What is chronic fatigue syndrome?

Feeling constantly exhausted, no matter how much you rest? You’re not alone. Chronic fatigue syndrome (CFS), sometimes called myalgic encephalomyelitis (ME), is a complex, long-term condition that goes far beyond ordinary tiredness.

Despite affecting millions worldwide, ME/CFS remains one of the most misunderstood and under-researched illnesses in medicine today. For those experiencing its symptoms, everyday tasks can become overwhelming, and the journey to diagnosis and effective treatment is often long and frustrating.

In this blog, we take a comprehensive look at what ME/CFS is, how it affects the body, and the latest insights into its causes. We’ll also explore promising approaches to managing symptoms, including Courier Pharmacy’s innovative 3R Treatment Program designed specifically for ME/CFS patients.

Five key takeaways

1. Chronic fatigue syndrome (ME/CFS) is a complex, long-term illness. It causes profound fatigue, sleep disturbances, “brain fog,” and worsening of symptoms after exertion, making daily life extremely challenging.
2. Diagnosis is difficult, as there is no single test or universally agreed-upon criteria for ME/CFS. This often leading to delayed recognition and years of unexplained symptoms.
3. Millions are affected worldwide, with ME/CFS impacting an estimated 17 to 24 million people globally. This inludes up to 2.5 million in the USA and over 250,000 in the UK. In addition many remain undiagnosed or misunderstood.
4. The causes are complex and multifactorial. They involve a mix of genetic predisposition and environmental triggers. These can include such as viral infections, toxins, stress, and certain medications, which lead to immune dysfunction, inflammation, and impaired energy production.
5. The 3R Treatment Program from Courier Pharmacy offers a new, holistic approachfor the treatment of CFS. It combines low dose naltrexone (LDN), melatonin buccal film, and CoQ10 buccal film to reduce fatigue, improve sleep, and boost energy for people with ME/CFS.

Introduction

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a long-lasting illness that can make daily life very difficult. People with ME/CFS experience a wide range of symptoms that affect their whole lives. Even though many people have this condition, it is still not well understood or studied by doctors and scientists.

There is no single test or agreed-upon way to diagnose ME/CFS, and different doctors use different criteria. At the moment, there are no proven treatments for the disease.

A holistic approach for CFS

Instead of looking at ME/CFS in bits and pieces, our new approach brings together all the current information to create a clearer picture.

We show that ME/CFS likely develops from a mix of genetic factors (things you inherit) and environmental triggers, such as viral infections. These triggers can cause a chain reaction in the body, including problems with the immune system, long-lasting inflammation, changes in gut bacteria, and disruptions in how the body uses energy.

By putting all these pieces together, we hope to help people better understand how ME/CFS works. This new way of looking at the illness may also lead to better research and, eventually, new treatments. We believe it’s essential to look at the whole picture when diagnosing, studying, and treating ME/CFS, and we encourage others to do the same [1].

What is CFS?

Myalgic encephalomyelitis (ME), also called chronic fatigue syndrome (CFS), is a long-lasting and complicated illness that affects many parts of the body.

It causes extreme tiredness that doesn’t improve with rest and often worsens after physical or mental activity [2].

Besides feeling very tired, people with ME/CFS may have problems with:

• thinking clearly,
• pain in their muscles and joints,
• trouble sleeping,
• feeling worse after exertion, and
• issues with their immune system.

How many people have chronic fatigue syndrome?

It is estimated that ME/CFS affects between 0.1% and 0.8% of people worldwide [1]. This means about 17 to 24 million people around the world have ME/CFS [3].

In the United States, health groups such as the Centres for Disease Control and Prevention (CDC) and the National Academy of Medicine estimate that between 836,000 and 2.5 million people have been diagnosed with ME/CFS [1], [4]. About one in four of these people is so sick that they cannot leave their home or bed [5].

How many people have CFS in the UK?

In the United Kingdom, recent data from the U.K. Biobank shows that more than 250,000 people in England and Wales live with ME/CFS [1]. In some parts of England, about 0.2% of the population has this illness [6].

What are the symptoms of chronic fatigue syndrome?

