Glucose Disposal Agents: What, when, why and how?
Glucose Disposal Agents: What, when, why and how?
Glucose Disposal Agents
You may have heard the term glucose disposal agent (a.k.a. GDA), insulin mimetic or nutrient partitioning agent. These are different terms for the same type of dietary supplement that has the purpose of aiding the body in breaking down carbohydrates from the diet and storing them in the form of muscle glycogen. Users of this type of dietary supplement have reported being able to eat larger quantities of food while staying leaner, having more visually "full-looking" muscles, and also being able to reach lower levels of body fat during fat loss-focused dieting phases without having to turn to harsh stimulants that can take their toll on the adrenal glands with prolonged use.
It does not matter what kinds of fitness goals you have, taking advantage of the power of the hormone insulin is a key aspect in reaching them. Insulin is a very potent inducer of amino acid uptake and muscle protein synthesis, and thus the key to growth and recovery of muscle tissue. Insulin is indeed the most anabolic hormone found in the body, but in terms of its' greatly positive effects on muscle gains, the door swings both ways. Insulin also directs both use and storage of glucose stemming from the carbohydrates ingested in the diet. Glucose gets stored as glycogen in either muscle or liver tissue, or as fat, in adipose tissue. It is very fortunate for us that we do in fact have an influence as to where the insulin directs the glucose to a certain degree. The glucose disposal agents or GDAs are used to help ensure that the carbohydrates from the diet get stored as glycogen in muscles rather than fat. GDAs take great advantage of the power that insulin possesses by working in cooperation with the body, optimizing its' response to the naturally produced insulin for an overall leaner, more muscular and healthier physique.
There are many different companies manufactring and selling glucose disposal agents on the market today, but if we were to dismantle one of these products to have a closer look at the active ingredients, we would more than likely be able to conclude that there are indeed lots of choices for individual glucose disposal agent ingredients available, and they all have different mechanisms of which they work through. A completely ideal scenario would be stacking several GDAs together, taking advantage of their different yet complementary effects on the insulin signalling. This is what is called synergy, where the whole is greater than the sum of the various parts. However, getting all of these different GDA ingredients together, and taking them in the correct and effective amounts at the right time certainly can be difficult. Fortunately for us once again, this has already been worked out by different companies, but this does beg the question: which one should we choose? More on that further on.
Now that we have established a basic understanding of what GDAs are all about, let us dive into the nitty-gritty part of insulin signalling, which can get quite hefty on the technical aspects. Fear not: there is a "take-home message" after the following sections that sums everything and gives a bit of practical information for the people reading who do not come from the school of science.
An overview of insulin and insulin signalling
All carbohydrates ingested via the diet get broken down and converted to glucose in the small intestine and are then absorbed into the blood stream. From here, one of two things can happen: the glucose can be used as an energy source for ATP synthesis or it can be stored, as directed by the insulin hormone. Glycogen from glucose is stored in the liver and muscle tissue, or gets converted to triglycerides and stored as body fat in adipose tissue. Our goal is obviously to maximise the muscle glycogen storage and protein synthesis happening in muscle tissue while also minimising fat gain. One problem we need to address here, though, is that glucose is going to be stored as glycogen only until the glycogen stores found in the muscles and liver tissue, are topped off, at which point the excess amount of glucose gets converted to fat. Muscle tissue is the major site of glucose disposal stimulated by insulin, meaning that any GDA should preferably maximise muscle glycogen storage, which will minimise the spillover to fat stores.
The take-home message here is that a muscle filled with glycogen is a bigger, fuller and much more anabolic muscle. The GDAs are capable of maximising the anabolic effects that insulin offers while also minimising body fat storage.
