While the cause or causes of chronic fatigue syndrome (ME/CFS) are still unclear researchers have documented numerous abnormalities that have sparked considerable speculation regarding its cause. Overall, research findings suggest chronic fatigue syndrome (ME/CFS) is a multi-systemic disorder involving the immune, neuroendocrine and cardiovascular systems.

Triggering Chronic Fatigue Syndrome (ME/CFS): A wide variety of events including infection, injury, physical or psychological stress and toxin exposure have been reported to trigger chronic fatigue syndrome (ME/CFS). Not all patients can identify a triggering event. How such a process occurs is still unclear but researchers are increasingly focused on the central nervous system and the ways that stressful events such as injury and infection can affect the functioning of the brain.

Central Nervous System Dysfunction: Several models of chronic fatigue syndrome (ME/CFS) begin with an external event (infection, toxin, physical or psychological stressor) that ultimately translates into central nervous system damage. Abnormal patterns of brain activity, reduced brain blood flows, reduced gray matter volume, altered metabolic findings, and others suggest areas of the brain involved in the stress response, energy production, concentration, motivation, fatigue and pain are damaged in chronic fatigue syndrome (ME/CFS).

Immune Defects: The flu-like symptoms chronic fatigue syndrome (ME/CFS) patients often experience at the diseases onset has made the immune system an important research emphasis. Several immune abnormalities could contribute to the problems patients face.

  • Impaired Cellular Immune Response - Two abnormalities in the responses cells have to infection in the ‘interferon pathway’ have been documented. An antiviral enzyme in this pathway called the RNase L has been shown to be fragmented in many patients. A subset of chronic fatigue syndrome (ME/CFS) patients also display increased activity of another enzyme called protein-kinase R (PKR) that is involved in killing cells infected with pathogens. These problems suggest the immune systems of chronic fatigue syndrome (ME/CFS) patients could have troubles finding pathogens and killing the cells they’ve infected.

  • Natural Killer (NK) and T-cell Dysfunction - NK and T-cells are two other components of the immune response to pathogens. A set of chronic fatigue syndrome (ME/CFS) patients have been shown to have reduced NK cell numbers and poor NK and T-cell functioning. These problems also could interfere with the ability of the immune system to find infected cells and kill them. Intriguingly some researchers believe that chronic immune activation due to an underlying chronic infection has caused these cells to ‘burn out’.

  • Th1/Th2 Imbalance - There are two general branches (Th1/Th2) of the immune system. Some patients appear to have an over activation of the anti-inflammatory (Th2) branch and an under activation of the pro-inflammatory (Th1) branch of the immune system. This could cause increased rates of allergy and sensitivity on the one hand and difficulty fighting off pathogens on the other.

An Undiagnosed Chronic Infection: Chronic fatigue syndrome (ME/CFS) patients were recently reported to be 18′s more likely to harbor a pathogen than healthy controls. The NK cell ‘burn-out’, increased T-cell activation and increased rates of cell suicide (apoptosis) in CFS could be caused by a chronic infection. Some study results suggest that antiviral drug therapy may be able to cure some CFS patients but much more study is needed.  Herpesviruses and enteroviruses are the main candidates.  

Impaired Stress Response: A significant number of patients have reduced hypothalamic-pituitary-adrenal (HPA) axis functioning and lowered cortisol levels. Since the stress response is important in mobilizing the bodies energy stores for activity an impaired stress response could contribute to the fatigue patients experience. Because the HPA axis also plays an important role in down regulating the immune response low HPA axis activity could also contribute to the chronic immune activation believed present.

Increased Sympathetic and Decreased Parasympathetic Nervous System (SNS/PNS) Activation: Increased SNS activity could result in narrowed blood vessels and the low blood volume, reduced brain and muscle blood flows, heart abnormalities under stress and other problems seen in chronic fatigue syndrome (ME/CFS). Reduced PNS activity could also contribute to unrefreshing sleep.

Genetics: Recent studies suggest there is a strong genetic component to chronic fatigue syndrome (ME/CFS). While chronic fatigue syndrome (ME/CFS) is not strictly hereditary some evidence suggests that it runs in family. Several gene mutation studies have found increased rates of neuro-endocrine and immune mutations in the disease.


Chronic Fatigue Syndrome A Biological Approach Ed. Patrick Englebienn,, Kenny DeMeirleir M.D, Ph.D., CRC Press. Washington D.C. 2002

Chronic fatigue syndrome is associated with diminished intracellular perforin. Maher KJ, Klimas NG, Fletcher MA. Clin Exp Immunol. 2005 Dec;142(3):505-11.

