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Old 08-20-2010, 07:39 PM   #1
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Default Purus Labs SlinShot



PURUS LABS SLIN SHOT


Optimal management of blood glucose (blood sugar) following feeding is of importance for all individuals. This includes those individuals reporting to a clinic with elevated fasting blood glucose levels (e.g., pre-diabetics and diabetics), as well as athletes looking to optimize glucose disposal into skeletal muscle. While the former population seeks to regulate blood glucose for the purpose of disease management (i.e., mitigation of health problems and premature death), the latter population primarily seeks enhanced energy utilization and glycogen resynthesis during and following strenuous exercise. (Note: Glycogen is a storage form of carbohydrate and is widely used as an energy source during physical activity, in particular of moderate to high intensity—e.g., moderate to high intensity resistance and aerobic exercise).

While the combination of regular physical activity/exercise and well-managed dietary intake should indeed be the first consideration in optimal blood glucose control, adjuncts to these two therapies have been used with success. Specifically, oral hypoglycemic agents, including both pharmacologic (i.e., prescription drugs) and non-pharmacologic (i.e., dietary supplements), are commonly prescribed/recommended and used by individuals worldwide. In relation to the latter, a wide array of dietary supplements are available for the supposed regulation of fasting and postprandial (post-meal intake) blood glucose elevations. The majority of these products target the overweight, pre-diabetic/diabetic market, citing the claim of “supporting healthy blood sugar levels”. While there do exist certain ingredients that have been reported in the scientific literature to have significant effects on blood glucose lowering (primarily in animals, with fewer data being derived directly from human subjects), one main problem remains; many dietary supplements contain such small amounts of the “active” efficacious ingredients, they most likely provide little, if any, benefit to the user. (Note: For more information pertaining to this topic of inferior dosages used within dietary supplements, see the Purus Labs™ White Paper for “Muscle Marinade™”).

Aside from the above issues (primarily enhancing glycogen synthesis), very few products currently focus on blood glucose disposal/management in athletes. This is surprising considering most athletes consume a high carbohydrate meal soon after the completion of their exercise training sessions with the goal of replacing depleted carbohydrate lost during the exercise session (i.e., skeletal muscle glycogen). While most young and healthy athletes have excellent glucose regulatory systems in place due to their training status and fitness level, it is possible that athletes consuming high carbohydrate meals may benefit from additional support in the form of novel glucose disposal agents. This is particularly true if the meals are comprised of simple, high glycemic carbohydrates, as is common for many post workout meals (whole food or meal replacement drinks).

This paper provides a brief overview of the process of glucose regulation and introduces a new dietary supplement focused on enhanced blood glucose uptake and nutrient delivery into muscle tissue. This product called SLINshot™, developed and marketed by Purus Labs™, may aid both athletes and non-athletes seeking enhanced blood glucose uptake via use of a natural, non-pharmacologic dietary supplement.

Although a significant body of evidence is not yet available pertaining to these findings in human subjects, use of SLINshot™ may lead to heightened blood glucose clearance post feeding (possibly promoting greater muscle glycogen storage), in addition to enhanced nutrient uptake into tissue (e.g., creatine). Data in support of these statements are presented later in this paper.


POST Workout Dietary Supplements and High Carbohydrate meals
Dietary Supplements (Meal Replacement Drinks and Bars)


The use of dietary supplements among the general population is rampant. This is certainly no different among athletes, who routinely use dietary supplements (an estimated 90% of all athletes) of one form or another (Erdman et al., 2007; Froiland et al., 2004). With regards to the athlete, one class of dietary supplement that receives a great deal of attention is the post workout drink or bar. These supplements (typically a powder mix, a “ready-to-drink” pre-mixed shake, or a meal replacement bar) serve the dual purpose of favorably impacting post exercise protein turnover and enhancing glycogen replacement in skeletal muscle. To achieve these goals, most products contain a combination of protein and carbohydrate of varying quantities, ratios, forms, etc.; these factors are dictated by the type of athlete and their overall objective pertaining to the post exercise meal (e.g., protein synthesis vs. glycogen synthesis). In general, most strength training athletes (e.g., bodybuilders) favor higher protein and lower carbohydrate ratios in the post workout drink, whereas most endurance trained athletes favor higher carbohydrate and lower protein ratios. Of course, this may differ based on individual tolerance to intake as well as overall goals. For example, many bodybuilders desire enhanced glycogen resynthesis as well as protein synthesis, because increased glycogen storage is often associated with a greater “muscle pump” and increased “muscle fullness”. Likewise, many endurance athletes need additional protein along with their carbohydrate due to experiencing substantial protein breakdown and muscle damage from the excessive strain placed on both muscle and enzymatic systems during high volume training.

