Monday, July 29, 2013

HMB Increases Lean Mass Loss (+22%) + Hampers Fat Loss (-18%) from Diet + Overtraining. HED of ~6g/Day Does Yet Retain Muscle Strength & Fiber Size in Fast Twitch Muscles

Dr. Jekyll & Mr. Hyde - Is HMB have another janus-faced supplement ?
I know "mice are no little men", ... I don't have to be reminded of that. Thank you. So, if you are not interested in today's SuppVersity article, just come back tomorrow for another article without our hairy friends in it... You are still here? Ok, then let's see what the researchers at the Florida State University have to tell us about the effects of HMB supplementation on trained vs.  overtrained and energy deprived rodents. Even though, the significance of the results for mammals with less body hair such as human beings is not clear, we may still expect similar trends, yet not identical numbers on the weight, muscle and fat loss, as well as parameters that were assessed in the study at hand.

Some details on the experimental protocol

The scientists started out with a total of 61 animals that were initially divided into three groups. The animals in the groups were either sedentary, had to exercise for 1h (endurance) 3x/week or followed the same exercise protocol, yet with an addition of 0.5g/kg body of HMB in their diets (the human equivalent dose would be 6-7g/day depending on your body weight).

After a four-week run-in phase there was an additional differentiation for the non-sedentary rats which leaves us with the following four groups:
    Table 1: Ingredients of the diets in the four groups.(Parks. 2013)
  • ALT: ad libitum fed fed + exercise (1h/d for 3d/wk)
  • ALTH: same as ALT + HMB (0.5 g/kg BW/day)
  • C: 30% energy restriction + exercise (6h/d for 6d/wk)
  • CH: same as C + HMB (0.5 g/kg BW/day)
So, in essence, we are dealing with a comparison of the effects of  HMB in conjunction with exercise and an ad libitum diet (=as much as the mice wanted to eat) vs. its effects as a supplement given as an adjunct to a highly catabolic overtraining + under-eating scenario, as you know it from the Athlete's Triad Series.

Without giving away too much, I can say that the results were not what you'd probably expect

As you can see in figure 1 part of the results are probably not like most people would expect them to be. While the provision of HMB did work its body recompositioning magic in the rodents that could eat as much as they wanted, it compromised the fat loss and increased the total loss of lean body mass in the rodents that were fed the -30% calorically reduced diet.
Figure 1: Changes in body composition (left), strength & motor function (right). Note that the effects of HMB depend on the energy content of the baseline diet (Park. 2013)
This result is particularly surprising in view of the fact that the caloric reduction was achieved by cutting back on sucrose and corn starch, wile the protein intake remained identical, all the time (see table 1), so that the purported "muscle building effects" of HMB should have had enough available substrate to produce at least an ameliorative effect on the loss of lean mass that is a necessary consequence of undernutrition + overtraining.
Figure 2: Dr. Jeckyll & Mr. Hyde effects of HMB ingestion during a caloric deficit; gastrocnemius CSA on the left, mTOR and p-AKT levels on the right of the central illustration (based on data from Park. 2013)
That the exact opposite was the case, i.e. that the provision of supplemental HMB blocked the fat loss and increased the loss in total lean mass is strange. After all, these highly undesirable effects took place in the presence of significantly reduced levels of the "catabolic" signalling proteins MuRF-1 & atrogin-1. The actual culprit here, may yet be that the provision of supplemental HMB to the overtrained and nutritionally deprived CH group also blunted the increased activity of the pro-anabolic proteins p-AKT and mTOR  in both fast- and slow-twitch muscle fibers (with a greater effect in slow twitch fibers, thoug; see figure 2, red). This effect may in fact have negated the decrease in protein loss, of which we can only assume that it did occur in response to the downregulation of the respecting signalling proteins, atrogin-1 and MuRF-1.With less being protein being catabolized but even less being pumped back in, this would leave us with a net protein loss that would explain the loss of lean mass - specifically in the soleus muscle which contains predominatnly slow-twitch fibers.

Devils advocate: "Why are the potential downsides not mentioned in the abstract?"

In view of the previously described observations, and the undeniable negative effect of HMB in the overtraining + undereating scenario (CH group), I'd like to disagree with the researchers' imho unwarranted hypothesis that
"[...]net protein synthesis may have been greater with HMB during the catabolic condition due to its greater inhibitory effect on the protein degradation pathway" (Park. 2013)
It's a neat ad-hoc hypothesis which is yet not, as the context would suggest, "based on [the scientists'] mRNA data", of which I already told you that both AKT and mTOR are lower in the gastrocnemius and soleus (fast & slow twitch) muscle of the HMB rodents in the CH group. And, this is certainly more important it stands in contrast with the overall effects on lean mass - so if anything, this argument could be made for the gastrocnemius, only. The overall net protein synthesis on the other hand, must clearly have been lower and not as Park et al. suggest higher.

Metabolic Technologies Inc. has not just licensed the paten for HMB, they are also a sponsor of the study at hand. Nothing bad, in general, but whenever these sponsorships coincide with not mentioning potential downsides in the abstract & conclusion of a paper, it reminds me of the usefulness of some healthy skepticism.
With data only from the soleus (7% greater mass loss vs. C group) and gastrocnemius muscle (11% greater mass retention vs C group) and an overall greater loss of lean mass in the HMB supplemented over-trained + starved rodents, it is however difficult to judge what exactly the rodents lost here. It could be organ mass or muscle mass from muscles that were not acutely working during the running exercises. In the end it may not even matter, because you would obviously want to avoid both, the loss of organ and muscle mass. So, the way the researchers ignore this observation in their abstract, where they state rightly state  that "HMB improves body composition and sensorimotor function during normal training", but follow that up with an at least questionable statement about how it also "attenuates muscle mass [...] loss during catabolic conditions" (Park. 2013) is odd.

Playing advocatus diaboli (lat. for "devil's advocate), I could argue this was a concession to Metabolic Technologies, Inc. who do not just happen to have the exclusive license for the patent on HMB (learn more), but are also among the sponsors of the study.

The beneficial effects of HMB that have been observed in previous human studies never dealt with a scenario like the one in the study at hand. The training load was usually low or easily manageable and the food intake sufficient just as it was in a recent study that was conducted on elite canoeists (read more)
Bottom line: The study at hand does support the generally beneficial findings that have been reported from human studies, conducted in realistic, and not so realistic training environments. In a calorically restricted scenario, however, the seemingly fiber-type specific effects of HMB on strength are the only plus and there is little evidence for "anti-cabatolic" effects in the original, broader sense of the word.

Based on the study at hand, of which we will obviously have to see, whether its results can be replicated in human beings, it does therefore not appear advisable to use HMB on a highly restrictive diet, if you do not happen to compete in weight classes and are more concerned about a loss of strength than negative effects a highly restrictive dietary regimen could have on your body composition.

It should go without saying, though that the overtraining + undereating approach to cutting body fat is a no-go with or without HMB, so in essence, all you need to do is to avoid following this path towards misery and you don't have to care much about the relevance of the results of this study.

  • Park BS, Henning PC, Grant SC, Lee WJ, Lee SR, Arjmandi BH, Kim JS. HMB attenuates muscle loss during sustained energy deficit induced by calorie restriction and endurance exercise. Metabolism. 2013 Jul 19. doi:pii: S0026-0495(13)00186-8.