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Creatine Supplementation Enhances Muscle Anabolics at Several Levels
The Creatine Revolution
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Creatine has literally revolutionized the supplement industry. Never before has a nutritional supplement received such wide scale acclaim by scientists and laypersons alike. The past decade has produced countless studies demonstrating that creatine supplementation provides a clear ergogenic effect. That is, creatine supplementation increases an athlete's capacity to perform physical work.
Creatine supplementation improves exercise performance by acting at several physiological levels, commencing at the individual cell and extending to a broad anabolic response. Although creatine's systemic attributes are currently the least understood of its effects, they are potentially the most important for overall health and athletic performance. With ongoing scientific research, however, the mechanisms of action behind these larger-scale hormonal responses soon will be revealed.
Creatine's best understood mechanism of action is that it increases cellular energy levels during moments of greatest energy consumption (next). Hence, an effect of creatine supplementation on physical performance is most obvious during strenuous exercise.
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Level 1. INDIRECT Anabolics: The Phosphate Connection
Training Adaptations: Creatine indirectly promotes muscle growth (anabolism) by extending an athlete's exercise output. Explicitly, our muscles adapt to the increased load brought on by creatine supplementation with the production of new muscle proteins that then allow them to generate greater amounts of force as well as to become more efficient at producing and utilizing energy. In the jargon of the field, these structural and metabolic changes induced by exercise are known as 'training adaptations'. Again, since this mode of creatine-based muscle anabolism is downstream of an enhancement in exercise output, it is indirect.
Below is a list of the key players (and the roles that they play) in this mode of muscle anabolism:
Phosphate Energy: Attaching a phosphate group to certain biological molecules endows them with the capacity to hold and store energy. And, although several biological molecules have evolved for this purpose (that is, to be 'energized' with an addition of a phosphate group) a molecule known as ATP is the most intimately linked to cellular processes and hence, is our most fundamental energy donor.
Adenosine Tri-Phosphate (ATP): Its name reflects its chemical structure, an adenosine with a tail of three phosphates at one end. ATP, by releasing one of its high-energy phosphate groups, liberates energy. This phosphate-bound energy is then made available to fuel a broad range of cellular processes such as, muscle contraction.
Adenosine Di-Phosphate (ADP): After donating a phosphate group (to provide energy), ATP becomes ADP, a singly de-phosphorylated and largely de-energized molecule. Therefore, in order for exercise to continue, ADP must first be 'recharged' with the re-addition of another phosphate group, thereby recreating ATP. This cycle then repeats with each subsequent bout of exercise and recovery.
Importantly, the rapid recreation of ATP largely relies on creatine. One of creatine's principal roles within the cell is to rapidly recreate ATP during moments of high energy consumption (see next).
PhosphoCreatine (PCr): Creatine serves as a high-energy phosphate reservoir for the rapid regeneration of ATP. In order for it to perform this important task, however, creatine must first be functionalized with the addition of a phosphate (within the cell). The product of this reaction is phospho-creatine (PCr).
PCr, in turn, replaces ADP's lost phosphate group to rapidly reform ATP during physical exertion (see figure below - back arrow (<----)).
PCr is Quick Energy: The process whereby phosphocreatine recreates ATP during exercise is much faster than the production of new ATP from the combustion of nutrients - a relatively slow process that requires the participation of oxygen.
Therefore, strenuous exercise will only continue as long as sufficient (stored) PCr is available to fuel muscular activity, afterwards the body will be limited by the relatively small amounts of ATP made available via cellular respiration and force output will be decreases accordingly.
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During moments of rest, however, the cell is at leisure to stockpile ATP that is produced from stored nutrients and oxygen; part of this new ATP is then diverted to replenish the cell's PCr supply. Our PCr reserves, in turn, are set aside for future use to power the next bout of strenuous exercise (see figure above - forward arrow (---->)).
Via such a mechanism the amount of phosphocreatine stored within our muscles determines our ultimate power output. Creatine
supplementation, since it increases the amount of phosphocreatine (and creatine) stored within our muscles, heightens our ability to repetitively perform explosive bouts of strenuous exercise.
PCr Shuttle: Despite the apparently subsidiary role that creatine plays with reference to ATP production, creatine (phosphocreatine) is indispensable for cell survival. Phosphocreatine, as it is more mobile than ATP, can more quickly reach regions of the cell that would otherwise starve if having to depend on the slow arrival of new ATP from the mitochondria (the powerhouse of the cell). Phosphocreatine, on the other hand, is largely generated at the mitochondria from where it can quickly diffuse to regions of the cell where energy (ATP regeneration) is needed. ATP is thus regenerated locally with the help of phosphocreatine, a process known as the PCr shuttle.
