The exact cause of CFS is currently unknown, however, there are likely multiple causes that are potential contributors to this condition.

​

​

Chronic Stress

​

There is an association between the dysfunction of our body's stress response and CFS. The hypothalamic-pituitary-adrenal (HPA) axis or in simpler terms, the brain-adrenal axis helps to prepare our body to be able to respond adequately to a stressful situation (fight-or-flight response). Dysfunction of the brain-adrenal axis also sometimes commonly referred to as "adrenal fatigue" is commonly seen in patients with CFS. More information on adrenal fatigue is available on our website.

​

Patients with CFS typically present with stage 2 or 3 adrenal fatigue where cortisol (the main stress hormone) output is reduced and the normal daily rhythm of cortisol is disrupted. As a result, minor physical or mental exertions can have the potential to trigger an exaggerated inflammatory response by the immune system leading to symptoms typically observed in CFS since one of the roles of cortisol is to regulate the immune system.(2)

​

​

Infections and Gut Microbiome

​

The gut microbiome consists of all the different types of microbes living in your gut such as bacteria, yeasts, and parasites. The health of your gut microbiome is important as they perform many functions that are beneficial for overall health such as producing certain vitamins and beneficial compounds, helping to efficiently convert foods that we consume into usable energy for the body, and also helping to maintain the structure and function of your gut.

 

Certain studies have indicated that the gut microbiome of individuals with CFS is more likely to become imbalanced meaning that there are higher levels of harmful microbes in comparison to beneficial microbes, a term known as "gut dysbiosis". Many factors can contribute to gut dysbiosis such as infections, stress, food sensitivities, and overuse of certain medications.

 

When this happens, it can disrupt the gut lining which acts as a barrier to prevent contents in your gut such as toxins and bacterial by-products to leak into your bloodstream, also referred to as "leaky gut". As this occurs, it stimulates an inflammatory response by the immune system to deal with these "foreign substances" that are not supposed to be in the bloodstream creating a state of chronic inflammation, particularly in the brain (neuroinflammation) leading to the cognitive symptoms of CFS.(3)

​

​

Oxidative Stress and Chronic Inflammation

​

Oxidative stress occurs when there are too many free radicals in the body and not enough antioxidants to protect against them. Free radicals are highly unstable molecules that can damage other components in our bodies such as DNA, protein, and lipids (fats). We naturally produce free radicals in our body as part of our body's normal metabolism, so the free radicals are not necessarily an issue unless they overwhelm our body's antioxidant defences creating a state of oxidative stress.

 

Similarly, inflammation is not necessarily a bad thing as it helps us to heal and repair when we get injured. Problems can occur when the inflammation doesn't resolve naturally as it should and continues to linger on creating a state of chronic inflammation in the body. Many factors can predispose a person to have oxidative stress and chronic inflammation ranging from diet & lifestyle to exposures to infections and environmental chemicals. Oxidative stress and chronic inflammation go hand-in-hand and it is potentially elevated in patients with CFS.(4)

​

​

Decreased Energy Production

​

Mitochondria which is one of the components in a cell, is often referred to as the "powerhouse of the cell" due to its role in converting the foods that we eat into a usable form of energy that our bodies can use known as ATP. Research has indicated that mitochondrial dysfunction is present in patients with CFS regardless of the severity of the illness which means that the mitochondria's ability to produce sufficient energy for the body is significantly reduced. This helps to explain some of the distinct features of CFS such as debilitating fatigue and post-exertional malaise (PEM).(5)