Sports Science Monthly – November 2017

This month, we start with a lengthily mini-review, looking at gaining a fuller understanding of how exercise causes adaptation. This is obviously paramount to coaches, because causing adaptations is what we’re interesting in; being able to understand the underpinnings of this can be useful. It gets a little heavy in places, but keep going and I’m sure you’ll find something useful within it. After that, we move back into the regular format; this month, we have a closer look at massage, repeated sprints as a marker of hamstring rehabilitation status, and the 24-hour athlete, along with a rapid-fire round-up at the end.

As always, the full Sports Science Monthly is available exclusively to HMMR Plus Members. The first topic below is free to everyone, but sign up now to read about all the research. To get an idea of what Sports Science Monthly is all about, the April 2016 edition is available in its entirety for free.

This Month’s Topics

How does exercise cause adaptation?

» Quick Summary: The way the body turns exercise to adaptation is complex and varied, and the result of a number of different molecular changes. Perhaps of most interest is the possible competition between pathways promoting improvements in strength, and those promoting improvements in aerobic fitness.

If you’re reading this, then you probably know that exercise is good for you. This can be in regard to general health, where the improvements experienced following exercise include loss of fat, increases in muscle mass to protect against falling, and improved cardiovascular fitness, which decreases disease risk. From an athlete preparation standpoint, exercise is used in order to drive specific physiological (alongside psychological and biomechanical) adaptations that can enhance performance; perhaps increasing strength allowing a javelin to be thrown further, or improving aerobic capacity to allow running greater distance in a set time.

But how does this actually happen? If you think about it, you might have a surface answer; your strength improves because your muscles get bigger. That’s correct, but how does that happen? If you read widely, or studied sports science at university, then you might know that resistance exercise causes an increase in muscle protein synthesis, which is what causes or muscles to grow. But how does this muscle protein synthesis start to occur? This is where things start to get a lot more complicated, and eventually leads us to the question; how does the body know it has undertaken exercise, and how does this “knowing” translate to physical improvements? These questions aren’t limited to the strength arena; aerobic training elicits its improvements through a number of different mechanisms, such as increased mitochondrial mass and density, improved stroke volume (volume of blood ejected from the heart), improved oxygen carrying capacity (more red blood cells), and also improved oxygen delivery to the muscles (through increased capillary density, for example). But again, this just scratches the surface of what happens after aerobic training, with greater depth required to understand how these processes occur.

Moving into the molecular exercise science era

Questions similar to those posed above were proposed by Kenneth Baldwin back in 2000. In his paper “Research in the exercise sciences: Where do we go from here?”, Baldwin referred to the period of the early 1970s to the mid-80s as the “biochemistry of exercise” era, whereby scientists better understood how exercise affected metabolism at the cellular level. The mid-80s to the time of that paper’s publication were referred to as the era of molecular exercise science, where improvements in technology allowed researchers to look at exercise science at an even deeper level. Such a transformation into being able to closely examine the molecular biology of our cells has enabled us to better understand how the body adapts to exercise.

Molecular example: concurrent training

We can very broadly categorize training as either strength training or endurance training. Most sports require some combination of the two; team sports players, for example, typically require high levels of strength and power, alongside a strong endurance engine. The requirement for these athletes to have a combination of these traits leads to them to undertake strength and endurance training side by side, which is called concurrent training. However, it has long been known that such training can lead to sub-optimal adaptations.

The first study to examine this “interference effect” was published in 1980. In this paper, subjects were placed into one of three exercise groups; a strength group, an endurance group, and a combined strength and endurance group. After 10 weeks of training, both the endurance only and the combined group improved their VO2max, by 25% and 20% respectively. The strength group had no improvements in VO2max, but did see large improvements in leg strength. So too did the combined group – initially they matched the strength group for strength increases, but this tailed off towards the end of the study period. The overall results were clear; endurance training improved VO2max, strength training improved strength, but the combined strength and endurance training resulted in a reduced ability to improve strength relative to the strength training group alone. Such a relationship has been replicated in a number of studies, such that it is now well established that endurance training reduces strength training adaptations, specifically when it comes to hypertrophy, strength, and power.