PCr Surplus: Due to PCr's phosphate buffering capacity, the cell typically stores several times more phosphocreatine (and creatine) than ATP. Moreover, the size of our creatine reserves increases with supplementation, effectively enhancing the energy buffering capacity of our muscles. This hoarding response is one of the principal reasons that creatine supplementation improves physical performance.
Click here to see the complete chemical structures of creatine, phosphocreatine, ATP (adenosine triphosphate) and ADP (adenosine diphosphate).
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Creatine Kinase
The enzyme that is responsible for switching a high-energy phosphate group from phosphocreatine to ADP, as well as from ATP to creatine, is known as Creatine Kinase - the same enzyme working in both directions. Those of you who follow the scientific literature will already be familiar with the importance of this enzyme for the proper functioning of the body.
Inherited disorders that produce severe reductions in cellular creatine kinase levels are associated with muscle wasting (atrophy) and developmental abnormalities. Moreover, reductions in cellular creatine kinase levels are also characterized by severe mental retardation as well as numerous devastating neurological deficits. The reasons for these surprising neurological consequences of phosphocreatine deficiency are discussed here.
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Creatine and Peak Power: At this point, certain importance consequences of creatine supplementation need to be emphasized. Firstly, creatine supplementation will not greatly alter the absolute amount of ATP stored within your muscles. However, creatine supplementation will increase the numbers times that the cell is able to locally regenerate ATP before having to resort to the new synthesis of ATP from nutrients. This means that creatine supplementation will not increase the peak amount of force you can generate, just the amount of time you can exercise at near maximum capacity.
An increase in peak force generation, however, will come later as new muscle proteins are added in response to the greater exercise stimulus afforded by creatine supplementation (review Training Adaptations above). The magnitude of these training adaptations, moreover, will be depend on key physiologic factors that are ultimately under your control. Therefore, given that the right set of physiologic conditions had been previously established, creatine supplementation in the long term will stimulate protein synthesis.
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How to make full use of creatine's anabolic potential through diet and exercise is a major focus of our creatine guide. Click here for more information about this informative fitness manual.
Creatine and Muscle Exhaustion: On the other hand, creatine supplementation does increase the number of times that the cell's ATP reserves are recycled, increasing the duration that intense efforts can be sustained before exhaustion sets in. Creatine supplementation also increases the rate at which the cell's phosphocreatine reserves are replenished during moments of rest. These effects translate into more rapid recovery following strenuous physical efforts and prolonged work output during repetitive bouts of intense exercise. Therefore, creatine supplementation enhances physical performance during explosive bouts of intense exercise, which then serves as a more potent stimulus for subsequent muscle development (review Training Adaptations above).
Click here for assistance in calculating a creatine dose designed to suit your particular set of physical parameters.
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Muscle Specificity of Creatine Supplementation
Explosive movements recruit a muscle class known as fast, or type II. Fast muscle fibers evolved to produce large forces, rapidly, but transiently. Hence, resistance exercise such as weight lifting, powerlifting, jumping and sprinting are mediated by fast muscle fibers. Slow muscle fibers, or type I, by contrast, are called into action by endurance tasks that require sustained levels of moderate energy output such as jogging.
Fast muscle fibers also require less oxygen to generate force, whereas slow muscle fibers depend heavily of oxidative metabolism to perform less powerful, but sustained physical tasks. Specifically, fast muscle fibers rely on their immediate energy reserves (ATP and PCr) to generate large amounts of force rapidly, without evoking the participation of oxygen. Not surprisingly, fast muscle fibers possess significantly larger PCr reserves than do slow muscle fibers.
In essence, creatine supplementation feeds fast muscle fibers, increasing power output, while leaving endurance tasks largely unaffected. This is why marathon performance is relatively unchanged by acute creatine supplementation, whereas performance in the 100 meter sprint is appreciably enhanced.
Nevertheless, creatine supplementation may offer benefits to the endurance athlete. For the special circumstances whereby creatine supplementation may favor endurance performance see this page.
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In summary, creatine supplementation increases the availability of energy (ATP) to working muscles, which enhances athletic performance. In this scenario, however, the direct stimulus for subsequent muscle growth is derived from our anabolic hormones, released by exercise and potentiated by creatine supplementation.
That is, the anabolic role traditionally ascribed to creatine supplementation was INDIRECT. Recent scientific findings, however, are rapidly revising this rather limited interpretation...