The 4 main symptoms of ME/CFS are:

• Feeling very tired all the time (fatigue), which can make simple things like showering or going to work or school hard [7].
• Trouble with sleep, such as insomnia, sleeping too much, feeling like you didn’t rest well, or waking up feeling exhausted or stiff [7].
• Problems with thinking, focusing, and remembering things (often called brain fog) [7].
• Symptoms getting worse after physical or mental activity, sometimes taking weeks to improve. This is called post-exertional malaise (PEM) [7].

Some people with ME/CFS also have pain in different parts of their body or flu-like symptoms like fever, headaches, and aching muscles or joints [7].

What is the key symptom of chronic fatigue syndrome?

Many symptoms are similar to those seen in other conditions, but one thing that makes ME/CFS different is that symptoms get much worse after even small amounts of physical, mental, standing up, or emotional effort [1].  This is called post-exertional malaise (PEM) or post-exertional symptom exacerbation (PESE) [1].

After doing even a little bit of activity, people with ME/CFS often feel much more tired, both in their body and mind. Their muscles and thinking skills can get tired very quickly [8] . This extra tiredness often starts a while after the activity, lasts a long time, and is much worse than you’d expect for the amount of effort made [8].

Fatigue is one of the main symptoms for most people with ME/CFS. Unlike normal tiredness, this fatigue does not go away no matter how much someone sleeps or rests [9].

Diagnosing ME/CFS

Right now, there is no single test or lab marker that can confirm if someone has ME/CFS. This means that people often live with their symptoms for years before getting a clear diagnosis. Scientists are hopeful that new tests looking at the immune system might help in the future [10]. Other researchers are attempting to develop an AI solution to help with the diagnosis of chronic fatigue syndrome [11].

The Centers for Disease Control (CDC) has set out some guidelines to help doctors diagnose ME/CFS [12]. According to these guidelines, a person must have:

• Ongoing, unexplained tiredness that lasts at least six months and is not improved by rest. This tiredness must make it much harder to work, go to school, or do normal daily activities.
• At least four other symptoms at the same time, such as memory or concentration problems, sore throat, tender lymph nodes, muscle or joint pain, new headaches, poor sleep, or feeling much worse after activity (post-exertional malaise, or PEM).

There are other guidelines which other physicians may use, which highlights the problem of getting a diagnosis for chronic fatigue syndrome, no one can agree on a formal diagnostic criteria. Maybe AI will be able to come up with a universal diagnostic criteria which can incorporates biomarkers.

What might cause ME/CFS?

Scientists believe that ME/CFS is a complicated illness with many possible causes [13]. There isn’t just one thing that leads to ME/CFS—rather, it likely happens when different factors come together [1]. For example, a person may be more likely to get ME/CFS if they have certain genes and then experience a stressful event, an infection, or even a small physical or emotional trigger [14]. Sometimes, even a short walk, a glass of wine, or a change in temperature can make symptoms worse [15].

Genetic predisposition

Some research suggests that ME/CFS may run in families, meaning genes might play a role [16]. However, we don’t yet know exactly which genes are involved, and studies have shown mixed results [1].

Viral triggers

Many people with ME/CFS say their symptoms started after a viral infection, such as glandular fever or Epstein-Barr virus [17], [18]. In fact, about two-thirds of ME/CFS cases seem to follow a viral illness [18]. Some scientists think that viruses can “wake up” in the body and trigger the immune system, which may lead to ME/CFS symptoms. However, not all studies agree, and no single virus has been found to cause ME/CFS in everyone.

Toxins and drugs

Exposure to certain chemicals or heavy metals, like organophosphates (found in some pesticides) or cadmium, may also play a role in some cases [19]. These substances can affect the nervous system, cause fatigue, and impact brain function  [1]. Some people worry about vaccines, but studies show that most vaccines do not increase the risk of ME/CFS or make symptoms worse [20].

Certain medicines, like fluoroquinolone antibiotics, have been linked to symptoms similar to ME/CFS in rare cases [21]. These drugs can sometimes affect the body’s energy systems and cause long-lasting problems in some people.

