Chronic Fatigue Syndrome

Leonard: Think about the worst type of flu you've ever had. How sick you were. Your whole body ached. You felt like there was almost a poison going through your body. Can you imagine if you basically felt that way for months and years? You can imagine what a tremendous toll it would take on you.

Brent: Welcome to Death Clock. I'm your host, Brent Franson. Today we speak with Dr. Leonard Jason about chronic fatigue syndrome. Dr. Jason is a professor of psychology at DePaul University. He's the director of the Center for Community Research, and he's considered one of the world's leading epidemiologists on ME/CFS, which is the official name for chronic fatigue syndrome. He's also a scientist-patient.

Brent: He contracted the illness in 1990, so he has this rare blend of clinical and personal expertise. He's a wonderful guest. I hope you enjoy.

Brent: Dr. Leonard Jason, welcome to the show.

Leonard: Thank you.

Brent: So today we're going to be talking about ME/CFS. I'm not going to try to say what the M stands for, but we're going to talk about chronic fatigue syndrome. I think this is going to elicit some interesting conversations about not only CFS, but some of these other diseases that can be hard to define, that are fairly vague in nature, but can be really problematic for the people who are suffering from them.

Brent: And so I'm excited to dive in. But before we do that, can you give us a quick sense of your bio?

Leonard: I've been studying ME/CFS for over 35 years, and M stands for Myalgic Encephalomyelitis. CFS is Chronic Fatigue Syndrome. I'm particularly interested in trying to understand the epidemiology and prevalence of the illness, as well as some of the reasons people tend to get this illness, including precipitating, triggering, and predisposing events.

Brent: Okay, so let's just define it quickly. ME/CFS: what is it? What are the symptoms? How do I know if I might be suffering from it? Maybe you can comment on your own experience with it as well. I think your story starts with you going through it yourself, but how do we define it?

Leonard: Generally, it's a situation where a person has classic symptoms. The first one is post-exertional malaise, which involves stress after exertion. If you do some exertion, you basically feel sick. It's almost as if you have the flu, but you don't get over it. While with exercise, people often feel better—

Leonard: In this case, when people exercise or push themselves, they actually feel worse. Other common symptoms are unrefreshing sleep and cognitive impairment. The Institute of Medicine came out with a case definition ten years ago, and I would say these are three of the key factors. Again, you want to make sure you rule out other things that might be causing these particular symptoms—

Leonard: For example, cancer or heart disease. Certainly, when a person has these types of symptoms for at least six months, that would be classified as ME/CFS.

Brent: And maybe let's speak quickly about the category more broadly. I'd be curious for your perspective on it. I would put Long COVID in this category. I would put restless leg syndrome in this category. Maybe Lyme disease falls into this category, where you have these symptoms. For the outsider looking in, they might say, "Doesn't that happen to everybody?"

Brent: Is this real? When you double-check and speak to experts like yourself on these topics, they are very real. We do have ways of identifying who has CFS and who has Long COVID, but can you speak to the difficulty of this category?

Brent: We don't have tests that can tell you specifically—there's no blood test for CFS. So maybe it's worth speaking to the skeptics or just about the difficulty of the category, because it's not like when flu goes through your house and you can stick something up your child's nose and say, "Yeah, they have flu" or "They don't," and treat it accordingly.

Brent: Could you speak to that?

Leonard: One of the big issues in this field is that people often wonder whether healthcare professionals respect and legitimize their illness. You're right: a lot of people get SARS-CoV-2, which causes Long COVID, or Epstein-Barr virus, which causes mono. Most people recover from these viruses and bacterial infections, but a certain percentage of people don't recover.

Leonard: If you go back to the Spanish flu of 1918, a certain percentage of people never recovered. That's what we're looking at. Why does a virus or bacterial infection trigger something where a certain percentage of people continue to be symptomatic over time? That is very hard for the healthcare and medical community to understand, because the vast majority of people recover.

Leonard: So if most people recover and you don't recover, people say, "Well, it must be psychogenic. It might be hysteria. It might be something psychological, and there's really nothing wrong with you." That's the dilemma patients face with Long COVID, ME/CFS, Lyme, and post-polio syndrome—the vast majority of these types of infections that people don't seem to recover from.

