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Archived Comments for: A new co-ultramicronized composite including palmitoylethanolamide and luteolin to prevent neuroinflammation in spinal cord injury

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  1. Neuroprotection with palmitoylethanolamide depends on concentration, not on co-ultramicronization

    jan keppel hesselink, institute neuropathic pain

    24 April 2014

    The results presented by Paterniti et al are interesting and should be interpreted in quite a different way as the authors did.

    In figure 2 the core results of the study are summarized. This figure clearly demonstrates that increasing doses of palmitoylethanolamide ( 1 uM, 2.7 uM and 27 uM ) are increasingly  effective in reducing cell death. As there are no controls added in the experiments of pure palmitoylethanolamide in the higher dose range (2.7-27 uM), it is not possible to draw the conclusion as the authors do that co-ultramicronization of palmitoylethanolamide and luteolin are the neuroprotective factor. Furthermore, in many of the other figures (3, 4a, 4b and 5) no control values are depicted, and only dose-ranges of 0,27, 2,7 and 27 uM co-ultramicronized palmitoylethanolamide and luteolin are presented.

    Therefore one should conclude these experiments by stating that palmitoylethanolamide (with or without luteolin) protects neurons in a dose-dependent way. 

    Competing interests

    No conflict of interest
  2. Replay to Dr Hesselink comment.

    Salvatore Cuzzocrea, University of Messina

    5 May 2014

     Dr. Jan Keppel Hesselink in his previous comment has ignored the key findings presented in Figure 6 of the paper by Paterniti et al., which clearly demonstrate that the dose of 1 mg/kg co-ultramicronized PEA/Lut provides a highly significant improvement in both motor function and histological alteration caused by spinal cord injury. In contrast, PEA alone (1 mg/kg), Luteolin alone (0.1 mg/kg), and the single administration of PEA (0.9 mg/kg) + Luteolin (0.1 mg/kg) were each without effect. Futhermore, Figure 4 shows that in injured spinal cord slice cultures, already at the lowest dose of co-ultramicronized PEA/Lut (0.27 uM + 0.27 uM) there are statistically significant effects on reduction of nitric oxide production and iNOS expression, and recovery of nNOS expression. PEA (1 uM) + Luteolin (0.1 uM) as combination treatment was without effect (nitric oxide, panel c). Finally, co-ultramicronized PEA/Lut (0.27 uM + 0.027 uM) significantly increased expression of PPARalpha and PPARbeta/delta, which had been reduced in the spinal cord slices subjected to mechanical damage. PEA (1 uM) and Lut (0.1 uM) alone had no effect on damage-induced PPAR down-regulation (page 7 of article).  Our conclusion remains as initially stated, that co-ultramicronized PEA/Lut proves for improved protection of injured spinal cord, in comparison to either PEA or Luteolin alone or in simple combination.  

    [The writer of the previous comment appears to have a conflict of interest, being associated with activities which promote the commercialization of PEA (].   

    Competing interests

    no conflict of interest
  3. Marketing messages in pharmacological papers and conflict of interest?

    jan keppel hesselink, institute neuropathic pain

    16 May 2014

    Related to the last remark of Dr Cuzzocrea the following. It is interesting to note that professor Cuzzocrea himself states that he has no conflict of interest, while he is a patent holder together with Epitech, the producer of Pealut (Glialia).

    Moreover, his esteemed colleague, professor Di Marzo, who is also a patent holder together with Epitech, recently did clearly report his conflict if interest regarding this issue in his paper on PEA. 

    Furthermore, Kriek recently pointed out in a recent paper of Dr Cuzzocrea there also is a clear conflict of interest, related to his presentation of facts around the pharmacology of ultramicronized PEA.

    And finally, PeaLut is a trademark owned by Epitech Group S.r.l.; in pharmacological papers one does not expect such trade names scattered through the entire paper.


    Kriek, R. Marketing messages in pharmacological papers and scientific chapters: The case of palmi- toylethanolamide and its formulations. Letter to the Editor, Pharmacological Research 2014 Available online 24 April 2014:  pii: S1043-6618(14)00047-4. doi: 10.1016/j.phrs.2014.04.007.

    Title of the patent WO 2013121449 A8: "Compositions and methods for the modulation of specific amidases for n-acylethanolamines for use in the therapy of inflammatory diseases." Applicants: Epitech Group S.r. : Francesco Della Valle (IT), Della Valle Maria Federica (IT), Vincenzo Di Marzo (IT) and Salvatore Cuzzocrea (IT).

    Competing interests

    no conflict of interest