by Mike Arnold
Increasing Insulin Sensitivity & Up-Regulating Glut-4
In the previous article, we discussed the importance of post-workout nutrition and touched on the relationship of insulin and Glut-4 within the context of muscle growth. In this article we will begin exploring the various steps one can take to help improve insulin sensitivity and enhance Glut-4 up-regulation.
As a leading risk factor in the development of Type II diabetes, poor diet, often in conjunction with obesity, can have a pronounced effect on blood sugar regulation leading to insulin resistance. So potent is diet in ameliorating this condition that its modification is generally accepted as the first line of defense in those who have been diagnosed with Type II diabetes.
The normal recommendation is to limit carbohydrate intake and although effective, it fails to take into consideration the unique dietary needs of the BB’r, who by hobby or profession, requires a substantial carbohydrate intake in order to optimize recovery & growth. Fortunately, these goals are not mutually exclusive. With a little planning, we can reduce the negative effects of carbohydrate intake on insulin sensitivity while continuing to receive their benefits.
When it comes to diet, perhaps the most important step one can take is to avoid the over consumption of simple sugars and other rapidly-digesting carbs, especially high fructose corn syrup, as they tend to cause relatively large spikes in blood sugar lasting only a short duration. Although this can be beneficial at certain times, doing so repeatedly lowers insulin sensitivity, not to mention encourages fat gain, causes inflammation, and increases the likelihood of developing cardiovascular and/or various metabolic disorders. By limiting these carbs mainly to the training window, rather than relying on them as a primary fuel source throughout the day, not only is insulin sensitivity less likely to be compromised, but they are they more likely to be used for recovery & growth. The 2nd best time to consume these carbs would be first rise in the morning (meal #1), but aside from that, slow-digesting carbs, such as whole-grains and vegetables, should be your go-to carb source for all your other energy needs. By eating in this fashion, stabilization of insulin levels leading to prolonged anabolism, decreased fat gain, and improved insulin sensitivity should be expected.
High-fat diets also tend to decrease insulin sensitivity, although not all fats are equal in this regard. In fact, fats such as fish oil and extra virgin olive oil, in addition to their health and muscle building benefits, have been clinically shown to increase insulin sensitivity when consumed in low-moderate amounts. This makes them a worthwhile addition to any BB’ing diet. On the other hand, trans-fats have the opposite effect, having been shown on numerous occasions to negatively affect insulin sensitivity; likely as a result of impaired insulin receptor signaling. When evaluating these fats individually, CLA appears to be the worst offender, having demonstrated the single most dramatic adverse effect on insulin sensitivity to date. Although found naturally in some foods and even associated with certain benefits, adding additional CLA to one’s diet through supplementation may not be the best idea, especially if insulin resistance is already an issue. Man-made trans-fat should be eliminated from the diet entirely, as they supply virtually no benefits.
Glut-4 transporters are affected similarly, with high-fat diets causing significant down-regulation in skeletal muscle tissue. In terms of specific fats, arachidonic acid is particularly troublesome, as it inhibits Glut-4 translocation to a greater degree than most. As an essential component of proper physiological functioning, dietary fats should not be avoided, but overall consumption should remain moderate, with emphasis placed on the balanced intake of both plant and animal sources in their naturally occurring forms.
Although the following is not technically a dietary fat, the words fat & bodyfat seem to fit together, making this the perfect introduction for the next risk factor—obesity. TNF-a, a potent mediator of inflammation and expressed abundantly in fat cells, is present in high quantities in obese individuals, resulting in the dysregulation of lipid and carbohydrate metabolism, as well as impaired insulin signaling frequently progressing to insulin resistance. Now considered a major health epidemic, obesity is often hard to control and seldom rectified quickly, as it is much easier to just pop a pill or get in a workout than it is to sustain long-term dietary modifications. Keep in mind that one doesn’t have to be clinically obese to begin experiencing negative effects in these areas. Even a BF% in the mid-teens, in men, while by no means excessive, will impair insulin sensitivity to at least some degree, while simultaneously increasing the rate of estrogen conversion. Still, for those who possess the motivation and discipline required to reach their ideal BF%, the accompanying benefits are so numerous and diverse that it often effects nearly every area of the individual’s life.
