PEA: Benefits, Dosage, Contraindications
PEA is manufactured by the body in response to stress and pain. Its production is generally stimulated by stress, inflammation, or injury.
PEA was discovered over 60 years ago. Earlier, Coburn - a doctor - described the clinical benefits of feeding poor children with dried egg yolks to prevent acute rheumatic fever despite streptococcal exposure. This observation led to the discovery of PEA a decade and a half later. Palmitoylethanolamide was finally isolated in 1957.
PEA is a cannabimimetic. The main targets of PEA have been clinically associated with analgesic, antidepressant, and anti-inflammatory activity.
Other name(s)
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Scientific name(s)
Palmitoylethanolamide
Family or group:
Fatty Acids
Indications
Rating methodology
EFSA approval.
Osteoarthritis ✪✪✪✪✪
A clinical study conducted on patients with osteoarthritis shows that taking 300 mg or 600 mg of PEA per day in two divided doses over 8 weeks moderately improves function and reduces pain, stiffness, and the need for rescue analgesics, compared to placebo. The number of patients reporting no pain over the previous 24 hours more than doubled in patients taking PEA, compared to placebo.
Posologie
Oral
300 mg
A double-blind randomized placebo controlled study assessing safety, tolerability and efficacy of palmitoylethanolamide for symptoms of knee osteoarthritis
The Potential Benefits of Palmitoylethanolamide in Palliation: A Qualitative Systematic Review
Back Pain ✪✪✪✪✪
Small clinical studies conducted on patients with sciatica show that taking 300 mg of PEA twice daily for 30 days alongside standard treatment reduces pain and physical aspects of quality of life compared to standard treatment alone.
Higher quality clinical research conducted on adults with sciatica and lumbalgia also shows that taking PEA at 300 mg or 600 mg daily for 21 days reduces pain by 45% to 70% in patients with lumbosciatica, compared to a 30% reduction with placebo.
Posologie
Oral
600 mg
N-palmitoylethanolamide in the treatment of neuropathic pain associated with lumbosciatica
Micronized Palmitoylethanolamide: A Post Hoc Analysis of a Controlled Study in Patients with Low Back Pain - Sciatica
Sex differences in N-palmitoylethanolamide effectiveness in neuropathic pain associated with lumbosciatalgia
Joint Pain ✪✪✪✪✪
A meta-analysis of available clinical research, along with an observational study, shows that the daily intake of 300 to 1200 mg of micronized or ultramicronized PEA for a period of up to 60 days reduces pain in people with chronic pain due to various causes, independently of the use of other analgesics. The meta-analysis estimated a five-fold reduction in pain every two weeks in patients using PEA compared to the control. A more recent meta-analysis of small clinical trials conducted in patients with pain of various etiologies taking PEA doses from 300 to 1200 mg for 10 to 180 days revealed no additional pain reduction with higher doses or longer durations. There was also no difference in pain reduction compared to a placebo or non-placebo control. The validity of these results is limited by the variability of the studies in the analysis and the lack of differentiation between patients with neuropathic and non-neuropathic pain.
Posologie
Oral route
300 - 1200 mg
Intestinal permeability ✪✪✪✪✪
In a randomized, double-blind, controlled trial aiming to evaluate the effect of PEA and CBD on gastrointestinal tract permeability in humans, participants received a 600 mg dose of aspirin (to induce increased intestinal permeability) administered orally with 400 ml of water and 600 mg of CBD, 600 mg of PEA or a placebo. PEA and CBD prevented inflammation-induced permeability, and these effects were mediated by different receptors. The authors conclude that in humans, PEA and CBD prevent increased permeability in the inflamed gut, which is very promising for the development of future intestinal therapies addressing increased intestinal permeability disorders such as IBD.
