Run faster: strategies for more mitochondria

The mitochondria are the energy producing factories of the cell; without mitochondria we wouldn’t be able to produce ATP and we wouldn’t have energy to fuel our runs. If the mitochondria are so important for our capacity to run, this also means that we’d be able to run faster with more of them. In this article I discuss the differences between strength and endurance exercise at a molecular level and I will provide a couple of practical strategies to stimulate the production of more mitochondria. At race day it is of extreme importance to get to the start with full glycogen supplies. However, to achieve optimal training adaptation and maximisation of mitochondria numbers, one or two runs a week on nothing but a single cup of coffee might not be such a bad idea.

Strength and endurance: the concurrent training effect

Resistance exercise consists of movements with a high intensity and a low frequency, whereas endurance exercise consists of movements with a low intensity and a high frequency. Resistance exercised results in increased muscle mass, thicker muscle fibres and strength gain, whereas endurance exercise results in more and improved functioning of mitochondria, higher capillary density and higher resistance against fatigue.1

When you combine resistance and endurance exercise you will experience the so-called ‘concurrent training effect’: the potential adaptation capacity of the muscle is strongly decreased and the strength of the athlete does not increase as compared to strength training alone. A good example of the concurrent training effect can be seen in athletes competing in the decathlon, their personal records are about 25% less as compared to specialized athletes.1 The divergent molecular pathways of resistance and endurance training are displayed, in a strongly simplified manner, in the figure below.

Strategies to increase the number of mitochondria

The most important function of the mitochondria is to supply the cell with energy. The generation of new mitochondria is stimulated whenever the energy requirements of the cell are increased and to compensate for cell damage. This process is mediated by the transcription factor peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), which is referred to as the master regulator of mitochondrial biogenesis.2,3

PGC-1α is activated by aerobic exercise via intracellular signals which are mediated by 5`AMP-activated protein kinase (AMPK) and p38 mitogen-activated protein kinase (p38 MAPK). An increase in mitochondrial numbers results in an increased capacity to utilize fat, in theory sparing the glycogen storages for a longer period of time during prolonged aerobic exercise.3

Recent studies have shown that periodical restriction of carbohydrates before aerobic training results in increased numbers of mitochondria.4,5 A combination of aerobic training and carbohydrate restriction result in a synergistic effect and could lead to greater training adaptations and improved aerobic performance. However, carbohydrate restriction could impair the capacity for muscle recovery. It has been suggested that by substituting the portion of restricted carbohydrates by an increased protein intake, muscle mass can be retained while simultaneously supporting mitochondrial biogenesis. See the figure below for an overview of these principles.3

From theory to practice: how do I achieve maximal activation of PGC-1α?

From a molecular perspective PGC-1α activity can be maximized  in two ways. The first one is by optimizing the interaction of PGC-1α and its binding partners. This can be achieved by coupling more phosphor and less acetyl groups to PGC-1α. As a result the PGC-1α molecule will have more negative and positive sides causing it to bind more strongly to its partners, thereby exerting a stronger effect on gene expression. The second strategy is to simply produce more PGC-1α.6

During prolonged muscle contraction (more intracellular calcium), high metabolic stress (ATP turnover, lactate production, glycogen depletion, energy deficiency) and whole body stress (increasing epinephrine) a group of enzymes are activated causing an increase in PGC-1α production and activity by increasing the charge of the molecule. The net result is more mitochondria and blood vessels, and thus an increased aerobic capacity.6

On basis of these observations the following strategies to maximize PGC-1α activity can be applied:

  1. Once or twice a week perform a training session on an empty stomach. This results in deacetylation of PGC-1α and will increase its activity. In addition, training in a glycogen-depleted state will increase the activity of AMPK and the production of epinephrine during long runs is increased; both stimulate production and activity of PGC-1α.
  2. Drink a strong cup of coffee before glycogen-depleted training sessions: this will decrease the perceived exertion during these sessions and will improve the intensity at which you can perform in a carbohydrate-depleted state.
  3. Run long and slow. Long slow distance runs maximize the amount of time all signals are turned on while minimizing mechanical strain on your body.
  4. Alternatively, perform two sessions where the first sessions depletes glycogen reserves and the second session is performed at high intensity in a glycogen-depleted state.

These recommendations are meant for experienced runners only. Performing too many sessions in a glycogen-depleted state can results in overtraining. One or two weekly sessions in a fasted state can be feasible; make sure that you are properly fuelled up during high quality sessions.6

The next time you feel sluggish or encounter the man with the hammer during a long slow distance run, remind yourself that you are probably doing good work with respect to the improvement of your oxidative capacity.

References

  1. Hamilton DL, Philp A (2013) Can AMPK mediated suppression of mTORC1 explain the concurrent training effect. Cellular and Molecular Exercise Physiology 2(1): e4 doi: 10.7457/cmep.v2i1.e4
  2. Archer SL. Mitochondrial dynamics–mitochondrial fission and fusion in human diseases. N Engl J Med. 2013 Dec 5;369(23):2236-51. doi: 10.1056/NEJMra1215233.
  3. Margolis LM, Pasiakos SM. Optimizing Intramuscular Adaptations to Aerobic Exercise: Effects of Carbohydrate Restriction and Protein Supplementation on Mitochondrial Biogenesis. Adv Nutr. 2013 Nov 6;4(6):657-664.
  4. Hawley JA, Burke LM. Carbohydrate availability and training adaptation: effects on cell metabolism. Exerc Sport Sci Rev. 2010;38:152–60.
  5. Yeo WK, Paton CD, Garnham AP, Burke LM, Carey AL, Hawley JA. Skeletal muscle adaptation and performance responses to once a day versus twice every second day endurance training regimens. J Appl Physiol. 2008;105:1462–70.
  6. Keith Baar. New ideas about nutrition and the adaptation to endurance training. Sports Science Exchange (2013) Vol. 26, No. 115, 1-5