Thursday, April 14, 2016

The benefits of exercise exist on a U-curve

Few would dispute the idea that intense exercise, as a hormetic stressor, is beneficial for improving human health. From reducing blood pressure and cardiovascular disease mortality rates, to aiding in the prevention of body fat accumulation after or during diet-induced weight loss, and more, exercise has innumerable, virtually unquestionable benefits. However, the type, volume and intensity of said exercise matters a great deal.

Many people begin with the supposition that there are "cardio" based exercises, like running and swimming, and "strength" based exercises, such as resistance training, as in a gym, lifting weights, or partaking in Crossfit, which is all-the-rage now. Sticking with this concept, endurance exercises, such as running, biking and swimming, can be classified neatly in the "cardio" category, and have been quite popular since about the 1970s. In the last few decades, one of the most common themes I have seen in individuals who proactively decide to go from living a traditional American lifestyle, to engaging in healthy lifestyle behavior changes, has been that of deciding to "run the marathon."

As I have not yet spent much time overseas, I do not know whether this is strictly a Western phenomenon, but it seems to me that if someone in our neck of the woods learns that something is beneficial, well, by golly, a whole lot more of it must be that much better. Implicit in this notion is that if running is good for my heart, then participating in an ultra-endurance activity like the Boston marathon should make me IronGirl.

Sorry, no cigar. The benefits of [endurance] exercise exist on a U-curve.*

*This is not to suggest that the benefits of resistance exercise do not also exist on their own U-curve. They very well might. I have just not seen any corroborating data, with respect to that question.

Just because something is healthy at one level of intensity, or by a certain volume, does not mean that if you ramp it up a few notches, it will confer the same benefit, let alone even more. Now, we could sift through an endless array of decently well-controlled studies that exist in the peer-reviewed literature touting the benefits of exercise, many of which have looked exclusively or predominantly at endurance training. But I should like, instead, to take a gander at some of the fascinating data demonstrating what might happen if we intentionally ramp up the intensity and volume of endurance exercise in both humans and experimental animals, and look at a few n=1 case reports of people who have voluntarily done the same thing, under the presupposition that because running is healthy, running a lot must be even healthier.

A few years ago, I randomly stumbled across this experiment, by Benito, et al, conducted in Barcelona, and published in Circulation,[1] where they took male Wistar rats and exposed a group of them to intensive 4, 8 or 16 week exercise regimes, while a Sedentary group got to essentially kick back and relax, and then compared the effects of the intervention on the rats' hearts.

Significant functional and morphologic changes occurred in the hearts of those rats in the Exercise group, after 8 weeks of intense training, such that, upon close postmortem inspection, they had marked increases in interventricular septum and left ventricular wall thickness. Statistically significant increases in overall cardiac hypertrophy was noted in the Ex group. Evidence of both left ventricular systolic and diastolic dysfunction occurred by week 8 and 16, respectively, based on echocardiographic results. (RV diastolic dysfunction was claimed evident, but was apparently not statistically significant, and so did not make much of an appearance in the paper, from what I could tell.) In contrast, of course, the Sed group of rats did not show any signs of these significant pathological changes, throughout the duration of the 16 week experiment.

Perhaps the most interesting thing, to me, since hypertrophy of the myocardium as a result of intense and chronic over-exertion is an anticipated, or at least relatively expected, outcome, was when the researchers then looked at the effects of this exercise regimen on "chamber-specific ultrastructural remodeling." A.k.a. The development of myocardial fibrosis.

Here is what they found:





"There is widespread interstitial collagen deposition with disarray of myocardial architecture." Aside from being a clever way to say, "These rat hearts are fucked, and this kind of training is probably not a good idea," (at least for Wistar rats) these results suggest that the formation of these fibrotic lesions may present a substantially increased risk of potentially fatal dysrhythmia -- this could be one possible explanation for the all-too-common ultra-endurance athlete who drops dead at 35 from sudden cardiac related death. So, naturally, that's precisely what their team looked for next.

According to figure 6, researchers were able to induce polymorphic ventricular tachyarrhythmias via ventricular stimulation in the Ex rats:


Luckily -- again, if you are an unreasonably trained Wistar rat -- there is an upside to all this. A period of "de-training" post-intervention could reduce the cardiac remodeling seen in this experiment, which may indeed mitigate the detrimental effects of the overtraining seen, here. There are some pretty big questions implicit in this, however. Such as, will this detraining benefit continue to exist, if the intervention period is stretched further? At what point will the negative effects of the intervention persist? What are the mechanisms involved in producing these effects? As the authors state in their discussion: 


The biggest question of all, as many of you reading this will have already been screaming at me for the last ten minutes, assuming you've made it this far, is... Will it translate to humans?

Here is where things get really interesting.

In 2011, Wilson and colleagues published a paper in the Journal of Applied Physiology[2] examining 12 veteran endurance athletes, many of whom had either completed 100 marathons or spent over ten years continuously training at an olympic level. This is about as close as I can imagine coming to an ecological replication of the Benito experiment, if ever I've seen one.

