In response to the paper published by Rafael Gálvez Mateos and Antonio Aguilar Ros entitled Practical update on oral palmythopylethanolamide (PEAum) in the management of chronic pain. Narrative review, I would like the following noted. The paper states “Micronised and ultra-micronised PEA have demonstrated faster dissolution and absorption rates, better bioavailability and pharmacokinetics and superior efficacy compared to the original form, which has a larger and more variable particle size (25,26)”. But the papers they have referenced are not absorption studies. They then go on to say that micronized PEA is better absorbed than the published study using the PEA formulation Levagen+. However, the references used to make this comparison are not human absorption papers like our published formulation. Therefore, I do not see how this claim can be made.

Rafael Gálvez Mateos and Antonio Aguilar Ros also state “In addition to micronisation, other dosage forms that improve the bioavailability of PEA have been tested, such as the LipiSperse® system. In the latter case, the addition of surfactants to a lipophilic molecule such as PEA, with a high particle size (> 100 microns), does not seem to favour an effective and prolonged dispersion of the active substance in the aqueous phase. Further studies are undoubtedly necessary to confirm the advantage in bioavailability of the LipiSperse® system over the use of non-micronised PEA. On the other hand, the appearance of twin plasma peaks after a single administration of PEA indicates the existence of an enterohepatic cycle (27).” This is also incorrect. Our manuscript shows LipiSperse achieved a superior absorption over a standard formulation. The paper appears to be trying to make comparisons between absorption studies and efficacy studies. We do not argue that other formulations may have efficacy, but they have not shown the same absorption and therefore cannot be compared. We also confirm that there is no study published comparing our published formulation to a micronized formulation. Therefore, such statements as above cannot be made.