Palmitoylethanolamide in the Management of Diabetic Neuropathy: A Systematic Review and Meta-analyses

A BSTRACT Diabetic neuropathy (DN) is a common and debilitating complication of diabetes. DN occurs when nerves are damaged due to chronic hyperglycemia, which overstimulates the nerve and results in damage. Currently available treatments for DN are limited, and consequently, new treatment options are critically needed. This systematic review aims to examine the effectiveness, safety, and possible protective mechanisms of palmitoylethanolamide (PEA) for the treatment of diabetic neuropathy. A general literature search was performed in major academic databases that included PubMed, Scopus, and Web of Science using the key terms associated with PEA and diabetic neuropathy. The studies that were included were randomized controlled trials, as well as preclinical studies, and measured pain relief, nerve-related measures, and inflammation-independent changes associated with PEA. Six studies were reviewed, indicating a statistically significant decrease in pain intensity and improvements in quality-of-life measures associated with PEA treatment. The pooled hazard ratio indicated a moderate analgesic effect (hazard rate = 2.08, 95% confidence interval: 1.71–2.53, P < 0.05). Most studies indicated that PEA was well tolerated, with only mild adverse effects. This review highlights the potential of PEA as an effective treatment for diabetic peripheral neuropathy, with not only definite improvements in pain but also in the quality of life. Although based on the variation in dosages and formulation of studies, further large scale randomized controlled trials would be required to establish the standard treatment protocols. PEA has promise as a worthwhile treatment option for some patients with neuropathic pain.