In summary:

ME/CFS likely happens when several risk factors come together, such as genetic makeup, infections, stress, toxins, or certain medications. Not everyone with these risk factors will get ME/CFS, and the exact causes are still being studied. Scientists are working hard to better understand why ME/CFS develops and how to prevent it.

What’s happening in the body with ME/CFS?

ME/CFS is a complex illness that affects many systems in the body. Scientists believe it starts when things like infections or stress upset the immune system, causing long-lasting inflammation and other changes. Over time, this can lead to problems with blood flow, energy production, and even how the brain and gut work.

Immune system and inflammation

When someone with ME/CFS gets an infection or faces a big stress, their immune system can go into overdrive. This can lead to chronic (long-term) inflammation, which means the body is always in “alert mode.”[22] Sometimes, the immune system may even start attacking the body’s own cells by mistake, a process called autoimmunity. This ongoing inflammation can affect blood vessels, making it harder for blood and oxygen to reach all parts of the body, which can cause tiredness and pain.

Gut health

Many people with ME/CFS have gut problems like pain, bloating, or irritable bowel syndrome. Studies show that the mix of bacteria in the gut is often different in people with ME/CFS. Good bacteria are sometimes lower, while bacteria that cause inflammation are higher. This imbalance can make the gut “leaky,” allowing bacteria and toxins to enter the blood and cause more inflammation in the body [23].

Blood flow and energy

Because of inflammation and changes in blood vessels, people with ME/CFS can have trouble getting enough blood and oxygen to their muscles and brain. This can make them feel weak, dizzy, or short of breath, especially when standing up or after exercise. Their bodies also have trouble making enough energy, which is why even small activities can feel exhausting [24].

Oxidative stress

ME/CFS is also linked to something called oxidative stress, where harmful molecules build up and damage cells. Usually, the body has ways to fight these molecules, but in ME/CFS, these defences are weaker. This can cause muscle pain, fatigue, and problems with thinking clearly [25].

Brain and nerves

Chronic inflammation can also affect the brain. Some people with ME/CFS have signs of “neuroinflammation,” which means their brains are inflamed [26]. This can cause problems with memory, concentration, and sleep. Sometimes, the barrier that protects the brain from harmful substances (the blood-brain barrier) becomes weaker, letting in things that can cause more problems.

Hormones

Stress hormones like cortisol and growth hormone can also be out of balance in ME/CFS. This can make people more sensitive to stress and may contribute to symptoms like fatigue, poor sleep, and changes in appetite or weight [27].

Blood clotting

Some studies show that people with ME/CFS may have tiny blood clots (called microclots) that block small blood vessels. This can reduce blood flow to tissues and cause symptoms like pain and tiredness [28].

Autoimmunity

In some people with ME/CFS, the immune system makes antibodies that attack parts of their own body, especially nerves and blood vessels. This can lead to more symptoms and may explain why ME/CFS is similar to some autoimmune diseases [29].

In summary:
ME/CFS is a complicated illness where the immune system, gut, blood flow, energy production, and even the brain are all affected. The body gets stuck in a cycle of inflammation and low energy, making it hard to recover. Scientists are still working to understand all the details, but this knowledge helps guide new research and possible treatments.

Managing ME/CFS: Medicines and Other Approaches

Medicines

There isn’t a cure for ME/CFS yet, but some medicines can help manage the symptoms. Doctors may recommend different drugs depending on what symptoms bother you most. Common medicines include:

• Painkillers and anti-inflammatories (like ibuprofen or naproxen): These help with pain, headaches, and inflammation.
• Anticonvulsants (like gabapentin or pregabalin): These are sometimes used for nerve pain and sleep problems.
• Antidepressants: These can help with pain, poor sleep, low mood, and anxiety. Some types (like amitriptyline) are used for sleep and pain, but it may take a few weeks to notice an effect.
• Narcotics (like tramadol or codeine): These are only used for severe pain and usually for a short time because of the risk of addiction.
• Antivirals and immune drugs: Some drugs, like Ampligen, have shown promise in research, but they aren’t widely available. Other antivirals can be used, but they may have side effects.

