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Chronic Fatigue Syndrome

Taking a walk around the block. Spending the day shopping. Paying the monthly bills.

If you have Chronic Fatigue Syndrome (CFS), one of these normal activities can put you into a tailspin leading to a cascade of symptoms and/or a few days in bed.

Post-exertional malaise (PEM) is a hallmark of CFS. Physical or even mental activity that most people tolerate easily results in neuroimmune exhaustion—a heightened response by the nervous and immune systems that’s out of proportion to the trigger.

Because multiple organs and systems are involved, the name Systemic Exertional Intolerance Disease (SEID) has been proposed. In some countries it’s called myalgic encephalomyelitis (ME). And because many cases of CFS/ME stem from an acute viral or bacterial infection, it’s also referred to as Post-Viral Fatigue Syndrome or Post-Infectious Fatigue Syndrome. The varied and changing terminology reveals the lack of consensus within the medical and scientific communities about this illness.

A lot of the information that applies to CFS applies to Post-Viral Fatigue Syndrome and vice versa, so be sure to check our separate page on that condition.

According to #MEAction, somewhere between 15 and 30 million people worldwide live with CFS/ME. About one million
Americans have it. Most people with CFS are young to middle-aged adults, and about three-quarters are women. Because there’s no single lab test to confirm it and doctors may not be familiar with the syndrome, it often goes undiagnosed.

While some people have mild cases that allow them to carry on a lifestyle that looks normal to others, many more must severely curtail their activities. About 75% of people who have CFS can’t work, and about 25% are bedridden.

In 1994, the so-called Fukuda criteria were established, and those are still used to diagnose CFS today. Your doctor might arrive at a CFS/ME diagnosis if you’ve had lifestyle-limiting fatigue for at least six months and if you also have at least four of the following symptoms: “post-exertional malaise (PEM) lasting more than 24 hours; substantial impairment in short-term
memory or concentration; sore throat; tender lymph nodes; muscle pain; multi-joint pain without swelling or redness; headaches of a new type, pattern, or severity; and unrefreshing sleep.” [1]

Before saying you have CFS, your doctor will seek to rule out any other causes for your symptoms—for example, a sleep disorder or a degenerative disease.

Because there’s no approved treatment for the syndrome itself, you may embark on a series of trials to address your most severe symptoms. Like others who live with CFS, you may find complementary and alternative medicine (CAM) approaches that work well for you. [2]

Read on to learn more about the symptoms of CFS and some potentially helpful CAM approaches.

Fatigue isn’t sleepiness. Ideally, doctors rule out sleep disorders like sleep apnea and narcolepsy before diagnosing someone with CFS/ME, but it’s complicated. You can have a sleep disorder and CFS/ME at the same time. Some people with CFS get average amounts of sleep, and others get more sleep than most people. [3] What those with CFS have in common is not feeling rested when they wake up. In one study that followed people with chronic fatigue for three years, unrefreshing sleep was the most common symptom—experienced by 79%—and the least likely to go away. [2]

Pain and poor sleep go hand in hand. Pain interferes with sleep, and lack of restful sleep worsens pain. You may find that your pain wakes you up a lot during the night. The same vigilant state of the body that produces pain and hypersensitivity during the day continues at night, keeping you from a solid, restorative sleep experience. Sleep studies on those with CFS have found that slow wave sleep (SWS), the deepest type of sleep, makes up a smaller portion of the sleep cycle for some people with CFS and a greater portion for others. Pro-inflammatory cytokines, proteins put out by the immune system, influence SWS, suggesting that inflammation may be linked to sleep disturbances. [3]

Normally, a person’s heart rate varies a lot during sleep. People with CFS, however, tend to have lower heart rate variability (HRV).This is so common in CFS that it helps diagnose the condition. If your heart rate doesn’t vary much while you sleep, it means that your body is on high alert even when it should be resting. Ideally, sleep allows your parasympathetic nervous
system to become dominant so digestion, detoxification, and healing can take place. For those with CFS, the sympathetic nervous system remains dominant during sleep. [3] No wonder sleep doesn’t refresh you!

