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How to Increase Mitochondrial Biogenesis with Exercise

What is the purpose of mitochondrial biogenesis?

Have you been feeling like you lack energy, or that you have trouble getting up the stairs? The cause of the problem might be your mitochondria, known as the powerhouse of the cell.

When they don’t work well, multiple problems can arise. This results in excess fatigue and loss of endurance. In the long term, mitochondrial dysfunction has also been linked to aging, metabolic disease such as diabetes and type 2 obesity, and neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease, and cancer.

Did you know that there are ways to boost your mitochondria? This can be achieved through mitochondrial biogenesis, which can be defined as an increase in either the mitochondrial content or an increase in the mitochondrial respiratory function. It is important to differentiate those two ways of increasing mitochondrial biogenesis, as each mitochondrial adaptation can be promoted through various types of exercise training.

So, how can we increase our mitochondrial biogenesis and live our best lives? Let’s get right into it.

Exercise and mitochondrial biogenesis

Exercise promotes mitochondrial biogenesis

Multiple studies have demonstrated that exercise training increases both mitochondrial content and respiration. These findings led to the realization that:

  1. We can delay mitochondrial dysfunction, thus slowing down aging and reducing the risk of multiple diseases, through exercise.
  2. If the mitochondria are damaged, for example, due to aging or disease, exercise could be a form of ‘behavioral medicine’ to improve the condition.

No wonder why elite athletes can have superior longevity (Yes, that was actually concluded by a systematic review of 54 peer-reviewed publications and three articles from online sources).

Now the question is, are there any types of exercise that are “better” than others to improve mitochondrial biogenesis? Or are they all equivalent?

Training volume

A bigger training volume, characterized by a longer training duration, is associated with a higher mitochondrial content

In a study, ten healthy men were recruited to perform high-intensity interval cycling during 3 consecutive training phases. The first phase, the normal-volume training (NVT), lasted for 4 weeks, at a frequency 3 days a week. The second phase, the high-volume training (HVT), lasted for 20 days and occurred twice a day. The third and last phase, the reduced volume training, lasted for 2 weeks and was comprised of a total of only 5 sessions.

After completing each training phase, participants had to go through a testing period where they cycled for 20km and completed a graded exercise test (GXT). Multiple mitochondrial parameters were monitored. I’m not going to go into details about the parameters to keep it simple, you can check out the article for more information.

What they found was that it was only after the HVT that mitochondrial content was increased. With the NVT and RVT, there was no change in mitochondrial content. Thus, the longer the duration of a workout session is or the higher the number of workout sessions you perform, given the intensity at which you perform remains the same, the more you can increase your mitochondrial efficiency.

Training intensity: SIT versus HIIT versus MIT

First, what are SIT, HIIT and MIT?

The definition varies from different research publications, but it looks something like this:

MIT: Moderate-intensity continuous training, high volume with intensity levels 50-75% of the maximal power

HIIT: High-intensity interval training, moderately high volume with sessions of 3-5 minutes of intensity levels 75-100% of the maximal power

SIT: Sprint interval training, sessions of an ‘all-out’ maximal effort that lasts less than 1 minute for each spring, performed at intensity ≥ 100% of the maximal power output

HIIT increases mitochondrial respiration the most, whereas SIT is the most effective if you don’t have much time in your hands to exercise.

Studies have shown that MIT results in a bigger improvement in mitochondrial volume but did not result in an increase in mitochondrial content. On the other hand, the maximal mitochondrial respiration increased significantly only after SIT (25%).

With HIIT, not only does the duration of the training is high enough to increase the mitochondrial volume, but the intensity is also high enough to increase mitochondrial function. You get to kill two birds with one stone.

Does that mean that you might be better off doing HIIT? Not necessarily. SIT seems to be the most effective type of exercise when taking into account training volume and time. If you have limited time available and desire to maximize your performance, you might obtain the best results with SIT protocols.

Detraining effect on mitochondrial biogenesis

Detraining rapidly reverses mitochondrial biogenesis. Lose it or keep it.

After only 1 week of complete detraining, studies indicate that mitochondrial respiration is reduced by as much as 50%.

To keep the increase in mitochondrial biogenesis, you need to either increase the duration of the workout or the intensity – or both.

In short…

1. Exercise is a powerful stimulus to increase mitochondrial biogenesis.

2. Training volume may increase mitochondrial content, while exercise intensity may increase mitochondrial respiratory function.

3. Training twice a day for 7 days a week shows the most improvements in mitochondrial function. Morning training involved continuous glycogen depleting exercises (e.g. running) and HIIT/SIT in the afternoon.

4. SIT may be more efficient if you have less time in your hands to exercise.

5. Work out regularly and use methods such as “progressive overload” to maintain mitochondrial biogenesis.

References

Granata, C., Oliveira, R. S., Little, J. P., Renner, K., & Bishop, D. J. (2016). Mitochondrial adaptations to high-volume exercise training are rapidly reversed after a reduction in training volume in human skeletal muscle. FASEB journal : official publication of the Federation of American Societies for Experimental Biology30(10), 3413–3423. https://doi.org/10.1096/fj.201500100R

Lemez, S., & Baker, J. (2015). Do Elite Athletes Live Longer? A Systematic Review of Mortality and Longevity in Elite Athletes. Sports Medicine – Open1(1). doi: 10.1186/s40798-015-0024-x. https://sportsmedicine-open.springeropen.com/articles/10.1186/s40798-015-0024-x

Holloszy J. O. (1967). Biochemical adaptations in muscle. Effects of exercise on mitochondrial oxygen uptake and respiratory enzyme activity in skeletal muscle. The Journal of biological chemistry242(9), 2278–2282. https://pubmed.ncbi.nlm.nih.gov/4290225/

Andrade-Souza, V. A., Ghiarone, T., Sansonio, A., Santos Silva, K. A., Tomazini, F., Arcoverde, L., Fyfe, J., Perri, E., Saner, N., Kuang, J., Bertuzzi, R., Leandro, C. G., Bishop, D. J., & Lima-Silva, A. E. (2020). Exercise twice-a-day potentiates markers of mitochondrial biogenesis in men. FASEB journal : official publication of the Federation of American Societies for Experimental Biology34(1), 1602–1619. https://doi.org/10.1096/fj.201901207RR

Gibala, M. J., Little, J. P., Macdonald, M. J., & Hawley, J. A. (2012). Physiological adaptations to low-volume, high-intensity interval training in health and disease. The Journal of physiology590(5), 1077–1084. https://doi.org/10.1113/jphysiol.2011.224725

Fiorenza, M., Lemminger, A. K., Marker, M., Eibye, K., Iaia, F. M., Bangsbo, J., & Hostrup, M. (2019). High-intensity exercise training enhances mitochondrial oxidative phosphorylation efficiency in a temperature-dependent manner in human skeletal muscle: implications for exercise performance. FASEB journal : official publication of the Federation of American Societies for Experimental Biology33(8), 8976–8989. https://doi.org/10.1096/fj.201900106RRR

Granata, C., Oliveira, R., Little, J. et al. Sprint-interval but not continuous exercise increases PGC-1α protein content and p53 phosphorylation in nuclear fractions of human skeletal muscle. Sci Rep 7, 44227 (2017). https://doi.org/10.1038/srep44227