Leonard: They suffer not only the trauma of being sick, but are then retraumatized by the societal, environmental, and medical reaction to the illness.

Brent: For all of these in this category, is it almost always a viral or bacterial infection that we tend to know something about, like COVID, followed by these symptoms?

Leonard: They—

Brent: Linger for an extended period—six months, a year, multiple years. Can we say definitively that it's always precipitated by a viral or bacterial infection across these conditions?

Leonard: With ME/CFS, it turns out that the infection seems to be Epstein-Barr virus, which causes mono. I would say for the majority of people who have a viral onset, it's because of that. But there are lots of other viral infections, and some people don't even have a viral or bacterial infection; there could be other triggering reasons.

Leonard: In fact, when we went over thousands of people and asked them what happened before they got sick, we came up with almost 100 different reasons for the onset. So yes, viral is probably the most prominent one, but there are lots of other things. Some people have had an accident; others have had a variety of events that caused some type of brain inflammation that ultimately triggers a cascade of events throughout the entire body.

Brent: When you say something like a trigger, I think of an on-off switch and immediately think of epigenetics. I have some lifestyle factor or dormant gene, and then living my life a certain way flips that gene on, which changes something about my health.

Brent: Do we look at epigenetics here, or brain inflammation? Am I on the right track when I think about epigenetics?

Leonard: I think you're on the right track. Think about a hundred people who get sick. A certain percentage, maybe 10% after six months, don't recover after mono. Two years later, that rate might be down to 4%. The question is, why are some people exposed to the same viral or bacterial stimuli, but—

Leonard: For some people, it causes a cascade of events? That's the holy grail of what we're trying to understand: what types of precipitating and predisposing conditions exist. For example, being older, having prior immunological infections, diabetes, or obesity are all risk factors that make it more likely that a viral attack will cause something—

Leonard: That makes it much harder for that person to get over it.

Brent: In the case of ME/CFS precipitated by mono, a typical experience might be: I'm not feeling well, I go to the doctor, and they say it sounds like mono. We test, and it's positive. So I expect to suffer from mono in all the typical ways.

Brent: Up to six months, we'd expect that's normal—it lingers a bit. But at six months, someone says, "I walk the dog and I'm exhausted, and I have brain fog all the time."

Brent: Then we start thinking about CFS. Is it that the symptoms don't abate at all, or do they decrease but not to an acceptable level? What does it look like at that six-month mark?

Leonard: Sometimes symptoms decrease, stay the same, or increase. ME/CFS is a multi-system problem where one system goes awry. I think brain inflammation ultimately affects the gastrointestinal system, which then affects the circulatory system. One system might be predominantly dysregulated, but then dysregulates other systems.

Leonard: You have this spiraling occurring, where sometimes the person feels a little better and sometimes worse. The biggest problem is that because we're not exactly sure, there's a lot of interest in understanding it, but many people end up blaming the victim.

Leonard: That's very unfortunate. What we should be doing is providing as much care as possible as early as we can; we don't need to wait six months. If you're feeling sick after a couple of weeks, that's when we should intervene. Six months is just a case definition. For Long COVID—

Leonard: It's closer to three months. The timeline is secondary; the key thing is helping the patient get back to where they were before getting ill.

Brent: How debilitating is it? If I'm constantly fatigued and have brain fog, can I work or be an engaged parent? What does the level of debilitation look like?

Leonard: About 25% of people with this condition are homebound, and a smaller percentage are bedbound. Some individuals can leave the house, grocery shop, or do part-time work, so it varies. But think of it this way: recall the worst flu you've ever had and how sick you were.

Leonard: Your whole body ached. You felt like there was poison going through your body. Imagine if you felt that way for months and years. You can imagine the tremendous toll it takes. There are varying severities, but most people going through the worst period are severely affected. Studies comparing the quality of life of people with ME/CFS to those with other very difficult illnesses show that—

Leonard: Quality of life compromise in ME/CFS is more significant than almost any other illness.

Brent: I can't imagine having that flu-like feeling and malaise for more than ten days, let alone six months or a year. How is it diagnosed? As I understand it, there isn't a simple blood test where you either have it or you don't.

Brent: It reminds me of mental health diagnostic methods, where you ask a series of questions to generate a score that determines the likelihood of having the condition.

Brent: There's no single definitive test, correct?