To find out whether you have a sleep disorder in addition to CFS, you could work with a sleep center and participate in a sleep study. Before trying that, you might want to experiment with CAM approaches. Using meditation and relaxation techniques throughout the day and at bedtime may help. According to the Sleep Foundation, tailoring sleep hygiene to suit your needs can make a difference. Blue light from the screens of your computer, tablet, phone, or TV can interfere with melatonin, a hormone that regulates the sleep-wake cycle, so experts recommend disconnecting at least an hour before bedtime.

Speaking of melatonin, taking melatonin supplements has been shown to improve sleep for some people with CFS. One test that sleep centers perform on their patients determines when their Dim Light Melatonin Onset occurs. In people who have a regular 24-hour circadian rhythm, melatonin production begins two hours before bedtime—ideally around 8 p.m. Someone who doesn’t start producing melatonin until later—say 9:30 p.m.—has “late DLMO.” Research found that taking melatonin for six months significantly improved fatigue, motivation, concentration, and activity. [4]

The primary distinguishing symptom of CFS/ME is post-exertional malaise (PEM). This type of exhaustion is more than just lack of motivation or vigor. It’s a bone-deep weariness that encompasses every inch of your body, making you feel that the smallest movement is a herculean task. It comes on after routine physical or mental activity that’s not a problem for others. When it hits, it lasts for at least a day, but often much longer. While you need to rest because you don’t have the strength for anything else, rest doesn’t really seem to help. Obviously, keeping up a normal schedule of work, home life, friendships, and hobbies is impossible when you’re living with that kind of fatigue.

Getting to the root causes this energy deficit has challenged medical researchers. Over the past decade, researchers turned their attention to the mitochondria, structures within the body’s cells that produce energy in the form of adenosine triphosphate (ATP). Mitochondria are known as the powerhouse of the cells.

For a while, it seemed that mitochondria might hold the key that would unlock the mysteries of CFS. Some studies found altered mitochondrial function in people with CFS, specifically low production of ATP. Further research, however, determined that there was nothing wrong with the mitochondria themselves and that CFS isn’t a mitochondrial disease. The new hypothesis is that something outside the mitochondria is interfering with ATP production. [5]

Some possible causes of reduced ATP production in the mitochondria are:

  • Low oxygen levels
  • Oxidative and nitroxidative stress (free radicals)
  • Immune system abnormalities
  • Inflammation
  • Reduced glucose transport into cells


Diet, lifestyle, and targeted nutritional supplements offer various ways to address these issues.

Scientists have also investigated whether muscles have anything to do with CFS/ME. It turns out that when people with CFS exercise, their muscles switch from aerobic to anaerobic respiration much more quickly than normal. Anaerobic respiration is a less efficient type of energy production that gives off lactate as a waste product. Lactate causes muscle cramps, muscle
fatigue, inflammation, and brain fog—all symptoms of CFS. This quick switch to anaerobic energy production could be an important part of the CFS/ME puzzle. [5]

These changes in muscle performance may be closely related ATP production (described above). Nutritional supplements that support ATP production as well as nutrients needed for muscle function—like magnesium, calcium, and carnitine—are often recommended for those with muscle pain.

If you’re like many people with CFS/ME, the worst of symptom you deal with every day may be “brain fog.” This cognitive impairment is considered “mild” in the larger context of memory and concentration conditions, but it interferes with almost every waking activity. Brain fog encompasses poor focus and concentration, memory problems, slow thinking, confusion, and/or generally hazy thought processes.

Evaluations of CFS participants found problems with working memory, information processing, attention, and reaction time. Although people with CFS can also have anxiety or depression, their cognitive symptoms are separate from any mental health conditions they may have. [6]

Normally, whenever we perform a difficult mental challenge, more blood flows to the brain. If you have CFS, though, that increased blood flow doesn’t happen, which could be why you don’t think as quickly or clearly—and why your brain feels so tired. Interestingly, both people with CFS and people with Postural Orthostatic Tachycardia Syndrome (POTS) have poorer cognitive function when they stand or sit than when they lie down. Brain fog accompanies the increased heart rate, higher blood pressure, and breathing changes they experience when moving from lying to sitting or standing.

