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Once considered to be the ‘powerhouse of the cell’, mitochondria are now perhaps better known as ‘the ultimate orchestrators of our cellular health’. In recent years our understanding of just how crucial these cellular organelles are for every aspect of our health has expanded significantly and brain health is no exception. In this article we take a closer look at just how important it is to look after your brain mitochondria and 3 key factors you need to consider for this.

Human brains need lots of power
Compared to other mammals, humans have unusually large brains relative to total body size. And literally millions of mitochondria are needed to power our brains. Mitochondria are the organelles within our cells that are responsible for energy production and many other cellular activities too, including regulating oxidative stress and apoptosis.

“Mitochondria are underrated, they’re the chief executive organelle of the cell.”

Martin Picard (Columbia University)

Neurons contain millions of mitochondria
Whilst an average cell may contain a few thousand mitochondria, each neuron will typically contain a staggering 1 – 2 million mitochondria. It will come as no surprise to learn then that the central nervous system (CNS) has an extraordinarily high metabolic rate. It consumes about 20% of our oxygen, yet accounts for around only 2% of our total body weight. The brain is energy-hungry yet is unable to store large amounts of energy reserves in the form of glycogen. In addition, such high levels of energy production generate reactive oxygen species (ROS), which may be toxic to cells in high amounts. Neurons are highly dependent on mitochondrial function to establish membrane excitability and to perform incredibly complex processes such as neurotransmission and plasticity. Even a resting cortical neuron consumes around 4.7 billion molecules of ATP (the body’s energy currency) every second!

Mitochondrial dysfunction & brain health
As a consequence of all this, the brain and nervous system is highly vulnerable when mitochondrial function is impaired, and this can have wide-ranging negative health effects. Considerable evidence now demonstrates that mitochondria-related alterations are prevalent during chronic stress and depression. In fact, anything from chronic psychological stress, fatigue, depression and anxiety, to cognitive deficits, neurodegenerative decline, dementia, Alzheimer’s Disease, Parkinson’s Disease and more may be linked to impaired mitochondrial function.

Supporting brain mitochondria – 3 Key factors to consider
In short, mitochondria are of crucial importance for the complex workings of the brain and nervous system, and taking care of them is absolutely vital. Fortunately, there are many ways you can nurture and protect your mitochondria.

Here are 3 key factors to consider:

1. Excessive or chronic inflammation is bad news for mitochondria. A growing body of evidence indicates that inflammation may cause harmful changes in mitochondrial function, affecting oxidative phosphorylation and membrane polarity. Studies have found that depressive patients usually exhibit altered inflammatory markers.1 And inflammation is considered a central mechanism in neurodegenerative diseases such as Alzheimer’s.2 Taking steps to keep inflammation in balance is vital. There are many diet, lifestyle and supplement steps you can take to help keep inflammation in check. Take a look at our comprehensive Inflammation Balance fact sheet here.

2. Mitochondria do not thrive in conditions of chronic or excessive stress. And since chronic stress can also promote a more inflammatory environment, this can be a vicious cycle for mitochondria. Mitochondria have a role to play in steroid hormone synthesis, yet another reason why chronic stress may be harmful - mitochondrial over-activity in response to excessive stress may lead to the generation of increased levels of reactive oxygen species (ROS) which can be toxic to cells in high amounts. In a 2018 meta-analysis of 23 studies on mitochondria and anxiety, 19 studies demonstrated significant adverse effects of psychological stress on mitochondria. And the other 4 studies noted changes in mitochondrial function or size in response to stress.3

It is important to note however a hormetic effect of stress on mitochondrial function, whereby chronic stress and high levels of circulating stress hormones are a risk, and low levels of stress can be beneficial. Balance is key here and there are many diet, lifestyle and supplement steps which can help to achieve this.

Magnesium helps the body to maintain a balanced stress response. Multiple studies have now demonstrated improved stress response, anti-depressant and anti-anxiety effects of magnesium supplementation.4-6 High levels of zinc are found in the hippocampus in the brain. It is likely that zinc deficiency excessively excites glutamatergic neurons in the hippocampus after exposure to acute stress, which in turn can negatively impact mitochondria. There is also strong evidence that depression is accompanied by lower serum zinc.7-10 Adaptogenic herbs such as ashwagandha, Rhodiola rosea, cordyceps and Asian ginseng may be particularly helpful for supporting stress balance. Find out more on supporting a balanced stress response here. And for a deeper dive, have a look at our Stress Research Summary here.