Chronic fatigue syndrome: probable pathogenesis and possible treatments. Drugs. 2002;62(17):2433-46. Review. Evengard B, Klimas N.

2007 IACFS Conference Summary: The Immune System, Gut, Pain and Sleep.

Polymorphisms in genes regulating the HPA axis associated with empirically delineated classes of unexplained chronic fatigue. Smith AK, White PD, Aslakson E, Vollmer-Conna U, Rajeevan MS. Pharmacogenomics. 2006 Apr;7(3):387-94.

Patients with chronic fatigue syndrome have reduced absolute cortical blood flow. Yoshiuchi K, Farkas J, Natelson BH. Clin Physiol Funct Imaging. 2006 Mar;26(2):83-6.  


{ 5 comments… read them below or add one }

angieishere44 February 22, 2013 at 11:00 am

What about EBV?


Nenej April 16, 2015 at 10:42 pm

I saw another website you commented on that included your statement that you see a CFS specialist in Scottsdale az, I’m looking for a CFS specialist in az and wondered if you could recommend anyone? Sorry for posting off topic here


Denise June 27, 2014 at 7:57 am

Undercooking food especially pork and grond meat is another excon trick, it’s also antisemitic. Some food parasites they recommend six test cups for stool in a row to detect.


Betty Mekdeci November 25, 2014 at 9:56 am

Since no one really knows the causes of CFS, Next Generation Sequencing testing might finally produce some answers. Researchers at the University of California, San Francisco have used Next Gen testing to diagnose a mysterious infection in a man that turned out to be caused by a sand fly bite. A hiker who returned from the Australian Outback with aching muscles and joints, a fever and constant sweating was diagnosed with an adult onset of herpes 7 virus. It would be informative for a researcher to test a group of CFS patients with Next Generation Sequencing to determine if we all have the same thing or different causes create similar symptoms


CAWS January 19, 2015 at 8:04 am

I know exactly when my FM/CFS began. It took me 15 years to figure it out though & unfortunately I was exposed multiple times to the “trigger”. I was a professional equestrian triathlete riding 5 horses daily,Teaching lessons, raising organic food for family of 4, no smoking ,drinking, drugging, slept like a rock & full of energy . I was treated with Cipro for sinus infection & ended up flat on my back for 6 months & took another 6 months to 95% recover. I was 38. Subsequent exposures to IV Levaquin , oral Cipro, & finally Factive 7 which turned me PURPLE from head to toe, gave me hallucinations & made my eyes extremely sensitive to light finished me off. Most people are not aware that this drug is chemotherapy and works by altering the DNA of bacteria at the point of replication. This means your immune system is permanently corrupted and malfunctioning . This drug adducts itself to all your cells which accounts for the laundry list of symptoms. It is a downward slide similar to radiation poisoning. With most of us full of heavy metals from amalgams, vaccines and pesticides from crop dusting & contaminated foods it is a miracle we are still alive. These drugs [fluoroquinolones] were not black boxed when I took them. They now have warnings for tendon rupture/pain, permanent peripheral neuropathy , and are in litigation for delayed retinal detachment. Bayer and Johnson & Johnson knew this but it took court orders to get the warnings. Doctors & patients are not given this info though and these drugs [including eye & ear drops] are being prescribed to infants & young children ; which is why we are seeing FM/CFS at younger ages.
Fluorine is the culprit here folks . As of the mid 80s it has been added to over 360 drugs [many of which had to be removed because of toxicity] in all classifications. Go to and click on the FTRC link for the only list on the internet posted by a pharmaceutical toxicologist. The reason for this is it allows the drugs to go into you faster, longer, stronger, deeper, and cheaper [for the drug companies not you].
Ask yourself what all the “triggers” medical science lists as possible causes have in common. Almost all usually involve a fluorine drug. Car accident, pnuemonia, ? 85% of anesthesia is Fluorinated. Most USA hospitals contract for Levaquin so you are hooked to an IV upon arrival. Then if you are depressed [divorce, death,etc] or traumatized there is Prozac, Paxil etc. Most of your antidepressants & antopyschotics have Fluorine. Many of your nasal sprays, antihistamines also . This is a cumulative poison that is used in pesticides, funcgicides, and rat poison. Plus they put it in our water [ not a pharmaceutical drug but comes from the scrapings of the smokestacks of the phosphate fertilizer industry in China] & allow high amounts of it in our food. Check for actual figures.


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