Reviews and meta-analyses
A meta-analysis pools the numbers from several trials. A narrative review summarises the literature in the authors' own words. Both depend on the quality of the trials they include, and this page states those limits for each one.
Two things to check on any review page here: who wrote it and how the studies were chosen. Several reviews of palmitoylethanolamide were written by authors linked to the companies that make it, and several meta-analyses pooled open-label studies with no comparison group. Each entry says so where it applies.
Meta-analyses
11 listed, newest first.
- Evaluation of the nutraceutical Palmitoylethanolamide in reducing intraocular pressure (IOP) in patients with glaucoma or ocular hypertension: a systematic review and meta-analysis
The authors report a significant reduction in intraocular pressure with palmitoylethanolamide across the pooled studies.
Meta-analysisHumans - Meta-Analysis of Palmitoylethanolamide in Pain Management: Addressing Literature Gaps and Enhancing Understanding
The authors reported a pooled standardised mean difference in pain of -0.36 at 4 weeks (95% CI -0.65 to -0.07), -0.9 at 6 weeks (-1.60 to -0.31), -0.98 at 8 weeks (-1.61 to -0.36) and -1.16 at 24 to 26 weeks (-2.15 to -0.17), all in favour of palmitoylethanolamide.
Meta-analysisHumans - Extended Treatment with Micron-Size Oral Palmitoylethanolamide (PEA) in Chronic Pain: A Systematic Review and Meta-Analysis
The authors reported a further fall in pain of 1.36 points between day 30 and day 60 (95% CI 0.98 to 1.74).
Meta-analysisHumans - Efficacy of Palmitoylethanolamide and Luteolin Association on Post-Covid Olfactory Dysfunction: A Systematic Review and Meta-Analysis of Clinical Studies
The authors reported that the combination, given with olfactory training, favoured recovery of smell compared with conventional therapy.
Meta-analysisHumansWith luteolin - Palmitoylethanolamide in the Treatment of Chronic Pain: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials
The authors reported a pooled standardised mean difference in pain scores of 1.68 in favour of palmitoylethanolamide (95% CI 1.05 to 2.31).
Meta-analysisHumans - Therapeutic effect of palmitoylethanolamide in cognitive decline: A systematic review and preliminary meta-analysis of preclinical and clinical evidence
In animal models the compound improved memory and learning and reduced oxidative, inflammatory and astrocyte markers, with the authors noting the protective effect may matter less once disease is established.
Meta-analysisHumansOther animals - Looking for Responders among Women with Chronic Pelvic Pain Treated with a Comicronized Formulation of Micronized Palmitoylethanolamide and Polydatin
More than half of women were good responders.
Meta-analysisHumansWith polydatin - Effects of Palmitoylethanolamide (PEA) on Nociceptive, Musculoskeletal and Neuropathic Pain: Systematic Review and Meta-Analysis of Clinical Evidence
The authors reported that the six non-randomised studies favoured palmitoylethanolamide over the control (p < 0.00001).
Meta-analysisHumans - Efficacy of Palmitoylethanolamide for Pain: A Meta-Analysis
PEA reduced pain more than inactive control: weighted mean difference 2.03 points (95 percent CI 1.19 to 2.87, p < 0.001).
Meta-analysisHumans - Micronized palmitoylethanolamide/trans-polydatin treatment of endometriosis-related pain: a meta-analysis
Across a mixed sample, the combination gave a clinically relevant improvement in pelvic pain and dysmenorrhoea, a limited improvement in deep dyspareunia and none in dyschezia.
Meta-analysisHumansWith transpolydatin - Palmitoylethanolamide, a Special Food for Medical Purposes, in the Treatment of Chronic Pain: A Pooled Data Meta-analysis
Pain fell by about 1.04 points every 2 weeks on PEA against 0.20 on control.
Meta-analysisHumans
Reviews in people
15 listed.
- Palmitoylethanolamide supplementation for human health: A state-of-the-art systematic review of Randomized Controlled Trials in patient populations
The authors rated most of the included trials as good quality on the Joanna Briggs Institute tool, and two as fair.
ReviewHumans - Mechanisms and clinical applications of palmitoylethanolamide (PEA) in the treatment of neuropathic pain
The authors summarise the mechanism literature and state that experimental evidence shows pain and inflammation reduction and a lower need for other drugs.
ReviewHumans - A Decades-Long Journey of Palmitoylethanolamide (PEA) for Chronic Neuropathic Pain Management: A Comprehensive Narrative Review
The authors describe anti-inflammatory and pain-related effects through PPAR-alpha and the endocannabinoid system, and describe the safety and tolerability record as favourable.
