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Chronic Fatigue Syndrome and Stress: A New Frontier for Treatment?

by Kelsey Kinney, RD

Published on


If you or someone you know suffers from Chronic Fatigue Syndrome (CFS), you know how devastating this condition can be. While some may function well, others can have their lives practically ripped out from under them – unable to work, go to school, or engage in many of their favorite activities.

CFS is a somewhat controversial disease due to its lack of objective findings in patients. Through the course of its history as a known syndrome, its definition has changed dramatically, but it is currently diagnosed when a person has (1):

  • Clinically evaluated, unexplained, persistent or relapsing fatigue that is of new or definite onset; is not the result of ongoing exertion; is not alleviated by rest; and results in substantial reduction in previous levels of occupational, educational, social or personal activities AND
  • Four or more of the following symptoms that persist or recur during six or more consecutive months of illness and that do not predate the fatigue
    • Self-reported impairment in short term memory or concentration
    • Sore throat
    • Tender cervical or axillary nodes
    • Muscle pain
    • Multi-joint pain without redness or swelling
    • Headaches of a new pattern or severity
    • Unrefreshing sleep
    • Post-exertional malaise lasting over 24 hours

Chronic fatigue syndrome is most commonly found in young to middle aged adults, and it is about twice as common in women than men. The prevalence of this syndrome is estimated to be under 10 percent of the population. (2,3)

The most common conventional treatment options include cognitive behavioral therapy (CBT) and graded exercise therapy. While some patients experience relief with these therapies, there is always a hunt for better therapies that provide more relief. The role of the hypothalamic-pituitary-adrenal (HPA) axis may be an important new treatment approach that should be explored.

Chronic Fatigue Syndrome and the Hypothalamic-Adrenal-Pituitary Axis

The HPA axis is the body’s control center for reactions to stress, and in turn regulates many other body functions like digestion and immunity. When we interact with a stressor, the body releases a cascade of hormones which eventually reach the adrenals and stimulate the production of other hormones like cortisol (the main stress hormone), dehydroepiandrosterone (DHEA), and aldosterone. These hormones work to keep blood sugar elevated and helps the body retain sodium and fluid so that blood pressure stays high and blood sugar levels can keep up with the fuel demands of the brain and other vital organs during times of stress. This process is important in maintaining life in a true “fight or flight” response, but in the modern world we constantly activate the HPA axis for small stressors like traffic or missing our train. With constant activation, the adrenals can become “worn-out”. Someone with hypoadrenalism will experience fatigue, depression, and low cortisol levels – all markers that are similarly found in chronic fatigue syndrome.

HPA axis dysfunction is not currently evaluated in potential chronic fatigue syndrome patients as  part of the diagnostic process, as evidenced by the CDC criteria listed above. However, looking at recent research, it is clear that HPA axis function is an important part of the symptoms experienced by CFS patients.

Hypoadrenalism (low or “worn out” adrenals) in its most severe state presents as Addison’s disease, which in industrialized nations is most commonly caused by an autoimmune attack of the adrenal glands. In Addison’s disease, some or all of the adrenal hormones are not produced in sufficient amounts, which as you can imagine, causes many problems including fatigue, anorexia and/or weight loss, nausea/vomiting, hypotension and/or postural hypotension, muscle and joint pain, salt cravings, sexual dysfunction, and psychiatric symptoms.(4) Chronic Fatigue Syndrome and Addison’s disease have many overlapping symptoms, the most important of which is fatigue.

