creatine monohydrate for massive

The latest scientific advances behind Cr uptake in the muscle cell, and how understanding the cellular & molecular mechanisms regulating creatine receptor activity can help us elevate our muscle creatine...

What would you pay if I could show you a method that increases your muscle creatine (Cr) levels ~30% higher than those achievable by traditional loading protocols, insulin mimics, or even glucose laden powders for FREE... ...got your ATTENTION!!!
Good... listen in as we explore the latest scientific advances behind Cr uptake in the muscle cell, and how understanding the cellular & molecular mechanisms regulating creatine receptor activity can help us elevate our muscle creatine (Cr) stores to a new level.
Yes we all know Cr is the most controversial BUT also the most successful ergogenic aid of the century. Above all it is looked upon by many as the savior & often cornerstone in the sports supplement road of developing awesome physiques, and enhanced performances de naturalis modus (by natural ways).
However, of the hundreds and maybe thousands of publications on the effects of Cr use since its inception in 1992; how many have looked at the effect of supplementation where it matters, the creatine receptor/transporter (Crt)? The answer is a surprising and disappointing 3; of which one is a review article. Nevertheless, since the early work of Professor's Harris (Chichester, UK) & Greenhaff (Nottingham, UK) little has been done to advance the typical 5 grams taken 4 x day loading phase. Below is a look at the scientific literature behind Crt technology and its implications for Cr use and for a better word: an intuitive user's guide based on this work.
Too Much Of A Good Thing?
This age-old axiom may be the best way to conclude the up and coming mini-review of Crt physiology and pharmacokinetics. The transport of most nutrients within the human body, with creatine being no exception are mediated by a specific membrane bound transport system. Think of this system as walking over a bridge to get to work where you can carry out your job; well for creatine the bridge it crosses before it can get to work is know as a creatine transporter (Crt).
These Crt proteins are constructed from a vast number of amino acids (635 for you fact junkies), which span muscle membranes allowing Cr to be transported directly into the muscle (see fig.1). Although this basic physiology is interesting what we really need to know are the factors regulating the activity and expression of these transporters? And how can we use this knowledge to our advantage?

