Chronic Fatigue

Paul L. Reller L.Ac. / Last Updated: August 03, 2017

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Understanding the Pathophysiology of Chronic Fatigue Syndromes

The array of presentations in Chronic Fatigue Syndromes are confusing, and suggest that a single disease classification, or even the array of current disease classifications, are misleading, and often resulting in improper diagnostic analysis and individualized treatment protocols. A 2010 study by DePaul University Center for Community Health Research found that of all current standard university medical texts, even mention of Chronic Fatigue Syndrome was seen in only 40 percent of texts, and of these, mention of the pathophysiology was found on only 0.09% of pages. The systemic and holistic nature of the pathophysiology does not suggest a standard allopathic approach to treatment. Instead, a growing field of holistic medicine in standard practice, sometimes called NeuroImmunoPsychology, is suggesting that the research evidence points to a complex interaction between the nervous and immune systems, resulting in autoimmune dysfunction with hormonal imbalance that affects the central nervous system.

Chronic Fatigue Syndrome is often called Encephalomyelitis today (CFS/EM), or Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS), based on research that has discovered mechanisms of dysfunction with inflammatory problems in the brainstem and spinal cord. These mechanisms of brain stem and spinal cord pathophysiology concern an overlap between the serotonin and estradiol-2 systems, with CNS (central nervous system) neurogates normally relating to pain sensation and control triggered by either sufficient levels of serotonin or estradiol2, often with deficiencies of dopamine and progesterone. Imbalances of serotonin or estradiol may affect the control of pain sensation, as well as CNS regulation of fatigue and other neurocognitive symptoms. Neurohormonal balance may be the important factor in Chronic Fatigue Syndrome, and diagnosis and therapy should address this issue.

Some experts have estimated a 400 percent increase in this disorder in the last 10 years and the CDC (Centers for Disease Control) have acknowledged CFS as a growing health problem in the United States. Subsequently, many causes are being investigated, including increase in vaccinations, use of antidepressants, use of synthetic hormones, sterols in commercial products etc. Debate continues concerning the role of subclinical viral illnesses in the syndrome, with a chicken/egg controversy obscuring the health picture (do viral illnesses cause CFS or does CFS predispose to chronic viral illnesses?). The picture of pathophysiology suggests that a complex cascade of events is responsible, with individuals perhaps taking differing courses of trigger and dysfunction leading to a systemic and holistic dysfunction that affects the interrelationship of the immune, nervous and hormonal systems. The U.S. CDC admits in 2013 that extensive research still has not found unifying evidence of a single cause, or even a small set of causative problems, and that the CFS pathology is probably related to a broad set of potential underlying causes or triggers. Focus instead is finally addressing treatment that must be holistic in nature to restore homeostatic functions, either effectively managing symptoms, or affecting a cure through a complex integrative treatment protocol.

Not only chronic low-grade viral illness, but bacterial infection, is now considered a likely factor in the pathology of CFS/ME. In 2016, a randomized controlled human clinical study of patients with CFS/ME, at Cornell University, found that, compared to health controls, that CFS/ME patients had significantly lower diversity of bacteria in stool samples, and higher levels of lipopolysaccharides (LPS), which are common bacterial endotoxins, indicating that the gut Biome may be unhealthy, and that low-grade bacterial infection and a superantigen response could explain many of the symptoms. The lead author, Dr. Maureen R. Hanson, a professor of molecular biology, stated that this study could lead to a diagnostic marker as well as a new direction in complementary treatment, and that this study should dispel any lingering belief in the medical community that CFS is a psychosocial disease, or psychological illness. Of course, CIM/TCM physicians have been using a broad array of protocols, including restoration of gastrointestinal health and the gut Microbiome, as well as clearing of inflammation, for a very long time. Such study should reassure patients that a persistent restorative treatment protocol that is comprehensive will yield success. To learn more about bacterial endotoxins and the superantigen response, you may go to the articles on this website entitled Bacterial Endotoxins, Lectins, and Chronic Inflammatory Disease, as well as Superantigens: Prevention, Treatment, and Their Role in Difficult Disease. These health problems may be overcome with a sensible approach, utilizing current research.

In 2015, the U.S. Institute of Medicine (IOM), a non-governmental non-profit organization founded in 1970 under the congressional charter of the National Academy of Sciences, released a comprehensive report entitled Beyond Myalgic Encephalmyelitis / Chronic Fatigue Syndrome - Redefining an Illness, suggesting that we should perhaps adopt the name Systemic Exertional Intolerance Disease (SEID) in order to move past the denial of diagnosis and care of these patients, who are now estimated to number between 836,000 and 2.5 million in the United States alone, with an estimated 84-91 percent of these patients fitting the diagnostic criteria of exclusion still undiagnosed. Prominent medical doctors from Johns Hopkins and Vanderbilt University again declared that standard medicine needs to stop saying that most of these patients are just imagining their symptoms and finally acknowledge that abundant evidence exists to start providing a real diagnosis and treatment plan.