Although there are a few inherent limitations in its use, such as it "relies on the signal intensity difference between fibrotic and normal myocardial tissue, and hence a region of 'normal' nulled myocardium is needed as a reference to detect abnormalities,"[3] Wilson, et al, used late gadolinium enhancement imaging (LGE) to detect patterns of myocardial fibrosis in the study participants. 50% of them had diffuse patterns of myocardial fibrosis. These are people who are supposed to be healthier than all of us, especially due in large part to their exceptional athleticism. In spite of it, they actually appear to be worse off, at least with respect to the health of their heart muscle! (Age is a factor for some of the athletes studied in this trial, but age-matched controls were examined, and the age-confounder was set aside as an important contributor.)

The study was of course a small one, and so generalizability may be a factor of consideration. But think about it, though. This is not supposed to be representative of the population at large, but of a small subset of elite athletes. Therefore, the sample may in fact be sufficient to generalize, at least to other extreme endurance athletes. And remember, all 12 of these individuals were "otherwise healthy" at the outset of the study. None of them were smokers, as far as they were willing to admit to on the inclusion data. (Though, being that they were all males, translating these data to females may prove challenging. Gosh, we could really use some more data on female athletes...)

Although I found this study fascinating because it was almost like a real-life corroboration of Benito and colleagues animal study, this is not the end of the line for similar research in human beings. Oh, no. There's actually quite a bit more, following this same line of logic:

In 2012, Dr. James O'Keefe, et al, published a review in Mayo Clinic Proceedings[4] suggesting that, although the hypothesis warrants further research for substantiation, there is good human and animal data to suggest, at least on a preliminary basis, that excessive endurance exercise (EEE) may predispose susceptible individuals to adverse cardiovascular events, including arrhythmia and extensive myocardial fibrosis.

In a 2011 issue of the European Heart Journal[5], La Gerche, et al, describe their study of 40 endurance athletes, after the completion of a marathon, and suggest that "although short-term recovery appears complete, chronic structural changes and reduced right ventricular function are evident in some of the most practiced athletes..."

In 2010, Wilson, et al, published a study in the European Journal of Applied Physiology[6] demonstrating that long-term, high intensity endurance activity is strongly associated with maladaptive changes in cardiac morphology and electrical conductivity, among other physiologic and pathophysiologic alterations, even connecting it to implications with respect to brain function.

In 2013, Doutreleau, et al[7] showed that such chronic and excessive endurance training could have negative consequences on the conduction pathways in the heart, presumably through this remodeling and fibrotic changes in the myocardium. In their study, they report two cases of type II second-degree atrioventricular block in well-trained, otherwise healthy, middle-aged adult athletes.

Although merely a case report, and not a study, per se, in 2012, in the Journal of Athletic Training[8], Poussem, et al, describe a highly-trained, 30 year old cyclist with "nonsustained ventricular tachycardia originating from the left ventricle on a stress test associated with myocardial fibrosis of the left ventricle as shown with magnetic resonance imaging." The unique thing about this case report was that most often these findings are seen after sudden cardiac death (SCD), on autopsy. Presumably, the diagnosis in this instance is being relegated to an effect of intense, unrelenting endurance exercise, but, there are probably too many confounding variables in this particular instance to be able to say one way or another. It is particularly interesting, however, that it happens to line up quite nicely with the rest of the data, thus far. (Was the cyclist in this case a recreational drug user? Could that have caused or contributed to the pathology seen, here?) Still...

In 2008, published in the British Journal of Sports Medicine,[9] professor Whyte and colleagues ask the question whether exercise may or may not have been the cause of the idiopathic left ventricular hypertrophy and idiopathic interstitial myocardial fibrosis found during the autopsy of an "experienced, highly trained" marathon runner, who died suddenly while running.

Published in the British Journal of Sports Medicine back in 2007[10], Mitchell M. Lindsay and Francis G. Dunn conducted the first experiment, to my knowledge, demonstrating that, in veteran endurance athletes with left ventricular hypertrophy, there is "biochemical evidence of disruption of the collagen equilibrium favoring fibrosis... suggest[ing] that fibrosis occurs as part of the hypertrophic process in veteran athletes."

In 2011, La Gerche published another trial[11], this time with 39 endurance athletes and 14 controls, looking for evidence that intense exercise might be putting an exorbitant load on the right ventricle of the heart. Despite some inherent limitations, which they carefully outline in the paper, the following is what they found after careful analysis of the data:




On top of all the myocardial fibrosis business, there are other potential risks that have been outlined in the literature, since Benito and others' work. For instance, just this year, M Sanz de la Garza, et al, published a study in the Scandinavian Journal of Medicine and Science in Sports[12] looking to examine the potential impact of intense endurance training on multiple thrombotic risk factors, and claim that excessive endurance exercise may actually increase the chances of pulmonary embolism, through the development of deep vein thromboses (DVT), or clots in the legs. Unlike the mechanisms that may be involved in the development of cardiac morphologic changes via collagen recruitment in cardiomyocytes, etc., these are likely to be due to extraneous complications from overexercising; including dehydration, inflammation and, as they put it in the abstract of the paper, "hemoconcentration."

So, ultimately, what does this mean? Does this mean that I think cardio is uniformly "bad" and that you should stop partaking entirely? Do I think any and all forms of endurance training are unhealthy?

Uh... No. Wait, that wasn't good enough. Can I get a hell no, instead?

Look at the one consistency in all these data. Everyone studied (including the rodents!) were pushed -- or, rather, pushed themselves, in the vast majority of cases -- to the breaking point. There is an unimaginable difference between running a weak 2 miles per day and running 11 miles per day, at 80% of your purported maximum heart rate.

