investigated, PA from soy triggered the largest increase in mTOR activity relative to all the other phospholipids, including egg-derived PA. The second experiment validated the findings from the first experiment, as soy-derived PA also produced a considerable increase in muscle mass of five pounds relative to the placebo group. This experiment also showed a statistically significant increase in leg press strength of 115 pounds within the PA-consuming group compared to the placebo group, which showed a smaller increase of only 50 pounds.

Taken together, this study effectively demonstrated that soy-derived PA more potently activates mTOR, improving muscle hypertrophy and maximal strength when combined with resistance training. This finding further supports the hypothesis that an unsaturated fatty chain found in soy-derived PA promotes superior gains in size and strength. Consequently, soy-derived PA appears to be the better source of PA relative to egg-derived PA, for enhancing the effects of resistance training on muscle mass and strength.

PA Prevents Muscle Breakdown

The ability of PA to stimulate muscle growth may also come from its recently discovered capacity to inhibit muscle protein breakdown, which ultimately leads to muscle hypertrophy— as decreased muscle protein breakdown tends to increase muscle protein levels, promoting muscle growth. The first indication that PA could inhibit muscle protein breakdown came from a study showing that increasing the amount of one of the enzymes that synthesizes PA in the body, PLD1, in isolated muscle cells increased PA levels. This increase in PA rapidly reduced expression of a set of genes that promote muscle protein breakdown.⁸ This study then went on to demonstrate that the same muscle-depleting genes could also be turned off by exposing these isolated muscle cells directly to PA.

Interestingly, some of the genes involved in the protein-degrading pathway that are turned off by PA can also be turned on by the extremely powerful muscle-depleting molecule myostatin, which suggests that PA may actually thwart some of the negative effects of myostatin on muscle growth.

Now, while these results are very intriguing, they certainly require additional experimentation, as the anti-catabolic effects of PA were only shown on muscle cells in vitro. Thus, more studies investigating the effects of PA in humans are required to fully confirm these findings.

In summary, all of the science indicates that PA increases muscle mass by activating the muscle-building enzyme mTOR, while potentially reducing muscle protein degradation. This prospective dual impact of PA on muscle protein levels is typically very advantageous for muscle growth— as it not only represents an effective way to trigger muscle protein synthesis, but also provides a way to mitigate the often underappreciated catabolic influence that intense weight training has on muscle tissue.

The positive influence of PA is even more pronounced when supplement use is optimally coordinated with weight-training sessions. So, the optimal supplementation protocol for PA should include at least 750 milligrams of soy-derived PA immediately after weightlifting, seeing that it is rapidly available within 30 minutes after oral ingestion and stays available for at least seven hours. Of course, this time frame of seven hours post-workout is when the catabolic effect from weight training is at or near its peak, and should be inhibited as quickly and strongly as possible to minimize any potential muscle loss, which will eventually provide superior gains in size and strength.

For most of Michael Rudolph’s career he has been engrossed in the exercise world as either an athlete (he played college football at Hofstra University), personal trainer or as a research scientist (he earned a B.Sc. in Exercise Science at Hofstra University and a Ph.D. in Biochemistry and Molecular Biology from Stony Brook University). After earning his Ph.D., Michael investigated the molecular biology of exercise as a fellow at Harvard Medical School and Columbia University for over eight years. That research contributed seminally to understanding the function of the incredibly important cellular energy sensor AMPK— leading to numerous publications in peer-reviewed journals including the journal Nature. Michael is currently a scientist working at the New York Structural Biology Center doing contract work for the Department of Defense on a project involving national security.

The nutritional supplement world has seen its fair share of “fat-burning” products claiming to be able to reduce body fat by simply increasing the rate at which fat is oxidized, or burned, within the body. While this approach to a leaner body seems pretty logical, it has one major drawback— as increasing the level of fatty acid oxidation simply results in the production of more of the energy-rich molecule ATP— which, at first glance, may not seem problematic. However, higher levels of ATP do not reduce body fat. In fact, what it will do is trigger homeostatic mechanisms within the body that will simply convert this ATP surplus back into body fat within a rather short period of time. So, the fundamental problem with merely converting body fat into ATP is that this process does not increase the amount of energy expenditure— which is the only valid way to reduce body fat.

Recent attempts to advance fat loss by explicitly boosting energy expenditure have included the use of several naturally occurring compounds that target brown adipose tissue, or brown fat. This type of fat, despite being fat itself, has the unique capacity to reduce the other type of fat, white adipose tissue, which is usually referred to as body fat. Brown fat minimizes body fat by activating a process known as thermogenesis that increases energy expenditure— which, once again, is essential to minimize body fat.

Brown fat is able to increase energy expenditure because it contains a different type of fat cell that uncouples fat burning with ATP production, converting the energy from fatty acid oxidation into heat instead. Most cells within the body can perform thermogenesis to varying degrees. However, brown fat performs thermogenesis most effectively— as each brown fat cell has more fat-incinerating mitochondria that possess a higher concentration of the UCP-1 protein that is directly responsible for the thermogenic function of uncoupling fat oxidation with ATP production. As a result, brown fat has a greater capacity than any other cell in the body to thermogenically burn more fat and uncouple this process to energy production, ultimately increasing energy expenditure and fat loss.

Thermogenesis in brown fat is typically triggered by exposure to cold temperatures, as thermogenically derived heat can be used to warm up the body. Cold temperatures stimulate the TRPV receptor within the brain, which triggers the sympathetic nervous system, resulting in the release of noradrenaline. The subsequent interaction between adrenaline and the beta-adrenergic receptors embedded within the cellular membranes of brown fat initiates uncoupled fatty acid oxidation or thermogenesis, generating heat. While prolonged exposure to cold temperatures for roughly two hours has been shown to effectively trigger brown fat activity and fat loss1, using this approach to lower body fat is rather impractical, based on the considerable amount of time necessary to trigger the fat-burning capacity of brown fat.

Many studies have shown that other members of the TRPV family are activated outside of the brain by various food-related compounds, instead of cold temperatures. Some of these compounds bind directly to TRPV receptors within the oral cavity, similarly activating the sympathetic nervous system and stimulating the thermogenic process within brown fat. Other compounds have been identified that also induce brown fat thermogenesis, either by directly stimulating noradrenaline release or activating the adrenergic receptors within brown fat. Several other thermogenic compounds have been identified that more directly enhance the functional capacity of brown fat by increasing UCP-1 production within the cell, effectively improving the thermogenic process. Since all of these compounds remove the requirement for prolonged cold exposure, they represent a much more practical way to generate thermogenic-driven fat loss.

There are many different compounds that trigger thermogenesis, with some being much more effective than others. So, after countless hours of scouring through the science, we’ve compiled a list of the top 10 thermogenic supplements that potently increase energy expenditure, giving an uncommon ability to burn fat and keep if off. Green tea extract containing concentrated catechins is not recommended in this review, because of possible liver toxicity!

1. Caffeine Raises Your Thermogenic Buzz

Caffeine is best known as the active ingredient in coffee that stimulates the central nervous system, impeding drowsiness and restoring alertness. Caffeine is also a potent thermogenic compound. In fact, a single dose of 100 milligrams of caffeine can increase thermogenically driven energy expenditure by approximately 100 calories per day2, demonstrating that regularly ingested doses of caffeine can have a significant influence on energy balance and fat loss.