The term fatigue is not clearly defined and may refer to a broad spectrum of symptom presentations. Short periods of fatigue are very common in the population, but persistent chronic fatigue, exemplified by daily exhaustion, weakness, malaise, or low energy resulting from mild exertion, or occurring inexplicably, is a cause of concern. While fatigue is the major symptom of concern, many other symptoms are associated with Encephalomyopathy or Myaglic Encephalomyelitis as well, though. Depression, poor memory, slow mental and cognitive function, anxiety, irritability, mood fluctuation, transient visual disturbances, insomnia, sleepiness, headache, chronic irritated throat, swollen lymph nodes and glands, appetite loss, nausea, muscle ache and joint pain are all common symptoms. Fibromyalgia has been linked to or included in the syndrome by many medical experts, and research has revealed that this syndrome of dysfunction may also be an encephalomyopathy. The symptom presentation may be very different from one case to another. This variety of symptoms indicates a wide variety of underlying health problems that could be associated with CFS. Individualized analysis and treatment protocol is thus important, and an understanding of not just one, but many potential aspects of pathophysiology is important to the patient and physician.

Recent studies have confirmed that a mitochondrial dysfunction and reduced ATP synthesis is seen in a large majority of patients with CFS, and more and more cases are finding that a mitochondrial disease related to the genetic code of the mitochondria may be involved. Advances in genetic testing are revealing the array of potential mitochondrial diseases that may be contributing to the CFS/ME, but even when these tests are negative, a disorder of mitochondrial dysfunction may still be occurring. Experts at the Oxford University School of Medicine showed that a 5-factor blood test for analysis of the degree of mitochondrial dysfunction is highly accurate in correlating mitochodnrial dysfunction to the severity of the CFS/ME, and in assessing the extent to which mitochondrial dysfunction plays in the fatigue. Mitochondria are the parts of our cells that efficiently produce energy, and ATP, or adenosine triphosphate, is both a source of energetic firing, and a coenzyme used in mechanisms of energy storage and transfer of cellular nutrients. Reduced production of ATP could explain an array of symptoms affecting both the central nervous system and the muscle function. Metabolic disorder, insulin resistance, and hormonal dysfunction could all contribute to likelihood of ATP dysfunction, and chronic low grade inflammatory states and inflammatory dysfunction are also at the heart of these, and other, health problems. This is why supplemental D-ribose, an important fuel for mitochondria, is often helpful in the treatment protocol to relieve fatigue symptoms. This does not address the mitochondrial dysfunction, or array of potential underlying causes, though. Nutritional cofactors of ATP function are also helpful in the protocol for many patients, and these include a combination of Vitamins B-2 and B-3 in a sustained-release form. There are many chemicals in the vitamin families, and the terms B2 and B3 could refer to a host of chemicals. The correct forms are riboflavin and inositol hexacotinate (a form of niacin). A simple B-complex supplement may not have much effect. 

Many Chinese herbs have been proven to improve mitochondrial function as well, including a host of adaptogens, such as Astragalus, Rhodiola rosea, Siberian Ginseng, etc. as well as Cordyceps (Dong chong Xia cao), a remarkable herb that combines the chemistry of animal and plant, and contains a number of key adenosine compounds. Cordyceps picked wild is now very expensive and in demand, but has been cultivated as well, which is not as potent, but very effective and affordable. Other nutritional supplements studied and found to benefit mitochondrial function and health include R-lipoic acid, and the combination of acetyl L-carnitine and L-tartrate. Coenzyme Q10, Gymnema sylvestre (Chi geng teng: rich in kaempferol and quercetin), and other herbs and nutrients are now clinically proven to help with mitochondrial dysfunction. A search on the NIH research database PubMed easily finds summaries of published studies confirming the efficacy of Chinese herbs and nutrient medicines. CoQ10 use is supported in human clinical trials in the treatment of mitochondrial encephalopathies. Often, the combination of nutrient chemicals used with CoQ10 are very important to an effective treatment result. A single part of this protocol may be only mildly effective, though, and a professional analysis and prescription is recommended. The knowledgeable Licensed Acupuncturist and herbalist is often the ideal professional to guide the therapy in Chronic Fatigue Syndromes.

