Effectiveness of palmitoylethanolamide on endothelial dysfunction in ocular hypertensive patients: a randomized, placebo-controlled cross-over study.

PURPOSE: We assessed the effect of palmitoylethanolamide (PEA) on systemic endothelial function in ocular hypertensive patients (OH). METHODS: We enrolled in this randomized, double-blind, placebo-controlled, crossover single-center study 40 never-treated OH patients and 40 healthy age-matched controls. At baseline, each participant underwent endothelium-dependent flow-mediated vasodilation (FMD) measurement using a noninvasive high-resolution 2-dimensional ultrasonographic imaging of the brachial artery. OH patients were assigned randomly to receive either 300 mg PEA (Group A) or a matching placebo (Group B), twice a day for three months (T1). The first medication period was followed by a two-month washout period (T2), and then patients switched to PEA or placebo (depending on the first drug received) for another three months (T3). FMD evaluations were repeated at T1, T2, and T3. RESULTS: At baseline FMD values in OH patients and controls were 6.06 ± 0.60% vs. 10.85 ± 1.80%, respectively (P < 0.001). At T1, FMD and IOP of Group A were, respectively, 8.46 ± 1.09% vs. 6.08 ± 0.62% (P < 0.001, r = 0.96) and 22.18 ± 1.26 vs. 23.03 ± 0.88 mm Hg (P < 0.001). At T2, Group A had better FMD values than at baseline (6.59 ± 0.33% vs. 6.08 ± 0.62%, P < 0.05). At T3, subjects in Group B showed better FMD and IOP than at T2 (8.52 ± 1.07% vs. 6.05 ± 0.68%, P < 0.001, r = 0.97; and 22.43 ± 1.17 vs. 23.03 ± 0.83 mm Hg, P < 0.01, respectively). No side effects were observed. CONCLUSIONS: Three-month PEA intake reduced IOP and led to significantly improved FMD values in OH patients compared to placebo, by ameliorating peripheral endothelial function, and its positive effect lasted longer than the period of PEA consumption. No adverse events were recorded. (Controlled-trials.com number, ISRCTN72647928.).