Will some regular, light endurance training destroy your heart? No! Will training at intensities similar to ultra-endurance triathletes destroy your heart? It's a little too soon to tell, but, it appears quite possible... so, again, what's "the answer?"

My recommendation would be to avoid participating in multiple marathons. Otherwise, I would be equally as concerned about the health of your heart muscle, if you remain seated on your love seat like a lazy slob eating Sun Chips all day, delicious though they are.

As I have said twice now, there is an undoubted U-curve associated with the benefits of [endurance] exercise. Too little is not good; way too much is also bad. My final recommendation? Adopt the Goldilocks principle of "just right" and you'll be good to go. But, whatever you do, please choose to move, rather than be a slug. "Eat less, move more" doesn't have to be "right" for me to know that exercise in appropriate amounts is incredibly beneficial and health promoting. The lesson in this post is more about what happens if you push it to an extreme on the spectrum -- and to suggest that, as with most things, there may be a sweet spot, somewhere in the middle, where a balanced approach confers the best results.

(Me? I'll stick with picking up heavy things and putting them back down, and the occasional sprint or HIIT session, here and there... but my rationale for that will have to wait. I've already kept you plenty long enough.)


REFERENCES

1. Benito, B., Gay-Jordi, G., Serrano-Mollar, A., Guasch, E., Shi, Y., Tardif, J. C., ... & Mont, L. (2011). Cardiac arrhythmogenic remodeling in a rat model of long-term intensive exercise training. Circulation, 123(1), 13-22.
2.Wilson, M., O'Hanlon, R., Prasad, S., Deighan, A., MacMillan, P., Oxborough, D., ... & George, K. (2011). Diverse patterns of myocardial fibrosis in lifelong, veteran endurance athletes. Journal of Applied Physiology, 110(6), 1622-1626.
3. Karamitsos, T. D., & Neubauer, S. (2013). Detecting diffuse myocardial fibrosis with CMR: the future has only just begun. JACC: Cardiovascular Imaging, 6(6), 684-686.
4. O'Keefe, J. H., Patil, H. R., Lavie, C. J., Magalski, A., Vogel, R. A., & McCullough, P. A. (2012, June). Potential adverse cardiovascular effects from excessive endurance exercise. In Mayo Clinic Proceedings (Vol. 87, No. 6, pp. 587-595). Elsevier.
5. La Gerche, A., Burns, A. T., Mooney, D. J., Inder, W. J., Taylor, A. J., Bogaert, J., ... & Prior, D. L. (2011). Exercise-induced right ventricular dysfunction and structural remodelling in endurance athletes. European heart journal, ehr397.
6. Wilson, M., O’hanlon, R., Basavarajaiah, S., George, K., Green, D., Ainslie, P., ... & Nevill, A. (2010). Cardiovascular function and the veteran athlete. European journal of applied physiology, 110(3), 459-478.
7. Doutreleau, S., Pistea, C., Lonsdorfer, E., & Charloux, A. (2013). Exercise-induced second-degree atrioventricular block in endurance athletes. Medicine and science in sports and exercise, 45(3), 411-414.
8. Poussel, M., Djaballah, K., Laroppe, J., Brembilla-Perrot, B., Marie, P. Y., & Chenuel, B. (2012). Left ventricle fibrosis associated with nonsustained ventricular tachycardia in an elite athlete: is exercise responsible? a case report. Journal of athletic training, 47(2), 224.
9. Whyte, G., Sheppard, M., George, K., Shave, R., Wilson, M., Prasad, S., ... & Sharma, S. (2008). Post-mortem evidence of idiopathic left ventricular hypertrophy and idiopathic interstitial myocardial fibrosis: is exercise the cause?. British journal of sports medicine, 42(4), 304-305.
10. Lindsay, M. M., & Dunn, F. G. (2007). Biochemical evidence of myocardial fibrosis in veteran endurance athletes. British journal of sports medicine, 41(7), 447-452.
11. La Gerche, A., Heidbuchel, H., Burns, A. T., Mooney, D. J., Taylor, A. J., Pfluger, H. B., ... & Prior, D. L. (2011). Disproportionate exercise load and remodeling of the athlete’s right ventricle. Med Sci Sports Exerc, 43(6), 974-981.
12. Sanz de la Garza, M., Lopez, A., & Sitges, M. (2016). Multiple pulmonary embolisms in a male marathon athlete: Is intense endurance exercise a real thrombogenic risk?. Scandinavian Journal of Medicine & Science in Sports.

Monday, January 11, 2016

Are dietary carbohydrates required for building muscle?

The question I am concerned with asking is not so much "Is it possible to build muscle while eating very low carb," but more like, "Can I build an appreciable amount of muscle, without adding extra carbohydrates into my ketogenic diet?"

The important question is not necessarily "Is it optimal?" or "Is it the easiest way?" or "Is it the best way?" It is definitely possible, at the very least; I know this from first-hand experience, anecdotal though that is. It may or may not be optimal, I don't know. Nor, for the time being, does it matter much. Let us concern ourselves with one question at a time.

We want to know whether it is reasonable to expect, coupled with resistance exercise, a ketogenic diet to be appreciably anabolic, without additional carbohydrates. Can one accrue significant muscle mass with this approach, or do we require supplemental carbohydrates to make this happen?

