Palmitoylethanolamide

COMMON NAME

Palmitoylethanolamide | PEA | Palmidrol | Impulsin

TOP BENEFITS OF PALMITOYLETHANOLAMIDE

  • Supports general immune health*
  • Supports upper respiratory tract health*
  • Supports joint and muscle function and comfort*
  • Supports balanced mood*
  • Supports healthy sensory nerve signaling*

WHAT IS PALMITOYLETHANOLAMIDE?

Palmitoylethanolamide, abbreviated PEA, is an endogenous (i.e., manufactured by the body) fatty acid amide (FAA). It is found throughout the body and, like the other, endogenously produced FAA, is a signaling molecule, used in cellular communication. During times of stress or when the need for healing is greater, cells produce and use more palmitoylethanolamide. Its biological actions are primarily mediated by peroxisome proliferator-activated receptor alpha (PPAR-α) and endocannabinoid receptors[1,2]. Palmitoylethanolamide plays especially important functional roles in sensory nerves, and in supporting microglia (the brain’s immune cells), mast cells, macrophages, and overall immune system communication. Palmitoylethanolamide was researched as a way to support general immune health and wellness in the 1960’s and 1970’s. More recently, much of the research on palmitoylethanolamide has focused on sensory nerve health, mood support, joint comfort, and muscle recovery. Palmitoylethanolamide also supports the richness of gut microbiota (i.e., the gut-immune axis).

NEUROHACKER’S PALMITOYLETHANOLAMIDE SOURCING

Palmitoylethanolamide is GRAS, non-GMO, gluten-free, and vegan.

PALMITOYLETHANOLAMIDE DOSING PRINCIPLES AND RATIONALE

Palmitoylethanolamide has been studied clinically over a fairly wide range of doses, with the common range being 300-1200 mg. Evidence suggests a threshold response (see Neurohacker Dosing Principles) when Palmitoylethanolamide is given by itself (i.e., much of the benefits occur within the lower end of the dosing range). The dose of palmitoylethanolamide used in a Neurohacker formulation can vary significantly depending upon what other ingredients it’s combined with and the intent of the formulation.

PALMITOYLETHANOLAMIDE KEY MECHANISMS

Immunity

  • Supports general immune health[3–6]  
  • Supports innate immunity[7–10]
  • Supports adaptive immunity[11]
  • Supports immune tolerance[12–15]
  • Supports immune signaling[3,8,11,12]
  • Supports healthy microglia function[4,16–18]
  • Supports healthy macrophage function[7,8,10]
  • Supports healthy T cell function[11]
  • Supports healthy mast cell function[9,18–21]

Gastrointestinal function

  • Supports GI immune signaling[22–24]
  • Supports gut barrier function[25,26]
  • Supports gut microbiota[27,28]

Brain and nerve function

  • Supports brain function[29,30]
  • Supports neuroimmune signaling[12,18,32–34]
  • Supports sensory nervous system health[29,35,36]
  • Supports a positive mental-emotional bias[37]
  • Supports healthy behavioral and cognitive responses to stress[12,38–40]
  • Supports neuroprotection[32–34,41–43]
  • Supports neural antioxidant defenses[33]
  • Supports endogenous cannabinoid (i.e., endocannabinoid) signaling[12,38,39,44]
  • Supports TRPV1 signaling

Muscle and joint function

  • Supports joint & muscle health, comfort, and  flexibility[45,46]
  • Supports exercise recovery and performance[47]

Synergies

  • Luteolin for brain, nerve, and microglia function[13,48–51]

