Just Tired – or Is It Something More?

For decades, chronic fatigue syndrome (CFS) has been recognized as a condition that is exactly as its name suggests: chronic (long-lasting) problem with fatigue (tiredness, lack of energy). It has been difficult for people with CFS to receive proper diagnosis and treatment, since the cause or causes are unknown, and there have been no lab tests or other objective studies to identify it with certainty. The condition is now known as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS, or just ME). Myalgic refers to muscle pain, a common symptom that goes along with the fatigue, and encephalomyelitis is inflammation of the brain and/or spinal cord. This recognizes that there is some immune system abnormality that affects the brain and contributes to ongoing fatigue.

In 2015, the Institute of Medicine provided this definition of the condition:

  1. a substantial reduction or impairment in the ability to engage in pre-illness levels of occupational, educational, social, or personal activities that persists for more than 6 months and is accompanied by fatigue, which is often profound, is of new or definite onset (not lifelong), is not the result of ongoing excessive exertion, and is not substantially alleviated by rest;
  2. postexertional malaise (often described by patients as a “crash” or “collapse” after even minor physical or mental exertion);
  3. unrefreshing sleep; and
  4. cognitive impairment and/or orthostatic intolerance.

There have been recent developments in this field that take some steps forward. In late 2016, the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (IACFSME) research conference emphasized the role of postexertional malaise (an energy “crash”) following physical exertion or emotional distress, rather than just general fatigue, as the most important aspect of ME/CFS. This has been verified through experiments that test physiologic function in ME/CFS patients following exercise.

Conference speakers also reported on some possible laboratory tests that could identify the abnormalities associated with ME/CFS. Kenny L. DeMeirleir, MD, PhD found that the four blood tests that were most helpful were prostaglandin E2, interleukin 8, soluble CD14, and CD57+ lymphocytes — all of which are associated with an inflammatory immune response. This combination of tests is already being used as a panel to diagnose ME/CFS in Belgium, where Dr. DeMeirleir is originally from. Jose Montoya, MD, professor of medicine at Stanford University, found abnormalities in levels of 17 specific cytokines (chemical messengers used by immune cells) that correlate with the condition. U.S. researchers caution that larger studies are needed before either panel is adopted in this country for diagnosis of ME/CFS.

Researchers at the University of California San Diego School of Medicine published an extensive study in 2016 about what is actually going on inside the body’s cells in ME/CFS. Without getting too deep into the technical information, they found several problems with the cell’s ability to produce energy from the nutrients that we get from food. Other scientists presented information at the IACFSME conference that suggested that a slightly altered gene (called a single nucleotide polymorphism, or SNP [pronounced “snip”]) may be responsible for the body’s inability to process energy correctly.

What is emerging, then, is a picture of a genetic predisposition toward less efficient energy production, that may be aggravated by some outside factor, such as infection or environmental toxins. Those outside influences then set up a chronic inflammatory state that affects the brain in particular. Physical exertion or emotional distress can aggravate the inflammatory messengers in the body, leading to “crashes” (postexertional malaise). I speculate that this could be the explanation of why some people are “wiped out” for years by something that should be temporary, such as a Lyme disease infection, or an adverse reaction to medication like Cipro. This is also why trying to fight the inciting factor is so often ineffective (like years of antibiotics for Lyme, or elaborate detox protocols for medication reactions). Careful evaluation of a patient’s metabolic state, and appropriate lifestyle and nutritional support (in particular, for mitochondrial energy production) is probably the more effective strategy.


  1. IOM Gives Chronic Fatigue Syndrome a New Name and Definition. Medscape. Feb 10, 2015.
  2. Postexertion ‘Crash,’ not Fatigue per se, Marks Syndrome. Medscape. Nov 04, 2016.
  3. Biomarker Research Advances in ‘Chronic Fatigue Syndrome’. Medscape. Nov 08, 2016.


  1. Greg McClure

    Thanks again, Dr. Peters, for your thoughtful insights! I want to mention that fatigue and cognitive impairment are also hallmark symptoms of Vitamin B12 Deficiency. Vitamin B12 Deficiency is often not definitively ruled out in these cases.

  2. Tim Oare

    I feel that I suffer from this condition I work on my feet all day and with neuropathy in my hands and feet the pain is constant and gets worse when I try to sleep.
    But I feel its not all do to neuropathy.
    Depression? Anxiety? Both?
    I’m always tired, fatigued,and everthing feels like an argues task.
    Would like to see of there is a Doctor for me to go to for thos in my area?

Leave a Comment