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Palmitoylethanolamide (PEA)

Endogenous fatty acid amide with meta-analysis signal for chronic pain, including sciatica, neuropathy, fibromyalgia and pelvic pain.

Why

Palmitoylethanolamide (PEA) is an endogenous fatty acid amide, the saturated equivalent of the endocannabinoid anandamide. Meta-analyses of RCTs (Paladini Pain Physician 2016, Artukoglu J Pain 2017) report modest reductions in chronic pain across diverse conditions including sciatica, diabetic neuropathy, fibromyalgia, pelvic pain and post-shingles neuropathic pain. Used clinically in Italy and several other European countries as a prescription dietary supplement (Normast).

How it works

Endogenous PPAR-α agonist with anti-inflammatory effects on mast cells, microglia, and astrocytes, distinct from cannabinoid receptor agonism. Modulates the 'entourage effect' on endocannabinoid signalling without binding CB1/CB2 directly.

Expected onset · Pain reduction often over 4–8 weeks; sustained effect with continuous use

How to take

Dosage

Standard: 300 mg three times daily (Normast / ultramicronised PEA). Higher doses (1,200 mg/day) used in some trials. Continue for at least 8 weeks before assessing.

Timing

Divided 2–3 times daily with meals

On the label

Ultramicronised PEA (um-PEA, Normast) is the trial-grade form with significantly better absorption than non-micronised. Stated mg per dose.

Ideal for

Adults with chronic pain conditions (sciatica, neuropathy, fibromyalgia, pelvic pain) under clinical guidance; people seeking analgesic adjunct with minimal side-effect profile.

Safety

Very favourable safety profile, minimal side effects across published trials. Mild GI upset rarely. Theoretical antiplatelet effect at very high doses. Pregnancy and breastfeeding data limited; coordinate with the prescribing clinician. No significant drug interactions documented.

Evidence

At a glance

Paladini 2016 Pain Physician pooled meta-analysis (12 trials, n=1,484): PEA reduced pain by an average of 8.6 points more than control on 0–100 VAS scale across diverse chronic pain conditions. Artukoglu 2017 confirmed signal across an independent meta-analysis. Favourable safety profile is a practical advantage in chronic-pain contexts.

Where to get it

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