Palmitoylethanolamide: A Natural Compound for Health Management

Int J Mol Sci. 2021 May 18;22(10):5305. doi: 10.3390/ijms22105305.


All nations which have undergone a nutrition transition have experienced increased frequency and falling latency of chronic degenerative diseases, which are largely driven by chronic inflammatory stress. Dietary supplementation is a valid strategy to reduce the risk and severity of such disorders. Palmitoylethanolamide (PEA) is an endocannabinoid-like lipid mediator with extensively documented anti-inflammatory, analgesic, antimicrobial, immunomodulatory and neuroprotective effects. It is well tolerated and devoid of side effects in animals and humans. PEA's actions on multiple molecular targets while modulating multiple inflammatory mediators provide therapeutic benefits in many applications, including immunity, brain health, allergy, pain modulation, joint health, sleep and recovery. PEA's poor oral bioavailability, a major obstacle in early research, has been overcome by advanced delivery systems now licensed as food supplements. This review summarizes the functionality of PEA, supporting its use as an important dietary supplement for lifestyle management.

Keywords: ALIAmides; bioactive lipids; dietotherapy; endocannbinoids; immunomodulation; immunomodulator; inflammation; lipid signaling; molecular mechanism; neuroinflammation; nutraceuticals; pain.

Publication types

  • Review

MeSH terms

  • Amides / metabolism*
  • Amides / pharmacology*
  • Animals
  • Anti-Inflammatory Agents / therapeutic use
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Dietary Supplements
  • Endocannabinoids / metabolism
  • Endocannabinoids / pharmacology
  • Ethanolamines / metabolism*
  • Ethanolamines / pharmacology*
  • Humans
  • Inflammation / immunology
  • Inflammation Mediators / therapeutic use
  • Neuroprotective Agents / therapeutic use
  • Pain / drug therapy
  • Palmitic Acids / metabolism*
  • Palmitic Acids / pharmacology*


  • Amides
  • Anti-Inflammatory Agents
  • Anti-Inflammatory Agents, Non-Steroidal
  • Endocannabinoids
  • Ethanolamines
  • Inflammation Mediators
  • Neuroprotective Agents
  • Palmitic Acids
  • palmidrol