If you are not immersed in today's exercise science dogma, you might find yourself wondering why supplemental carbs should be necessary for muscle building, at all. The hypothesis essentially goes as follows:

Carbohydrates stimulate the secretion of insulin; insulin is a highly anabolic hormone (one of its essential functions is to regulate tissue hypertrophy); therefore, driving insulin by eating carbohydrates around your workouts will accelerate muscle protein synthesis (MPS) and accretion on a greater scale than would have been possible without them.

Or, stated a different way:

Because carbohydrates stimulate insulin, and insulin is one of the body's most anabolic hormones, it is reasonable to think that, without the additional insulin secretion caused by the consumption and absorption of these carbs, muscle protein accretion on a very low carbohydrate diet will be minimal, blunted, or otherwise unlikely.

(AKA: Without supplemental carbs, and, therefore, bursts of hyperinsulinemia, building muscle mass while on a very low carbohydrate diet is unlikely to occur. That's the presumption, anyway.)

This latter proposition is, in a roundabout sort of way, how I've seen the argument formed, more times than not. In my opinion, there are a few important caveats to consider, with regard to this particular argument, before moving on.

a.) We are not just considering the potential effects of consuming a ketogenic diet, alone, on muscle protein synthetic rates, but as coupled with weight training (or some other form of resistance exercise), designed for skeletal muscle hypertrophy. Assuming dietary protein, and, therefore, the plasma free amino acid pool, is appropriately topped off, and exercise intensity sufficient to promote tissue growth and remodeling is present, is it reasonable to think that the amount of dietary carbohydrate matters all that much?*

*Remember, we are thinking specifically of intracellular (myofibrillar) hypertrophy, at the moment, not of myocyte bioenergetics and energy utilization to fuel specific workouts, per se. Let's not confuse fuels that may or may not be required to sustain certain types of contractions with fuels that may or may not maximize hypertrophy. As far as we can tell, right now, the exercise science literature seems to show, rather consistently, that carbohydrates are quite useful for sports performance purposes, and have their place, depending on the context and the activities in question. However, this may not be reflective of what metabolic fuels best suit muscular hypertrophy. (e.x. Elite long-distance runners and other high-volume endurance athletes typically consume large quantities of carbohydrates, yet remain quite... frail, for lack of a better term.* No offense intended, of course.)

*Just a random consideration, but, something to ponder: These ultra-endurance athletes are quite emaciated, despite large quantities of dietary carbohydrate and, thus, big bursts of hyperinsulinemia.... Hence my perspective that this popular conception of "more insulin = bigger anabolic response" is too simplistic.

b.) Oftentimes, for the sake of simplicity, we like to talk about "The" Ketogenic Diet, as though it is a single, uniform approach to nutrition. For the most part, this seems to be sufficient for the purposes of discussing very low carbohydrate diets versus diets higher in carbohydrate, in general. Naturally, however, distinctions must be made, when certain points of discussion or contention are brought up. In this situation, to say The ketogenic diet is not necessarily appropriate, because there is not just one approach to ketogenic dieting. There is the traditional, pediatric, anti-epileptic approach to ketogenic dieting that was low in protein, virtually zero carbohydrate, and even restricted water intake (for whatever reason). We are not talking about that. Nor are we talking about the kind of ketogenic diet that is used as a neuropsychiatric therapy, today, to keep glucose and glutamate low and insulin at bay, for neuronal health. Because I tend to occam's razor most things, where possible, I think we could simplify this into ketogenic diets that restrict protein as well as carbohydrates, and ketogenic diets that contain ample dietary protein.

In most circumstances, for healthy persons, it is my personal and professional opinion that it is unreasonable to suggest one should be asked to restrict dietary protein -- even for the purposes of keeping glucose and insulin at its absolute floor. (It is highly unlikely that you will experience souring plasma glucose excursions by eating 10 oz of chicken, instead of 3.5 oz of 80:20 ground beef.) Therefore, "the ketogenic diet" I am considering, here, with special regard to the aforementioned question(s) regarding muscular hypertrophy, include not only concomitant and consistent resistance exercise, but also an appropriate amount of protein to maximize hyperaminoacidemia.

c.) Lastly, I used the word "significant," earlier in the post, re: building muscle on keto. How much muscle are we talking about, here? Massive, Lee Priest-like, bodybuilding muscles are never built by anyone without (1) a genetic propensity, and a vast, inborn number of myocytes for it, or are (2) taking exogenous anabolic steroid hormones. Will the ketogenic diet help me in my unlikely pursuit to look like Ronnie Coleman? Not a chance. Then again, neither will a high carbohydrate, high protein, traditional bodybuilding-style diet, so...

I don't intend for that to come across as snarky so much as to say that it is imperative that for this discussion to have any meaning, we must first define our terms. What level of bulk are we considering "built," here? (I may have my own view on what constitutes built, and your view may differ significantly from that, maybe by a few orders of magnitude. For the sake of this argument, I'd like to use a pictorial example of what, in competitive bodybuilding circles, is considered a "physique" build. Below is a picture of a friend of mine. Although he is not a bodybuilder in the traditional sense, in that he isn't ridiculously massive, he is quite muscular and symmetrical, even after cutting down to a low body fat percentage. This is what I would consider sufficiently muscular to make this discussion worth having:



This is probably how I would distinguish muscular, in this context, because anything less can be construed as simply "lean" or "toned," and anything more might be taken to be "unachievable muscularity" for most normal people. You might disagree, and that's fine, but I'm simply putting this here as a point from which to argue from, for the sake of logic. It can't just be some up-in-the-air, random target post, on which none of us agree, or have even attempted to nail down. At least not if we can hope to achieve anything meaningful in having this discussion. Perhaps important to note is that Ari was not using a low carbohydrate diet to bulk, as far as I know. That is beside the point, however. The picture is meant to serve as a reference point, not evidence on behalf of my position.


