Benefits
Bioavailability (formulation note)
Levagen+ combines PEA with LipiSperse dispersion technology from Pharmako Biotechnologies. A single-dose study of 28 people, funded by Gencor Pacific and Pharmako and published in a journal not indexed in PubMed, found about 1.75 times higher total blood levels over 4 hours than "standard" PEA, with no significant difference in peak levels. It did not test any health outcome.
Pain trials used 300 to 600 mg a day
Maker-funded Levagen+ trials (knee pain, diabetes-related nerve pain) used 300 to 600 mg a day. No trial has compared Levagen+ with other PEA forms, so there is no evidence it works at a lower dose.
Faster sleep onset in a subgroup of one maker-funded trial
In one Gencor Pacific-funded trial (Rao 2021, 350 mg before bed, 8 weeks, 125 randomized), time to fall asleep improved only in a subgroup of 78 who took over 10 minutes at baseline; overall sleep quantity and quality did not differ from placebo.
Memory test: one small maker-funded trial
In a 39-person crossover funded by Gencor, 6 weeks of Levagen+ (about 600 mg PEA a day) reduced errors on one memory test and raised blood BDNF; another memory measure did not differ. Not repeated.
Inflammation markers: 5 of 6 unchanged in one maker-funded trial
In a maker-funded COVID-19 trial, 5 of 6 main inflammation markers did not differ from placebo. No trial shows that better absorption gives better results.
Mechanism of action
LipiSperse® dispersion technology
LipiSperse is owned by Pharmako Biotechnologies (Australia) and is designed to help water-insoluble PEA disperse. A single-dose study of 28 people, funded by Gencor Pacific and Pharmako and published in a journal not indexed in PubMed, found about 1.75 times higher total blood levels over 4 hours than "standard" PEA, with no significant difference in peak levels.
PPAR-alpha activation
PEA activates PPAR-alpha nuclear receptors, which regulate inflammation and lipid metabolism.
Endocannabinoid-like signaling
PEA may raise anandamide levels indirectly by competing for the breakdown enzyme FAAH; it does not act directly on cannabinoid receptors, and whether this contributes to any measured effect is unknown.
Clinical trials
Randomized, double-blind, placebo-controlled trial of PEA at 300 or 600 mg/day for 8 weeks in knee osteoarthritis. (Steels et al. 2019, Inflammopharmacology)
n=111 adults with knee osteoarthritis.
Both PEA doses significantly reduced total WOMAC scores and pain versus placebo. The study was industry-funded, and the published abstract reports generic “PEA” rather than the Levagen+® brand name. The 2023 meta-analysis lists it as company-funded; a 2021 review's conflict statement says co-author R. Venkatesh has personal relations to a member of Gencor Pacific. A second 12-week knee trial missed its main goal.
Double-blind, randomized, placebo-controlled trial of Levagen+® after damaging leg-press exercise in healthy men. (Mallard et al. 2020, Nutrients)
n=28 healthy men.
Levagen+® lowered post-exercise myoglobin and blood lactate, but muscle soreness itself was not significantly reduced.
Double-blind, randomized, placebo-controlled trial of Levagen+® 350 mg/day for 8 weeks for sleep disturbance. (Rao et al. 2021, Sleep Science and Practice)
125 adults with sleep disturbance randomized, 103 completed.
In a subgroup of 78 with longer baseline latency, Levagen+® shortened sleep-onset latency and improved cognition on waking, but actigraphy- and diary-measured sleep quantity and quality did not differ from placebo (mixed).
Randomized controlled trial of Levagen+® 600 mg twice daily for 4 weeks in unvaccinated adults recently diagnosed with COVID-19. (Fessler et al. 2022, Journal of Nutrition)
Unvaccinated adults recently diagnosed with COVID-19.
5 of 6 primary markers (IL-6, CRP, ferritin, ICAM-1 and neutrophil-to-lymphocyte ratio) did not differ from placebo; only soluble P-selectin did. IL-1β and IL-2 were secondary outcomes, and no clinical outcomes were measured. Funded by Gencor Pacific.