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What the Research Shows

What the Research Shows

Most Relevant to Mast Cells & Histamine

Allergic Rhinitis & Histamine

Placebo-controlled human trial

In a double-blind randomized trial, 108 people with seasonal allergic rhinitis received 350 mg of Levagen+ PEA or placebo daily for two weeks. Overall nasal-symptom scores were not significantly different between groups, but the PEA group showed a significant reduction in circulating histamine and several inflammatory markers. A subgroup that started with more pronounced nasal symptoms also improved more than placebo.

Population
108 people with seasonal allergic rhinitis
Formulation
Levagen+
Dose
350 mg
Frequency
Once daily
Duration
14 days
Study type
Double-blind randomized placebo-controlled human trial
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Human Intestinal Tissue & Mast-Cell Activation

Human tissue/cell study

Researchers exposed duodenal biopsy tissue from people with functional dyspepsia and controls to acid. Acid increased mast-cell activation and mediator release, while added PEA counteracted mast-cell activation and TRPV1/TRPV4 upregulation in the tissue.

Population
Human duodenal biopsy specimens from people with functional dyspepsia and controls
Study type
Human tissue / ex vivo study
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Mast-Cell Degranulation & Histamine Release

Human tissue/cell study

In a laboratory mast-cell model, PEA reduced substance P-induced mast-cell degranulation and histamine release. The study also explored a DAGL/2-AG pathway that may help explain this mast-cell effect.

Population
Mast-cell laboratory model
Study type
In vitro laboratory study
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Broader Human Research

Diabetic Nerve Pain

Placebo-controlled human trial

In a quadruple-blind placebo-controlled trial of 70 people with diabetic peripheral neuropathic pain, 600 mg of PEA daily for eight weeks reduced total pain and pain interference compared with placebo. Several sleep measures also improved, and the treatment was reported as well tolerated.

Population
70 people with diabetic peripheral neuropathic pain
Formulation
PEA formulation used in the trial
Dose
600 mg
Frequency
Daily
Duration
8 weeks
Study type
Quadruple-blind randomized placebo-controlled human trial
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Chronic Pain: 11 Double-Blind Randomized Trials

Systematic review / meta-analysis

A 2023 systematic review and meta-analysis pooled 11 double-blind randomized trials involving 774 participants and found lower pain scores with PEA compared with control conditions. The studies covered different pain conditions, formulations, and dosing approaches.

Population
774 participants across 11 double-blind randomized trials
Formulation
Multiple PEA formulations
Study type
Systematic review and meta-analysis of double-blind randomized trials
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Knee Pain & Stiffness

Placebo-controlled human trial

In a double-blind placebo-controlled trial of 111 adults with mild-to-moderate knee osteoarthritis, 300 mg or 600 mg of PEA daily in divided doses for eight weeks improved several WOMAC measures of pain and stiffness compared with placebo.

Population
111 adults with mild-to-moderate knee osteoarthritis
Formulation
PEA
Dose
300 mg or 600 mg
Frequency
Daily, divided twice daily
Duration
8 weeks
Study type
Double-blind randomized placebo-controlled human trial
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Other Areas Studied

Migraine

Placebo-controlled human trial

In a double-blind randomized study, participants took 600 mg of Levagen+ PEA or placebo when a migraine began, with a second dose allowed after two hours if the migraine had not resolved. PEA was associated with lower pain at some time points, more resolved headaches, and less rescue-medication use.

Population
Otherwise healthy adults reporting migraine events
Formulation
Levagen+
Dose
600 mg
Frequency
At migraine onset; second dose permitted after 2 hours if unresolved
Duration
Acute migraine treatment
Study type
Double-blind randomized placebo-controlled human study
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Sleep Onset & Waking

Placebo-controlled human trial

In a double-blind randomized trial of 103 adults with sleep problems, 350 mg of Levagen+ daily for eight weeks shortened sleep-onset latency and improved some measures after waking. Overall sleep quality and sleep quantity improved similarly in both groups.

Population
103 adults with sleep problems
Formulation
Levagen+
Dose
350 mg
Frequency
Once daily
Duration
8 weeks
Study type
Double-blind randomized placebo-controlled human trial
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