The Institute for Molecular Medicine








Chronic Fatiguing Illnesses Research

Prof. Garth L. Nicolson

Chronic Fatigue Syndrome, Fibromyalgia Syndrome and Other Fatigue Conditions

Chronic fatigue is reported by 20% of all patients seeking medical care and is considered as a nonspecific sign that is associated with many well known medical conditions. Chronic Fatigue Syndrome (CFS), Myalgic Encephalomyelitis (ME), and Fibromyalgia Syndrome (FMS) patients suffer from complex overlapping signs and symptoms. (see 'Signs/Symptoms' Questions, above) CFS is primarily characterized by persisting or relapsing fatigue without previous history of comparable symptoms that does not resolve with rest. In these patients other clinical conditions are absent that can explain the signs and symptoms such as malignancies or autoimmune diseases. In contrast, FMS patients have overall muscle pain, tenderness, and weakness as primary complaints, but they have most if not all of the commonly found signs and symptoms for CFS. We previously proposed that CFS/ME patients might be suffering from chronic infections that can cause, in part, their complex signs and symptoms. For example, systemic mycoplasmal infections can cause chronic fatigue, muscle pain and a variety of additional signs and symptoms, some of which are related to dysfunctional immune responses and in extreme cases autoimmune-like disorders. Some mycoplasmas can invade virtually every human tissue and can compromise the immune system, permitting opportunistic infections by other bacteria, viruses, fungi and yeast. When mycoplasmas exit certain cells, such as synovial cells, nerve cells, among others that can be infected, they can stimulate autoimmune response. Our recently published studies demonstrated a possible link between mycoplasmal infections and CFS and FMS, since we found high frequencies of mycoplasmal infections in these patients. Previously we examined patients with chronic illnesses for the presence of mycoplasmal infections. We found that about one half of patients with Gulf War Illness and two third of patients with CFS/ME and FMS were positive for mycoplasmal infections in their blood. The Gulf War Veterans suffer from signs and symptoms similar to patients diagnosed with CFS and FMS. They can be treated using antibiotics effective against mycoplasmal infections, and once they recover, their blood is no longer positive for the presence of mycoplasmal infections. Our recent results indicate that Rheumatoid Arthritis is also associated with mycoplasmal infections. (see 'Autoimmune Diseases')

Recent reports and publications indicate that in addition to mycoplasmal infections, CFS/ME and FMS patients have other chronic infections caused by other intracellular bacteria and viruses. For example, patients with Lyme Disease, caused by intracellular Borrelia infections, have been diagnosed with CFS/ME. Also, CFS/ME and FMS patients can have intracellular Chlamydia species infections. These patients can also have infections by other bacteria that enter their bodies through 'leaky gut' problems. Chronically ill patients often have inflammatory bowel syndrome and other gut problems, and this can allow pathogenic bacteria to enter their systems.

Patients with CFS/ME and FMS can also have viral infections that complicate their conditions and cause morbidity. Such infections can occur with or without the bacterial infections described above. Viruses that have been associated with CFS/ME and FMS are Human Herpes Virus-6 (HHV-6) and Cytomeglovirus (CMV). These viruses have been found at high incidence in chronically ill patients, and especially those with CFS/ME. Patients with CFS/ME or FMS can have predominantly intracellular bacterial infections, predominantly viral infections, or a combination of intracellular bacterial and viral infections. This may be one reason why the underlying causes of these chronic illnesses are so difficult to determine and effectively treat. The other reason could be the persistent nature of the infections and their ability to hide inside cells where they are essentially refractory to immune system responses, their slow growing natures and their relative insensitivity to therapeutic drugs (see references below).

A new direction at the Institute is studying the role of decreased cellular energy in causing fatigue.  Cellular energy is mainly produced by the mitochondria, subcellular organelles that contain the machinery that converts fats and sugars to energy in the form of the high-energy molecules, such as ATP.  Mitochondrial function requires an intact inner membrane where the electron transport chain or energy machinery is located.  When the inner mitochondrial membrane is damaged, the efficiency of the electron transport chain is reduced along with the ability of cells to produce the energy that they need for vital functions—thus fatigue becomes a problem.   Various environmental insults and even aging produce excess oxidation molecules that can damage the mitochondrial membrane, including chronic infections of the type mentioned above.  At the Institute for Molecular Medicine clinical studies have shown the benefits of dietary membrane lipids (Lipid Replacement Therapy) in replacing damaged mitochondrial membrane lipids, increasing the efficiency of the electron transport chain, increasing energy and reducing fatigue.  A number of non-pharmaceutical approaches to decreasing fatigue are being investigated at the Institute.