Level 2. DIRECT Anabolics: Cellular Methylation
Again, the anabolic role traditionally ascribed to creatine supplementation was INDIRECT, mediated by its ability to enhance exercise performance. This classical description of creatine's mechanism of action, however, falls far short of explaining the breadth of anabolic properties recently being revealed in scientific studies. New research is now showing that creatine possesses broad metabolic attributes. For instance, an improvement in systemic methylation status is one manner in which creatine supplementation may provide a noticeable anabolic boost.
S-Adenosyl Methionine (SAM) Supports Methylation: Methylation is an extremely important cellular process that is essential for life itself. Many of our most essential growth factors rely on methylation to become functional. The body's principal methyl donor is a molecule known as SAM. Ergo, SAM deficiencies compromise whole body anabolism.
So, what does creatine supplementation have to do with cellular methylation status? Nearly everything!
Creatine Supplementation Conserves SAM: The single largest drain of the body's precious SAM reserves is the synthesis of creatine. By inference therefore, circumventing creatine synthesis should positively influence one's methylation status. And, the best way to avoid creatine synthesis is to provide the body with enough creatine to meet its daily needs. That is, creatine supplementation alleviates the need to synthesize creatine and boosts one's methylation status. Therefore, creatine supplementation contributes to a more healthful methylation status, which, in turn, lays down the foundation for all other anabolic processes in the body.
Click here to see for a step-by-step depiction of creatine synthesis.
B-Vitamins Regenerate SAM and Enhance Endogenous Creatine Synthesis: Essential B vitamins, namely folic acid, vitamin B12 and vitamin B 6, help regenerate SAM after its consumption in cellular methylation reactions. Moreover, since creatine is the single largest drain of our precious body's SAM reserves, these same B-vitamins will improve the body's capacity to produce creatine. Therefore, to get the most from your methylation potential, include these essential B-vitamins in your creatine supplementing routine (see box below).
Click here to be directed to a page describing how creatine supplementation in combination with specific B-vitamins enhances muscle anabolics as well as improves indices of overall health.
Creatine Optimization
Combine Creatine Supplementation with Essential B Vitamins for Maximal Muscle Anabolism
Creatine supplementation stimulates muscle anabolism by accentuating training output as well as by biochemically priming muscles for growth and development. Importantly, including essential B-vitamins in your supplementing regimen will consolidate both these anabolic aspects of creatine supplementation. Nevertheless, it is absolutely imperative that you get these B-vitamins in the correct proportions and concentrations in order for this strategy to work effectively. In other words, merely taking a vitamin pill will not be sufficient to produce the greatest possible effect.
How to correctly combine creatine and essential B-vitamin supplementation to fully take advantage of this important anabolic process is only discussed in Creatine: A practical guide.
Click here to automatically have a creatine dose calculated to fit your specific needs.
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Level 3. Muscle Volumization: Creatine-Induced Cell Swelling is an Anabolic Stimulus
Another anabolic attribute of creatine is mediated via a process known as 'cell volumizing'. Creatine has the property that it causes cells to inflate with water, effectively increasing their volume. Similar cases of cell volumizing in different cell types and in response to distinct agents has been shown to be a potent stimulus for protein synthesis. That is, increasing the volume of the cell because of increased water retention signals to the cell that it has grown. The cell then responds by increasing its production of structural and key enzymatic proteins. By inference therefore, creatine-based cell volumization should likewise promote cellular anabolism.
Another common consequence of muscle volumizing is an increase in body mass, which may, or may not, be a desired consequence of creatine supplementation. An athlete can gain up to a few kilograms of water weight solely as a result of creatine-based muscle volumizing.
Click here to be directed to our page discussing the pitfalls and benefits of creatine supplementation for the endurance athlete.
Levels 4 - 6. Creatine is an Antioxidant, Buffers Muscle Acidity and Improves Myoplasmic Calcium Homeostasis: Combating Oxidative Stress, Reducing Muscle Fatigue and Facilitating Force Generation.
Creatine also appears to behave as an antioxidant, a neutralizer of muscle acidity (arising from exercise) as well as facilitates the coordinated and efficient production of force by muscle, facts that just recently came to light. These aspects of creatine supplementation will clearly enhance an athlete’s ability to recover from strenuous exercise as well as to build long-lasting muscle tissue.
Creatine: A practical guide explains the various ways that creatine promotes muscle anabolism and how to consolidate their effects to yield the greatest improvement in health and physical performance.
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