The exact pathophysiology of mitochondrial dysfunction was still elusive in 2010. The CFS/ME and Pain Research Center in Amsterdam, Netherlands, is a leading force in current clinical research, and has found that a shift in cellular energy metabolism is seen in Chronic Fatigue Syndrome, with an increase in anaerobic metabolism over aerobic (oxygen utilization). Insulin resistance may be tied to this basic change in cellular energy metabolism, as Metabolic Syndrome and insulin resistance changes the way our cells utilize basic fuels, such as glucose and fatty acids. Researchers are looking to other health problems that create an excess of anaerobic cellular metabolism to find that answers to what could cause this dysfunction. Ketoacidosis is a condition that produces excess anaerobic metabolism. When a chronic state of acidity occurs, the liver shifts to a metabolism utilizing ketone anions (acetoacetate, beta-hydroxybutyric acid, and acetone) to furnish fuel for our cells, instead of relying on glucose and free fatty acids. A relative or absolute insulin deficiency is present in all cases of ketoacidosis. The term relative insulin deficiency may refer to a deficiency in the hormone insulin despite the normal production by the pancreas, and this occurs due to an increased need for insulin in cases of insulin resistance at the cells and muscle tissues. Insulin is not only used to regulate sugar and fatty acid metabolism, but is found to be integral to other metabolic aspects in the brain. Metabolic syndrome is the term typically used to describe insulin resistance states, and typically the body eventually starts creating excess insulin in circulation to compensate for insulin resistance, though. Increased alcohol consumption may also contribute to ketoacidosis, especially when the liver is not functioning optimally. Accumulation of aldehydes in the liver are implicated in alcoholic ketoacidosis. Excess aldehyde accumulation is also seen in systemic candidiasis, and accounts for many of the fatigue and foggy mental states seen in patients diagnosed with candidiasis. The measure of the reactive oxygen species malondialdehyde (MDA) is a chief measure of oxidant stress in the body, and an indicator of aldehyde toxicity. Often, the patient with Chronic Fatigue Syndrome presents with a variety of underlying subclinical health problems that could be integral to the pathology. Improvement in all of these areas is a daunting task at times, but may be necessary to fully resolve the CFS.

Abnormal or defective adaptive responses to oxidative stress is also seen in a large majority of CFS/ME patients. Various adaptogenic marker molecules are being investigated to find a better diagnostic profiling to guide individualized therapy, including heat shock protein (HSP). This family of regulatory proteins is expressed in relation to various stressors, including elevated body temperatures, infection, inflammation, toxin exposure, starvation, hypoxia, nitrogen deficiency, or water deprivation. A combination of chronic stressors may be responsible for this dysfunction of protein signalling, and chronic inflammation, accumulation of heavy metal toxins, iron overload syndrome, autonomic dysfunction related to adrenal stress syndrome, and oxidative stress seem to be the likely culprits. Studies have also noted markers of oxidative stress in CFS/ME that are apparent in Major Depressive Disorder as well, such as increased ventricular lactate and decreased glutathione metabolism (GSH). The inability to clear circulating lactic acid and detoxify reactive oxygen species (ROS), or oxidants may be an integral part of the pathology in CFS/ME. Studies in 2005, at the University College London (SL Chow et al), reviewed the study of lactic acid and lactate in cerebral spinal fluid (CSF) as a marker of disease and found that this was highly correlated with inflammatory disorders, ischemia, seizure disorders, and other metabolic disorders, but not for lactic acidosis. The high lactic acid or lactate in CSF was correlated with chronic disorders much more than acute.

Dysfunctional immune responses to exertion have also been noted in studies of CFS patients, with exertion resulting in increases in circulating immune cytokines IL-6 and TNF-alpha, which are associated with a number of chronic diseases, including neurodegenerative diseases. The field of ImmunoNeuroPsychology has also identified that these cytokines have an integral relationship to neurotransmitter imbalances, hormonal health, and psychological disease. TGF beta (transforming growth factor) is found to be significantly elevated in most cases of CFS/ME, and this molecule, mainly produced by immune macrophages and other lymphoid cells, has multiple anti-inflammatory mechanisms, and is seen in a variety of chronic diseases. Markers for interferon, namely the enzymes 25A and PKR, have also been associated as diagnostic markers for viral-induced Chronic Fatigue Syndrome, and interferon has been shown to increase the levels of TGF beta. We see that much research is pointing to the need to restore immune homeostasis in a more complex manner to cure such diseases as CFS/ME. Restoration of homeostasis is the primary goal of Traditional Chinese Medicine, and a wealth of research is revealing how acupuncture, herbal and nutrient medicine works in specific ways to achieve this goal, which is traditionally called a balance of Yin and Yang, Qi and Blood.

The most important aspect of the pathophysiology of CFS/ME that is starting to be realized in standard medicine is that this syndrome is not a specific disease, but that a diverse array of disease mechanisms underlie the syndrome, and the treatment and diagnostic approaches need to reflect this fact, rather than continue to seek one specific unifying allopathic medicine to treat it. Experts at the University of Groningen, in the Netherlands, in 2008, stated that it is clear that CFS is now recognized as a systemic, or medial, disorder, and that the variety of causes and divergent reactions to various therapies show that CFS is a syndrome defined by a diverse array of subgroups of patients. Individual analysis of patients is needed to devise an effective treatment protocol. These experts state that there are 4 main sets of identified underlying causes, including association with viral infection, anomalies of the HPA axis, immune dysfunction, and a psychiatric or psychosocial aspect. Oxidative stress and genetic and epigenetic predisposition are also identified. The challenge of addressing this array of problems in individual assessment and treatment protocol points to the need to integrate Complementary Medicine into the standard treatment of CFS/ME.