3. High amounts of ROS (reactive oxygen species) are harmful to mitochondria, yet similar to the hormetic effects seen with stress, low levels may be beneficial. Fortunately, our bodies have in-built antioxidant systems in place that can help to mitigate the harmful effects of ROS and it is essential that these are well supported. Glutathione is often referred to as the ‘master antioxidant’ - it is produced by our bodies in response to oxidative stress and plays an important role in protecting cells and their components against ROS. Glutathione has a key role to play in protecting brain mitochondria. It is notable that major depressive disorder is usually accompanied by a decrease in antioxidant enzyme activities (such as glutathione peroxidase) and total antioxidant capacity. In a 2017 study, researchers found adolescents with depression had lower glutathione levels.11 Our bodies are able to make glutathione from the amino acids cysteine, glycine and glutamic acid. It is key therefore to include good protein sources in the diet. Cysteine is often regarded as the rate-limiting amino acid in glutathione production; supplementation with N-Acetyl Cysteine (NAC) may therefore help to support this process. It is also possible to supplement directly with glutathione and this may be especially beneficial for those with increased need or alterations in genes involved in glutathione production. Find out more on glutathione here.

Protect your brain mitochondria, now and for good
The importance of mitochondria cannot be overestimated, and it is clear they have a central role to play in supporting and protecting many aspects of brain and nervous system health. There is much you can do to support your mitochondria; targeting inflammation, stress and ROS is a great place to start. Find more ways to protect your mitochondrial health here.

References:
1. Vargas Visentin AP, Colombo R, et al. Targeting inflammatory-mitochondrial response in major depression: current evidence and further challenges. Oxidative Medicine and Cellular Longevity. Vol 2020, Article ID 2972968, 20 pages, 2020.
2. Kinney JW, Bemiller SM, et al. Inflammation as a central mechanism in Alzheimer’s disease. Alzheimers Dement (NY). 2018; 4: 575-590.
3. Picard M & McEwen BS. Psychological stress and mitochondria: a systematic review. Psychosomatic Medicine: 2/3 2018 – Volume 80 -Issue 2-p 141-153
4. Boyle NB, Lawton C et al. The effects of magnesium supplementation on subjective anxiety and stress – a systematic review. Nutrients 2017 May; 9(5): 429
5. Tarleton EK, Littenberg B, MacLean CD et al. Role of magnesium supplementation in the treatment of depression: A randomized clinical trial. PLOS One June 27 2017. https://doi.org/10.1371/journal.pone.0180067
6. Barragán-Rodríguez L, Rodríguez-Morán M, Guerrero-Romero F. Efficacy and safety of oral magnesium supplementation in the treatment of depression in the elderly with type 2 diabetes: a randomised, equivalent trial. Magnes Res 2008; 21: 218–23.
7. Doboszewska U, Wlaz P et al. Zinc in the monoaminergic theory of depression: Its relationship to neural plasticity. Neural Plast. 2017; 2017: 3682752
8. Watanabe M., Tamano H., Kikuchi T., Takeda A. Susceptibility to stress in young rats after 2-week zinc deprivation. Neurochemistry International. 2010;56(3):410–416. doi: 10.1016/j.neuint.2009.11.014.
9. Takeda A, Taramano H et al. Behavioural abnormality induced by enhanced hypothalamo-pituitary-adrenocortical axis activity under dietary zinc deficiency and its usefulness as a model. Int J Mol Sci. 2016 Jul; 17(7): 1149
10. Takeda A., Tamano H., Nishio R., Murakami T. Behavioral abnormality induced by enhanced hypothalamo-pituitary-adrenocortical axis activity under dietary zinc deficiency and its usefulness as a model. International Journal of Molecular Sciences. 2016;17(7, article 1149) doi: 10.3390/ijms17071149.
11. Freed RD, Hollenhorst CN, et al. A pilot study of cortical glutathione in youth with depression. Psychiatry Research: Neuroimaging. Volume 270, 30 December 2017, pages 54-60

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