Saanroo’s Levagen+ PEA modulates muscle lipids after exercise, but not strength or soreness

A new double-blind, randomized crossover study involving 10 healthy young men finds that supplementation with Saanroo’s Levagen+, a bioavailable palmitoylethanolamide (PEA) ingredient, maintained several bioactive lipid levels in skeletal muscle after strenuous, muscle-damaging exercise. 

Levagen+ uses Pharmako Biotechnologies’ LipiSperse technology, a specialized delivery system that keeps fat-soluble ingredients easily dispersible in water, allowing the body to absorb them more efficiently, according to the companies.

“This started as a Ph.D. research project looking at PEA, exercise, and muscle health,” says John Quilter, CEO of Saanroo. “What makes this research particularly valuable is that independent academic investigators were able to look beyond traditional markers and examine what was happening within skeletal muscle at the lipidomic level.”

“The findings raise new questions about how PEA may influence the body’'s response to strenuous exercise, and that is exactly what we want our research program to do: generate evidence that advances our understanding of PEA while identifying where the next questions should be asked.”

Study design

Strenuous exercise induces microstructural muscle damage, leading to delayed -onset muscle soreness and reduced performance, note the study authors.

“Although structural changes are well documented, subsequent inflammatory responses are not fully understood. Research has mainly examined leukocyte infiltration and cytokine expression, while low-abundance bioactive lipid mediators remain understudied,” they write in the paper.

In the study published in Pflügers Archiv – European Journal of Physiology, the men were administered either 350 mg of Levagen+ or a placebo twice daily (700 mg/day) for six days. After the sixth day, they completed one muscle-damaging exercise protocol comprising 24 sets of 10 eccentric knee-extension contractions.

Strenuous exercise induces microstructural muscle damage, leading to delayed-onset muscle soreness and reduced performance, note the study authors.

Researchers collected skeletal muscle biopsies at baseline and 48 hours following exercise and analyzed the samples using lipidomics. They selected this 48-hour time point because they noted that muscle soreness and reductions in muscle strength typically peak around this time following strenuous exercise.

According to the findings, Levagen+ reduced the drop in bioactive lipid levels typically seen in muscle after strenuous exercise.

Lipid pathways

Multiple lipid mediators that declined following exercise with placebo were maintained or increased with PEA supplementation, according to the paper. Mediators are bioactive fats that control inflammation, tissue repair, and cellular communication. The authors note they have historically received limited research attention.

These included pro-inflammatory as well as pro-resolving mediators, which the authors note contrasts with earlier research suggesting PEA dampens pro-inflammatory pathways.

The study found that MCTR3, a mediator linked to tissue regeneration, was consistently higher with PEA than placebo regardless of exercise, while two other pro-resolving mediators, LXB4 and AT-RvD3, were consistently lower.

The researchers found no differences between PEA and placebo in muscle strength, explosivity, pain, or muscle-damage markers, and noted that further research is needed to determine whether the observed lipid changes translate into physiologically meaningful outcomes for performance and recovery.

The research was led by Moniek Schouten as part of her Ph.D. work at KU Leuven in Belgium. Saanroo provided Levagen+ and did not financially fund the study. Research Foundation Flanders funded the work through a Ph.D. fellowship awarded to Schouten, and the authors declared no commercial or financial relationships that could represent a potential conflict of interest.

“Independent academic research can take the science in directions you may not initially anticipate,” says Quilter. “This study gives us a deeper look at what is happening within skeletal muscle at the lipidomic level, while also highlighting important questions that remain unanswered.”

“For us, that is the value of continued research.” He adds that each of the studies on Levagen+ add to Saanroo’s understanding of PEA and “help inform where the science should go next.”

Levagen+ body of research

According to Saanroo, Levagen+ has been studied across a wide range of health areas, including joint support, sleep, sports performance and recovery, cognitive function, everyday aches and discomfort, and women’s health. It notes this paper is the 19th study involving the ingredient.

In other research, a human clinical trial with Levagen+ published in Biomedicines suggests the ingredient can influence gut microbial activity, reduce intestinal inflammation, and even lower triglycerides.

Another human trial suggested Levagen+ may support people with seasonal allergies, finding that 350 mg daily significantly reduced plasma histamine levels compared with placebo in 101 participants.

An Australian study explored Levagen+ as a potential sleeping aid capable of reducing sleep onset time and improving cognition upon waking. The researchers position Levagen+ as an alternative to CBD, while suggesting it may promote better sleep via the endocannabinoid system.