Posologie
Oral route
600 mg
Synergies
Palmitoylethanolamide and Cannabidiol Prevent Inflammation-induced Hyperpermeability of the Human Gut In Vitro and In Vivo-A Randomized, Placebo-controlled, Double-blind Controlled Trial
Endometriosis ✪✪✪✪✪
A meta-analysis of clinical and observational research in patients with endometriosis-related pain shows that taking 400 mg of micronized PEA twice daily for 3 months moderately improves pelvic pain and dysmenorrhea and modestly enhances pain during sexual intercourse compared to placebo. Limited research has also evaluated PEA in combination with alpha-lipoic acid. Preliminary clinical research shows that taking a combination of 300 mg of PEA and 300 mg of alpha-lipoic acid twice daily for 6 to 9 months reduces pelvic pain associated with endometriosis and improves quality of life and sexual function compared to baseline values.
Posologie
Oral route
600 - 800 mg
Synergies
Chronic pelvic pain, quality of life and sexual health of women treated with palmitoylethanolamide and α-lipoic acid
Effectiveness of the association micronized N-Palmitoylethanolamine (PEA)-transpolydatin in the treatment of chronic pelvic pain related to endometriosis after laparoscopic assessment: a pilot study
Multiple sclerosis ✪✪✪✪✪
Anecdotal evidence from case reports has suggested that PEA may reduce pain related to MS. Preliminary clinical research conducted on patients with the relapsing form of MS being treated with subcutaneous interferon beta-1a shows that daily intake of 600 mg of ultramicronized PEA for 12 months improves some symptoms of MS, but not all, as well as the adverse effects of interferon treatment. However, taking PEA does not seem to enhance physical or emotional well-being or overall quality of life.
Posologie
Oral route
600 mg
Multimodal stepped care approach with acupuncture and PPAR-α agonist palmitoylethanolamide in the treatment of a patient with multiple sclerosis and central neuropathic pain
Therapeutic utility of palmitoylethanolamide in the treatment of neuropathic pain associated with various pathological conditions: a case series
The Potential Benefits of Palmitoylethanolamide in Palliation: A Qualitative Systematic Review
COVID-19 ✪✪✪✪✪
COVID-19 infection has been associated with persistent disturbances of smell or taste. A small preliminary clinical trial shows that daily intake of 700 mg of PEA plus 70 mg of luteolin for 30 days, combined with olfactory rehabilitation, modestly improves olfactory recovery based on threshold, discrimination, and identification compared to olfactory rehabilitation alone. However, patients randomized to the PEA plus luteolin group had a poorer baseline olfactory status and had suffered from olfactory disturbances for about twice as long as those in the control group. These baseline differences may have confounded the outcomes.
Posologie
Oral route
700 mg
Glaucoma ✪✪✪✪✪
In patients with normal-tension glaucoma, preliminary clinical research shows that taking 600 mg of ultramicronized PEA in divided doses for 6 months reduces intraocular pressure and improves visual field indices without impacting visual acuity compared to baseline values. Other preliminary clinical research conducted in patients with stable open-angle or normal-tension glaucoma already using standard topical treatment shows that taking 600 mg of PEA per day for 4 months modestly improves retinal ganglion cell function, intraocular pressure, and quality of life compared to not taking PEA. However, in this study, there was no effect on the visual field. PEA has also been evaluated for general intraocular pressure reduction. In patients undergoing bilateral laser iridotomy for primary angle-closure glaucoma prevention, a small clinical study shows that taking a PEA-based product at 300 mg twice daily for 15 days before surgery prevents an increase in intraocular pressure within 2 hours of the procedure compared to placebo. In patients with ocular hypertension but without other glaucoma symptoms, preliminary clinical research shows that taking 300 mg of PEA twice daily for 90 days reduces intraocular pressure levels by about 3% compared to baseline values. The validity of these results is limited by the absence of a control group.
