Myostatin Update

Interactions between myostatin and anabolic hormones.

by Jerry Brainum

The word myostatin literally means “stoppage of muscle growth,” and that’s precisely the protein’s function. It was first isolated by scientists from Johns Hopkins University in 1997. Early studies of animals born without the genes that code for myostatin production clearly demonstrated that myostatin regulates muscle growth. The animals showed extensive muscle hypertrophy and seemed devoid of bodyfat.

The researchers followed up by selectively breeding rats that lacked myostatin. The rats had huge muscles, just like animals that naturally lacked myostatin. Subsequent research revealed that myostatin works mainly by inhibiting the activity of satellite cells, which are stem cells vital for muscle repair and hypertrophy.

More recent studies have focused on interactions between myostatin and anabolic hormones, such as growth hormone and testosterone. One recent experiment examined muscle growth factors and myostatin in rats that either had intact pituitary glands or had their pituitary glands removed—the pituitary gland, located in the brain, produces growth hormone. The rats were given GH alone, testosterone and sesame oil or a combination of testosterone and GH. Athletes and bodybuilders frequently combine GH and testosterone, hoping for synergistic anabolic benefits.

The results: Rats with pituitary glands gained muscle mass when given GH alone or with testosterone. The GH alone stimulated a significant rise in anabolic factors, without affecting myostatin. That effect, however, was eliminated when testosterone was added.

The study suggests that myostatin counteracts the anabolic effects of GH and IGF-1. That may also explain the frequent observation that using GH alone produces poor anabolic results. The large increase of GH boosts myostatin and effectively curtails muscle growth.

Because testosterone blunts myostatin release in muscle, it would seem that combining testosterone with GH would offset the increased myostatin release.

This study, however, showed that testosterone also blunts IGF-1, which is the primary anabolic effector of GH in muscle. The authors suggest that anabolic effects produced by a combination of GH and testosterone or anabolic steroids would be entirely due to the steroid use.

A new study that had humans as subjects revealed the development of a more direct assay of free or active myostatin in the body. Previous studies had measured the activity of myostatin bound to proteins. Using this new assay, the study noted that younger men had more myostatin than older men.

The researchers found no relationship between body mass and myostatin in either younger or older men. When men are given testosterone, however, myostatin increases 56 days later and returns to baseline after 20 weeks of testosterone treatment.

Why would myostatin rise with continuing testosterone treatment? One suggestion is that the anabolic effects of testosterone spur the release of myostatin as a brake on excessive muscle growth. That’s more apparent in younger men, who are more prone to muscle growth than older men. The body reduces myostatin in older men to counter excessive loss of muscle.

Myostatin also counters the anabolic activity of IGF-1. Bodybuilders who use large doses of GH, which stimulates IGF-1, often experience enlarged internal organs because of that. Normally, myostatin would counter the effect, but the combination of large doses of GH and testosterone blunts myostatin, which leads to organ growth and a bloated abdomen.

Having a large percentage of bodyfat makes it harder to build muscle. Bodyfat level is often associated with insulin resistance. When combined with a great amount of amino acids in the blood, insulin brings on muscle protein synthesis.

Alone, insulin inhibits excessive muscle protein breakdown and counters the catabolic effects of cortisol. Insulin resistance adversely affects those processes. A new study suggests an even more sinister mechanism.

The researchers examined the myostatin levels in extremely obese women and found that their muscle cells produced a nearly threefold increase in myostatin. Isolated-cell studies show that myostatin itself may inhibit the uptake of glucose into cells, which adds to the insulin resistance associated with excess bodyfat. Conversely, extreme calorie restriction and starvation also boost myostatin activity in muscle. The authors suggest that insulin resistance boosts myostatin because of the inhibited insulin activity, which leads to cellular starvation. Underscoring that suggestion is the fact that a loss of muscle mass is common with type 2 diabetes.

While researchers are exploring several drugs as potential inhibitors of myostatin, bodybuilders have already been exposed to a few myostatin-inhibiting supplements. One, released a few years ago, was based on a seaweed that locked on to myostatin in a test tube. Sadly, it completely failed to work in people, but that didn’t prevent purveyors of myostatin blockers from claiming to have produced more effective versions. One company sells what it calls follistatin, an established myostatin blocker, but studies that have used follistatin have involved gene therapy or directly injecting follistatin into animal bodies. The newer follistatin supplements are derived from eggs, and there is zero proof that they’re any more effective than the seaweed-based versions.

What does inhibit myostatin synthesis and release is weight training. Studies show that consistent training blunts myostatin activity in the body. One study found that eccentric muscle contractions—lowering the weight, which results in greater damage to muscle fibers—lead to a greater release of myostatin, but only in men. Women are protected from that because their bodies have more estrogen.4 Stretching also increases myostatin release, but that’s countered by the release of several muscle growth factors.

Finally, racial characteristics may influence myostatin behavior and muscle gains in humans. Several studies have found that many black people have naturally higher muscle density, strength, muscle mass and percentage of type 2 muscle fibers than Caucasians (which raises the question: Where is Caucasia?). In a recent study that compared ethnic groups, the black subjects showed gene activity consistent with lower myostatin than the other groups. That resulted in greater upper-arm gains in the black subjects after 12 weeks of training.

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