To date, there is no recommended treatment by the standard health community, except perhaps cognitive and behavioral therapy, although it is acknowledged that many patients have benefited by a holistic regimen of therapies. No single therapy has proven effective by itself. Obviously, this syndrome is a multifaceted health problem affecting various systems in the body. These various systems work as a network and dysfunction in one system leads to dysfunction in another. Improvement in the endocrine, nervous and immune systems is the best chance for cure or decrease in active symptoms. Attention to the various associated functional somatic disorders, including fibromyalgia, irritable bowel syndrome, chronic pelvic pain syndrome, temporomandibular joint dysfunction, and multiple chemical sensitivity may be very helpful if apparent. Treatment of sleep disorders, often themselves undiagnosed and ignored by the patient as well, could be helpul in individual cases. Some manifestations of sleep disorders include apnea, restless leg syndrome, and nocturnal teeth clenching and grinding (bruxism). A more restorative approach to anxiety and depressive disorders may also be important. Many of these health problems are addressed in articles to better educate the proactive patient on this website. A holistic medical approach seems mandatory for these functional somatic syndromes such as chronic fatique, though, and the search for the allopathic magic pill may only prolong the health disorder.

Theories of ME/CFS and their therapeutic implications

There is now a wide array of studied causes and contributing factors that may be causing CFS/ME, and almost no simple definitive diagnostic tests or markers. The diagnosis is one of exclusion, and so your physician or physicians must be able to take the time to evaluate each individual thoroughly. The likely culprits point to various therapeutic protocols, and if there is not sufficient progress over time, other protocols should be initiated. This is of course extremely frustrating, especially for patients suffering from chronic fatigue and related symptoms, but this is the course that must be pursued. Success depends on a very proactive role by the patient, both in the diagnostic puzzle and in persistent therapy and changing therapy.

