What does the research show about palmitoylethanolamide?

Palmitoylethanolamide

Two meta-analyses of randomized trials report lower chronic pain scores than with placebo or comparators, from trials of mixed quality. Nerve pain results split, with lower diabetic nerve pain and no change in chemotherapy nerve damage. Knee osteoarthritis trials disagree. Inflammation marker findings come from two small trials. No major side effects were attributed to PEA.

Add to Bio HackChecked 2026-11-09

Status: Sold as a dietary supplement in the US. Not FDA-approved as a drug for any condition.
Also called: PEA, palmidrol, palmitoyl ethanolamide, palmitoylethanolamine, micronized PEA, ultramicronized PEA, um-PEA, Levagen+, Normast
Taken for: chronic pain, nerve pain, neuropathy, inflammation, joint pain, osteoarthritis

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Shown to help2

StrongShown to lower chronic pain scores more than placebo or comparators in adults with nerve, joint and widespread pain.
ModerateShown to lower nerve pain, including diabetic nerve pain, though one trial in chemotherapy nerve damage found no benefit over placebo.

Reported risks0

No risks sourced yet.

What people take it for, and what was found

Shown to help2

Strong

Chronic pain

Shown to lower chronic pain scores more than placebo or comparators in adults with nerve, joint and widespread pain.

The numbers and sources

Effect: In 11 double-blind RCTs (774 patients), PEA lowered pain scores more than placebo or active comparators (SMD 1.68, 95% CI 1.05 to 2.31) [1]. In 18 RCTs (1,196 patients), pain was lower at 6 weeks (SMD -0.9, 95% CI -1.60 to -0.31), 8 weeks (SMD -0.98) and 24 to 26 weeks (SMD -1.16, 95% CI -2.15 to -0.17), and quality of life was higher (SMD -0.61) [2]. In 9 studies (742 patients) of micron-size PEA for at least 60 days, pain fell 2.08 points on a 10-point scale in the first month and a further 1.36 points by day 60 [3].
Population: Adults with chronic pain from many causes, including nerve, joint and widespread pain [1][2][3].
Sources: [1], [2], [3]
Caveats: Trials covered many conditions, doses and formulations. The day 60 against day 30 analysis compares PEA with itself, with no placebo arm [3].

Moderate

Nerve pain

Shown to lower nerve pain, including diabetic nerve pain, though one trial in chemotherapy nerve damage found no benefit over placebo.

The numbers and sources

Effect: Across 18 RCTs, pain classed as neuropathic fell more on PEA (SMD -0.97, 95% CI -1.54 to -0.39) [2]. A meta-analysis of 3 studies (188 patients) in diabetic nerve pain reported lower pain scores (SMD -5.44, I² 96%) [4]. In 70 people with diabetic nerve pain, 600 mg a day for 8 weeks lowered pain and pain interference scores against placebo (p ≤ 0.001), and improved sleep [5]. In 88 people with nerve damage from chemotherapy lasting at least 3 months, PEA for 8 weeks did no better than placebo on symptoms or quality of life [6].
Population: Adults with neuropathic pain [2], diabetic nerve pain [4][5], and nerve damage after paclitaxel, oxaliplatin or cisplatin [6].
Sources: [2], [4], [5], [6]
Caveats: The diabetic meta-analysis had very high heterogeneity, and its studies often used PEA in combination products [4].

Mixed results2

Limited

Knee osteoarthritis

Small trials found mixed results in knee osteoarthritis: one found lower symptom scores than placebo, and another found no significant difference.

The numbers and sources

Effect: In 111 adults, 300 or 600 mg a day for 8 weeks lowered total WOMAC scores against placebo (p 0.0372 and p 0.0012), with lower pain and stiffness at both doses [7]. In a 12-week trial of low and high doses, WOMAC fell 16.05 and 15.43 points against 11.76 on placebo, not a significant difference. Placebo improved more at week 4 [8].
Population: Adults with mild to moderate knee osteoarthritis [7][8].
Sources: [7], [8]
Caveats: Two trials with opposite main results. The responder benefit in the second trial came from a post hoc analysis [8].

Limited

Inflammation markers (CRP, IL-6)

Small trials found lower IL-6 and CRP in diabetic nerve pain, while a COVID-19 trial lowered other markers but not those two.

