Information for specialists and GP’s: Palmitoylethanolamide

Palmitoylethanolamide is a safe painkiller. We have established that all Dutch PEA capsules that have been clinically tested and described in medical journals are safe and effective, as long as they carry the PEA-opt quality marker.

Palmitoylethanolamide: choose natural pain relief

Palmitoylethanolamide (PEA) has been available as a supplement in the Netherlands since 2010.

PEA is a pain relieving substance that has been extensively researched during numerous clinical studies. You can find several summaries of these among the references below.

In 2015 a peer reviewed pain journal discussed the largest clinical PEA study and its effectiveness (the calculated NNT was 1.5).

PEA is the foundation of our self-healing ability.

Because PEA is a supplement it is often unknown by doctors (not on the pharmaceutical radar).  However it is a very helpful substance against chronic pain, with proven effectiveness.

The substance was first mentioned as a natural anti-inflammatory agent (an autacoid) in 1957 (1) and as a pain relief agent in the Lancet in 1975. The working mechanisms first became clear in 1993, through the work of Nobel Prize winner professor Rita Levi-Montalcini.

Since the seventies, numerous clinical studies have been conducted on over 5000 patients about safety and effectiveness of this bodily substance. Because most of the doctors that performed these studies were not native English speakers, a lot of the research remained unpublished or only appeared in Italian and Spanish neurological journals.

This changed in 2010, when palmitoylethanolamide became available as a supplement. In the meantime (2015), over 500 articles about PEA can be found in Pubmed, including numerous ones about its clinical significance. In the references below you will find a clinical summary of all studies conducted in the area of pain relief and anti-inflammatory properties of palmitoylethanolamide. The largest placebo controlled study was conducted amongst 636 patients with severe pain due to a hernia and the results supported the findings of other studies (3). Included in the references is also a report of a number of Dutch patients with varied pain syndromes. (4).  Use of PEA can even improve mood during chronic pain.

Palmitoylethanolamide is safe to use and clearly effective with chronic pain, there are no known negative side effects. The Number Needed to Treat (NNT) of palmitoylethanolamide is 1.5.  We first presented these results at the Italian neurologist and anesthetist congress (SIAARTI) in 2011. With an NNT of 1.5, palmitoylethanolamide is an important addition to the treatment of chronic and neurological pain.

Palmitoylethanolamide: extensive reviews and source articles available

Several reviews in peer-reviewed journals are freely available on the internet and can be found under the references below. The most recent one is from 2015.

Palmitoylethanolamide: produced in the Netlerlands

Palmitoylethanolamide is available as a supplement in the Netherlands and the capsules have been produced in a Dutch GMP certified facility, and tested for purity by an independent US laboratory; can be checked here. It contains 100% pure PEA. Always choose a PEA product that has been clinically tested and described in medical literature as safe and effective.

PEA contains only the pure and natural bodily substance palmitoylethanolamide and is available in 400mg capsules. The supplement is easily obtained online, see more information under this link.

There are no negative interactions with other medicine and no known negative side effects. Palmitoylethanolamide is simply build in all cells of the body from cell fat membrane and easily broken down by the bodies enzymes in the cytoplasm, with no need of hepatic or renal clearance.

PEA can be used in combination with other analgesics.

Several formal interaction studies have been conducted with other painkillers like Pregabaline and Oxycodon, which showed that palmitoylethanolamide supported the pain relieving properties of other analgesics and the substances can be prescribed together well. Experiences with Dutch neuropathic pain patients have been described in reference 5. Reference 6 contains a summary of 6 double-blind randomized clinical studies done before the turn of the century.

PEA dosage

The starting dose is 400mg of PEA 3 times daily, with the possibility of 2 in the morning and 1 capsule in the evening. The effects are slow, as palmitoylethanolamide works through the biological modulation of the cell nucleus and some cell membrane receptors.

PEA: dose recommendations

We always advise to prescribe palmitoylethanolamide for a period of 2 months and to evaluate with the patient during that period if it is useful to continue or to quit.  Usually patients notice a pain relieving effect within 1-3 weeks, but some patients need more time. In certain cases, with insufficient medical response, it can be considered to double the dose. Doses of up to 100mg per kg of body weight can be taken without any complications. We advise not to prescribe doses higher than 30-40mg per kg of body weight, as higher doses don’t seem to give better results.

No problematic side effects have been reported. We treated thousands of patients in the Netherlands since 2011 and can vow for that.

Quality recommendations: which PEA supplement?

Since 2014 many supplements have become available of which the quality is unclear or which contain other substances. Therefore we always recommend to exclusively work with a supplement that is protected by a patented formula. Only these supplements have been proven effective by a large number of clinical studies. These include supplements by Russell Science, Greenleaves, Vitals and Epitech.

In case of any questions, GP’s and specialists can contact our Institute’s PEA specialist to discuss individual patients or indications.

Literature about PEA

  1. Kuehl, F.A., Jacob, T.A., Ganley, O.H., Ormond, R.E., Meisinger, M.A.P. 1957. The identification of N-2-hydroxyethyl-palmitamide as a natural occurring antiinflammatory agent. Journal of the American Chemical Society 79:5577-5578
  2. Aloe,L., Leon, A., Levi-Montalcini, R. A proposed autacoid mechanism controlling mastocyte behaviour. Agents and actions 1993; 39:C145–C147.
  3. Keppel Hesselink,, J.M. New Targets in Pain, Non-Neuronal Cells, and the Role of Palmitoylethanolamide. Open Pain Journal2012; 5: 12-23
  4. Keppel Hesselink, JM, Hekker, TA. Therapeutic utility of palmitoylethanolamide in the treatment of neuropathic pain associated with various pathological conditions: a case series Journal of Pain Research 2012; 5:437 – 442

5.Keppel Hesselink JM. Chronic idiopathic axonal neuropathy and pain, treated with the          endogenous lipid mediator palmitoylethanolamide: a case collection. Int Med Case Rep J.    2013 Sep 13;6:49-53. doi: 10.2147/IMCRJ.S51572.

  1. Keppel Hesselink JM, de Boer T, Witkamp RF.Palmitoylethanolamide: A Natural Body-Own Anti-Inflammatory Agent, Effective and Safe against Influenza and Common Cold. Int J Inflam. 2013;2013:151028. Epub 2013 Aug 27. Review.
  2. Keppel Hesselink, JM, Kopsky, DJ. Error! Hyperlink reference not valid.Journal Pain Research 23 October 2015 Volume 2015:8 Pages 729—734.
  3. Jan M. Keppel Hesselink, Ciro Costagliola, Josiane Fakhry, and David J. Kopsky, “Palmitoylethanolamide, a Natural Retinoprotectant: Its Putative Relevance for the Treatment of Glaucoma and Diabetic Retinopathy,” Journal of Ophthalmology, vol. 2015, Article ID 430596, 9 pages, 2015. doi:10.1155/2015/430596
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