Body fat storage and insulin sensitivity
Body fat is stored in adipose tissue as triglycerides, which consist of three fatty acid molecules with a so-called glycerol backbone. If someone said that carbohydrate intake above a certain point is going to cause a "spill" into fat cells, the person in question would actually only be half-right. Fat cells are stimulated by insulin to take up glucose all the time - where it is converted to fatty acids - both of which are required for the body to be able to form triglycerides that are stored as body fat. Ideal circumstances would involve high glucose uptake in the muscles and the liver, low fat glucose uptake and with only a small amount of insulin needed to get the job done. Under these conditions, there will be no fat stored. The very small amount of glucose absorbed by adipose tissue gets converted into glycerol; rather than being used to form triglycerides, it gets returned to the liver where it is going to be used to produce more glucose. Under these conditions, the body in which everything previously mentioned was happening in would be called "insulin sensitive" - a small amount of insulin creates big effects. If the same body was provided with too many or the wrong kind of carbohydrates, and things could indeed change; glucose will only be deposited into muscle and liver tissue until the glycogen stores are saturated; the rest of this excess amount of energy is going to be converted into fatty acids and then stored as triglycerides in adipose tissue. The bigger an insulin response is, the more resistant the insulin signalling machinery will become to the effects of more insulin, especially in muscle tissue. This is going to increase the amount of insulin that is required to get the job done and overcome this "insulin resistance". Increased levels of insulin as a result of insulin resistance can cause more glucose to be diverted into adipose tissue and thus stored as body fat - and this can indeed happen very quickly. If one would ingest an overabundance of carbohydrates in just one singe meal, the big insulin response that gets generated would temporarily desensitise insulin receptors located on the muscle, ultimately causing a spillover of glucose into fat stores. If this was done over a longer period of time (especially if done by people with a certain genetic predisposition), conditions such as diabetes and obesity could indeed very potentially be the end-result. Genetic factors are indeed of great importance here; leaner people in generel have a tendency to be much more insulin sensitive and have lower levels of insulin. On the other hand, people with a genetic predisposition to becoming obese are more likely to be resistant to the effects of insulin in the body. It is not possible for us to change our specific genetic makeup, but we can indeed use GDAs to increase insulin sensitivity and cause more carbohydrates to be stored in muscle tissue as glycogen rather than being converted to body fat.
The take-home message of this section is that more insulin means that more carbohydrates get stored as body fat. An insulin sensitive person is more likely to store glucose as glycogen in muscle rather than storing it as body fat. An overabundance of carbohydrates (even short-term) can decrease insulin sensitivity and cause fat storage. GDAs help you become more insulin sensitive, promote muscle growth and glycogen storage while minimising fat gain from the carbohydrates that you eat.
Insulin signalling 101:
In order for anyone to be able to understand how a GDA works, it is necessary for us to briefly have a dive into the science of insulin signalling. This is insulin signalling 101: Insulin action happening in target cells such as muscle or adipose tissue (for our specific purposes in this case) initiates when insulin binds to the insulin receptor located on the cell membranes. This causes an activation of the insulin receptor tyrosine kinase activity, which phosphorylates and activates a protein by the name of insulin receptor substrate 1 or IRS-1. In turn, this IRS-1 protein activates two parallel signalling pathways called the ERK/MAPK pathway, which go on to activate downstream genes that are responsible for the growth-promoting effects of which insulin possesses, and the PI3K/Akt pathway, which activates the transport of glucose as well as both protein and glycogen synthesis.
Insulin simply acts in the role of a messenger; the "real" action occurs with the GLUT4 protein, which is activated downstream of PI3K/Akt. Upon activation the GLUT4 is sent from the cytosol to the cell membrane, where it acts as a gateway for glucose to enter the cell. The more of the GLUT4 molecules that are sent to the cell membrane, the more glucose will be allowed to enter the cell. In fact, the exact details of how insulin activates the translocation of GLUT4 and uptake of glucose are currently still in the works of being figured out, but the basics here are the key for understanding the term "insulin sensitivity"; the less insulin that is needed to transport the GLUT4 to the cell membrane for uptake of glucose, the more insulin sensitive someone is. Likewise, anything that can either directly or indirectly activate the translocation of GLUT4 is going to increase insulin sensitivity. A good GDA product will activate GLUT4 by various mechanisms, which results in a synergistic increase in insulin sensitivity.
That was the nuts and bolts of insulin signalling as an attempt to help you understand how insulin works in the body, why it is favorable to have a high insulin sensitivity and that GDAs can increase insulin sensitivity. Now it is time for the question you have most likely been waiting for this entire time: what makes the best possible GDA product?
What To Expect From A (Good) Glucose Disposal Agent
In order for a GDA product to be a "good" one, it would have to do all of the following:
- Amplify the effects of insulin to make your body need to use less of it. This is the actual definition of insulin sensitivity and it gives you more “bang for your insulin buck”.
- Possess activity mimicking insulin, meaning that it should be able to activate glucose uptake independent of exogenous insulin use (subcutaneous insulin injections).
- Reduce inflammation since inflammation has a largely decreasing effect on insulin sensitivity
- Optimize oxidation since too much or too little reactive oxygen greatly reduces insulin sensitivity. A "good" GDA would possess antioxidant activity to protect the body from oxidative stress while also optimizing reactive oxygen production for maximized insulin sensitivity.
