How to Improve Mitochondrial Function

This method is simple and free!

What Is the Main Function of Mitochondria?

Mitochondria are best known for their role in producing adenine triphosphate (ATP), cellular energy. Every process in every cell needs energy to function. Therefore, healthy, optimally functioning mitochondria are necessary for good health. The reverse is also true. Virtually every chronic disease in which it has been studied is associated with impaired mitochondrial function and low energy production.

Of particular interest to our community, low energy production has been reported in ME, CFS
and long COVID as well as other common conditions, including metabolic syndrome, cancer,
and neurodegenerative diseases like Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis (ALS).

What is REDOX and What Role Do the Mitochondria Play?

It is less well-known that mitochondria do much more than produce energy. In fact, research suggests that mitochondria seem to be at the center of all cell functions through their key role in the balance between oxidation and reduction (Redox). Redox is the movement of electrons between molecules. As with a battery, electrons flow downstream from where they are plentiful to where they are needed. This flow of electrons down the gradient produces energy. Redox balance is critical for virtually every function, especially for the stress response.

In most molecules, electrons are found in pairs. This is a stable configuration. However, when mitochondria produce cellular energy called ATP from glucose (sugar) and oxygen, they also create free radicals (molecules with unpaired electrons). The extra electrons on free radicals are desperate to pair up and steal electrons from other molecules, causing damage to those molecules. This oxidation is like rust and is a major source of damage to mitochondria, DNA, proteins and more.

The mitochondria continually assess the redox status of their surroundings. If there are too many free radicals, the mitochondria judge it as too dangerous to continue producing energy. They shift from oxidative phosphorylation—a process that produces 32 ATP per glucose molecule and lots of free radicals to aerobic glycolysis.  This much less efficient process only produces 2 ATP per molecule of glucose.

Aerobic glycolysis was discovered in the 1920s by Otto Warburg, a fascinating Nobel prize winner (1931), a Jew who lived in Nazi Germany with Hitler’s personal protection. Hitler’s mother died young of breast cancer, and Adolf was scared of contracting the disease. Much of Warburg’s research focused on cancer. His key discovery was that aerobic glycolysis is the primary metabolism of cancer cells. Aerobic glycolysis is now called the Warburg Effect. Three scientists who studied with Warburg, including Hans Krebs, who discovered the citric acid cycle, went on to receive Nobel prizes.

Being in a state of aerobic glycolysis doesn’t mean the mitochondria are dysfunctional or broken. It means they are doing their job protecting our cells from being irreparably damaged, being flexible and adjusting to environmental conditions. When you read that energy production is low in ME or the mitochondria are producing excess lactate from aerobic glycolysis, it implies that the mitochondria in the brains of people with ME are shifting down into this protective mode of function.

The downside of being in a chronic state of aerobic glycolysis is that it is associated with disease states because insufficient energy is produced to complete cell functions and repair broken molecules. In previous blogs, I have talked about Robert Naviaux’s cell danger response hypothesis. He explains how cells encountering stressors shifting into aerobic glycolysis for protection can get stuck in that low-energy state. He believes this failure to return back to a normal energetic state is associated with chronic diseases of all types.

How Does Diet Affect Mitochondrial Function

Nutritional imbalance – taking in more calories than we burn through activity is one of the most common causes of mitochondrial downregulation to aerobic glycolysis. When we constantly have high levels of core nutrients in our bodies, the mitochondria get the message that it is time to build new molecules such as fats, proteins, DNA and RNA and to replicate, creating new cells.

To accomplish this, protein, fat and sugars activate nutrient sensors, which turn on aerobic glycolysis, which is needed to build the new cell components. These signals turn off key pathways such as AMPK and sirtuins that repair damaged molecules. The anabolic (cell-building) mTOR pathway, which is needed to build new molecules, is turned on. 

In my book More Light, Chapter 6: Healing Through Diet, I discuss how intermittently switching between feasting and fasting is ideal for maintaining metabolic and mitochondrial health. Periods of eating allow us to build new molecules and cells as needed, and during fasting, we repair and recycle damaged and older molecules—a perfect balance. The mitochondria control this process. The problem arises when we are chronically in a low-energy state due to excess consumption. This leads to weight gain, inflammation, metabolic syndrome, cancer and neurodegeneration.

