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Old 08-20-2010, 08:40 PM   #2
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Artemisia Dracunculus L. var. inodora
Description, Mechanism of Action, and Evidence for Effect

The ingredient known as Artemisia Dracunculus L. var. inodora has been used for centuries in Russia and middle Asia as a digestive, diuretic and antipyretic herbal medicinal drug. Today, Artemisia Dracunculus L. var. inodora is classified as a Generally Recognized as Safe (GRAS) material after removal of the harmful components of the essential oil (e.g., Estragol and Methyleugenol). This ingredient is widely studied for its blood glucose lowering effects, earning its position as a target candidate ingredient to be used in the treatment of metabolic syndrome (Cefalu et al., 2008a). Novel ethanol and aqueous extracts have been developed and these have shown promise with regards to blood glucose regulation (Ribnicky et al., 2006) and nutrient (i.e., creatine) transport (Jäger et al., 2008). Collectively, the clinical effects of Artemisia Dracunculus L. var. inodora on carbohydrate metabolism may be secondary to enhancing insulin post receptor signaling (Wang et al., 2008). The polyphenolic compounds 6-demethoxycapillarisin and 2',4'-dihydroxy-4-methoxydihydrochalcone are believed to be responsible for much of the glucose-lowering activity of the Artemisia Dracunculus L. var. inodora (Govorko et al., 2007).

In a comparison study conducted using genetically diabetic KK-A(gamma) mice, an alcoholic extract of Artemisia Dracunculus L. var. inodora was reported to lower elevated blood glucose levels by 24%, while treatment with the antidiabetic drugs Troglitazone and Metformin (Glucophage®) decreased blood glucose concentrations by 28% and 41%, respectively. Blood insulin concentrations were also reduced in the KK-A(gamma) mice by 33% with the Artemisia Dracunculus L. var. inodora extract, 48% with Troglitazone, and 52% with Metformin (Ribnicky et al., 2006). Based on these data, there appears extraordinary potential for Artemisia Dracunculus L. var. inodora as a natural agent involved in glucose clearance. This is particularly true if this agent is delivered along with a bioenhancer/solubilizer (Labrosol®), as reported recently by Ribnicky and coworkers (2009).

Creatine Disposal

Although the majority of studies involving Artemisia Dracunculus L. var. inodora have focused on aspects of blood glucose regulation, one interesting study having direct application to athletes involves co-ingestion of the dietary supplement creatine monohydrate. Creatine is a naturally occurring nitrogenous organic compound produced in relatively small amounts in the human body from the amino acids arginine, glycine, and methionine. Supplemental creatine likely represents the most widely used and studied sport supplement of all time, with the possible exceptions of caffeine and carbohydrate. Once creatine enters muscle tissue, it aids in adenosine triphosphate (ATP) resynthesis and can lead to high intensity exercise performance improvements. Although supplemental creatine is well-absorbed by many individuals, others are “non-responders” and may benefit from co-ingestion of a high carbohydrate feeding along with the creatine (Green et al., 1996). In this way, the carbohydrate stimulates an insulin response which is thought to activate creatine transporters to help facilitate creatine uptake into tissue. The concern here is that many athletes 1) do not use excess simple carbohydrate routinely during the day (e.g., pre-contest bodybuilders) or 2) do not want to consume an additional high glycemic carbohydrate meal outside of their post workout meal. Because many athletes ingest creatine more than one time per day, other methods of enhancing creatine uptake into muscle aside from carbohydrate ingestion are desired.

It has been reported that a dosage of 1000mg of Artemisia Dracunculus L. var. inodora ingested 15 minutes prior to ingestion of the creatine monohydrate (at a dosage of 60mg/kg body mass) resulted in a significant reduction of plasma creatine levels at 60, 90 and 120 minutes following ingestion (Jäger et al., 2008; see Figure 1 for a graphical depiction of these findings). The investigators suggested that the effect of Artemisia Dracunculus L. var. inodora is seen as comparable to that of glucose, a macronutrient that has been used in prior studies in an effort to stimulate creatine uptake into skeletal muscle (Green et al., 1996). While it is thought that the increased creatine clearance from the plasma reflects enhanced uptake into skeletal muscle, this was not determined in the study by Jäger and colleagues (2008). Therefore, admittedly, this is merely a hypothesis at the present time and needs confirmation through additional research. In a similar manner, although speculative at the present time, as with creatine, it is possible that the use of Artemisia Dracunculus L. var. inodora might yield a similar effect on nutrient transport for other ingredients such as amino acids.

It is possible that the effect of Artemisia Dracunculus L. var. inodora on creatine clearance is mediated by the insulinogenic action, in a similar manner as carbohydrate ingestion elevates insulin and allows for enhanced creatine uptake into skeletal muscle. Considering this, coupled with the fact that some individuals would prefer not to ingest high glycemic carbohydrates in order to facilitate hyperinsulinemia and subsequent creatine uptake, use of Artemisia Dracunculus L. var. inodora appears logical. This effect on creatine clearance, coupled with the blood glucose lowering effect, is the dual rationale for selecting Artemisia Dracunculus L. var. inodora as the exclusive ingredient to be used within PURUS LABS™ SLINshot™.

