The Top Causes Of Chronic Fatigue Syndrome + Exactly How To Reverse It

Chronic Fatigue Syndrome

We’re a country bogged down by extreme exhaustion. According to the CDC, Chronic Fatigue Syndrome affects anywhere between 836,000 to 2.5 million people (1) – more people than multiple sclerosis, lupus, and some forms of cancer. Out of this shocking number of individuals diagnosed with Chronic Fatigue Syndrome, close to a quarter are bedridden due to their extreme level of exhaustion.

As a functional medicine expert, I see day in and day out just how debilitating this condition can be. And it doesn’t discriminate - people of all races, gender (although it is between 2-4 times higher in women than men), and age come to me for help restoring their energy levels. So if you have been struggling to get through your day, know that you are not alone. But just because something is common doesn’t make it normal. Read on to learn more about Chronic Fatigue Syndrome, its causes, and exactly what you can do to overcome this health problem and reclaim your energy.


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What is chronic fatigue syndrome?

Chronic Fatigue Syndrome, or CFS for short, is a complex and debilitating medical condition characterized by constant, unexplained fatigue that is not linked to any specific medical condition. The problem with chronic fatigue is that it lacks specific diagnostic markers and its symptoms can overlap with a wide-range of other health problems. While the exact cause of CFS is unknown, researchers believe it is a multifactorial condition with various contributing factors including viral infections and hormonal imbalances. CFS can manifest itself in a number of symptoms, including:

  • Constant or recurrent extreme fatigue
  • Fatigue that’s not significantly alleviated by sleep
  • Fatigue that interferes with daily activities and work
  • Exhaustion and body aches after physical activities
  • Impaired memory or concentration
  • Waking up tired, even after a full night’s sleep
  • Frequent headaches
  • Muscle or joint pain
  • Constant or recurrent sore throat
  • Tender or swollen lymph nodes in the neck or armpits

If you’re experiencing at least four of these symptoms, chronic fatigue syndrome might be to blame. 

The Top Causes Of Chronic Fatigue

1. Thyroid problems

Around 20 million Americans struggle with thyroid issues, and low thyroid function, or hypothyroidism, is one common problem. Every cell of your body needs the thyroid hormone for energy. Sadly, there are many underlying thyroid problems that go undiagnosed.

What to do: If you suspect you have a thyroid problem, the first step is to ask your doctor about complete lab testing to find out for sure. Thyroid conversion dysfunctions, thyroid resistance, and autoimmune attacks on the thyroid, such as Hashimoto’s disease, all require different approaches. Take our quiz here to help you find out if you are likely struggling with thyroid problems.

2. Insulin resistance

Metabolic syndrome and diabetes are two different manifestations of the same problem: insulin resistance. When your body is resistant to insulin, glucose cannot get into your cells to create ATP, your body’s gasoline. This can leave you feeling tired and irritable. This problem is also associated with sleep apnea, (2) which can further fuel fatigue.

What to do: In addition to eating a clean diet filled with fruits, vegetables, meats, and healthy fats, I also recommend natural medicines such as alpha-lipoic acid, cinnamon, and chromium – some of my favorite blood sugar balancers.

3. Adrenal fatigue

Your brain tells your adrenal glands what to do through a complex web of communication called the hypothalamic-pituitary-adrenal axis (HPA axis) or simply, the brain-adrenal axis. Adrenal fatigue happens when that brain-adrenal communication isn’t working well, causing your stress hormone, cortisol, to be too high or too low. This leaves you feeling exhausted and cranky and not sleeping well.

What to do: Focus on things that activate your resting, parasympathetic system. Adaptogenic herbs like maca, ashwagandha, holy basil, and rhodiola are some of my favorite tools to help balance cortisol levels. I also rehabbed my own adrenal fatigue with consistent mindfulness meditation. Take our quiz here to help you find out if you are likely struggling with adrenal problems.