Why is this? Well, it turns out that the signaling pathways underpinning adaptations to strength and endurance training are different, and may even compete. With regards to muscle hypertrophy (which drives many of the adaptations associated with strength training), the key signaling molecule is called mTOR – the mechanistic target of rapamycin. mTOR stimulates protein synthesis, as well as the creation of new ribosomes (termed ribosome biogenesis). This later aspect is important, because ribosomes are the point in the cell where protein synthesis occurs; ribosomal biogenesis, therefore, increases the ability of the cell to synthesize proteins. Finally, mTOR may inhibit protein breakdown in some cases, which again will be advantageous. We know that mTOR is a crucial pathway in protein synthesis, because if we block it, protein synthesis and muscle hypertrophy is significantly reduced. This pathway is also sufficient to stimulate hypertrophy by itself, although is not the only pathway to drive hypertrophy; a study from 2010 used genetically engineered mice to show this.

We could take our understanding of mTOR a step further by understanding what promotes the activation of this pathway, although this is somewhat poorly understood. It is likely that there is some sort of mechanoreceptor which senses that movement and tension is occurring within the muscle, resulting in activation of a signal cascade that stimulates mTOR. Both IGF-1 and insulin are part of this signal cascade, as are amino acids, in particular leucine.

Adaptations to endurance exercise follow different pathways, and are considerably more varied as endurance adaptations affect the heart and cardiovascular system, muscle, and lungs. Within the muscle, the two major signals for adaptation are an increase in calcium ion concentration (which occurs due to muscular contraction), and an increase in ADP and AMP (which occurs due to increased utilization of ATP for energy). The increase in calcium ions leads to increases in calcineurin and calmodulin-activated protein kinase (CaMK), both of which increase the expression of PGC-1a, a protein which is the master regulator of mitochondrial biogenesis. It’s the second pathway that we are going to focus slightly more on in this section. Here, increases in the concentration of ADP and AMP as ATP is broken down for energy result in the activation of AMP-activated protein kinase (AMPK). AMPK regulates a variety of both acute and chronic adaptations, including the development of new blood vessels (angiogenesis), increased fat breakdown, and mitochondrial biogenesis. Like the calcium pathway, AMPK also increases PGC-1a expression.

We can use our knowledge of these different pathways to help us understand why the interference effect occurs. It appears that an increase in levels of AMPK reduces the activity of the mTOR pathway. This was shown very nicely in a 2009 study from researchers based in Australia. Here, subjects underwent either resistance training followed by repeated sprint training, or repeated sprint training followed by resistance training. When resistance training took place first, there was an increase in S6K phosphorylation (which indicates greater mTOR activation). However, when resistance training followed repeated sprint training, there was no increase in S6K phosphorylation, indicating that the mTOR response was blunted. In addition, metabolic stress – which causes an increase in AMPK – results in inhibition of mTOR. When endurance exercise intensity is low – such as cycling at 70% VO2max for 30 minutes – there appears to be no inhibition of mTOR, indicating that exercise intensity is important.

However, activation of AMPK does not completely explain the reduction in mTOR, and hence the interference effect. This indicates that there must be an additional explanation. One of the proposed mechanisms is via the SIRT1 pathway. SIRT1 is activated by metabolic stress (just like AMPK), and has been shown to inhibit mTOR. (As another aside, resveratrol, the compound found in grapes and red wine, activates SIRT1. There is some evidence that regular activation of mTOR decreases lifespan, along with evidence that resveratrol can increase the lifespan. Resveratrol’s activation of SIRT1, and SIRT1s inactivation of mTOR, is one potential mechanism by which this might occur).

Whatever the specific mechanism, it’s clear that resistance training and endurance training elicit their adaptations through vastly different, and likely competing molecular pathways. Based on the information derived from molecular physiology studies, Keith Baar, a researcher from University of California Davis, has proposed some recommendations for reducing the interference effect of concurrent training:

  1. Where possible, high-intensity endurance training should occur first, and early in the day. A period of at least three hours should then be allowed before taking part in resistance training; this allows AMPK levels to return to baseline.
  2. Conduct resistance training later in the day; whilst AMPK returns to baseline in about 3 hours, the mTOR pathway remains active for 18 hours post-training; allowing this a longer time period potentially enhances the adaptations seen.
  3. Consume a leucine-rich source of protein immediately after resistance training; this will enhance mTOR activity and promote protein synthesis.
  4. Consume sufficient carbohydrates between endurance and resistance training. Both AMPK and SIRT1 are activated by low glycogen and caloric restriction; the consumption of both calories and carbohydrates will reduce their activity.
  5. Low-intensity endurance training appears to have no negative effects on the hypertrophic response to a subsequent resistance training session. In fact, a strength training session immediately following a low-intensity endurance training session may enhance the adaptations seen from the endurance training session.

Do I need to know this?