Although pretty much a no-brainer at this point, no discussion on insulin sensitivity would be complete without mentioning the use of exogenous insulin. If chronic elevations in insulin levels via diet can be harmful to insulin sensitivity, one would expect the excessive use of exogenous insulin to act in the same way…and it does. Out of all the PED’s a BB’r might employ to help stimulate muscle growth, insulin and growth hormone have the greatest potential for harm in this area. With excessive, indiscriminate use, insulin sensitivity drops rapidly—often to the point of clinical insulin resistance. If the goal of using insulin is to enhance growth through increased nutrient transport, then this is the last thing we want, as it defeats the entire purpose of using insulin in the first place.
I have personally witnessed several cases in which an insulin user’s sensitivity had been damaged so badly that they only required 2 grams of carbs per IU in order to stabilize blood sugar levels. With the average individual requiring between 6-10 grams of carbs per IU in order meet insulinogenic demand, it shows just how detrimental exogenous insulin use can potentially be. Let’s look at things from a different perspective. If we compare the insulin to carb ratios of the two groups above, we see that the insulin resistant group is only receiving 1/3rd to 1/5th the benefit per IU of insulin injected. In other words, they would have to administer 3-5X as much insulin just to transport the same amount of nutrients to the muscle cell that someone with a normal degree of insulin sensitivity would require. At this point, although these individuals may be using large dosages of insulin, its effectiveness has diminished so greatly that they are no longer receiving anywhere close to the same benefits they did initially. A 100 IU daily dose now works no better than the 20-30 IU they started with!
Because they now require so much more insulin in order to transport an equivalent amount of nutrients, what do you think happens during the times when exogenous insulin is not active? Their own pancreas is forced to produce insulin on a massive level just to deal with the increase in blood sugar that occurs from a normal meal. Over time, these insulin producing cells of the pancreas, called islets, begin to burn-out. This is exactly how one becomes a Type II diabetic—they lose the ability to produce enough insulin to properly regulate blood sugar levels. So, my recommendation to avoid these extreme, thoughtless insulin programs is about more than just muscle growth—it is about maintaining your health in a major way—and this is just ONE of the many health problems that can take place as a result of insulin resistance. If the goal of using insulin is to grow as much as possible—preferably while minimizing health risk—then any method/pattern of use which causes an unreasonable degree of insulin resistance works directly against that goal.
Among those who use insulin, it is common to begin at a fairly low dose of say, 10-15 IU per day. However, some soon decide that this isn’t enough. They hear stories about the “pros” using 100-200 IU per day (which in many cases is bullshit) and automatically assume that they need to do the same if they want to reach the same level of development. Unfortunately, this approach almost always results in serious insulin resistance. After a while, the individual realizes he isn’t getting the same effect from the drug as he used to, which inevitably leads him to increase the dose even further. Therefore, the problem continues to perpetuate itself, while the root of the problem fails to be addressed.
Now, I am not saying that one can’t or shouldn’t increase their dose beyond 10-15 IU/day–that is ridiculous, but in my experience, by the time one reaches 30-40 IU per day, they will begin experiencing measurable insulin resistance. Rather than continuing to increase the dose from there, which will only make the problem worse, I suggest forgetting about a further hike in dosage and instead placing one’s focus on optimizing insulin sensitivity & Glut-4 expression. By increasing the efficiency with which your body can use insulin, it is just like using a higher dose from an effectiveness standpoint, but without the negative health risks that accompany such programs—and the benefits don’t stop there. You will also get better results from your own natural production, in addition to all the other physique & health benefits that come along with improved sensitivity.
As with diet, resistance training also has the ability to modify carbohydrate metabolism. This is accomplished through both improved insulin receptor signaling and local-contraction mediated mechanisms. The former takes place when insulin receptors become more receptive—or sensitive—to the actions of insulin, improving the efficiency with which it is able to regulate blood glucose levels. The mechanisms by which weight training up-regulates Glut-4 is a bit more complex and has yet to be fully elucidated, but is believed to occur as a result of the muscle contraction process itself. More specifically, researchers believe that two particular cellular consequences of muscle contraction—a transient increase in intracellular calcium concentration and an increase in AMP/ATP ratio—are primarily responsible for mediating the positive effects of resistance exercise on Glut-4 translocation (expression).
Endurance exercise (cardio) is another star-player in the area of reversing insulin resistance. While both resistance and endurance training enhance glucose uptake in skeletal muscle and improve insulin sensitivity, they differ in their ability to enact change in these areas. Most notably, resistance training leads to a greater increase in glucose uptake capacity, improving insulin sensitivity indirectly, while endurance training is superior at improving insulin receptor signaling, leading directly to improved insulin sensitivity. I should also mention that the up-regulation of Glut-4 that occurs in response to endurance exercise is rapid and substantial, resulting in a 1.5-2.0 fold increase after only a single session. With each form of exercise working through different mechanisms, the evidence supports a combined approach.