From my perspective, most significant muscle building seems to occur, predominantly, as a result of two things: Amino acid availability, and consistent strength training, intense enough to maximally stimulate the muscle fibers and fatigue the motor units. Bing, bang, boom. Little to no evidence, from what I have seen, demonstrates a further need for carbohydrate to augment the process of muscle protein accretion.*

*I am not denying the anabolic effect of insulin. That would be silly. In fact, I am suggesting that perhaps the post-prandial insulinemia achieved by obtaining a nice big bolus of protein, post-workout, should be sufficient to induce this process.[1] (For the record, that wasn't really meant to be a sly reference to the "anabolic window," which is sort of a bunk concept.) Unless you are a type I diabetic producing so little insulin that if you don't inject it you will wither away and die, it is unlikely, in my opinion, that hyperinsulinemia to the degree that is presumed to be necessary from the aforementioned pro-high-carb camp is, in any way, a requirement for substantial skeletal muscle hypertrophy.





As you may have already noticed, this experiment looked at a 50 g bolus of protein, from chicken, as compared to a 50 gram bolus of glucose, and then a 50 g bolus of each, coupled together. As you can see, 50 grams of protein rather substantially increases serum insulin concentrations; quite similarly to dietary glucose alone. Recall, however, that, under the circumstances of most therapeutic ketogenic diets, people do not tend to consume 50 g boluses of protein in single meals. Hence, insulin levels may not go nearly that high. But, again, we are considering a very low-carb diet with more protein than is typical.


We know from metabolic ward overfeeding experiments -- even in sedentary people (or, more specifically "untrained individuals") -- that lean body mass (LBM) can increase concomitantly (though not necessarily proportionally) with adipose tissue growth, even in spite of lower protein intakes sometimes. Therefore, I contend that perhaps we are putting far too much stake on "what should I eat for growth?" Importantly, muscle building is about more than just diet. Arguably, more than anything else, it is about lifting; or otherwise maximally fatiguing the muscle tissue with resistance training. Are you sleeping like shit, always stressed out and constantly over-trained? Prepare for more muscle protein degradation, due to chronically elevated cortisol levels and a dysregulated circadian rhythm, even if your diet is considered well-formulated by some standard or other. A well-formulated diet is imperative for success in this area, of course, but, it is not the only component involved.

It has been hypothesized that poor sleep quality and sleep deprivation could both decrease the muscle protein synthetic response to exercise and protein ingestion and increase muscle protein degradation.[7] Speaking of lifestyle factors other than nutrition that impact muscle mass, cigarette smoking can impair muscle protein synthesis and may increase the expression of myostatin, a powerful muscle growth-inhibitor.[8]

Up until this point, much of the discussion has centered around anecdotes. In fairness, that's probably because there is little to no substantive and controlled data on muscular hypertrophy in the context of ketogenic dieting. In fact, I only know of one research group actively studying this specific area, right now. Whatever answer one chooses to accept must, if we are being honest, inevitably come from a piecing together of various data points from random, and sometimes seemingly arbitrary, trials, and then a commonsense summation of all the data.

Now, let's take a look at some relevant data.

Throughout my career in the fitness industry, nothing else has been claimed or cited as the gospel truth with more vehemency than the notion that there is an anabolic window that ends about 45-60 minutes post-exercise. That if you don't get all the protein and sugar in the world into your system within that period of time, the fucking moon will explode and Jupiter will shit molten meteorites that will fall into your grandmother's living room and kill her and your favorite childhood cat in one fell swoop. Basically, 30 minutes post-workout, you had better pound that protein shake, or else all your hard work will have gone to Hell in a handbag.

In reality, there is very little reason to believe this concept. At least nothing that has really been substantiated by the scientific literature. In fact, if there is an anabolic window, per se, it likely spans the course of several hours after an intense workout, not one. An interesting bit of evidence in favor of this idea is the fact that GLUT4 translocation occurs in skeletal muscle cells after a workout, irrespective and totally independent of insulin secretion,[2-3] which allows for amino acids to be taken up into the myocytes and initiates the physiological process of exercise-induced muscle protein synthesis -- and also for glucose to be oxidized, which is one of the reasons exercise is prescribed for hyperglycemic diabetic patients. This GLUT4 transmembrane receptor translocation alone is maintained for a few hours after the workout is over, meaning a good percentage of the subsequent glucose and amino acids you absorb will likely be shuttled preferentially to fuel the muscle tissue.

