Hypertension is an important risk factor for kidney failure and renal events in the general population. Palmitoylethanolamide (PEA) is a member of the fatty acid ethanolamine family with profound analgesic and anti-inflammatory effects, resulting from its ability to activate peroxisome proliferator activated receptor (PPAR)╬▒. A role for this nuclear receptor has been addressed in cardiovascular system and PPAR╬▒ ligands have been shown to protect against inflammatory damage especially resulting from angiotensin II hypertension. In this study, we demonstrated that PEA significantly reduced blood pressure in spontaneously hypertensive rats (SHR) and limited kidney damage secondary to high perfusion pressure. To investigate the mechanisms involved in PEA effect, we found that PEA reduced cytochrome P450 (CYP) hydroxylase CYP4A, epoxygenase CYP2C23 and soluble epoxide hydrolase enzyme expression in the kidney, accompanied by a reduction of 20-hydroxyeicosatetraenoic acid excretion in the urine. Moreover, it markedly reduced kidney oxidative and nitrosative stress accompanied by decreased expression of renal NAD(P)H oxidase and inducible nitric oxide synthase and increased expression of Cu/Zn superoxide dismutase, in the kidney of SHR. Moreover, angiotensin II receptor (AT) evaluation revealed a decrease in AT1 receptor expression and a restoration of AT2 receptor level in the kidney from PEA-treated SHR. Consistently, angiotensin converting enzyme expression was reduced, implying a decrease in angiotensin II synthesis. These results indicate that PEA treatment lowers blood pressure and can protect against hypertensive renal injury by increasing the antioxidant defense and anti-inflammatory response and modulating renin-angiotensin system.

Italian and Dutch PEA

Palmitoylethanolamide is especially in Italy and the USA at the moment hot for the treatment of glaucoma. We prefer treatment either with the Italian PEA tablets, based on PEA-um or PEA-m, or by administrating the Dutch PEA capsules containing PEA-opt. Dutch capsules do not contain any chemical excipients and are 100% pure in vegetarian capsules.

For pain relief and for inhibiting inflammation, most patients choose:

  • PEA capsules produced in the Netherlands by Russell
  • PEA tablets produced in Italy by Epitech

Only for these the Dutch and the Italian formulations long term safety and efficacy data gathered under the supervision of MDs are available. And only for these formulations (PEA-um, PEA-m and PEA-opt) there are currently data available proving that after intake PEA levels in the body significantly rise. Such data do not exist for me-too PEA formulations.


N-Palmitoylethanolamide protects the kidney from hypertensive injury in spontaneously hypertensive rats via inhibition of oxidative stress.
Mattace Raso G, Simeoli R, Russo R, Santoro A, Pirozzi C, d’Emmanuele di Villa Bianca R, Mitidieri E, Paciello O, Pagano TB, Orefice NS, Meli R, Calignano A.
Pharmacol Res. 2013 Oct;76:67-76. doi: 10.1016/j.phrs.2013.07.007. Epub 2013 Aug 2.