The diagnosis of Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS) is generally based upon subjective measures reported by patients (e.g. fatigue and physical functioning) and has been marred by much controversy. For successful diagnosis, the patient must therefore rely on the recognition of particular signs and symptoms by an astute and highly qualified practitioner.
Given the controversy that still exists with some practitioners (those who refuse to acknowledge ME/CFS as a biological illnesses), the need for established biomarkers for the development of validated diagnostic criteria is undoubtedly of huge importance to sufferers. Encouragingly, and despite subjective and unclear criteria and measures, research has observed specific abnormalities in ME/CFS repetitively; immunological abnormalities, oxidative and nitrosative stress, neurological anomalies, circulatory deficits and mitochondrial dysfunction.
Immune signatures and ME/CFS
The most recent addition comes from a US research team, who published their findings in the February edition of the journal ‘Science Advances’, led by Mady Hornig and Ian Lipkin. The team tested blood samples from nearly 300 ME patients and 350 ‘healthy’ people. They found that those who had suffered from ME for three years or less had increased amounts of inflammatory cytokines and particularly high levels of interferon gamma (IFN-g), which has been linked to the fatigue people feel following a viral infection like flu. Interestingly, the group reported that the distant alterations in the plasma immune ‘signatures’ observed in those individuals in the early course of the illness were not present in the subjects who had suffered for a longer duration.
What does this tell us?
Firstly, it is important to note that this is not the first study to report increased cytokine patterns in ME/CFS. Maes and co-workers reported increased levels of interleukin (IL)-1 and tumor necrosis factor, (TNF) whilst Fletcher and co-workers reported altered levels of several cytokines including IL-1α and IL-1β (but normal levels of TNF). The significance of the findings reported by Hornig and colleagues concerns the marked differences in cytokine patters in suffers at different stages of the condition as it progresses. Indeed, the strong correlation of cytokine alterations observed with illness duration, rather than with illness severity, implies that the immunopatholgy of ME/CFS is not static. Simply put, healthy patients and those who had had the disease for longer than three years did not show the same cytokine pattern.
Lead author Dr Mady Hornig states, “It appears that ME/CFS patients are flush with cytokines until around the three-year mark, at which point the immune system shows evidence of exhaustion and cytokine levels drop.” This shows there are distinct stages to the disease; when the cytokine response starts to settle down, the disease also appears to quieten down.
Targeting pro-inflammatory cytokines
As many as 60% of ME/CFS patients suffer from autoimmune responses that are directly linked to a wide range of reported abnormalities. Cytokines are directly affected by eicosanoids – hormone-like substances derived from long-chain polyunsaturated fatty acids (PUFA) – and treatment targeted at normalising pro-inflammatory cytokines therefore seems plausible as an early intervention. Dietary supplements containing the eicosanoid-regulating fatty acids eicosapentaenoic acid (EPA) and omega-6 gamma-linolenic acid (GLA) are well documented to improve many of the symptoms associated with ME/CFS.
EPA & GLA regulate inappropriate autoimmune responses observed in ME/CFS
The persistent viral infection associated with ME/CFS appears to impair the ability of sufferers to manufacture adequate amounts of omega-6 and omega-3 PUFA by inhibiting the activity of delta-6 desaturase, the enzyme required in the process of making these key fats. Given their role in immune and inflammatory function (amongst many others), the low levels observed in ME/CFS  impairs the proper functioning of cell membranes, including cell signalling, and has an adverse effect on the synthesis of eicosanoids from dihomo-gamma-linolenic acid (DGLA) and EPA, thereby explaining some of the symptoms associated with ME/CFS. Bypassing delta-6 desaturase with GLA and EPA normalises fatty acid levels, whist also providing the building blocks required for anti-inflammatory cytokine production. Given that at even relatively low concentrations EPA is directly virucidal, the benefits derived from pure EPA and GLA may offer great potential therapeutically.
Vegepa and the management of ME/CFS
Increasing evidence suggests an inappropriate immune response is linked to the progression of ME/CFS. The most recent evidence suggests that there is a phasic nature to the condition, with high inflammation a key feature in the early stages. Treatment with EPA and GLA as part of a nutrition protocol can result in significant improvement in symptoms, most likely via virucidal effects and the reduction of key pro-inflammatory products such as IFN-g. Vegepa provides purified, high-strength pure EPA combined with GLA and has been shown to be highly successful as an adjuvant treatment for ME/CFS and recommended by top CFS/ME specialists including Sarah Myhill and Professor Basant Puri.
Research continues to outline the complexity of the causes and mechanisms related to ME/CFS. Undoubtedly a complex and chronic condition, identifying biomarkers related to ME/CFS will help towards successful diagnosis. Until such time, practitioners must rely on treating the core symptoms with interventions aimed at ‘treating’ those existing players, namely; immunological abnormalities, oxidative and nitrosative stress, neurological anomalies, circulatory deficits and mitochondrial dysfunction.
- Twisk FN: The status of and future research into Myalgic Encephalomyelitis and Chronic Fatigue Syndrome: the need of accurate diagnosis, objective assessment, and acknowledging biological and clinical subgroups. Frontiers in physiology 2014, 5:109.
- Maes M, Twisk FN, Ringel K: Inflammatory and cell-mediated immune biomarkers in myalgic encephalomyelitis/chronic fatigue syndrome and depression: inflammatory markers are higher in myalgic encephalomyelitis/chronic fatigue syndrome than in depression. Psychotherapy and psychosomatics 2012, 81:286-295.
- Fletcher MA, Zeng XR, Barnes Z, Levis S, Klimas NG: Plasma cytokines in women with chronic fatigue syndrome. Journal of translational medicine 2009, 7:96.
- Puri BK: The use of eicosapentaenoic acid in the treatment of chronic fatigue syndrome. Prostaglandins Leukot Essent Fatty Acids 2004, 70:399-401.
- Maes M, Mihaylova I, Leunis JC: In chronic fatigue syndrome, the decreased levels of omega-3 poly-unsaturated fatty acids are related to lowered serum zinc and defects in T cell activation. Neuro endocrinology letters 2005, 26:745-751.
- Puri BK: Long-chain polyunsaturated fatty acids and the pathophysiology of myalgic encephalomyelitis (chronic fatigue syndrome). Journal of clinical pathology 2007, 60:122-124.