Also, intense muscular contractions (acute resistance exercise) cause a complicated intracellular biomolecular cascade called mammalian target of rapamycin complex 1 (mTORC1), which is a powerful regulator of protein synthesis. Although you can augment this process with supplemental leucine, as would be found in a BCAA drink or whey protein shake, or by consuming more protein in general, intense exercise, by itself, is sufficient to initiate the mTOR redox signal and lead to an impressive increase in rates of muscle protein synthesis.[4-6] Albeit an extremely complicated process, as you can see from the chart below, this signaling cascade does not appear to be reliant on post-workout carbohydrate consumption for activation. (That's not to suggest insulin does not play its own interesting role in regulating mTORC1. Merely that it is more complicated than this, and does not rely exclusively or necessarily upon either carbohydrates or insulin for activation.)



From Hulmi, et al. (2009). [ref 6]...


So why were people so adamant that this refueling immediately post-workout was a downright necessity for optimal recovery and hypertrophic muscular adaptations to exercise? I think, to a large extent, it had something to do with the hypothesis that tapping off muscle glycogen levels as quickly as possible is an essential component to post-workout recuperation.

I'm not sure I believe there is any good published literature that substantiates the claim that we must replenish intramuscular glycogen stores immediately after an intense bout of exercise for recovery or performance -- unless one is an elite athlete, or overreaching. Or, indeed, that these energy storage sites would not appropriately refill themselves, as the day goes on and you eat your normal diet. Frankly, with rare exceptions for elite ultra-endurance athletes and the like, virtually no one is totally wiping out their glycogen stores in a single workout.

That said, Camera, et al, in 2012, showed that low intramuscular glycogen levels do not appear to have any suppressive effect with respect to the anabolic impact of resistance exercise on muscle growth.[9] When I first read the conclusions of that paper, I thought to myself, Well, even if the hypertrophic response to low intramuscular glycogen isn't impaired, perhaps athletic performance is a different beast.... It turns out that Symons, et al, studied this back in 1989 and found that there is no such performance declination as a result of training with low intramuscular glycogen, either.[10]

Over the last few years, there have been some rather fascinating studies in the exercise physiology literature that have set out to examine whether or not increasing carbohydrates along with an athletes post-workout protein might aid in building more muscle than with the protein, alone. If the answer to these questions clearly favors the hypothetically anabolic role of supplemental carbohydrate, in this context, it would mean, of course, that more carbohydrate would be better for building muscle, while a diet lower in carbohydrate, like the ketogenic diet, might be decidedly less effective in promoting the same level of muscle growth. If, on the other hand, the answer is negative, we cannot necessarily suggest, then, that a very low carbohydrate diet is better or even equal to a high-carbohydrate diet for muscle protein accretion; just that supplemental carbohydrates, post-workout, are not a necessary requirement for additional hypertrophy beyond consuming protein alone. A standard training diet, already high in carbohydrates, without extra post-workout carbs =/= a ketogenic diet without post-workout carbs.

There are three specific studies I would like to touch on, quickly, each of which I believe did a fantastic job at covering this particular topic:

~ [11] Figueiredo, et al (2013).
~ [12] Koopman, et al. (2007).
~ [13] Staples, et al. (2011).


Overall, I think the JISSN review is a good one. The authors asked some very interesting questions, not the least of which was Does leucine require insulin to stimulate protein synthesis? The answer they arrived at, by the way, was no. Not necessarily.


In the end, as anticipated, Figueiredo and Cameron-Smith concluded, after a well thought out and provocative article, that there is currently (circa 2013) insufficient evidence to suggest that supplemental carbohydrates should be expected to provide any muscle building effects beyond protein alone; but that, as always, further investigations are warranted.


The Koopman study was a randomized-controlled crossover trial of 10 healthy, physically fit men, designed to answer the same basic question: Do supplemental carbohydrates contribute to further muscle protein synthesis, above and beyond the consumption of protein, alone?

Even though the sample population seems small, it was statistically powered to detect an effect, and this population is sufficiently representative of that which we are interested in extrapolating to. Their answer was another resounding No, seen clearly in their title: "Co-ingestion of carbohydrate with protein does not further augment post-exercise muscle protein synthesis."

Figure 1 shows the between group insulin levels, which were significantly greater in the PRO + HCHO group, yet, despite this difference, as the results demonstrate, there was no difference in muscle protein synthesis. This seems to lend further credence to my hypothesis that adequate protein and exercise intensity are the two most important factors for muscular hypertrophy.



Lastly, we have the Staples study. This is easily one of my all-time favorite papers. I thought the authors did a fantastic job writing up this experiment and connecting all the dots. Here are some important highlights, relevant to the same study question as before:



"Muscle protein synthesis increased by approximately 54% after exercise, compared with the values in the non-exercised leg, but there were no differences between the protein and protein + carbohydrate trials in the non-exercised or the exercised legs."

"Muscle protein breakdown was increased by approximately 37% after exercise compared with values from the non-exercised leg, but there were no differences between the protein and protein + carbohydrate trials in the non-exercised leg or after exercise."


There was a statistically significant difference between the PRO vs PRO + CHO, in favor of the latter, with respect to Akt phosphorylation, as shown above. However, it clearly wasn't important enough to cause any discernible changes in muscle protein accretion between groups which would be necessary to show that the CHO supplemented group reaped additional benefit. (This alteration in Akt, favoring the PRO + CHO group is likely due, from what I understand of the mechanisms of this molecular signaling pathway, from the significantly higher insulin levels in the PRO + CHO group, as compared with PRO alone. As is clear, though, this was insufficient to contribute to an appreciable difference in MPS in favor of PRO + CHO over PRO alone.)


