Revisiting Caffeine + Lactate - In Combination They May be Powerful Muscle Builders Which Boost Satellite Cell Activity + Anabolic Signalling And Trigger Muscle Hypertrophy

High intensity training builds muscle and maximizes lactate build up. Caffeine helps you to train at maximal intensities. Correct, but there appears to be a more direct link between lactate accumulation, caffeine supplementation and skeletal muscle hypertrophy.

No, you are not mistaken: The headline says and means that caffeine and lactate are powerful agents that may promote skeletal muscle hypertrophy by boosting satellite cell activity and anabolic signalling in favor of muscle hypertrophy.

After a thorough review of the existing literature discussing the individual effects of caffeine and lactate on skeletal muscle metabolism and anabolism, Yoshimi Oishi and colleagues from the Ritsumeikan University hypothesized that "a lactate-based supplement containing caffeine, an activator of intracellular calcium signals, could elicit proliferation and differentiation of satellite cells, activate anabolic signals in skeletal muscle, and thereby increase muscle mass when combined with low-intensity exercise training."

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Well, you already know that they were able to proof their hypothesis, right? Let's still take a look at how they did that - at least briefly:

"To assess this hypothesis, we initially examined whether lactate and/or lactate-caffeine treatment could elicit proliferation and differentiation of satellite cells or activate anabolic signals in C2C12 skeletal muscle cells. Furthermore, we examined whether the administration of a mixed lactate and caffeine compound (LC compound), concomitant with endurance exercise training, could effectively increase muscle mass via activated satellite cells and/or anabolic signals in rat skeletal muscle" (Oishi. 2015)

I know, the human study is missing, but if you think about the intensity dependent increase in lactate production it appears logical to assume that increasing lactate levels which as previously been shown to...

• upregulate the expression of MCT1 and genes coding for other components of the mitochondrial reticulum in skeletal muscle (Brooks. 2009)
• increase myogenin (the satellite cell activator) mRNA in skeletal muscle cells in the petri dish (Hashimoto. 2007)

Now, this raises the question how calcium comes into play. According to Oishi et al. its beneficial effects are related the ability of caffeine supplements to increase the amount of intracellular calcium (Lu. 2007), which activates calcineurin, which will in turn induce slow and fast fiber hypertrophy (Talmadge. 2008) - unfortunately, this effect appears to favor type I (=endurance fiber) over type II hypetrophy, but this may well depend on the trigger that's used, i.e. endurance training as it was the case in a rodent study by Talmadge et al. or your strength workouts.

Figure 1: Graphical illustration of the mechanism by which caffeine and lactate may increase your gains.

Too complicated? Well, check out my graphical summary in Figure 1. I guess this should explain the basic mechanism: Lactate up = increase satellite cell proliferation = hotbed for muscle hypertrophy + calcium up = increased calcineurin = trigger for increased hypertrophy.

Bicarbonate supplementation buffers the decline in muscle pH and allows for 15% greater increases in lactate levels while still increasing training performance on a high volume, high intensity leg workout | read more

High intensity = high lactate, high intensity + bicarbonate = even higher lactate: The study at hand used lactate + caffeine supplementation and low intensity exercise. With high intensity exercise the increase the usefulness of additional lactate supplements may be significantly reduced, because higher intensity equals higher lactate accumulation anyway. As a previously discussed study on high intensity high volume leg training indicates, this effect can be augmented by sodium bicarbonate supplementation which allows for increased lactate levels in the absence of the debilitating effects of skeletal muscle acidosis (read more).

In the study at hand, the researchers quantified the effects on skeletal muscle hypertrophy by weighing the gastrocnemius and tibialis muscle of the rodents after 4 weeks of treadmill training and the effects on muscle restructuring via incorporation of new muscle nuclei (learn more) by measuring the increase in DNA content from exercise training alone and exercise training in conjunction with lactate + caffeine supplementation.

Figure 2: Exercise and exercise + supplementation induced changes in muscle weight and DNA content of skeletal muscle in mice exposed to four weeks of low intensity treadmill running (Oishi. 2015).

As the data in Figure 2 indicates, both muscle hypertrophy and the exercise induced increase in satellite cell activity were further augmented by the addition of lactate and caffeine in dosages of 1g/kg sodium-lactate and 36mg/kg caffeine.

