How HMB Works

The leucine metabolite HMB, according to its discoverers, has a mild anticatabolic and anabolic effect because HMB stimulates the synthesis of cholesterol – a component of cell membranes – in the muscle cells. According to an animal study done at the Federal University of Sao Paulo, the way in which HMB works is more complex. The Brazilians discovered that HMB inhibits cortisol and activates the classic anabolic signal molecule mTOR.

Surprisingly little research has been done on the mechanism through which HMB works, and the Brazilians decided to try and fill this knowledge gap by doing an animal study. They gave male rats a daily oral dose of 340 mg HMB per kg bodyweight every day for a month. This corresponds to a human dose of 3-6 g per day.

During this period the rats did indeed develop more muscles than those in the control group, which had not been given HMB. The researchers found no effects on fat mass, although they don’t exclude the possibility of the HMB having reduced fat deposits somewhere in the body where they hadn’t looked.

EDL: extensor digitorum longus muscle, RPAT: retroperitoneal adipose tissue, MEAT: mesenteric adipose tissue.

The concentration of the stress hormone cortisol decreased by a significant amount in the animals’ blood. The testosterone concentration rose, but not significantly. The fasting insulin level rose by 245 percent.

HMB boosted the production of the anabolic signal molecule mTOR by 430 percent in the muscle cells of the lab animals. The number of p70S6K molecules did not increase, but the molecules became 470 percent more active. The researchers found no effect on GLUT-4 or AMPK or on the anabolic signal molecule combo Akt/PKB.

Czech researchers announced in 2009 that HMB supplementation boosted the synthesis of protein in the liver of lab animals. [Food Chem Toxicol. 2009 Jan; 47(1): 255-9.] The Brazilians discovered how this was possible: HMB boosts the synthesis of the insulin receptor in the liver, but doesn’t do this in the muscle cells.

“HMB treatment leads to skeletal muscle hypertrophy via increases in mTOR expression and decreases in serum corticosterone concentrations”, the Brazilians conclude. “Our results suggest that HMB supplementation can be used to increase muscle mass without adverse health effects.”