Low-grade inflammation in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS); treatment by palmitoylethanolamide supplement (PeaPure)


Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): a disorder difficult to understand for many, especially for doctors who too often think this disorder does not exist. Well it does! Modern neurobiological research clearly found new insights in the cause of this disease. New findings point out that inflammatory pathways and immunity derangements play an important role in the pathophysiology of Myalgic Encephalomyelitis or Chronic Fatigue Syndrome (ME/CFS).

Signs of low-grade inflammation, including increased levels of inflammatory markers, such as cytokines, are known to induce fatigue and many somatic symptoms, frequently seen in ME/CFS patients. These serum markers for low-grade inflammation, such as IL-1, TNFα, neopterin and lysozyme are all significantly higher in Individuals with ME/CFS  than in controls.

It is also known that such Increased parameters (IL-1 and TNFα) are significantly correlated with fatigue, sadness, autonomic symptoms, and a flu-like malaise. Furthermore in many ME/CFS patients the primary cause seems to be a flu-like infection which lingers (1-2)

Natural treatment against lingering inflammation such as in ME/CFS

Palmitoylethanolamide (PeaPure)

Palmitoylethanolamide (PeaPure)

Treatment with the natural anti- inflammatory compound palmitoylethanolamide (PeaPure) therefore seems a useful option, the more so, as palmitoylethanolamide has been proven to be active against flu and viral-induced infections/inflammations in 6 clinical trials, in a total of nearly 3000 patients (3-4).

Furthermore, PEA has been used in many patients suffering from fibromyalgia and related disorders. More and more the medical community starts to appreciate the documented safety and efficacy of this endogenous compound (3-6)

PeaPure is a supplement easily obtainable via the internet, also in the USA; PJ’s Prescription Shoppe is a compounding pharmacy in San Diego that carries PeaPure. They order from the Netherlands.

Dose recommendations of PeaPure

Dose recommendation: start with 1200 mg daily in 2 to 3 doses (e.g. 2 capsules after breakfast and 1 capsule after diner).

PEA is the body’s own modulator and anti-inflammatory compound, and not a painkiller such as NSAIDs and morphine. PEA does therefore mostly need some weeks to slowly bring the body in balance on a number of biological levels. As PEA has a number of modulating effects, both on the short term as well as slowly increasing, there are patients experiencing quick symptom relief within some days. There are also patients who need more time (especially in chronic pain situations). Therefore the recommendation is to test the efficacy of PEA during two months in cases of chronic pain or chronic inflammation such as in ME/CFS before deciding on its efficacy.

If symptoms of ME/CFS decreases more than 30% one can reduce the dose of PeaPure to 2 times 400 mg. If symptoms increases under PeaPure treatment, as some chronic pain or inflammation syndromes sometimes waxes and wanes (given the weather, given exercise, food, etc) it is recommended to increase the dose to 800 mg twice daily.


1. J Maes M, Twisk FN, Kubera M, Ringel K. Evidence for inflammation and activation of cell-mediated immunity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): increased interleukin-1, tumor necrosis factor-α, PMN-elastase, lysozyme and neopterin. Affect Disord. 2012 Feb;136(3):933-9. doi: 10.1016/j.jad.2011.09.004. Epub 2011 Oct 4.

2. Morris G, Berk M, Galecki P, Maes M.. The Emerging Role of Autoimmunity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/cfs).Mol Neurobiol. 2013 Sep 26.

3. Keppel Hesselink, J.M. 2012. New Targets in Pain, Non-Neuronal Cells, and the Role of Palmitoylethanolamide. Open Pain Journal 5: 12-23

4. Keppel Hesselink, J.M., Hekker, T.A. 2012. Therapeutic utility of palmitoylethanolamide in the treatment of neuropathic pain associated with various pathological conditions: a case series Journal of Pain Research 5:437 – 442

5. Keppel Hesselink JM, Kopsky DJ, Treatment of chronic regional pain syndrome type 1 with palmitoylethanolamide and topical ketamine cream: modulation of nonneuronal cells. Journal of Pain Research 2013

4. Keppel Hesselink, J M,  Tineke de Boer, and Renger F. Witkamp. Review Article. Palmitoylethanolamide: A Natural Body-Own Anti-Inflammatory Agent, Effective and Safe against Influenza and Common ColdInternational Journal of Inflammation Volume 2013 (2013), Article ID 151028, 8 pages http://dx.doi.org/10.1155/2013/151028

6. Keppel Hesselink JM. Chronic idiopathic axonal neuropathy and pain, treated with the endogenous lipid mediator palmitoylethanolamide: a case collection. International Medical Case Reports Journal Published Date September 2013 Volume 2013:6 Pages 49 – 53

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