Palmitoylethanolamide supplementation for human health: A state-of-the-art systematic review of Randomized Controlled Trials in patient populations

= 10). The strongest evidence emerged from RCTs exploring PEA impact on pain management and measures of general wellbeing, especially in its ultramicronized/micronized or cold-water dispersible formulations, showing good tolerability compared to controls. Also, alongside symptom improvement, PEA demonstrated to modulate biomarkers early altered in the initial phases of an illness or contributing to its progression, suggesting a disease-modifying potential. This systematic review provided a comprehensive overview of the therapeutic potential of PEA across RCTs, highlighting its versatility either as monotherapy or add-on treatment for various clinical conditions.