Non-Medicine Approaches

Other ways to manage ME/CFS include:

• Adaptive Pacing Therapy (APT): This helps people balance activity with rest. The idea is to listen to your body, avoid overdoing things, and set realistic goals. APT is safer and more helpful for many people than pushing through symptoms.
• Cognitive Behavioural Therapy (CBT): This is a type of talking therapy. It may help some people cope with symptoms, but it doesn’t cure ME/CFS.
• Graded Exercise Therapy (GET): This involves slowly increasing exercise. However, many people with ME/CFS find that GET makes their symptoms worse, especially post-exertional malaise (PEM). Because of this, GET is not recommended for most people with ME/CFS.

Ongoing Debates

There is still debate about the best ways to manage ME/CFS. Some experts think it is mainly a psychological condition, while others believe it is caused by problems in the immune system, hormones, or after a viral infection.

The previously endorsed treatments of CBT ad GET have been discredited with evidence suggesting that they offer minimal, if any benefits and may cause more harm than good [30], [31], [32].

More research is needed to find out what causes ME/CFS and how to treat it best.

Patient experiences

People with ME/CFS often struggle to get a diagnosis and may feel misunderstood. The illness can affect daily life, work, and relationships. While some people see improvements, full recovery is rare.

Many patients face the added challenge that some doctors don’t fully recognize ME/CFS as a real disease. Because its symptoms can be vague and overlap with other conditions, and there are no clear tests to confirm it, some healthcare professionals mistakenly believe ME/CFS is mainly psychological or “all in the mind.”

This misunderstanding can leave patients feeling dismissed, not taken seriously, or even blamed for their illness.

The controversy with Graded Exercise Therapy (GET) and Cognitive Behavioural Therapy (CBT)

The controversy around treatments like Graded Exercise Therapy (GET) and Cognitive Behavioural Therapy (CBT) has made things worse for many. Many patients report that GET made their symptoms worse, and some feel their experiences were ignored when these therapies were promoted as solutions. This has caused frustration, anxiety, and a sense of isolation from the medical community.

Because we don’t yet fully understand what causes ME/CFS, preventing it before it starts (primary prevention) is difficult. However, it is possible to reduce delays in diagnosis, prevent severe cases, and lower healthcare costs by improving early recognition and care (secondary prevention).

A key step is changing how doctors view ME/CFS and reducing the stigma around the illness. The World Health Organization classified ME/CFS as a neurological disease in 1969, recognizing its effects on the nervous system. Unfortunately, in 1970, two psychiatrists wrongly described some outbreaks of ME/CFS as “mass hysteria” [33]. Their work was later criticized for not properly studying the patients, and their conclusions were discredited [34]. However, this mistake sparked stigma that still affects ME/CFS patients today.

LDN for CFS

Low Dose Naltrexone (LDN) is being studied as a potential treatment for Chronic Fatigue Syndrome (CFS), also known as ME/CFS. Originally used in higher doses to treat opioid addiction, LDN at much lower doses is thought to work by modulating the immune system and reducing inflammation, which are believed to contribute to CFS symptoms. Some small studies and patient reports suggest that low-dose naltrexone may help reduce fatigue, ease pain, improve sleep, and enhance overall quality of life for people with CFS.

One notable retrospective study looked at 218 patients with ME/CFS who were treated with LDN. In this study, about 70% of patients reported improvements in symptoms such as fatigue, pain, and cognitive function after starting low-dose naltrexone treatment. Many also experienced better sleep and overall quality of life. The medication was generally well tolerated, with few side effects that were mostly mild and temporary [35]. However, because this study looked back at patient records rather than following patients in a controlled, prospective way, its findings are less definitive than those from randomised controlled trials.

While these early results are encouraging, LDN is not yet widely approved or recommended as a standard treatment for CFS.

As research continues, low-dose naltrexone may become a valuable option in the growing list of therapies aimed at improving the lives of those with CFS.

If you are want to learn more about low dose naltrexone and its use in CFS, please contact us. Alternatively, complete the online CFS consultation form to start your LDN journey today.