Both Addison’s disease patients and CFS patients show low cortisol output. Morning cortisol levels measured in the saliva have been shown to be low in CFS patients (5), and 24-hour urinary free cortisol is also lower in CFS patients than controls. (6) CFS patients are likely to have undergone early trauma (7), which, even in healthy adults, is associated with lowered HPA axis reactivity. (8, 9)  The lowered HPA axis reactivity often found in CFS patients with history of trauma is associated with having increasing symptoms compared to CFS patients without a history of trauma. (10)

Despite this research, it’s still not clear whether HPA axis dysfunction is a cause of CFS or if it comes as result of the condition. Nonetheless, it has been proposed that HPA axis dysfunction in CFS is a vicious cycle, meaning HPA axis dysfunction may be involved in the genesis of CFS, but it also propagates ongoing symptoms once the syndrome manifests. (11)

Whether HPA axis dysfunction is the chicken or the egg in CFS may be determined by future research, but for those of us trying to deal with it today, it’s important to determine whether normalization of the HPA axis improves symptoms. Treatment with replacement doses of hydrocortisone have been shown to be helpful but at the expense of adrenal suppression, (12) while treatment with low dose hydrocortisone (5 or 10 mg daily) was shown to be effective without associated adrenal suppression. (13) Another study showed that symptom responders to low dose hydrocortisone (those whose fatigue levels were reduced) showed significant increases in cortisol to human CRH, which reversed the previously observed blunted response compared to non-responders. (14) Though there are limited studies on hydrocortisone treatment of CFS, these studies show that improving cortisol levels is likely important in reducing symptoms.

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Improving HPA Axis Activity Naturally

Because there seems to be a connection between HPA axis functioning and CFS symptoms, it is important to make sure that your adrenals are working their best. Pay special attention to the lifestyle factors like sleep and stress reduction with mind-body activities for the best results. These are perhaps the most important (and most overlooked) factors for recovery of adrenal function and improvement of CFS symptoms.

Adrenal Testing

If you have been diagnosed with CFS and don’t know how your adrenals are functioning, it’s an excellent idea to do a salivary adrenal panel which will measure your cortisol output over four different intervals during the day. This is different from having your cortisol level tested at the doctor’s office, as that is a one-time test and doesn’t give you the picture of what the adrenals are doing the whole day. In some states, you can order your own test kit from directlabs.com. Otherwise, you’ll have to have your healthcare practitioner order one for you.


A healthy whole foods diet that minimizes food toxins and emphasizes nutrient dense foods (such as the Paleo diet) is an excellent start. A diet like this will be high in many of the nutrients important for the CFS patient which help the HPA axis function including Vitamin C (15,16,17) magnesium, (18,19,20) pantothenic acid, (21) and pyridoxine (22).

Patients with CFS who are on a Paleo diet may want to consider increasing their sodium intake. It can sometimes be difficult to consume a lot of sodium, and those with CFS and/or hypoadrenalism should be sure to get a fair amount of it so as to minimize the symptoms of low blood pressure. If low blood pressure is a concern it may also be a good idea to supplement with licorice root which potentiates the action of cortisol. (23) Note that licorice root supplementation is contraindicated if you have high blood pressure.

You’ll also want to consume foods (or supplements) with probiotic bacteria, such as kombucha, kefir, yogurt, and sauerkraut. It has recently been shown that the gut flora of rats has an effect on the HPA axis. Rats that had no exposure to microorganisms (germfree; GF) had significantly higher ACTH and corticosterone responses to restraint stress than did rats with normal gut bacteria. (24) Another study in rats showed that those exposed to endotoxin (like that which a human would be exposed to if they acquired a pathogen) displayed altered HPA axis activity. (25)  Stress is known to alter the gut microbiota, and in turn this change alters the HPA axis. (26) It seems that normal gut flora is required for proper HPA axis activity and that clearing of pathogens and replacing lost beneficial bacteria with probiotic supplementation will likely benefit those suffering from HPA axis dysfunction.

