Combination PEA supplement reduces neuropathic pain by 33%: Study

Published in the journal Nutrients, ​the research explored the effects of Epineuron, a supplement developed by Greek manufacturer Pharma Unimedis, on relieving diabetic neuropathy-related pain in a group of 73 participants recruited from the outpatient clinic of the Diabetes Center at the University General Hospital of Thessaloniki.

Epineuron is formulated with Palmitoylethanolamide (PEA), superoxide dismutase (SOD), alpha lipoic acid (ALA), vitamins B6, B1, B12 and E, nicotinamide, magnesium and zinc. 

"We found an impressively, almost unexpectedly, large reduction in the pain score (by 33%) in the active group," the researchers from Greece and Germany reported. "Such a magnitude of improvement of the neuropathic pain is comparable with the efficacy of pain of antiepileptics and anti-depressive drugs."

Neuropathic pain ​

Neuropathic pain predominantly caused by diabetic neuropathy can affect quality of life and contribute to depression. Current medications like duloxetine and gabapentin provide only partial relief to less than half of the patients​. 

The researchers found in previous studies​ that vitamin B12, alone or combined with other compounds such as ALA and acetylcarnitine (ALC), improved some DN symptoms, but with only modest pain relief.

"Since there is only one approved formulation containing PEA in our country, we had to use a tablet containing not only PEA and vitamin B12, but also SOD, ALA, vitamins B1, B6, nicotinamide and the trace elements Mg and Zn," they wrote.

PEA, an endogenous fatty acid, is known for its anti-inflammatory and neuroprotective properties​, however, its effects on diabetic neuropathic pain have been minimally studied.

PEA​

Research has previously identified PEA as a 'biological counterpart' to the pro-inflammatory Nerve Growth Factor (NGF), showing​ that it reduces mast cell activity dose-dependently. 

Initially, this was thought to involve peripheral endocannabinoid receptors, and researchers later proved that it works through cannabinoid-like G-coupled receptors. Additionally, PEA may have neuroprotective effects by interacting with PPAR-α receptors​.

Despite its promising nerve-specific properties, PEA has not been studied in clinical trials until recently due to a lack of patent protection and poor solubility and bioavailability, according to the authors of the new study.

However, scientists recently developed​ micronized (m-PEA) and ultra-micronized (um-PEA) forms, improving dissolution, absorption, bioavailability and efficacy. 

Reduced pain ​

The randomized placebo controlled trial assigned participants (average age 63) to either the active treatment group, which received two tablets a day of the Epineuron supplement for six months, or the placebo group.  

To assess neuropathy and related measures, the study used the Michigan Neuropathy Screening Instrument (MNSIQ and MNSIE), vibration perception threshold (VPT), cardiovascular autonomic reflex tests (CARTs) and nerve function tests (DPN Check). Pain and quality of life were also evaluated through validated questionnaires. 

"The combination of the ten elements in one tablet for 6 months at a daily dose of two tablets in people with diabetic neuropathy significantly improved neuropathic pain," the researchers wrote. "It also increased vitamin B12 levels, and, despite the somehow short follow-up duration, improved some aspects of nerve functionality, such as vibration perception threshold.

"Our findings suggest that PEA can be administered for an extended period without significant side effects and may be helpful in alleviating the mild to moderate neuropathic pain of diabetic neuropathy."

The placebo group showed no significant changes in pain or other parameters, and the assessment showed a worsening of the MNSIE score. 

The researchers suggested that PEA played a crucial role in pain reduction by binding to receptors involved in reducing inflammation and pain. Vitamin B12, ALA and SOD, while beneficial for nerve function, were considered to contribute less to pain relief. 

As limitations, the study noted that the small sample size and the inability to isolate the effects of individual ingredients as  and called for further research to confirm the findings in larger, more diverse populations.

Journal: Nutrients​ 
doi: 10.3390/nu16183045​
“Efficacy and Safety of the Combination of Palmitoylethanolamide, Superoxide Dismutase, Alpha Lipoic Acid, Vitamins B12, B1, B6, E, Mg, Zn and Nicotinamide for 6 Months in People with Diabetic Neuropathy.”
Authors: Didangelo, Triantafyllos, et al.