Coenzyme Q10 and chronic fatigue syndrome

CoQ10 is an antioxidant that helps the body make energy (ATP).. CoQ10 also protects the body’s cells from damage and helps reduce inflammation.

In one study, people who took both NADH and CoQ10 had more energy, better sleep, improved quality of life, a higher heart rate during exercise, and better overall health [36].

Another study found that taking CoQ10 with selenium helped reduce tiredness, improved quality of life, lowered harmful fats in the blood, boosted antioxidants, and reduced inflammation [37].

CoQ10 absorption and the new buccal film from Courier Pharmacy

CoQ10 is an important antioxidant that helps the body make energy and protects cells from damage. However, one big problem with CoQ10 supplements is that they are not absorbed well when taken by mouth. Studies have found that common forms like capsules, tablets, and even some fancy liposome or nano-formulations do not significantly improve how much CoQ10 actually gets into the body [38].

This is because CoQ10 does not dissolve easily in water, making it hard for the gut to absorb. Even in healthy people, most of the CoQ10 from these products passes through the digestive system without being used.

Why is buccal delivery so effective?

Because of these challenges, Courier Pharmacy has teamed up with APC Labs to develop a new CoQ10 buccal film. This innovative product is designed to be placed inside the cheek, where it dissolves and is absorbed directly through the lining of the mouth (the buccal mucosa).

This method skips the digestive system and helps more CoQ10 enter the bloodstream quickly and efficiently. By improving absorption, the buccal film could help people with ME/CFS and others get the full benefits of CoQ10, such as more energy and better cell protection.

This new approach is based on research showing that medicines and supplements delivered through the mouth’s lining can be much more effective than traditional pills, especially for nutrients like CoQ10 that are hard to absorb. As research continues, this buccal film could be a game-changer for anyone needing better CoQ10 support.

To order the CoQ10 buccal film you will first need to complete the CFS consultation form.

Melatonin buccal film for ME/CFS

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex and very disabling illness that affects many parts of the body. Unfortunately, there are no approved drugs that can effectively treat it yet. Some studies have suggested that melatonin and zinc supplements might help reduce symptoms like fatigue, sleep problems, anxiety, and low quality of life in chronic illnesses, but more research is needed specifically for ME/CFS [39].

What do the studies say about melatonin and chronic fatigue syndrome?

A recent 16-week clinical trial tested the effects of taking oral melatonin (1 mg) combined with zinc (10 mg) daily in 50 people with ME/CFS. Half of the participants received the melatonin-zinc combination, while the other half took a placebo (a dummy pill). The study measured fatigue, sleep quality, mood, and overall health at the start, during, and after treatment [39].

The results showed that those taking melatonin and zinc had a significant reduction in physical fatigue and better physical health compared to the placebo group. Melatonin levels in the body increased as expected, but zinc levels did not change significantly. The treatment was safe and well tolerated, suggesting that melatonin plus zinc may help improve fatigue and quality of life in ME/CFS [39].

Building on this, Courier Pharmacy has teamed up with APC Labs to develop a melatonin buccal film designed for improved absorption through the lining of the mouth. This new form helps melatonin enter the bloodstream more effectively than traditional pills. The melatonin buccal film can only be obtained by completing the ME/CFS questionnaire, ensuring it is used safely and appropriately for those who may benefit most.

The Three R Treatment from Courier Pharmacy: Recover, Rest, and Recharge

Courier Pharmacy is proud to introduce the “Three R” treatment program for people with ME/CFS, focusing on Recover, Rest, and Recharge. This innovative approach brings together three specially formulated products—Low Dose Naltrexone (LDN), a melatonin buccal film, and a Coenzyme Q10 (CoQ10) 50mg buccal film—to help support the unique needs of those living with chronic fatigue syndrome.

Each of these treatments has shown benefits for people with CFS when used on their own.

Studies suggest that:

• LDN can help reduce pain, fatigue, and inflammation by balancing the immune system
• Melatonin is well known for improving sleep and may also help with fatigue and mood
• CoQ10 is a powerful antioxidant that supports energy production in cells, but it is often poorly absorbed in traditional pill form

That’s why Courier Pharmacy, in partnership with APC Labs, has developed advanced buccal films for both melatonin and CoQ10. These films dissolve inside the cheek, allowing the active ingredients to be absorbed directly into the bloodstream for better and faster results.