Melatonin Is Our Natural Antioxidant

We think of melatonin as a hormone produced by the pineal gland in the brain to help us know when it is day and night. However, did you know that, by far, the majority of melatonin in the body is not produced by the pineal gland but by the mitochondria? Melatonin is a powerful antioxidant. Since the mitochondria are where free radicals are made and since mitochondrial DNA is very vulnerable to damage, it makes sense they would (if they have enough energy to do so) make melatonin on site to moderate the effect of the free radicals and limit damage to cells and molecules.

In addition to direct antioxidant effects in the mitochondria, melatonin also acts by turning on important antioxidant genes, including those needed for the production of glutathione, our most important cellular antioxidant, superoxide dismutase, a crucial enzyme that helps transform free radicals into less dangerous molecules and the important anti-inflammatory NRF-2 pathway.

Melatonin is strongly neuroprotective. It is being studied as a remedy for people with brain injuries and stroke. Melatonin is also being studied in dementia, with some evidence it may help slow cognitive decline.

So, back to the topic at hand. Healthy levels of tissue melatonin require healthy mitochondria—mitochondria that make lots of energy through oxidative phosphorylation, often with brief breaks of aerobic glycolysis to build new organelles and cells. This is one reason why mitochondrial health is important for neuroplasticity. If we want to learn new things, our brains need ample energy and an environment free of inflammation.

 
There’s More!

What Do the Mitochondria Produce?

I am a psychiatrist, and I had no idea that mitochondria produce neurotransmitters like noradrenaline (NA), serotonin (5HT) and dopamine (DA), molecules we usually think of as solely associated with the brain. Through the production of these neurotransmitters, mitochondria are in constant communication with the brain and impact our neural function. Healthy mitochondria, healthy brain.

Also relevant to the brain is the role the mitochondria play in the circadian rhythm— our body clock. When our eyes are exposed to blue wavelengths of sunlight in the early morning, our main body clock, called the suprachiasmatic nucleus in the brain, sets all the clocks in every organ, cell, and gene around the body. This ensures that all our organs are ready to do their assigned tasks at the right time and synchrony with all the other body parts. For example, we want our bodies to be able to be active in the daytime and to rest and sleep at night.

If the mitochondria are not functioning optimally due to being in a low energy state, keeping a steady rhythm is impossible. I wonder if this may be part of the problem in people with complex chronic diseases who can’t stabilize their body clocks. My body clock was delayed for years.

Did You Know the Mitochondria Connect the Brain, the Gut and the Immune System?

The mitochondria are the hub of the connection between the circadian clock in the brain, the microbiome (the bacteria living in our bowel) and the immune system. Without healthy mitochondria, we are prone to developing leaky gut, which leads to low-grade inflammation. This chronic inflammation starting in the gut is a root cause of many chronic diseases.

Mitochondrial dysfunction is connected to neuroinflammation, now known to exist in many diseases, including ME, CFS and FM. As described above, the mitochondria in the brain produce melatonin to stem this inflammation but can only do so when producing enough energy. If the redox balance isn’t just right, energy production drops, and less melatonin is produced. Melatonin is a main regulator of microglial activity. Microglia are immune cells in the brain implicated in neuroinflammation. Melatonin switches glial cells from a pro-inflammatory (M1) to an anti-inflammatory (M2) state. This is likely more effective with fewer side effects than many of the fancy drugs being considered.

Little Known Fun Fact - Not All Mitochondria Are Found Inside Cells

An exciting new discovery is that mitochondria also exist outside cells (cell-free mitochondria). Between 200,000 – 3.7 million cell-free mitochondria live in every ml of blood. The existence of cell free mitochondria was only recently discovered, and their role remains unclear. These tiny organelles may travel around the body, communicating between all the cells and organs, keeping them in sync.

Sunlight Could Be the Key to Recovery?