  • Chronic Fatigue and Immunodeficiency Syndrome: Many experts contend that a lingering deep viral infection that is subclinical (no apparent symptoms directly attributed) stimulates a chronic immune response that depletes the body. Theories exist that some types of virus associated more often with ME/CFS stimulate an immune reaction that results in an excess of the enzyme RNase-L, which destroys not only the viral RNA but RNA in many human cells as well (sick-cell syndrome), and mutates to a more destructive and persistent form of RNase-L. Fungal overgrowth such as Candidiasis has also been implicated, as well as yeast overgrowth and Giardia infestation. Spirochete population, as in Lyme disease, has also been implicated. Overuse of antibiotics to counter the mycobacteria sprirochete has been blamed for many of the health problems allowing these chronic subclincial and inflammatory states to exist, especially concerning imbalance of the symbiotic flora and fauna of the intestines, or Microbiome, and in the stress engendered from the growing array of antibiotic-resistant strains of bacteria and other microbes. Studies at Cornell University in 2016 found that a significantly decreased array of gut bacteria in stool samples predicted CFS in 83 percent of cases, and that bacterial endotoxins, or lipopolysaccharides (LPS) were measured in blood, implying that low-grade bacterial infection or the effects from overuse of antibiotics created a chronic immune response. Whatever the cause or causes, it appears certain that a chronic CNS inflammatory state, Myalgic Encephalomyelitis results, and this is the widely accepted name for Chronic Fatigue Syndrome today. Professional herbal medicine offers broad spectrum treatment of these deep-seated subclinical viral, fungal and parasitic infections that is supported by a growing array of scientific studies. Herbal medicine and probiotics may help restore gut health and the Micorbiome, as well as clear endotoxins, and reduce the chronic inflammatory responses that result. Nutrient medicine and naturopathic research is also uncovering specific physiological mechanisms that perpetuate these systemic low-grade infections and offers more and more researched methods of countering the physiological dysfunctions and unwanted manifestations of such chronic inflammatory states. Over time, a decrease in the stress of the chronic low-grade viral, fungal, parasitic, or bacterial infections may allow the body to focus on the resultant overload of toxins that are not cleared in this scenario. Finally, a third phase of restoration may be achieved with a holistic and individualized protocol. These phases of treatment, clearing, detoxification, and restoration, seem to be a sensible approach.
  • The Epstein-Barr Virus (EBV) has long been linked to Chronic Fatigue and Immunodeficiency Syndrome, along with a number of other opportunistic viruses, including herpes 6, cytomegalovirus, coxsackie B and HTLV. The mechanisms of this immunodeficiency that allows the nervous system to be so adversely affected may lie in a number of systems in the body. Healthy liver function is necessary for the effective response to deep viral disorders by the cytotoxic immune system. The liver both detoxifies the blood and produces many of the cytokines needed. Many factors may stress the healthy liver function, including environmental chemicals, excess pharmaceutical drug use, hepatitis C viruses and poor dietary habits. Clearing of these deep seated viruses depends on health of both the liver and immune systems. When liver function is stressed, GI problems are often seen as a contributor. If the liver is inefficient in processing proteins, and/or the health of the GI membranes allows digestive protein fragments to bypass the liver (leaky gut syndrome), certain chemicals, such as nitrogen wastes from protein breakdown may accumulate in the blood, which is toxic to healthy brain function and the glutamine metabolism. Heliobacter pylori, a common GI bacteria that produces urease to break down these nitrogen wastes, often overgrows in the stomach and small intestine and creates further problems. Imbalances like these may lead to candida overgrowths that further stress the system.
  • Mononucleosis is a disease that is now known to be chiefly caused by Epstein-Barr virus (EBV) and often leads to Chronic Fatigue Syndrome, yet EBV acute mononucleosis accounts for only a small percentage of the total number of chronic fatigue syndrome cases worldwide. Mononucleosis is a term that refers to an infection of the immune monocytes, chiefly the B-cells, after an incubation of 4-7 weeks. The virus may first attack the membranes of the throat and upper bronchials, getting into the epidermal cells, but then moves to the B-cells as the body responds. The B-cells are part of the adaptive immune system, and the chief cells of the antibody system, so these are cells adapting to the new virus EBV, and trying to rid the body of the virus. EBV often produces very mild initial symptoms, compared to influenza viruses, but has acquired the ability to get into the immune cells. Mononucleosis is diagnosed when a percentage of circulating monocytes are derformed by this infection. Of course, in this scenario, we see how a virus could get into the whole body, and eventually infect the brainstem. In the United States, a high majority of the population tests positive for the EBV antibody, indicating widespread or universal infection. The difference between one patient and another appears to be the ability of a particular patient to respond with a strong immune reaction to control the EBV spread. Those patients with the mildest intial immune response, or no initial symptoms, but a weak complement response to a deep viral infection, are the patients most likely to be afflicted with chronic fatique syndrome.
