Breakthrough HMB Research: Additional(!) 10% Reduction in Body Fat, 5% Higher Lean Mass + 2x Higher Strength Gains After 12W of Heavy Lifting in Trained Individuals

HMB-FA could be for ladies, too - or don't you want to look good naked, girls?
First, it was "as potent as oxandrolone", then it was "disappointing", "dysfunctional" and "tasted like crap"... you know what I am talking about? Well, then you've been around in the bodybuilding and fitness community for some time. And since you are here, at the SuppVersity, your goto source for the latest information from the realms of nutrition, exercise and supplementation science, you will probably be aware, that HMB, the molecule, I have obviously been referring to in the first sentences of this article, is about to make a comback - in liquid form and without the calcium bond in calcium β-hydroxy-β-methylbutyrate the studies that were presented at the last ISSN conference (read previous article) caused quite sensation in the fitness community.

Now, more than 6 months later, I got a message from Jacob Wilson that he and his colleagues have "just published the first long term periodized HARDCORE training study using HMB-Free acid." It's, as Jacob says, and I can confirm, the "most controlled study to date" (Wilson, 2014 - Facebook).
Is this study a hoax? While I cannot tell you if it is, I can tell you that commenters with and without credentials have been questioning the results of the study at hand. With the latest (and as of yet only) published doubts coming from Phillips et al. noting "that HMB has been shown to result in a trivial training‐induced adaptive advantage and that the gain in lean body mass was in previously resistance‐trained subjects who would have had less propensity to gain lean body mass" (Phillips. 2017). You can review the criticism, here, and should, for the time being, and previously pointed out, take the results of the study with a healthy grain of skepticism. For a more detailed discussion that goes beyond the unreflected comparison to Bhasins classic "testosterone promotes muscle gains" study, I suggests Greg Nuckols' article on HMB.
And after a brief with Jacob about the study design that revealed that the authors omitted the (imho critically important) information that the subjects received both HMB and a whey protein supplement (the latter is not mentioned in the methodology section), I would even agree that Jacob's conclusion that "his" study shows that HMB "clealy works in trained athletes" (Wilson, J. Facebook Conversation. 2014) is accurate as well.

