Scientific Research
Technical Review of Effervescent Delivery System for Oral CreatineDr. Brian Sakurada, Pharm. D.
Joe Carnazzo,
RPh
Creatine monohydrate is currently used by competitive and recreational athletes for its performance enhancing or ergogenic properties. It has been shown in numerous studies to be of benefit in activities, which are dependent on the anaerobic energy system. These include sports such as powerlifting, sprinting, swimming and field events. These sports involve high intensity, short duration movements comes primarily from stored skeletal muscle ATP and ATP regenerated from phosphocreatine stores. Anaerobic glycolysis is another potential energy source, through its relatively slow rate of ATP production prevents it from contributing to short duration activities (<30 seconds).
Oral creatine supplementation has been shown to increase total muscle creatine stores. Increases in creatine and phosphocreatine have been demonstrated by muscle biopsy, and correlate well with studies, which measure anaerobic work performance. To date, no serious adverse effects have been associated with creatine supplementation. An undetermined percentage of the creatine consumer population has reported stomach upset, diarrhea and cramping, suggestive of poor intestinal absorption. Athletes may be susceptible to overtraining, or develop or exacerbate an imbalance between muscle groups during periods of accelerated strength and performance improvements.
Creatine monohydrate is typically provided in powder form. Manufacturer directions recommend consuming the creatine monohydrate in 8 – 16 ounces of water, juice or isotonic sports drink. A "loading phase" is recommended at the beginning of a creatine "cycle" and consists of 4 to 6 servings of 5 grams of creatine monohydrate taken daily for 4 to 6 days. A "maintenance" phase then follows, with recommended consumption being from 5 to 20 grams of creatine monohydrate. Deviations from these recommendations are seen, but there is little evidence to support alternative modes of creatine use.
The majority of complaints associated with creatine monohydrate supplementation occur during the loading phase. Typically, individuals will complain of poor intestinal tolerance, leading to cramps or diarrhea. Commonly, increased fluid consumption will lead to the resolution of these complaints, which are rarely mentioned during the maintenance phase.
Numerous creatine monohydrate products are available on the market. One adaptation, which has been shown to be of benefit, is the addition of high glycemic carbohydrates to the creatine. Creatine uptake into the muscle has been shown to be enhanced in the presence of insulin. This increased uptake leads to increase muscle creatine stores over creatine supplementation without carbohydrates. Of the remaining formulary additions to creatine monohydrate, none have been shown to be of great benefit. One possible exception may be the addition of inorganic phosphate salts. The addition of phosphates may aid in maintaining the creatine: phosphocreatine ratio within the muscle cell.
The addition of carbohydrates has improved the ergogenic value of creatine. However, an initial barrier must be addressed and corrected before the complete ergogenic value of creatine can be realized. That barrier is the poor intestinal absorption. Creatine uptake is mediated by an active sodium dependent transporter. Extremely little passive absorption of creatine occurs in the intestine due to the poor solubility in water and ionic nature of creatine in the native gastric and intestinal environment. Compounding this problem is the putative down regulation of the creatine transporter that occurs during supplementation. A decremental trend in creatine absorption is clearly demonstrated even during the relatively short loading period. This finding is consistent with the findings of other guanido-compounds, such as taurine, in which the intestinal receptor is shown to down regulate following oral supplementation.
Overcoming this barrier should provide a significant improvement to the ergogenic profile of creatine, both in the acute loading phase and the chronic maintenance phase. Prior to the introduction of effervescent delivery, no such means were available. The only recourse was to bypass the oral route, which involved intravenous administration. While there may be a place for this route in the therapeutic environments (e.g. care of patients with certain mitochondrial conditions), it is unacceptable as an option for athletic enhancement or recreational use.
Effervescence is the combination of weak acids and bases to create a buffered solution at a stable pH. It typically involves the use of bicarbonate salts, which form carbon dioxide gas upon activation. The appearance of the carbon dioxide gas gives the "bubbling" effect, which has been made quite familiar in over the counter indigestion and allergy remedies.