Posologie
Oral route
600 mg
Effect of palmitoylethanolamide on visual field damage progression in normal tension glaucoma patients: results of an open-label six-month follow-up
Effectiveness of palmitoylethanolamide on endothelial dysfunction in ocular hypertensive patients: a randomized, placebo-controlled cross-over study
Effect of palmitoylethanolamide on inner retinal function in glaucoma: a randomized, single blind, crossover, clinical trial by pattern-electroretinogram
Diabetic neuropathy ✪✪✪✪✪
Preliminary clinical research conducted in adults with diabetic neuropathy shows that taking micronized PEA at 300 mg twice daily for 60 days reduces neuropathic pain compared to baseline values. Case studies confirm pain reduction with PEA intake in patients with chronic idiopathic axonal polyneuropathy and more generally in cases of neuropathic pain. PEA represents a promising addition for neuropathic pain with good tolerance and a wide safety margin.
Posologie
Oral route
600 mg
Therapeutic utility of palmitoylethanolamide in the treatment of neuropathic pain associated with various pathological conditions: a case series
Short-term efficacy of ultramicronized palmitoylethanolamide in peripheral neuropathic pain
Chronic idiopathic axonal neuropathy and pain, treated with the endogenous lipid mediator palmitoylethanolamide: a case collection
Chronic idiopathic axonal neuropathy and pain, treated with the endogenous lipid mediator palmitoylethanolamide: a case collection
Fibromyalgia ✪✪✪✪✪
Retrospective and prospective observational studies conducted on fibromyalgia patients taking duloxetine and pregabalin (two medications used to treat various pain-related conditions and neurological disorders) show that taking 600 to 1200 mg of micronized or ultramicronized PEA per day for 3 months reduces pain and tender points compared to duloxetine and pregabalin alone.
Posologie
Oral route
600 - 1200 mg
Carpal Tunnel Syndrome ✪✪✪✪✪
Preliminary clinical research conducted on patients with moderately severe carpal tunnel syndrome shows that daily intake of 600 or 1200 mg of PEA in divided doses for 30 days reduces or delays discomfort compared to no treatment. The validity of these results is limited by the absence of an adequate comparison group. Another small preliminary clinical trial in patients with moderate to severe carpal tunnel syndrome shows that daily intake of 1200 mg of ultramicronized PEA before carpal tunnel surgery improves sleep disturbances and pain compared to the control group. Two doses of 600 mg of the product were used daily for 10 days, followed by one dose of 600 mg per day for 50 days.
Posologie
Oral route
600 - 1200 mg
Respiratory Infections ✪✪✪✪✪
Some low-quality clinical studies conducted on adults and children show that taking PEA up to 1800 mg per day in divided doses for at least 12 days reduces the risk of developing an acute respiratory infection by 32% to 59%. Retrospective and observational research on children with recurrent respiratory infections shows that taking PEA, bovine colostrum, and phenylethylamine, in the form of one sachet per day for 10 to 20 consecutive days each month for 4 months, reduces the need for antibiotics. The combined product reduced the need for antibiotic treatment to only 52% of children, compared to 95% of children taking a probiotic extract. In the 1960s, SPOFA United Pharmaceuticals marketed PEA in the form of 300 mg tablets under the brand name Impulsin. This nutraceutical was presented as a treatment for flu and cold. Multiple studies at the time demonstrated that PEA reduced viral symptoms and clinical flu. 0It was later discovered that PEA reduced the viral serology of the flu virus. This benefit has been largely ignored in recent literature, which now focuses on the benefits of PEA as an analgesic and modulator of neurological disorders.
Posologie
Oral route
600 - 1800 mg
Prophylactic efficacy of N-2-hydroxyethyl palmitamide (impulsin) in acute respiratory tract infections
Studies on prophylactic efficacy of N-2-hydroxyethyl palmitamide (Impulsin) in acute respiratory infections. Serologically controlled field trials
The Potential Benefits of Palmitoylethanolamide in Palliation: A Qualitative Systematic Review
Retrospective observational study to investigate Sinerga, a multifactorial nutritional product, and bacterial extracts in the prevention of recurrent respiratory infections in children
Depression ✪✪✪✪✪
Circulating levels of PEA are significantly lower in depressed women than in healthy controls. A double-blind randomized trial added 1200 mg/day of PEA or placebo to citalopram in 58 patients. The Hamilton Depression Rating Scale was used to measure outcomes at 2, 4, and 6 weeks. Palmitoylethanolamide shows significantly greater improvement in depressive symptoms compared to the placebo group throughout the trial period.
