Naturally produced in the kidneys, pancreas and liver, creatine is transported to muscle tissue where it is transformed into creatine phosphate, from which the energy molecule ATP is produced to regenerate the muscles' ability to contract and generate power during short-burst (anaerobic) activity. This translates to more productive workouts and faster muscle growth.
Volek, J. S., Ratamess, N. A., Rubin, M. R., Gomez, A. L., French, D. N., McGuigan, M. M., Scheett, T. P., Sharman, M. J., Hakkinen, K., and Kraemer, W. J. The effects of creatine supplementation on muscular performance and body composition responses to short-term resistance training overreaching. Eur.J.Appl.Physiol 2004;91(5-6):628-637. View abstract.
The structure of cyclocreatine is fairly flat (planar), which aids in passive diffusion across membranes. It has been used with success in an animal study, where mice suffered from a SLC6A8 (creatine transporter at the blood brain barrier) deficiency, which is not responsive to standard creatine supplementation.[97] This study failed to report increases in creatine stores in the brain, but noted a reduction of mental retardation associated with increased cyclocreatine and phosphorylated cyclocreatine storages.[97] As demonstrated by this animal study and previous ones, cyclocreatine is bioactive after oral ingestion[97][98] and may merely be a creatine mimetic, able to phosphorylate ADP via the creatine kinase system.[97]

However, in the beginning weeks of starting a new workout routine, the majority of strength gains aren't actually a result of this muscle protein synthesis and hypertrophy. Rather, they are a result of the body's neurological system learning when and how to fire the needed muscle cells, explains Abbie E. Smith-Ryan, associate professor of exercise physiology at the department of exercise and sport science at the University of North Carolina–Chapel Hill. Think of it this way: The first time you perform a new exercise, say a bench press, you likely feel pretty shaky. Your arms aren't totally in sync and the weights may sway a bit from side to side. But by the time you perform your second or third set of that same exercise, the practice gets a little smoother. That's your neurological system at work.


When it comes to building muscle, there are numerous theories, methods, and preferences. Whether the goal is improved health, aesthetics, performance, or a combination of all three, there is no shortage of advice to help you get there. So much so that it can sometimes become overly complicated and you forget about the basic facts. But, it’s simpler than it seems.
If you're a serious strength or physique athlete, you've surely heard that supplements can help you get the most from your intense training sessions and on-point diet. But which supplements? The market is overstuffed like a bodybuilder in a child's blazer! You might be tempted to wander through a digital forest of get-big blogs and personal guru websites, but unfortunately those places can often be rife with misinformation.
Lung disease (Chronic obstructive pulmonary disease). Early research on the effects of creatine in people with chronic obstructive pulmonary disease (COPD) is inconsistent. Some research suggests that taking creating daily does not improve lung function. However, other research suggests that taking creatine may improve lung function or exercise capacity.
In regard to the blood brain barrier (BBB), which is a tightly woven mesh of non-fenestrated microcapillary endothelial cells (MCECs) that prevents passive diffusion of many water-soluble or large compounds into the brain, creatine can be taken into the brain via the SLC6A8 transporter.[192] In contrast, the creatine precursor (guanidinoacetate, or GAA) only appears to enter this transporter during creatine deficiency.[192] More creatine is taken up than effluxed, and more GAA is effluxed rather than taken up, suggesting that creatine utilization in the brain from blood-borne sources[192] is the major source of neural creatine.[193][192] However, “capable of passage” differs from “unregulated passage” and creatine appears to have tightly regulated entry into the brain in vivo[193]. After injecting rats with a large dose of creatine, creatine levels increased and plateaued at 70uM above baseline levels. These baseline levels are about 10mM, so this equates to an 0.7% increase when superloaded.[193] These kinetics may be a reason for the relative lack of neural effects of creatine supplementation in creatine sufficient populations.
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