The 3R treatment plan, Recover, Rest and Recharge

By combining these three scientifically backed therapies, Courier Pharmacy’s Three R program offers a comprehensive approach for the first time in the UK. The program is designed to help patients recover energy, rest better at night, and recharge their bodies and minds throughout the day. All three products are compounded specifically for this program and are available exclusively through Courier Pharmacy.

This new program was developed after reviewing research showing that each of these treatments can help people with CFS on their own. Now, by bringing them together, the Three R program aims to offer even greater support for those struggling with the daily challenges of ME/CFS. If you’re interested in learning more or want to find out if the Three R program is right for you, contact Courier Pharmacy for details on how to get started.

Looking to the future for CFS

Scientists are working to find better ways to diagnose and treat ME/CFS. They are studying genes, the immune system, the gut, and using new technologies like brain scans and wearable devices. The hope is to find reliable tests (biomarkers) and develop treatments that work for each person.

How Nutrigen test can help optimise your nutrition to improve chronic fatigue syndrome

Chronic Fatigue Syndrome (CFS), also known as Myalgic Encephalomyelitis (ME), is a complex condition that affects multiple systems in the body, leading to profound fatigue, cognitive difficulties, and a range of other symptoms. While there is no one-size-fits-all treatment, emerging personalized approaches such as nutrigenetic testing offer promising ways to optimize nutrition and support symptom management.

What is the Nutrigen test?

Nutrition genetic testing analyzes specific variations in your genes that influence how your body processes nutrients, vitamins, and minerals. These genetic differences can affect your metabolism, nutrient absorption, and even your body’s response to certain foods and supplements. By understanding your unique genetic profile, healthcare providers can tailor nutritional recommendations that suit your individual needs.

Why Nutrition matters in CFS

People with CFS often experience nutrient imbalances or deficiencies that can worsen symptoms like fatigue, brain fog, and immune dysfunction. For example, some may have difficulties metabolizing B vitamins, vitamin D, or antioxidants, all of which are crucial for energy production and immune health. Optimizing nutrition can help reduce inflammation, improve mitochondrial function, and support overall wellbeing.

How Nutrigen test supports CFS management

1. Personalized Supplementation: Instead of generic vitamin advice, nutrigenetic testing identifies which nutrients you may need more of or less of, helping to avoid ineffective or harmful supplementation.
2. Targeted Dietary Guidance: Genetic insights can guide dietary choices that improve digestion, reduce oxidative stress, and support gut health—areas often disrupted in CFS.
3. Enhanced Energy Production: By identifying genetic variants affecting mitochondrial function and metabolism, tailored nutrition plans can focus on boosting cellular energy, a key challenge in CFS.
4. Immune System Support: Nutrigen test information can reveal susceptibilities to inflammation or immune dysregulation, allowing for nutrition strategies that help modulate immune responses.

Integrating Nutrigenetics with treatment

At Courier Pharmacy, the Nutrigen test is used alongside advanced treatments like low dose naltrexone (LDN), melatonin, and CoQ10 buccal films to create a comprehensive, personalized care plan. This integrated approach aims to address the root causes and symptoms of CFS more effectively than conventional methods.

Getting started

If you’re living with CFS and want to explore how personalised nutrition could support your health, consider nutrition genetic testing as part of your care journey. To begin your journey to optimise your nutrional health, order your Nutrigen test today.

Summary

ME/CFS is a challenging illness with no single cure. Treatments focus on managing symptoms, and what works can be different for each person. Listening to your body, pacing activities, and working with knowledgeable healthcare professionals are key. Ongoing research offers hope for better answers and treatments in the future.

Disclaimer: This article is for informational purposes only and does not replace professional medical advice.

References:

[1] Arron, H.E., Marsh, B.D., Kell, D.B., Khan, M.A., Jaeger, B.R. and Pretorius, E., 2024. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: the biology of a neglected disease. Frontiers in Immunology, 15, p.1386607.