You might think that, as interesting as this new science is, it doesn’t really affect your sporting practice. Broadly speaking, right now you’re probably right; the research at present doesn’t dramatically change training practices, but tends to explain what we see following training in terms of adaptation. This will cause coaches who rally against the scienceification of sport to scoff – but remember, you’re a scientist too! The training methods used by coaches have for years been refined in order to enhance results; whilst you couldn’t measure or understand the molecular processes governing these, you saw their results. The ability to explain what we see if the second step of sports science (after being able to measure it), and this is where molecular exercise physiology is right now. But the future holds promise; if we understand what happens and why, we can manipulate things in order to better promote the adaptations we do want. Over the last ten years, this has started to happen, with a number of studies using the knowledge gleaned from molecular physiology studies to enhance training adaptation. A great example of this comes from the use of carbohydrates in endurance sport, the manipulation of which can be used to drive specific adaptations.

Carbohydrate cycling provides an example: because we now know that energy depletion increases the expression of a number of different molecular signaling pathways, including AMPK, and that glycogen/glucose “switches” them off, it makes sense that if we alter the availability of carbohydrate, we can target specific adaptations. This is obviously of use during a periodized training year, where we might focus on a specific adaptation at one point in time – such as improvements in endurance mediated by increased mitochondrial density – before moving to another, such as improvements in maximal strength. Cycling through phases like this can reduce the interference effect of concurrent training, and maximize performance.

A further layer of complexity; genetic expression and variation

If you’ve managed to stick with this so far, well done; we’ve gone pretty deep. There is just one further layer of complexity we need to add to our understanding, that of genetic expression. The molecules found in these pathways, such as mTOR, AMPK, myostatin, PGC-1a, are all proteins. Proteins are made from our genes. Whilst it might be tempting to think that these genes are always “switched on”, or expressing their protein, this isn’t the case – it would be very inefficient and energy costly, and so wouldn’t make sense from an energy standpoint. Instead, your body waits for a signal to start expressing these genes, and, as we’ve already discussed, exercise is the prime signal, although other signals, such as reduced energy intake, can also contribute. This can increase genetic expression through epigenetic mechanisms, which I have covered previously here. These processes make the gene easier to “read”, either by removing methyl groups that block translation to mRNA (DNA has to be converted to mRNA, which travels to the ribosomes for the protein encodes for the gene to be created), or by opening up the tightly bound DNA structure in a process termed chromatin remodeling. Exercise can also alter the concentrations of microRNAs (miRNA, different to mRNA), which can enhance or reduce the impact of other mRNAs on protein transcription.

Whilst fairly complex, we can summarize the above steps as exercise increasing the expression of genes in order to create proteins, and these proteins drive the various different pathways associated with exercise adaptation. Finally, we have genetic variation; we might have versions of these genes which predispose us to produce more or less of these proteins, which can make certain exercise adaptations more efficient. For example, variation in a gene called PPARGC1A influences how much PGC-1a you produce; given that PGC-1a impacts mitochondrial biogenesis, those that produce more of it tend to have greater levels of mitochondrial biogenesis post-exercise, which in turn leads to greater improvements in VO2max following exercise. Similarly, when it comes to resistance training, a very rare mutation in the myostatin gene impacts muscle hypertrophy. Myostain tends to reduce or limit muscle hypertrophy;; post-resistance training, it is down regulated for a short period to allow hypertrophy to occur. However, the small number of people with this mutation don’t produce myostatin, which means that muscle hypertrophy is less tightly regulated – as such, they have much bigger muscles.


Ok, let’s take a breath – we’ve gone over a lot of complex information there, and hopefully you’ve managed to follow along without any issues. As a summary, we’ve covered how the body adapts to exercise, utilizing recent knowledge gleaned from molecular biology and physiology. In a nutshell, exercise is “sensed” by the body through sensor protein. This sensation is then translated into a signal by signaling proteins, and these signals stimulate a number of adaptation regulators , such as mTOR and AMPK. Whilst this information is, at present, used to explain why and how exercise adaptation occurs, I’m convinced that at some point in the near future, we will be able to use knowledge of these molecular pathways along with knowledge of genetic variation in order to guide our training, either through interventions such as carbohydrate cycling for endurance athletes, or by focusing on training methods that each athlete, with their own unique genetic make-up, is best primed to adapt to. As always, we need more research to further enhance our knowledge in this area, and make the mechanisms and their effects clearer. For example, some research doesn’t report that the interference effect exists, and some research even suggests that prior exhaustive aerobic exercise can enhance the adaptations seen post-resistance training; further research will enable us to get a stronger evidence base and better understand what actually happens, and how it might affect training – but for now, it seems clear that we should try and separate exhaustive endurance exercise and resistance training.

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