In conjunction with the likewise observed increases in myogenin and follistatin expression of the fast twitch (that's what you use for lifting weights) gastrocnemius muscle relative to the exercise alone, the results of the study at hand clearly warrant the scientists conclusion that the administration of sodium lactate and caffeine "can effectively increase muscle mass concomitant with elevated numbers of myonuclei, even with low-intensity exercise training, via activated satellite cells and anabolicsignals" (Oishi. 2015).

So, what does this mean in practice? Assuming the same effects would occur in human beings the effective dosages of sodium lactate and caffeine would be 81mg/kg and 2.9mg/kg, respectively. Practically speaking you would have to take ~6.5g of sodium lactate and 232mg of caffeine.

Remember? Study suggests, significant increases in mitochondrial builder PGC1-a with HIIT + sodium bicarbonate | read more

That's quite a reasonable amount and should not have nasty side effects. Whether the sodium lactate offers additional benefits to trainees who work out far beyond the lactate threshold (remember: the rodents did only "light exercise"), remains questionable. The same goes for the question whether the addition of sodium bicarbonate would elicit similar beneficial effects on the lactate induced increase in satellite activity. In view of the fact that previous studies show that it does potentiate the beneficial effects on another albeit not directly related marker of mitochondrial changes in muscle structure, namely PGC-alpha (see previous SuppVersity article), I personally believe this would be worth investigating | Comment on Facebook!

References:

• Brooks, George A. "Cell–cell and intracellular lactate shuttles." The Journal of physiology 587.23 (2009): 5591-5600.
• Hashimoto, Takeshi, et al. "Lactate sensitive transcription factor network in L6 cells: activation of MCT1 and mitochondrial biogenesis." The FASEB Journal 21.10 (2007): 2602-2612.
• Lu, Ying-Mei, et al. "Imbalance between CaM kinase II and calcineurin activities impairs caffeine-induced calcium release in hypertrophic cardiomyocytes." Biochemical pharmacology 74.12 (2007): 1727-1737. 
• Oishi, Yoshimi, et al. "Mixed lactate and caffeine compound increases satellite cell activity and anabolic signals for muscle hypertrophy." Journal of Applied Physiology (2015): jap-00054.
• Talmadge, Robert J., et al. "Calcineurin activation influences muscle phenotype in a muscle-specific fashion." BMC cell biology 5.1 (2004): 28.

There is Such a Thing As Overtraining, Beware! When IGF-1, MyoD & Myogenin Plummet and MAFbx Gnaws Away Your Muscles, It'll Already be Too Late to Acknowledge

Overtraining is real and it's blocking future and reversing past gains.

I am well aware that somewhere out there in the broscientific spheres of the pseudo-experts on the various bulletin boards of a world people call the Internet statements like "there is no overtraining, just undereating" are not uncommon. And in fact, there is a certain connection between the effects / symptoms we usually associate with overtraining on the one, and the consequences of undereating on the other hand. It's a perfect synergy, if you will - a synergy I have been writing about in the past (suggested read: "The SuppVersity Athletes' Triad Series" | read more), but it's not what the most recent study from the Sao Paulo State University in Brazil is about (Alves Souza. 2014).

Overtraining comes in two forms

If this is not your first visit to the SuppVersity the phrases "sympathetic" and "parasympathetic" overtraining will probably sound vaguely familiar. While the latter is the form of overtraining that develops after weeks of 2-4h of daily cardio-training - usually in the presence of undereating, the former is supposed to occur after heavy lifting sessions and is thus more common in sprint type sports.

Check your training status with a heart rate monitor: In spite of the fact that there is no 100% reliable method to test, whether you're overtraining, the heart rate variability - or rather the way it's changing in the course of a training cycle can give you a good idea of whether you're doing too much, already (learn more in "Are You Overtraining? Two Scientifically Proven Methods to Test Yourself" | Part I, Part II).

In the early phases sympathetic overtraining may feel like being "overstimmed", i.e. similar to the strange agitated weakness caffeine naive individuals may experience after their fourth cup of coffee. That's before a deliberating fatigue will take over, episodes of hypoglycemia during (and after) exercise will occur and your life will start to suck as much as your performance (yes, depression is another symptom of overtraining).

