Wednesday, November 23, 2011

HMB Exhibits Differential Effects on ATP and Glycogen Content of Fast & Slow Twitch Fibers and Maximizes Tetanic Force Development in Rodent Study

Image 1: This is where HMB could actually make a difference, the two more reps, the one more sprint, which after weeks and months of training can decide over victory or defeat.
Sometimes, or I should say, time and again (!), it amazes me how the same people who are willing to invest hundreds of bucks in a supplement, which (according to the patent holder) "has been shown in scientitfic studies" (which were conducted by the researcher and a buddy of his at a remote lab, only to file the patent) to "increase testosterone by up to 147.34%", keep telling me that they "would never waste their hard earned money on supplements like HMB..." hello? Am I missing something, here? I mean, right; HMB does not produce the steroid-like effects the same sort of shady businessmen who are now promoting a new natural testosterone booster as legal alternative to Anavar on a monthly base once claimed it would have, but in all  honesty, the scientific research on HMB is by far more promising than the mostly non-existent research on 99% of the "legal anabolics" out there.

HMB works, we just don't know exactly how and for whom

As Dr. Connelly pointed out on the last BodyRX Show (highly recommended, especially for Layne's intellectual exchange with Dr. Jeff Volek), it stands out of question that HMB works. There are in fact more than a dozen of studies which show that supplementation with adequate amounts of this leucine metabolite has anti-catabolic effects in various conditions of skeletal muscle atrophy (Nissen. 2003; Smith. 2005). What  is still debatable, though is whether and to which extent athletes, in general, and bodybuilders, in particular can benefit from these effects. In view of the increasing awareness of the importance of leucine, the metabolic precursor of b-hydroxy-b-methylbutyrate (HMB), most athletes in this subgroup probably consume somwhere between 20-30g of leucine from the 300g of protein they are feeding themselves in the form of protein shakes and lean meats alone (with reference to the data that is presented in figure 1 it is noteworthy that the comparison Nissen made is not "fair", because the many of the HMB studies were conducted with "sick" people, while the majority of studies on protein supplements used either healthy people or athletes). With an average conversion rate of ~5% (of dietary leucine), we would have to estimate their daily HMB "production" to roughly 1.0-1.5g, which is interestingly at the lower range of what has been shown to ameliorate muscle wasting in cancer cachexia studies (Eley. 2007; Kovarik. 2010).
Figure 1: Calculated effect sizes of creatine, HMB, chromium, androstendione, DHEA and protein supplements on strength and lean mass gains (adapted from meta-review by Nissen et al.; Nissen. 2003)
And even if we discard the question of whether or not additional HMB is really necessary on a high protein diet and whether or not respective dietary differences could explain the negative results from some, yet by no means all, trials with professional athletes, we must still admit that even in those cases where it does work, we (i.e. scientists) do not really understand how HMB does its anti-proteolytic magic. The results of a recently published study from scientists from the Institute of Biomedical Science at the University of Sao Paulo, could thusly be of particular importance, as this is - at least to my mind - the first study to investigate the effects HMB supplementation had on ATP and glycogen levels, citrate synthase and changes in the contractive properties of individual muscle fibers (Pinheiro. 2011).
Figure 2: Changes (vs. placebo) in ATP and glycogen content, as well as citrate synthesis in red and white portion of rat gastrocnemius muscle after 4 week supplementation with 320mg/kg HMB (data adapted from Pinheiro. 2011)
The data in figure 2 shows, that after 4 weeks of daily supplementation with 320mg/kg HMB (in the study the usual calcium salt, you can buy in bulk on the Internet was used), the ATP and glycogen levels in the gastrocnemius muscle of the rats were profoundly elevated. In that, it is particularly interesting that the leucine metabolite had differential effects on the slow-twitch oxidative red portion of the muscle and the fast-twitch glycolytic white portion: In the slow twitch fibers the increase in ATP is 10x higher than it is in the fast twitch fibers, where the +400% increase in glycogen content should yet provide a similarly extensive buffer of readily (yet not immediately) available energy. Moreover, the increase in citrate synthesis (+67%) in the slow twitch fibers suggests that part of this effect was mediated by an "increased lipid availability due to increased lipolysis", or, put simply, by an increased oxidation of fatty acids to generate more ATP.
Figure 3: Tetanic force production (normalized to muscle weight) in rats receiving 320mg/kg HMB or placebo for 4-weeks; successive tetanic contractions were evoked at 100 Hz each 10 s of interval (data adapted from Pinheiro. 2011)
These increase in both readily available energy stores and the ability to replenish the former via fatty acid oxidation, is - according to Pinheiro et al. - also the underlying reason for the "increase in resistance to fatique" the scientists observed when they subjected the rat muscle to electrical stimulation in order to evaluate the tetanic (=constantly contracting) force production (cf. figure 3). Contrary to the twitch force, which was identical in supplemented and non-supplemented rats, the tetanic force production (normalized for either muscle weight or muscle cross-sectional area) increased by +17% (p<0.05; meaning that the chance that this was mere coincidence is <5%).

Fine!? Now, tell me: Is HMB worth it?

In view of the fact that neither the muscle size (cross-sectional area) nor the lean mass of the rodents in the HMB group differed from their placebo supplemented peers (btw. the animals were not "trained" in the course of the 4-week study), we must conclude that the effects of HMB, similar to those of creatine, are not what you would call "immediately anabolic". In a real world training scenario the metabolic advantage (increased ATP stores, increased glycogen stores and increased oxidative capacity) the rats in the HMB group gained over the 4-week study period, would allow trainees to do those 1-2 reps more which in weeks and months would then translate into this one additional pound of muscle or the 10th of a second that can make the difference between victory or defeat - whether those 1-2 reps are worth the roughly 64$ it would cost to copy the supplementation regimen used in the study (320mg/kg in rats would equate to 53mg/kg per day for humans), does yet depend on who you are, what you want to achieve and how much money you have to spend... and if you do not have your regular diet and training in check, don't even think of HMB (let alone one of those "test boosters" ;-)