2. P-Synephrine (from Citrus aurantium) Safely Boosts Thermogenic Fat Loss

P-Synephrine is an alkaloid found in bitter orange and other citrus fruits including oranges and grapefruits3, and is widely used for weight management. Studies show that P-synephrine specifically binds to beta-3 adrenergic receptors found in brown fat.4 This class of adrenergic receptor explicitly activates thermogenesis within brown fat. In line with this finding, P-synephrine has been shown to elicit a thermogenic effect by increasing resting metabolic rate in humans, with no adverse impact on heart rate or blood pressure, which typically occurs by activating the beta-1 and beta-2 adrenergic receptors.5

3. Dopamine Activators: Tyrosine and L-Dopa (from Mucuna pruriens) Drive Thermogenesis

Consumption of the dopamine precursors tyrosine and L-Dopa increases dopamine production and function.6,7,8 The neurotransmitter dopamine regulates neurons that initiate the thermogenic process. In fact, energy expenditure was shown to increase in subjects infused with dopamine in a dose-dependent manner, where greater levels of dopamine increased the amount of energy expenditure.9 Consequently, the capability of tyrosine and L-Dopa to increase dopamine levels should produce a robust thermogenic effect, supporting considerable fat loss.

4. Ursolic Acid Increases BAT Levels for Enhanced Thermogenesis

Another powerful approach that exploits the thermogenic potential of brown fat involves increasing the amount of brown fat in the body. A compound found in many fruits and herbs, known as ursolic acid, has recently been shown to increase brown fat levels.10 Ursolic acid has also been shown to increase the expression of UCP-1, effectively increasing the thermogenic capacity of brown fat. This combined action gives ursolic acid the unique capacity to increase both the activity and quantity of brown fat, providing an extraordinary capacity to increase thermogenically driven energy expenditure and considerable fat loss.

5. Bile Acids Activate Thermogenesis by Stimulating Thyroid Hormone Activity

Bile acids typically emulsify fat for improved digestion. The use of bile acids as a supplement also provides resistance to diet-induced obesity by upregulating thyroid hormone function, which boosts thermogenesis in brown fat.11 More precisely, bile acids have the capacity to bind to the TGR-5 receptor embedded in the cellular membrane of brown fat. The interaction between bile acids and the TGR-5 receptor escalates the expression of the enzyme deiodinase, which catalyzes the production of the active thyroid hormone triiodothyronine or T3. Greater T3 results in the stimulation of UCP-1 production, which enhances brown fat thermogenesis.

6. Kaempferol and 7. Oleuropein – Polyphenols That Improve Thyroid Function and Fat Burning

A wide variety of polyphenolic compounds also enhance thermogenic fat loss. One of the more potent being oleuropein, a polyphenolic found in extra-virgin olive oil, which can enhance noradrenaline secretion and increase UCP-1 in brown fat, triggering thermogenesis.12 Another polyphenolic with remarkable thermogenic properties isolated from different sources such as tea, broccoli and grapefruit is the compound kaempferol. This compound uniquely activates the thermogenic process in muscle cells. All cells have the capacity to burn fat and expend energy via thermogenesis. Kaempferol also stimulates thyroid hormone production, which stimulates thermogenesis in brown fat13, giving kaempferol the unusual capability to activate thermogenesis in different cell types within the body, which most certainly contributes to its robust fat-scorching capacity.

8. Spices: Capsaicin, Piperine, Ginger (Gingerols), Cinnamon (Cinnamaldehyde)

Capsaicin is the spice found in chili peppers that contributes to the hot and spicy flavor of the chili pepper. Capsaicin directly binds and activates the TRPV1 receptor within the oral cavity— which releases noradrenaline, boosting thermogenesis in brown fat. Several studies have shown that a single ingestion of capsaicin can activate brown fat thermogenesis14,15, while longer term ingestion of roughly six weeks increased thermogenesis in brown fat, resulting in reduced body fat.16 Interestingly, this six-week study also showed thermogenic activity in brown fat contributed significantly to fat loss in individuals who had an extremely low amount of brown fat before the study began, which strongly suggests that long-term intake of capsaicin can also increase the amount of brown fat in the body.
Three more spices— piperine, the spicy compound from black pepper; cinnamaldehyde, the pungent ingredient in cinnamon; and gingerol, the active constituent in ginger— also strongly induce thermogenic fat loss. Like capsaicin, piperine and gingerol activate the TRPV1 receptor while cinnamaldehyde activates the TRPA1 receptor, a member within the TRPV1 family of receptors. Activation of this family of receptors triggers thermogenic energy expenditure in a similar fashion to capsaicinoids17,18, which ultimately depletes body fat in a similarly powerful way. For best results, take quick-release supplements of capsaicin. Coated or delayed-release capsaicin may not be as effective because they bypass TRPV1 receptors in the stomach and upper gastrointestinal tract.

9. Forskolin (from Coleus forskohlii)

Forskolin is a chemical produced by the Indian coleus plant that activates the enzyme adenylyl cyclase within brown fat, resulting in greater cyclic AMP (cAMP) levels. Increased levels of cAMP in brown fat cells also occur when noradrenaline binds to the beta-adrenergic receptor, triggering thermogenesis. Therefore, the ability of forskolin to increase cAMP levels in brown fat also enhances thermogenesis. In fact, it has been reported that hamsters and rats given forskolin increased oxygen consumption and thermogenic activity of brown fat.19 Furthermore, forskolin does not interact with beta-receptors in brown fat cells like noradrenaline does20, indicating that forskolin could have an additive impact on thermogenesis when taken with other thermogenic compounds that directly trigger noradrenaline release and beta-adrenergic production of cAMP— producing superior levels of thermogenic fat loss.

10. Melatonin

Melatonin is a hormone secreted by the pineal gland in the brain that regulates the sleep/wake cycle, helping you fall asleep. Melatonin is also involved in energy metabolism and bodyweight control. Many studies show that melatonin reduces bodyweight and abdominal fat21 without eating less or increasing physical activity. Conceivably, melatonin reduces fat without decreasing food consumption or physical activity by activating thermogenesis in brown fat22, which increases energy expenditure and thus fat loss.

For most of Michael Rudolph’s career he has been engrossed in the exercise world as either an athlete (he played college football at Hofstra University), personal trainer or as a research scientist (he earned a B.Sc. in Exercise Science at Hofstra University and a Ph.D. in Biochemistry and Molecular Biology from Stony Brook University). After earning his Ph.D., Michael investigated the molecular biology of exercise as a fellow at Harvard Medical School and Columbia University for over eight years. That research contributed seminally to understanding the function of the incredibly important cellular energy sensor AMPK— leading to numerous publications in peer-reviewed journals including the journal Nature. Michael is currently a scientist working at the New York Structural Biology Center doing contract work for the Department of Defense on a project involving national security.

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The human brain is made up of approximately 80 billion interconnected neurons that function as the core “information processing center” for the entire body. Normal brain function requires the precise communication between these neurons via chemical messengers called neurotransmitters. Dopamine is one of these important neurotransmitters that regulate motivation, productivity and overall focus by eliciting a pleasurable response to certain stimuli that reinforces the above-mentioned behaviors. While the impact of dopamine function normally bolsters positive health benefits, abnormal dopamine signaling in the brain can also support some unwanted consequences. For instance, eating foods loaded with fat and sugar triggers the release of copious amounts of dopamine, producing the gratification commonly experienced while eating this kind of food. Evidently, the frequent consumption of fatty and sugary food tends to reduce dopamine function in the brain over time, which is why the consumption of more fat and sugar is needed to receive the same pleasurable sensation, thus increasing the prospect for unhealthy weight gain.