Muscle loss instead of gains

While performance oriented athletes usually pull the emergency break, when the notice that their strength, speed, agility, dexterity and all the other qualities that are relevant for world-class performance decline, Mr. Average Joe and his wife Jane tend to ignore the signs until it's already too late and the hormonal changes, Alvez Souza et al. observed in their latest study have already started to gnaw on their precious muscle mass.

Figure 1: Expression of hyptrophy relevant protein and hormones after 12 weeks of (over-)training, as well as subsequent effects on cross-sectional area (CSA) of plantaris muscle; trained vs. sedentary animals (Alves Souza. 2014)

What you can see in Figure 1 are the consequences of 12 weeks of training, in the course of which, the labrats of the Brazilian researchers were subjected to a 1training program with excessive training
load and insufficient recovery time between bouts using a water jump-exercise model of squatting (Figure 1, right):

"Briefly, rats underwent to consecutive training sessions (5 day/week) that consisted of jumps (repetitions) to the water surface (38 cm deep; approximately 150% of rat body length), carrying an overload strapped to a vest on the animal's chest. Initially, all animals completed a 1-week pretraining (once daily) that consisted of a progressive number of sets (2-4) and repetitions (5-12) with a 30-s rest between each set, and carrying an overload of  50%  body  weight  (BW).  Subsequently,  the  rats  began  the  12-week  training  program,  which consisted of progressive overload corresponding to  60% (1 to 3 week), 65% (4 to 6 week), 70% (7th to 8th week), 80% (9th to 10th week), and 85% (11th to 12th week) of BW." (Alves Souza. 2014)

As Alves Souza et al. point out, they have previously demonstrated that this training protocol is effective in promoting type IIA and IID  fiber  atrophy  in  rat  plantaris  muscle  - as long as it is done in a sane and not the typically Western "more helps more" way that was applied in the study at hand.

Overtraining leads to significant changes in muscle specific hormones and proteins: If you discard the fact that most gymbros don't train legs at all (you know, they play football or soccer, right ;-) the above looks pretty much like the "5-days a week, why don't I grow" regimen of the average self-proclaimed hardgainer, whose consternation about his lack of gains is hardly surprising in view of ...

• 

  When it comes to IGF-1 looking at systemic levels is not enough - rather than the circulating "full" version of MGF, it's the presence of its local splive-variants like MGF that's actually igniting muscle growth. You can learn more about MGF and other factors that contribute to muscle growth in the "Intermittent Thoughts on Building Muscle" Series | go ahead!

  the upregulation of MAFbx, a muscle protein and that is released if you bath muscles in petri dishes full of glucocorticoids has emerged as a central regulator of skeletal muscle catabolism in previous studies (6, 13, 34),
• the reduction in MyoD and myogenin and the consequent inability to compensate for the exercise induced damages (let alone build new muscle) due to the lack of satellite cell (=muscle stem cell | learn more) activity,
• the drop in IGF-1 and it's local splice variants that decline with decreasing systemic levels of IGF-1 and play an (imho) still largely underestimated role in the concert of skeletal muscle hypertrophy (see "IGF-1 and its Splice Variants MGF, IGF-IEa & Co - Master Regulators or a Bunch of Cogs in the Wheel of Muscle Hypertrophy?" | read more)

Although we may still be light-years away from understanding the exact interplay of all these factors, I can tell you one thing for sure: As productive as a short 2-week phase of overreaching may be - don't be fooled to believe that the gains would keep coming if you just kept pushing.

References:

• Alves Souza et al. "Resistance Training With Excessive Training Load and Insufficient Recovery Alters Skeletal Muscle Mass-Related Protein Expression." Journal of Strength and Conditioning Research (2014). Publish Ahead of Print

Vitamin D Builds Muscle: 70% Reduction in Myostatin, 45% Increase in Myotube Size in 10 Days - So, What's the Catch? Plus: Where Could Retinoic Acid (Vitamin A) Figure In?

If rely on the results of the most recent study from Australia, the answer to the above question probably reads "Yes, to a certain degree it does".

It has been a while that a vitamin D study has made it into the SuppVersity news (see previous articles). The reason for that is simple. I am not interested in study no. 9235235 that discusses random associations of low vitamin D with whatever ailment is plaguing us or review no. 89359252 that presents a selection of papers and concludes: "Man, there are vitamin D receptors everywhere, so it must be the f*** most important vitamin in your body!" The upcoming publication of a paper in the scientific journal Endocrinology did yet appear to be a good reason to stop the vitamin D radio silence. It's an in vitro study, I know, but it could answer a question many of will be interested in.

