What are the health benefits of palmitoylethanolamide (PEA), and is it safe?

Answer:

Palmitoylethanolamide (PEA) is a naturally occurring compound that is produced in all tissues of the body, as needed, in response to cellular injury. It can also be found in extremely small amounts (0.0001 mg to 0.0067 mg per gram) in foods such as roasted coffee, soybean, peanuts, whole wheat flour, walnuts, corn, and eggs (Gugliandolo, Vet Sci 2020). PEA used in supplements is synthetically produced (Gunawan, J Phys Conf Ser 2019) and typically used at dosages of 300 to 1,200 mg per day.

Laboratory studies have shown that PEA can activate a certain cell receptor (peroxisome proliferator-activated receptor-alpha or PPAR-alpha) that promotes anti-inflammatory effects. PEA can also activate and then desensitize a cellular channel called transient receptor potential vanilloid 1 (TRPV1), resulting in a pain-relieving effect (Clayton, Int J Mol Sci 2021; Rankin, Int J Mol Sci 2020). Based on these effects, PEA is promoted for treating conditions marked by pain and inflammation, including joint pain, peripheral neuropathy, multiple sclerosis (MS), low back pain/sciatica, glaucoma, and menstrual pain, as well as seasonal allergies, respiratory tract infections, post-COVID olfactory impairment, and conditions linked with brain and spinal cord inflammation, including Parkinson's disease, migraines, mood disorders, and tinnitus. While several preliminary studies have shown modest benefit of PEA for these conditions, all of these studies have all been short-term, and higher quality studies are needed to confirm the results.

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