The aforementioned undesirable metabolic result occurs because eating large amounts of fat and sugar stimulates more insulin release, which can activate certain negative feedback mechanisms that, in due course, diminish insulin function. Because of the decreased insulin performance, the amino acid L-tyrosine is not transported into the brain to the same extent, as insulin facilitates L-tyrosine transport across the blood-brain barrier into the brain. Since L-tyrosine is required for dopamine production, the brain produces less dopamine, meaning decreased dopamine function in the brain. This increases the need for unhealthy food intake to get the same pleasurable impact, initiating a cycle of excessive eating that increases the likelihood of weight gain, while also making it seemingly impossible to lose weight. In fact, studies have shown that obese individuals elicit weaker dopamine release in response to high-fat food intake— indicating that obesity is associated with reduced sensitivity to the food-reward receipt, which ultimately contributes to the overindulgence of food, perpetuating the cycle of weight gain.¹

Dopamine and Addiction

The capacity of dopamine to trigger feelings of pleasure also makes the dopamine system vulnerable to manipulation by certain types of addictive drugs like cocaine and prescription drugs like Adderall, which stimulate feelings of pleasure by increasing dopamine activity within the brain. Regrettably, a physical dependence of this enjoyable stimulus can develop, making it extremely difficult to overcome many of these addictions. For example, according to the Drug Enforcement Administration, approximately 1.5 million Americans are addicted to cocaine and nearly 80 percent of those trying to quit relapse within the first six months of trying.²

Excessive release of dopamine from drug use also reduces dopamine function. However, the negative influence on dopamine from drug use occurs in a different fashion— as many addictive drugs that trigger excessive dopamine signaling in the brain wind up increasing the rate of dopamine degradation within the neuronal synapse while simultaneously reducing dopamine synthesis, which together diminish dopamine activity greatly. A well-established example of this is the drug cocaine, which triggers an initial feeling of euphoria from the short-term increase in dopamine. Then, over time, dopamine becomes depleted, leading the user to require higher doses of drug to experience the same pleasurable effect. It has been proposed that the decreased dopaminergic function associated with drug use underlies the addiction to drugs such as cocaine.³

Alleviate Addiction to Food and Drugs

Since chronically reduced dopamine levels brought on by excessive food intake or drug abuse seemingly escalates the impulse to consume more food or drug, enhancing dopamine production in the brain should mitigate these unhealthy behaviors. Some prescription drugs, such as Ergoset, have been specifically prescribed to increase dopamine function, resulting in weight loss. However, like most drugs, Ergoset use can cause several unwanted side effects including dizziness and nausea, making the use of this drug unwarranted for healthy individuals looking to get in shape. Likewise, other dopamine-enhancing prescription drugs, like Ritalin, have also been prescribed for addiction to drugs like cocaine. Yet, Ritalin also has its fair share of adverse side effects including nausea, insomnia and increased blood pressure.

On the other hand, it is much healthier to boost dopamine naturally by consuming a diet that supports dopamine production, while also performing the best exercise regimen that further augments dopamine function. Add to this the most potent dopamine-enhancing supplement on the market, Dopa Rush™ from Advanced Molecular Labs, and you’ve got a recipe for superior dopamine activity in the brain that should help suppress unhealthy urges for fat-promoting foods and harmful drugs. Increasing dopamine naturally should also provide a greater capacity to lose body fat, as dopamine stimulates thermogenesis in brown adipose tissue. Thermogenesis is a process that burns fat, turning it into heat instead of ATP, thus increasing energy expenditure— which is absolutely required to lose weight.⁴

The Dopa Rush™ Diet

Adding foods to your diet that are full of the amino acid L-tyrosine is an exemplary way to increase dopamine production in the brain. L-tyrosine is a key biosynthetic precursor of dopamine, meaning more L-tyrosine intake in the diet stimulates greater dopamine production. Some nourishing foods loaded with L-tyrosine include poultry, lean beef, oatmeal, beans, eggs and fish, especially salmon. Interestingly, salmon is also chock-full of omega-3 fatty acids, which, in addition to being able to reduce body fat⁵, also improves dopamine production. The positive impact of omega-3s on dopamine production is likely caused, in large part, by the positive influence omega-3 fatty acids have on insulin sensitivity— as studies have shown that certain omega-3 fatty acids reduce the amount of insulin required to shuttle glucose into muscle cells.⁶ The lower requirement for insulin precludes any potential negative feedback influence on insulin signaling, ultimately enhancing insulin function that likely encourages L-tyrosine transport, and dopamine synthesis, in the brain.

The Most Potent Dopamine-Enhancing Supplement, Dopa Rush™

Supplementing the aforementioned diet with the breakthrough product Dopa Rush™ provides an additional 2,000 milligrams of L-tyrosine, further supporting dopamine production. In addition to boosting exercise performance, this amount of tyrosine intake can also enhance mental performance just as impressively, as shown by Thomas et al. where test subjects consuming two grams of tyrosine had a vastly improved memory.⁷

Dopa Rush™ also has 100 milligrams of Mucuna pruriens, providing a considerable amount of another vital dopamine precursor, L-dopa, at 40 milligrams. L-dopa has been shown to effectively increase diminished dopamine levels, particularly in patients with Parkinson’s disease, an illness that occurs due to low dopamine.^8,9 The use of Mucuna pruriens together with tyrosine likely augments dopamine function more potently, especially when these two compounds are combined with two other ingredients in this remarkable formula, caffeine and theacrine, as each compound vigorously drives dopamine release.^10,11

Dopa Rush™ also contains folic acid, which is involved in the biosynthesis of the cofactor tetrahydrobiopterin (BH4) that is required to produce dopamine, meaning more folic acid in the diet promotes greater dopamine synthesis.¹² Another key ingredient in Dopa Rush™ is piperine, a compound that activates the TRPV receptor in the brain, stimulating the sympathetic nervous system and resulting in dopamine release.¹³ Piperine also inhibits the enzyme that degrades dopamine— monoamine oxidase— giving this all-important ingredient the capacity to increase dopamine amounts as well as dopamine release in the brain.¹⁴

High-Intensity Training Means High Dopamine Levels

Together with diet and nutritional supplementation, exercise is an approach that also safely and vigorously enhances dopamine activity in the brain. By and large, most forms of exercise appear to improve dopamine function. However, some types of exercise are apparently better than others. Cardiovascular exercise done at a fixed pace tends to improve dopamine function, partly explaining the euphoric state known as “runner’s high” periodically achieved from this type of training. Yet, research is starting to show that high-intensity interval training (HIIT) appears to improve dopamine function more potently, relative to steady-state cardio. In fact, one investigation by Marusiak et al.¹⁵ showed that HIIT improved overall mobility in patients with mild to moderate Parkinson’s disease, signifying improved dopamine function within these patients.

Another intense training modality using heavy resistance training, at 10 reps per set with relatively short rest periods of 10 seconds, also had a considerable impact on dopamine activity. This effect was shown in a recent study by Kraemer et al.¹⁶, where highly trained competitive bodybuilders and powerlifters performing this training mode showed large increases in dopamine levels.