Does vitamin D build muscle?

I guess all of you will tell me that, in view of the results of pertinent studies (cf. Girgis. 2013a), the answer is "no, it doesn't, but deficiency seems to hamper muscle growth and impair skeletal muscle function". This conclusion is hard to debate, especially in view of the fact that we don't even know what exactly vitamin D does in human muscle cells.

Exactly this, i.e. the question "what exactly happens, when muscle cells are exposed to vitamin D" must have been bother Girgis et al., too. Therefore they devised a very simple yet interesting in-vitro study in the course of which they treated C2C12 cells, which are a commonly used model (see bottom line for a comment on this) for human skeletal muscle with both, the active 1,25(OH)2D and inactive 25(OH)D form of 'vitamin D' and observed the effects on cell proliferation and growth.

Figure 1: Number of live cells (10^4/dish; middle) and images of the cells w/out & w/ 25(OH)D2 (Girgis. 2013b)

The first intriguing finding the scientists present in their paper is yet not related to the growth or proliferation of the cells, but to their ability to convert active into inactive vitamin D and vice versa. What we are talking about here, specifically, is the increased expression of CYP24A1. This enzyme is responsible for the 'deactivation' of active vitamin D into calcitriotic acid. This supposedly inactive metabolite (you never know with these vitamin Ds ;-) is then excreted in the urine. The reason that I mention this ostensibly unimportant observation is that the expression of CYP24A1 and CYP27B1, which will convert 25OHD into the active 1,25(OH)2D is evidence of the presence of an auto-regulatory vitamin D-endocrine system in muscle cells.

Ok, enough of the enzymes what about "getting big"?

Let's briefly forget about the mechanisms and return to the actual effects on growth and proliferation. Effects such as the 30-50% increases in G0/G1, a gene that's responsible for arresting the cell cycle, and the 30% and 20% decreases in Myc and Cyclin-D1 the scientists observed in response to both 25(OH)D and 1,25(OH)2D.

In view of the fact that these genes are necessary for the progression of the cell cycle, it is not surprising that the exposition to both forms of vitamin D brought the cycle to a screeching halt. In the end, this is yet a long-known phenomenon. The antiproliferative effects of 1,25(OH)2 D in muscle cells were first described in 1985 and are, as Girgis et al. point out, ...

"[...] they are consistent with antiproliferative effects of 1,25(OH)2 D in a number of other cells and tissues including skin, cancer cells and immune cells ." (Girgis. 2013b)

What's news though, is that the researchers were able to confirm that even 25OHD, the "prohormone" (Girgis. 2013b) to 25(OH)D2, displays antiproliferative effects in C2C12 cells.

Don't forget the "Underestimated Vitamin D Sources: Especially Eggs, But Also Chicken, Pork, Fish & Dairy Contain an Overlooked, Physiologically Relevant Amount of Ready-Made 25OHD" | read more

In that, it's important to acknowledge that these effects are not necessarily brought about by direct receptor interaction. They could also be mediated by the 'activation' of 25OHD via the previously mentioned CYP27B1. With CYP27B1 and its counterpart CYP24A1 the cells would thus be able to produce and clear active vitamin D on demand - and in this case the muscle cells were using it for anti-proliferative purposes.

"What? Vitamin D kills muscle growth?"

At first sight the cell-cycle arrest really suggest that high, and not the often cited low vitamin D levels should have anti-anabolic effects. Since muscle does not necessarily depend on proliferation, or more specifically cell devision, to grow this is yet not the case. At least up to a volume time-point your muscle cells and with them your total muscle volume can grow by simply taking up more protein. This process is called hypertrophy and it works quite nicely until a certain threshold is reached and myostatin pulls the emergency break (if you read my previous article "Getting Big Means Growing Beyond Temporary Physiological Limits" you will know that this is the point, when the activation and incorporation of satellite cells becomes important; learn more)

Figure 2: There may be less live cells, but once the cell cycle arrests, the cells that are bathed in serum with high amounts of acvite vitamin D 1,25(OH)2D grow like crazy, but probably only until they are 'ready to burst' (Girgis. 2013b)

Irrespective of all growth limits, it is thus no irreconcilable contradiction that the data in Figure 2 confirms that 'vitamin D builds muscle. Since proliferation and hypertrophy are independent (or rather mutually exclusive processes) the individual cell growth, while the total cell mass remains the same (remember: cell cycle arrest does not mean that the cell dies).