When CFS research subjects were given a challenging mental task to perform, more parts of their brains were activated than in non-CFS subjects.[6] Again, this could explain why people with CFS feel mentally fatigued when they have to think hard.

Improving your stress response via meditation or relaxation techniques may improve blood flow to the brain. Supplements that support the brain and nervous system may also help improve thinking processes.

Being chronically ill takes its toll on your mental health. When you can’t do the things you enjoy or have an active social life because of your fatigue, it’s hard to be upbeat. Because you look fine outwardly and can’t show a blood test to confirm what you’re experiencing, your family members, friends, and coworkers—and even your doctor—may have a hard time understanding what you’re going through.

CFS isn’t all in your head. Multiple physical signs and markers associated with CFS prove its physiological reality. Still, there are many interrelationships between CFS and mental health, mood, and stress. About 25% of people with CFS also have depression, and CFS is often misdiagnosed as clinical depression. However, physicians who are familiar with CFS use specific criteria to tell the two conditions apart. [7]

Generalized anxiety disorder is also common among people with CFS. In many cases, the onset of CFS is preceded by trauma or life stressors, suggesting stress sets off a chronic cycle of inflammation and oxidation within the body. [8] Some research shows that those who develop CFS tend toward perfectionism and that as their condition continues, they experience a lower case of self-efficacy—that is, they don’t feel capable of meeting the demands of life. [9]

How you handle your moods and stress is an important part of managing CFS. Unfortunately, some recommended psychological treatments have proven to be useless or worse. Cognitive Behavioral Therapy (CBT) is used widely among psychologists, but research shows it’s not that helpful for CFS, especially over the long term. According to a survey by ME Association, 26% of respondents said CBT made their symptoms better, but 20% said it made them worse. The difference could be whether the therapist recognizes CFS as a physiological rather than psychiatric condition. [7] You may need to interview several therapists to find one with empathy toward chronic illness.

There are other ways to manage stress and improve your mood. Pacing—figuring out how to do enough but not too much—improved symptoms in 71% of survey respondents. That was the single most effective therapy reported. Meditation and relaxation techniques helped over half of those with CFS. Websites, books, and videos teach various approaches. Here’s one.

Just be sure to start slowly and listen to your body so you can find what works for you.

The thyroid gland releases hormones that are associated with energy levels and fatigue. Both an underactive and overactive thyroid gland can lead to fatigue according to the British Thyroid Foundation. A recent study found that subjects with CFS/ME had significantly different levels of several thyroid hormones compared to healthy controls.[10] Because the thyroid gland may still put out appropriate amounts of hormones but the body uses them differently, the condition is considered a problem
with thyroid hormone function rather than an issue with the thyroid gland itself.

A theory that’s gaining traction is the vicious cycle among three important players that keep coming up again and again in CFS/ME research: pro-inflammatory cytokines, oxidative and nitrosative stress, and reduced thyroid hormone function.[11]

It goes like this:

Inflammation that is set in motion by trauma (whether illness, stress, or environmental exposure) suppresses hormone levels and energy production at the cellular level. Over 100 pro-inflammatory cytokines have been shown to affect hormone function.

Oxidative and nitrosative stress result from the inflammatory processes, generating free radicals that destroy cells and further interfere with the immune system and normal metabolic functions.

Reduced thyroid hormone activity impairs the functioning of various immune-related cells and interferes with other hormones, such as those related to the stress response. It affects multiple organs and systems and leads to a state of general hypometabolism, or reduced activity of body functions.

These three maladaptive responses feed on each other and interfere with recovery, leading to
symptoms that won’t go away and a chronic state of illness.