Moving on, let’s look at a few of the drugs which can increase insulin sensitivity/Glut-4 expression. Although there are tons of diabetic drugs used for this purpose, the medical establishment has yet to uncover a pharmaceutical invention capable of directly turning on Glut-4 expression and believe me, they are trying every day. As a possible cure for Type II diabetes, the potential implications of such a drug would be far-reaching and life-changing for millions of people. In theory, such a drug would allow BB’rs to use massive doses of insulin without fear of developing insulin resistance—an advantage many BB’rs would love to have at their disposal.
As it now stands, there are many diabetic drugs currently available, but with unfavorable side effect profiles, they’re rarely used by anyone but diabetics. In reality, we are left with only a limited number of effective and relatively safe drugs capable of promoting meaningful increases in insulin sensitivity/Glut-4 expression. Metformin is one of these. As the first line of defense in the treatment of Type II diabetes, Metformin is widely considered a safe & effective insulin sensitizer. Unlike most pharmaceutical agents, which typically result in at least some degree of internal damage/dysfunction when used as directed, Metformin’s side effect profile is extremely mild, with significantly more positive side effects than negative. In the overwhelming majority of cases, Metformin can be used problem-free while greatly increasing insulin sensitivity.
Although many are unaware, T3 also has insulin sensitizing and Glut-4 up-regulating effects. This does not justify the abuse of the drug, as excessive dosages of T3 are injurious to one’s BB’ing progress through excessive calorie burning, but thyroid deficiency will have a negative effect on the body’s ability to use insulin properly. In fact, T3 will continue to provide additional insulin sensitizing & Glut-4 up-regulating benefits as one moves from the low/mid-normal range into the upper-range of normal. So, while T3 is not typically viewed as an insulin sensitizer/Glut-4 up-regulator, it can have meaningful benefits in this area, especially for those who are currently deficient. Therefore, optimizing one’s T3 levels (high end of normal) is probably a good idea.
IGF-1 is commonly considered to be an insulin sensitizer by those in the BB’ing community, but is it? When looking at the available studies, it is revealed that IGF-1 can act as either a sensitizer or contribute to insulin resistance. Research shows a low-normal, as well as high-normal IGF-1 level can negatively affect insulin sensitivity. Therefore, these stipulations make IGF-1 unviable as a sensitizer for anyone but those with below-normal levels.
When it comes to OTC supplements, we are provided with so many selections that choosing can be difficult, but some of the best are as follows: Alpha lipoic acid, 4-hydroxyisoleucine, vanadyl sulfate, cinnamon, and apple cider vinegar. Many of these products work through different mechanisms, providing a synergistic effect when used in combination. Let’s look at a few of them. ALA (alpha lipoic acid) boasts an impressive research-based resume. With literally dozens of clinical studies validating its effectiveness, ALA can rightfully claim to be one of the best OTC insulin sensitizer available. The combination of effectiveness, price, and vast clinical research makes this supplement a no-brainer. Some German studies have demonstrated the ability of evening primrose oil to act as a potentiator, boosting the effectiveness of ALA when taken together.
While much newer than ALA, 4-hydroxyisoleucine (4-HIL for short) has caused quite a stir in the short time it has been on the market. A leucine derivative, 4-HIL’s insulin sensitizing properties have recently caught the eye of diabetic researchers as a possible therapy for diabetes. 4-HIL is one of the better OTC insulin sensitizing supps out there. While it is not quit as inexpensive as ALA, it can still be purchased at a relatively low price by online distributors.
The next product on the list, chromium picolinate, plays an itegral role in the regulation of blood sugar at a foundational level, but is not considered an insulin sensitizer or mimetic, per say. In fact, taking more than needed can actually decrease insulin sensitivity by up to 25% (according to one study) when taken by individuals with normal chromium levels. This supplement is only beneficial for those with chromium deficiencies.
