What is PEA?

PEA goes by many names, it is short for palmitoylethanolamide, but is also known as palmidrol. It is a fatty acid, and part of the endocannabinoid family ⁽¹⁾. PEA is found in all tissues of the body, including the brain. Interestingly, it is also found in some foods, including meat, egg yolks, peanuts, and soybeans ⁽²⁾.

PEA has been studied for over 80 years, with interest in PEA as a potential therapeutic treatment for pain growing in recent years, leading it to become a key area of interest for research into strategies for pain management.

PEA is naturally produced within the body cells as a repair mechanism in response to pain and inflammation. It forms part of the body’s natural pain management strategy. During prolonged pain and inflammation, levels of PEA within the body decline, as it is utilised on demand. In these instances, dietary and supplemental PEA can increase PEA levels in the body, to restore its protective, anti-inflammatory, and analgesic actions ^(1,3).

Inflammation is a natural response to injury, and when the body detects an injury, it begins a cascade of events. It signals for the immune system to send immune and pro-inflammatory cells to the affected area, and increases blood flow to the area, as the blood carries oxygen and important nutrients to aid healing. While some inflammation is beneficial and part of the body’s natural healing process, not all inflammation is good, and prolonged inflammation can lead to further issues ⁽⁴⁾.

PEA works by binding to receptors in the endocannabinoid system and interacting with inflammatory mediators to reduce pain and excess inflammation ⁽⁵⁾. The actions of PEA in pain have been well documented, with numerous studies showing a benefit in conditions of prolonged inflammation such as mild joint pain and symptoms of mild arthritis ⁽³⁾.

Supplemental PEA is well tolerated by the body, however given that PEA is a fatty molecule, it is lipophilic (oil-loving), and almost insoluble in water. This can lead to poor bioavailability when taken orally as a supplement. To overcome this, PEA included in dietary supplements can be micronized, emulsified, or partnered with a novel delivery system ^{(1, 6)}.

When looking at solubility, size does matter, as an ingredient’s solubility is closely tied to how well it can be absorbed by the body. The more soluble an ingredient is, the better it can be absorbed by the body. Micronization is the process of taking a large molecule, such as PEA, and reducing its particle size. Micronized PEA has improved solubility, and therefore is more bioavailable for the body to use ⁽¹⁾. A non-micronized form of PEA would be less soluble, less bioavailable, and therefore not as easily absorbed by the body.

The majority of clinical trials conducted on PEA have been done using the micronized or ultra-micronized form.

References:

1. Rankin, L & Fowler, C. (2020). The Basal Pharmacology of Palmitoylethanolamide. International Journal of Molecular Science, 21(21). doi: 10.3390/ijms21217942
2. Peritore, A, Siracusa, R, Crupi, E, et al. (2019). Therapeutic Efficacy of Palmitoylethanolamide and Its New Formulations in Synergy with Different Antioxidant Molecules Present in Diets. Nutrients, 11(19):2175, doi: 10.3390/nu11092175
3. Clayton P, Hill M, Bogoda N, et al. (2021) Palmitoylethanolamide: A Natural Compound for Health Management. International Journal of Molecular Science, 18;22(10). doi: 10.3390/ijms22105305.
4. Harvard Health Publishing. (2020). Understanding acute and chronic inflammation, Accessed 14 Aug 2022 < https://www.health.harvard.edu/staying-healthy/understanding-acute-and-chronic-inflammation >
5. Gabrielsson, L, Mattsson, S & Fowler, C. (2016). Palmitoylethanolamide for the treatment of pain: pharmacokinetics, safety and efficacy. British Journal of Clinical Pharmacology, 82(4), 932-942. doi: 10.1111/bcp.13020
6. Nestmann, E. (2017). Safety of micronized palmitoylethanolamide (microPEA): lack of toxicity and genotoxic potential. Food Science & Nutrition, 5(2), 292-309. doi: 10.1002/fsn3.392