Many people with CFS have digestive issues that could be called Irritable Bowel Syndrome. Discomfort after eating, bloating, belching, gas, constipation, or diarrhea are common complaints. Patients with diagnoses of IBS and CFS both have increased levels of pro-inflammatory cytokines. In some cases of CFS, the source of inflammation that creates the vicious cycle described above could be the gut. People with CFS have been found to have different microbiota in their intestinal tracts.[internal link] Harmful bacteria in the gut can communicate with the central nervous system—an relationship known as the gut-brain axis—and produce anxiety and depression. [12] Taking probiotic supplements orally could decrease pro-inflammatory cytokines that regulate moods as well as decrease oxidative stress. In one study, 40% of patients who took probiotics for four weeks had improved mental function and reported feeling better. [13]

If you’re living with CFS, be sure to consider what role dysbiosis may be playing in your symptoms. Improving your gut health is key to feeling better and moving toward recovery.

1 Fukuda K, et al. The chronic fatigue syndrome: A comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group. Ann Intern Med. 1994;121(12):953-959. doi:10.7326/0003-4819-121-12-199412150-00009

2 Nisenbaum R, Jones JF, Unger ER, Reyes M, Reeves WC. A population-based study of the clinical course of chronic fatigue syndrome. Health Qual Life Outcomes. 2003;1:49. doi:10.1186/1477-7525-1-49

3 Jackson ML, Bruck D. Sleep abnormalities in chronic fatigue syndrome/myalgicencephalomyelitis: A review. J Clin Sleep Med. 2012;8(6):719-728. doi:10.5664/jcsm.2276

4 van Heukelom RO, Prins JB, Smits MG, Bleijenberg G. Influence of melatonin on fatigue severity in patients with chronic fatigue syndrome and late melatonin secretion. Eur J Neurol. 2006;13(1):55-60. doi:10.1111/j.1468-1331.2006.01132.x

5 Stephens C. MEA summary review:The role of mitochondria in ME/CFS. The ME Association, 2019.

6 Ocon AJ. Caught in the thickness of brain fog: Exploring the cognitive symptoms of Chronic Fatigue Syndrome. Front Physiol. 2013;4:63. doi:10.3389/fphys.2013.00063

7 Griffith JP, Zarrouf FA. A systematic review of chronic fatigue syndrome: Don't assume it's depression. Prim Care Companion J Clin Psychiatry. 2008;10(2):120-128. doi:10.4088/pcc.v10n0206

8 Pall ML. Common etiology of posttraumatic stress disorder, fibromyalgia, chronic fatigue syndrome and multiple chemical sensitivity via elevated nitric oxide/peroxynitrite. Med Hypotheses. 2001;57(2):139-145. doi:10.1054/mehy.2001.1325

9 van Dam A. Subgroup analysis in burnout: Relations between fatigue, anxiety, and depression. Frontiers in Psychology. 2016;7:90. DOI=10.3389/fpsyg.2016.00090

10 Ruiz-Núñez B et al. Higher prevalence of “Low T3 Syndrome” in patients with ChronicbFatigue Syndrome: A case–control study. Frontiers in Endocrinology, 2018; 9. DOI:10.3389/fendo.2018.00097

11 Stanculescu D et al. Hypothesis: Mechanisms that prevent recovery in prolonged ICU patients also underlie Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Frontiers in Medicine. 2021.

12 Lakhan SE, Kirchgessner A. Gut inflammation in chronic fatigue syndrome. Nutr Metab (Lond). 2010;7:79. Published 2010 Oct 12. doi:10.1186/1743-7075-7-79

13 Sullivan A, Nord CE, Evengård B. Effect of supplement with lactic-acid producing bacteria on fatigue and physical activity in patients with chronic fatigue syndrome. Nutr J. 2009;8:4. doi:10.1186/1475-2891-8-4


Supplements that may help:

Based on volumes of research into the causes and biological processes of CFS/ME, the main targets for nutritional intervention are inflammation, oxidative/nitrosative stress, gut health, sleep, muscles, and immune support. Here are some of our favorite formulas:

Dynamic Inflam-Eze

Since some of the key symptoms of CFS/ME come from inflammatory processes, so taming inflammation is a priority. Dynamic Inflam-Eze is our go-to favorite for that task.

This ready-to-mix meal-replacement drink contains a balance of macro and micronutrients that can help calm inflammatory processes in your body. In addition to supplying important vitamins and minerals, it’s packed with anti-inflammatory and anti-oxidant herbs like turmeric, milk thistle, ginger, and broccoli sprouts.