Update: please also check out this paper[18], by Glynn, et al., from 2013. This one in particular -- because of the way the experiment was designed -- coupled with the strength of the Staples paper, is, from my perspective, sufficient to conclude, once and for all, that supplemental carbohydrates are in no way required for building muscle.

As it stands, it seems that the answer to the question we have been asking is that supplemental post-workout carbohydrate ingestion is not needed to further augment the well-established benefits of protein alone. However, as was mentioned previously, this does not serve as sufficient evidence in favor of ketogenic diets for muscle building, in and of itself. Moving on...

What about some other biochemical changes that result from altering the macronutrient composition of the diet?

At the University of Connecticut, in 2002, Dr. Jeff Volek and his team conducted an experiment[14] where they examined various biochemical assays to assess the effects of a carbohydrate-restricted diet on different hormones, such as thyroid hormone, testosterone and others. Unfortunately, this particular trial did not look at the effects of the intervention on female hormonal status, so we cannot extrapolate from the 20 otherwise healthy men who were involved, here, to whether this would also apply equally to women. However, with respect to male physiology, the 12 men who were randomized to receive carbohydrate restriction as a therapy for 6 weeks saw some rather dramatic changes in their blood panels.

Even though the authors make no mention that I can see of having the participants of this trial exercise, the low carb arm lost a mean of 3.4 kg in body fat over the 6 weeks, while increasing their lean body mass by an average of over 1 kilogram. These changes were apparently the direct result of changing just the macronutrient composition of their diets, favoring fats and restricting carbohydrates.

Interesting changes occurred with many of the assays, it seems, but, of particular importance to the question we are interested in, here, both total and free testosterone increased significantly, while sex-hormone binding globulin decreased. Depending on how substantial this difference is, this should mean that the men who were lucky enough to be randomized to the intervention group would experience an increase in lean mass and a decrease in fat mass. And, as we have just learned, that is precisely what happened. (Some of the reduction in body fatness was probably also due to increases in total and free thyroxine, in the carbohydrate-restricted arm, as well, as compared with the controls, whose laboratory findings, as predicted, remained largely the same throughout the duration of the trial.)

Fascinating though I think Volek and colleagues findings are, the impact of higher fat, lower carbohydrate dietary modifications on sex and steroid hormones has been well-established for many years. In 1986, Reed, et al, conducted an experiment to see what would happen to sex-hormone binding globulin (SHBG), free testosterone and total cholesterol concentrations, should the macronutrient ratios be shifted in this manner.[15] They, too, came to conclusions similar to those Volek and his team eventually reached.*



*Many traditional bodybuilders are indoctrinated to believe they need to eat very low fat diets for fat loss during the cutting aspect of their training, and, while reducing total fat intake can, under the right circumstances, certainly aid in the loss of body fat, to reduce it too low is to risk reducing total and free testosterone, as demonstrated in the two studies mentioned above. For both fat mass reduction and the inhibition of muscle protein breakdown, it would seem this is a bad plan.

More recently, in 2014, Jeremy Silva put together a nice little study on the effects of a very low carb, high fat diet on lipid and anabolic hormone status.[16] Like Volek and Reed, Silva, et al, also found that increasing dietary fat and decreasing carbohydrate led to a significant increase in total testosterone, as compared with the control group on the standard western diet.


So far, it seems there are no apparent strikes against the ketogenic diet as it pertains to building muscle, yet, with specific regard to these last three trials, there may be some interesting strikes against high carbohydrate, low-fat diets for muscle building -- the implications of which, if there are any such implications worth noting, will have to be further elucidated elsewhere.

Lastly and perhaps most importantly of all, these bits and pieces of articles will mean nothing, if a good randomized-controlled trial comes along and proves that very low carbohydrate diets significantly impede muscle growth or drastically increase protein degradation and that carbohydrate supplementation is necessary to attenuate this process, or something like that. However, as it happens, there is only one published trial that has ever set out to research the effect of a ketogenic diet on skeletal muscle strength and hypertrophy in trained individuals. Dr. Jacob Wilson is another active voice in the online fitness community, and he is how I learned about this study, which he contributed to, along with esteemed Drs. Volek and D'Agostino.

Wilson's trial (Rauch, et al[17]) of 26 trained, college-aged men used ultrasonography of the quadriceps muscles to determine that the VLCKD group increased their lean body mass by an average of 4.3 kg, while the traditional western diet controls only increased their lean body mass by 2.2 kg, even though the two groups were matched equally with dietary protein and exercise.

To be honest, I am not so sure about the use of ultrasound to accurately and reliably determine subtle changes in muscle tissue with enough sensitivity to be reasonably precise. Then again, I don't know, because it's the first time I've seen it. They did, however, use DEXA to determine bone and fat mass, which we know is one of the most reliable tools we have for measuring body fatness in trials like these. Perhaps if the authors juxtaposed the results of both pieces of equipment...?

In any case, this particular trial -- first of its kind -- actually looked directly at the impact of a ketogenic diet on muscle protein synthesis and skeletal muscle hypertrophy and body composition, and the very low carbohydrate diet in this case was actually superior! Significantly so, it seems. (Then again, I think each group may have had these measurements taken after glycogen and water replenishment, at the end of the trial, so that figure might actually be a bit confounded. However, when considering the only experiment we have, so far, on this very particular outcome question, one cannot say that a ketogenic diet of the sort we mean, here, is less anabolic than one higher in carbohydrate. At the very least, when matched for dietary protein intake and exercise intensity, they are equivalent, and seem to lead to virtually identical outcomes.)