In regards to glucose disposal from the bloodstream into target tissue, and the subsequent storage of glucose as glycogen, it should be understood that insulin assists in activating this process. Specifically, insulin is secreted from the pancreatic beta cells in response to a post-feeding rise in blood glucose. Insulin then binds the insulin receptor and promotes a cascade of “signaling” events that ultimately allows for the “translocation” of glucose-4 transport protein (GLUT4) from an intracellular site to the cell surface. It is GLUT4 that is chiefly involved in glucose uptake into tissue when in the fed state (e.g., post exercise feeding). This increase in circulating insulin is often a goal of most post workout products. Hence, many products contain high glycemic carbohydrate sources that act to rapidly raise blood sugar and illicit an insulin spike. While most well-trained athletes tolerate such high intake of carbohydrate post exercise (due to a heightened state of insulin sensitivity observed post exercise as well as the increase in GLUT4 activity—topics discussed in a later section within this paper), some athletes may need additional support in terms of aiding glucose delivery into muscle tissue or simply want to amplify this process for enhanced recovery, improved athletic performance (as related to the enhanced glycogen storage), and possibly “nutrient partitioning” (assuming glucose is shuttled into skeletal muscle tissue in favor of adipose tissue—a topic often discussed within the bodybuilding literature but requiring confirmation through scientific study).

Meals

Aside from the post workout meal in athletes, many individuals (athletes and non-athletes) consuming large, simple, refined, or high glycemic carbohydrate meals may benefit from dietary support in the form of a glucose regulatory agent. While dietary supplement manufacturers and the mainstream media simply focus on lethargy, impaired focus, and potential body fat gain as the negative effects of acute elevations in blood glucose, detailed scientific study indicates that such acute elevations in blood glucose (particularly if not lowered within the clinically expected timeframe—see info below on the oral glucose tolerance test [OGTT]) may be harmful to overall health. Specifically, spikes in blood glucose noted as “postprandial hyperglycemia” may be associated with an increase in free radical production which can cause harm to cellular components such as lipids, proteins, and DNA (Note: This is particularly true in those with impaired glucose tolerance). While this discussion is far beyond the scope of this paper, the reader is referred to the following reviews on this topic (Fisher-Wellman and Bloomer, 2009; Tucker et al., 2008). The bottom line is, certain individuals can indeed tolerate a high carbohydrate load, transport the available glucose from the bloodstream into skeletal muscle, and not present any significant elevation in oxidized biomolecules in the process. In such a case (which is very likely the scenario for some), individuals may not need additional dietary support in the form of a glucose uptake-enhancing agent; however, some individuals are not so fortunate. While the ideal solution is to begin/continue with a program of structured and strenuous exercise coupled with a nutrient balanced diet aimed at blood glucose control (consisting of low glycemic, fiber-rich carbohydrate and complete protein sources), the simple reality is most people will not follow such recommendations. This includes many athletes. Therefore, dietary support in the form of an agent that enhances glucose uptake from the bloodstream into target tissue may be beneficial.