REFERENCES

[1] J. Lo Verme, J. Fu, G. Astarita, G. La Rana, R. Russo, A. Calignano, D. Piomelli, Mol. Pharmacol. 67 (2005) 15–19.
[2] E. Ryberg, N. Larsson, S. Sjögren, S. Hjorth, N.-O. Hermansson, J. Leonova, T. Elebring, K. Nilsson, T. Drmota, P.J. Greasley, Br. J. Pharmacol. 152 (2007) 1092–1101.
[3] J.M. Keppel Hesselink, T. de Boer, R.F. Witkamp, Int. J. Inflam. 2013 (2013) 151028.
[4] E.C. Heide, L. Bindila, J.M. Post, D. Malzahn, B. Lutz, J. Seele, R. Nau, S. Ribes, Front. Immunol. 9 (2018) 2671.
[5] K. Masek, F. Perlík, J. Klíma, R. Kahlich, Eur. J. Clin. Pharmacol. 7 (1974) 415–419.
[6] R. Kahlich, J. Klíma, F. Cihla, V. Franková, K. Masek, M. Rosický, F. Matousek, J. Bruthans, J. Hyg. Epidemiol. Microbiol. Immunol. 23 (1979) 11–24.
[7] P. Rinne, R. Guillamat-Prats, M. Rami, L. Bindila, L. Ring, L.-P. Lyytikäinen, E. Raitoharju, N. Oksala, T. Lehtimäki, C. Weber, E.P.C. van der Vorst, S. Steffens, Arterioscler. Thromb. Vasc. Biol. 38 (2018) 2562–2575.
[8] V. Lackovic, L. Borecký, J. Kresáková, Arch. Immunol. Ther. Exp. 25 (1977) 655–661.
[9] S. Mazzari, R. Canella, L. Petrelli, G. Marcolongo, A. Leon, Eur. J. Pharmacol. 300 (1996) 227–236.
[10] S. Redlich, S. Ribes, S. Schütze, R. Nau, J. Neuroinflammation 11 (2014) 108.
[11] V. Chiurchiù, A. Leuti, R. Smoum, R. Mechoulam, M. Maccarrone, FASEB J. 32 (2018) 5716–5723.
[12] N.S. Orefice, M. Alhouayek, A. Carotenuto, S. Montella, F. Barbato, A. Comelli, A. Calignano, G.G. Muccioli, G. Orefice, Neurotherapeutics 13 (2016) 428–438.
[13] G. Contarini, D. Franceschini, L. Facci, M. Barbierato, P. Giusti, M. Zusso, Journal of Neuroinflammation 16 (2019).
[14] A. Rahimi, M. Faizi, F. Talebi, F. Noorbakhsh, F. Kahrizi, N. Naderi, Neuroscience 290 (2015) 279–287.
[15] F. Loría, S. Petrosino, L. Mestre, A. Spagnolo, F. Correa, M. Hernangómez, C. Guaza, V. Di Marzo, F. Docagne, Eur. J. Neurosci. 28 (2008) 633–641.
[16] F. Guida, L. Luongo, S. Boccella, M.E. Giordano, R. Romano, G. Bellini, I. Manzo, A. Furiano, A. Rizzo, R. Imperatore, F.A. Iannotti, E. D’Aniello, F. Piscitelli, F. Sca Rossi, L. Cristino, V. Di Marzo, V. de Novellis, S. Maione, Sci. Rep. 7 (2017) 375.
[17] R. Nau, S. Ribes, M. Djukic, H. Eiffert, Front. Cell. Neurosci. 8 (2014) 138.
[18] S.D. Skaper, L. Facci, P. Giusti, Mol. Neurobiol. 48 (2013) 340–352.
[19] L. Facci, R. Dal Toso, S. Romanello, A. Buriani, S.D. Skaper, A. Leon, Proc. Natl. Acad. Sci. U. S. A. 92 (1995) 3376–3380.
[20] D. De Filippis, L. Luongo, M. Cipriano, E. Palazzo, M.P. Cinelli, V. de Novellis, S. Maione, T. Iuvone, Mol. Pain 7 (2011) 3.
[21] E. Esposito, I. Paterniti, E. Mazzon, T. Genovese, R. Di Paola, M. Galuppo, S. Cuzzocrea, Brain Behav. Immun. 25 (2011) 1099–1112.
[22] G. Sarnelli, L. Seguella, M. Pesce, J. Lu, S. Gigli, E. Bruzzese, R. Lattanzi, A. D’Alessandro, R. Cuomo, L. Steardo, G. Esposito, J. Neuroinflammation 15 (2018) 94.
[23] G. Esposito, E. Capoccia, F. Turco, I. Palumbo, J. Lu, A. Steardo, R. Cuomo, G. Sarnelli, L. Steardo, Gut 63 (2014) 1300–1312.
[24] D.G. Couch, C. Tasker, E. Theophilidou, J.N. Lund, S.E. O’Sullivan, Clin. Sci. 131 (2017) 2611–2626.
[25] D.G. Couch, H. Cook, C. Ortori, D. Barrett, J.N. Lund, S.E. O’Sullivan, Inflamm. Bowel Dis. 25 (2019) 1006–1018.
[26] M.A. Karwad, T. Macpherson, B. Wang, E. Theophilidou, S. Sarmad, D.A. Barrett, M. Larvin, K.L. Wright, J.N. Lund, S.E. O’Sullivan, FASEB J. 31 (2017) 469–481.
[27] F. Guida, S. Boccella, C. Belardo, M. Iannotta, F. Piscitelli, F. De Filippis, S. Paino, F. Ricciardi, D. Siniscalco, I. Marabese, L. Luongo, D. Ercolini, V. Di Marzo, S. Maione, Brain Behav. Immun. 85 (2020) 128–141.
