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The Root of Chronic Fatigue: Is It Cell Deep?

For those struggling with chronic fatigue, the answer may lie deep within trillions of cells.

It's inevitable that as we get older, our energy supply starts to dwindle. It's different for everyone, of course, but many people consider their youth "the good old days." Those days when all you needed was a caffeinated beverage in the morning to get you going, and the rest was easy. However, for many people at all stages of life, it's never been that simple. 

While a good night's sleep is vital for everyone, feeling "tired" isn't always just a lack of zzz's. There’s a root cause to fatigue, and you most likely guessed it, right? Our cells are fundamental to our energy production. Proper cellular function provides our body with the energy it needs to perform both physically and mentally throughout our day; if they’re not working as efficiently as they could, you’ll notice.

While the topic of mitochondria has been getting the meme treatment recently, understanding its functions is actually central to hacking the process of energy. Impaired mitochondrial function can lead to less than desirable cellular states where energy production is low, impacting the normal function of various processes throughout the body. 

representation of the inner workings of a cell, specifically mitochondria

When cells have trouble producing energy, the body struggles to perform. Let’s think of the cells as cylinders in a car engine, connected indirectly to the wheels. When the cylinders burn gasoline, they move up and down through a series of connections, allowing the wheels to turn. To create maximum power and turn the wheels at full force, it's essential for all four cylinders to be working effectively. If one of the cylinders stops working, the other three cylinders have to work harder to make up for it. This is similar to how the body relies on mitochondrial function – we really want to be running at full capacity, with all cylinders firing.  

In this context, you may begin to see how impaired cellular health (i.e., mitochondrial dysfunction) is related to feelings of fatigue. Your body may feel like it’s struggling to keep up, working harder than the average person just to have the same amount of energy.   

A starting point to ensure your cells continue to “fire on all cylinders” is reducing inflammation-inducing oxidative foods and drink while increasing antioxidants in the diet. Moderate exercise can also help keep this in check.   

However, for those living with chronic fatigue syndrome (CFS) it’s not that simple. They live every day without their engines firing at full capacity. As a result, mundane tasks can seem daunting and extremely tiring… but CFS runs deeper, cell deep to be exact.

Chronic fatigue syndrome: symptoms and possible causes 

Otherwise known as myalgic encephalomyelitis, CFS is condition that is characterized by more than simple tiredness. Instead, those with this disease tend to experience a range of symptoms, including extreme tiredness and breathlessness that presents even after simple tasks like walking to the mailbox or up a flight of stairs. They can also tend to feel other physical symptoms that mimic a cold or flu like headache, sore throat, trouble sleeping dizziness, and cloudy thinking when in a flare up.  

Currently, there are no known direct causes of CFS, only triggers. While some believe CFS is a result of energy deficiency, others believe it is rather an issue of energy distribution. Here’s another real-life comparison -- if you imagine building a campfire, you know a good fire results from a sufficient distribution of kindling under the fire logs. When done right, lighting multiple areas of kindling beneath will allow the fire logs to catch efficiently and quickly. On the other hand, taking a match to a couple of logs can get you a fire…but it'll take a much longer time, and won’t be as strong or sustainable.  

Potential triggers of CFS stem from the idea of the dauer state, which is a bodily state where metabolism is abnormally slowed down. Triggers include infection, trauma, famine, hypoxia, and seasonal change, all of which can influence changes in the function of mitochondria, and why mitochondria is considered a key component.

Any and each of these environmental factors can activate the cellular danger response (CDR), which is a biochemical response known to stimulate inflammation and slow mitochondrial processing of oxygen, reducing energy production as a result. CDR also occurs in the context of stressed cells, where both natural and self-induced factors can influence cellular energy production. 

It makes sense then, that CFS can especially affect those with poor diets, who are impacted significantly by seasonal allergies, or who regularly experience infection. Interestingly, many individuals with CFS report experiencing an acute infection prior to the onset of symptoms, and many tend to experience a higher rate of infections compared to people without. This has provided support for the idea that this syndrome is a result of altered immune function, at least in some.