It turns out our modern lifestyle is a disaster for mitochondria. Sitting too much, not getting enough exercise, eating more than we need, experiencing chronic stress and loneliness, and being exposed to air pollution, light pollution, toxins and medications have all been associated with decreased mitochondrial energy production. And when the mitochondria don’t have enough energy to function, inflammation results.

One cause of mitochondrial dysfunction rarely mentioned is the lack of exposure to natural sunlight. Humans evolved while living under the sun all day, from dawn to dusk, and in pitch-black darkness at night. There is growing evidence from an emerging field called quantum biology that sunlight is essential to health, and that  our bodies crave and require ample sunlight to be healthy.

 We are not as different from plants as we may think. Plants use photons of energy from the sun to produce chlorophyll, a form of energy they use to grow and reproduce. We then utilize that sunlight indirectly when we burn the food for energy. But we benefit much more directly from sunlight. It turns out we have many photoreceptors in our skin. The mitochondria absorb red and infrared light, which makes up about half of the light emitted by the they use that energy to make ATP quite independently of the energy we get from our food!

And there’s more. Quantum biologists suggest that many organelles, including mitochondria and DNA, make their own light, sometimes converting frequencies from the sun into frequencies not found in the sunlight that reaches us, as a way to communicate internally. This new research is pretty mind-blowing and I’m reading voraciously, trying to get my head around it. If you want to learn more, you can check out the Quantum Biology Collective podcast on the provider of your choice.

 Eight of the Many Health Benefits of Sun Exposure

 Sunlight

• provides energy to cells in the form of light photons
• enables the production of vitamin D (optimal levels are above 46 ng/ml (USA) or 115 mmol/l (SI units))
• releases nitric oxide, which helps moderate blood pressure and decreases the risk of stroke
• thickens the outer layer of the skin and increases the production of melanin, which protects us from damaging ultraviolet light
• stimulates the production of beta-endorphins, our naturally occurring opioids, in response to UVB exposure. Beta-endorphins may be why we feel better on sunny days.
• improves immune function and wound healing,
• increases the production of melatonin and serotonin
• sets the circadian (body) clock

Why the Sun Is the Best Light

Why am I recommending sunlight exposure rather than purchasing new light bulbs or expensive light panels?

• Artificial lights, no matter how complex and well-made, emit the same one or small range of wavelengths all the time.
• The wavelengths of sunlight vary from dawn to dusk, and all are important for our health in different ways.
• Exposure to the wrong wavelengths of light at the wrong time of day can cause more harm than good. The most well-researched example of this is exposure to pure blue light from screens. Blue light alone, without all the other wavelengths, never occurs in nature.
• The intensity of sunlight varies throughout the day, depending on its position in the sky and cloud cover. Artificial lights are static and don’t change in ways our bodies expect.

What I love most about the benefits of sunlight is that they are free and available to almost everyone. Some of the most severely ill individuals may have trouble getting outside, but, in that case, sitting or lying next to an open window has some benefits. Glass blocks important wavelengths, so opening a window even for short periods if you live in a cold climate is a step in the right direction. It feels ridiculously simple to say get more exposure to sunlight, but it’s a research-based statement. The benefits are many and the risks, if you avoid overexposure and sunburns, are few.

What I’m learning about quantum biology is changing how I think of health and disease. If you want to join me on this learning journey, consider subscribing to Live! with Dr. Stein–live sessions every other week in which I discuss no-to-low-cost strategies for living healthier and longer.

References

Casanova, A., Wevers, A., Navarro-Ledesma, S., & Pruimboom, L. (2023). Mitochondria: It is all about energy. Front Physiol, 14, 1114231. doi:10.3389/fphys.2023.1114231

Melhuish Beaupre, L. M., Brown, G. M., Gonçalves, V. F., & Kennedy, J. L. (2021). Melatonin’s neuroprotective role in mitochondria and its potential as a biomarker in aging, cognition and psychiatric disorders. Translational Psychiatry, 11(1), 339. doi:10.1038/s41398-021-01464-x