[28] C. Cristiano, C. Pirozzi, L. Coretti, G. Cavaliere, A. Lama, R. Russo, F. Lembo, M.P. Mollica, R. Meli, A. Calignano, G. Mattace Raso, Brain Behav. Immun. 74 (2018) 166–175.
[29] Z. Alshelh, E.P. Mills, D. Kosanovic, F. Di Pietro, P.M. Macey, E.R. Vickers, L.A. Henderson, J. Pain Res. 12 (2019) 2427–2439.
[30] S. Boccella, C. Cristiano, R. Romano, M. Iannotta, C. Belardo, A. Farina, F. Guida, F. Piscitelli, E. Palazzo, M. Mazzitelli, R. Imperatore, L. Tunisi, V. de Novellis, L. Cristino, V. Di Marzo, A. Calignano, S. Maione, L. Luongo, Neurobiology of Disease 121 (2019) 106–119.
[31] A. Franklin, S. Parmentier-Batteur, L. Walter, D.A. Greenberg, N. Stella, J. Neurosci. 23 (2003) 7767–7775.
[32] M.I. Holubiec, J.I. Romero, J. Suárez, M. Portavella, E. Fernández-Espejo, E. Blanco, P. Galeano, F.R. de Fonseca, Psychopharmacology 235 (2018) 2929–2945.
[33] S. Beggiato, M.C. Tomasini, T. Cassano, L. Ferraro, J. Clin. Med. Res. 9 (2020).
[34] A. Ahmad, R. Crupi, D. Impellizzeri, M. Campolo, A. Marino, E. Esposito, S. Cuzzocrea, Brain Behav. Immun. 26 (2012) 1310–1321.
[35] F. Guida, L. Luongo, F. Marmo, R. Romano, M. Iannotta, F. Napolitano, C. Belardo, I. Marabese, A. D’Aniello, D. De Gregorio, F. Rossi, F. Piscitelli, R. Lattanzi, A. de Bartolomeis, A. Usiello, V. Di Marzo, V. de Novellis, S. Maione, Mol. Brain 8 (2015) 47.
[36] S.R. Andresen, J. Bing, R.M. Hansen, F. Biering-Sørensen, I.L. Johannesen, E.M. Hagen, A.S.C. Rice, J.F. Nielsen, F.W. Bach, N.B. Finnerup, Pain 157 (2016) 2097–2103.
[37] M. Ghazizadeh-Hashemi, A. Ghajar, M.-R. Shalbafan, F. Ghazizadeh-Hashemi, M. Afarideh, F. Malekpour, A. Ghaleiha, M.E. Ardebili, S. Akhondzadeh, J. Affect. Disord. 232 (2018) 127–133.
[38] K.O. Jonsson, S. Vandevoorde, D.M. Lambert, G. Tiger, C.J. Fowler, Br. J. Pharmacol. 133 (2001) 1263–1275.
[39] A.M. Moise, S.A. Eisenstein, G. Astarita, D. Piomelli, A.G. Hohmann, Psychopharmacology 200 (2008) 333–346.
[40] M. Li, D. Wang, W. Bi, Z.-E. Jiang, R. Piao, H. Yu, J. Pharmacol. Exp. Ther. 369 (2019) 163–172.
[41] S. Boccella, I. Marabese, M. Iannotta, C. Belardo, V. Neugebauer, M. Mazzitelli, G. Pieretti, S. Maione, E. Palazzo, International Journal of Molecular Sciences 20 (2019) 1757.
[42] R. Crupi, D. Impellizzeri, M. Cordaro, R. Siracusa, G. Casili, M. Evangelista, S. Cuzzocrea, Mol. Neurobiol. 55 (2018) 8455–8472.
[43] C. Scuderi, M.R. Bronzuoli, R. Facchinetti, L. Pace, L. Ferraro, K.D. Broad, G. Serviddio, F. Bellanti, G. Palombelli, G. Carpinelli, R. Canese, S. Gaetani, L. Steardo, L. Steardo, T. Cassano, Translational Psychiatry 8 (2018).
[44] B.N. Okine, M.K. Madasu, F. McGowan, C. Prendergast, J.C. Gaspar, B. Harhen, M. Roche, D.P. Finn, Pain 157 (2016) 2687–2696.
[45] E. Steels, R. Venkatesh, E. Steels, G. Vitetta, L. Vitetta, Inflammopharmacology 27 (2019) 475–485.
[46] J.M.K. Hesselink, T.A. Hekker, J. Pain Res. 5 (2012) 437–442.
[47] A. Mallard, D. Briskey, A. Richards, D. Mills, A. Rao, Nutrients 12 (2020) 596.
[48] I. Paterniti, M. Cordaro, M. Campolo, R. Siracusa, C. Cornelius, M. Navarra, S. Cuzzocrea, E. Esposito, CNS Neurol. Disord. Drug Targets 13 (2014) 1530–1541.
[49] M. Cordaro, D. Impellizzeri, I. Paterniti, G. Bruschetta, R. Siracusa, D. De Stefano, S. Cuzzocrea, E. Esposito, J. Neurotrauma 33 (2016) 132–146.
[50] E. Parrella, V. Porrini, R. Iorio, M. Benarese, A. Lanzillotta, M. Mota, M. Fusco, P. Tonin, P. Spano, M. Pizzi, Brain Res. 1648 (2016) 409–417.
[51] R. Siracusa, I. Paterniti, D. Impellizzeri, M. Cordaro, R. Crupi, M. Navarra, S. Cuzzocrea, E. Esposito, CNS Neurol. Disord. Drug Targets 14 (2015) 1350–1365.