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Quite simply Meta-CEL attempts to gather the new era of creatine transport science, derived from human, animal, and in vitro (test tube) investigations. Here's a look at what's in it and the science behind each ingredient:
PhosphitolTM Complex
Creatine Monohydrate
To date, no other forms of creatine, e.g. creatine citrate, creatine pyruvate, creatine-magnesium complex, have convincingly shown superior real-world results in comparison to creatine monohydrate. Moreover, these "designer" forms of creatine cost more. One of the most thoroughly tested dietary supplements overall, and perhaps the most exhaustively tested sports nutrition ingredient outside of carbohydrates, is creatine monohydrate. Until several studies show that a different form of creatine is superior to creatine monohydrate when it is directly compared to creatine monohydrate, and that "superiority" is defined by significantly greater increases in fat-free mass and/or muscular performance, the jury rests. There is no compelling reason, scientific or rational, to use a different form of creatine than the monohydrate. Period. All other forms of creatine may be considered ineffective until proven effective and superior to creatine monohydrate.
InzitolTM (D-Pinitol)
This cousin of the nutrient inositol was first characterized in sugar pine trees. It is classified as a cyclitol, a sugar derivative that serves to protect plants from harsh environmental conditions. It is also present in soy meal, at a concentration of about 1% by weight, and is abundant in citrus fruits and legumes. Animal and muscle cell studies with D-pinitol have shown it to have insulin-mimicking effects, suggesting that it exerts the same actions as insulin independent of the presence of insulin. However, human studies in subjects with insulin resistance have yet to show a positive effect on insulin sensitivity. Based on the promising animal and muscle cell studies, we were asked by Humanetics, marketers of Inzitol® pure D-pinitol, to undertake a pilot study to assess D-pinitol's ability to increase whole body creatine retention in people who had not been using creatine and comparing it to other creatine cocktails.
Led by Dr. Rick Kreider, we had subjects take one of the following four times daily for three days:
5 grams of dextrose with one 500-mg capsule of corn starch (placebo)
5 grams of creatine monohydrate with one 500-mg capsule of corn starch (CM)
Creatine monohydrate plus alternating servings of one 500-mg capsule of corn starch or Inzitol, for a total of 1,000 mg of D-pinitol/day (LDP)
Creatine monohydrate plus one 500-mg capsule of Inzitol (HDP)
Pre-loading with one 500-mg capsule of Inzitol twice daily for 5 days (before starting creatine monohydrate supplementation), followed by 5 grams of creatine monohydrate with alternating servings of one 500-mg capsule of corn starch or Inzitol (Preload)
All of the different capsules and powders were prepared to look and taste the same. Each group was comprised of four subjects. As in the study above, whole body creatine retention was measured exactly the same way, but we collected 24-hour urine over each of the three days, which involved a total of 60 grams of creatine monohydrate ingestion among those receiving creatine monohydrate. Despite "claims" of creatine causing excessive urination, we found no differences in total urine volume among any of the groups, while creatinine excretion also did not differ. To our surprise, we did find the low dose pinitol (LDP) group to show the greatest average whole body creatine retention: 50 of the 60 grams ingested, or 83%. The groups broke out as follows:
Supplementation regimen: Creatine retained (whole body)
Placebo: 0%
CM: 61%
LDP: 83%
(To date there are no studies that have shown whole body creatine retention of this magnitude!) HDP: 61%
Preload: 78%
The low-dose Inzitol and Preload Inzitol regimens were essentially equal and were statistically superior to the high-dose Inzitol or straight creatine monohydrate regimens. Given the convenience and economic advantage of using the low dose Inzitol + creatine monohydrate regimen (500 mg twice daily), there does not appear to be any reason to employ the Preload regimen.