4. Viral infections

Low-grade viral infections, especially herpes viruses like the Epstein-Barr virus (EBV) and human herpes virus 6 (HHV-6) and HHV-7 have been linked (3) in some studies to chronic fatigue. Another recent study published in 2021 (4) found that EBV infection was directly linked to the development of Chronic Fatigue Syndrome through increased T-cell activation and inflammation levels within 6 months of being infected.

To learn more about the connection between the top four hidden viral infections and chronic fatigue, check out my article here.

What to do: Try attacking viruses naturally with antiviral herbs and vitamins such as astragalus, olive leaf, larrea tridentata, bee propolis, zinc, vitamin C, melissa Officinalis, and L-lysine. A functional medicine doctor can help you determine the best ones for you.

5. Toxicity

The food we eat, the water we drink, and the air we breathe are not what they used to be, thanks to pervasive environmental toxins. One study (5) published in the journal Science of the Total Environment showed an association between exposure to environmental toxins and an increase in chronic fatigue.

What to do: Include detoxing foods in your daily diet, especially garlic, cilantro, parsley, plantain leaf, spirulina, sage, and red clover blossom. Whether you use them in smoothies, include them on salads, or enjoy them with your main-course meals, rotating these foods throughout your week is a great way to make every meal a detox experience.

6. Nutrient deficiencies

Any nutritional deficiency could potentially cause fatigue, but deficiencies in vitamin D, iron, and B vitamins are especially likely to leave you feeling groggy and spent. In fact, studies have found that chronic fatigue is one of the leading symptoms (6) of iron deficiency and iron metabolism problems.

Listen to my episode on The Art Of Being Well to learn more about iron deficiency, the top warning signs of deficiency, how to check your iron levels, and exactly how to get your levels back in check.

What to do: Run labs to check your levels and confirm which nutrients you might be missing. Supplementing and focusing on foods that contain these nutrients can help address any deficiencies.

7. A diet unbalanced in macronutrients

The foods you eat are your medicine as well as your fuel. I often see fatigue occur when patients are not eating the right ratio of fat, protein, and carbohydrates, or drastically limiting any of these macronutrients.

What to do: I recommend starting with a macronutrient ratio of 20 percent carbohydrates (coming from fruits and starchy vegetables) 65 percent fat (coming primarily from coconut products, avocados, olive oil, and grass-fed meats,) and 15 percent protein (coming primarily from clean organic meats.) Then, adjust over time to see where you feel the best. Everyone is different, so this is just a starting point.

8. Gut problems

“Leaky gut” is a term for what happens when your intestinal lining is damaged, allowing undigested food proteins and bacteria to pass into the bloodstream. This can cause a misplaced immune response and consequential inflammation throughout the body. One study (7) in the Journal of Affective Disorders showed a link with increased intestinal permeability and chronic fatigue.

Candida overgrowth and undiagnosed food intolerances, also gut-related, can contribute to you feeling drained.

What to do: Healing your gut involves a comprehensive approach. The elimination diet is the gold standard for this. I also like to use natural medicines such as probiotic therapy, L-glutamine, and bone broth to help heal the gut.

Take our quiz here to help find out if you are likely struggling with gut problems.

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9. Inflammation

Most health problems involve at least some chronic inflammation, which can weaken your body’s ability to handle stress, leading to brain fog and fatigue.

What to do: Turmeric, green tea, astragalus, and skullcap are some of my favorite tools to help soothe inflammation and modulate the immune system.

10. Medications

Every pharmaceutical drug has side effects, and fatigue is one of the most common. It amazes me how little people know about the side effects of the drugs they take every day.

What to do: If you take any medications, find out if fatigue is one of the side effects. If you think your medication is causing or adding to your fatigue, talk with your doctor about other potential options.

11. Genetic variants

Everyone’s genetic makeup looks different and certain genetic variants have been linked to an increased risk of developing specific conditions. While more research needs to be done, some studies have found a link (8) between CFS and certain HLA gene variants. Human Leukocyte Antigen (HLA) gene variants are a group of genes that play a crucial role in your immune system. Researchers also believe CFS is highly associated with HLA gene variants because these variants are present in certain conditions like autoimmune disease and infections like lyme disease which directly contribute to symptoms of chronic fatigue.