Reduce Fatigue and Enhance Mental Focus

Enhanced dopamine function from an optimal diet, exercise and nutritional supplementation regimen can also significantly reduce fatigue caused by an exhausted central nervous system (CNS), providing greater focus and more intense training in the gym for longer periods of time. Although many variables contribute to fatigue experienced while training, one of the primary culprits for this fatigue is a weary central nervous system (CNS) that requires more than simply consuming carbohydrates, fats and protein to restore metabolic energy. That is because a tired CNS requires something other than caloric energy— it needs more dopamine, and lots of it— as intense exercise reduces dopamine, drastically generating fatigue and decreased exercise performance.

Studies have shown that the use of the psychostimulant buproprion, which inhibits neuronal reuptake and degradation of dopamine, improves performance significantly during exercise.¹⁷ This is probably why this class of drug has been used to enhance athletic performance. Of course, using psychostimulants as an ergogenic aid is extremely dangerous, and should be avoided at all costs. Yet, reversing the impact of dopamine degradation from intense training, by natural means, represents a safe way to mitigate CNS fatigue for more energy and better performance while training.

In closing, the neurotransmitter dopamine has many vital roles influencing divergent functions within the human body that range from mental acuity, psychological well-being and overall vitality. Therefore, enhancing dopamine activity with the Dopa Rush™ diet, exercise and supplement plan will reestablish, or even embellish, the capacity of this neurotransmitter to advance physical and mental health. Moreover, the ability to stop unsound lifestyle habits should also be improved, as improved dopamine activity most certainly alleviates much of the torment provoked when attempting to conquer poor habits and addiction.

For most of Michael Rudolph’s career he has been engrossed in the exercise world as either an athlete (he played college football at Hofstra University), personal trainer or as a research scientist (he earned a B.Sc. in Exercise Science at Hofstra University and a Ph.D. in Biochemistry and Molecular Biology from Stony Brook University). After earning his Ph.D., Michael investigated the molecular biology of exercise as a fellow at Harvard Medical School and Columbia University for over eight years. That research contributed seminally to understanding the function of the incredibly important cellular energy sensor AMPK— leading to numerous publications in peer-reviewed journals including the journal Nature. Michael is currently a scientist working at the New York Structural Biology Center doing contract work for the Department of Defense on a project involving national security.

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The central dogma in molecular biology states that DNA makes protein. While this scientific creed is accurate, a more philosophical interpretation of this rule asserts that DNA does more than simply produce protein; DNA produces human behavior. This is particularly true because some proteins encoded within our DNA enhance the production, and function, of chemicals known as neurotransmitters within the brain. Since neurotransmitters directly influence brain function and thus behavior, the ability of the genetic code to influence neurotransmitter function directly impacts the way we behave. Consider, for example, the neurotransmitter dopamine, which plays a major role in reward-motivated behavior— which increases dopamine activity within the brain, producing a euphoric-like feeling that ultimately reinforces that behavior.

Dopamine and Addiction

The capacity of dopamine to trigger feelings of pleasure also makes the dopamine system vulnerable to manipulation by certain types of addictive drugs like cocaine, prescription drugs like Adderall, and behaviors such as gambling— which all stimulate feelings of pleasure by increasing dopamine activity within the brain. Regrettably, a physical dependence for this enjoyable stimulus can develop, making it extremely difficult to overcome many of these addictions. In fact, according to the Drug Enforcement Agency (DEA), approximately 1.5 million Americans are addicted to cocaine, and nearly 80 percent of those trying to quit will relapse within the first six months of trying. In addition, there are an astounding 4 million American children who are prescribed drugs like Adderall for attention-deficit/hyperactivity disorder (ADHD), despite mounting evidence suggesting that combined therapeutic approaches lowers the need for these potent psychotropic drugs.¹ Adding to this problem are many high school and college students, who use dopamine-enhancing prescription drugs to increase their ability to concentrate for longer periods of time, enhancing their capacity to study for exams. Then there is also the chronic use of other drugs, such as marijuana, that appear to reduce the brain’s response to dopamine— lowering motivation and sensitivity to rewards, ultimately increasing the reaction to emotional stress and irritability.²

Alleviate Addiction

The new breakthrough product DOPA RUSH™ from Advanced Molecular Labs (AML) has been scientifically formulated with natural ingredients to address all of the aforementioned addiction issues. DOPA RUSH™ does this by suppressing the incessant craving for addictive drugs and behaviors, by naturally boosting the production of dopamine— thus mitigating the urge to crank up dopamine levels with harmful substances, or behavior, while perhaps even alleviating the harmful effects that smoking pot has on dopamine function in the brain.

Reinvigorate Completely With DOPA RUSH™

Greater dopamine from DOPA RUSH™ will also revive a tired central nervous system (CNS). The CNS, composed of the brain and spinal cord, serves as the main “processing center” for the entire nervous system that controls all the workings of your body by monitoring and coordinating organ function and responding to all external stimuli. Neurons, or nerve cells, are the fundamental components of the CNS that give and receive all of this information by electrical and chemical signaling. Neuronal electrical signaling is ultimately converted at the nerve ending into chemical signaling in the form of neurotransmitters, which are chemical substances that diffuse across the synapse to the next neuron, triggering further electrical signaling down that neuron and so on— until the desired effect is produced. After neurotransmitters diffuse across the synapse and activate the appropriate neuron, they are reabsorbed and degraded by the surrounding neurons— tightly regulating neuronal activity. Therefore, neuronal activity increases the degradation of certain neurotransmitters— effectively depleting their levels, inducing CNS fatigue.

This is one reason why after a long day at work, it is a bit harder to get in a great workout or do anything else that requires focus and attention. Personally, I usually can’t wait to get into the gym and hit the weights. Yet every once in a while, especially after a long work week, I’m a little less motivated and intense during the workout. I’ve also noticed during these workouts that my strength levels are usually depleted, making me wonder what could boost my energy levels and overcome this muscle-depleting fatigue. Although it may seem that the exhaustion I’m experiencing is mainly due to muscle fatigue that can be dealt with by eating a high-energy meal that replenishes muscle cell energy, the most likely contributor to my low energy and poor workout performance is a weary CNS that requires more than carbohydrate, fat and protein— no, this kind of CNS fatigue demands DOPA RUSH™!

Boost Dopamine

The most accepted mechanism explaining a lethargic CNS is the “central fatigue hypothesis.”³ This hypothesis states that an increase in the ratio of the neurotransmitter serotonin to the neurotransmitter dopamine within the CNS is associated with feelings of tiredness and lack of motivation. On the contrary, a low serotonin to dopamine ratio favors improved performance through the maintenance of motivation and arousal. Since serotonin is a neurotransmitter that has been linked to fatigue because of its well-known effects on sleep and drowsiness, it was originally thought that the serotonin to dopamine ratio was increasing during times of fatigue because of greater serotonin production, which increased fatigue. However, it turns out that the serotonin to dopamine ratio was increasing, primarily because of the degradation of dopamine associated with neuronal activity within the CNS during exercise.⁴ This new insight is completely logical, as dopamine has well-defined roles that positively influence motivation and arousal— so dopamine removal would reduce motivation and initiate fatigue. Consequently, increasing dopamine levels with DOPA RUSH™ will improve CNS function, reducing fatigue and improving the capacity to focus on the task at hand— ultimately providing superior mental function and overall performance, in and out of the gym.