The numbers and sources

Effect: In 70 people with diabetic nerve pain, IL-6 and raised CRP fell more on 600 mg a day than on placebo (p 0.05), and fibrinogen did not differ [5]. In 60 unvaccinated adults recently diagnosed with COVID-19, 600 mg twice a day for 4 weeks lowered soluble P-selectin, IL-1 beta and IL-2 against placebo. IL-6 and CRP were primary outcomes and are not among the markers reported as reduced [9].
Population: 70 adults with type 1 or type 2 diabetes [5], and 60 adults aged 19 to 53 with COVID-19 not in hospital [9].
Sources: [5], [9]
Caveats: Two small trials. A systematic review of 47 RCTs lists 10 that measured blood or tissue markers but gives no pooled estimate [10].

Doses studied

Knee osteoarthritis trials used 300 or 600 mg a day in divided doses for 8 to 12 weeks [7][8]. The diabetic nerve pain trial used 600 mg a day for 8 weeks [5], and the COVID-19 trial 600 mg twice a day for 4 weeks [9]. The extended-treatment meta-analysis included micron-size PEA given for at least 60 days [3].

Risks

Checked, no increase found1

Moderate

Adverse events in trials

Side effects were about as common on PEA as on controls, with no major side effects attributed to it in trials.

The numbers and sources

Effect: Across 11 double-blind RCTs, no major side effects were attributed to PEA in any study [1]. A systematic review of 47 RCTs reported tolerability similar to controls [10]. Safety blood tests did not change in the diabetic nerve pain trial [5], clinical markers did not change in the knee trial [7], and toxicity did not differ in the chemotherapy nerve trial [6].
Population: Trial participants with chronic pain and other conditions [1][5][6][7][10].
Sources: [1], [5], [6], [7], [10]
Caveats: Most trials were short and small, and many tested PEA in combination with other ingredients.

Claims tested and not found

That PEA eases established nerve damage from chemotherapy. Neither PEA arm did better than placebo over 8 weeks in 88 people [6].
That PEA lowers knee osteoarthritis scores more than placebo at 12 weeks. The main WOMAC result did not differ significantly from placebo [8].

Sources

Lang-Illievich K, Klivinyi C, Lasser C, et al. Palmitoylethanolamide in the Treatment of Chronic Pain: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials. Nutrients. 2023. https://doi.org/10.3390/nu15061350
Viña I, López-Moreno M. Meta-Analysis of Palmitoylethanolamide in Pain Management: Addressing Literature Gaps and Enhancing Understanding. Nutrition Reviews. 2025. https://doi.org/10.1093/nutrit/nuae203
Schweiger V, Schievano C, Martini A, et al. Extended Treatment with Micron-Size Oral Palmitoylethanolamide (PEA) in Chronic Pain: A Systematic Review and Meta-Analysis. Nutrients. 2024. https://doi.org/10.3390/nu16111653
Prado MB, Nisce NRB, Cayanong EJB, Adiao KJB. Efficacy, safety, and tolerability of palmitoylethanolamide in the management of diabetic neuropathic pain: a systematic review and meta-analysis. Journal of Diabetes and Metabolic Disorders. 2026. https://doi.org/10.1007/s40200-026-01888-6
Pickering E, Steels EL, Steadman KJ, et al. A randomized controlled trial assessing the safety and efficacy of palmitoylethanolamide for treating diabetic-related peripheral neuropathic pain. Inflammopharmacology. 2022. https://doi.org/10.1007/s10787-022-01033-8
Davis MP, Ulrich A, Segal R, et al. Treatment of Established Chemotherapy-Induced Neuropathy with N-Palmitoylethanolamide: A Randomized, Double-Blind Phase II Pilot Study. Cancers. 2024. https://doi.org/10.3390/cancers16244244
Steels E, Venkatesh R, Steels E, et al. A double-blind randomized placebo controlled study assessing safety, tolerability and efficacy of palmitoylethanolamide for symptoms of knee osteoarthritis. Inflammopharmacology. 2019. https://doi.org/10.1007/s10787-019-00582-9
Srivastava S, Karvir S, Shende T. Temporal effects of Palmitoylethanolamide (PEA) in modulating knee osteoarthritis symptoms: A randomized, double-blind, placebo-controlled trial. Journal of Back and Musculoskeletal Rehabilitation. 2026. https://doi.org/10.1177/10538127261477951
Fessler SN, Liu L, Chang Y, et al. Palmitoylethanolamide Reduces Proinflammatory Markers in Unvaccinated Adults Recently Diagnosed with COVID-19: A Randomized Controlled Trial. The Journal of Nutrition. 2022. https://doi.org/10.1093/jn/nxac154
Bortoletto R, Comacchio C, Garzitto M, et al. Palmitoylethanolamide supplementation for human health: A state-of-the-art systematic review of Randomized Controlled Trials in patient populations. Brain, Behavior, and Immunity Health. 2025. https://doi.org/10.1016/j.bbih.2024.100927

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