Let's first take a look at what Wilson et al. did

Before we go on with the results, of which I know that they are what intrigues you most, let's briefly take a look at the pretty unique design of the combined exercise training + supplementation regimen the scientists from the University of Tampa, the IMG Acadamy, the University of Central Florida, and the Iowa State University came up with for this experiment:
  • 12 weeks is the study length we are looking at -- plenty of time for muscle growth, you would say, but if you want to use trained athletes, this is probably as short as it may be to make sure that you get measureable results 
  • Table 1: Overview of Phase 1-3 (Wilson. 2014)
    three training phases -- with Phase 1 (Table 1, top) consisting of a daily undulating periodized
    resistance-training program 3 days per week during,  Phase 2 (Table 1, middle) 2-week
    overreaching cycle during weeks 9 and 10, and Phase 3 (Table 1, bottom) tapering (volume) for weeks 11 and 12 - needless to say that this is an intense protocol which will, even without HMB, produce serious gains
  • 20 is the number of resistance trained men who participated in the study -- with 9 guys in the placebo and 11 guys in the HMB group enough to detect statistically significant differences, if those are actually physiologically relevant (in other words: a single outlier, maybe a "non-responder" - if there was such a thing - won't ruin the whole data set)
  • standardized baseline tests for strength & body comp, as well as blood draws and analyses -- this is so basic that I actually thought about even mentioning it
  • 3g of per day that's the dosage of HMB in a free acid form (HMB-FA) -- the free form of HMB has been shown by Fuller et al. in 2011, already, to have a superior bioavailability
There is more than just a superior bioavailability to HMB-FA! What's in fact more important than the increased relative amount of HMB that makes it into your blood stream, is the speed at which this process takes place. Improved absorption kinetics, ie. faster absorption ➲ greater anabolism - if we apply what we've learned about the difference between 30g of whey protein and a quarter-pounder, this would mean that cannot expect to see the same results with 3g and probably niot even with 9g of calcium bound "regular" HMB - even if the total amount of HMB that hits your blood stream would be higher!"
  • 30g of whey protein isolate (Dymatize ISO100, chocolate) that's the dosage of additional whey protein all subjects received -- this information is unfortunately missing from the original paper - a mishap that had me question the value of the data, initially; and if I had not been able to acquire it from Jacob directly, I would probably have torn the study apart, pointing to the possibility that HMB (FA or not) would produce similar non-existent results as the 3g+ of leucine people add to their whey protein shakes, falsely hoping this would increase the protein synthesis "beyond 100%"
I know the above is more than some of you want to process; so if you don't want to read it just keep in mind that we are dealing with a highly anabolic exercise protocol, which is - if anything - too intense to be considered "what the average fitness enthusiast will do in the gym". This does not change, though, that the results I plotted in Figure 1 are more representative of what the majority of you could achieve on a corresponding regimen (exercise + supplementation), than the albeit impressive results of the myriad of classic HMB studies in elderly patients (Wilson. 2008).
Figure 1: Changes in strength and body composition over the course of the 12-week study (Wilson. 2014))
Apropos, "impressive" - I should say that this attribute applies to the results Wilson et al. present in their recent paper, as well; and that's true for both, the supplement and placebo group!
"HMB-FA resulted in increased total strength (bench press, squat, and deadlift combined) over the 12-week training (77.1  ±  18.4 vs. 25.3  ±  22.0  kg, p  <  0.001); a greater increase in vertical jump power (991 ± 168 vs. 630 ± 167 W, p < 0.001); and increased lean body mass gain (7.4  ±  4.2 vs. 2.1  ±  6.1  kg, p < 0.001) in HMB-FA- and placebo-supplemented groups, respectively." (Wilson. 2014)
Whether or, the more appropriate question probably is, to which degree the superior lean and strength gains in the HMB group are a result of the blunted increase in creatine kinase (−6 ± 91 vs. 277 ± 229 IU/l, p < 0.001), an (imho) very unreliable marker of muscle damage and cortisol (−0.2 ± 2.9 vs. 4.5 ± 1.7 μg/dl, p  <  0.003), a suspected catabolic, the role of which in the orchestrate of muscle growth does yet remain highly elusive (learn more in "All About Cortisol" | read more), in the HMB-FA group during the overreaching cycle is questionable and imho of corelative, not causal nature.
No, soccer mums! HMB is not going to kill your kid: I am nor sure why, but whenever supplements work (best example creatine), it won't take long until the first rumors of potentially hazardous side effects appear (Fuller. 2014). First on the Internet, then on TV (see the WPXI News Item Jose Antonio posted recently on the ISSN Facebook site). Against that background it's good to know that the no-observed-adverse-event-level (NOAEL) for HMB is 2.48 and 2.83 g/kg BW d−1 in male and female rats, respectively. For a human being this would translate to ~70-100g/per day and thus certainly more than you'll be able to afford, when the free acid form of HMB will hit the market.
Previously, HMB turned out to be particularly useful in scenarios where muscle loss was an issue (the previously mentioned studies in elderly individuals). You also know from a previous article of mine that Wilkinson et al. were able to show that HMB - contrary to leucine, by the way - an excellent inhibitor of protein breakdown. In am overreaching scenario, of which you can see based on the significant strength decreases in the placebo group at the end of the overreaching phase (see Figure 1, left), it is thus possible that the added anti-catabolic effects of HMB are what actually made the difference. In turn, this would yet mean: If you don't train like a maniac, even high amounts of additional HMB may fail to induce changes, as Jacob and his colleagues observed in the study at hand.
When is HMB-FA going to be available? As of now no supplement company has officially announced a free form HMB product (at least none I know of). Based on the hype the study at hand will certainly generate, I would yet expect that John Rathmacher, John Fuller, Shawn Baier, Steve Nissen, and Naji Abumrad who hold a patent on an "Improved method of administering beta-hydroxy-beta-methylbutyrate (hmb)" (Rathemacher. 2011), which is basically HMB-FA, will already be locked in talks with several companies.
I am impressed! By both, the study design and the results, by the way. That's the type or dietary research on dietary supplements that's done by exercise enthusiasts instead of office sitters; and it's the kind of science of which I would like to see more in the future.

That being said, let me tell you something important before you scroll down to the comment area and ask: I don't know when the first HMB-FA products are about to hit the market. All I can tell you is that I personally would not try to emulate the results with regular HMB. As I pointed out in the red box towards the top, chances that you'd see the same benefits, when you're supplementing with calcium-HMB and whey are slim and if you know how "regular" HMB tastes, you will be aware that a "test run" would probably hurt your tastebuds even more than it would hurt your purse ;-)
  • Fuller Jr, John C., et al. "Subchronic toxicity study of β-hydroxy-β-methylbutyric free acid in Sprague-Dawley rats." Food and Chemical Toxicology (2014).
  • Phillips, et al. "Changes in body composition and performance with supplemental HMB-FA+ATP." Journal of Strength and Conditioning Research (2017). Publish Ahead of Print -DOI: 10.1519/JSC.0000000000001760
  • Rathemacher, John, et al. "Improved method of administering beta-hydroxy-beta-methylbutyrate (hmb)" WO 2011075741 A1. 2011
  • Wilson, Gabriel J., Jacob M. Wilson, and Anssi H. Manninen. "Effects of beta-hydroxy-beta-methylbutyrate (HMB) on exercise performance and body composition across varying levels of age, sex, and training experience: A review." Nutr Metab (Lond) 5 (2008): 1.
  • Wilson, Gabriel J., et al. "The effects of 12 weeks of beta-hydroxy-beta-methylbutyrate free acid supplementation on muscle mass, strength, and power in resistance-trained individuals: a randomized, double-blind, placebo-controlled study." European Journal of Applied Physiology (2014)
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