The effects of nutrients and exercise on mitochondria

The effects of nutrients and exercise on mitochondria, the energy-producing organelles in our bodies, may improve health and performance.

What are mitochondria

Mitochondria (plural of mitochondrion) are organelles located within all of our cells which are responsible for generating adenosine triphosphate (ATP), used for energy. They do so via various metabolic pathways, including the famous Krebs cycle, oxidative phosphorylation and fatty acid beta-oxidation (1, 2).

Mitochondria also fulfil other roles, including intracellular signalling, cellular longevity regulation (3, 4, 5), calcium regulation, reactive oxygen species (ROS) generation, glucose and lipid metabolism (4).

Mitochondria and health

There are some genetically inherited mitochondrial health conditions, however their prevalence is low.

Given the presence of mitochondria in every single cell of the body, their dysfunction can lead to all sorts of health issues, including type 2 diabetes (1, 4, 6), aging, inflammation, cancer, neurodegenerative diseases and cardiovascular disease (1).

Some organs are more susceptible to suffer from improper mitochondrial function because they have higher energy demands. These include the central nervous system, muscles, retinas, kidneys and pancreas (4).

Mitochondrial homeostasis

Like many other biological entities, mitochondria exist in homeostasis, or a constant flux of new mitochondria being generated (a.k.a. biogenesis) and old or damaged mitochondria being cleared out (a.k.a. mitophagy) (1, 3, 7).

Mitochondrial biogenesis is influenced by several factors including exercise, hormonal and developmental signals, and cellular energy demand (1).

The effects of nutrients and exercise on mitochondria

Nutrients and exercise are lifestyle factors that have an impact on mitochondria and may be used to enhance health outcomes and performance.

Nutrients and other food-derived components

The following micronutrients and bioactive substances play roles in mitochondrial function. Therefore, it is important to correct deficiencies via dietary intake or supplementation.

• Vitamins: thiamin (B1), riboflavin (B2), niacin (B3), pantothenic acid (B5), biotin (B7), folate (B9), cobalamin (B12), ascorbic acid (C), tocopherol (E)
• Minerals: selenium, zinc
• Bioactive substances: coenzyme Q10 (5, 8), caffeine, melatonin, carnitine, creatine, nitrate, lipoic acid, taurine (5)

The following compounds may stimulate mitochondrial biogenesis: resveratrol (1, 7, 8), citrus tangeretin (1, 7), quercetin, hydroxytyrosol, certain isoflavones, certain flavones, flavan-3-ol, green tea polyphenols, epicatechin-rich cocoa, curcumin, yerba mate, epigallocatechin-3-gallate (EGCG), anthocyanins (1), retinoic acid (8), salidroside and saffron (7). However, most of the studies on those compounds have been conducted on animals, in vivo (on isolated cells) and in vitro (in petri dishes). A couple of the few clinical studies on human subjects include quercetin (young adult males) and epicatechin-rich cocoa (type 2 diabetics) (1).

On the other hand, among the things that can hinder mitochondrial biogenesis is a high glucose, high fat environment (a.k.a. junk food).

Exercise

Mitochondrial content (i.e. how many) and respiratory function (i.e. ability to generate ATP) have been directly correlated with measures of endurance performance (2).

Conversely, exercise can improve the quantity and quality of mitochondria (2, 3, 4). Different muscle fibre types have different contents of mitochondria. Slow-twitch type I fibres have the most mitochondria, which makes sense considering these fibres are preferentially recruited for endurance exercise (3).

It seems that all modalities of exercise, including resistance and high intensity interval training (HIIT) have an effect on the mitocohondrial population of the fibre types that are recruited in the working muscles. It has been estimated that prolonged endurance exercise can increase the volume of mitochondria by 40-50% and HIIT by 25-35% (3).

It is important to note that there is no consensus regarding the extent to which different types of exercise affect mitochondrial content and function, nor of the effect of different recruited muscle fibre types on mitochondrial adaptations, mainly because different studies use different measures. The best recommendations seems to be to perform a mix of moderate- and high-intensity exercise (2).

On the other hand, the energy demands of exercise generate stress that stimulate mitophagy, leading to mitochondria turnover (3).

Ageing and a sedentary lifestyle lead to a reduction in quantity and function of mitochondria in muscles. This happens alongside other hallmarks of ageing, such as declines in muscle protein synthesis (a.k.a. anabolic resistance) (3). Regular exercise, especially resistance exercise, can help mitigate the aforementioned mithochondrial losses (3, 4).

Muscle contraction during exercise causes mitochondria to release multiple compounds named myokines, which can have beneficial effects in surrounding or distant organs including the brain (3).

The beneficial effects of exercise apply also to individuals who suffer from mitochondrial diseases such as those caused by DNA mutations (8).

References

1. Chodari L, Dilsiz Aytemir M, Vahedi P, Alipour M, Vahed SZ, Khatibi SMH, et al. Targeting Mitochondrial Biogenesis with Polyphenol Compounds. Oxid Med Cell Longev. 2021;2021:4946711.
2. Bishop DJ, Botella J, Genders AJ, Lee MJ-C, Saner NJ, Kuang J, et al. High-Intensity Exercise and Mitochondrial Biogenesis: Current Controversies and Future Research Directions. Physiology (Bethesda). 2019 Jan;34(1):56–70.
3. Memme JM, Erlich AT, Phukan G, Hood DA. Exercise and mitochondrial health. J Physiol. 2021 Feb;599(3):803–17.
4. Krako Jakovljevic N, Pavlovic K, Jotic A, Lalic K, Stoiljkovic M, Lukic L, et al. Targeting Mitochondria in Diabetes. Int J Mol Sci. 2021 Jun;22(12).
5. Wesselink E, Koekkoek WAC, Grefte S, Witkamp RF, van Zanten ARH. Feeding mitochondria: Potential role of nutritional components to improve critical illness convalescence. Clin Nutr. 2019 Jun;38(3):982–95.
6. Miller VJ, LaFountain RA, Barnhart E, Sapper TS, Short J, Arnold WD, et al. A ketogenic diet combined with exercise alters mitochondrial function in human skeletal muscle while improving metabolic health. Am J Physiol Endocrinol Metab. 2020 Dec;319(6):E995–1007.
7. Popov L-D. Mitochondrial biogenesis: An update. J Cell Mol Med. 2020 May;24(9):4892–9.
8. Hirano M, Emmanuele V, Quinzii CM. Emerging therapies for mitochondrial diseases. Essays Biochem. 2018 Jul;62(3):467–81.

[Photo by lucas Favre on Unsplash]

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