Regardless of how little biology you understand, the term growth factors gives you a good idea of what they do. While there are numerous growth factors, for bodybuilders and their quest to build bigger muscles, it all comes down to insulin like growth factor-1 (IGF-1). Knowing how to maximize this growth factor can help you add the kind of muscular size that will turn heads everywhere you go.


THE 411 ON IGF-1

As the name implies, IGF-1 is a protein with a similar structure to insulin. Its presence in the body was first discovered in 1957 when scientists realized that growth hormone (GH) seemed to have another chemical that mediated its anabolic effects—somatomedin C, or as it’s now known, insulin-like growth factor-1 (IGF-1).

Originally, it was thought that IGF-1 was produced and released from the liver. From there, it is carried in the blood by one of its binding proteins to various tissues, such as muscle cells, where it instigates growth. While there are a host of IGF-1 binding proteins (IGFBPs), the two most important ones are IGFBP-1 and IGFBP-3. Most of the IGF-1 released from the liver is bound to IGFBP-3. This binding protein appears to facilitate IGF-1’s anabolic actions. IGFBP-1, on the other hand, appears to negate IGF-1’s anabolic actions.

It was later realized that IGF-1 is also produced in the muscle cells themselves. Muscle actually produces three differ
ent kinds of IGF-1: 1) IGF-1Ea, IGF-1Eb, and IGF-1Ec. IGF-1ea is similar to the IGF-1 produced by the liver, while IGF-1Ec is better known as mechano-growth factor (MGF) due to the fact that it is expressed in muscle following mechanical stress, for example, from weightlifting. While the exact mechanism behind how these growth factors are produced in the muscle is still debatable, both circulating GH and testosterone levels may play a key role in increasing their expression in muscle. 

The main way that circulating IGF-1 is believed to kick-start muscle growth is by binding to its receptor found on the membrane of muscle cells, where it sets off a cascade of events that leads to an increase in muscle protein synthesis—that is, a buildup of the protein that makes muscle and therefore results in growth. Binding IGF-1 to its receptor also decreases muscle protein breakdown. Muscle protein is constantly being shredded and built up. A decrease in muscle protein breakdown with a boost in its buildup (synthesis) leads to growth. Circulating IGF-1 has also been found to provide a brain-boosting affect, which may be the link between exercise and better brain function.


MGF, which is produced locally in the muscle cells, appears to stimulate muscle growth through an entirely different process than circulating IGF-1. It does so by stimulating satellite cells, which are dormant muscle cells, or muscle stem cells, that sit outside muscle fibers. When the muscle fiber is damaged, such as during an intense workout, these satellite cells move into the muscle fiber and mature, growing bigger and stronger. Since they are actual cells,
they each contain a nucleus, and
so they bring along new nuclei to the muscle fiber. Because the nuclei are where the process of muscle protein synthesis is initiated, the more nuclei a muscle has, the bigger it can become. The increased number of nuclei in muscles has recently been found to be the reason for “muscle memory,” or the ability of someone who has previously trained consistently and built up muscle mass, to gain it back rapidly after a layoff. IGF-1Ea produced locally in muscle fibers, on the other hand, appears to act in a similar manner to the IGF-1 produced by the liver. That means it also instigates the process of muscle protein synthesis and decreases muscle breakdown.

(L) Bettmann (M) Sunset Boulevard (R) Steve Granitz / Getty


Some recent research on IGF-1 suggests that circulating IGF-1 is not critical for muscle growth. And some bodybuilding experts out there are latching on to these few and limited studies and stating that circulating IGF-1 is inconsequential to muscle growth and that only locally expressed IGF-1s from the muscle are important. As one of the few bodybuilding experts who has actu
ally worked with both circulating IGF-1 and muscle IGF-1s in the laboratories at the University of Connecticut and Yale University School of Medicine, I feel that I am well qualified to tell you that it is just too early to discount circulating IGF-1. The truth of the matter on muscle hypertrophy and growth factors is that no one knows with certainty how muscle grows. No one. Not me, not any scientist at Yale University or Harvard, or any bodybuilding expert or guru out there. What is known is that the IGF-1s appear to be players in the process of muscle growth. Locally produced MGF and IGF-1Ea likely play a very important role in muscle growth. After all, if your muscle fibers have a limited number of nuclei, they can grow only so big. The more nuclei the muscle fiber has, the greater its growth potential.

A few limited studies done in either untrained individuals or in animals suggest that circulating IGF-1 doesn’t play a key role in muscle growth. But other studies suggest that circulating IGF-1 levels may be important, especially for trained lifters, such as most FLEX readers. And medical research shows that patients with GH insensitivity (Laron syndrome) increase muscle mass when their circulating IGF-1 levels are increased.

It is still way too early to interpret the data. So don’t disregard circulating IGF-1 just yet. Currently, both circulating IGF-1 and the IGF-1s produced in the muscle seem to play roles in building muscle. While MGF brings more nuclei into the muscle fiber, circulating IGF-1 and IGF-1Ea can increase the protein synthesis that occurs from those nuclei, not to mention decrease muscle breakdown. This tag-team effort can lead to bigger and stronger muscles.

Close the books and put this new information to good use with this breakdown of the proper reps and rest