To learn more about HLA gene variants and their connection to CFS, mold toxicity, and Lyme disease, check out my article here.

12. Mold toxicity

Mold toxicity is an insidious problem that can wreak havoc on your health in a number of different ways, including Chronic Fatigue Syndrome. Studies have continued to look at the link between CFS and mold exposure, with one study in particular (9) showing that 93% of individuals with CFS had at least one mycotoxin in their urine. 

Read my article here to learn more about mold toxicity, how to test for mold exposure, and how to start healing.

8 Next-Level Ways To Reverse Chronic Fatigue

1. Fuel your mitochondria

Your body is made up of trillions of cells. The energy factory of your cells is the mitochondria, and several studies have found evidence of mitochondrial dysfunction in those with chronic fatigue. Another study, (10) published in NMR in Biomedicine, found low levels of the powerfully healing antioxidant glutathione in the brains of patients with CFS.

What to do: Supplementing with L-arginine, alpha lipoic acid (ALA), and CoQ10 are three natural ways to help increase glutathione as well as protect and boost your mitochondria and the production of adenosine triphosphate (ATP), your cell’s high-energy fuel.

2. Get more BCAAs

Branched Chain Amino Acids (BCAAs) refers to three amino acids: leucine, isoleucine, and valine. BCAAs compete (11) with your “sleepy-time” amino acid tryptophan and prevent its transport into the blood, thus decreasing fatigue.

What to do: Talk to your health care practitioner about supplementing with BCAA to fight fatigue. A typical daily dose of BCAAs is around 20 to 30 grams of the three combined amino acids one to three times per day.

3. Heal your leaky gut

Your gut is your second brain. In fact, your gut and brain were formed from the same fetal tissue and are inextricably linked for the rest of your life through the vagus nerve and the gut-brain axis. Most of your serotonin, the “happy” neurotransmitter, is made and stored in the gut.

Leaky gut syndrome, or increased intestinal permeability, happens when your intestinal lining is damaged, allowing undigested food proteins and bacterial endotoxins to pass into the bloodstream, causing an immune response and inflammation throughout the body.

A study (12) published in the Journal of Nuclear Medicine found an increase in symptoms of fatigue and depression after endotoxin administration, so leaky gut could be a culprit.

What to do: I recommend having labs done to evaluate your gut health. Endotoxins will raise immune labs, such as white blood cell count and inflammatory proteins such as C-reactive protein and IL-6.

Research shows (13) that probiotics such as bifidobacterium and lactobacillus can improve microbiome health. Bone broth is rich in collagen and glutamine, which are both helpful in healing the gut. Bone broth is also rich in glycine, (14) which has likewise been shown to improve brain performance and energy.

4. Manage stress and increase restorative sleep

Most of us are stressed, overly busy, and sleep deprived, but you can manage these problems through lifestyle changes.

What to do: Start and end your day with mindfulness meditation – apps such as Headspace and Calm can help.

An amino acid called theanine has also been shown (15) to improve sleep and allows you to feel rested and rejuvenated when you wake up. Low-caffeine teas like white tea or decaf green tea are great food sources for this sleepy-time medicine. I have a cup every night.

5. Correct hormonal imbalances

Underlying hormonal dysfunctions can wreck your energy levels. Adrenal fatigue, thyroid problems, and sex hormone imbalances of estrogen and testosterone can all fuel fatigue.

What to do: Your course of action largely depends on your specific issue. Read my article on the subject for a complete list, and talk to a functional medicine practitioner for a professional perspective on your specific health case.

6. Maximize your nutrients

Low levels of iron, vitamin D, B12, and folate can all contribute to fatigue.

What to do: Get labs to check your nutrient levels and address deficiencies with food. Focus on eating a clean diet with a wide variety of nutrient-dense whole foods such as vegetables, fruits, organic meats, and healthy fats.

7. Boost your immunity

Chronic infections (including Epstein-Barr virus, which causes mononucleosis, and Lyme disease) are a likely common cause of chronic fatigue but are widely undiagnosed.

