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 Mark J. Tallon 
Real Nutrition: Signaling Real Growth, Part I
PHOSPHITOL...Signaling Real Growth
by Mark J. Tallon, Clinical Reviews Editor
Has the time for a leap in creatine technology arrived?
Rumor has it that a new creatine delivery system is about to make waves in the nutrition market. I have great pleasure in presenting the first scientific article to help you understand why the team at iSatori Global Technologies has released Meta-CEL, a product based on peer-review research and exciting advances in creatine transport technology.
At the foundation of Meta-CEL are Phosphitol and Potentin, a new dual-ingredient-based-product developed over four years with leaders in the nutritional industry and university research. We bring you a sneak preview of why great things are expected from this product, what inferences can be made based on case studies and the current scientific literature for accelerating muscle growth, and why evidence suggests an ingredient not in Meta-CEL could enhance creatine uptake even further!
The "Gateway to Growth"—Greater Uptake Is Better, But Why?
There seems to be really only two schools of thought when it comes to finding out why elevating creatine uptake or its transport is advantageous. First, the release of factors such as growth hormone and catecholamines, shown to enhance creatine uptake, peak 10 minutes after intense exercise. It's vital that during this period we speed the delivery of creatine to the working muscles. This is our window of opportunity not only because of the hormonal factors but also because of elevated blood flow. Harris, et al., demonstrated that creatine uptake was markedly enhanced in muscle when blood flow was elevated. About 40 minutes after exercise, most of these variables are back to their pre-exercise states. So getting creatine over the intestinal and through the blood transport systems to the muscles must occur during the 40- to 60-minute gap.
Second, the greatest rationale for bettering creatine uptake without overloading its transport system with excessive dosing is in the maintenance phase. We hear so many anecdotal reports of people still taking up to 20 grams of creatine after loading, yet this practice is simply crazy and probably will lead to suboptimal creatine stores.
You see, once loaded, the muscle will simply not take in any more creatine. And based on current evidence and delivery systems, if you keep up this excessive dosage (above 0.0136 g per lb of bodyweight) which may double blood creatine concentrations above that found at rest (20 to 30 um), the creatine transport system is inhibited 70 to 80% after 24 hours. Therefore, a short, intense high-quality delivery of creatine is what the muscle ordered.
The maintenance phase is also important when it comes to performance. The typically suggested intake of two grams per day may be effective in maintaining those loaded creatine levels but not necessarily the related performance effects.
In a classic study by Aaserud, et al. (1998), following the standard loading phase, subjects maintained a two grams per day creatine intake for nine days. Subjects were then performance tested, and although they exhibited better than pre-exercise values, they did not keep improving. In another study by Thompson, et al. (1996), subjects yet again followed a two grams per day creatine routine for six weeks. Previously shown to fully elevate muscle creatine stores, it did not improve their performance results. It seems, therefore, that we must fully load skeletal muscle with higher creatine absorption/uptake than that typically found using only a two-gram-a-day dose.
A History of Gimmicks!
It's been a crazy ride over the last decade with the creatine products that clamored for market share. An assortment of concoctions for sure—some so abstract they belong in Ripley's Believe It or Not. You've seen them... products such as effervescent, micronized, liquid, buffered, and even transdermal.
But for all the pretenders, the functional food and sports nutrition industry has also given us some real winners—mainly plain old creatine monohydrate and, above all, creatine plus carbohydrates/protein.
Dr. Paul Greenhaff—one of the world's most eminent creatine researchers from Nottingham medical school in the UK—really blew the creatine combo lid wide open in the early 1990's. Dr. Greenhaff's approach, as most of you already know, was based around the manipulation of one of the most powerful hormones of them all: "insulin." This delivery hormone was to be the key, or the
gatekeeper you might say, to enhance the already awesome capacity of creatine. In a series of studies over a five-year period, Greenhaff's research group showed when creatine was combined with carbohydrates (to elevate insulin levels), creatine transport into muscle was increased. "Wow!" consumers cried, "Creatine delivered faster and more efficiently into my muscles?! Where can I buy it?" But that's where the fairytale ends. It was time for the Atkins revolution to hit the U.S.: carbs became the plague of the 20th century, and with it, the creatine carb combo was to slump, but what would be its victor?
