Palmitoylethanolamide is a great break-through in pain management, due to its proven efficacy in a significant number of painstates and inflammatory conditions. The compound however is known since 1957 and patents to protect its use are impossible. Therefore some companies developed and patented special palmitoylethanolamide formulations, sometimes refered to as ‘life cycle management’. The advantages of such formulations over pure PEA has never been proven, and its costs are higher. In addition to that all major double blind placebo-controlled studies conducted in more than 3000 patients have been conducted with pure PEA in simple tablets and not with such patented formulations.
Recently the companies developing special (micronized and ultramicronized) palmitoylethanolamide formulations, Epitech, Prismic and Innovet (brandnames amongst others Normast, Glialia, PeaLut, Adolene, Pelvilen) have increased their marketing activities, and sadly enough have done so in pharmacological papers and scientific chapters by mispresenting scientific data, as Kriek pointed out in two recent papers.
These misrepresentations of data are discussed as scientific misconduct in one of the key-journals in the field, Pharmacological Research by Kriek. Data on PEA published in 5 different pharmacological journals are misrepresented by the authors as related to the special patented formulations, while the experiments were conducted with pure PEA.
One of the headers in the paper is:
Unconventional marketing and communication efforts by Epitech Group S.r.l., Innovet Italia S.r.l. and Prismic related to micronized and ultramicronized PEA
These highly debatable marketing communications were hidden in a recent scientific pharmacological review paper published in Pharmacol Res. (March 3, 2014) by the group of professor Cuzzocrea (Impellizzeri et al.,2014) and related to palmitoylethanolamide and its value for the treatment of Chronic Kidney Disease. A number of statements (5) made in this paper were incorrect and misleading, related to the efficacy of a specific patented formulation of palmitoylethanolamide, while the studies were conducted without such formulations.
Kriek points out a clear conflict of interest in the Pharm Res paper, not mentioned: one of the authors, James Attley is currently Vice President (VP) Business Development and Licensing of Prismic, a company developing together with Epitech a special PEA formulation for kidney disorders.
According to Kriek, one needs to draw a totally different conclusion based on the facts. It is not PEA in the (patented) ultramiconized and micronized formulations that is active in protecting the kidney, but PEA in its pure form (not micronized, neither ultramicronized). He makes it clear that marketing motives were the driving force behind the choice of the authors to misrepresent the scientific facts as done in their paper.
One of the major findings of Kriek is the fact that the Italian companies Innovet and Epitech also manipulated Wikipedia: Members of the patent-holding companies repeatedly tried to amend the Wikipedia chapter on PEA, by inserting marketing-driven information on micronization and ultramicronization PEA formulations and their brand names.
He documented this fact by analyzing the backside of WIKI were IP addresses can be found and changes can be tracked.
As the conclusion of the paper is not presented in PubMed we herewith give an verbatim quote:
The authors presented the data discussed as facts to prove and make plausible that PEA in the ‘ultramicronized’ formulation leads to a number of positive results that were summarized in this article. The writer of this letter to the editor has made it clear that the statements of the authors related to the ‘ultramicronized’ formulation have no foundation in the facts presented.
Each scientific article needs to represent the facts correctly and unbiased, which sadly enough is not the case at all. The writer of this letter to the editor suggests that there is only one sound conclusion based on all the data presented: PEA in a non-ultramicronized formulation leads to all the positive results, PEA being a nephroprotectant compound.
We have demonstrated that conflicts of interest that arose in 2014 are still important aspects to deal with, and that reporting conflicts of interest does not necessarily help to achieve objective papers.
Jumps to conclusions in first micronized patent
It is highly interesting to read one of the early mictronization patents on PEA. For instance: PHARMACEUTICAL COMPOSITIONS CONTAINING N-PALMITOYLETHANOLAMIDE AND USE THEREOF IN THE VETERINARY FIELD, European patent, filed in 1999, European Patent EP1207870: the first and most important claim of this patent was: Use of N-palmitoylethanolamide for the preparation of a pharmaceutical composition for the treatment of eosinophilic granuloma in Felines, in which the N-palmitoylethanolamide is present in micronized form or is co-micronized with an excipient.
In the patent only 1 example was given were 15 cats were treated with pure PEA, micronized PEA and cortisone. The results after 30 days treatment were improvement of symptoms in resp. 52%, 67%, and 65%. For the pathological signs (plaques in skin) the improvement was resp. 51%, 67% and 65%. This trial was unblinded and unclear was whether the clinical and pathological scores were conducted blindly for the therapy. The conclusions however favored the micronized PEA formulation:
It is clear from the results given above that N-palmitoylethanolamide in micronized form or comicronized with an excipient, can advantageously be used in the treatment of eosinophilic granuloma in cats, for both EP and EG lesions, both when these conditions are acute and when they are chronic.
Of course a controlled open trial with 15 cats enclosed (5 in each arm) cannot be used to make any superiority claims. So, we can conclude that the marketing strategy supporting new (ultra-)micronized PEA products started in 1999 in the afore mentioned patent.
Kriek R. Marketing messages in pharmacological papers and scientific chapters: The case of palmitoylethanolamide and its formulations. Pharmacol Res. 2014 Apr 24. pii: S1043-6618(14)00047-4. doi: 10.1016/j.phrs.2014.04.007. [Epub ahead of print]
Kriek R. Palmitoylethanolamide: problems regarding micronization, ultra-micronization and additives.
Inflammopharmacology. 2014 Mar 20. [Epub ahead of print]
Impellizzeri D, Esposito E, Attley J, Cuzzocrea S. Targeting inflammation: new therapeutic approaches in Chronic Kidney Disease (CKD). Pharmacol Res. 2014 Mar 3. pii: S1043-6618(14)00020-6. doi: 10.1016/j.phrs.2014.02.007.