So, is this good or bad news? Whether the cell cycle arrest is a problem that could haunt you, in the long term, i.e. whence the limits of natural growth are reached (learn more) is something this study can't tell us, because...

... firstly, the cells the researchers used cells express proteins necessary for muscle contraction and display the morphology of individual fiber unit, but C2C12 cells are not adult muscle cells. With a varying degree of maturation, and mode (Langelaan. 2011) of glucose transport (Kotliar. 1992), even Girgis et al. have to admit that "effects in C2C12 cells do not always translate to adult muscle." (Girgis. 2013b) and ...

Figure 3: Primary C2 cells (chicken & mouse) were either untreated (A,C,E) or treated w/ 10 µM RA (B,D,F). A + B panels display satellite cells incubated w/ or w/out RA for 24 hr. C,D and E,F panels show satellite cells and C2 cells, respectively, after 48hr of incubation.

... sedondly, as with every in-vitro study, we cannot tell if the effects that are observed under direct exposition of cells to pharmacological doses of 1,25(OH)D will correspond with those of physiological levels of vitamin D - even high ones.

In the end, we are thus as clueless as before. Even if everything works as it does in the  model, the data in Figure 2 would suggest that after a couple of days of increased hypertrophy, the myostatin levels are identical and the D-advantage disappears.

When this 'growth limit' is reached it would require proliferative effects and new cells, or rather myonuclei, to grow further (learn more). With vitamin D alone, that's not going to happen. What could help though, is the villain of the average vitamin D enthusiast: Retinoic acid (RA) aka vitamin A. The latter has after all been shown to "induces adult muscle cell differentiation mediated by the retinoic acid receptor‐α", ten years ago (see Figure 2 from Halevy. 1993).

Now you tell me: Isn't it funny how we always end up with vitamin A (learn more), whenever we realize that 'vitamin D, without vitamin A' sucks? That cannot be mere coincidence, can it?

References:

• Girgis, Christian M., et al. "The roles of vitamin D in skeletal muscle: form, function, and metabolism." Endocrine reviews 34.1 (2013a): 33-83. 
• Girgis, Christian M., et al. "Vitamin D Signaling Regulates Proliferation, Differentiation and Myotube Size in C2C12 Skeletal Muscle Cells." Endocrinology (2013b): en-2013.
• Halevy, Orna, and Orna Lerman. "Retinoic acid induces adult muscle cell differentiation mediated by the retinoic acid receptor‐α." Journal of cellular physiology 154.3 (1993): 566-572.
• Kotliar, N., and P. F. Pilch. "Expression of the glucose transporter isoform GLUT 4 is insufficient to confer insulin-regulatable hexose uptake to cultured muscle cells." Molecular Endocrinology 6.3 (1992): 337-345. 
• Langelaan, Marloes LP, et al. "Advanced maturation by electrical stimulation: Differences in response between C2C12 and primary muscle progenitor cells." Journal of tissue engineering and regenerative medicine 5.7 (2011): 529-539.

The Myostatin Inhibiting & Myogenic Effects of Epicatechin: Cacao & Tea Contain Well-Known But Overlooked Anabolic

Does a flavanol in "real chocolate" help you shed the fat and build the muscle?

If you are like me, you are probably already using cacao to build muscle. Whether the effects of the occasional dark chocolate bar are so profound that you'd notice if you'd skip them, is however questionable. Irrespective of the latest results from Gabriela Gutierrez-Salmean and her colleagues from the University of California, VA San Diego Health Care Systems and the Escuela Superior de Medicina del Instituto Politécnico Nacional at the Seccion de Posgrado in Mexico City present in a soon-to-be-published paper in the The Journal of Nutritional Biochemistry (Gutierrez-Salmean. 2013), by the way.

"Epi" as in "Epistane" (*) was yesterday...