  • Membrane Lipid Replacement—a functional approach to repairing cellular membranes, reducing symptoms, and restoring function, by Nicolson GL. Functional Food Science 2022; 2(8): 198-204. pdf_doc

  • Aging and chronic illnesses: Membrane Lipid Replacement for restoring mitochondrial function and reducing fatigue, pain, and other symptoms in aged individuals, by Nicolson GL, Breeding PC. Settineri R, Ferreira de Mattos G. Bioactive Compounds in Health & Disease 2020; 3(10): 194-203. pdf_doc

  • Membrane Lipid Replacement: reduction of pain, fatigue, gastrointestinal and other symptoms in patients with peripheral pain: case reports, by Nicolson GL, Breeding P. Journal of Healthcare & Prevention 2020; 3(2): 1-4. pdf_doc

  • An integrative model of chronically activated immune-hormonal pathways important in the generation of fibromyalgia, by Paul C. Breeding, Nancy Russell and Garth L. Nicolson. Brit. J. Medical Practitioners 2012; 5(3): a524-a534. pdf_doc

  • Considerations When Undergoing Treatment For Gulf War Illness/Chronic
    Fatigue Syndrome, Fibromyalgia Syndrome, Rheumatoid Arthritis And Other
    Autoimmune Illnesses
    Reprinted from the International Journal of Medicine 1998;
    1:123-128. Supplemental Suggestions: Prof. Nicolson 1/15/11

  • Mitochondrial dysfunction and chronic disease: treatement with natural supplements, by Prof. Garth Nicolson, Alternative Therapy in Health nd Medicine 2013; 19: e5027 [Epub ahead of print]. pdf_doc

  • Lipid Replacement Therapy with a glycophospholid formulation with NADH and CoQ10 significantly reduces fatigue in intractable chronic fatiguing illnesses and chronic Lyme disease, by G.L. Nicolson, R. Settineri, R. and R.R. Ellithorpe, International Journal of Clinical Medicine 2012; 3(3): 163-170, pdf_doc

  • An integrative model of chronically activated immune-hormonal pathways important in the generation of fibromyalgia, by P.C. Breeding, N.C. Russell and G.L. Nicolson, British Journal of Medical Practitioners 2012; 5(3): a524-a534. pdf_doc

  • Lipid Replacement Therapy Drink Containing a Glycophospholipid Formulation
    Rapidly and Significantly Reduces Fatigue While Improving Energy and
    Mental Clarity,
    by R. Ellithorpe, R. Settineri, C. Mitchell, B. Jacques,
    E. Ellithorpe, and G. L. Nicolson, Functional Foods in Health and Disease,
    2011; 8: 245-254.

  • Chronic Fatigue Syndrome Patients Subsequently Diagnosed with Lyme Disease Borrelia burgdorferi: Evidence for Mycoplasma species Co-Infections - by Garth L. Nicolson, PhD, Nancy L. Nicolson, PhD and Joerg Haier, MD, PD, Journal of Chronic Fatigue Syndrome 2008; 14(4):5-17. - pdf doc

  • Metabolic Syndrome and Mitochondrial Function: Molecular Replacement and Antioxidant Supplements to Prevent Membrane Peroxidation and Restore Mitochondrial Function, Garth L. Nicolson, Journal of Cellular Biochemistry 2007; 100: 1352-1359. pdf doc

  • Lipid replacement and antioxidant nutritional therapy for restoring mitochondrial function and reducing fatigue in chronic fatigue syndrome and other fatiguing illnesses, by Nicolson and Ellithorpe, Journal of Chronic Fatigue Syndrome 2006; 13(1): 57-68. pdf doc

  • Evidence for Brucella spp. And Mycoplasma ssp. Co-Infections in Blood of Fatigue Syndrome Patients, by Nicolson et al., Journal of Chronic Fatigue Syndrome 2005; 12(2): 5-17.  pdf doc