Fig.1 Muscle cell diagram & Crt - Click to enlarge.
When we investigate and dissect the research on nutrient uptake, it is the process of negative feedback/inhibition of these transport systems that control the levels of amino acids and related metabolites (Cr) in muscle. This regulatory system seems to be directly and intrinsically linked to the concentration & time muscle cells are exposed to extracellular creatine1, 2.
Basic creatine pharmacology demonstrates that with a 5 gram dose that passes intact through the intestinal lumen then into the blood stream reaches a peak concentration in plasma after about 60 mins (see fig.2). Beyond this period there is a slowing in the pharmokinetic profile until we return to baseline values (8hrs-post ingestion). Figure 2 demonstrates the plasma effects of the suggested loading protocol against the typical 5g 4x a day approach currently adopted.
As we can see there is a much lower creatine value in the plasma using the new method. Don't be dissuaded in using this approach because there are lower levels of Cr compared to the old method. The maximum capacity of Cr transport is reached at around 150umol/l, which may be why the old method leads to such a rapid downregulation (see later text) of Crt (nb. There may be a system within the cell or on the cell membrane that recognizes supramaximal levels of Cr in plasma and as such down regulates uptake accordingly).
So with our newly found knowledge of creatine appearance in plasma how will this effect the creatine transporters? There are two possible alterations that may occur; first is the acute response, which generally relates to the minutes and hours after Cr consumption, this typically involves sodium changes across the cell membrane and decreased transport rates3, 4. The chronic response is a different matter altogether and relates to alterations in the expression/number of Crt on the plasma membrane5.
Downtime
Looking at the typical loading phase developed back in 921, the effects on human receptors over the first 5 days of loading have not been studied directly; what we do know is that with high levels of intracellular Cr a ~50% decline in transporter activity has been observed4. This decrease in activity may not only be correlated to the extra cellular concentration of Cr, but also the intracellular levels of Cr (we will come back to this later, so hold that thought).
Over the 5 days we get less and less uptake of Cr into the muscle as transport speed decreases. This decrease in uptake in muscle eventually levels off at values of circa 140 - 160 mmol/kg (dry muscle)1. This negative feedback is a bit of a pain because we probably make 80-90% of our total increase of muscle Cr in 48 hrs, then it's really a case of maintaining this elevated level.
Express Yourself
Hang in their guys the science bit is nearly over then we can get to the real application of this science... So back to our friends the transporters; not only do we start to get a decrease in the speed of uptake we get a double whammy because the body can recognize this new increase in creatine and starts to decrease the number of transporters on the muscle membranes5, 6.
Think of trying to catch fish with two nets now I steal one (sorry) and now you can only catch half the amount. The same is true of a decrease in transporters leading to less creatine caught for our muscles. SO HOW DO WE GET AROUND THIS?
A Window Of Opportunity: Your Guide To Increasing Uptake
We've got all the facts, now what are we going to do with them? The key is in the first 24-48 hours of supplementation were Crt activity is still very high, before the body has time to downregulate the speed of uptake or the expression of Cr transporter proteins.
Looking at the pharmacology of our Cr curve and the physiology of the factors affecting the transporters we need to keep plasma levels elevated to saturate the receptors consistently over this 48hour window. This approach will not elevate Cr to the same Cr values seen in typical loading protocols and as such will not saturate and cause down regulation and expression of the Crt.
To achieve this little trick we need to use small but regular Cr doses. Avoiding the peak and trough approach demonstrated with regular Cr loading is the way forward. A program of 1.5 - 2g taken 10 times a day will allow receptors constant access to Cr before the body can slow uptake down. In this way we decrease the stress placed on the renal system and make available the best possible plasma Cr delivery system for enhanced uptake.
A Better Body Through Science
So what does this elevation mean as regards to performance? Well the truth is nobody knows, but we could argue that there maybe a further increase in both the ability to sustain high power outputs and to better tolerate muscle acidosis (the burning sensation we get towards the end of a set...ring any bells?) through Cr's buffering effect.
If the intensity and volume of our workouts can be prolonged then it goes without saying increased muscle mass will be a definite by-product of the appliance of science to our loading regimes. Those athletes that will benefit most will be power athletes looking to get a supramaximal increase in power over a short period of time.
Whether we could maintain these greater increases in muscle creatine is unknown and with the down regulation of activity &/or expression of Crt in muscle; we will just have to wait for further research. Remember this is mostly theoretical based on only what we know at this time and the practicalities of a multiple dosing routine maybe taking supplementation a little to far…how for are you willing to go for a better body?
The Creatine Curve & Beyond
Be careful on what you are reading on Cr, especially if it's on animals as the uptake pharmacology and physiology of Cr in rats is very different to humans and as such bioavailablity studies on Cr cannot be used to determine the effects occurring in humans 100%. Future studies will start to elucidate the effects of chronic supplementation on the loss of Crt and the time for their re-expression giving us the truth behind the debate of whether to "cycle" Cr or not. We will also find out many other discoveries such as: Can exercise up regulate these transporters and enhance Crt expression? Finally can training itself affect the expression and sensitivity for Cr uptake into the muscle?
You won't need to remember every detail from this article just the take home messages on loading. A regimen of 1.5 - 2 g per day 10 times a day for the first 48 hours followed by a maintenance dose of 1.5 - 2g 3x per day should see you achieve optimally Cr loaded muscles. The effects of adding insulin mimics to yet further this effect such as the use of 4-hydroxyisolucine, d-pinitol or even plain old carbs or protein are unknown, but may even further elevate uptake.
This area is highly complex and purely theoretical at this time. We have only started to scratch the surface of this work in the present article, its function is to act as a forum for scientific debate, critique, and to help you the trainer maximize your efforts in the gym. Although the benefits of Cr loading can be great don't neglect your core nutrition for the use of a singular sport supplement; rather use supplementation to optimize what you're already doing.
The greater our understanding on the intricacies controlling our cellular physiology including the issues surrounding Cr use will only help us push the performance envelope yet further, leading to better bodies and healthier lifestyle changes through the appliance of science.