What is CFS?

• [2] Graves, B.S., Patel, M., Newgent, H., Parvathy, G., Nasri, A., Moxam, J., Gill, G.S., Sawhney, V. and Gupta, M., 2024. Chronic fatigue syndrome: diagnosis, treatment, and future direction. Cureus, 16(10).

How many people have chronic fatigue syndrome?

• [3] Lim, E.J. and Son, C.G., 2020. Review of case definitions for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Journal of translational medicine, 18(1), p.289.
• [4] Jason, L.A., Richman, J.A., Rademaker, A.W., Jordan, K.M., Plioplys, A.V., Taylor, R.R., McCready, W., Huang, C.F. and Plioplys, S., 1999. A community-based study of chronic fatigue syndrome. Archives of internal medicine, 159(18), pp.2129-213
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How many people have CFS in the UK?

• [6] Nacul, L.C., Lacerda, E.M., Pheby, D., Campion, P., Molokhia, M., Fayyaz, S., Leite, J.C., Poland, F., Howe, A. and Drachler, M.L., 2011. Prevalence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in three regions of England: a repeated cross-sectional study in primary care. BMC medicine, 9(1), p.91.

What are the symptoms of chronic fatigue syndrome?

• [7] NHS. Chronic fatigue syndrome (CFS). Available at: https://www.nhs.uk/conditions/chronic-fatigue-syndrome-cfs/ (Accessed: 21 October 2025).

What is the key symptom of chronic fatigue syndrome?

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Diagnosing ME/CFS

• [10] Yamano, E., Watanabe, Y. and Kataoka, Y., 2021. Insights into metabolite diagnostic biomarkers for myalgic encephalomyelitis/chronic fatigue syndrome. International journal of molecular sciences, 22(7), p.3423.
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• [12] Lim, E.J., Ahn, Y.C., Jang, E.S., Lee, S.W., Lee, S.H. and Son, C.G., 2020. Systematic review and meta-analysis of the prevalence of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). Journal of translational medicine, 18(1), p.100.

What might cause ME/CFS?

• [13] Pheby DFH, Friedman KJ, Murovska M, Zalewski P. Turning a corner in ME/ CFS research. Medicina (Kaunas) 57. (2021). doi: 10.3390/medicina57101012
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Genetic predisposition

• [16] Underhill, R.A. and O’gorman, R., 2006. Prevalence of chronic fatigue syndrome and chronic fatigue within families of CFS patients. Journal of Chronic Fatigue Syndrome, 13(1), pp.3-13.

Viral triggers

• [17] Lerner, A.M., Ariza, M.E., Williams, M., Jason, L., Beqaj, S., Fitzgerald, J.T., Lemeshow, S. and Glaser, R., 2012. Antibody to Epstein-Barr virus deoxyuridine triphosphate nucleotidohydrolase and deoxyribonucleotide polymerase in a chronic fatigue syndrome subset. PloS one, 7(11), p.e47891.
• [18] Blomberg, J., Gottfries, C.G., Elfaitouri, A., Rizwan, M. and Rosén, A., 2018. Infection elicited autoimmunity and myalgic encephalomyelitis/chronic fatigue syndrome: an explanatory model. Frontiers in immunology, 9, p.229.

Toxins and drugs

• [19] Behan, P.O., 1996. Chronic fatigue syndrome as a delayed reaction to chronic low-dose organophosphate exposure. Journal of Nutritional & Environmental Medicine, 6(4), pp.341-350.
• [20] Feiring, B., Laake, I., Bakken, I.J., Greve-Isdahl, M., Wyller, V.B., Håberg, S.E., Magnus, P. and Trogstad, L., 2017. HPV vaccination and risk of chronic fatigue syndrome/myalgic encephalomyelitis: a nationwide register-based study from Norway. Vaccine, 35(33), pp.4203-4212.
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What’s happening in the body with ME/CFS?