ReviewHumans - Palmitoylethanolamide in the Treatment of Pain and Its Clinical Application Prospects
The authors describe multi-target effects through PPAR-alpha and the endocannabinoid system and a low rate of adverse reactions, mainly mild gastrointestinal discomfort and dizziness.
ReviewHumans - Therapeutic Potential of Palmitoylethanolamide in Gastrointestinal Disorders
The authors describe benefit in irritable bowel and inflammatory bowel disease studies and a lack of toxicity at high doses, and call for more human studies.
ReviewHumans - Questioning the role of palmitoylethanolamide in psychosis: a systematic review of clinical and preclinical evidence
The authors reported that six observational studies found raised plasma levels of palmitoylethanolamide in people with psychosis, which they describe as a possible early compensatory response.
ReviewHumans - Orofacial Pain Management: An Overview of the Potential Benefits of Palmitoylethanolamide and Other Natural Agents
The authors conclude that clinical data on palmitoylethanolamide in orofacial pain are still lacking, and set out the mechanism case for testing it.
ReviewHumans - Palmitoylethanolamide: A Nutritional Approach to Keep Neuroinflammation within Physiological Boundaries. A Systematic Review
The authors present the case that neuroinflammation is controlled by locally made palmitoylethanolamide and that oral micronised forms restore that control, and review the trials in that light.
ReviewHumans - The Potential Benefits of Palmitoylethanolamide in Palliation: A Qualitative Systematic Review
The authors find a significant number of trials showing pain relief, weaker evidence for non-pain symptoms, no reported drug interactions and few adverse effects, and note that little is known about pharmacokinetics.
ReviewHumans - Palmitoylethanolamide for the treatment of pain: pharmacokinetics, safety and efficacy
The authors concluded that for treatment of up to 49 days, the data argue against serious adverse reactions at a rate of 1 in 200 or more.
ReviewHumans - Palmitoylethanolamide, a neutraceutical, in nerve compression syndromes: efficacy and safety in sciatic pain and carpal tunnel syndrome
The authors conclude PEA reduced pain in each trial reviewed, including the 636-patient Guida trial (VAS 7.1 to 2.1 on 600 mg versus 6.6 to 4.6 on placebo), a 111-patient replication by Canteri, and several open-label carpal tunnel and sciatica studies.
ReviewHumans - Palmitoylethanolamide, a Natural Retinoprotectant: Its Putative Relevance for the Treatment of Glaucoma and Diabetic Retinopathy
The authors state that the compound has been tested in at least nine double-blind placebo-controlled studies, two in glaucoma, and found safe and effective up to 1.8 g a day.
ReviewHumans - Marketing messages in pharmacological papers and scientific chapters: the case of palmitoylethanolamide and its formulations
The author argues that some scientific papers on palmitoylethanolamide carry marketing messages for particular formulations.
ReviewHumans - Palmitoylethanolamide: problems regarding micronization, ultra-micronization and additives
The author notes that at least two authors of the reviewed paper have direct connections to Epitech and Innovet, and that no study had compared micronised or ultramicronised palmitoylethanolamide against the pure compound in patients, the minimum needed to support the claim.
ReviewHumans - Palmitoylethanolamide: A Natural Body-Own Anti-Inflammatory Agent, Effective and Safe against Influenza and Common Cold
The authors note that palmitoylethanolamide has been known as a food component since 1957, and that most research since the work of Levi-Montalcini in 1993 has concerned nerve pain and mast cell disorders.
ReviewHumans
Reviews in animals
19 listed.
- Palmitoylethanolamide in Human and Animal Obesity
The authors argue that, given the inflammation-obesity link, palmitoylethanolamide could be a strategy in human obesity, noting it is already sold as a veterinary food supplement.
ReviewHumansDogsCats - Investigating Properties of Palmitoylethanolamide in Physiology and Disease: Far Beyond an Anti-Inflammatory Shield
The authors describe wide-ranging protective effects in laboratory work and report a good tolerability record in people, with minimal risk of drug interactions.
ReviewHumansOther animals - Palmitoylethanolamide in Postmenopausal Metabolic Syndrome: Current Evidence and Clinical Perspectives
The authors describe laboratory and preliminary clinical data suggesting effects on blood lipids, insulin sensitivity and inflammation through PPAR-alpha.
