What Is CFS
Between 836,000 to 3.3 million people in the US have CFS. It more often affects women and is most common in people aged 40–60, but can impact people of all ages and genders.
CFS often happens after an infection, a stressful period of life or another trigger. While we do know some of the triggers for this condition, we don't understand the specifics of what causes it.
What Causes CFS
While we don't fully understand what causes CFS, researchers are investigating many different factors that seem to be linked to the disease.
Energy production
CFS seems to be a condition that's driven by systemic energy failure and immune system dysfunction, with impaired mitochondrial function, systemic inflammation and immune system exhaustion (Van Campenhout et al., 2025).
In CFS, the energy-producing mitochondria seem to be working less efficiently (Van Campenhout et al., 2025), which may mean the body is unable to produce enough energy for normal function.
Immune function
In individuals with CFS, immune system abnormalities seem to be related to how severe disease symptoms are (Heng et al., 2025; Van Campenhout et al., 2025). In many cases, an infection can cause immune dysfunction that acts as an initiator for CFS. Infection with the Epstein-Barr virus seems to be the trigger in around 30% of CFS cases (Jason et al., 2021).
Nutrition and gut imbalances
Imbalances in the gut microbiome are also commonly found in people with CFS, but it's less clear whether these gut microbiome changes actually cause CFS. The gut and brain are strongly connected, and there does seem to be a link between gut health and chronic inflammation in people with CFS (Stallmach et al., 2024).
There's some evidence linking low magnesium and/or B vitamin levels to CFS, partly due to their importance in mitochondrial health and energy production (Castro-Marrero et al., 2017).
HPA-axis dysregulation
Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is also involved in chronic fatigue syndrome. This is a collection of glands that secrete hormones and work together to regulate stress, energy and mood. Individuals with CFS may have a weakened response to the hormones released by the HPA axis and may dysregulate the axis, reducing its activity (Zhang & Wang, 2024).
Who Is At Risk
We know that people with certain characteristics are more likely to experience chronic fatigue syndrome, including:
Young to middle-aged adults – this age group are most likely to experience CFS, but it can affect anyone including children
Women – being female means you have an increased risk of being diagnosed with CFS
Having another complex health condition – people with conditions like fibromyalgia, autoimmune conditions, allergies, or irritable bowel syndrome are more likely to develop CFS
Recent infection with Epstein-Barr or other viruses – recent viral infections can increase the risk of CFS (especially if symptoms are severe), although most people who are infected with these viruses don't get CFS
Recent physical or psychological stress
A family history of CFS – genetics may play a part in developing the disease, although we're yet to identify any specific genes
Research into the link between these factors and chronic fatigue is still ongoing.
What Are The Symptoms
The four main symptoms of chronic fatigue syndrome are:
Extreme tiredness/fatigue
Issues with sleep
Difficulties with memory or thinking (brain fog )
Post-exertional malaise (symptoms worsen after or are triggered by, social, mental or physical activity)
In some cases, CFS can also cause other physical symptoms including pain, a fever, flu-like symptoms, nausea, heart palpitations, sensitivity to stimuli (like light, noise or touch) and dizziness or fainting when standing up.
Symptoms can be mild, allowing you to still continue your usual activities with increased effort, or more severe. With severe symptoms, you may struggle to do any of your usual activities and can even find it hard to get out of bed or to eat and drink.
How Is CFS Diagnosed
There's no specific test that can tell you whether you have CFS, but blood tests and/or urine tests may be used to rule out other medical causes for your symptoms like an underactive thyroid, anemia or liver/kidney problems.
To be diagnosed with CFS, you must have:
Reduced activity for more than 6 months along with fatigue that doesn't get better with rest
Sleep that doesn't refresh you or relieve your fatigue AND
Post-exertional malaise
Post-exertional malaise means your CFS symptoms get worse after physical or mental activities that wouldn't usually be tiring. Sometimes new symptoms can also appear, including:
Sleep problems
Headaches
Dizziness
Tiredness
Brain fog
Alongside reduced activity/fatigue, unrefreshing sleep and post-exertional malaise, you must also have:
Difficulty thinking or concentrating
OR
Fainting/dizziness when standing up
A physician will consider all of these things when considering a CFS diagnosis and may refer you to a specialist if your symptoms are severe or they want a second opinion.