... "epi" as in chocolate epicatechin is the future (*Epistane was the brand name of a "pro-steroid"). This could be the take home message of future follow up studies in human beings, if the results Gutierrez-Salmean et al. observed in isolated rodent and human muscle cells translate to the real world.

Chocolate milk is an outstanding muscle builder, but as you will remember from previous SuppVersity Articles and Facebook News, chocolate milk owes its muscle building prowess to the combination of milk protein and sugar which make it an excellent recovery fuel (Saunders. 2011; Spaccarotella. 2011; Pritchett. 2012) that can easily compete with commercial recovery drinks (Lunn. 2012)

Other than the benficial effects of chocolate milk, which are brought about not by chocolate but by the amino acids and (milk-)sugars in the sweet brew, the myostatin inhibiting effects of chocolate appear to depend exclusively on the flavanol (-)-epicatechin which has been shown in previous studies to

• produce a +50% increase in exercise capacity in mice (Nogueira. 2011), and
• improve skeletal muscle structure / mitochondrial capacity in older patients with heart failure and type 2 diabetes (Taub. 2012)

Unfortunately, the total amount of this flavenol in chocolate is not only relatively low, it does also vary according to the type and origin of your cacao (assuming that whatever chocolate product you may be using, does even have real cacao in it).

Figure 1: Relative change in myostatin, Myf5, MyoD and Myogenin levels after incubation of cells from skeletal muscle of young vs. old rodents with (-)-epicatechin (Gutierrez-Salmean)

It is thus by no means guaranteed that you will experience any, not even a non-significant reduction in myostatin, when you increase your chocolate consumption; and let's be honest (!) - the weight you gained on your last "chocolate cycle" was not all muscle, was it?

Additional Read: "The Myostatin <> Clenbuterol Connetion" | read more

As far as the myostatin suppression goes you may even argue that it's a good thing that the myostatin-inhibiting effects of a 90% cacao chocolate bar are negligible. Whe? Well, we all know what happens when you suppress myostatin too much, right? Right! Your muscles will balloon up until they eventually seize working and you will - just like the poor myostatin negative mice, no longer be able to support your own weight.

Ok, so it could in fact be a good thing that the "next anabolic revolution", let's call it Chocobolic™ won't make you look like the Belgian Blue bull in the image on the right...

Rigth, that's really a good thing. What's not so good, though is that it would also lack the exciting effects on MyoD, Myogenin (sorry for the typo in Figure 1) and Myf5 and with them the ability for the recruitement of satellite cells and the genesis of new myonuclei (learn more) - exactly those processes that will avoid the loss of skeletal muscle function.

Contrary to the futile "baloon"-like gains in response to an increase in protein synthesis, these "gains" are meant to stay. In fact, the presence of additionally myonuclei could be the explanation about the miraculous rapid muscle (re-)gain in "roid using mice" you've read about just yesterday in the SuppVersity Facebook News... but I am getting off topic, here - if you want to learn more about the said study and never miss news like this again go to and like the SuppVersity Facebook page.

Remember the anti-androgenic effects of green tea catechins I wrote about in September 2011? Well guess what EPI, or here EC, is one of the exceptions to the rule that has been shown to increase testeosterone by up to +24% (EC) | learn more

So what's the verdict then? If it were not for dosing and delivery issues, the study at hand would be pretty exciting. It does after all provide evidence that most of us have been consuming tiny amounts of an effective and above all potentially side effect-free myostatin inhibitor for years.

There is still a long way to go from rodent and human myocytes in the petri dish to the average supplement costumer and I am not sure whether or not epicatechin will ever make it across the finish line - irrespective of the promising results Noguiera et al. and Taub et al. already observed in rodent skeletal and human heart muscle in response to the provision of 2x 1.0 mg/kg of pure (-)-epicatechin (2x HED 6.5mg; Nogueira. 2011) or dark chocolate and a beverage containing 100 mg of Epi per day for 3 months (Taub. 2012).