What to do: In addition to getting tested for underlying infections, consider blends of Siberian ginseng, samento, sarsaparilla, guaiacum, astragalus, resveratrol, and cat’s claw for their immune-strengthening properties.

8. Make every meal a detox

Chronic exposure to mold and mercury (16) and other toxins such as heavy metals and pesticides have been linked to chronic fatigue.

What to do: Many food medicines can amp up the body’s natural detoxification mechanisms. Try adding more of these detoxing foods into your daily diet: Garlic, cilantro, parsley, plantain leaf, spirulina, sage, and red clover blossom. Whether you use them in smoothies, on salads, or with your meals, rotating these foods throughout your week is a great way to make every meal a detox.

As one of the first functional medicine telehealth clinics in the world, we provide webcam health consultations for people around the globe. 


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  1. National Institutes of Health "About ME/CFS" Accessed October 2023.
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  4. Fevang, Børre et al. “Lasting Immunological Imprint of Primary Epstein-Barr Virus Infection With Associations to Chronic Low-Grade Inflammation and Fatigue.” Frontiers in immunology vol. 12 715102. 20 Dec. 2021, doi:10.3389/fimmu.2021.715102
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  6. Świątczak, Michał et al. “Chronic Fatigue Syndrome in Patients with Deteriorated Iron Metabolism.” Diagnostics (Basel, Switzerland) vol. 12,9 2057. 25 Aug. 2022, doi:10.3390/diagnostics12092057
  7. Maes, Michael et al. “Increased serum IgA and IgM against LPS of enterobacteria in chronic fatigue syndrome (CFS): indication for the involvement of gram-negative enterobacteria in the etiology of CFS and for the presence of an increased gut-intestinal permeability.” Journal of affective disorders vol. 99,1-3 (2007): 237-40. doi:10.1016/j.jad.2006.08.021
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  9. Brewer, Joseph H et al. “Detection of mycotoxins in patients with chronic fatigue syndrome.” Toxins vol. 5,4 605-17. 11 Apr. 2013, doi:10.3390/toxins5040605
  10. Shungu, Dikoma C et al. “Increased ventricular lactate in chronic fatigue syndrome. III. Relationships to cortical glutathione and clinical symptoms implicate oxidative stress in disorder pathophysiology.” NMR in biomedicine vol. 25,9 (2012): 1073-87. doi:10.1002/nbm.2772
  11. Blomstrand, Eva. “A role for branched-chain amino acids in reducing central fatigue.” The Journal of nutrition vol. 136,2 (2006): 544S-547S. doi:10.1093/jn/136.2.544S
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  13. Choi, Chang Hwan, and Sae Kyung Chang. “Alteration of gut microbiota and efficacy of probiotics in functional constipation.” Journal of neurogastroenterology and motility vol. 21,1 (2015): 4-7. doi:10.5056/jnm14142
  14. Bannai, Makoto et al. “The effects of glycine on subjective daytime performance in partially sleep-restricted healthy volunteers.” Frontiers in neurology vol. 3 61. 18 Apr. 2012, doi:10.3389/fneur.2012.00061
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  16. Shin, Sae-Ron, and A-Lum Han. “Improved chronic fatigue symptoms after removal of mercury in patient with increased mercury concentration in hair toxic mineral assay: a case.” Korean journal of family medicine vol. 33,5 (2012): 320-5. doi:10.4082/kjfm.2012.33.5.320

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Dr. Will Cole, DNM, IFMCP, DC is a leading functional medicine expert who consults people around the globe, starting one of the first functional medicine telehealth centers in the world. Named one of the top 50 functional and integrative doctors in the nation, Dr. Will Cole provides a functional medicine approach for thyroid issues, autoimmune conditions, hormonal imbalances, digestive disorders, and brain problems. He is the host of the popular The Art Of Being Well podcast and the New York Times bestselling author of Intuitive Fasting, Ketotarian, The Inflammation Spectrum and the brand new book Gut Feelings: Healing the Shame-Fueled Relationship Between What You Eat and How You Feel.

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Gut Feelings

Healing The Shame-Fueled Relationship
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