Abstract
It can be established that at least two of the writers of the article published in ‘Inflammopharmacology’, title: ‘Palmitoylethanolamide (PEA), a naturally occurring disease-modifying agent in neuropathic pain’ have a direct connection to the companies Epitech and Innovet. These companies produce micronized and ultra-micronized PEA. Therefore it is of eminent importance to determine whether the statements in this paper have also taken into consideration the European guidelines for Good Clinical Practice and the codes of good scientific practices. This is very questionable. A minimum condition in clinical studies for proving the claim that PEA in its micronized and ultra-micronized formulations works better than in its pure form or in other formulations is that a comparison be made between: PEA in pure form or in other formulations, on the one hand; PEA in the micronized and ultra-micronized formulations, on the other hand. This minimum condition is not complied with. Based on additional studies discussed in this commentary and in view of the effects of ultra-micronization on the parameters discussed, as well as the potential side-effects of additives such as excipients and herbal extracts added to the products cited in the article, the preference should be for the time being to treat patients with pure PEA without any of these additives.
References
Aloe L, Leon A, Levi-Montalcini R (1993) A proposed autacoid mechanism controlling mastocyte behaviour. Agents Actions 39:C145–C147
Alvheim AR, Torstensen BE, Lin YH, Lillefosse HH, Lock EJ, Madsen L, Hibbeln JR, Malde MK (2013) Dietary linoleic acid elevates endogenous 2-arachidonoylglycerol and anandamide in Atlantic salmon (Salmo salar L.) and mice, and induces weight gain and inflammation in mice. Br J Nutr 109:1508–1517
Baldassarri S, Bertoni A, Bagarotti A, Sarasso C, Zanfa M, Catani MV, Avigliano L, Maccarrone M, Torti M, Sinigaglia F (2008) The endocannabinoid 2-arachidonoylglycerol activates human platelets through non-CB1/CB2 receptors. J Thromb Haemost 10:1772–1779
Brantl SA, Khandoga AL, Siess W (2013) Mechanism of platelet activation induced by endocannabdinoids in blood and plasma. Platelets 24:1369–1635
Comelli C, Della Valle MF, Della Valle F, Marcolongo G (1999) Pharmaceutical compositions containing N-palmitoylethanolamide and use thereof in the veterinary field. http://www.google.com.mx/patents/US6548550
Della Valle F, Marcolongo G, Della Valle MF (2009) Composition containing ultra-micronized palmitoylethanolamide. WO 2011027373 A1 http://www.google.com/patents/WO2011027373A1
Ghosh I, Schenck D, Bose S, Ruegger C (2012) Optimization of formulation and process parameters for the production of nanosuspension by wet media milling technique: effect of vitamin E TPGS and nanocrystal particle size on oral absorption. Eur J Pharm Sci 47:718–728
Iocob (2013) Glialia (Palmitoylethanolamide, PeaLut), a new non-rational nutraceutical. http://www.iocob.nl/english-articles/glialia-palmitoylethanolamide-pealut-a-new-nutraceutical.html
Keppel Hesselink JM (2013a) Professor Rita Levi-Montalcini on nerve growth factor, mast cells and palmitoylethanolamide, an endogenous anti-inflammatory and analgesic compound. J Pain Relief 2:1 http://dx.doi.org/10.4172/2167-0846.100011
Keppel Hesselink JM (2013b) Chronic idiopathic axonal neuropathy and pain, treated with the endogenous lipid mediator palmitoylethanolamide: a case collection. Int Med Case Rep J 6:49–53
Keppel Hesselink JM (2013c) Evolution in pharmacologic thinking around the natural analgesic palmitoylethanolamide: agonist and effective nutraceutical PEA and the sociology of science. J Pain Res 2013:625–634
Keppel Hesselink JM, Kopsky DJ (2013) Treatment of chronic regional pain syndrome type 1 with palmitoylethanolamide and topical ketamine cream: modulation of non-neuronal cells. J Pain Res 6:239–245
Keppel Hesselink JM, de Boer T, Witkamp RF (2013) Palmitoylethanolamide: a natural body-own anti-inflammatory agent, effective and safe against influenza and common cold. Int J Inflamm Article ID 151028; doi:10.1155/2013/151028
Masek, K, Perlik, F (1975) Slow encephalopathies, inflammatory responses, and arachis oil. Lancet 20 558
Masek K, Perlík F, Klíma J, Kahlich R (1974) Prophylactic efficacy of N-2-hydroxyethyl palmitamide (impulsin) in acute respiratory tract infections. Eur J Clin Pharmacol 7:415–419
Mazzari S, Canella R, Petrelli L, Marcolongo G, Leon A (1996) N-(2-hydroxyethyl) hexadecanamide is orally active in reducing edema formation and inflammatory hyperalgesia by down-modulating mast cell activation. Eur J Pharmacol 300:227–236
Miolo A, Re G, Barbero R, Giorgi M, Leotta R et al (2006) Aliamides modulate skin mast cell degranulation in dogs and cats. J Vet Pharmacol Therap 29 (Suppl. 1):201–210
Rasková H, Masek K, Linèt O (1972) Non-specific resistance induced by palmitoylethanolamide. Toxicon 10:485–490
Taliou A, Zintzaras E, Lykouras L, Francis K (2013) 2013 An open-label pilot study of a formulation containing the anti-inflammatory flavonoid luteolin and its effects on behavior in children with autism spectrum disorders. Clin Ther 35:592–602
Valdeolivas S, Pazos MR, Bisogno T, Piscitelli F, Iannotti FA, Allarà M, Sagredo O, Di Marzo V, Fernández-Ruiz J (2013) The inhibition of 2-arachidonoyl-glycerol (2-AG) biosynthesis, rather than enhancing striatal damage, protects striatal neurons from malonate-induced death: a potential role of cyclooxygenase-2-dependent metabolism of 2-AG. Cell Death Dis 4:e862. doi: 10.1038/cddis.2013.387
Vernia P, Frandina C, Bilotta T, Ricciardi MR, Villotti G, Fallucca F (1995) Sorbitol malabsorption and nonspecific abdominal symptoms in type II diabetes. Metabolism 44:796–799
Conflict of interest
The author is director of JP Russell Science Limited and writes this article in this capacity, on behalf of said company. JP Russell Science Limited is producer of PeaVera and PeaPure. JP Russell Science Limited declares conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kriek, R. Palmitoylethanolamide: problems regarding micronization, ultra-micronization and additives. Inflammopharmacol 22, 195–198 (2014). https://doi.org/10.1007/s10787-014-0202-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10787-014-0202-3