Leonard: Most primary care providers don't have specialized tools. They look at blood tests, see normal results, and rely mainly on the patient reporting severe fatigue and pain. Self-reporting is very important.

Leonard: There are more sophisticated tests that can help determine whether a person has this. It is possible to diagnose it reliably using standard case definitions, though not every provider knows how to do so. That remains a challenge for the field.

Brent: So doctors aren't as educated on ME/CFS as they could be, so they don't always know how to test for it.

Leonard: We conducted a study reviewing medical textbooks for information on ME/CFS and found two things: there is very little information, and most of it is incorrect.

Brent: How many people suffer from this? What's the prevalence?

Leonard: Before the 2020 pandemic, the best estimates were about 0.5%, or 1 in 200 people. Today, because Long COVID affects about 7% of the population—where someone hasn't recovered from COVID after at least three months—

Leonard: Those rates and economic costs are going to be much higher. Art Mirin and I published papers on this issue, and we are talking about millions of people.

Brent: So maybe 2 to 3 million people in the US.

Leonard: Yes, easily. That's likely where the numbers are.

Brent: How do you tell the difference between Long COVID and ME/CFS? The descriptions sound remarkably similar from an outsider's perspective.

Brent: How do you distinguish between them?

Leonard: Long COVID has a broad case definition, which carries risks: if it's so broad that many people qualify while remaining fairly functional, those who are severely ill become even more stigmatized. Under Long COVID, having any of hundreds of symptoms for over three months classifies you.

Leonard: That general definition can inaccurately capture people. ME/CFS has a more specific case definition, requiring specific symptoms to be present at least half the time with moderate severity. Having clearer criteria for symptom duration and severity provides greater diagnostic precision.

Leonard: That precision is vital for scientific research and patient care. In mental health, diagnoses consider not just symptoms but functional impact—like how depression or anxiety limits daily activities.

Leonard: In the ME/CFS and Long COVID field, it's crucial not to push these into mental health diagnostic manuals. With cancer, a physical health condition, the diagnosis itself is distinct from the functional impact on work or life activities.

Leonard: In physical health conditions, the underlying symptoms and functional limitations should be kept independent. Conflating them risks misclassifying physical conditions as mental disorders, which increases stigma. Keep the symptoms and functional limitations as separate dimensions.

Leonard: They are two separate dimensions.

Brent: So as an advocate, you're fighting against the push to classify these as mental health disorders under the DSM.

Brent: You're emphasizing that these are physical illnesses and should be treated as such.

Leonard: It's a slippery slope. Many people with good intentions don't realize how they contribute to the stigma of the illness.

Brent: You suspect the culprit is brain inflammation. Is there a reliable biomarker? We can test for high-sensitivity C-reactive protein for body inflammation, or look for brain plaque in Alzheimer's risk, but is there a way to reliably measure brain inflammation?

Brent: We can look at plaque in the brain, we can look at different things, is there's not a way to measure inflammation in the brain reliably.

Leonard: We are studying the immune system, natural killer cells, and antibodies. There is encouraging research that the general public and physicians aren't aware of. I'm particularly interested in the CGRP pathway, which gets dysregulated by enzymes stimulated by these viruses.

Leonard: Incredible research is being funded through RECOVER for COVID studies. It's expensive research, but it's the missing link. Medicine is good at fixing broken bones or simple infections, but understanding complex, debilitating systemic illnesses will revolutionize medical practice.

Leonard: And I think that this is the missing link to medicine fixing. And bones have been broken. Being able to deal with a simple infection, we're good at that at these complex system illnesses that are so debilitating. As we get closer to understanding them, the implications of what we're going to find are going to be revolutionary for the practice of medicine.

Leonard: In primary care, about 25% of patients present with fatigue and pain, and many physicians don't know how to handle it. They often assume it's depression and prescribe antidepressants or exercise. But prescribing antidepressants and exercise to people with ME/CFS are the wrong treatments.

Leonard: It's not what these patients need.

Brent: That feels counterintuitive compared to typical health advice, where sleep, diet, and exercise are the standard solutions for physical and mental health.

Brent: That isn't the case here, particularly regarding exercise. How is it treated when someone is bedbound with flu-like malaise for hundreds of days?

