Beta-hydroxy-beta-methylbutyrate, abbreviated HMB, is found naturally in living matter as a metabolite of the essential amino acid L-leucine. There is preliminary evidence suggesting HMB may have anticatabolic, as well as immunomodulatory, properties. As a nutritional supplement, it is popular among athletes engaged in strenuous physical activity. HMB is also known as hydroxymethylbutyrate, beta-hydroxyisovalerate and 3-hydroxyisovalerate.
It is hypothesized that HMB supplements may signal the body to slow down destruction of muscle tissue. Although the evidence is based on small studies, HMB may enhance strength and muscle mass in response to weight training and may help prevent muscle damage during prolonged exercise. Some studies indicate that HMB may have greater effect when used with creatine. In addition, it may help prevent wasting in people with AIDS — particularly in combination with amino acids such as glutamine (See the Encyclopedia on this site for more information about HMB).
As is the goal of many of today's top supplements, including Creatine Monohydrate and L-Glutamine, HMB is used in an attempt to boost strength levels, enhance gains in muscle size and strength, and prevent muscle tissue breakdown that can occur subsequent to strenuous exercise. Scientists are not sure exactly how HMB works, but it is believed that this amino acid metabolite aids in the body's attempts to minimize protein breakdown that can occur subsequent to intense exercise. Therefore, by minimizing the breakdown of protein, or muscle, HMB may help the body recover faster from exercise which can lead to quicker and greater gains in muscle size and strength.
The mechanism of HMB's possible actions is unknown. There is, however, speculation. The branched-chain amino acids L-leucine, L-isoleucine and L-valine are known to be beneficial to catabolic patients (sepsis, trauma, burns, etc.) by improving hepatic protein synthesis and nitrogen economy. These amino acids make up about one-third of muscle protein. Of these amino acids, L-leucine has the highest oxidation rate. Further, L-leucine has been shown to stimulate protein synthesis in muscle, and decreases in leucine levels in skeletal muscle and in serum have been noted following exhaustive exercise. However, L-leucine supplementation has not been found to have a significant effect on athletic performance. It has been speculated that the L-leucine metabolite HMB may be responsible for the inhibitory effect of L-leucine on protein breakdown. How this may happen is unknown.
In pigs, HMB is produced from alpha-ketoisocaproate, a metabolite of L-leucine, via the enzyme alpha-ketoisocarproate dioxygenase, an enzyme that requires oxygen and iron for its activity. This pathway, located in the cytosol, may also exist in humans. L-leucine is also metabolized in mitochondria to produce HMB in the form of HMB-coenzyme A (HMB-CoA), rather than free HMB.