For a while protein (50 g) + carbs (50 g) was shown to work as well as carbohydrates in its ability to elevate insulin and creatine uptake, but again, it still contained excess calories and sugars. So it took until 2003, three years since the early protein and eight years from the carb studies, but at last we may have the next in the lineup of advanced creatine delivery systems knocking at our door...
Transport the Package: How Creatine Gets Delivered to Cells!
The transport of most nutrients within the human body, creatine being no exception, are mediated by a specific membrane-bound transport system. Think of this system as a bridge between plasma (blood) and your muscle. For creatine, the bridge it needs to cross is known as a creatine transporter. Creatine transport proteins are constructed from a vast number of amino acids, which span muscle membranes, allowing creatine 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 movement of creatine across this transport system and how the iSatori team has used this knowledge to bring you a product light years ahead of the competition...
Fig.1 Creatine transport system demonstrating sodium (Na) and chloride (Cl) co-transport
Creatine is a fairly simple molecule made up of a few amino acids, but its transport system is another matter. From fairly early on in the discovery of creatine's performance-enhancing (ergogenic) effects, we knew its ability to pass into the muscle was dependent on two metabolites, namely sodium (Na) and chloride (Cl). These two co-factors are there to "piggy-back" creatine into muscle (See Fig. 1); however, the exact ratio of Na and Cl needed to promote creatine transport from the intestines directly to the muscles via the creatine transporter proteins has only recently been discovered.
This is where the science of Potentin (an Na-Cl and synephrine complex) is applied to the creatine delivery system. Therefore, it's of no surprise to find this ratio of sodium and chloride ions (2:1 ratio) in the Potentin complex. The importance of the sodium/chloride system can be summed up simply in recent data showing when the sodium based ATPase system was inhibited, creatine uptake decreases 28%.
D-What?
D-Pinitol, known chemically as "3-o-methyl-D-chiro-inisitol," is one of the most interesting commercial compounds adapted for both sports nutrition and self-medication on the market today. Derived from soybeans and found in food stuffs such as legumes, citrus fruits, and the herb Bougain spectabilis, this naturally occurring inositol (B-vitamin) has some marvelous effects on human muscle.
Fig. 2 The Structure of D-Pinitol
Pinitol's real metabolic potential was first realized (like many nutritional products) through its medical application—in this case to diabetes. Its role for the treatment of insulin-dependent medical conditions became apparent following a study by Kelly, et al. Following this early work, the baton was picked up for team sport nutrition by researchers at Baylor University headed by Drs. Kreider and Greenwood. Supplementation with one gram of D-pinitol and 20 g of creatine monohydrate daily (in divided doses for three days)—the loading protocol—produced an 83% creatine retention effect, or for the 60 g taken, in total around 50 g of it was retained in skeletal muscle, compared to only 61% or 36.6 g for those receiving creatine only. That's a 23% higher retention of creatine with D-pinitol than the traditional carbohydrate + creatine mix.
Team iSatori have put this great study to full effect by incorporating D-pinitol in what they claim is the central component in Meta-CEL, which incorporates the technologies of both Phosphitol and Potentin. It is also one of the only nutrition products to use the exact dose investigated in the Greenwood, et al., paper of 0.5 g per 5 g serving of creatine, making Phosphitol a true science-based product.
Can Beta-Cell Control Make 100% Creatine Retention Possible?
Well, it may be pretty darn close in combination with the ingredients listed above and beta-cell stimulators. Beta-cells, like creatine transporters, can be located on cell membranes, and it now seems that just as exercise, growth hormone, and IGF-1 play a significant role in creatine transport, so do catecholamines and thyroid hormones. One of the primary product developers of the Meta-CEL muscle system and particularly of the creatine transport systems was the first to pick up on the possible importance of beta-cell stimulation and creatine uptake.
Mr. Almada was recently asked about the importance of stimulating beta-cells and creatine uptake, and he replied "This 'dual door' control, when activated, produces substantial increases in intracellular creatine transport and retention, so far shown in vitro."
Do not under-estimate the influence of stimulating this system, as recent data from a team of researchers from the University of Oxford, U.K., showed that with use of a beta2 agonist, muscle cell total creatine content increased 30% compared to controls.