References:

• Gutierrez-Salmean G, Ciaraldi TP, Nogueira L, Barboza J, Taub PR, Hogan M, Henry RR, Meaney E, Villarreal F, Ceballos G, Ramirez-Sanchez I. Effects of (-)-epicatechin on molecular modulators of skeletal muscle growth and differentiation. Journal of Nutritional Biochemistry. Oct. 2013 [accepted manuscript].
• Lunn WR, Pasiakos SM, Colletto MR, Karfonta KE, Carbone JW, Anderson JM, Rodriguez NR. Chocolate milk and endurance exercise recovery: protein balance, glycogen, and performance. Med Sci Sports Exerc. 2012 Apr;44(4):682-91. 
• Nogueira L, Ramirez-Sanchez I, Perkins GA, Murphy A, Taub PR, Ceballos G, Villarreal FJ, Hogan MC, Malek MH. (-)-Epicatechin enhances fatigue resistance and oxidative capacity in mouse muscle. J Physiol. 2011 Sep 15;589(Pt 18):4615-31.
• Pritchett K, Pritchett R. Chocolate milk: a post-exercise recovery beverage for endurance sports. Med Sport Sci. 2012;59:127-34.
• Saunders MJ. Glycogen replenishment with chocolate milk consumption. Curr Sports Med Rep. 2011 Nov-Dec;10(6):390.
• Spaccarotella KJ, Andzel WD. The effects of low fat chocolate milk on postexercise recovery in collegiate athletes. J Strength Cond Res. 2011 Dec;25(12):3456-60. 
• Taub PR, Ramirez-Sanchez I, Ciaraldi TP, Perkins G, Murphy AN, Naviaux R, Hogan M, Maisel AS, Henry RR, Ceballos G, Villarreal F. Alterations in skeletal muscle indicators of mitochondrial structure and biogenesis in patients with type 2 diabetes and heart failure: effects of epicatechin rich cocoa. Clin Transl Sci. 2012 Feb;5(1):43-7.

More Muscles For Old Chaps, Less Fat for Baby Boomers: The Age Specific Anabolic Anti-Obesity Effect of HMB

Image 1: Nutrition, exercise and most importantly the right mindset will always be the foundation of leading a long, strong and healthy life - irrespective of how many supplements you take - you cannot out-supplement a bad diet, laziness and a lack of motivation and determination.

The hype was, as usual, huge, when back in the day Beta-Hydroxy-Beta-Methl-Butyrate (HMB), marketed as the natural alternative to Deca (Nandrolone; update: thx to anonymous for the heads-up that it was not just Anavar, as I original thought ;-), hit the market. What was yet even bigger than the hype, though, was the disappointment of customers who felt ripped off; and that not without reason, because the early HMB supplements were not only touted to be as effective as the previously mentioned anabolic steroid, they were also sold at similarly high prices and low doses, of which every scientists could easily have told you that the one thing that would grow were the purses of the manufacturers.When the marketing bubble eventually burst, the (at that time) pretty expensive and incredibly disgustingly tasting (no way you put a working amount of that stuff into a tasty pre- or postworkout amount without ruining the taste!) supplement disappeared from the market, literally overnight. Today, HMB is, if at all, sold as a standalone in 250mg-500mg capsule form or 250-1,000g pouches from bulk suppliers and leads an overall miserable existence being perceived as a probably useful, but simply unnecessary metabolite of the contemporary "natural Deca", leucine.

HMB - More than expensive leucine for old folks!?

The astonishing results of a recently published study from Jacob M Wilson's lab at the Department of Nutrition, Food and Exercise Sciences at The Florida State University in Tallahassee do yet suggest that at least the best-agers among the SuppVersity students, beta-hydroxy-beta-methl-butyrate could derive  undeniable advantages from the almost forgotten leucine metabolite (5% of a normal dietary leucine intake from food sources are metabolized into HMB; cf. Van Koevering et al.1993, according to Wilson. 2012). In what was allegedly "only another rodent study" (before you start complaining, please acknowledge that as long as you don't have your rodents "work out", those studies usually elicit pretty accurate results), the scientists enriched the diets of twelve young (44 wk.), 6 middle-aged (60 wk.), 10 old (86 wk.), and 5 very old (102 wk.) male rats with ~500mg/kg body weight HMB per day, which, using the standard conversion chart (cf. "Ask Dr. Andro: What Are Human Equivalent Doses "), yields a human equivalent of ~81mg/kg or 6.5g for a person who weighs 80kg.

