From Ergo Log
If you know a little bit about sports supplements, it sounds like a bad idea: combining leucine and HMB to maximise muscle growth. Because HMB is a metabolite of leucine it would seem unlikely that there would be synergy between the two. But according to researchers at the University of Nottingham in England and McMaster University in Canada, the world of muscle physiology is more complex than we thought.
HMB and leucine are two of the preferred supplements among strength athletes. Several studies have confirmed their effect and side effects are unlikely to occur when they are taken in normal amounts. HMB received negative publicity for a while, but a continuous stream of positive studies and empirical evidence has changed matters.
Leucine is the substance through which muscle cells 'see' amino acids. Of all amino acids, leucine is the one that metabolises most easily. So maybe muscle cells not only 'see' leucine but also its metabolites, such as KIC and HMB. If the concentration of leucine and its metabolites [the metabolism sequence for leucine is shown below; click on the diagram for a larger version] rises in the muscle cell, then the cell revs up its anabolic machinery.
Until recently, no studies had been published that compare the anabolic effects of HMB and leucine. The two groups of researchers have rectified this. The ones in Nottingham looked at HMB and those in Canada looked at leucine.
The researchers gave sedentary students 2.42 g Free Acid HMB or 3.42 g leucine in the morning on an empty stomach and then monitored the anabolic activity in their muscles using labeled amino acids. The data they collected is represented in the two figures below.
Below left shows the effect of leucine and HMB on the Myofibrillar FSR [in simple language: the synthesis of muscle proteins]. Leucine boosted muscle protein synthesis by 110 percent; HMB boosted it by 70 percent. Strictly speaking the difference between the muscle building effect of HMB and that of leucine was not statistically significant.
Above right shows the effect of HMB on muscle breakdown [MPB]. The researchers didn't look at the anticatabolic effect of leucine. They were already aware that leucine only has an indirect anticatabolic effect. Leucine boosts the synthesis of insulin, and it is via this hormone that it has an anticatabolic effect. If you block the insulin level rise by giving leucine, then the anticatabolic stimulus of the leucine is reduced. [Am J Physiol Endocrinol Metab. 2008 Sep;295(3):E595-604.]
Leucine and HMB didn't work in exactly the same way in the muscle cells. Both substances activated the signal protein AKT, but not at the same time and to the same degree: leucine created a substantial activation of short duration, HMB a moderately intensive but longer activation.
In addition, leucine resulted in a better activation of the anabolic signal molecule p70S6K than HMB did.
So leucine and HMB both enhance muscle growth, but not using the same mechanism, the researchers conclude. That might mean that you can boost muscle building by combining leucine and HMB.
J Physiol. 2013 Jun 1;591(Pt 11):2911-23.