Potentin, which we have already discussed, contains sodium and chloride, factors important for creatine uptake. But what you won't have seen anywhere else or in any other product is the application of synephrine for the sole purpose of enhancing creatine uptake. The brain child of Anthony Almada, Potentin contains the phenolamine synephrine, a weak but highly effective beta-agonists. To date, the only
natural phenolamine shown to stimulate human beta-adrenergic receptors appears to be synephrine, not octopamine. Potentin incorporates a specific synephrine-centered phenolamine extract to help complete the perfect creatine transport system available today.
As a biochemist, I find this new field in creatine manipulation fascinating. Although still in its infancy, it gives us new hope to further increase, maintain, and enhance the effects of creatine monohydrate.
Boosting Meta-CEL's Effects Even Higher?
Although we talk about the transport system as a revolving door, it is really much more than this. As James O'Byrne explained in issue 4 of Real SOLUTIONS magazine, creatine is a VIP and the revolving door is the creatine transporter, which allows creatine to enter the club (a.k.a. the muscle). Rather than working in sync with the door, the sodium-dependent ATPase pump is more like the electricity switch. A switch that controls the power to the revolving door. And there are a variety of substances that make the potential to switch this power supply on, in effect enhancing creatine intake. One of the most recent discoveries as discussed above is synepherine, but another is thyroid hormone. Thyroid, or T3 as many of us recognize it, has demonstrated the ability to increase total muscle creatine concentrations by 280%. This fascinating finding made me remember back to an article I wrote on 7-Keto (the central component of Lean System 7). In a recent study, 7-Keto was shown to elevate T3 85% above placebo concentrations. This elevation may be just the kickstart you need to crank creatine retention up to the magic 100% and provide a synergist advantage to muscle growth and fat loss by using both Meta-CEL and Lean System 7 together. This brings us on to why iSatori is pouring some serious cash into new clinical and public supplementation trials.
Future Trials: Clinical Vs. Public
iSatori has just released some of the data from the first mass field study on Meta-CEL, more affectionately known as "PROJECT MAS," and the results look astounding. Here's a peak:
The Average Strength Increases:
Bench Press (Barbell): 30 lbs
Squat (Barbell) Strength: 65 lbs
Average Circumference Increases:
Chest: 1.75 inches
Biceps: 1.05 inches
Leg/Thigh: 2.30 inches
Positive effects noticed by users of Meta-CEL:
Improved Strength: 93%
Increased Energy: 45%
Better "Pumps": 72%
Improved Muscularity: 71%
Increased Recovery Time: 42%
Increased Definition: 62%
Now if these fantastic results are not enough to convince you that they're onto a great product, there is a new university-based study involving some of the world's best creatine researchers that's just been given the go-ahead... We will keep you updated as the results start to flow in in early 2004.
A Real Solution!
I have really enjoyed putting this article together for you, and I hope you look forward to the next in the series of "Real Nutrition," but it's only fair that I leave the last word to the developer of both Phosphitol and Potentin, Mr. Anthony Almada, CEO of IMAGInutrition:
"With Meta-CEL, we have tried to gather the new era of creatine transport science, derived from human, animal, and in vitro investigations. Our next step is to begin and complete human studies, done by expert researchers, putting Meta-CEL into a head-to-head battle against straight creatine monohydrate and look for the real-world differences. These are not measured in grams (of whole body creatine retention, although this is an encouraging start) but in kilograms... of fat-free mass gained and weight lifted or pushed. This is what defines a product that works or one that fails. We have worked hard to produce Meta-CEL and look forward to sharing the results of these pivotal studies by year end."
Editor's Note: At this time, Meta-CEL is available in stores on a very limited basis. Right now, it is being distributed through a 4-week field study called "Project MAS." iSatori is now taking applications for the third Phase of "Project MAS." For more information on Meta-CEL, or to find out how you can qualify for Phase III of their field study, please visit them online at Meta-CEL Field Study Information, or for faster service, call them direct (toll-free) at 1-866-688-7679 (press option #4), and an operator for Meta-CEL will be glad to help you.
For complete references for this article, please email us at Editors@RealSOLUTIONSmag.com, and we'll email them to you directly. (They simply wouldn't fit.)
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