  • Multiple co-infections (Mycoplasma, Chlamydia, human herpes virus-6) in blood of chronic fatigue syndrome patients: association with signs and symptoms. By G. L. Nicolson et al., Acta Pathol. Microbiol. Immunol. Scand.(APMIS) 2003; 111: 557-566. pdf doc

  • Evidence for Bacterial (Mycoplasma, Chlamydia) and Viral (HHV-6) Co-Infections in Chronic Fatigue Syndrome Patients by G.L. Nicolson et al., Journal of Chronic Fatigue Syndrome 2003; 11(2):7-20. pdf doc

  • High Prevalence of Mycoplasma infections among European Chronic Fatigue Syndrome patients. By J. Nijs et al., FEMS Immunol. Med. Microbiol. 2002; 34:209-214. pdf doc

  • Diagnosis and integrative treatment of intracellular bacterial infections in Chronic Fatigue and Fibromyalgia Syndromes, Gulf War Illness, Rheumatoid Arthritis and other chronic illnesses. by G.L. Nicolson et al., Clin. Pract. Alt. Medicine 2000; 1(2): 92-102 pdf doc

  • Role of Mycoplasmal Infections in Fatigue Illnesses: Chronic Fatigue and Fibromyalgia Syndromes, Gulf War Illness and Rheumatoid Arthritis, by G.L. Nicolson et al., J. Chronic Fatigue Syndr. 2000; 6(3/4):23-39 pdf doc

  • Identification And Treatment Of Chronic Infections In CFIDS, Fibromyalgia Syndrome And Rheumatoid Arthritis, by G.L. Nicolson, CFIDS Chronicle 1999; 12(3): 19-21 pdf doc

  • Multiple Mycoplasmal Infections Detected in Blood of Chronic Fatigue Syndrome and Fibromyalgia Syndrome Patients, Eur. J. Clin. Microbiol. Infect. Dis. 1999 ; 18 : 859-865 pdf doc

  • Mycoplasmal Infections in Chronic Illnesses: Fibromyalgia and Chronic Fatigue Syndromes, Gulf War Illness, HIV-AIDS and Rheumatoid Arthritis, by G.L. Nicolson et al., Med. Sentinel 1999; 4: 172-176  pdf doc

  • The Pathogenesis and Treatment of Mycoplasmal Infections, by G.L. Nicolson et al., Antimicrob. Infect. Dis. Newsl. 1999; 17(11) : 81-88 pdf doc

*PDF files can be opened by obtaining a free copy of Adobe Acrobat from:



  • Fatigue, Immunity and Inflammation: their resolution using natural medicine, by M. Ash, R. Settineri and G.L. Nicolson. Townsend Letter 2012; 352(10): 48-51. pdf_doc

  • Finally an answer to the most common medical complaint—Fatigue, by Garth
    L. Nicolson Public Health Alert 10(10): 1-5 (2011).

  • Mycoplasmas: the Missing Link in Fatiguing Illnesses by Michael Guthrie Alternative Medicine; 2001; Sept: 60-70. rtf doc

  • Research Overview: Professor Garth Nicolson's Studies and Treatments Explained By Deborah Cooper, ImmuneSupport.com Treatment & Research Library rtf doc

  • CFS National Radio Program 11/21/00 with Dr. Roger G. Mazlen interviewing Prof. Garth Nicolson  rtf doc

  • The Role of Chronic Infections in the Maintenance and Progression of Chronic Fatigue Syndrome, Fibromyalgia Syndrome, Rheumatoid Arthritis, Immune Deficiency Syndromes and Gulf War Illness, by G.L. Nicolson et al., ME/CFS Congress, Sydney, Australia, 1999 rtf doc

  • Identification and Treatment of Chronic Infections in CFIDS, Fibromyalgia Sydrome and Rheumatoid Arthritis Patients that Cause Morbidity and Illness Progression, by Prof. Garth Nicolson, Doctor's Educational Booklet, CFIDS Assoc. of America, 1998 rtf doc

*PDF files can be opened by obtaining a free copy of Adobe Acrobat from:



back to the top