  • Retrovirus XMRV (xenotropic murine leukemia virus-related virus) was found in 68 of 101 patients diagnosed with CFS in a study published in 2009 in the journal Science, co-authored by researchers at the Cleveland Clinic, National Cancer Institute, and the Whittemore Peterson Institute, a nonprofit center devoted to the study of CFS. The lead author, Dr. Judy A. Mikovits, believes that this study, which found the retrovirus in only 3.7% of healthy subjects, finally proved that the syndrome was an infectious disease. This retrovirus is in the same family of viruses as HIV. Like Acquired Immune Deficiency Syndrome (AIDS), there may be underlying factors that make one prone to systemic infection by this RNA retrovirus. A retrovirus is composed of RNA, unlike a virus, which is usually composed of DNA. A xenotropic virus is a retrovirus that does not produce disease in its natural host, but replicates in cells derived of a different species, and the term murine relates to a family of animals, Muridae, related to mice. Leukemia, or cancer of the blood cells, has long been researched in light of a viral cause, and scientists agree that XMRV retrovirus is likely an oncovirus (causing cancer) via paraendocrine (hormonal) actions. The fact that this retrovirus in located in blood cells would explain the many symptoms found in chronic fatigue syndrome, and the hormonal relationship of its RNA expression would also explain some of the mysteries of CFS. This retrovirus was discovered in cancerous prostate tissues and was found in 40% of men with a specific cell mutation (R462Q). A retrovirus is very difficult for the immune system to target, and a retrovirus carried in blood cells would be even more difficult for our immune system to remove. A subsequent study of XMRV in a CFS patient population at Brigham and Women's Hospital in Boston, Massachusetts, found no evidence of XMRV in 293 diagnosed patients, and in 2011 two more prominent studies, one from the University of California in San Francisco, also found that CFS patients previously tested positive for XMRV now revealed no trace of the virus in their blood, and that the retrovirus may actually be a recombination of two mouse leukemia viruses created accidentally in the initial laboratory experiments. Still, the author of these studies stated that it would be wrong to surmise that CFS is not an infectious disease, especially as CFS patients appear to have signs of a robust immune response. A Th2 dominant immune cytokine response in CFS patients reveals the potential variety of underlying disease mechanisms possible in this elusive and confusing syndrome, including a superantigen response and an autoimmune like response. This demonstrates the need for a broad array of therapeutic strategies in treatment of CFS/EM and demonstrates the difficulty of allopathic medicine in devising specific cures.
  • Investigations into XMRV retrovirus in CFS patients has led investigators to identify other related retroviruses that may be tied to CFS pathophysiology and cause. Research in 2010 at the Center for Biologics Evaluation and Research at Bethesda, Maryland (Lo SC et al, Proc Natl Acad Sci USA. 2010 Sep 7;107(36):15874-9) tested the blood of over 100 patients diagnosed with CFS and found that polymerase chain gene sequencing revealed a genetically diverse group of murine leukemia virus (MLV) related viruses in the blood samples. These MLV-related viruses occurrred in 86.5% of the CFS blood samples compared to only 6.8% of the blood samples of healthy controls. This confirms that these more unusual viruses are related to the pathology of CFS/ME, but that the subject of deep viral illness and effects in chronic disease are complex. Viruses are not living cells, but bits of genetic material encapsulated by protein and lipid membranes. The diversity of genetic variance and mutability of viruses and retroviruses is considerable, and constantly changing. The ability of allopathic pharmacological medicine to find specific chemicals to target this complex viral threat is unlikely. On the other hand, nature has evolved, and continues to evolve, many biochemicals that protect both plants and animals from this ocean of diverse strains of pathogenic viruses and retroviruses. This is the most compelling reason to utilize herbal medicine.
  • Investigation of Chronic Fatigue Syndrome (CFS) has led researchers to evaluate the long-term effects of comorbid conditions, not isolation of individual causes. Large studies have determined that about 75 percent of CFS patients are female, and that incidence of chronic low-grade infection is much higher in CFS patients. Microbial infection with Myocoplasma species, Chlamydia pneumoniae, and HHV-6 are predominant in many studies, and the effects of multiple co-infections are being investigated to explain the neurohormonal immunological dysfunctions, as these low-grade chronic co-infections are seen at a much higher rate in CFS patients than in the general population. Multiple Mycoplasma infections were seen in a high percentage of CFS patients, and Mycoplasma fermentans and Mycoplasma hominis were the most common species. Mycoplasma species are commonly found in the urogenital tract, intestines and oral cavity, and are found to have a more complex relationship with the immune system, effectively evading host immune responses, and penetrating into the blood circulation to colonize in organs and tissues. Mycoplasmas have been linked to rheumatoid arthritis, systemic lupus erythematosis, demyelinating neuropathies, and chronic respiratory conditions, all of which have a predominance of female incidence. Mycoplasmas are also synergistic with other microbial infections. Mycoplasmas are a genus of small bacteria that lack a cell wall, and thus many common antibiotics, which target the bacterial cell wall, are ineffective at controlling Mycoplasma infection. Mycoplasmas may become parasitic, and may be seen systemically in women more than men due to the short urethra and higher incidence of chronic urogenital tract infection. Some of these common types of Mycoplasma seen in CFS are also seen in cancer cells, including M. fermentans, M. genitalium, M. penetrans, and M. hyorhinis.
  • Fibromyalgia and Chronic Fatigue Syndromes linked: recent studies show that there is a strong link of these syndromes in the subclinical hormonal deficiencies and immunological changes linked to endocrine, or hypothalamic dysfunction. The hypothalamus/pituitary is the central command center of the endocrine system, producing hormones that stimulate other hormone production in a feed back system. The hypothalamus is directly linked to the limbic system in the brain, which is intimately tied to emotional responses as well as many regulatory mechanisms.
