In a letter to the editor Kriek highlights some very disturbing messages related to the marketing of a certain formulation of palmitoylethanolamide in scientific literature, the ultramicronzied PEA formulation (PEA-um)
He points out a number of grave mistakes in a recent article: Short-Term Efficacy Of Ultramicronized Palmitoylethanolamide In Peripheral Neuropathic Pain, by Dario Cocito, Erdita Peci, Palma Ciaramitaro, Aristide Merola, and Leonardo Lopiano. 
We cite parts of his letter:
The article we discuss here is not the first to wrongly attribute efficacy data gathered by pure, unmicronized palmitoylethanolamide to the so called PEA-um formulation.
For instance, the authors state on p. 1:
“PEA-um demonstrated a significant
efficacy on pain in the murine model of diabetic neuropathy”, and refer to the data on
palmitoylethanolamide published by the group of professor B. Costa in 2008.  These
data however are not based on studies conducted with PEA-um. The PEA used in the
Costa study is explicitly described as unmicronized, pure PEA. Costa et al describe the
PEA they tested as: “PEA was purchased from Cayman Chemical (Ann Arbor, MI, USA),
dissolved in ethanol:saline (1:9), and used at a dose of 10 mg/kg.” Cayman only provides
laboratories with pure, unformulated PEA (purity: 99%). Nowhere in the Costa (2008)
paper do the authors refer to ultramicronized PEA.
Secondly, the authors state: “However, the highly lipophilic PEA crystalline structure has a
poor oral adsorption, thus requiring to be micronized and converted into particles with an
elevated surface area to volume ratio, in order to enhance its assimilation.” This claim is
not substantiated by any data in man. There are no pharmacokinetic data available of
PEA to substantiate this claim, nor are there data available comparing plasma kinetics
and dynamics of pure PEA versus ultramicronized PEA in man. Furthermore, all clinical
double blind placebo controlled studies published so far in more then 3000 patients
have been conducted with simple PEA formulations.
PEA was never tested as an ultramicronized or micronized formulation in such trials. It has recently come to our attention that the most impressive double blind placebo controlled PEA study in 636 patients suffering from sciatic pain, received ethics committee agreement in 1992 and was conducted with LG 2110/1, a code for pure PEA.
Although the authors claim PEA
has a poor oral absorption, the results of the clinical studies so far prove that, even if
true, this is irrelevant as PEA does have significant and clinical relevant effects in simple,
As the study of Cocito et al only reports the short-term follow-up data of a single center
open-label study, in the absence of a placebo group, none of the conclusions of the
authors are supported by the study.
The paper proceeds pointing out that the discussed study only supports the safety of PEA-um, and certainly not the efficacy, but he safety of PEA in all known formulations has been documented already sufficiently.
Therefore, the author ends, we need to conclude that the entire paper can only be seen as support for the
market introduction of ultramicronized PEA, partly based on experiments conducted
with unmicronized PEA. And as we pointed out elsewhere: never has there been any
clinical trial conducted and published supporting superiority of any PEA formulation
over another. 
And he concludes:
On the contrary, all double-blind placebo controlled trials to date have
been conducted with unmicronized PEA and are supportive for such pharmaceutical formulation.
Letter to the Editor
Comment on “Short-Term Efficacy Of Ultramicronized Palmitoylethanolamide In Peripheral Neuropathic Pain”
Received 17 July 2014; Accepted 27 August 2014
 Dario Cocito, Erdita Peci, Palma Ciaramitaro, Aristide Merola, and Leonardo Lopiano. Short-Term Efficacy of Ultramicronized Palmitoylethanolamide in Peripheral Neuropathic Pain. Pain Research and Treatment Volume 2014, Article ID 854560, 4 pages http://dx.doi.org/10.1155/2014/854560.
 Kriek R. Marketing messages in pharmacological papers and scientific chapters: The case of palmitoylethanolamide and its formulations. Pharmacol Res 2014, http://dx.doi.org/10.1016/j.phrs.2014.04.007.
 B. Costa, F. Comelli, I. Bettoni, M. Colleoni, and G. Giagnoni, “The endogenous fatty acid amide, palmitoylethanolamide, has anti-allodynic and anti-hyperalgesic effects in a murine model of neuropathic pain: involvement of CB1, TRPV1 and PPAR receptors and neurotrophic factors,” Pain, vol. 139, no. 3, pp. 541– 550, 2008.
 Kriek R. Palmitoylethanolamide: problems regarding micronization, ultra- micronization and additives. Inflammopharmacology 2014, http://dx.doi.org/10.1007/s10787-014-0202-3.