Mind-Body Medicine

It has been shown that those of us who are highly neurotic and who experience depression and self-consciousness have blunted responses to stress tests. (19) When we work to change these thoughts and behaviors, we can start to re-train the HPA axis and feel better. Mind-body medicine techniques can help to re-train the HPA axis. Yoga, in particular, can help to reduce anxiety, depression, and perceived stress. (20) In a study on mindfulness-based stress reduction, 40% of participants had abnormal cortisol secretion patterns before the intervention and afterwards there was a change to a more normal cortisol rhythm. (21) The important thing is to find a mind-body medicine technique that you enjoy and will do on a regular basis. The more consistently you practice, the more benefits you’ll receive. Some examples include tai chi, meditation, deep breathing, biofeedback, the Feldenkrais method and more! Try them all and find out which one you like best.


If you have chronic fatigue syndrome, don’t overlook sleep! Sleep deprivation and disordered sleeping cause HPA axis hyperactivity, (22) so make sure to get to get at least 7-9 hours nightly, and try to go to bed at the same time each night. Chris has some great tips about sleep in his upcoming book, Your Personal Paleo Code (published in paperback as The Paleo Cure in December 2014), so be sure to check that out! You can also read more about better sleep on this site here.

Time Management

Another successful strategy that helps a lot of my patients is practicing time management skills. A lot of us tend to run around like chickens with our heads cut off, trying to do everything at once but actually accomplishing very little. With proper time management, you can find time to fit in proper sleep, mind-body medicine, and make delicious, healthy meals and you’ll probably find that you get more done in less time. Check out both of Chris’ podcasts about time management here and here for more information. When we know exactly what we should be doing at any given moment, we spend a lot less time procrastinating. Plus, when we’re getting things done our stress level goes way down, helping the HPA axis to function more appropriately.

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Chris Kresser in kitchen
Kelsey Marksteiner
Kelsey Kinney, RD

Kelsey Kinney, RD, is devoted to helping the world achieve great digestive health through her blog, private practice, and prebiotic & probiotic drink mix company Gut Power Drinks. Check out her blog, Gut Power Drinks website, or visit her on Facebook for more.

Kelsey is a registered dietitian specializing in digestive and hormonal health. She graduated from New York University with a Bachelor of Science degree in Nutrition and Dietetics and went on to complete her dietetic internship at Milford Regional Medical Center in Milford, Massachusetts. She also has a Master of Science degree in Human Nutrition and Functional Medicine from the University of Western States.

Kelsey loves helping people find their unique, personalized diet that will help them heal, not anyone else. She has always been interested in nutrition and health, and is honored to now help people find a diet that brings them happiness and longevity.

Professional website: https://kelseykinney.com

Gut Power Drinks website: https://gutpowerdrinks.com

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Join the conversation

  1. Hello Ron,


    I am suffering from CFS since three years, and below are my current symptoms:

    -Constant pain in Thighs muscles, Calf muscles and Legs and I always feel exhausted.
    -Brain Fog
    -Weak memory
    -Unable to concentrate.
    -Not getting deep sleep.
    -Not able to do physical activity.

    Initially I was not able to understand what is happening with me, I went to the doctor and they advised to take some Multivitamins and Multi minerals but it didn’t help. later on I went to see a neuro-physician and after doing several test they found following issues:

    B12 (Highly deficient)
    D3 (Highly Deficient)

    And rest everything was fine in the report, My doctor prescribed me supplement for B12 and D3, Tablet for Thyroid and anti-depression.

    It helped me little bit but not much, after few months my B12,D3 and Thyroid test was normal, but I didn’t get much relief in CFS. My doctor said you have CFS and IBS that is incurable and you got a live with it. I tried acupressure and Homeopathic medicines, there is a medicine “Nux Vomica” that worked in IBS issue but only for few weeks, however no improvement in CFS.

    Today I was going through this forum and you have advised to take “Prednisone”, I have few questions If you could help me out it would be highly appreciated:

    -Is there any criteria to take this medicine ?
    -Is there any side effects that I need to be aware of ?
    -How long should I take this medicine ?
    -How much time does it take to see the improvement ?
    -Is there any supplement do you recommend ? or any do’s or don’t ?
    -Do I need to take this medicine at night or in the morning ?

    In case if you need any information then please let me know, your help would be greatly appreciated.