  • Fibromyalgia has been identified as a central nervous system sensory problem and past theories of definition of it as an inflammatory disorder or myofascial syndrome have been discounted, although concurrent myofascial disorder and chronic inflammatory states may occur. The recent evidence points to a link of the pain sensory nervous system dysfunction to both the serotonin and estradiol systems in the central nervous system (brain and spinal cord). Regulatory mechanisms of pain sensation are controlled by chemical gates that respond either to levels of serotonin or estradiol in the brain and spinal cord. These systems are also linked to a variety of regulatory mechanisms involved in the regulation of immune responses, inflammatory regulation, mood, sleep and the autonomic nervous system. Imbalance in this complex system would create the variety of symptoms seen in fibromyalgia and chronic fatigue syndromes. These syndromes have always disproportionately affected women, and a link to the female hormone balance has been investigated since the 1920's. You should go to fibromyalgia on this website to explore further.
  • Myalgic encephalomyelitis: this means that a chronic inflammatory state in the brain stem and spinal cord may be responsible for the pain sensation throughout the body. The GABA neurotransmitter is responsible for much pain modulation, which allows us all to function without the sensation of pain. To understand this, we must realize that pain is a neurological signal set off by threshold excess of a variety of normal chemicals in the body. Pain is not the actual injury. Tissue injury causes accumulation of chemicals that trip the pain signal. This pain signal may occur when these signals are not properly modulated by a variety of neurochemicals. Both the neurotransmitters and inflammatory mediators play a big role in this complex biochemical process. When something is out of balance pain signals may arise where they shouldn't. When something is chronically out of balance, the body sometimes reacts badly.
  • Candida is a common symbiotic microorganism in the human body, usually acting as a yeast that helps ferment food in the small intestine, and produces nutrient byproducts in the process. Unfortunately, when the complex balance of microorganisms in the intestinal tract is upset, candida may overgrow and many candida may assume its second form, which is a branching, or hypal, fungus, and cause an array of problems, not the least of which is a chronic fatique syndrome that is multifactorial, or attributed to a number of health problems generated by candidiasis. Systemic candidiasis may be the link between irritable bowel syndrome, chronic fatique, and aldehyde toxicity. Candida casts are found in about 65% of the feces samples of the population, and some scientists believe that the other 35% may have an immune and clearing response that eliminates the candida before it is excreted, with perhaps 100% of humans having a symbiotic commensal relationship with candida. Adverse pathology would occur only when the Candida overgrows in the hyphal, or fungal, form and disseminates in the blood or lymph. Candida is the fourth most common infectious agent found in blood samples in hospitals when sepsis is examined, and is thus not easily dismissed as a potential systemic pathogen. Overgrowth of candida may produce fatigue in a variety of ways, but the chief mechanism is the excess amount of acetaldehyde that is produced from activity of candida. Acetaldehyde is a common chemical in our bodies, but excess, or poor rate of catabolism, causes such symptoms as we see in an alcohol hangover. In a hangover, excess alocohol that is insufficiently processed by the liver results in an excess of the alcohol byproduct acetaldehyde, and this excess acetaldehyde is thought to produce most of the symptoms of the hangover. Chronic fatigue may be thought of as a chronic hangover. But a number of other mechanisms of candidiasis will also contribute to chronic fatigue, including CNS dysfunction, hormonal dysfunction, and immune dysfunction. The increased stress on the organism from this array of dyfunctions is also tiring. You may go to the article on Candida on this website to learn more.
  • Giardias are microscopic parasitic organisms called protozoa, and have become more prevalent in urban environments and water supplies as modern farming methods have promoted ill health of feedlot animals, especially with overuse of antibiotics and unhealthy biota. Giardiasis, usually the infection by Giardia lamblia in the small intestine, often produces symptoms after 1-2 weeks of infection, with abdominal bloat, diarrhea, excess gas, and upset stomach. Although these symptoms often resolve in 6-8 weeks, chronic cases of Giardiasis may explain many cases of Irritable Bowel Syndrome. A study, published in 2012 at the Institute of Clinical Medicine of Haukeland University Hospital in Bergen, Norway, after a large community outbreak of Giardiasis, followed 96 patients with long-lasting post-infectious fatigue after giardiasis, with 60 percent eventually diagnosed with Chronic Fatigue Syndrome. Of the total 1262 patients diagnosed with Giardiasis, 5 percent developed Chronic Fatigue Syndrome (PMID: 22316329). The Department of Public Health, and the University of Bergen, Norway, also had conducted a long-term study of patients afflicted with Giardia lamblia infection, and concluded that "infection with Giardia lamblia in a non-endemic area was associated with a high prevalence of IBS (Irritable Bowel Syndrome) and chronic fatigue 3 years after acute illness, and the risk (for CFS and IBS) was significantly higher than in the control group." These experts stated that Giardia lamblia is a common cause of gastroenteritis worldwide, and the potential consequences of giardiasis are more serious than previously known (PMID: 21911849). Many cases of CFS could be explained by parasitic Giardia infection. To read more about parasitic disease, go the article on this website entitled Parasites and Parasitic Disease.