DOPA RUSH™, the Natural Alternative to Dangerous Psychostimulant Drugs

The ability to crank up dopamine production for performance enhancement has already been established with a class of drugs known as psychostimulants. Altogether, these drugs effectively overcome fatigue while restoring focus and motivation. In fact, recent findings⁵ have shown that the use of the psychostimulant bupropion, which inhibits neuronal reuptake and degradation of dopamine, improves performance during exercise, particularly in very warm temperatures. In fact, the consumption of the highest dosage of bupropion enabled subjects to maintain a higher power output than the placebo group, yet only at elevated temperatures. Interestingly, the test subjects who consumed bupropion performed a significantly greater amount of work, while they reported no changes in the rate of perceived exertion. This phenomenon suggests an altered motivation or drive to continue exercise brought on by an increase in dopamine levels, as this would tend to decrease CNS fatigue and perceived exertion, despite exercising in a high-temperature environment.

Interestingly, the consumption of the dopamine precursor L-tyrosine, which also boosts dopamine production⁶, has also been shown to improve exercise performance in warmer temperatures, where subjects performed an exercise test while consuming either a placebo or L-tyrosine in a double-blind manner, one hour before cycling to exhaustion in 86 degrees Fahrenheit.⁷ The results showed the L-tyrosine-consuming group exercised for 16 percent longer, compared to the placebo group— while showing no increase in the rate of perceived exertion, despite a longer exercise time. This is the same result seen in the previous study, where test subjects consumed the psychostimulant bupropion— indicating that L-tyrosine intake had a similar impact on dopamine levels, which enhanced motivation and determination to exercise. So, consuming 2,000 milligrams of the potent dopamine activator L-tyrosine— the exact amount found in DOPA RUSH™— mimics the strong performance-enhancing effect of psychostimulants, yet in a much more natural, safer manner.

L-Tyrosine Builds Brain Power

In addition to boosting exercise performance, L-tyrosine intake can also enhance mental performance just as impressively. In fact, one study by Thomas et al. found test subjects who consumed 2,000 milligrams of L-tyrosine showed a vastly improved memory.⁸ While a second study found that consuming the same amount of L-tyrosine apparently also improves creative thinking, as test subjects who were given 2,000 milligrams of L-tyrosine showed an enhanced capacity to perform convergent thinking— indicating that 2,000 milligrams of L-tyrosine likely improves creative thinking, as convergent thinking indicates a greater capacity for creative thinking.⁹ That’s the same amount found in DOPA RUSH™.

Mild Caffeine Dosage in DOPA RUSH™ Improves Overall Mood and Cognitive Function

Caffeine is one of the powerful components in DOPA RUSH™, enhancing dopamine production. While caffeine is normally used as an ergogenic aid to improve exercise performance by increasing muscular contraction force and energy production within muscle, it is caffeine’s ability to stimulate the CNS that impacts the mental aspect of training, influencing overall mood and well-being. Caffeine stimulates the CNS, in part, by inhibiting the adenosine receptor in the brain. The inhibition of this receptor triggers the release of dopamine.¹⁰ The surge of dopamine from caffeine consumption will amp-up your neurochemistry for superior concentration and intensity while training in the gym. In fact, studies have shown that 200 milligrams of caffeine is the optimal dose for elevated mood and focus^11,12 … the same amount found in DOPA RUSH™! Additionally, the plateauing effect of caffeine on mood is believed to match the adenosine receptor effects on dopamine areas of the brain, and their involvement in the feelings of well-being.¹³ Moreover, additional studies have shown that similar doses of caffeine, at around 200 milligrams, also improved cognitive function, both during and after strenuous exercise, while enhancing concentration— and this improved cognitive ability correlated with improved dopamine production within the brain.

Get an Extra Jolt of Dopamine With DOPA RUSH™’s Theacrine (as TeaCrine™)

Although caffeine is a remarkable performance-enhancing supplement that can raise dopamine levels on its own, combining caffeine with theacrine apparently heightens dopamine production even more so, further improving energy and reducing fatigue. Theacrine is a protoalkaloid, with a similar chemical structure to caffeine that triggers dopamine release in a similar fashion to caffeine, increasing arousal and motivation. This effect was shown in an initial study where theacrine increased energy, diminished fatigue and improved concentration just like caffeine.¹⁴ However, unlike caffeine, which can produce a tolerance after as little as four days of consumption¹⁵, theacrine use for up to seven days showed no signs of desensitization— indicating that the combined intake of caffeine with theacrine should enhance mood and energy, with no decrease in potency for longer periods of time, effectively increasing overall arousal and focus before hitting the gym.¹⁵ Furthermore, the combined use of caffeine and theacrine likely stimulates the release of greater levels of dopamine, as a study by Kuhman et al.¹⁶ showed that combining theacrine with caffeine had a greater impact on feelings of energy and mood, relative to the consumption of caffeine alone, indicating an additive impact on dopamine levels. Consequently, in addition to DOPA RUSH™ having 200 milligrams of caffeine (the optimal dose for elevated mood and focus!), it also has 125 milligrams of the optimal dose of theacrine as TeaCrine™, generating an even greater surge in dopamine levels.

Improved Mood With Folic Acid

Another key ingredient in DOPA RUSH™ is folic acid, as some evidence links a shortage of folic acid with sluggishness and depression.¹⁷ While the exact mechanisms involved in the development of depression are not entirely transparent, some insight comes from the observation that folic acid is involved in the biosynthesis of the cofactor tetrahydrobiopterin (BH4) that is required for the production of dopamine. So, low folic acid probably results in lower dopamine levels fostering depression, as low dopamine levels have been linked to depression characterized by a low-energy, demotivated state.¹⁸ Consequently, more folic acid from DOPA RUSH™ will augment the catalytic production of dopamine, delivering an overall better mental state.

More Dopamine for More Motivation and Focus?

DOPA RUSH™ also has 100 milligams of Mucuna pruriens, providing a considerable amount of the dopamine precursor L-dopa, at 40 milligrams¹⁹, which is a compound that has been shown to effectively increase diminished dopamine levels— particularly in patients with Parkinson’s disease, a disease that occurs due to low dopamine.²⁰ Interestingly, an additional clinical trial also indicated that Mucuna pruriens was just as effective as some pharmaceuticals in the treatment of Parkinson’s disease, illustrating the powerful ability of Mucuna pruriens to increase dopamine levels in the brain.¹⁹ Consequently, taking Mucuna pruriens along with tyrosine should bolster dopamine production and function even more potently, particularly when these two dopamine-enhancing compounds are combined with caffeine and theacrine in DOPA RUSH™. Overall, this potent blend will augment dopamine synthesis and release, giving DOPA RUSH™ an extraordinary capacity to increase dopamine activity for exceptional mental clarity and physical performance.

Trigger More Dopamine and Halt Dopamine Degradation With Piperine

DOPA RUSH™ is also loaded with the compound piperine, which is naturally found in black pepper. Piperine triggers dopamine release by activating the TRPV receptor in the brain, which stimulates the sympathetic nervous system, resulting in dopamine release.²¹ Piperine also inhibits the enzyme that degrades dopamine— monoamine oxidase— resulting in a surge in dopamine, giving this all-important ingredient the capacity to increase dopamine amounts as well as dopamine release in the brain.²² Piperine also improves the gastrointestinal absorption and systematic utilization of the other dopamine-boosting nutrients in DOPA RUSH™ which, altogether, makes piperine an indispensable ingredient in this dopamine-enhancing supplement.

Weight Loss Made Easier

Enhanced dopamine levels brought about by DOPA RUSH™ will also improve dieting and weight loss, as evidence has shown that obese people tend to have an underactive dopamine response to food intake— requiring them to eat more in order to trigger a sufficient dopamine release that fully rewards and satiates them.²³ So, the ability of DOPA RUSH™ to increase dopamine levels should diminish the desire to overeat, improving and promoting weight loss.