Figure 1: Changes in body composition (left) and strength (right) during 16-week transition from young to middle age and old to very old age with and without supplementation in male Fisher rats (data adapted from Wilson. 2012)

As the data in figure 1 clearly shows this supplementation protocol (16 weeks, transition from young to middle aged and from old to very old) did not only prevent the decline in muscle strength, it had also pretty profound effects on the body composition of the aging animals. In case of the very old rodents, those effects were so profound (-56% body fat!) that it is questionable whether they were actually able to eat or rather metabolize enough food (food intake was not different) to accommodate for the +10% increase in lean mass.

HMB shuts down atrophic and ramps up myogenic factors, but why does it burn fat?

The late, but profound increase in lean mass in the very old animals (102wk) was brought about by a totally blunted increase in the "catabolic" Atrogin-1 signaling, the expression of which is so characteristic of aging skeletal muscle, and (and this is actually surprising) an increase of the "anabolic" myogenin expression that yielded myogenin levels which exceed those of the young (44 week) control group by +40%!

Although these changes in Atrogin-1 and myogenin expression can explain the anti-sarcopenic (=working against the age-induced decline in muscle mass) effects of HMB and would even suggest tat it is a very useful "muscle builder" in the elderly population, where similar amounts of leucine (7.5g) have hitherto not yielded not the desired results (Verhoeven. 2009), they do not explain the unquestionably profound effect on the total fat mass of the animals, which reached statistical significance during both, the transition from young to a middle age (HMB body fat change not significant vs. +49% body fat mass in control) and the transition from the old to the very old age (HMB body fat -56%, control -8% n.s.) and of which Wilson et al. say (Wilson. 2012):

To date, the underlying mechanisms that HMB exerts its effects on adipose remain to be elucidated. It may be that HMB directly increases oxidative capacity in myofibers, as exposure of cultured myotubes to the leucine metabolite increased palmitate oxidation by 30%.

If the latter, i.e. the increase in palmitate oxidation transfers to human studies, Skelton et al. observed in their in-vitro studies (Skelton. 1994, according to Wilson. 2012), was dose dependent, I would be interested to see studies on the effect of twice the amount of the 3.0g/day HMB per day that did already produce greater increases in lean and decreases in fat mass over the course of a four week resistance training program in a twelve-year-old study in young (Panton. 2000), as well as an eleven-year-old study in 70-year old individuals (Vukovic. 2001), in younger and older trainees, and sedentary individuals.

Something to think about

Also, what if HMB was in fact one of the rare cases, where "more" actually yields "more". I mean, wouldn't it be remotely possible that our body's ability to convert leucine to HMB is not just rate limited, but that the rate decreases with age (this would explain why leucine works much better in younger folks) and saturates, when a certain concentration of HMB is achieved (if that was the case even the 5% conversion could be questionable, because you could have an upper limit of say 500mg, which would be 5% of 10g leucine and just 1% of 50g)? The latter would mean that you could not produce more than x grams of HMB total per day and would imply that the "old natural Deca" could in fact turn out to be superior to the "new natural Deca" for trainees (and maybe even non-trainees) from all age groups - as long as the dosage was appropriate, i.e. beyond what your body would produce from dietary leucine.

References:

1. Panton LB, Rathmacher JA, Baier S, Nissen S. Nutritional supplementation of the leucine metabolite beta-hydroxy-beta-methylbutyrate (hmb) during resistance training.Nutrition 2000,16(9):734-739.
2. Skelton DA, Greig CA, Davies JM, Young A. Strength, power and related functional ability of healthy people aged 65-89 years. Age Ageing 1994, 23(5):371-377
3. Van Koevering M, Gill DR, Smith RA, Owens F, Nissen S, Ball R. Effect of β-hydroxy-β-methyl butyrate on the health and performance of shipping-stressed calves.Oklahoma State Univ Res Rep; 1993, 312-331.
4. Vukovich MD, Stubbs NB, Bohlken RM. Body composition in 70-year-old adults responds to dietary beta-hydroxy-beta-methylbutyrate similarly to that of young adults. J Nutr. 2001 Jul;131(7):2049-52.
5. Wilson JM, Grant SC, Lee SR, Masad IS, Park YM, Henning PC, Stout JR, Loenneke JP, Arjmandi BH, Panton LB, Kim JS. Beta-hydroxy-beta-methyl-butyrate blunts negative age-related changes in body composition, functionality and myofiber dimensions in rats. J Int Soc Sports Nutr. 2012 Apr 18;9(1):18.