The last ten years have seen a huge increase in our understanding of what makes a muscle bigger and reminded us that a bigger muscle isn’t always a stronger muscle. This research directly affects how and when we train and what and when we eat in relation to training.
Immune system and muscle growth
Over the years, we’ve learnt that in order for muscle to grow normally we need an intact immune system. Mice that lack a protein called urokinase-type plasminogen activator (uPA – see box 1, below), which is essential for immune function, struggle to put on muscle tissue(1). One of the things that uPA prevents is how many immune cells are mobilised in the muscle following damage.Normally, immune cells enter our muscles after heavy exertion to help clear away debris. Along with removing any damaged muscle fibres, these immune cells might also give the muscle an important signal to grow. To test whether it was the decrease in immune cells that prevented muscle growth, scientists tested muscle tissue using a nonsteroidal anti-inflammatory drug (NSAID), which interferes with part of the normal inflammatory response of immune cells. As in the mice experiment above, using NSAIDs blocked muscle growth(2).
What this means for strength athletes is that taking anti-inflammatory drugs might do more than dull the pain after a hard workout. By decreasing inflammation, we might actually be preventing normal muscle growth in response to resistance exercise. Of course these studies were done in mice and might not translate to people, but the fact that our immune system is needed to increase muscle mass means that strength athletes should stay away from anti-inflammatories during training.
Hormones and muscle mass
In 1992, Dr Kevin Yarasheski showed that taking growth hormone while doing resistance exercise did not lead to greater increases in muscle mass and strength than training without growth hormone(3). In the noughties, Dr Espen Spangenburg built on this finding, showing that neither insulin nor IGF-I (see box 1) is needed to increase muscle mass and strength(3). Together with other research in this area, these findings suggest that most hormones aren’t important in training-induced changes in muscle size and strength.This statement is still quite controversial. Obviously, hormones play an important role in how big and strong our muscles are and how big and strong they can get, but we are learning that hormones are not as important as we once believed. For instance, we have known for 15 years that IGF-I can make muscles bigger. As a result, a number of high profile athletes have used insulin and IGF-I to try to increase their muscle mass and strength. However, what Dr Spangenburg showed (see figure 1, below) was that even though IGF-I and insulin were important in determining the size of muscles before training, the amount of increase in muscle mass and strength was the same in mice who had no insulin and IGF-I present naturally as those who had these hormones present.
This is similar to testosterone. We know that testosterone determines that on average a man’s muscles will be bigger than a woman’s muscles. However, we also know that men and women increase their strength the same amount through training. This means that testosterone is not needed to increase muscle strength in response to training but instead sets the upper limit of muscle size.
Without question, testosterone, IGF-I and similar hormones determine how big our muscles are before we start training. Some hormones may also dictate when our muscle growth will plateau. But it is now becoming clear that hormones don’t affect how much muscle mass we can add through training. This should reassure strength athletes that hard training and proper nutrition are all that they need to gain muscle mass and strength!
mTORC1
The single biggest advance in understanding strength over the past decade was the discovery that the mammalian target of rapamycin complex 1 (mTORC1) controls protein synthesis and muscle mass(5). At the end of the 1990s, we discovered that the activity of mTORC1 could predict how much muscle mass would increase in rats following training(6). In the last decade this finding has been extended to show that in people, mTORC1 activation predicts the increase in not only muscle size, but also strength following training (see Sports Performance Bulletin issue 270). We have also learned two other important things about mTORC1:- Its activation is directly related to the load on a muscle.
- It is also activated by amino acids.
Beyond load, mTORC1 is also activated by amino acids. In 1999, we learned that lifting weights in the fasted state actually caused muscle breakdown and that taking essential amino acids could reverse this. In the past decade we learned that amino acids had this positive effect by turning on mTORC1. For strength athletes, this means that having enough amino acids in the blood when, or soon after, we lift is important for our ability to activate mTORC1, increase muscle protein synthesis and make our muscles grow bigger and stronger.
Together, all of these discoveries have shown us how athletes should train to maximise growth and strength – ie by training with heavy weights using forced reps, by taking amino acids (protein) during or shortly after training, by not using NSAID medication and also by not trying to manipulate growth factors and hormones!
Endurance training
Even though we have clearly discovered a number of things about how to increase strength, the last decade has seen an even more impressive increase in our understanding of how we can increase endurance. The fact that endurance training increases the number of mitochondria and fat burning enzymes in our cells has been known for over 40 years. But, in the last decade we have identified the genes that cause the increase and we are learning more every day about how to use nutrition and exercise to effectively turn these genes on and maximise our endurance.PPAR∂ and increased endurance
In 2003, Dr Ron Evans and his colleagues showed that mice with an active form of the transcription factor PPAR∂ had more enzymes to breakdown fat and to power their muscles. As a result, they could run for longer on a treadmill(7).In a follow-up study, the Evans group gave mice a drug that activates PPAR∂ and showed that increasing PPAR∂ activity during training doubles the increase in endurance compared with training alone (see figure 2, below)(8). Most of this increase in endurance was due to an increase in enzymes that break down fat.