Ethanol vs. Aqueous Extracts

Although several papers focused on Artemisia Dracunculus L. var. inodora have been published using the ethanol extract of this ingredient, an aqueous extract has recently been developed and reported to provide even greater effects on glucose lowering (Walbroel et al., 2009). In this work, an OGGT was administered in a group of rats following oral ingestion of an aqueous or ethanol extract of Artemisia Dracunculus L. var. inodora (at a dosage of only 6mg∙kg-1). The diabetic drug Glibenclamide was used for comparison (at a dosage of 18mg∙kg-1). The glucose area under the curve was similar but slightly lower for the aqueous extract as compared to both the ethanol extract and Glibenclamide. An additional experiment using dosages ranging from 1.5 to 60mg∙kg-1 indicated that while the blood glucose peak was not as pronounced (approximately 200mg∙dL-1 vs. 240mg∙dL-1) and occurred at a later time following a 30 and 60mg∙kg-1 dosage (30 minutes vs. 15 minutes post OGTT) compared to a 1.5 and 6mg∙kg-1 dosage, the glucose area under the curve was similar. These data indicate that a dosage of Artemisia Dracunculus L. var. inodora as low as 1.5mg∙kg-1 may actually be effective at lowering blood glucose following an OGTT. While such findings are exciting to note, it is important to remember that these data are from animals and not humans; therefore, results may not be directly transferred. However, the text below describes some initial case study data obtained from human subjects using Artemisia Dracunculus L. var. inodora in an attempt to aid in glucose disposal following an OGTT.

Introducing SLINshot™
Overview and Rationale for use

Before we begin the discussion of PURUS LABS™ SLINshot™ it is important to understand that while other ingredients targeting glucose regulation appear promising in their own right, PURUS LABS™ has made the careful decision to use Artemisia Dracunculus L. var. inodora exclusively within SLINshot™. The reason for this decision is threefold. First, Artemisia Dracunculus L. var. inodora has been used in several studies to date with results that all essentially parallel each other; that is, the studies support one another rather than refute each other. This is often not the case when studying nutritional ingredients. Second, when designing a dietary supplement PURUS LABS™ believes that not only do the appropriate ingredients need to be included within the product, but the correct and efficacious dosage of ingredient needs to be included. Each single serving of SLINshot™ contains 1000mg of Artemisia Dracunculus L. var. inodora. If several ingredients were to be included within SLINshot™ simply to compete with other companies attempting to fill the label with ingredients, the dosage of each ingredient would need to be significantly lower than the believed effective dosage. This makes little scientific sense and is not something PURUS LABS™ will ever do. Alternatively, if all (or many) of the ingredients that appear to have some promise in terms of glucose regulation were included at the believed effective dosage, consumers would need to consume 10-12 capsules per serving rather than 2 capsules, and the per unit cost of the product would be 5-6 times higher. Again, when considering the potential benefit of doing this based on the currently available evidence for effect, it simply does not make sense. PURUS LABS™ believes the exclusive use of Artemisia Dracunculus L. var. inodora within SLINshot™ will provide consumers with a scientifically sound, effective product at a reasonable intake level and cost. This dietary supplement may serve the dual purpose to allow for enhanced glucose and creatine uptake into tissue. Third, PURUS LABS™ has personally experimented with Artemisia Dracunculus L. var. inodora (aqueous extract) and has observed the effects of this ingredient first hand. Of course, further well-controlled research is necessary to provide confirmation for the proposed effects in human subjects.

Preliminary Human Subject Findings

As mentioned earlier in the paper, the majority of work involving Artemisia Dracunculus L. var. inodora has been conducted in animals. While findings from animals can often be interesting and sometimes translate to humans, this is not always the case. This is especially true considering the route of administration in many animal studies is not oral (like that for human dietary supplements), and the dosage of ingredient used in many animal studies is often far greater than most humans will want to consume or could afford to use. Fortunately, Artemisia Dracunculus L. var. inodora has been delivered to animals via oral ingestion and at a dosage that is actually manageable in terms of translation to human daily ingested amounts. Moreover, Artemisia Dracunculus L. var. inodora has been previously used by humans at an oral dosage of 1000mg, with favorable effects noted for creatine clearance from plasma (Jäger et al., 2008).

Considering the work of Jäger and colleagues (2008) using Artemisia Dracunculus L. var. inodora to enhance creatine clearance from plasma, the effects of both 1000mg (equivalent to 1 serving of SLINshot™) and 2000mg (equivalent to 2 servings of SLINshot™) of Artemisia Dracunculus L. var. inodora on blood glucose following an OGTT has been studied using a case analysis in an effort to generate pilot data to guide future research studies (unpublished data). The text below describes this work.