• [22] Proal, A. and Marshall, T., 2018. Myalgic encephalomyelitis/chronic fatigue syndrome in the era of the human microbiome: persistent pathogens drive chronic symptoms by interfering with host metabolism, gene expression, and immunity. Frontiers in pediatrics, 6, p.373.
• [23] Newberry, F., Hsieh, S.Y., Wileman, T. and Carding, S.R., 2018. Does the microbiome and virome contribute to myalgic encephalomyelitis/chronic fatigue syndrome?. Clinical Science, 132(5), pp.523-542.
• [24] Fluge, Ø., Tronstad, K.J. and Mella, O., 2021. Pathomechanisms and possible interventions in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The Journal of Clinical Investigation, 131(14).
• [25] Paul, B.D., Lemle, M.D., Komaroff, A.L. and Snyder, S.H., 2021. Redox imbalance links COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome. Proceedings of the National Academy of Sciences, 118(34), p.e2024358118.
• [26] Natelson, B.H., Weaver, S.A., Tseng, C.L. and Ottenweller, J.E., 2005. Spinal fluid abnormalities in patients with chronic fatigue syndrome. Clinical and Vaccine Immunology, 12(1), pp.52-55.
• [27] De Bellis, A., Bellastella, G., Pernice, V., Cirillo, P., Longo, M., Maio, A., Scappaticcio, L., Maiorino, M.I., Bellastella, A., Esposito, K. and Montoya, J.G., 2021. Hypothalamic-pituitary autoimmunity and related impairment of hormone secretions in chronic fatigue syndrome. The Journal of Clinical Endocrinology & Metabolism, 106(12), pp.e5147-e5155.

Managing ME/CFS: Medicines and Other Approaches

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• [29] Sotzny, F., Blanco, J., Capelli, E., Castro-Marrero, J., Steiner, S., Murovska, M. and Scheibenbogen, C., 2018. Myalgic encephalomyelitis/chronic fatigue syndrome–evidence for an autoimmune disease. Autoimmunity reviews, 17(6), pp.601-609.
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Patient Experiences

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LDN for CFS

• [33] McEvedy, C.P. and Beard, A.W., 1970. Concept of benign myalgic encephalomyelitis. Br Med J, 1(5687), pp.11-15.
• [34] Evengård, B., Schacterle, R.S. and Komaroff, A.L., 1999. Chronic fatigue syndrome: new insights and old ignorance. Journal of Internal Medicine, 246(5), pp.455-469.
• [35] Polo, O., Pesonen, P. and Tuominen, E., 2019. Low-dose naltrexone in the treatment of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Fatigue: Biomedicine, health & behavior, 7(4), pp.207-217.

Coenzyme Q10 and chronic fatigue syndrome

• [36] Castro-Marrero, J., Cordero, M.D., Segundo, M.J., Sáez-Francàs, N., Calvo, N., Román-Malo, L., Aliste, L., Fernández de Sevilla, T. and Alegre, J., 2015. Does oral coenzyme Q10 plus NADH supplementation improve fatigue and biochemical parameters in chronic fatigue syndrome?
• [37] Castro-Marrero, J., Domingo, J.C., Cordobilla, B., Ferrer, R., Giralt, M., Sanmartín-Sentañes, R. and Alegre-Martín, J., 2022. Does coenzyme Q10 plus selenium supplementation ameliorate clinical outcomes by modulating oxidative stress and inflammation in individuals with myalgic encephalomyelitis/chronic fatigue syndrome?
• [38] Vitetta, L., Leong, A., Zhou, J., Dal Forno, S., Hall, S. and Rutolo, D., 2018. The plasma bioavailability of coenzyme Q10 absorbed from the gut and the oral mucosa. Journal of Functional Biomaterials, 9(4), p.73.

Melatonin Buccal Film for ME/CFS

• [39]Castro-Marrero, J., Zaragozá, M.C., López-Vílchez, I., Galmés, J.L., Cordobilla, B., Maurel, S., Domingo, J.C. and Alegre-Martín, J., 2021. Effect of melatonin plus zinc supplementation on fatigue perception in myalgic encephalomyelitis/chronic fatigue syndrome: a randomized, double-blind, placebo-controlled trial. Antioxidants, 10(7), p.1010.