PEA: benefits, dosage, contraindications
Scientific name(s)
Palmitoylethanolamide
Family or group:
Fatty Acids
Indications
Scoring methodology
EFSA approval.
Osteoarthritis ✪✪✪✪✪
A clinical study conducted in patients with osteoarthritis shows that taking 300 mg or 600 mg of PEA per day in two divided doses for 8 weeks modestly improves function and reduces pain, stiffness, and the need for rescue analgesics, compared with placebo. The number of patients reporting no pain over the previous 24 hours more than doubled in patients taking PEA compared with placebo.
Posologie
Orally
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
Low back pain ✪✪✪✪✪
A few small clinical studies conducted in patients with sciatica show that taking 300 mg of PEA twice a day for 30 days in conjunction with standard treatment reduces pain and the physical aspects of quality of life compared with standard treatment alone. Some higher-quality clinical research conducted in adults with sciatica and low back pain also shows that taking PEA at 300 mg or 600 mg per day for 21 days reduces pain by 45% to 70% in patients with lumbosciatic pain, compared with a 30% reduction with placebo.
Posologie
Orally
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 the available clinical research, as well as an observational study, show that daily intake of 300 to 1200 mg of micronized or ultramicronized PEA for a period of up to 60 days reduces pain in people suffering from chronic pain due to various causes, regardless of the use of other analgesics. The meta-analysis estimated a five-fold reduction in pain every two weeks in patients using PEA compared with control. A more recent meta-analysis of small clinical studies conducted in patients suffering from pain of diverse etiologies and taking PEA at doses of 300 to 1200 mg for 10 to 180 days did not reveal any additional pain reduction with the use of higher doses or longer durations. There was also no difference in pain reduction compared with placebo or non-placebo control. The validity of these results is limited by the variability of the studies included in the analysis and by the lack of differentiation between patients suffering from neuropathic and non-neuropathic pain.
Posologie
Oral
300 - 1200 mg
Intestinal permeability ✪✪✪✪✪
In a randomized, double-blind, controlled trial whose objectives were to evaluate the effect of PEA and CBD on the permeability of the human gastrointestinal tract, participants received a 600 mg dose of aspirin (to induce a state of increased intestinal permeability) which was 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 the increase in permeability in the inflamed intestine, which is very promising for the development of future intestinal therapies treating disorders of increased intestinal permeability such as IBD.
Posologie
Orally
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 women suffering from endometriosis-related pain shows that taking 400 mg of micronized PEA twice daily for 3 months moderately improves pelvic pain and dysmenorrhea and modestly improves pain during sexual intercourse compared with placebo. nnLimited 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 endometriosis-associated pelvic pain and improves quality of life and sexual function compared with baseline. nn
Posologie
Oral
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 MS-related pain. Preliminary clinical research conducted in patients with the relapsing form of MS treated with subcutaneous interferon beta-1a shows that daily intake of 600 mg of ultramicronized PEA for 12 months improves some, but not all, MS symptoms, as well as the adverse effects of interferon treatment. However, taking PEA does not appear to improve physical or emotional well-being or overall quality of life.
Posologie
Oral
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 taking 700 mg of PEA plus 70 mg of luteolin daily for 30 days, in combination with olfactory rehabilitation, modestly improves olfactory recovery — based on threshold, discrimination, and identification — compared with olfactory rehabilitation alone. However, patients randomized to the PEA plus luteolin group had worse olfactory function at baseline and had experienced olfactory disorders for about twice as long as those in the control group. These baseline differences may have confounded the results.nn
Posologie
Oral
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 with baseline. Other preliminary clinical research conducted in patients with stable open-angle or normal-tension glaucoma who were already using standard topical therapy 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 with no PEA. However, in that study there was no effect on the visual field. PEA has also been evaluated for general reduction of intraocular pressure. In patients undergoing bilateral laser iridotomy to prevent primary angle-closure glaucoma, a small clinical study shows that taking a PEA-based product at 300 mg twice daily for 15 days before the surgical procedure prevents an increase in intraocular pressure within 2 hours after the procedure, compared with placebo. In patients with ocular hypertension but without other signs of glaucoma, preliminary clinical research shows that taking 300 mg of PEA twice daily for 90 days reduces intraocular pressure levels by about 3% from baseline. The validity of these results is limited by the absence of a control group.
Posologie
Oral
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 with baseline values.nnCase studies confirm pain reduction with PEA administration in patients with chronic idiopathic axonal polyneuropathy and, more generally, in cases of neuropathic pain.nnPEA represents a promising adjunct for neuropathic pain, with good tolerability and a wide safety margin.nn
Posologie
Oral administration
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 in patients with fibromyalgia who are taking duloxetine and pregabalin (two drugs used to treat various pain-related conditions and nerve disorders) show that taking 600 to 1200 mg of micronized or ultramicronized PEA per day for 3 months reduces pain and tender points compared with duloxetine and pregabalin alone.
