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Insulin and Muscle Mass

The combination of insulin, testosterone and growth hormone is primarily responsible for the monstrous muscle size many pro bodybuilders display.

Why do we lose muscle as we age? The obvious answer for most people is lack of sufficient exercise. Muscles work on a use-it-or-lose-it basis, as do most of the organs and tissues of the body. Without the stimulation provided by exercise, the neuromuscular connections between the brain and the muscular system gradually fade, and muscles atrophy, or shrink. The loss of muscle mainly affects the type 2 muscle fibers, those linked to muscular size and strength, and the balance between type 1s, the weaker, so-called endurance muscle fibers, and the more powerful type 2 fibers veers toward a dominance of type 1s. That explains much of the frailty associated with the aging process.

Besides a lack of exercise that places stress on type 2 fibers, namely resistance exercise, such as weight training, a major cause of muscle loss with aging is the gradual decline in the synthesis and secretion of anabolic hormones, including testosterone, growth hormone and insulin. There’s crossover between anabolic hormones and exercise, since regular exercise helps maintain measures of the hormones with age. Inevitably, of course, they drop to some extent in most people.

People who are clinically deficient in any of the anabolic hormones often experience dramatic beneficial changes in body composition and strength when the missing hormones are supplied. That explains the current popularity of growth hormone therapy to treat aging symptoms. Giving GH to an older person who’s deficient in it results in significant improvements in such factors as skin thickness and bodyfat, which in turn often leads to a subjective feeling of turning back the clock.

Testosterone is even more important for those who want to maintain or develop muscle with age. Without adequate testosterone, you simply won’t make any gains. Testosterone begins to decline about age 40, as does GH, while muscle gains begin to significantly slow. The drop of testosterone—that is, T—with age is most noticeable in those who are sedentary, but it also affects many of those still engaged in regular exercise. I’ve spoken with countless men over the years who were diagnosed with low T. In those who also lifted weights regularly, taking supplemental testosterone produced often dramatic changes in body composition and muscular strength.

While testosterone and growth hormone therapy are commonly used to treat symptoms of aging, the only accepted medical use for insulin is to treat diabetes mellitus. Type 1 diabetics lack the pancreatic cells to synthesize insulin, so they must take insulin injections. The more common type of diabetes, type 2, can often be treated with oral medications, exercise and diet, although in some cases insulin injections are required to control elevated blood glucose.

In recent years athletes have used insulin for several reasons. A common side effect of using large doses of GH is elevated blood glucose, which can be controlled with an insulin-injection kicker. Insulin also triggers amino acid uptake into muscle for use in muscle protein synthesis. Insulin activates the primary enzyme that converts carbohydrate into glycogen, which aids muscle recovery after training and gives the muscle a fuller appearance to muscle; each gram of glycogen is stored with 2.7 grams of water.

So, is insulin an anabolic hormone? It certainly is if you want to gain bodyfat. Indeed, insulin is the most potent fat-stimulating hormone in the body. It’s often referred to as a “storage hormone” because it promotes energy storage both as fat and as carbohydrate in the form of glycogen. In relation to muscle, insulin is conditionally anabolic, meaning that in the presence of large amounts of amino acids in the blood, it aids in amino acid uptake into muscle, which facilitates muscle protein synthesis, a definite anabolic effect.

Absent a high concentration of amino acids in the blood, insulin’s chief role in muscle is anticatabolic, meaning it prevents the loss of muscle, an indirect anabolic effect. Several studies have shown that insulin has a synergistic anabolic effect when combined with testosterone and growth hormone. That explains the popularity with athletes of that particular trio of anabolic hormones, a combination largely responsible for the monstrous muscle size many pro bodybuilders display. On the flip side, the combo is the culprit behind many formerly rare side effects you see these days, such as bloated abdomens.