  • Vagus Nerve Infection is a more recent addition to the theories that may explain at least some of the varied presentations in ME/CFS. In 2013, researchers at Tufts University and Massachusetts General Hospital, in Bedford and Boston, Massachusetts, U.S.A. hypothesized that the unique chemoreceptors on the vagus nerve may be responsible for initiating the responses of fatigue and malaise, myalgia and depression, and that persistent low-grade infections, perhaps a combination of viral, fungal, parasitic and/or bacterial, may persistently stimulate this sickness response to the CNS from the vagal nerve dysfunction. The vagus nerve is the tenth of twelve cranial nerves, leading from the medulla and brainstem to the stomach, intestines, lung and heart. Sensory neural aspects of the vagus nerve link to the trigeminal nucleus, and are involved with perception of touch, pain and temperature affecting the throat, face, scalp and ears. The vagal system is also intimately connected to the autonomic nervous system, explaining the many visceral and uncontrolled symptom manifestations. Vagal nerve disorders are the subject of an increasing array of studies, linking the vagal system to tinnitus, gastrointestinal disorders, and tachycardia/fibrillation. Autonomic dysfunction associated with the vagal system has been linked to vasovagal syncope, and reductions in heart rate and blood pressure, as well as episodes of poor urinary control, and may be stimulated by emotional distress.
  • Somatoform Disorder is again being recognized as a very prevalent problem, yet once again denied in diagnosis and treatment due to the inherent difficulties in both understanding and reaching a diagnosis, and in the lack of simple, and profitable, treatment strategies. Somatoform Disorders are defined as a group of psychological disorders marked by physical complaints for which no organic or physiological explanation is found. The somatic, or physical, symptoms are real in Somatoform Disorders, yet thorough testing does not uncover the causes. A great many patients unfortunately arrive at this point in the differential diagnostic process, yet rarely is a diagnosis of Somatoform Disorder even considered. In the United States, a systematic exclusion of competent cognitive and behavioral psychotherapy has occurred, and has been linked to a massive campaign by the pharmaceutical industry to promote chronic drug dependency and deny psychological therapy and counseling. Often, when the symptoms of a somatic syndrome are still mild, the medical doctor attributes these symptoms to stress, which is a pathetic and nonspecific explanation. While various physical, mental and emotional stresses may precipitate a somatic disorder, this is not a useful diagnosis. The disease process is real and studied in somatic disorders and should be treated with the same degree of seriousness and attention as all other diseases. A Mind-Body approach to both understanding somatic symptoms and correcting them should be applied. Often, simply gaining objective understanding of the somatic process allows the patient to heal, with neurological adaptation and focus on actual corrections of the problem. This process must involve a more holistic course of therapy than simply taking a pill and ignoring the problem, though. Whether the Somatoform Disorder starts as a Body Dysmorphic Disorder in youth, a Somatic Pain Syndrome after an injury, emotional or physical trauma, or a Somatisation Disorder, where emotional constraint may lead to physical dysfunction, the patient needs to understand the mechanisms involved and work holistically to resolve them. Here, Complementary Medicine provides time intensive integrative care that can be very useful in the treatment protocol.
  • Mitochondrial Disease: in the last few years, the diagnosis of mitochondrial disease has become an accepted theory for inexplicable cases of chronic fatigue, especially with advancement of genetic testing. The mitochondria are a part of every human cell that generate much of the energy, and have their own DNA, symbiotic to the human DNA of the cell. This is because the mitochondrial were a microbial friend that got conscripted into our human cells at an early stage of evolution. These disorders are a large group of somewhat rare disorders that may be caused by a mutation of mitochondrial genes, or not. The mitochondrial DNA or RNA may be mutated, and hence the tests may be negative but not rule out a mitochondrial disease, which is called a false negative. While the government websites of the CDC still imply that these are childhood diseases related to autism, research has confirmed that adults often are afflicted as well. While one may see reports that these mitochondrial diseases indicate various specific pathologies, and organ systems, the truth is apparent that mitochondrial diseases are widely varied and no specific presentation can be used as a definition of mitochondrial disease. This type of expansive diagnostic criteria of course presents a problem in standard medicine, which does not like anything to exist outside of a box, and does not like it when there is not a specific treatment that addresses most of the disorders. Mitochondrial disease is another set of disorders that demand a more complex holistic approach in treatment. The hallmarks of many of these mitochondrial disorders are muscle weakness that may come and go in episodes, exercise intolerance, ataxia (difficulty with gait and walking), spasticity, drooping eyelids, lactic acidosis, and CNS disorder. The array of causes is still listed as unknown, but some evidence now points to an array of drugs that may cause mitochondrial dysfunction and mutation, as well as heavy metal toxins in the environment. and as oxidative stress. In 2014, the U.S. CDC mentioned vaccines as a potential cause of some cases in childhood, and the strong denial of proof, as well as the mere mention has led many to suspect vaccines as a potential cause, which is not explored or elucidated, and may never be. The diagnosis with molecular genetic testing will only occur when the condition becomes severe, and the complexity is so great that these tests may be negative, yet the patient may still have a mitochondrial disease. In this case, the use of MRI with magnetic resonance spectroscopy (MRS) and exercise testing may be used to measure the degree of muscle lactidosis, or lactate in the blood circulation after exertion. Diabetes is often associated. There is no specific treatment other than support therapies. Of course, one may just bypass all of this frustrating diagnostic runaround, and start treating the disorder, if suspected, immediately with Complementary and Integrative Medicine. This is sensible. Studies have indicated that ATP cofactors of Vitamin B2 and B3, CoQ10, and D-ribose may benefit, but of course, the research and clinical trials of acupuncture and other herbal and nutrient medicine are years away. In general, improved health will alleviate the stress that adds to flare-ups, and resolution of chronic inflammatory problems will help as well.