The cynics will see this as yet another drug for improving performance. But if we understand how PPAR∂ is activated normally, we can find out how to use nutrition and exercise to increase PPAR∂ naturally. PPAR∂ is normally activated by fat.
The more fat that our muscles use as fuel the higher the activity of PPAR∂. But, just eating more fat is not the best way to increase endurance and just activating PPAR∂ alone is not enough to increase endurance (compare the red and grey bars at week zero in figure 2).
What we need to do to increase PPAR∂ (and get more endurance) is to use more fat when we are exercising. This is not easy to do. Normally, when we increase our exercise intensity we shift to using carbohydrates and not fat.
One way to increase how much fat we burn in our muscles during exercise is to exercise in a glycogen-depleted state. When we exercise with low muscle glycogen stores, we increase the amount of fat we use as a fuel and this results in an increase in our fat burning enzymes and endurance. Therefore, if endurance is important for your performance, adding in a few sessions in a glycogen depleted state will really give this a boost.
AMPK, PGC-1α and new mitochondria
PGC-1α (see box 1) regulates the synthesis of new mitochondria. In 2002, Dr Bruce Spiegelman and his colleagues showed that if there is more active PGC-1α in our muscles we get more mitochondria and endurance (see figure 3, below)(9). We showed at the start of the decade that after endurance exercise there was an increase in PGC-1α and this was important for the training effect(10).AMPK is an enzyme that measures the energy status in our cells. When lots of energy is being consumed (such as when we exercise) or when not enough energy is being produced (such as when we fast) AMPK is activated. When active, AMPK turns on processes that increase energy production (fat burning, glucose uptake, etc) and decrease energy use (protein synthesis, etc).
One of the things turned on by AMPK, either directly or indirectly, is PGC-1α. This may be how exercise increases our endurance. Therefore, activating AMPK and PGC-1α should be the goal of endurance athletes. For endurance athletes and coaches, this translates into three practical points:
- Train at a high intensity since higher intensity exercise increases AMPK more than low intensity exercise;
- Do not use carbohydrate supplements when training since CHO supplements may decrease AMPK activation in response to exercise;
- Consider adding one of the natural activators of AMPK to your training to maximise AMPK activation. Resveratrol (an extract from red wine) activates AMPK as does Berberine (an extract of the goldenseal plant).
Concurrent training
Although we know a lot about increasing strength or endurance, very few athletes want just one or the other. Most sports combine both strength and endurance and therefore it is important to be able to develop both simultaneously. Dr Bob Hickson was the first to show that training for both strength and endurance resulted in less of an improvement in strength than training for strength alone(11). At least part of the reason for this is due to give and take between AMPK and mTORC1. AMPK can directly block the activation of mTORC1 (see figure 4, below).Since AMPK is turned on by endurance exercise, this means that performing endurance exercise after or immediately before resistance exercise will decrease strength gains. For athletes, remembering two important points about diet and the timing of training sessions can help overcome this conundrum.
First, as mentioned above, eating carbohydrate quickly turns off AMPK. Second, mTORC1 levels have to be raised for a long time to promote muscle growth, whereas AMPK needs only a short period to have its effects. Taking these two facts into account, in the last decade we have learned that to maximise simultaneous increases in strength and endurance we need to:
- Do our endurance exercise before our resistance exercise;
- Between the bout of endurance and resistance exercise consume a source of carbohydrate (to turn off AMPK) and protein, which supplies amino acids (to help activate mTORC1);
- Restrict the number of sets performed when weight training (too many sets will increase metabolic stress and activate AMPK);
- Let your muscles grow while you sleep.
Conclusions
The last decade has seen huge growth in our understanding of the physiology of exercise. From this, a number of genes and proteins have been identified that are central to improving performance. Cynics say that this has provided athletes with more tools with which to cheat. But a thorough understanding of these discoveries tells us that we can activate these genes and proteins and maximise performance simply by using the right intensity of exercise and the right diet!Keith Baar runs the Functional Molecular Biology laboratory at the University of California Davis where his research explores how exercise results in changes in muscle function and performance. He is also a scientific advisor to the English Institute of Sport and British Cycling
References
1. Am J Physiol Cell Physiol. 2007 Oct;293(4):C1278- 85
2. Am J Physiol Regul Integr Comp Physiol. 2009 Apr;296(4):R1132-9
3. Am J Physiol. 1992 Mar;262(3 Pt 1):E261-7
4. J Physiol. 2008 Jan 1;586(1):283-91
5. Eur J Appl Physiol. 2008 102: 145-52
6. Am J Physiol. 1999 276: C120-7
7. Faseb J. 2003 Dec;17(15):2299-301
8. PLoS Biol. 2004 Oct;2(10):e294
9. Faseb J. 2002 16: 1879-86
10. J Appl Physiol. 2008 104: 625-32
11. Eur J Appl Physiol Occup Physiol. 1980;45(2-3): 255-63