Leonard: This applies across post-viral fatigue illnesses. Robert Naviaux has a theory about hibernation: across species, injured animals hibernate to allow the body to repair itself. A wounded animal goes into the brush and rests without pushing itself.

Leonard: The body needs rest to nurture itself back to health, not exertion. If you don't understand this illness, you tell patients to do what typical healthy or depressed individuals do: go work out.

Leonard: When physicians tell patients to push themselves or go to the gym, it harms them. These patients need to respect their physiological limits, avoid post-exertional crashes, and match their activity to available energy levels.

Leonard: I call this staying within the "energy envelope." Good diet and rest matter, but regarding exercise, I can easily differentiate between major depressive disorder and ME/CFS with a simple question.

Leonard: If you ask an ME/CFS patient what they would do tomorrow if they felt well, they give you a list of 20 things. If you ask a depressed patient the same question, they often say, "I don't know." Anhedonia is generally not present in ME/CFS.

Leonard: If an ME/CFS patient goes to the gym and pushes past their energy boundaries, they experience post-exertional malaise. If a depressed patient works out, they usually feel better. These clinical details highlight distinct conditions.

Leonard: Two other vital factors are control and agency. Having agency over daily decisions reduces physiological stress. Finding meaning in daily activities is crucial for coping with chronic illness.

Leonard: Another critical area is social connection. Social isolation worsens fatigue severity and mortality risk. Being believed and supported reduces stress, making community support life-preserving.

Brent: So there isn't a single pill or quick fix. It's about pacing, conserving energy, and allowing the body to recover, but we lack a definitive cure.

Brent: We're not yet at a place where a specific treatment protocol guarantees recovery.

Leonard: When people get sick, they look for a magic pill, but it's rarely that simple. It requires a multidisciplinary, multimodal approach using the best medical care—a team supporting the host's immune, physiological, and psychological systems to endure these severe stressors.

Brent: Primary care physicians might misdiagnose this as depression and prescribe SSRIs, painkillers, or sleeping pills. Those medications can cause dependence without resolving the underlying illness.

Brent: It seems the lack of education leads to patients taking unnecessary medications with significant risks.

Leonard: There's also the problem of people unverifiedly claiming they can cure 90% of patients. When you're very sick, you're vulnerable to those promises.

Leonard: It takes time to manage the illness, and current medical knowledge rarely restores patients fully to their premorbid state.

Leonard: Long-term disability and mortality studies show higher rates of chronic conditions, including heart disease, cancer, and suicide, in ME/CFS patients.

Leonard: People with ME/CFS develop heart disease and cancer at earlier ages, pointing to systemic dysregulation. Long-term follow-up studies confirm that full recovery is rare.

Leonard: Complete cures are very unusual.

Brent: So it's about managing and reducing symptoms. What do we know about dietary interventions like keto, carnivore, vegan diets, or fasting? Is there strong evidence supporting specific diets?

Leonard: Many healthy diets exist, but the standard American diet—high in processed foods, salt, sugar, and unhealthy fats—is detrimental to health.

Leonard: Processed foods don't give the body what it needs to heal. Whole-food diets are far better, but high obesity and diabetes rates show most people aren't eating healthily.

Brent: So there isn't evidence showing one specific diet superiorly alleviates ME/CFS symptoms. We had Dr. Thomas Seyfried on discussing the benefits of the keto diet in cancer treatment, but there's no equivalent specific diet proven for ME/CFS?

Brent: We can't state definitively that one particular diet is best for ME/CFS?

Leonard: Direct research in ME/CFS is limited, but broader nutrition research shows eating unprocessed, healthy foods is generally beneficial. When severely ill, people often default to convenient, lower-quality foods.

Leonard: Choosing less processed foods high in quality nutrients is universally beneficial.

Leonard: That evidence is clear.

Brent: Looking ahead 50 or 100 years, where do you think the most promising breakthroughs or cures will come from?

Brent: What trajectory are you most excited about?

Leonard: For major illnesses like cancer, specialized multidisciplinary treatment centers drive research forward. We used to treat lung cancer as a single illness; now we recognize dozens of subtypes with targeted treatments.

Leonard: ME/CFS will eventually be categorized into subtypes with targeted treatments. We need specialized clinical centers for post-viral illnesses and Long COVID.

