600–1,200 mg/day of PEA (often micronized).
Randomized pilot study: adding a PEA + luteolin supplement to olfactory rehabilitation helped recover smell in patients with post-COVID anosmia, due to its anti-inflammatory effect. Preliminary and in few patients.
View the study (study) →⏱ 1 min read
Palmitoylethanolamide, or PEA, is an endogenous fatty acid amide with documented anti-inflammatory and analgesic activity, belonging to the family of "endocannabinoid-like" compounds although it acts mainly through PPAR-alpha receptors (not directly on cannabinoid receptors), modulating the activation of mast cells and microglia, two key cell types in the pathophysiology of chronic and neuropathic pain; commercial formulations combining PEA with luteolin (a flavonoid with complementary activity on mast cells) have become available as a dietary supplement or medication with modest clinical support for chronic neuropathic pain and refractory inflammatory conditions.
The indication with the most studied clinical support is chronic neuropathic pain of various causes: several Italian and European trials have documented significant reductions in pain scores with supplementation at 600-1,200 mg/day of PEA (alone or combined with luteolin) for 4-12 weeks, especially in low back pain with a radicular component, diabetic neuropathy, and other conditions refractory to conventional treatments.
In chronic inflammatory processes with a component of mast cell or microglial activation, the PEA + luteolin combination takes advantage of the mechanistic synergy of both compounds, a formulation with interesting clinical support although the clinical data are still limited to small studies.
The doses studied are 600-1,200 mg/day of PEA, divided into 2-3 doses with or without food; combined formulations with luteolin typically contain 350-600 mg of PEA + 100-200 mg of luteolin per dose; the effect on pain appears gradually and requires at least 4-8 weeks to evaluate.
Generally very well tolerated with an excellent safety profile; adverse effects are rare and mild (mild digestive discomfort); no significant drug interactions have been described; people taking treatments for chronic pain (opioids, antiepileptics, antidepressants) can combine them with PEA as a complement under medical supervision; in pregnancy and breastfeeding, specific data as a supplement are limited and avoidance is recommended as a precaution; commercial formulations vary enormously in purity and bioavailability, and it is advisable to choose products with good clinical documentation.
Information, not medical advice. Scientific evidence reflects the quality of the studies.