Take DOPA RUSH™ Without Food for Optimal Effect

In order to optimize all of the positive effects associated with DOPA RUSH™, this product should be taken on an empty stomach to avoid any potential antagonistic effects that certain foods may have on the ability of DOPA RUSH™ to boost dopamine. For instance, the amino acid leucine, found in many different protein sources, prevents the uptake of the dopamine-precursor tyrosine into the brain, reducing dopamine production.²⁴ Of course, this could potentially counteract any positive influence that DOPA RUSH™ would have on dopamine production, making it pretty clear that co-ingesting DOPA RUSH™ with any protein source loaded with leucine or tryptophan is ill-advised, as this would diminish the impact of DOPA RUSH™ on dopamine levels. As a result, DOPA RUSH™ does not contain any compounds that diminish the production of dopamine. Moreover, DOPA RUSH™ should be consumed separately on an empty stomach, to optimize the production of dopamine.

For more information or to purchase DOPA RUSH™, visit www.advancedmolecularlabs.com.

 For most of Michael Rudolph’s career he has been engrossed in the exercise world as either an athlete (he played college football at Hofstra University), personal trainer or as a research scientist (he earned a B.Sc. in Exercise Science at Hofstra University and a Ph.D. in Biochemistry and Molecular Biology from Stony Brook University). After earning his Ph.D., Michael investigated the molecular biology of exercise as a fellow at Harvard Medical School and Columbia University for over eight years. That research contributed seminally to understanding the function of the incredibly important cellular energy sensor AMPK— leading to numerous publications in peer-reviewed journals including the journal Nature. Michael is currently a scientist working at the New York Structural Biology Center doing contract work for the Department of Defense on a project involving national security.

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The Antagonistic Effects of Caffeine and Taurine in Energy Drinks

Energy drinks have become a billion-dollar industry, challenging the eye-popping popularity of Starbucks and the likes. Obviously, the main component of energy drinks is caffeine, with some being more potent than others. However, many manufacturers feel the need to add supplemental ingredients to their drinks to “boost” their energizing effects. Whether this is for marketing or real effect is left to be determined.

One of the most popular additives to energy drinks is the non-essential amino acid taurine. Taurine is thought to modulate cell volume, muscle contraction and aid in antioxidant defenses from stress in muscle. Unfortunately for the college student during finals week, the scientific literature does not support using taurine to enhance the vitalizing effects of your caffeinated beverage.

A recent animal study evaluated the muscle ergogenic effects of caffeine alone or in combination with taurine, and found no beneficial effect to adding taurine. Two human, placebo-controlled studies evaluated the effects of using caffeine, taurine or a combination of the two on attention/“energy.” One double-blind, placebo-controlled study compared 80 milligrams of caffeine with or without one gram of taurine and found that co-administration of taurine attenuated the facilitative effects of caffeine. Another study compared 200 milligrams of caffeine with or without two grams of taurine, and further showed that taurine inhibited feelings of vigor normally resulting from caffeine alone.
In summary, the makers of Red Bull and Monster energy drinks may not be out for your best interest when trying to boost your vigor. Not only does taurine have little effect on its own, but it may also have a detrimental effect on the function of your precious caffeine!

CAN LEUCINE CONSUMPTION BEFORE EXERCISE HINDER PERFORMANCE?

One of the more well-characterized muscle-building supplements is the branched-chain amino acid leucine, which has clearly been shown to inhibit muscle protein breakdown while simultaneously increasing the rate of muscle protein synthesis, ultimately promoting substantial muscle growth. Leucine consumption promotes muscle protein accumulation and muscle growth by activating the extremely important nutrient-sensing molecule mTOR, which directly turns off muscle protein degradation while activating muscle protein synthesis. Several studies have shown mTOR activation by leucine intake, specifically during and after resistance exercise.

Although it has been well established that leucine consumption during and after resistance exercise promotes muscle growth, the verdict is still out regarding the performance-enhancing effect from leucine consumption before training. Some of the uncertainty about leucine’s pre-workout consumption stems from the fact that leucine consumption decreases energy production within the muscle cell, potentially diminishing muscle performance during exercise. Another concern about pre-workout leucine consumption involves the likely desensitization of the potent muscle-building hormone insulin, resulting from additional leucine consumed before working out. The final concern involves the negative influence that leucine consumption may have on the central nervous system (CNS) where pre-workout leucine consumption might increase the rate of CNS fatigue, promoting overall sluggishness that decreases exercise performance.

 Pre-workout Leucine Decreases Muscle Cell Energy

In order to build muscle, you’d think that you need to be in an anabolic state at all times— which might also make you believe that the ubiquitous consumption of muscle-building compounds, like leucine, should enhance muscle growth. Yet the reality is being constantly in an anabolic state is not optimal for muscle size and strength. This is mainly because maximal muscle growth requires the perfect blend of muscle-building anabolism combined with energy-producing catabolism. In other words, if you want to build muscle, something has to supply it with energy to function. Well, that’s where catabolic processes like glycogenolysis, the breakdown of glycogen into glucose for energy, play a huge role mainly because intense weightlifting requires glucose for energy. So, although leucine potently stimulates muscle growth, it also prevents the breakdown of glycogen into glucose, reducing available energy that is necessary for muscle contraction. Of course, reduced muscular contraction decreases strength output— which likely compromises the ability to get huge.

 Too Much Leucine Diminishes Muscle Growth

Insulin is the most potent muscle-building hormone produced in the human body, possessing the ability to drastically increase muscle protein synthesis and enhance muscle growth. Insulin achieves this muscle-building effect by binding to the insulin receptor and setting off a cascade of signaling events that eventually activates the enzyme mTOR, triggering muscle growth. However, insulin signaling is very sensitive to overstimulation— where too much insulin signaling can rapidly trigger negative feedback mechanisms that turn down insulin-driven muscle growth.

In addition to the well-known influence that glucose has on insulin secretion and activity, one of the more potent insulin activators is leucine. Interestingly, several studies have shown that insulin resistance can occur with increased amino acid consumption, especially the branched-chain amino acid leucine. The exact mechanism by which leucine modulates insulin sensitivity is currently unclear. Although the decreased insulin sensitivity may be associated with greater insulin secretion induced by leucine, potentially inducing insulin resistance. Of course, insulin resistance from too much leucine consumption would reduce all of insulin’s anabolic properties, meaning a decrease in muscle protein accumulation and therefore muscle growth.

 Leucine Consumption Before Your Workout Promotes Sluggishness and Fatigue

The CNS, composed of the brain and spinal cord, serves as the main “processing center” for the entire nervous system that controls all the workings of your body. Neurons, or nerve cells, are the core components of the CNS that function to receive and confer all of this body-regulating information by electrical and chemical signaling. Neuronal electrical signaling is ultimately converted at the nerve ending or synapse into chemical signaling utilizing neurotransmitters that diffuse across the synapse to adjacent neurons, triggering further electrical signaling down those neurons, which eventually control numerous processes in the body.

Serotonin is a neurotransmitter secreted within the neuronal synapse that induces sleep and drowsiness. Intense exercise has been shown to increase the release of serotonin in the brain, putatively contributing to exercise-induced fatigue. Initially, it was thought that the increase in serotonin alone triggered fatigue. However, it turns out that greater fatigue from exercise is influenced more specifically by an increase in the ratio of serotonin to another neurotransmitter known as dopamine.