Adjuncts to Post Workout Dietary Supplements and Ancillary Uses of such Agents


As alluded to above, aside from the commonly marketed “protein and carbohydrate” mixes currently available, multiple adjuncts to this post workout mix are heavily marketed. These often include agents that supposedly stimulate protein synthesis and attenuate protein degradation via mechanisms ranging from hormone manipulation to stimulation of satellite cell proliferation. One additional class of dietary supplement not heavily marketed, but that PURUS LABS™ believes has significant potential as a post workout dietary supplement aid (in particular when consumed with a high glycemic carbohydrate) is that of glucose disposal/regulatory agents. These agents not only have utility in terms of post exercise dietary support, but also for daily dietary support to assist in the management of healthy blood glucose levels and nutrient partitioning (disposal of glucose into skeletal muscle rather than adipose tissue). This applies to both athletes and non-athletes alike. Although athletes may primarily use such an agent for the purpose of stimulating enhanced glycogen resynthesis following an acute exercise session, both athletes and non-athletes may use such an agent for purposes of controlling postprandial blood glucose at times unrelated to acute exercise. In this regard, regulating blood glucose may help to improve overall health and well-being (e.g., reduce the potential harmful effects of free radicals, improve energy and mood, reduce excess body fat accumulation, etc.). While mentioned briefly above, the following section provides more details related to the mechanism of action of such a glucose disposal/regulatory agent, as well as the application for use.

Glucose Disposal Agents

The Need

Data published in 2005 by the American Diabetes Association indicated that within the United States alone nearly 21 million individuals, or about 7% of the population, have diabetes while another 54 million Americans have pre-diabetes (ADA, 2005). This number increased to 23.6 million (7.8% of the population) diagnosed with diabetes and 57 million Americans diagnosed with pre-diabetes in 2007 (ADA website data; American Diabetes Association Home Page - American Diabetes Association). The overall prevalence of both conditions is likely higher today in 2010, with more and more individuals being diagnosed with obesity, a co-morbid condition that has a strong association with type II diabetes (the most prevalent form of diabetes, accounting for approximately 95% of all diagnosed cases). Also important to note, there are an estimated 6 million undiagnosed individuals within the United States (ADA website data; American Diabetes Association Home Page - American Diabetes Association). Clearly, a need exists to aid millions of individuals with blood glucose management. (Note: It should be understood that a diagnosis of pre-diabetes does not necessarily indicate the future diagnosis of diabetes; however, the incident rate is certainly higher).

Diabetes is a complex disease accompanied by both microvascular (e.g., neuropathy) and macrovascular (e.g., atherosclerosis) complications. These changes often lead to a significant loss in physical function (e.g., loss of eye site, amputations) in addition to nonfatal or fatal outcomes (e.g., stroke, heart attack). Therefore, attempts to control blood glucose through exercise, dietary intake, pharmacologic agents, and nutritional supplements should be of utmost importance for all with this condition. It should be understood that unlike many other chronic diseases, diabetes absolutely can be controlled through appropriate changes in lifestyle (dietary modification and physical exercise in particular). Individuals not seeking to modify lifestyle components in an attempt to control their blood glucose are doing themselves a great disservice.

Outside of the specific problems associated with poor blood glucose control, diabetes is strongly associated with cardiovascular disease (CVD). The link between the two disease states appears to be the production of free radical species (sometimes referred to as Reactive Oxygen Species [ROS]) and the ensuing condition known as oxidative stress (Baynes and Thorpe, 1999; Ceriello, 2005; Evans et al., 2002). As mentioned briefly in a previous section, free radicals can be generated with excessive hyperglycemia, often in response to acute intake of high glycemic carbohydrate meals. Oxidative stress occurs when the production of free radicals exceeds the body’s antioxidant defense against this production (Valko et al., 2007). Individuals with poor blood glucose control are more susceptible to postprandial oxidative stress, partly due to the fact that they often experience prolonged periods of hyperglycemia following feeding (Miyazaki et al., 2007; Schindhelm et al., 2007; Serin et al., 2007). Such an elevation in blood glucose is directly linked to superoxide anion production (Bae et al., 2001), a potent radical which is known to react with other molecules causing further radical generation (Brownlee, 2005; Nishikawa et al., 2000). While this appears to be greater in pre-diabetics and diabetics compared to those with normal blood glucose levels, many individuals consuming frequent high glycemic carbohydrate meals may experience an increase in free radical production. This includes some athletes who purposefully consume such meals in an attempt to stimulate post workout glycogen resynthesis. Therefore, methods to control blood glucose following feeding may be important for all individuals.