The Experiments Described

For data collected from experiments described here please refer to Table 1 and Figure 2. Two adult resistance trained men (Subject X: 225 pounds, 10% body fat; Subject Y: 180 pounds, 7% body fat) performed two OGTTs with and without experimental research grade SLINshot™. Subject X used 1000mg (1 serving) of SLINshot™ and subject Y used 2000mg (2 servings) of SLINshot™. The SLINshot™ was ingested 15 minutes prior to consuming 75 grams of dextrose solution (300 calories). This is standard procedure for a clinically administered OGTT. Blood samples were collected from subjects before ingesting the SLINshot™ (after a 10 minute quiet rest period) and at 15, 30, 45, and 60 minutes following ingestion of the dextrose solution. (Note: As opposed to a blood collection every 30 minutes and a duration of collection of 2-3 hours, often employed for an OGTT administered in a clinical setting, it was decided to obtain more frequent blood samples but to cease measurements at one hour post ingestion. This decision was based on prior work involving young, healthy subjects performing an OGTT—for which blood glucose more quickly returns to pre-meal values as compared to individuals with impaired glucose tolerance). During the 60 minute post ingestion period subjects remained relaxed and ingested no additional food or calorie containing beverages. Following blood sample collection, glucose was analyzed in serum using standard enzymatic procedures. Assays were performed in triplicate.

Table 1 provides values for each time point of sample collection for both placebo and SLINshot™ trials. The area under the curve (AUC) is also presented which uses a mathematical model to represent the “sum” over the course of the one hour post ingestion period. Percent difference values between placebo and SLINshot™ trials are included for each time point as well as for AUC. Figure 2 provides a graphical representation of the data. As can be seen, oral intake of SLINshot™ provides for blood glucose disposal effects in healthy men averaging 20.5%.

Pertaining to the above, while only two subjects were used in this case study analysis, it cannot be concluded that all individuals will respond in the same manner. Clearly, additional research using a sample of 10-20 individuals is needed to provide further support for these initial findings. This is true for all herbal forms of glucose regulatory agents recommended for use in human subjects (Cefalu et al., 2008b). However, when collectively considering the evidence from both animals and humans (in relation to both glucose and creatine clearance), the results are indeed noteworthy.

It should be understood, as with all dietary supplements, individual results to treatment may vary. Therefore, individuals may require more or less than 1 serving of SLINshot™ in order to achieve the desired result (i.e., glucose or creatine clearance). Keep in mind that in much of the work related to Artemisia Dracunculus L. var. inodora, test subjects/animals consumed 75 grams of research grade dextrose (a simple sugar), or the equivalent. Individuals not consuming such high amounts of carbohydrate (in particular simple sugar) may not require as much SLINshot™ in order to optimally manage blood glucose levels (or may not require any glucose disposal agent at all). However, SLINshot™ was developed with the idea that athletes would use this supplement along with their post-exercise carbohydrate meal which typically contains a significant amount of carbohydrate (often in the form of simple sugars). In this situation, it is recommended that SLINshot™ be used at 1000-2000mg (1-2 servings) depending on age, glucose tolerance, and overall health status. For example, subjects X and Y experienced similar effects of SLINshot™ despite two different dosages being used. As with all dietary supplements, experimentation by each individual is suggested. This applies to both athletes and non-athletes and should be considered relative to meals associated with exercise bouts as well as those outside of the context of acute exercise.

Conclusions and Practical Applications

Management of blood glucose following feeding is of importance for athletes and non-athletes. In relation to the former group, it is possible that post exercise feedings that contain high amounts of carbohydrate for purposes of glycogen replenishment may better be taken up into tissue via dietary support in the form of SLINshot™ (Artemisia Dracunculus L. var. inodora). Moreover, this ingredient may facilitate uptake of other nutrients commonly used by athletes (e.g., creatine). Collectively, the product SLINshot™ from PURUS LABS™ may be used as an adjunct to an already well-designed exercise and nutrition plan targeting optimal blood glucose regulation and/or glycogen supercompensation. Daily use of this product in conjunction with high carbohydrate meals, either post workout or at other times of the day as needed, may aid in heightened glucose clearance from the blood and uptake into tissue. This may not only improve glycogen replenishment in athletes seeking this outcome but may also maintain overall health as related to optimal blood glucose management (e.g., reduce the potential harmful effects of free radicals, improve energy and mood, reduce excess body fat accumulation, etc).

As with all nutritional supplements, potential users should consult their personal physician prior to using SLINshot™. This especially applies to those individuals with known problems related to blood glucose regulation. In addition, potential users should review the product nutrition panel and label for information regarding the ingredient, dosing, and precautions for use. For more information on PURUS LABS™ and its other performance/physique-enhancing products, please visit Purus Labs | Research Forged.
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