How Is CFS Treated With Regenerative Therapies
CFS is a complex condition and there's a lack of high-quality evidence and clinical trials data to support any particular treatment as the “gold standard”, whether that's regenerative or traditional therapies.
Standard treatment is personalized, but tends to involve one (or several) of the following:
Cognitive behavioral therapy (CBT) – talking therapy where people with CFS learn different ways to manage their thoughts about the condition
Activity management/pacing – learning to balance activity and rest in a way that minimizes post-exertional malaise
Painkillers – to deal with muscle pain, headaches or other pain
Antidepressants – for mood and sleep problems
Input from a dietitian – to avoid malnutrition or nutrient deficiencies
Equipment and home adaptations – to make your activities of daily life easier, often with the help of an occupational therapist
The regenerative approach to CFS focuses on creating the right environment within the body to support and improve general health, often focusing on nutrition, diet and gut health.
In a double-blind RCT, weekly intramuscular magnesium injections improved energy and reduced pain in 80% of CFS patients compared to just 18% taking a placebo (Cox et al., 1991). Other studies conducted since have failed to replicate this result, so magnesium supplementation is not recommended in clinical guidelines for treating CFS.
A systematic review found that B-complex vitamin supplementation can improve fatigue and functional outcomes in patients with CFS (Idris et al., 2025). While B supplementation may help with some people's symptoms, there's not enough data for this to be a standard recommendation and supplements, especially at higher than standard doses, do come with some risks.
Supplementation with coenzyme Q10 and NADH has been found to improve fatigue in CFS in multiple RCTs, but overall the evidence quality is low (Castro-Marrero et al., 2015; Dorczok et al., 2025; Maksoud et al., 2021). Again, more research is needed before this type of supplementation can be widely recommended.
A 2025 systematic review found that gut microbiome-supporting interventions like probiotics, prebiotics or dietary changes may reduce neuropsychiatric symptoms and improve the quality of life in people with CFS (Hsu et al., 2025). It's thought that these effects happen via gut-brain axis modulation.
There is also a very small amount of evidence that stem cell treatment may help with CFS symptoms. This is based on a few case studies that found stem cell treatment could improve fatigue, cognitive function and physical well-being in people with CFS (Mantle et al., 2025; Pada Vinski et al., 2024).
What Are Possible Complications
If you ignore CFS and continue as normal, it's likely that any physical symptoms will get worse and your quality of life will gradually reduce over time.
You may find that your post-exertional malaise becomes more severe or happens more often after smaller amounts of activity. Managing your activity levels (also known as pacing) can help you to avoid doing too much and exhausting yourself to a point where you have to rest in bed for a prolonged period of time. It will also allow you to experience the benefits of exercise, helping to avoid muscle deconditioning without overexerting yourself.
Without management, physical symptoms like orthostatic intolerance (lightheadedness when upright) may get worse. This can increase the risk of dizziness, fainting and falls, which can cause physical injuries. Medication or lifestyle/environmental changes can help to manage these symptoms and avoid further injury.
Can CFS Be Prevented
As we don't fully understand why CFS happens it isn't possible to prevent it. However, it is possible to avoid some known triggers and to do things that can reduce the risk of flare-ups.
High stress situations (whether that's physical or mental) can trigger both the onset of CFS and may cause flare-ups, so it's helpful to find ways to avoid stress or manage it as effectively where this isn't possible.
Pacing is a way to keep activity levels within your energy limits which can help to avoid post-exertional malaise, while CBT may help you to manage how you feel about your diagnosis.
Takeaway
Chronic fatigue syndrome is a complex condition that we don't fully understand. However, we do know that problems with energy production, the immune system, hormone levels and the gut microbiome are all involved.
While there is currently no cure for CFS, supporting your body holistically (including taking supplements or probiotics in some cases), managing your energy levels through pacing and controlling your symptoms with medication when necessary may help.