Like all the other supplements mentioned previously, the use of vanadyl sulfate for improving insulin sensitivity is supported by substantial clinical research. Originally introduced to the BB’ing community by EAS back in the early-mid 90’s, vanadyl sulfate was marketed as a natural glucose disposal agent capable of increasing glycogen synthesis and improving “the pump”. The marketing hype generated some initial interest, but it trailed off quickly, leading to poor sales and the product’s eventual demise. However, the problem wasn’t with the product—it was with the marketing and perhaps, the targeted demographic. Vanadyl sulfate never should have been marketed as a pump-inducing, stand-alone performance enhancer, as this product just isn’t capable of providing those kind of acute, physique altering benefits.
The value of this compound lies in its ability to help improve the uptake and utilization of everything we eat, leading to long-term benefits in every area of our BB’ing performance. This is especially valuable for insulin & GH using BB’rs, as many of these individuals suffer from clinical insulin resistance or impaired blood glucose regulation to varying degrees. Vanadyl sulfate works primarily by enhancing insulin-mediated glucose uptake and inhibiting hepatic glucose production. The end result is improved insulin sensitivity in combination with increased glycogen synthesis. In one particular study, glycogen synthesis accounted for 80% of the increased rate of glucose disposal witnessed with vanadyl sulfate administration, while glycogen synthase (the enzyme responsible for converting glucose to glycogen), was lowered by approximately 30%. This dramatic increase in the rate of glycogen production, in spite of decreased levels of glycogen synthase, indicates an improvement in glycogen synthase efficiency via enhanced insulin sensitivity.
Either by adding it to your food or when taken in supplement form, cinnamon has been shown to result in significant improvements insulin sensitivity and resting blood glucose levels (18-29%), as well as total cholesterol (12-26%) and LDL cholesterol (7-27%). This effect is largely due to the Type A polyphenols that reside naturally in cinnamon. Keep in mind that it takes several weeks of daily cinnamon supplementation in order to maximize benefits.
Another common household item, vinegar, has been shown to improve insulin sensitivity in insulin resistant subjects. Scientists speculate that vinegar may work in a similar manner to Metformin, as acetic acid has been shown to suppress disaccharidase activity and raise glucose-6-phosphate concentrations in skeletal muscle. Although the effects of vinegar are rather modest in comparison to say, Metformin, I consider it one of the better sensitizers when evaluated in terms of cost-effectiveness. 16 ounces of apple cider vinegar, which provides slightly over 22 twenty gram servings (the dose used in some studies), can be purchased for only a few dollars, making it affordable for nearly everyone. On top of that, vinegar consumption helps regulate the body’s PH balance in favor of alkalinity.
Systemic acidity—a condition which occurs primarily as a result of an imbalanced diet, has been implicated in literally 100’s of health problems and goes completely undetected by most. In fact, some doctors have attributed nearly all disease to excessive acidity, as it damages and impairs the functioning of virtually every system in our body. Foods such as meat, eggs, diary, processed grains, and sugars are all acidic, as are coffee, soft drinks, artificial sweeteners, and numerous OTC & prescription drugs. The typical American diet is heavily tipped in favor of acid-forming foods and a result, the health of the American public has deteriorated greatly. Unfortunately, many BB’rs believe that “eating clean” means they are eating healthy, but this is often the farthest thing from the truth. In fact, most BB’ing diets are extremely acidic, consisting almost solely of meat, various complex carbs (many of which are refined), and sugars. Of course, many BB’rs also regularly consume coffee, artificial sweeteners, and several other acid-forming drugs & supplements.
Vegetables (especially green vegetables) are our primary source of alkaline food, yet most BB’rs consume barely any of them—at least in proportion to the massive amount of acid-forming foods they eat on a daily basis. It is estimated that in order to restore/maintain a healthy PH balance, the diet should be tailored to contain 80% alkaline foods and 20% acid-forming foods. Although not everyone agrees on this ratio, they are all within the same general vicinity. I realize I have gotten off-track a bit here, but with apple cider vinegar being useful for both insulin sensitivity and restoring PH balance—two common ailments experienced by BB’rs that can potentially impact our health in a multitude of ways, I wanted to take a moment to elaborate on this inexpensive, yet highly beneficial food source.
There are many other OTC supplements out there which can lead to various improvements in insulin sensitivity. Some are quite good, while others do little to nothing, despite manufacturer claims. I recommend you use only those products which have been clinically validated by multiple, well-controlled studies, just as the products above have. There are others which are worthy of inclusion in this article, but due to time limitations, we will stop here.
In the following article, we will learn how to incorporate all of the previously discussed elements into a single program, while introducing some additional variables designed to further augment its effectiveness.
Part 3 coming soon…