The use of effervescence is useful and applicable to the delivery of creatine for many reasons. First and possibly most importantly, is the buffering effect of the effervescent delivery. Stabilizing the pH of the creatine containing solution the pl or isoelectric point promotes an electrically balanced or neutral creatine molecule known as a "Zwitterion". The net electrical charge of the zwitterion is zero. As creatine is a small molecule, it is now theoretically available for passive absorption in addition to the active transport that has been shown to down regulate. This is important for two reasons. It provided an alternate and less restricted means of accessing the mesenteric venous system. The transport system can be quickly saturated even during the initial presentation of creatine. Second, it allows for the continued absorption of creatine even during the chronic maintenance phase.
An additional benefit of the buffering effect of the effervescence is the so-called dumping effect. Creatine is of maximal benefit during select times of the day (e.g. post fasting, post training). These "window" periods are of short duration. Gastric emptying studies suggest that a 200-ml volume be held in the stomach for forty minutes to one hour. If a greater volume is consumed or meal high in fat or protein is present, this may extend for hours. The effervescent delivery of creatine causes a pH shift to occur in the stomach. This shift is sensed as a signal to "dump" the stomach contents into the duodenum. The duodenum and the remainder of the small intestine are sites of the absorption. Very little absorption takes place in the stomach by design. The stomach’s role is predominantly to grind and break down the food by acidic digestion. The mucosal lining of the stomach is nearly impermeable to protect it from the destructive effect of the stomach acids. Once the creatine is passed to the duodenum, the greater surface area and absorptive function of the intestinal lining quickly absorb the creatine zwitterion. Additionally, the creatine transporters are located in the jejunum ad ileum, two other sections of the small intestine.
As the effervescently delivered creatine is near completely absorbed, the water efflux problems inherent with creatine use are resolved. Typically, non-effervescently delivered creatine, particularly after transporter down regulation, was passed down the small intestine, drawing water in the lumen of the bowel in and attempt to dilute and dissolve the creatine monohydrate crystals. The creatine crystals act as an irritant and have a high osmotic pull. Unfortunately, the majority of water transfer takes place in the large intestine, which has very little absorptive capacity. This leaves the creatine to reside in the colon, along with the attendant water load. This water efflux and the presence of the colonic creatine are what lead to the diarrhea, cramps, and dehydration problems. Again, the greater absorption with effervescent delivery should absolve creatine consumers of this "curse".
Thus far we have discussed the mechanisms by which the effervescent delivery improves creatine delivery. The specific formulation lies within a protected patent held by Joe Carnazzo of Fortress Systems International. The greatest benefit to the end user is the improved ergogenic value of the effervescently delivered creatine.
It is important to bear in mind that creatine is designed to augment work performance. This would be the type of work that is encountered by muscle performing at near maximal exertion to fatigue. This type of work is highly dependent on the amount of available ATP during the period of exertion. Long distance races and low intensity load exercise are not significantly affected by creatine supplementation. Thus it would be appropriate to measure changes in repetitive sprints, isotonic, isometric or timed recovery resistance training, but not marathon running or long distance cycling.
A study, which is performed in the exercise science laboratory, is the measurement of anaerobic work performance on a cycle ergometer. This measures maximal energy output, which are dependent upon ATP and the phosphocreatine shuttle. This study has shown an increase in anaerobic work performance (AWP) of 10% following a loading phase of creatine monohydrate. The addition of carbohydrates increased the AWP to 20% over the control group. This had been the standard by which creatine products were gauged for the last three years. Effervescent creatine with carbohydrate has demonstrated a significant improvement in AWP to 30% over the control.
Many marketing groups will present these benefits and figures in confusing terms. The basic facts shown by these studies are summarized as follows:
One further benefit of the effervescent creatine is packaging specific, rather than a physiologic effect. Effervescent creatine is dose metered packaged which means that each ingredient is added to each package individually. This ensures that each serving contains exactly the measured amount of each ingredient. This is in contrast to the large tubs of batched products, like the creatine and carbohydrate blends. The mixing process is imprecise and settling occurs both during manufacturing and shipping. Creatine may be nearly nonexistent in one portion of the batch and over the stated amount in another. Additionally, the effervescent system requires a foil-sealed pack, serving packs also makes for a more convenient means of use leading to greater compliance.
In summary, effervescent creatine represents a novel and effective use of pharmaceutical delivery, which enhance the positive benefits of creatine an negate the adverse effects. This will allow for significantly improved product performance and consumer compliance.