Leonard: Patients often fall out of the care system. We need care centers that involve patients in designing accessible environments, taking into account sensitivities like light or chemical exposures.

Leonard: Environments must adapt to patient sensitivities, such as mold or environmental triggers.

Leonard: Patients must be equal partners in healthcare decisions, co-producing their treatment plans alongside clinicians. That is the future of healthcare.

Leonard: Okay.

Brent: It comes down to funding and dedicated focus. With sufficient resources, specialized centers can bring patients and clinicians together to accelerate learning and scientific progress.

Brent: It reminds me of the Cleveland Clinic, where centralizing expertise and resources dramatically advances care.

Leonard: Places like the Mayo Clinic show the power of integrated team care over fragmented treatment. That integrated approach is the future of medicine.

Brent: You aren't pointing to specific tools like CRISPR or GLP-1s as primary solutions. While not off the table, they aren't your primary focus.

Leonard: Different methods will help specific subgroups of patients. Some ME/CFS patients suffer severe cognitive impairment, while others face significant mobility limitations.

Leonard: Symptoms overlap, but individual impairment levels vary and fluctuate over time.

Leonard: We need precision medicine tailored respectfully to each person's specific biological needs.

Brent: Skepticism surrounding ME/CFS harms patients and misinforms clinicians, which is why your educational research work is so critical.

Brent: Are any related conditions legitimately questionable, or do conditions like restless leg syndrome or Lyme disease suffer from the same reputation and diagnostic challenges?

Brent: Are they all legitimate physical conditions facing early science challenges, or are there invalid conditions in this space?

Leonard: It's similar to the Black Plague in the 1500s, when people wondered if some were faking illness. While minor secondary gain might exist occasionally, the overall situation is disastrous.

Leonard: Patients have their lives devastated by illness, lose jobs and relationships, and are then questioned about whether they are truly sick.

Leonard: SOCIETY pushes back with comments like "Everyone gets tired," dismissing genuine suffering. In the future, we will look back on how these patients were treated with regret, similar to medical mistreatment centuries ago.

Leonard: I receive calls from patients living in cars, facing eviction, lacking medical care, and struggling to secure food—sick people left without a safety net.

Brent: Historically, unknown conditions were blamed on supernatural causes or bad attitudes. Here, naming it "chronic fatigue syndrome" leads people to dismiss it as ordinary tiredness.

Brent: There is a vast difference between day-to-day stress and suffering from ME/CFS.

Leonard: Calling someone a "CFS patient" reduces them to a disease label. The CDC introduced "chronic fatigue syndrome" in 1988, replacing the European term "Myalgic Encephalomyelitis."

Leonard: It's a trivializing term, equivalent to calling a condition "chronic cough syndrome." Since fatigue is extremely common, using it in the diagnosis minimizes the illness. That is why adopting ME/CFS or ME is less stigmatizing.

Leonard: You'd say, who cares? Everyone coughs because fatigue his present almost 25% of people, one out of four. This feeling fatigue at any one time. It is such a common symptom. You don't want to use that term to basically call that syndrome. And that's why they basically have tried to use an Emmy CFS term, because it's a little bit less stigmatizing.

Leonard: In Europe, they call it ME rather than CFS.

Brent: "Myalgic Encephalomyelitis" sounds official and medical, whereas "chronic fatigue syndrome" sounds trivialized.

Brent: And it's like, well, we've all got that.

Leonard: We tested this in studies by presenting identical case descriptions under different names. Labeling it "chronic fatigue syndrome" caused healthcare workers to hold more negative attributions toward patients.

Leonard: The diagnostic name directly affects perceptions and attributions.

Brent: Where can listeners go to find reliable resources and learn more about your work?

Leonard: Look for local or online support groups covering ME/CFS, Long COVID, or Lyme disease. Key advocacy and research organizations offer excellent resources.

Leonard: For scientific information, the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (IACFS/ME) offers scientific research resources on their website. I am based at DePaul University in Chicago.

Leonard: If I can be helpful to anyone, please feel free to reach out to me.

Brent: Dr. Leonard Jason, thank you for your work and for joining us today.

Leonard: Thank you for having me on your show.

Brent: Death Clock is recorded in Boulder, Colorado and San Francisco, California. Produced by Patrick Gudino, music by Patrick Lee, and hosted by Brent Franson.