Posologie
Oral
600 - 1200 mg
Carpal tunnel syndrome ✪✪✪✪✪
Preliminary clinical research conducted in patients with moderate 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 with no treatment. The validity of these results is limited by the lack 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 with the control group. Two 600 mg doses of the product were used daily for 10 days, then a 600 mg dose per day for 50 days.
Posologie
Oral
600 - 1200 mg
Respiratory infections ✪✪✪✪✪
Some low-quality clinical studies conducted in 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%. A retrospective observational study in 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 the children, compared with 95% of children taking a probiotic extract. In the 1960s, SPOFA United Pharmaceuticals marketed PEA as 300 mg tablets under the brand name Impulsin. This nutraceutical was promoted as a treatment for influenza and the common cold. Multiple studies at the time showed that PEA reduced viral symptoms and clinical influenza. It was later found that PEA reduced serological markers of influenza virus infection. This benefit has been largely ignored in recent literature, which now focuses on PEA's benefits as an analgesic and as a modulator of neurological disorders.
Posologie
Oral
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 PEA levels 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 a significantly greater improvement in depressive symptoms compared with the placebo group throughout the trial.
Posologie
Oral
1200 mg
Properties
Analgesic
The use of PEA to treat pain is attracting interest. Its analgesic effects are likely related to its local anti-inflammatory effects at the site of the nerve injury. However, PEA could also prolong the action of endocannabinoids (substances similar to the active compounds in cannabis produced by our bodies) by inhibiting the fatty acid amide hydrolase (FAAH) enzyme. In patients with multiple sclerosis, PEA appears to decrease the activity of the gene responsible for FAAH production, which increases levels of endocannabinoids such as anandamide and oleoylethanolamide. These compounds reduce inflammatory cytokines, substances that contribute to inflammation and pain. PEA also affects TRPV1 channels on sensory neurons, making them less sensitive and thus reducing the perception of pain. When applied topically, as in the case of vulvar pain, PEA targets nerve endings and other cell types to reduce the production of factors that contribute 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 such as histamine and various proteins (cytokines, chemokines, tryptases, proteases). Next, it activates a specific receptor called PPAR-alpha, which prevents the translocation of certain molecules (NF-kappa B) to the cell nucleus, thereby blocking the activation of inflammatory processes. This helps reduce inflammation and the associated pain. nnIn animal studies, micronization of PEA appears to increase its anti-inflammatory effects after oral administration.nn
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 the processes that lead to cell death (apoptosis) by decreasing lipid peroxidation and protein nitration, two processes that are harmful to brain cells. It has 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 to improved formation of new nerve cells (neurogenesis) and synaptic plasticity, which are essential for proper brain function. Finally, PEA has also shown promising results in neuronal protection after stroke (cerebral ischemia) in animals. It appears to reduce neurological damage by protecting against neuron and astrocyte death, by maintaining levels of growth factors essential for brain cells, and by limiting the infiltration of mast cells, immune cells involved in inflammation.
Usages associés
Vision
PEA is found naturally in ocular tissues. The anti-inflammatory effects of PEA are thought to play a role in protecting ocular tissues such as the retina. This could be useful in diabetic retinopathy, glaucoma, and other diseases. The anti-inflammatory effects of PEA likely protect the retina against oxidative stress and inflammatory cytokines. In animal models with high glucose levels, PEA may protect against toxicity associated with advanced glycation end products, thereby reducing activation of retinal glial cells and others. In human research, the possible benefits of PEA may be related to improved peripheral endothelial function, measured by flow-mediated dilation.
Usages associés
Gastroprotective
PEA is of interest for inflammatory intestinal 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 decreases intestinal permeability and inflammation. The mechanism of action appears to involve TRPV1, CB2, GPR55, and PPAR-alpha receptors. Human studies show that PEA attenuates the increased absorption of lactulose and mannitol that was experimentally induced by aspirin intake.
Usages associés
Safe dosage
Adults (18 years and older): 300 mg - 1400 mg
PEA has been used with apparent safety at doses up to 1400 mg per day for periods of up to 3 months.
Children ages 4 to 17 years: 300 mg - 600 mg
PEA has most often been used at doses of 300 to 600 mg once or twice daily for periods of up to 3 months.
Precautions
Pregnant women: avoid
Avoid due to lack of data.
Breastfeeding women: avoid
Avoid due to lack of data.