- NOT BE A DRUG. This might seem like a no-brainer but it is very important to mention that drugs are in fact absolutely vital for people who suffer from diabetes, but their usage of these also comes at a cost in the form of potentially very harmful side effects. A "good" GDA would strictly contain natural ingredients and have no drug-like toxicity nor side effects.
- Actually work. Yes, another absolute no-brainer here. A "good" GDA should promote lean muscle gain and fat loss by making real and actual changes in the level of insulin sensitivity in people who already have their nutrition and training program in check.
The Ingredients Necessary For A (Good) Glucose Disposal Agent and Their Synergistic Effect On Insulin Sensitivity
This ingredient is a plant that is found in the central and southern parts of India, tropical Africa and tropical Australia. The active chemical in here is gymnemic acid, which is actually a mixture of 12 naturally occurring saponins. This ingredient has a potent effect on insulin sensitivity and glucose disposal, affecting a number of different aspects of insulin signalling. What exact cell signalling pathways that Gymnema Sylvestre activates is still something that scientists are currently working on finding out, but there is already a large amount of substantial evidence for the positive effects on insulin signalling of the ingredient. First and foremost, it acts to decrease the uptake of glucose from the small intestine. It also increases peripheral insulin sensitivity, and causes significant improvements in glucose uptake and glycogen synthesis in liver and muscle tissue. This means that more glycogen gets transported into the muscles after ingesting carbohydrates, which results in muscle that both look and feel harder as well as less body fat gain. Another favorable property of Gymnema Sylvestre is the fact that it actually helps regenerate damaged pancreatic beta cells, which is most probably related to its anti-inflammatory properties. While this is more important for patients suffering from diabetes, pancreatic beta cells are the only site of insulin production in the body. It is always a good idea to take care of these cells no matter who you are. When these cells are overwhelmed by an increased demand for insulin of which they are unable to keep up with as a result of continued inflammation, you have what we know as the medial condition type-1 diabetes, meaning that you will indeed be dependent on taking insulin as medication for the rest of your life.
Alpha Lipoic Acid
Alpha Lipoic of ALA occurs naturally in small amounts in muscle meats, heart, kidney and liver pre-dominantly but is also found in some fruits and vegetables as well. It needs to be supplemented in order to obtain any positive effects from it, though. First and foremost, ALA is a very potent antioxidant because of its' ability to neutralize hydroxyl radicals and singlet oxygen; two of the absolute most destructive free radicals. A great thing about this ingredient in particular is the fact that it is neutral against hydrogen peroxide. This is important since some natural hydrogen peroxide production is necessary to have around for having an optimal level of insulin sensitivity as well as muscle growth. ALA can also aid in regenerating other endogenous antioxidants such as vitamins C and E. This is how ALA optimizes oxidation and thus protects cells from oxidative stress while optimizing reactive oxygen production for a maximized insulin sensitivity. It also increases intracellular (inside the cell) L-Glutathione (the most powerful antioxidant in the body) levels, making it a really a potent liver detox agent as well. Like Gymnema Sylvestre, ALA has a powerful effect on inflammation which also contributes to its' insulin-sensitizing effects. It is responsible for the activation of multiple pathways downstream of the insulin receptor including Erk/MAPK, which goes on to activate genes related to muscle-growth. Furthermore, ALA possesses a synergistic effect on glucose uptake in muscle cells by activating the GLUT4 protein via multiple pathways including AMPK, PI3K/Akt, and by another PI3K/Akt independent pathway. This means that ALA amplifies cell signalling that leads to muscle growth, insulin sensitivity and glycogen storage.
*note on R-ALA vs. ALA
People frequently ask questions on the difference between ALA and R-ALA, so here it is: All alpha lipoic acid is by no means the same. The alpha lipoic acid molecule has what is called a “chiral center”, meaning that it can exist in two different confirmations which are mirror images of each other. It might not be easily comprehensive but try looking at your right and left hand. These two are in fact the same, but you cannot superimpose one on top of the other because they are mirror images of each other. The same thing goes for chiral molecules; one conformation can be thought of as being the “right handed” one and the other as being the “left handed” one. When these are synthesized in a lab, chiral molecules usually exist as enantiomeric pairs (a technical term for a molecule that exists in both the right- and the left-handed conformation). Alpha lipoic acid is produced by the body naturally, and as it is with the majority of biological molecules, it normally does not exist as an enanthiomer (alpha lipoic acid produced naturally is in the "R" form). The alpha lipoic acid that is available commercially as "ALA" is the enantiomeric mixture (the label is just going to say "ALA" in this case). Similar to this, "R-ALA" that is available commercially is the "R" isomer or the "right-handed" form as mentioned earlier. Evidence shows that the R-form of the ALA is the most potent form of alpha lipoic acid when it comes to insulin sensitisation. Because of the fact that ALA is a mixture of right- and left-handed forms (R-ALA and S-ALA), taking regular ALA will have some of the insulin-sensitizing effects of pure R-ALA. The equivalent amount of ALA that is necessary to obtain the same effect of a given dose of R-ALA is up for debate. As it is with most enantiomers, ie. ibuprofen, the non-active form often tends to block the effect of the active form. In other words, with ALA, you will most likely experience the best effects when choosing the R-form.