Diabetes is most commonly diagnosed using either a fasting blood glucose test or an OGTT. A fasting glucose test involves only a single blood sample analysis with a normal value falling below 100mg∙dL-1. A value between 100 and 125mg∙dL-1 is indicative of “pre-diabetes” while a value ≥126mg∙dL-1 is indicative of diabetes. An OGTT usually involves ingestion of a carbohydrate drink (dextrose) at a dosage of 75 grams (300 kilocalories). Blood samples are typically taken before and at 30 minute intervals for 2-3 hours following consumption. Blood glucose should rise after consumption and then lower towards the pre-intake value. The two hour post consumption time is typically viewed as the diagnostic measure. A normal blood glucose value at this time should be <140mg∙dL-1. A value between 140 and 199mg∙dL-1 is indicative of “pre-diabetes”, while a value ≥200mg∙dL-1 is indicative of diabetes.

Agents, Mechanisms of Action, and Effects

With the above understanding, several pharmacologic and non-phamacologic agents are available to aid in blood glucose clearance following feeding. While a detailed discussion of this topic is beyond the scope of this paper, it should be noted that common oral hypoglycemic agents such as Glucophage® (generic: Metformin) are widely prescribed to diabetic patients and often used with success. Other non-pharmacologic agents have been studied in both animals and human subjects and used for years within Ayurvedic medicine. While scientific animal data are moderate to strong for some agents and anecdotal reports in humans are favorable for certain agents, few scientific data are available to support the use of glucose uptake-enhancing agents in human subjects. However, due to the increased need for and interest in natural, non-pharmacologic varieties of glucose disposal agents for both non-athletes and athletes, more research is now being done in this area of investigation.

The potential mechanisms of action of such agents can be multiple, including enhanced insulin secretion from the pancreatic beta cells, improved insulin-insulin receptor binding, enhanced post-receptor signaling, and superior GLUT4 translocation (movement) to the cell surface to allow for blood glucose to be taken into the cell (Interested readers are referred to the following article pertaining to this very complex process [Muoio and Newgard, 2008]). As stated earlier, it is important to remember that regular exercise training may be the single most important activity an individual can perform to facilitate an overall improvement in the above processes. This is because exercise (or more precisely, skeletal muscle contraction) promotes glucose uptake into cells in an insulin-independent manner (Merry and McConell, 2009). This is well-documented in numerous scientific investigations involving both animals and human subjects. Beyond exercise, optimal dietary intake and glucose regulatory agents may be components of non-pharmacologic treatments targeted at blood glucose control and enhanced glucose uptake into muscle tissue.

In terms of the overall effectiveness of these agents, many have been tested using the outcome measures of fasting blood glucose and OGTT, with evidence of effect coming from both animal and human studies. In these regards, drugs such as Glucophage® (generic: Metformin) often result in a decrease in fasting blood glucose and OGTT values following chronic use, as well as a more rapid return of blood glucose towards pre-intake values when administered in a single dosage prior to an OGTT (e.g., lower area under the insulin and glucose curves). For example, in human trials in which subjects were administered Metformin for a period of several weeks, a decrease in the glucose area under the curve of 20-30% has been noted (Carlsen et al., 1998). Similar findings have been observed in animal models using a wide variety of herbal, non-pharmacologic agents.

Due to the multiple studies performed using both pharmacologic and non-pharmacologic agents, no attempt is made here to review such studies. This area of investigation continues to expand and several candidate agents for blood glucose control may eventually be discovered and marketed to both healthy athletes and non-athletes for purposes of blood glucose disposal. This may have the dual focus of enhancing glycogen resynthesis following strenuous exercise as well as simply controlling blood glucose for overall health purposes. PURUS LABS™ has been following this area of research closely and believes the strongest candidate at the present time for consideration as a non-pharmacologic agent to enhance glucose and nutrient uptake into skeletal muscle is Artemisia Dracunculus L. var. inodora. This is underscored by a recent article published based on work performed at the Botanical Research Center suggesting that a novel extract of Artemisia Dracunculus L. var. inodora is a chief candidate of interest as a glucose disposal agent, as it may manifest a genotype-specific insulin-sensitizing phenotype (Zuberi, 2008). This product manufactured by PURUS LABS™ is called SLINshot™ and contains Artemisia Dracunculus L. var. inodora as the exclusive ingredient, provided at the same per serving dosage believed to be effective in facilitating glucose (and creatine) clearance from the bloodstream, with the potential of increasing uptake into skeletal muscle (see section below for more information).
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