The neurotransmitter dopamine has well-defined roles including increased mental arousal, improved motor control and greater levels of motivation, which all tend to improve exercise performance. Therefore, a lower serotonin to dopamine ratio, by either decreasing performance-inhibiting serotonin or increasing performance-enhancing dopamine, should improve exercise capacity. Interestingly, leucine consumption has been shown to inhibit serotonin production by preventing transport of the serotonin-precursor tryptophan into the brain. Because tryptophan is a building block for serotonin, lower tryptophan in the brain reduces serotonin production— suggesting that leucine consumption before exercise could actually mitigate exercise-induced fatigue.

On the other hand, a recent study by Choi et al. showed that leucine also competitively inhibits dopamine production by preventing the uptake of the dopamine-precursor tyrosine into the brain. Since greater brain dopamine function improves physical performance, the finding that leucine reduces dopamine levels in the brain highlights why leucine consumption, especially before exercise when motivation and energy levels are paramount, may have a detrimental influence on physical performance despite leucine’s ability to also reduce serotonin levels.

In conclusion, leucine’s capacity to trigger anabolic processes, such as muscle growth and glycogen production, makes the timing of leucine consumption very important. While leucine consumption during and after lifting weights effectively prevents muscle breakdown while enhancing muscle growth, consuming leucine before your workout appears to have several drawbacks that negatively influence exercise performance— suggesting that pre-workout leucine consumption is not best for optimal muscular performance.

For most of Michael Rudolph’s career he has been engrossed in the exercise world as either an athlete (he played college football at Hofstra University), personal trainer or as a Research Scientist (he earned a B.Sc. in Exercise Science at Hofstra University and a Ph.D. in Biochemistry and Molecular Biology from Stony Brook University). After earning his Ph.D., Michael investigated the molecular biology of exercise as a fellow at Harvard Medical School and Columbia University for over eight years. That research contributed seminally to understanding the function of the incredibly important cellular energy sensor AMPK— leading to numerous publications in peer-reviewed journals including the journal Nature. Michael is currently a scientist working at the New York Structural Biology Center doing contract work for the Department of Defense on a project involving national security.

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Twitter: @AML_Nutrition

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Increase Energy Expenditure – Burn Fat and Keep It Off!

Most weight-loss programs involve caloric restriction combined with some kind of rigorous exercise program. This generates an energy deficit that prompts the body to burn fat in order to replenish energy, which in due course promotes fat loss. In theory, this approach seems very logical and should work well, but it has been rather ineffective at achieving fat loss based on the fairly high levels of obesity seen in the United States.¹ Furthermore, the typical fat-burning regimen generally involves extensive cardiovascular work that inhibits muscle growth, especially while cutting calories, making this an ineffective choice for those trying to lose fat while maximizing muscle.

Burn Fat With BAT

In view of the above-mentioned shortcomings, alternate ways to reduce body fat have recently gained considerable interest. One fat-loss target that has emerged as potentially groundbreaking is brown adipose tissue (BAT) or brown fat. BAT normally generates body heat by vigorously burning body fat, by a process known as non-shivering thermogenesis, in response to cold temperature exposure in order to maintain normal body temperature. The ability to burn fat with BAT represents a promising way to improve fat loss.

BAT is composed of a unique type of fat cell that generates a considerable amount of heat, because of its remarkable capacity to uncouple the normally linked process of fat burning with cellular energy (ATP) production within the mitochondria. As a result, instead of the energy from fat being used to synthesize ATP, it is instead converted into heat. To some degree, all cells can generate heat by thermogenesis, especially when body temperature is below a regulatory threshold. However, BAT is the most proficient thermogenic tissue in the body for two basic reasons. First, each cell has a higher number of mitochondria compared to other cells. Second, these mitochondria have a higher-than-normal concentration of a protein known as uncoupling protein 1 (UCP-1) within their mitochondria. UCP-1, as its name implies, is the protein that directly uncouples fat oxidation with ATP production, producing heat instead.

Interestingly, BAT has been long recognized as a thermogenic organ in other species, yet has only recently been found to exist in adult humans. Despite only recently discovering the existence of BAT in adults, there has been an abundance of scientific inquiry into BAT function that has produced a ton of evidence demonstrating that BAT has a significant regulatory function controlling whole-body energy expenditure and body fat levels in adult humans.^2-6 Furthermore, additional research has led to the discovery of many naturally occurring compounds that strongly augment BAT-induced fat burning.

Compounds That Trigger Thermogenesis

There are many different compounds that trigger thermogenesis, with some being much more effective than others. This month, we’ve compiled a list of the top 10 thermogenic supplements that based on scientific evidence, potently increase energy expenditure— giving an uncommon ability to burn fat and keep it off. Green tea extract containing concentrated catechins is not recommended, despite its capacity to trigger thermogenesis, because of possible liver toxicity.

1. CAFFEINE – Helps Raise Thermogenic Buzz

Caffeine is the active ingredient in coffee that stimulates the central nervous system, so it impedes drowsiness and restores alertness. Caffeine is a potent thermogenic compound. In fact, a single serving of 100 milligrams of caffeine can increase the body’s thermogenically driven energy expenditure by a significant amount of calories per day, suggesting that if caffeine is ingested on a regular basis, it can exert a significant influence on energy balance and fat loss.

 2. P-SYNEPHRINE (from Citrus aurantium) – Safely Boosts Thermogenic Fat Loss

P-Synephrine, an alkaloid found naturally in bitter orange and other citrus fruits, including Tarocco and Naveline oranges and grapefruits, has been widely adopted as a useful supplement in bringing about the successful control of bodyweight. Studies have shown that p-synephrine specifically binds to the beta-3 adrenergic receptors found in brown fat. This class of adrenergic receptor specifically activates thermogenesis within brown fat. Inspired by this finding, scientists delved further and found that p-synephrine can elicit thermogenesis, ultimately increasing the resting metabolic rate in humans. Even better is the significant finding that no adverse impact on heart rate or blood pressure occurred during this process. This stands in marked contrast with the negative effects on heart rate and blood pressure that occur when beta-1 and beta-2 adrenergic receptors are activated.

 3. DOPAMINE ACTIVATORS

Tyrosine and L-Dopa (from Mucuna pruriens) Drive Thermogenesis

Dopamine production and function within the body are aided with the consumption of the dopamine precursors tyrosine and L-Dopa. Dopamine controls and regulates the neurons that initiate the thermogenic process. In fact, energy expenditure has been shown to increase in subjects infused with dopamine in a dose-dependent manner, where greater levels of dopamine increased the amount of energy expenditure. With this, the capability of tyrosine and L-Dopa to optimize dopamine levels produces a desirable thermogenic effect, which results in fat loss.

 4. URSOLIC ACID

Increases BAT Levels for Enhanced Thermogenesis

Another approach that makes use of the thermogenic potential of brown fat is one that is designed to increase the amount of brown fat contained within the body. Ursolic acid, a compound found in many fruits and herbs, has been shown to increase brown fat levels. It also acts as a stimulus for the expression of UCP-1, which effectively increases the thermogenic capacity of brown fat. Taken together, the ability of ursolic acid to bring about these two beneficial processes makes it a key supplement for producing thermogenically driven energy expenditure and considerable fat loss.