So, do we need carbs to build muscle?

Based on my experience, and all the #anecdata I am aware of, I would say absolutely not. Based on the state of the evidence, right now, I don't think we can appropriately answer that question, in the context we are inquiring about, without better and more exhaustive research. That said, I do think we have enough bits and pieces of data, as compiled above, to at least tentatively suggest that a ketogenic diet is not "less than" a carbohydrate-rich diet, for the purposes of building muscle. I am willing to stick my neck out a little and wager that the results of these future studies, if and when they hit the press, will probably conclude that it really doesn't matter much whether you eat high or low carb, if your primary outcome is to maximize hypertrophy. (Although, if I'm being honest, I have a sneaking suspicion that similar results to Volek, Wilson and D'Agostino paper might make a consistent appearance over time...)

What should we do in the meantime, if building a decent amount of muscle is the goal?

1. Don't be afraid to eat enough food.

2. Maximize the anabolic potential of your diet by consuming sufficient protein. (Right now, this seems to peak at ~2x the RDA.)

3. Exercise to muscular fatigue a few times per week.

* * * * * * * * * *

TL;DR

1. Given sufficient dietary protein to maximize plasma hyperaminoacidemia and the anabolic response to exercise, and consistent resistance training with the right level of intensity and appropriate recovery, supplemental carbohydrate does not seem to be a requirement for the average person to build an appreciable amount of muscle.

2. Exercise, itself, as a means of initiating the mTORC1 cascade and other cellular anabolic signaling pathways is likely the single most important stimulus for promoting skeletal muscle cell protein synthesis, independent of any other factor, including carbohydrate consumption and insulin secretion.

3. Genetics arguably plays the biggest role in determining whether or not your muscle tissue will grow substantially. If I have some significant number of myocytes less than you, from birth, and we train and eat and sleep and live in exactly the same way, for the same exact same length of time, no matter what I do, I will never be able to build more muscle than you; muscle cells do not divide. This is genetic. I'm sorry. We do our best with the hands we're dealt... (Someone could have taken Jay Cutler as a young man, pre-bodybuilding, fed him a strict, low protein vegan diet, and he would still be the biggest guy in the room as soon as he picked up something heavy and put it back down.) In other words, it is highly doubtful, in my opinion, that extra carbs will really be your edge. (Bear in mind: whether or not supplemental carbohydrates are healthy and/or useful for other things, in other contexts, is beyond the scope of this post.)

4. If there did happen to be some advantage of higher carbohydrate, hyperinsulinemic diets, over very low carbohydrate diets, with respect to building muscle mass, it is probably so small as to be negligible. (At least as predicated on the data I have available to me, at this time.)

5. Carbohydrate-restricted diets higher in fat may have other anabolic benefits, distinct from insulin, like increased total and free-testosterone, as shown in Volek's study. But again, whether this will turn out to hold true in further human clinical trials remains to be seen. (Who knows, someday there may be data suggesting that "training low" is ideal for building muscle mass. Only time, and good experiments, will tell.)



REFERENCES

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2. Holloszy, J. O. (2005). Exercise-induced increase in muscle insulin sensitivity. Journal of Applied Physiology99(1), 338-343.
3. Kennedy, J. W., Hirshman, M. F., Gervino, E. V., Ocel, J. V., Forse, R. A., Hoenig, S. J., ... & Horton, E. S. (1999). Acute exercise induces GLUT4 translocation in skeletal muscle of normal human subjects and subjects with type 2 diabetes. Diabetes48(5), 1192-1197.
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10. Symons, J. D., & Jacobs, I. (1989). High-intensity exercise performance is not impaired by low intramuscular glycogen. Medicine and science in sports and exercise21(5), 550-557.
11. Figueiredo, V. C., & Cameron-Smith, D. (2013). Is carbohydrate needed to further stimulate muscle protein synthesis/hypertrophy following resistance exercise. J Int Soc Sports Nutr10(1), 42.
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13. Staples, A. W., Burd, N. A., West, D. W., Currie, K. D., Atherton, P. J., Moore, D. R., ... & Phillips, S. M. (2011). Carbohydrate does not augment exercise-induced protein accretion versus protein alone. Med Sci Sports Exerc43(7), 1154-61.
14. Volek, J. S., Sharman, M. J., Love, D. M., Avery, N. G., Scheett, T. P., & Kraemer, W. J. (2002). Body composition and hormonal responses to a carbohydrate-restricted diet. Metabolism51(7), 864-870.
15. Reed, M. J., Cheng, R. W., Simmonds, M., Richmond, W., & James, V. H. T. (1987). Dietary lipids: an additional regulator of plasma levels of sex hormone binding globulin. The Journal of Clinical Endocrinology & Metabolism64(5), 1083-1085.
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18. Glynn, E. L., Fry, C. S., Timmerman, K. L., Drummond, M. J., Volpi, E., & Rasmussen, B. B. (2013). Addition of carbohydrate or alanine amino acid mixture does not enhance human skeletal muscle protein anabolism. The Journal of nutrition, 143(3), 307-314.