ReviewHumansOther animals - Ultramicronized N-palmitoylethanolamine associated with analgesics: Effects against persistent pain
The authors summarise the case that micron-size forms have higher oral efficacy than plain powder, cross the gut wall and blood-brain barrier, and can be used as an add-on to analgesics, including data that it limits opioid tolerance in animals.
ReviewHumansOther animals - Neuropathic pain in cats: Mechanisms and multimodal management
The author presents a structured approach to recognising and managing neuropathic pain in cats, drawing on the literature and her own experience.
ReviewCats - Synaptic Effects of Palmitoylethanolamide in Neurodegenerative Disorders
The authors describe actions through PPAR-alpha, GPR55 and TRPV1, and early clinical signs of effect on cortical plasticity in frontotemporal dementia.
ReviewHumansOther animalsWith luteolin - Is It Time to Test the Antiseizure Potential of Palmitoylethanolamide in Human Studies? A Systematic Review of Preclinical Evidence
In animal models, supplementation reduced seizure frequency and severity, in some cases comparably to antiseizure drugs, with pretreatment more effective.
ReviewOther animals - Palmitoylethanolamide and Related ALIAmides for Small Animal Health: State of the Art
The authors summarise studies in dogs and cats, including an open multi-centre study of 160 dogs given 10 mg/kg a day for 56 days, and the cat trial by Noli and colleagues.
ReviewDogsCats - Effects of Palmitoylethanolamide on Neurodegenerative Diseases: A Review from Rodents to Humans
The authors describe laboratory evidence of protective and anti-inflammatory effects in models of the major neurodegenerative diseases.
ReviewHumansOther animals - Palmitoylethanolamide and Its Biobehavioral Correlates in Autism Spectrum Disorder: A Systematic Review of Human and Animal Evidence
Altered PEA and endocannabinoid levels and receptor expression are reported in autism.
ReviewHumansOther animals - Chronic Pain in Dogs and Cats: Is There Place for Dietary Intervention with Micro-Palmitoylethanolamide?
The authors conclude that the available evidence suggests a place for micronised palmitoylethanolamide in the dietary management of chronic pain.
ReviewDogsCats - Chronic Pain in Dogs and Cats: Is There Place for Dietary Intervention with Micro-Palmitoylethanolamide?
The authors conclude that the evidence supports a place for micronised palmitoylethanolamide in the dietary management of chronic pain in dogs and cats.
ReviewDogsCats - Ultramicronized Palmitoylethanolamide (um-PEA): A New Possible Adjuvant Treatment in COVID-19 patients
The authors propose, from earlier laboratory and clinical work, that its effects on immune response and inflammation could limit organ damage in COVID-19.
ReviewHumansOther animals - Successful and Unsuccessful Brain Aging in Pets: Pathophysiological Mechanisms behind Clinical Signs and Potential Benefits from Palmitoylethanolamide Nutritional Intervention
The authors state that ultramicronised palmitoylethanolamide has been tested repeatedly in animal models of age-related neurodegeneration with promising results and suggest it may support brain ageing in pets.
ReviewDogsCats - An Update of Palmitoylethanolamide and Luteolin Effects in Preclinical and Clinical Studies of Neuroinflammatory Events
The authors describe palmitoylethanolamide as protective and anti-inflammatory in laboratory models, and note that it has no antioxidant activity of its own.
ReviewHumansOther animalsWith luteolin - ALIAmides Update: Palmitoylethanolamide and Its Formulations on Management of Peripheral Neuropathic Pain
The authors describe clinical trials of several formulations in diabetic neuropathy, chemotherapy-related neuropathy, carpal tunnel syndrome, sciatica-type pain and jaw joint pain, and describe safety and tolerability as high.
ReviewHumansOther animals - The Basal Pharmacology of Palmitoylethanolamide
The authors describe PPAR-alpha as the best supported target, with further evidence for TRPV1 and GPR55 and for effects on mast cells.
ReviewHumansOther animals - Role of palmitoylethanolamide (PEA) in depression: Translational evidence
The authors report antidepressant-like activity in animal models and cite a randomised double-blind trial showing a fast antidepressant action when added to citalopram (Ghazizadeh-Hashemi 2018), while noting the limited number of studies.
ReviewHumansOther animals - The pharmacology of palmitoylethanolamide and first data on the therapeutic efficacy of some of its new formulations
The authors describe palmitoylethanolamide as a compound made in many plant and animal foods and in mammalian tissues, with protective, anti-inflammatory and pain-related actions in laboratory work.
ReviewHumansOther animals