Cinnamon Extract (CE)
This ingredient has an almost ever-lasting list of positive effects. First and foremost, CE is not only helpful at making insulin do its' job better, but it also has insulin mimetic properties. CE hugely affects glucose uptake and can directly increase the levels of GLUT4 via mechanisms that are dependent and independent of insulin respectively. CE also has an enhancing effect on the activation of IRS-1 by insulin, which increases insulin sensitivity. It is also a very potent anti-inflammatory agent, which is highly important because of the fact that excess inflammation can have a largely negative effect on insulin sensitivity. There has been loads of research done on the positive effects of CE on human insulin signalling. In diabetic patients, CE has been shown to decrease fasting blood glucose levels, and decrease LDL-cholesterol levels and triglyceride levels (the bad kind of cholesterol) while increasing HDL-cholesterol (the good kind of cholesterol). One study that was carried out on people suffering from metabolic syndrome demonstrated that CE decreased fasting blood glucose levels, systolic blood pressure as well as body fat levels while actually increasing lean mass at the same time. It is very important to mention that the positive effects of CE has also indeed been shown to work in normal, healthy people and thus they can also experience the improved glucose tolerance and insulin sensitivity when using the ingredient.
A GDA is not a GDA without the addition of this ingredient. Chromium is an essential trace nutrient that is necessary for carbohydrate metabolism. It is another of the ingredients that is able to directly affect insulin sensitivity by the activation of GLUT4. It has also been demonstrated to be a potent potentiator of insulin signalling in general. There are also some effects of chromium that indeed do sound promising but have not yet been confirmed. These include enhanced interaction of insulin with the insulin receptor, increased pancreatic beta-cell sensitivity and an increase in the number of insulin receptors in the body. There is great discrepancy in the scientific research as to whether or not chromium has an effect. In many of the studies that demonstrated chromium to be ineffective, the dosing of the ingredient used was relatively low. Another factor needed to be taken into consideration is that to date, scientists are still not sure how chromium actually works. When looking at experiments that investigate cell signalling, it is very difficult to measure an effect if you do not know exactly what to look for. What we do know, however, is that chromium indeed does support insulin signalling by several known and unknown mechanisms, and that a deficiency is indeed very harmful for insulin sensitivity. This is exactly the reason why no GDA supplement would be complete without including chromium as one of the ingredients.
The ingredients listed above are the main things that should be included as active constituents of any "good" glucose disposal agent.
At Only Approved Supplements, we offer a glucosal disposal agent by the name of "SLIN-RX" by the British company Muscle Rage. What is great about "SLIN-RX" is that it first of all contains all of the ingredients mentioned above plus four other ones that have all been proven to be effective at improving insulin sensitivity and affecting glucose uptake positively. "SLIN-RX" is indeed suitable for anyone and everyone no matter phase of training they currently find themselves in. If in a muscle-gaining phase, a larger caloric intake is needed to grow. "SLIN-RX" is an ideal supplement to add in here since it helps ensure that the additional calories that make the intake a surplus are being put to good use and not just stored as body fat. If in a dieting phase, the more insulin sensitive you are, the more your hard work sticking to the diet will pay off, making "SLIN-RX" a great choice for dieting phases as well. The most ideal time of the day to use a supplement such as "SLIN-RX" would be post-workout since insulin is a potent inducer of protein synthesis as well as amino acid uptake. "SLIN-RX" can be used with any meal that contains carbohydrates, but because of the product's extreme potency, please do be aware of the fact that a sufficient amount of carbohydrates is needed in order for the product to not make you go hypoglycemic (low blood sugar). This usually equates to +50 grams of carbohydrates per 4 capsule serving of "SLIN-RX". No matter what your personal goals are, being leaner, healthier and stronger is always beneficial. "SLIN-RX", with it's synergistic effects on insulin sensitivity, inflammation and oxidative stress, is a great addition to any supplement arsenal. Harness the true power of insulin with "SLIN-RX" by Muscle Rage and take your training to whole new and higher levels. Have a look at the product on our website right here. To visit Muscle Rage's own website, click here.