 5. BILE ACIDS

Activate Thermogenesis by Stimulating Thyroid Hormone Activity

Bile acids are typically recommended by physicians and allied professionals for their ability to emulsify fat so that the digestive process can be improved. Bile acids, when used as a supplement, also help promote resistance to dietary-induced weight gain/excess weight by their ability to maximize thyroid hormone function, which turns on thermogenesis in brown fat cells. Bile acids have the capacity to bind to the G-protein TGR-5 receptors embedded in the cell membranes of brown fat. The interaction between bile acids and the TGR-5 receptor triggers the expression of the enzyme deiodinase, which acts as a catalyst to increase the production of the active thyroid hormone triiodothyronine (T3). When there are adequate amounts of T3 circulating in the bloodstream, there will be an accompanying enhanced production of UCP-1 in brown fat. And when UCP-1 production is increased, the furnace of brown fat thermogenesis will be ignited.

6. KAEMPFEROL and 7. OLEUROPEIN

Polyphenols That Optimize Thyroid Function and Fat Burning

There is a wide assortment of polyphenols that have the power to accelerate thermogenic fat loss. Among the more potent members of this group of compounds is oleuropein, which is found naturally in extra-virgin olive oil. Oleuropein has the ability to trigger noradrenaline secretion while concomitantly increasing UCP-1 levels inside the brown fat cell.

Another polyphenolic with remarkable thermogenic properties is kaempferol, which is isolated and extracted from a wide variety of foods such as tea, broccoli and grapefruit. This compound has the ability to activate the thermogenic process in muscle cells. Kaempferol also stimulates thyroid hormone production, which brings about thermogenesis in brown fat. Kaempferol is unique in its ability to activate thermogenesis in different cell types throughout the body, giving it a unique capacity to scorch body fat.

 8. SPICES

Capsaicin, Piperine, Ginger (Gingerols), Cinnamon (Cinnamaldehyde)

Capsaicin is the ingredient found in chili peppers that contributes to the hot and spicy flavor of the chili pepper. Capsaicin directly binds and activates the TRPV-1 receptor within the oral cavity— which releases noradrenaline, boosting thermogenesis in brown fat. Several studies have shown that a single ingestion of capsaicin can activate brown fat thermogenesis, while longer term ingestion of roughly six weeks increased thermogenesis in brown fat, resulting in reduced body fat. Interestingly, this six-week study also showed thermogenic activity in brown fat contributed significantly to fat loss in individuals who had an extremely low amount of brown fat before the study began, which strongly suggests that long-term intake of capsaicin can also help increase the amount of brown fat in the body.

Three more spices— piperine, the spicy compound found in black pepper; cinnamaldehyde, the pungent ingredient in cinnamon; and gingerol, the active constituent in ginger— also strongly induce thermogenic fat loss. As does capsaicin, piperine and gingerol can activate the TRPV-1 receptor, while cinnamaldehyde activates the TRPA-1 receptor, which is a member of the TRPV-1 family of receptors. Activation of these receptor sites triggers thermogenic energy expenditure in a fashion similar to capsaicinoids. These mechanisms can be strong contributors toward accomplishing desired weight loss.

9. FORSKOLIN (from Coleus forskohlii)

Forskolin, a chemical produced by the Indian coleus plant, has the ability to activate the enzyme adenylyl cyclase within brown fat, which results in elevated cyclic adenosine monophosphate (cAMP) levels. Increased levels of cAMP in brown fat cells also result when noradrenaline binds itself to the beta-adrenergic receptor, which then triggers thermogenesis. There is scientific evidence that when hamsters and rats are fed forskolin, there is an increase in oxygen consumption and thermogenic activity in their brown fat cells. An added benefit of forskolin is that, unlike noradrenaline, forskolin has the ability to stimulate thermogenesis without binding to the beta receptors in brown fat cells. This finding indicates that forskolin could have an additive impact on thermogenesis if taken along with other thermogenic compounds that can trigger noradrenaline release and beta-adrenergic receptor production of cAMP— producing an additive thermogenic effect that will conceivably drive superior levels of fat loss.

 10. MELATONIN

Melatonin, a hormone secreted in the brain by the pineal gland, is the regulator of the sleep/wake cycle and specifically promotes restful sleep. It is also involved in energy metabolism and bodyweight control. Scientific studies have demonstrated melatonin’s ability to promote the reduction of bodyweight and abdominal fat (even controlling food consumption). The likely mode of action of melatonin involves its ability to activate thermogenesis in brown fat, with a subsequent increase in energy expenditure that drives the accompanying fat loss.

GREEN TEA AND LIVER TOXICITY

Green Tea Extract With Concentrated EGCG Not Recommended

Green tea extract is an extremely popular supplement that people take to promote weight loss. The active ingredients in green tea include caffeine and epigallocatechin gallate (EGCG). Green tea extract appears to have few side effects other than elevated heart rate and small increases in blood pressure, but research indicates that green tea extract can be toxic to the liver and has no long-term effects on body composition.

Epigallocatechin gallate (EGCG) is a polyphenol found in green tea extract. A study on mice from China and Rutgers University found that EGCG was toxic to the liver by reducing important antioxidants that protect it from free radical damage. Free radicals are highly reactive chemicals linked to cell membrane damage, destruction of DNA and cell death.

A study led by Herbert Bonkovsky at the Wake Forest University School of Medicine reported that EGCG is toxic to the liver when taken in high doses. Researchers reported that at least 20 cases of liver injury have stemmed from green tea extract supplements. They stated, however, that these findings do not apply to consumption of green tea because the EGCG levels do not approach those found in green tea extract supplements.

We are in the dark about the dangers of herbal products such as green tea extract. While people from China have consumed green tea for centuries, it is only recently that we have been able to concentrate key ingredients in herbal products such as EGCG, promoting the consumption of higher dosages that may lead to adverse side effects.

Another study linked the consumption of green tea extract to liver cancer. Catechins are a second group antioxidants also found in green tea. In a study of more than 18,000 men, Lesley Butler and colleagues, from the University of Pittsburgh Cancer Institute, found that high levels of catechins were linked to markers of liver cancer in people who were prone toward the disease. Blood catechins increase in direct proportion to their consumption in the diet. Taking high doses of green tea extract could be deadly in high-risk people. The researchers noted that the incidence of liver cancer was much higher in China than in the United States as green tea is a staple of the Chinese diet.

High intake of green tea and green tea extract might be toxic to the liver. In one of the first case reports associating hepatitis with the consumption of brewable green tea, a healthy 16-year-old girl in England developed acute hepatitis after drinking three cups per day of Chinese brewable green tea, purchased online, for three months. After the consumption of green tea was stopped, there was a rapid and sustained recovery from hepatitis.

Other research found that green tea has no long-term effects on body composition. A 12-week study of 60 young adult men and women showed that it had no effect on fat absorption, resting energy expenditure and body composition. By itself, EGCG is not effective for increasing weight loss.

New reports are emerging that describe mechanisms or conditions involved in possible liver damage as well as continuing cases of “drug-induced liver injury” occurring in people using EGCG-containing products. There are many reports that support both the idea that consumption of a great amount of EGCG can induce hepatocellular toxicity (liver damage) and that certain common drugs and supplements may exacerbate this. The limited benefit of green tea extracts for weight loss does not appear to be worth the risk. Therefore, green tea extract containing concentrated EGCG is not recommended because of possible liver toxicity.

For more information about compounds that trigger thermogenesis, including the latest research, as well as green tea and liver toxicity, see the Thermo Heat™ Weight Loss Revolution available at www.advancedmolecularlabs.com

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