This preliminary study is limited by having only four subjects per group, but it does suggest that adding Inzitol to a creatine monohydrate loading regimen would produce greater gains, in both fat-free mass and skeletal muscle performance. This is based on the relationship of greater creatine retention leading to greater performance. Although we did not measure blood insulin concentrations, we would not expect it to have changed, based on previous studies. These results lend additional support to the theory that D-pinitol does indeed have insulin modulating or mimicking effects, independent of insulin "spikes." Alternatively, D-pinitol may be exerting an unknown effect(s) on creatine pharmacokinetics and pharmacodynamics, resulting in increased accumulation of creatine in muscle cells.
Pushing Creatine Gains Even Further...
If we were to peer into the muscle cell membrane, we would see what resembles a Saturday night at an exclusive dance club/bar. Inside the building is where all the action is taking place, but what's making the action happen are the VIP's gaining entry into the club. Creatine is a VIP during the loading stage, and when a creatine transporter "sees" creatine in the crowd, the revolving door is opened and creatine is ushered inside (much to the dismay of the others anxiously waiting in line). Creatine transporters are a series of closely related proteins that weave in and out of muscle, intestinal, and brain cell membranes. When they are abundant and in contact with the "outside" world, namely the world of chemicals floating in the blood, they can be stimulated by various agents. Welcome insulin and beta-adrenergic receptors.
PotentinTM Compound
Synephrine and other phenolamines present in Citrus species extracts (e.g., Citrus aurantium) have been advocated as thermogenic, appetite-reducing, and body-composition-altering agents. The phenolamine synephrine is a "fraternal" chemical twin of the naturally occurring neurochemical epinephrine (a.k.a. adrenaline), but does not appear to share the same trait of causing a "fight or flight" experience, at least in relation to blood pressure elevation. The rationale behind the use of Citrus-derived synephrine and other phenolamines is that they are weak stimulators of alpha- and beta-adrenergic receptors. These are the same cellular receptors (from a variety of tissues) that are stimulated by ephedrine. To date, the only Citrus-derived phenolamine shown to stimulate human beta-adrenergic receptors appears to be synephrine.
Creatine transport into muscle cells in vitro is potently stimulated by insulin and agents that stimulate beta-adrenergic receptors, the latter known as beta-adrenergic agonists (BAA's). What is the link between insulin and BAA's? Both appear to turn on a "pump" that spins with the creatine transporter revolving door, the sodium/potassium ATPase (Na+-K+ ATPase). This muscle membrane pump works in synchrony with, and "next door" to, creatine transporter proteins. This "dual door" control, when activated, produces substantial increases in creatine transport and retention within cells, so far shown in vitro. What is intriguing is whether weak BAA's like synephrine would increase whole body creatine retention above that from using creatine monohydrate alone...
Elemental Creatine Transporter Cofactors: Sodium and Chloride
Creatine transporters, as stated above, also localize in the intestines and thus are the "first line" of creatine transport. Because of the not uncommon experience of intestinal distress (loose stools, diarrhea) among a minority of creatine users, especially during the loading phase, one wonders whether optimizing creatine transport conditions within the gut could make a distinctively positive difference. Using animal intestinal segments and cells, intestinal creatine transport has recently been shown to have a critical requirement for a specific ratio of sodium and chloride ions - a 2:1 ratio - and no apparent requirement for potassium. Because creatine transporter proteins are sodium and chloride dependent transporters, the provision of an optimal ratio of sodium and chloride, but not at an amount posing a concern for sodium-sensitive individuals, may foster greater gut tolerability during loading or single high-dose creatine monohydrate supplementation. Additionally, this transporter cofactor ratio may push absorption to the theoretical maximum of 100% of an oral dose.
The Mission of Meta-CEL
The defining signature of any sports nutrition product is not its ingredients, their amounts, or the research behind them on an individual basis, but the sum of the parts - does the product you buy work? No other question is relevant and no other question deserves attention. Thus, MAS will be the subject of an ongoing human research program targeting real-world outcomes - fat-free mass, muscular strength and other performance variables, and secondary subjective outcomes like muscle pump sensation, soreness, and definition. The only way to claim any product works is to test it, in the hands of exercise science experts. This is the mission of Meta-CEL — the Muscle Augmentation System.
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