Both ginger and curcumin (from turmeric) have been shown to suppress inflammatory cytokines. Ginger and milk thistle have been used traditionally to cleanse the lymphatics.

Inflam-Eze Plus

A powerful herbal formula designed to control inflammation, Inflam-Eze Plus combines eight herbs known for their anti-inflammatory actions, including turmeric, hops, boswellia, and ginger. The power of turmeric to fight inflammation is well established. Hops extracts have pain-relieving, antioxidant, and anti-inflammatory properties, and boswellia inhibits inflammatory enzymes.

Exciting new research shows that the special formulation of curcumin and fenugreek in this product may allow the anti-inflammatories to cross the blood-brain barrier where they can potentially calm inflammatory processes in the brain.

Nutridyn Fruits & Greens:

For the antioxidant power of 20+ fruits and vegetables, mix yourself a daily drink of this product that comes in a variety of great flavors. Because of its high fat content, the brain is particularly susceptible to insult from free radicals, so antioxidants are foundational to a healthy brain strategy.

Immune Support

East and West unite in this potent blend of mushrooms, vitamins, and trace elements valued for their benefits to the immune system. Immune Support contains a variety of mushroom extracts that have been used in traditional Eastern medicine.

Modern clinical evidence verifies the role beta-glucans, polysaccharides derived from mushrooms, play in immunity, such as enhancing natural killer cells. In the West, vitamins D, C, zinc, and selenium have been shown to enhance immunity in various ways.

Immune Resilience

This formula is packed with natural ingredients that have powerful antioxidant and anti-inflammatory activity. Quercetin and green tea extract aid your body’s stress response. According to research, elderberry extract, resveratrol, and luteolin enhance immune cell responses. Andrographis paniculata and Houttuynia cordata are herbal extracts that boost immunity by supporting T-cell activity.

Brain Support

This herbal formula combines a variety of plant-based compounds that recent research has shown to benefit cognitive functions. Green tea extract supports blood vessels to help ensure good blood flow to the brain; curcumin reduces inflammatory processes that can interfere with brain function; sage has been found to promote memory function, including primary, secondary, and working memories; and Chinese skullcap extract and resveratrol reduce oxidation, which can be detrimental to the brain.

Probiotic Pro

The good bacteria in your GI tract help it metabolize food, absorb nutrients, and keep foreign microbes in check. They play an important role in immunity, and they even help your mood and cognitive functions via the gut-brain axis. This multi-strain probiotic formula contains Bifidobacterium lactis, which appear to be the most important organisms in the intestine for promoting a healthy intestinal lining. It also contains multiple strains of Lactobacillus, which have been shown to alleviate the symptoms of Irritable Bowel Syndrome.

Melatonin 20

Many people turn to melatonin to help them get to sleep, especially night owls whose natural melatonin kicks in later at night. This formula provides a potent dose of the highest-purity melatonin available without any other ingredients.

Muscle Eze Advanced

When your muscles are tight, it’s hard to relax and fall asleep. Muscles require calcium and magnesium for optimal function. In addition, this formula contains high-potency extracts of herbs that can help muscles relax and help prevent delayed-onset soreness after increased activity. And if you have fibromyalgia pain, you may find it easier to fall asleep after taking this formula, since it contains magnesium and malic acid, a combination that research suggests may reduce fibromyalgia pain.

Nerve Eze

This formula contains two of the most potent ingredients to promote healthy nerve function: PEA (palmitoylethanolamide) and ALA (alpha lipoic acid).Together they promote healthy functioning of the body’s endocannabinoid system to support nerve function, stress response, relaxation, and healthy immunity. With its calming effect on neurological pathways, PEA can contribute to a stronger immune system, balanced moods, and better quality of life.

Cellular Energy

Keeping your blood flowing freely to your tissues is essential for good energy levels. According to research, CoQ10, NAC, ALA, and grape seed extract promote proper blood flow throughout the cardiovascular system by preserving the activity of nitric oxide—a molecule that expands blood vessels. This supplement can help energize your mitochondria, your cells’ powerhouses.