Posologie
Oral route
1200 mg
Properties
Analgesic
The use of PEA to treat pain is of interest. Its analgesic effects are likely related to its local anti-inflammatory effects at the site of nerve injury. However, PEA could also extend the action of endocannabinoids (substances similar to the active compounds in cannabis produced by our bodies) by inhibiting the enzyme fatty acid amide hydrolase (FAAH).
In patients with multiple sclerosis, PEA seems to reduce the activity of the gene responsible for the production of FAAH, which increases levels of endocannabinoids like anandamide and oleoylethanolamide. These compounds reduce inflammatory cytokines, substances that contribute to inflammation and pain.
PEA also affects TRPV1 channels present on sensory neurons, making them less sensitive and therefore reducing the perception of pain. With topical application, as in the case of vulvar pain, PEA targets nerve endings and other cell types to reduce the production of factors contributing to pain and inflammation.
Usages associés
Anti-inflammatory
PEA reduces inflammation in two main steps. First, it inhibits the activation of mast cells, immune cells activated at the site of nerve injury that normally release inflammatory substances like histamine and various proteins (cytokines, chemokines, tryptases, proteases). Then, it stimulates a specific receptor named PPAR-alpha, which blocks the movement of certain molecules (NF-kappa B) into the cell nucleus, thus preventing the activation of inflammatory processes. This helps reduce inflammation and associated pain.
In animal research, micronization of PEA appears to increase its anti-inflammatory effects after oral consumption.
Usages associés
Neurological
Palmitoylethanolamide (PEA) shows promising potential for neuroprotection in various neurological conditions. In Alzheimer's disease, PEA has demonstrated its ability to reduce processes leading to cell death (apoptosis) by decreasing lipid peroxidation and protein nitration, both harmful processes for brain cells. It also protected neurons and astrocytes in culture in the presence of amyloid substances, involved in Alzheimer's disease.
Regarding autism spectrum disorders, PEA improved behavior in an animal model. This behavioral improvement is linked to a reduction in inflammatory cytokines in the brain and an enhancement in the formation of new nerve cells (neurogenesis) and synaptic plasticity, crucial for proper brain functioning.
Finally, PEA has also shown promising results in neuronal protection after a stroke in animal models. It seems to reduce neurological damage by protecting against neuron and astrocyte death, maintaining levels of growth factors essential for brain cells, and limiting mast cell infiltration, immune cells involved in inflammation.
Usages associés
Vision
PEA is naturally found in eye tissues. PEA's anti-inflammatory effects are thought to play a role in protecting eye tissues, such as the retina. This could be useful in cases of diabetic retinopathy, glaucoma, and other diseases. PEA's anti-inflammatory effects likely protect the retina against oxidative stress and inflammatory cytokines.
In animal models with high glucose levels, PEA could protect against toxicity associated with advanced glycation end products, thus reducing the activation of retinal glial and other cells. In human research, the potential benefits of PEA could be linked to improved peripheral endothelial function, measured by flow-mediated dilation.
Usages associés
Gastroprotective
PEA is of interest for inflammatory bowel disorders such as Crohn's disease or ulcerative colitis, which are associated with increased intestinal permeability and inflammation. In animal and in vitro research, PEA reduces intestinal permeability and inflammation. The mechanism of action seems to involve TRPV1, CB2, GPR55 and PPAR-alpha receptors. Research in humans shows that PEA attenuates the increased absorption of lactulose and mannitol, which was experimentally induced by taking aspirin.
Usages associés
Safety dosage
Adults from 18 years: 300 mg - 1400 mg
PEA has been used safely at doses up to 1400 mg per day for up to 3 months.
Children from 4 to 17 years: 300 mg - 600 mg
PEA has most often been used at doses of 300 to 600 mg one or two times per day for up to 3 months.
Precautions
Pregnant women: avoid
Avoid due to lack of data.
Breastfeeding women: avoid
Avoid due to lack of data.