Cellular events associated with CFS 

There is growing research about what happens at the cellular level in the context of CFS, but it’s far from conclusive. One significant finding involves the role of adenosine triphosphate (ATP)—the molecule that provides energy for the cell.  We talked a lot about this process here, if you'd like some more context before continuing!

Proper cellular function provides our body with the energy it needs to perform both physically and mentally throughout our day, and if they’re not working as efficiently as they could, you’ll notice.

As is commonly seen, stressed cells release ATP into the extracellular environment. From here, ATP binds to protein receptors (called purinergic receptors, because ATP is purine). When bound to these receptors, ATP stimulates many different cellular events like increased inflammatory activity, changes in gene expression, reduced mitochondrial activity, and reduced energy production.  

The latter certainly makes sense because we know an increase in ATP in the extracellular space signals high ATP to other cells to put them on alert. When mitochondria burn oxygen to produce ATP, the cells take that as a signal to stop producing it. Naturally, mitochondria stop producing ATP because that’s what they’ve been signaled. Put simply, stressed cells release ATP, which is an artificial signal to other cells that cellular energy is high, so other cells stop producing energy (although energy production has not, in fact, increased). 

The real problem arises when the stress subsides because now the cells that were told to stop producing energy are no longer generating ATP, which may lead to a significant drop in energy levels. This is what may be happening at the cellular level for those dealing with CFS.  

Does CFS impact other bodily systems? 

As you can imagine, lack of energy on a cellular (and physical) level can absolutely cascade to other areas of the body. For example, patients with CFS seemingly have reduced metabolism in the brainstem, which is a major part of the central nervous system responsible for autonomic processes like breathing and managing heart rate, leading us to think this may be why some people with CFS experience respiratory and cardiovascular problems. 

Other studies have reported both an over- and underactive stress response in patients with CFS, suggesting that this syndrome in some way interacts with the endocrine system. This would make sense, given CFS is stressful in of itself on cells as they try to work twice as hard to help one with CFS perform everyday tasks. 

There’s also evidence that CFS impacts the gastrointestinal tract as many people experience digestive issues such as irritable bowel syndrome and other disruptive symptoms. This implies that CFS quite possibly influences the enteric nervous system, which controls digestive processes. It may also be that CFS impacts both the enteric nervous system and the endothelial cells that line the digestive tract. It’s possible that the endothelial cells are impacted by slowed metabolism (and therefore, low energy levels to move food through the digestive system), and enteric system goes awry due to abnormal metabolism in digestive nervous tissue.  

What are some ways to manage CFS symptoms? 

As there is no known cure to date, patients and sufferers of chronic fatigue have learned how to manage symptoms to improve their quality of life. Most often, the most effective way is to isolate and tackle individual symptoms, and go from there, instead of trying to manage the entirety of the illness in one fell swoop. 

For example, muscle and joint pain are often reported along with CFS, and this kind of pain is normally associated with elevated inflammation. That being said, one approach to mitigate muscle and joint pain would be to target inflammation through anti-inflammatory diet, proper cellular care, and as much exercise as one could achieve, given exercise can be a daunting task in itself.

Of course, patients may turn to over-the-counter non-steroidal anti-inflammatory drugs (NSAIDs), but as CFS is a chronic disease, it is generally not advised to resort to NSAIDS for a long period of time due to increased risk of side effects. Instead, try incorporating anti-inflammatory foods that are also rich in vitamins and antioxidants to reduce inflammation. There is evidence that supports the idea that nutritional approaches could be leveraged to treat symptoms of CFS (see Bjorklund et al. 2019). 

One case study reported positive benefits when cognitive behavioral therapy (CBT) was combined with periods intermittent fasting, but this should be taken with a grain of salt. CBT is a common treatment for chronic fatigue sufferers because it helps the patient focus on other things aside from their symptoms…in other words, it trains them to remain distracted so they can focus on necessary life tasks as opposed to their symptoms. This method may work for some, but definitely not all, and it's very much so more of management strategy, than a cure.

An anti-inflammatory, antioxidant-rich diet is certainly one way to reduce strain on your mitochondria, but other methods may also be beneficial to your mitochondrial function. Taking care of cellular health can help regulate ATP function and help some of these symptoms at the root cause, by facilitating proper energy production at a cellular level. 


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