Some recent studies have found an interesting effect related to insulin and muscle loss with aging. It seems that aging muscles become insulin resistant. While insulin resistance is the hallmark of diabetes and is even known as prediabetes, the type of resistance that occurs in older people is distinct. All forms of diabetes-related insulin resistance cause elevated blood glucose, but older people experience resistance even if they have normal blood glucose. The point is, without the anticatabolic effects of insulin, they lose muscle. Emerging scientific thought postulates that the insulin resistance of aging may be the primary cause of muscle mass loss in older people.

One study of older people found that doing aerobic exercise restored a normal protein anabolic response to physiologically elevated insulin in those with normal glucose tolerance.1 In another study older people who were given more insulin than is normally produced after a meal showed restoration of muscle protein synthesis and anabolic signaling comparable to those seen in younger people. When the older people injected insulin in amounts comparable to that produced after a meal, no muscle protein synthesis occurred. The insulin improved amino acid uptake because of vasodilation, or expansion, of blood vessels, which led to efficient delivery of amino acids to muscle.

In short, the defect that causes insulin resistance with aging not related to diabetes is caused by damage to the lining of blood vessels, or endothelium. A blood vessel with a damaged endothelium can’t sufficiently dilate to properly distribute blood to tissues, including muscle. When large amounts of insulin are present, they bypass the defect and let the blood vessel expand, thereby restoring optimal circulation and nutrient delivery.

The primary factor that dilates blood vessels is nitric oxide, which is synthesized from the amino acid L-arginine. Many sports supplements touted to be NO boosters contain forms of arginine as the primary ingredient. The dose of arginine in most of those products is four to five grams because doses of arginine more than nine grams often cause nausea.

In contrast, the studies that showed a boost of NO from arginine involved intravenous administration in doses of 18 grams or more. Yet many people who have used NO supplements claim to get a noticeable muscle pump effect that would be indicative of increased blood flow. The answer to that apparent paradox is that many NO supplements also contain simple carbohydrates, which rapidly trigger insulin secretion. The insulin, rather than the arginine, is likely the source of the pumped sensation.

So insulin’s ability to dilate blood vessels is related to rapid NO synthesis. From that perspective, it appears that the NO products are actually increasing NO, but the effect is due to their carb rather than arginine content; a few case studies have identified side effects in users of NO supplements that point to elevated NO. While no one wants to experience side effects, the fact that they occurred means that the products really worked. On the other hand, as the source was a rapid insulin-and-NO effect, you could get the same effect from taking a large amount of amino acids and a simple carb—that is, a postworkout recovery supplement. Since dilation of blood vessels combined with a high concentration of amino acids in the blood makes insulin anabolic rather than just anticatabolic, the use of simple carbs with concentrated aminos or a rapidly acting protein, such as hydrolyzed whey, makes a lot of sense if you’re after muscle gains.

As for older people who are insulin resistant, a recent study found that giving them insulin restored all the muscle anabolic-signaling processes that are blunted with aging. In the subjects insulin fully restored the anabolic processes in muscle, which would enable them to both preserve and build muscle. That requires a dose of insulin twice what the body produces after a meal.

A few unanswered questions remain. For example, exercise reverses age-related insulin resistance because the shearing effect of increased blood flow produced by exercise induces NO synthesis. The increased NO, in turn, widens the blood vessels and enables insulin to more efficiently deliver nutrients to muscle. Most of the older people who showed age-related insulin resistance had normal blood glucose and weren’t diabetic, but they were sedentary. Does that mean that regular exercise, including both weight training and aerobics, can prevent age-related insulin resistance? Preliminary data show that to be precisely what happens. It also means that without consistent training, age-related insulin resistance will ensue, followed by a loss of muscle.

Editor’s note: Jerry Brainum has been an exercise and nutrition researcher and journalist for more than 25 years. He’s worked with pro bodybuilders as well as many Olympic and professional athletes. To get his new e-book, Natural Anabolics—Nutrients, Compounds and Supplements That Can Accelerate Muscle Growth Without Drugs, visit  IM

1 Fujita, S., et al. (2007). Aerobic exercise overcomes the age-related insulin resistance of muscle protein metabolism by improving endothelial function and Akt/mammalian target of rapamycin signaling. Diabetes. 56:1615-22.

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